start-ver=1.4 cd-journal=joma no-vol=1 cd-vols= no-issue=1 article-no= start-page=15001 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2016 dt-pub=20160111 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A capsidless ssRNA virus hosted by an unrelated dsRNA virus en-subtitle= kn-subtitle= en-abstract= kn-abstract=Viruses typically encode the capsid that encases their genome, while satellite viruses do not encode a replicase and depend on a helper virus for their replication1. Here, we report interplay between two RNA viruses, yado-nushi virus 1 (YnV1) and yado-kari virus 1 (YkV1), in a phytopathogenic fungus, Rosellinia necatrix2. YkV1 has a close phylogenetic affinity to positive-sense, single-stranded (+)ssRNA viruses such as animal caliciviruses3, while YnV1 has an undivided double-stranded (ds) RNA genome with a resemblance to fungal totiviruses4. Virion transfection and infectious full-length cDNA transformation has shown that YkV1 depends on YnV1 for viability, although it probably encodes functional RNA-dependent RNA polymerase (RdRp). Immunological and molecular analyses have revealed trans-encapsidation of not only YkV1 RNA but also RdRp by the capsid protein of the other virus (YnV1), and enhancement of YnV1 accumulation by YkV1. This study demonstrates interplay in which the capsidless (+)ssRNA virus (YkV1), hijacks the capsid protein of the dsRNA virus (YnV1), and replicates as if it were a dsRNA virus. en-copyright= kn-copyright= en-aut-name=ZhangRui en-aut-sei=Zhang en-aut-mei=Rui kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HisanoSakae en-aut-sei=Hisano en-aut-mei=Sakae kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TaniAkio en-aut-sei=Tani en-aut-mei=Akio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KondoHideki en-aut-sei=Kondo en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KanematsuSatoko en-aut-sei=Kanematsu en-aut-mei=Satoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SuzukiNobuhiro en-aut-sei=Suzuki en-aut-mei=Nobuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Agrivirology Laboratory, Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=2 en-affil=Agrivirology Laboratory, Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=3 en-affil=Agrivirology Laboratory, Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=4 en-affil=Agrivirology Laboratory, Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=5 en-affil=NARO Institute of Fruit Tree Science kn-affil= affil-num=6 en-affil=Agrivirology Laboratory, Institute of Plant Science and Resources, Okayama University kn-affil= en-keyword=Molecular evolution kn-keyword=Molecular evolution en-keyword=Viral genetics kn-keyword=Viral genetics END start-ver=1.4 cd-journal=joma no-vol=11 cd-vols= no-issue=1 article-no= start-page=238 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20200113 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Structural basis for the adaptation and function of chlorophyll f in photosystem I en-subtitle= kn-subtitle= en-abstract= kn-abstract=Chlorophylls (Chl) play pivotal roles in energy capture, transfer and charge separation in photosynthesis. Among Chls functioning in oxygenic photosynthesis, Chl f is the most red-shifted type first found in a cyanobacterium Halomicronema hongdechloris. The location and function of Chl f in photosystems are not clear. Here we analyzed the high-resolution structures of photosystem I (PSI) core from H. hongdechloris grown under white or far-red light by cryo-electron microscopy. The structure showed that, far-red PSI binds 83 Chl a and 7 Chl f, and Chl f are associated at the periphery of PSI but not in the electron transfer chain. The appearance of Chl f is well correlated with the expression of PSI genes induced under far-red light. These results indicate that Chl f functions to harvest the far-red light and enhance uphill energy transfer, and changes in the gene sequences are essential for the binding of Chl f. en-copyright= kn-copyright= en-aut-name=KatoKoji en-aut-sei=Kato en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ShinodaToshiyuki en-aut-sei=Shinoda en-aut-mei=Toshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NagaoRyo en-aut-sei=Nagao en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=AkimotoSeiji en-aut-sei=Akimoto en-aut-mei=Seiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SuzukiTakehiro en-aut-sei=Suzuki en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=DohmaeNaoshi en-aut-sei=Dohmae en-aut-mei=Naoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ChenMin en-aut-sei=Chen en-aut-mei=Min kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=AllakhverdievSuleyman I. en-aut-sei=Allakhverdiev en-aut-mei=Suleyman I. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=ShenJian-Ren en-aut-sei=Shen en-aut-mei=Jian-Ren kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=AkitaFusamichi en-aut-sei=Akita en-aut-mei=Fusamichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=MiyazakiNaoyuki en-aut-sei=Miyazaki en-aut-mei=Naoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=TomoTatsuya en-aut-sei=Tomo en-aut-mei=Tatsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil=Research Institute for Interdisciplinary Science and Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Faculty of Science, Tokyo University of Science kn-affil= affil-num=3 en-affil=Research Institute for Interdisciplinary Science and Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=4 en-affil=Graduate School of Science, Kobe University kn-affil= affil-num=5 en-affil=Biomolecular Characterization Unit, RIKEN Center for Sustainable Resource Science kn-affil= affil-num=6 en-affil=Biomolecular Characterization Unit, RIKEN Center for Sustainable Resource Science kn-affil= affil-num=7 en-affil=School of Life and Environmental Sciences, University of Sydney kn-affil= affil-num=8 en-affil=K.A. Timiryazev Institute of Plant Physiology RAS kn-affil= affil-num=9 en-affil=Research Institute for Interdisciplinary Science and Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=10 en-affil=Research Institute for Interdisciplinary Science and Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=11 en-affil=Institute for Protein Research, Laboratory of Protein Synthesis and Expression, Osaka University kn-affil= affil-num=12 en-affil=Faculty of Science, Tokyo University of Science kn-affil= END start-ver=1.4 cd-journal=joma no-vol=11 cd-vols= no-issue=1 article-no= start-page=4387 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20200128 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Formation of bridgmanite-enriched layer at the top lower-mantle during magma ocean solidification en-subtitle= kn-subtitle= en-abstract= kn-abstract=Thermochemical heterogeneities detected today in the Earth's mantle could arise from ongoing partial melting in different mantle regions. A major open question, however, is the level of chemical stratification inherited from an early magma-ocean (MO) solidification. Here we show that the MO crystallized homogeneously in the deep mantle, but with chemical fractionation at depths around 1000 km and in the upper mantle. Our arguments are based on accurate measurements of the viscosity of melts with forsterite, enstatite and diopside compositions up to similar to 30 GPa and more than 3000 K at synchrotron X-ray facilities. Fractional solidification would induce the formation of a bridgmanite-enriched layer at similar to 1000 km depth. This layer may have resisted to mantle mixing by convection and cause the reported viscosity peak and anomalous dynamic impedance. On the other hand, fractional solidification in the upper mantle would have favored the formation of the first crust. en-copyright= kn-copyright= en-aut-name=XieLongjian en-aut-sei=Xie en-aut-mei=Longjian kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YonedaAkira en-aut-sei=Yoneda en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YamazakiDaisuke en-aut-sei=Yamazaki en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ManthilakeGeeth en-aut-sei=Manthilake en-aut-mei=Geeth kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HigoYuji en-aut-sei=Higo en-aut-mei=Yuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TangeYoshinori en-aut-sei=Tange en-aut-mei=Yoshinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=GuignotNicolas en-aut-sei=Guignot en-aut-mei=Nicolas kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KingAndrew en-aut-sei=King en-aut-mei=Andrew kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=ScheelMario en-aut-sei=Scheel en-aut-mei=Mario kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=AndraultDenis en-aut-sei=Andrault en-aut-mei=Denis kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Institute for Planetary Materials, Okayama University kn-affil= affil-num=2 en-affil=Institute for Planetary Materials, Okayama University kn-affil= affil-num=3 en-affil=Institute for Planetary Materials, Okayama University kn-affil= affil-num=4 en-affil=Laboratoire Magmas et Volcans, Universit? Clermont Auvergne, CNRS, IRD, OPGC kn-affil= affil-num=5 en-affil=Japan Synchrotron Radiation Research Institute kn-affil= affil-num=6 en-affil=Japan Synchrotron Radiation Research Institute kn-affil= affil-num=7 en-affil=Synchrotron SOLEIL kn-affil= affil-num=8 en-affil=Synchrotron SOLEIL kn-affil= affil-num=9 en-affil=Synchrotron SOLEIL kn-affil= affil-num=10 en-affil=Laboratoire Magmas et Volcans, Universit? Clermont Auvergne, CNRS, IRD, OPGC kn-affil= END start-ver=1.4 cd-journal=joma no-vol=10 cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20200129 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Association between maternal periodontal status and ultrasonographic measurement of fetal growth: A longitudinal study en-subtitle= kn-subtitle= en-abstract= kn-abstract=The aim of this prospective cohort study was to investigate the association between intrauterine fetal growth patterns and periodontal status in pregnant women. Fifty-three pregnant women were recruited. Periodontitis was diagnosed based on probing pocket depth and clinical attachment level. Maternal urinary 8-hydroxy-2'-deoxyguanosine levels and body mass index were recorded. Ultrasonographic measurements of the biparietal diameter (BPD), abdominal circumference (AC), and femur length (FL) were recorded, and estimated fetal weight (EFW) was calculated. In addition, approximation spline curves of BPD, AC, FL, and EFW were obtained throughout the gestation period. Recorded delivery outcomes were gestational age (GA), birth weight and length, sex, placental weight, and umbilical cord length. Forty-four participants (34.1 +/- 4.9 years) were analyzed. Mean neonatal birth weight was 2906.0 +/- 544.4g. On multiple regression analysis, birth weight was related with periodontitis (standardized beta=-0.21, P=0.001). For EFW and BPD, the curves of the periodontitis group were located lower than those of the non-periodontitis group, with significant differences after 32 weeks and 20 weeks of GA, respectively. In conclusion, periodontal treatment before conception may be recommended and a good periodontal condition in the early stage of pregnancy at the latest is desirable for infant growth. en-copyright= kn-copyright= en-aut-name=Taniguchi-TabataAyano en-aut-sei=Taniguchi-Tabata en-aut-mei=Ayano kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TakeuchiNoriko en-aut-sei=Takeuchi en-aut-mei=Noriko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=UchidaYoko en-aut-sei=Uchida en-aut-mei=Yoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=EkuniDaisuke en-aut-sei=Ekuni en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MoritaManabu en-aut-sei=Morita en-aut-mei=Manabu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Department of Preventive Dentistry, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Preventive Dentistry, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Preventive Dentistry, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Preventive Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Preventive Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Periodontitis kn-keyword=Periodontitis en-keyword=Risk factors kn-keyword=Risk factors END start-ver=1.4 cd-journal=joma no-vol=10 cd-vols= no-issue=1 article-no= start-page=9323 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20200609 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Neural regulation in tooth regeneration of Ambystoma mexicanum en-subtitle= kn-subtitle= en-abstract= kn-abstract=The presence of nerves is an important factor in successful organ regeneration in amphibians. The Mexican salamander, Ambystoma mexicanum, is able to regenerate limbs, tail, and gills when nerves are present. However, the nerve-dependency of tooth regeneration has not been evaluated. Here, we reevaluated tooth regeneration processes in axolotls using a three-dimensional reconstitution method called CoMBI and found that tooth regeneration is nerve-dependent although the dentary bone is independent of nerve presence. The induction and invagination of the dental lamina were delayed by denervation. Exogenous Fgf2, Fgf8, and Bmp7 expression could induce tooth placodes even in the denervated mandible. Our results suggest that the role of nerves is conserved and that Fgf+Bmp signals play key roles in axolotl organ-level regeneration. The presence of nerves is an important factor in successful organ regeneration in amphibians. The Mexican salamander, Ambystoma mexicanum, is able to regenerate limbs, tail, and gills when nerves are present. However, the nervedependency of tooth regeneration has not been evaluated. Here, we reevaluated tooth regeneration processes in axolotls using a three-dimensional reconstitution method called CoMBI and found that tooth regeneration is nerve-dependent although the dentary bone is independent of nerve presence. The induction and invagination of the dental lamina were delayed by denervation. Exogenous Fgf2, Fgf8, and Bmp7 expression could induce tooth placodes even in the denervated mandible. Our results suggest that the role of nerves is conserved and that Fgf+Bmp signals play key roles in axolotl organ-level regeneration. en-copyright= kn-copyright= en-aut-name=MakanaeAki en-aut-sei=Makanae en-aut-mei=Aki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TajikaYuki en-aut-sei=Tajika en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NishimuraKoki en-aut-sei=Nishimura en-aut-mei=Koki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SaitoNanami en-aut-sei=Saito en-aut-mei=Nanami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TanakaJun-Ichi en-aut-sei=Tanaka en-aut-mei=Jun-Ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SatohAkira en-aut-sei=Satoh en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Okayama University Research Core for Interdisciplinary Sciences (RCIS) kn-affil= affil-num=2 en-affil=Gunma University, Department of Anatomy, Graduate School of Medicine kn-affil= affil-num=3 en-affil=Okayama University Research Core for Interdisciplinary Sciences (RCIS) kn-affil= affil-num=4 en-affil=Okayama University Research Core for Interdisciplinary Sciences (RCIS) kn-affil= affil-num=5 en-affil=Okayama University Research Core for Interdisciplinary Sciences (RCIS) kn-affil= affil-num=6 en-affil=Okayama University Research Core for Interdisciplinary Sciences (RCIS) kn-affil= en-keyword=Cell proliferation kn-keyword=Cell proliferation en-keyword=Differentiation kn-keyword=Differentiation en-keyword=Morphogenesis kn-keyword=Morphogenesis END start-ver=1.4 cd-journal=joma no-vol=10 cd-vols= no-issue=1 article-no= start-page=10122 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20200622 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Emergent cholecystectomy in patients on antithrombotic therapy en-subtitle= kn-subtitle= en-abstract= kn-abstract=The Tokyo Guidelines 2018 (TG18) recommend emergent cholecystectomy (EC) for acute cholecystitis. However, the number of patients on antithrombotic therapy (AT) has increased significantly, and no evidence has yet suggested that EC should be performed for acute cholecystitis in such patients. The aim of this study was to evaluate whether EC is as safe for patients on AT as for patients not on AT. We retrospectively analyzed patients who underwent EC from 2007 to 2018 at a single center. First, patients were divided into two groups according to the use of antithrombotic agents: AT; and no-AT. Second, the AT group was divided into three sub-groups according to the use of single antiplatelet therapy (SAPT), double antiplatelet therapy (DAPT), or anticoagulant with or without antiplatelet therapy (AC +/- APT). We then evaluated outcomes of EC among all four groups. The primary outcome was 30- and 90- day mortality rate, and secondary outcomes were morbidity rate and surgical outcomes. A total of 478 patients were enrolled (AT, n=123, no-AT, n=355) patients. No differences in morbidity rate (6.5% vs. 3.7%, respectively; P=0.203), 30-day mortality rate (1.6% vs. 1.4%, respectively; P=1.0) or 90-day mortality rate (1.6% vs. 1.4%, respectively; P=1.0) were evident between AT and no-AT groups. Between the no-AT and AC +/- APT groups, a significant difference was seen in blood loss (10mL vs. 114mL, respectively; P=0.017). Among the three AT sub-groups and the no-AT group, no differences were evident in morbidity rate (3.7% vs. 8.9% vs. 0% vs. 6.5%, respectively; P=0.201) or 30-day mortality (1.4% vs. 0% vs. 0% vs. 4.3%, respectively; P=0.351). No hemorrhagic or thrombotic morbidities were identified after EC in any group. In conclusion, EC for acute cholecystitis is as safe for patients on AT as for patients not on AT. en-copyright= kn-copyright= en-aut-name=YoshimotoMasashi en-aut-sei=Yoshimoto en-aut-mei=Masashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HiokiMasayoshi en-aut-sei=Hioki en-aut-mei=Masayoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SadamoriHiroshi en-aut-sei=Sadamori en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MondenKazuteru en-aut-sei=Monden en-aut-mei=Kazuteru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OhnoSatoshi en-aut-sei=Ohno en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TakakuraNorihisa en-aut-sei=Takakura en-aut-mei=Norihisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of Gastroenterological Surgery, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Gastroenterological Surgery, Fukuyama City Hospital kn-affil= affil-num=3 en-affil=Department of Gastroenterological Surgery, Fukuyama City Hospital kn-affil= affil-num=4 en-affil=Department of Gastroenterological Surgery, Fukuyama City Hospital kn-affil= affil-num=5 en-affil=Department of Gastroenterological Surgery, Fukuyama City Hospital kn-affil= affil-num=6 en-affil=Department of Gastroenterological Surgery, Fukuyama City Hospital kn-affil= en-keyword=Cholecystitis kn-keyword=Cholecystitis END start-ver=1.4 cd-journal=joma no-vol=10 cd-vols= no-issue=1 article-no= start-page=14889 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20200910 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Identification of effector candidate genes of Rhizoctonia solani AG-1 IA expressed during infection in Brachypodium distachyon en-subtitle= kn-subtitle= en-abstract= kn-abstract=Rhizoctonia solani is a necrotrophic phytopathogen belonging to basidiomycetes. It causes rice sheath blight which inflicts serious damage in rice production. The infection strategy of this pathogen remains unclear. We previously demonstrated that salicylic acid-induced immunity could block R. solani AG-1 IA infection in both rice and Brachypodium distachyon. R. solani may undergo biotrophic process using effector proteins to suppress host immunity before necrotrophic stage. To identify pathogen genes expressed at the early infection process, here we developed an inoculation method using B. distachyon which enables to sample an increased amount of semi-synchronous infection hyphae. Sixty-one R. solani secretory effector-like protein genes (RsSEPGs) were identified using in silico approach with the publicly available gene annotation of R. solani AG-1 IA genome and our RNA-sequencing results obtained from hyphae grown on agar medium. Expression of RsSEPGs was analyzed at 6, 10, 16, 24, and 32 h after inoculation by a quantitative reverse transcription-polymerase chain reaction and 52 genes could be detected at least on a single time point tested. Their expressions showed phase-specific patterns which were classified into 6 clusters. The 23 RsSEPGs in the cluster 1-3 and 29 RsSEPGs in the cluster 4-6 are expected to be involved in biotrophic and necrotrophic interactions, respectively. en-copyright= kn-copyright= en-aut-name=AbdelsalamSobhy S. H. en-aut-sei=Abdelsalam en-aut-mei=Sobhy S. H. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KouzaiYusuke en-aut-sei=Kouzai en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=WatanabeMegumi en-aut-sei=Watanabe en-aut-mei=Megumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=InoueKomaki en-aut-sei=Inoue en-aut-mei=Komaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MatsuiHidenori en-aut-sei=Matsui en-aut-mei=Hidenori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YamamotoMikihiro en-aut-sei=Yamamoto en-aut-mei=Mikihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=IchinoseYuki en-aut-sei=Ichinose en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=ToyodaKazuhiro en-aut-sei=Toyoda en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TsugeSeiji en-aut-sei=Tsuge en-aut-mei=Seiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MochidaKeiichi en-aut-sei=Mochida en-aut-mei=Keiichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=NoutoshiYoshiteru en-aut-sei=Noutoshi en-aut-mei=Yoshiteru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=2 en-affil=Bioproductivity Informatics Research Team, RIKEN Center for Sustainable Resource Science kn-affil= affil-num=3 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=4 en-affil=Bioproductivity Informatics Research Team, RIKEN Center for Sustainable Resource Science kn-affil= affil-num=5 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=6 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=7 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=8 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=9 en-affil=Graduate School of Agriculture, Kyoto Prefectural University kn-affil= affil-num=10 en-affil=Institute for Plant Science and Resources (IPSR), Okayama University kn-affil= affil-num=11 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= en-keyword=Fungi kn-keyword=Fungi en-keyword=Microbiology kn-keyword=Microbiology en-keyword=Pathogens kn-keyword=Pathogens en-keyword=Plant immunity kn-keyword=Plant immunity en-keyword=Plant sciences kn-keyword=Plant sciences en-keyword=Transcription kn-keyword=Transcription END start-ver=1.4 cd-journal=joma no-vol=10 cd-vols= no-issue=1 article-no= start-page=14928 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20200910 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Dysfunction of CD8+PD-1+T cells in type 2 diabetes caused by the impairment of metabolism-immune axis en-subtitle= kn-subtitle= en-abstract= kn-abstract=The metabolic changes and dysfunction in CD8+T cells may be involved in tumor progression and susceptibility to virus infection in type 2 diabetes (T2D). In C57BL/6JJcl mice fed with high fat-high sucrose chow (HFS), multifunctionality of CD8+splenic and tumor-infiltrating lymphocytes (TILs) was impaired and associated with enhanced tumor growth, which were inhibited by metformin. In CD8+splenic T cells from the HFS mice, glycolysis/basal respiration ratio was significantly reduced and reversed by metformin. In the patients with T2D (DM), multifunctionality of circulating CD8+PD-1+T cells stimulated with PMA/ionomycin as well as with HLA-A*24:02 CMV peptide was dampened, while metformin recovered multifunctionality. Both glycolysis and basal respiration were reduced in DM, and glycolysis was increased by metformin. The disturbance of the link between metabolism and immune function in CD8+PD-1+T cells in T2D was proved by recovery of antigen-specific and non-specific cytokine production via metformin-mediated increase in glycolytic activity. en-copyright= kn-copyright= en-aut-name=NojimaIchiro en-aut-sei=Nojima en-aut-mei=Ichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=EikawaShingo en-aut-sei=Eikawa en-aut-mei=Shingo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TomonobuNahoko en-aut-sei=Tomonobu en-aut-mei=Nahoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HadaYoshiko en-aut-sei=Hada en-aut-mei=Yoshiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KajitaniNobuo en-aut-sei=Kajitani en-aut-mei=Nobuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TeshigawaraSanae en-aut-sei=Teshigawara en-aut-mei=Sanae kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MiyamotoSatoshi en-aut-sei=Miyamoto en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=ToneAtsuhito en-aut-sei=Tone en-aut-mei=Atsuhito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=UchidaHaruhito A. en-aut-sei=Uchida en-aut-mei=Haruhito A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=NakatsukaAtsuko en-aut-sei=Nakatsuka en-aut-mei=Atsuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=EguchiJun en-aut-sei=Eguchi en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=ShikataKenichi en-aut-sei=Shikata en-aut-mei=Kenichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=UdonoHeiichiro en-aut-sei=Udono en-aut-mei=Heiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=WadaJun en-aut-sei=Wada en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= affil-num=1 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Hematology/Oncology, Hess Cancer Institute, Icahn School of Medicine At Mount Sinai kn-affil= affil-num=3 en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Internal Medicine, Diabetes Center, Okayama City Hospital kn-affil= affil-num=6 en-affil=Diabetes Center, Okayama S kn-affil=italama Univ, Dept Med & Clin Sci, Grad Sch Med Dent & Pharmaceut Sci affil-num=7 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=8 en-affil=Diabetes Center, Okayama Saiseikai General Hospital kn-affil= affil-num=9 en-affil=Department of Chronic Kidney Disease and Cardiovascular Disease, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=13 en-affil=Department of Immunology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=14 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Cytokines kn-keyword=Cytokines en-keyword=Diabetes kn-keyword=Diabetes en-keyword=Endocrine system and metabolic diseases kn-keyword=Endocrine system and metabolic diseases en-keyword=Immunology kn-keyword=Immunology en-keyword=Tumour immunology kn-keyword=Tumour immunology END start-ver=1.4 cd-journal=joma no-vol=10 cd-vols= no-issue=1 article-no= start-page=15509 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20200923 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A nationwide trend analysis in the incidence and mortality of Creutzfeldt-Jakob disease in Japan between 2005 and 2014 en-subtitle= kn-subtitle= en-abstract= kn-abstract=In the era of hyper-ageing, Creutzfeldt-Jakob disease (CJD) can become more prevalent as an important cause of dementia. This study aimed to evaluate the trends in crude and age-adjusted CJD-associated mortality and incidence rates in Japan using national vital statistics data on CJD-associated deaths among individuals aged over 50 years, as well as the government-funded nationwide CJD surveillance data (pertaining to the years 2005-2014) in Japan. The data were analysed using the Joinpoint Regression Program to estimate the long-term trends and average annual percentage changes (AAPCs). Overall, the AAPCs of age-adjusted CJD-associated mortality rates rose significantly over the study period (3.2%; 95% confidence interval [CI] 1.4-5.1%). The AAPC of the age-adjusted incidence rates also increased (overall 6.4%; 95% CI 4.7-8.1%). The CJD-associated increases in the mortality and incidence rates were especially prominent among adults over the age of 70 years. Given this trend in aging of population, the disease burden of CJD will continue to increase in severity. Our findings thus recommend that policymakers be aware of the importance of CJD and focus on preparing to address the increasing prevalence of dementia. en-copyright= kn-copyright= en-aut-name=NishimuraYoshito en-aut-sei=Nishimura en-aut-mei=Yoshito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HaradaKo en-aut-sei=Harada en-aut-mei=Ko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KoyamaToshihiro en-aut-sei=Koyama en-aut-mei=Toshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HagiyaHideharu en-aut-sei=Hagiya en-aut-mei=Hideharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OtsukaFumio en-aut-sei=Otsuka en-aut-mei=Fumio kn-aut-name=大塚文男 kn-aut-sei=大塚 kn-aut-mei=文男 aut-affil-num=5 ORCID= affil-num=1 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Pharmaceutical Biomedicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Epidemiology kn-keyword=Epidemiology en-keyword=Health policy kn-keyword=Health policy en-keyword=Neurological disorders kn-keyword=Neurological disorders END start-ver=1.4 cd-journal=joma no-vol=10 cd-vols= no-issue=1 article-no= start-page=15754 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20200925 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=3D imaging of proximal caries in posterior teeth using optical coherence tomography en-subtitle= kn-subtitle= en-abstract= kn-abstract=Optical coherence tomography (OCT) can create cross-sectional images of tooth without X-ray exposure. This study aimed to investigate the diagnostic accuracy of 3D imaging of OCT for proximal caries in posterior teeth. Thirty-six human molar teeth with 51 proximal surfaces visibly 6 intact, 16 slightly demineralized, and 29 distinct carious changes were mounted to take digital radiographs and 3D OCT images. The sensitivity, specificity and area under the receiver operating characteristic curve (AUC) for the diagnosis of enamel caries and dentin caries were calculated to quantify the diagnostic ability of 3D OCT in comparison with digital radiography. Diagnostic accuracy was evaluated by the agreement with histology using weighted Kappa. OCT showed significantly higher sensitivity, AUC and Kappa values than radiography. OCT can be a safer option for the diagnosis of proximal caries in posterior teeth that can be applied to the patients without X-ray exposure. en-copyright= kn-copyright= en-aut-name=ShimadaYasushi en-aut-sei=Shimada en-aut-mei=Yasushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=BurrowMichael F. en-aut-sei=Burrow en-aut-mei=Michael F. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ArakiKazuyuki en-aut-sei=Araki en-aut-mei=Kazuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ZhouYuan en-aut-sei=Zhou en-aut-mei=Yuan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HosakaKeiichi en-aut-sei=Hosaka en-aut-mei=Keiichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SadrAlireza en-aut-sei=Sadr en-aut-mei=Alireza kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YoshiyamaMasahiro en-aut-sei=Yoshiyama en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MiyazakiTakashi en-aut-sei=Miyazaki en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SumiYasunori en-aut-sei=Sumi en-aut-mei=Yasunori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=TagamiJunji en-aut-sei=Tagami en-aut-mei=Junji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Operative Dentistry, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Faculty of Dentistry, The University of Hong Kong, Prince Philip Dental Hospital kn-affil= affil-num=3 en-affil=Department of Oral Diagnostic Sciences, Division of Radiology, Showa University School of Dentistry kn-affil= affil-num=4 en-affil=Department of Preventive Dentistry, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine kn-affil= affil-num=5 en-affil=Department of Cariology and Operative Dentistry, Graduate School of Medical and Dental Sciences kn-affil= affil-num=6 en-affil=Department of Restorative Dentistry, University of Washington School of Dentistry kn-affil= affil-num=7 en-affil=Department of Operative Dentistry, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Conservative Dentistry, Division of Biomaterials and Engineering, Showa University School of Dentistry kn-affil= affil-num=9 en-affil=Department for Advanced Dental Research, Center of Advanced Medicine for Dental and Oral Diseases, National Center for Geriatrics and Gerontology kn-affil= affil-num=10 en-affil=Department of Cariology and Operative Dentistry, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University kn-affil= en-keyword=Dental caries kn-keyword=Dental caries en-keyword=Dental lasers kn-keyword=Dental lasers en-keyword=Laboratory techniques and procedures kn-keyword=Laboratory techniques and procedures END start-ver=1.4 cd-journal=joma no-vol=11 cd-vols= no-issue=1 article-no= start-page=5081 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20201008 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Structural basis for energy transfer in a huge diatom PSI-FCPI supercomplex en-subtitle= kn-subtitle= en-abstract= kn-abstract=Diatom is an important group of marine algae and contributes to around 20% of the global photosynthetic carbon fixation. Photosystem I (PSI) of diatoms is associated with a large number of fucoxanthin-chlorophyll a/c proteins (FCPIs). We report the structure of PSI-FCPI from a diatom Chaetoceros gracilis at 2.38?? resolution by single-particle cryo-electron microscopy. PSI-FCPI is a monomeric supercomplex consisting of 12 core and 24 antenna subunits (FCPIs), and 326 chlorophylls a, 34 chlorophylls c, 102 fucoxanthins, 35 diadinoxanthins, 18 β-carotenes and some electron transfer cofactors. Two subunits designated PsaR and PsaS were found in the core, whereas several subunits were lost. The large number of pigments constitute a unique and huge network ensuring efficient energy harvesting, transfer and dissipation. These results provide a firm structural basis for unraveling the mechanisms of light-energy harvesting, transfer and quenching in the diatom PSI-FCPI, and also important clues to evolutionary changes of PSI-LHCI. en-copyright= kn-copyright= en-aut-name=XuCaizhe en-aut-sei=Xu en-aut-mei=Caizhe kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=PiXiong en-aut-sei=Pi en-aut-mei=Xiong kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HuangYawen en-aut-sei=Huang en-aut-mei=Yawen kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HanGuangye en-aut-sei=Han en-aut-mei=Guangye kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ChenXiaobo en-aut-sei=Chen en-aut-mei=Xiaobo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=QinXiaochun en-aut-sei=Qin en-aut-mei=Xiaochun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HuangGuoqiang en-aut-sei=Huang en-aut-mei=Guoqiang kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=ZhaoSonghao en-aut-sei=Zhao en-aut-mei=Songhao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=YangYanyan en-aut-sei=Yang en-aut-mei=Yanyan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KuangTingyun en-aut-sei=Kuang en-aut-mei=Tingyun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=WangWenda en-aut-sei=Wang en-aut-mei=Wenda kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=SuiSen-Fang en-aut-sei=Sui en-aut-mei=Sen-Fang kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=ShenJian-Ren en-aut-sei=Shen en-aut-mei=Jian-Ren kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= affil-num=1 en-affil=Photosynthesis Research Center, Key Laboratory of Photobiology, Institute of Botany, The Chinese Academy of Sciences kn-affil= affil-num=2 en-affil=State Key Laboratory of Membrane Biology, Beijing Advanced Innovation Center for Structural Biology & Frontier Research Center for Biological Structure, School of Life Sciences, Tsinghua University kn-affil= affil-num=3 en-affil=State Key Laboratory of Membrane Biology, Beijing Advanced Innovation Center for Structural Biology & Frontier Research Center for Biological Structure, School of Life Sciences, Tsinghua University kn-affil= affil-num=4 en-affil=Photosynthesis Research Center, Key Laboratory of Photobiology, Institute of Botany, The Chinese Academy of Sciences kn-affil= affil-num=5 en-affil=Photosynthesis Research Center, Key Laboratory of Photobiology, Institute of Botany, The Chinese Academy of Sciences kn-affil= affil-num=6 en-affil=School of Biological Science and Technology, University of Jinan kn-affil= affil-num=7 en-affil=State Key Laboratory of Membrane Biology, Beijing Advanced Innovation Center for Structural Biology & Frontier Research Center for Biological Structure, School of Life Sciences, Tsinghua University kn-affil= affil-num=8 en-affil=Photosynthesis Research Center, Key Laboratory of Photobiology, Institute of Botany, The Chinese Academy of Sciences kn-affil= affil-num=9 en-affil=Photosynthesis Research Center, Key Laboratory of Photobiology, Institute of Botany, The Chinese Academy of Sciences kn-affil= affil-num=10 en-affil=Photosynthesis Research Center, Key Laboratory of Photobiology, Institute of Botany, The Chinese Academy of Sciences kn-affil= affil-num=11 en-affil=Photosynthesis Research Center, Key Laboratory of Photobiology, Institute of Botany, The Chinese Academy of Sciences kn-affil= affil-num=12 en-affil=State Key Laboratory of Membrane Biology, Beijing Advanced Innovation Center for Structural Biology & Frontier Research Center for Biological Structure, School of Life Sciences, Tsinghua University kn-affil= affil-num=13 en-affil=Research Institute for Interdisciplinary Science, and Graduate School of Natural Science and Technology, Okayama University kn-affil= en-keyword=Bioenergetics kn-keyword=Bioenergetics en-keyword=Cryoelectron microscopy kn-keyword=Cryoelectron microscopy en-keyword=Photosystem I kn-keyword=Photosystem I END start-ver=1.4 cd-journal=joma no-vol=10 cd-vols= no-issue=1 article-no= start-page=17102 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20201013 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Therapeutic benefit of Muse cells in a mouse model of amyotrophic lateral sclerosis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive motor neuron loss. Muse cells are endogenous reparative pluripotent-like stem cells distributed in various tissues. They can selectively home to damaged sites after intravenous injection by sensing sphingosine-1-phosphate produced by damaged cells, then exert pleiotropic effects, including tissue protection and spontaneous differentiation into tissue-constituent cells. In G93A-transgenic ALS mice, intravenous injection of 5.0x10(4) cells revealed successful homing of human-Muse cells to the lumbar spinal cords, mainly at the pia-mater and underneath white matter, and exhibited glia-like morphology and GFAP expression. In contrast, such homing or differentiation were not recognized in human mesenchymal stem cells but were instead distributed mainly in the lung. Relative to the vehicle groups, the Muse group significantly improved scores in the rotarod, hanging-wire and muscle strength of lower limbs, recovered the number of motor neurons, and alleviated denervation and myofiber atrophy in lower limb muscles. These results suggest that Muse cells homed in a lesion site-dependent manner and protected the spinal cord against motor neuron death. Muse cells might also be a promising cell source for the treatment of ALS patients. en-copyright= kn-copyright= en-aut-name=YamashitaToru en-aut-sei=Yamashita en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KushidaYoshihiro en-aut-sei=Kushida en-aut-mei=Yoshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=WakaoShohei en-aut-sei=Wakao en-aut-mei=Shohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TadokoroKoh en-aut-sei=Tadokoro en-aut-mei=Koh kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NomuraEmi en-aut-sei=Nomura en-aut-mei=Emi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OmoteYoshio en-aut-sei=Omote en-aut-mei=Yoshio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TakemotoMami en-aut-sei=Takemoto en-aut-mei=Mami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=HishikawaNozomi en-aut-sei=Hishikawa en-aut-mei=Nozomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=OhtaYasuyuki en-aut-sei=Ohta en-aut-mei=Yasuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=DezawaMari en-aut-sei=Dezawa en-aut-mei=Mari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=AbeKoji en-aut-sei=Abe en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Stem Cell Biology and Histology, Tohoku University Graduate School of Medicine kn-affil= affil-num=3 en-affil=Department of Stem Cell Biology and Histology, Tohoku University Graduate School of Medicine kn-affil= affil-num=4 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Stem Cell Biology and Histology, Tohoku University Graduate School of Medicine kn-affil= affil-num=11 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Mesenchymal stem cells kn-keyword=Mesenchymal stem cells en-keyword=Neurological disorders kn-keyword=Neurological disorders END start-ver=1.4 cd-journal=joma no-vol=10 cd-vols= no-issue=1 article-no= start-page=17237 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20201014 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=5-aminolevulinic acid-mediated photodynamic therapy can target aggressive adult T cell leukemia/lymphoma resistant to conventional chemotherapy en-subtitle= kn-subtitle= en-abstract= kn-abstract=Photodynamic therapy (PDT) is an emerging treatment for various solid cancers. We recently reported that tumor cell lines and patient specimens from adult T cell leukemia/lymphoma (ATL) are susceptible to specific cell death by visible light exposure after a short-term culture with 5-aminolevulinic acid, indicating that extracorporeal photopheresis could eradicate hematological tumor cells circulating in peripheral blood. As a bridge from basic research to clinical trial of PDT for hematological malignancies, we here examined the efficacy of ALA-PDT on various lymphoid malignancies with circulating tumor cells in peripheral blood. We also examined the effects of ALA-PDT on tumor cells before and after conventional chemotherapy. With 16 primary blood samples from 13 patients, we demonstrated that PDT efficiently killed tumor cells without influencing normal lymphocytes in aggressive diseases such as acute ATL. Importantly, PDT could eradicate acute ATL cells remaining after standard chemotherapy or anti-CCR4 antibody, suggesting that PDT could work together with other conventional therapies in a complementary manner. The responses of PDT on indolent tumor cells were various but were clearly depending on accumulation of protoporphyrin IX, which indicates the possibility of biomarker-guided application of PDT. These findings provide important information for developing novel therapeutic strategy for hematological malignancies. en-copyright= kn-copyright= en-aut-name=SandoYasuhisa en-aut-sei=Sando en-aut-mei=Yasuhisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MatsuokaKen-Ichi en-aut-sei=Matsuoka en-aut-mei=Ken-Ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SumiiYuichi en-aut-sei=Sumii en-aut-mei=Yuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KondoTakumi en-aut-sei=Kondo en-aut-mei=Takumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=IkegawaShuntaro en-aut-sei=Ikegawa en-aut-mei=Shuntaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SugiuraHiroyuki en-aut-sei=Sugiura en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NakamuraMakoto en-aut-sei=Nakamura en-aut-mei=Makoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=IwamotoMiki en-aut-sei=Iwamoto en-aut-mei=Miki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MeguriYusuke en-aut-sei=Meguri en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=AsadaNoboru en-aut-sei=Asada en-aut-mei=Noboru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=EnnishiDaisuke en-aut-sei=Ennishi en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=NishimoriHisakazu en-aut-sei=Nishimori en-aut-mei=Hisakazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=FujiiKeiko en-aut-sei=Fujii en-aut-mei=Keiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=FujiiNobuharu en-aut-sei=Fujii en-aut-mei=Nobuharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=UtsunomiyaAtae en-aut-sei=Utsunomiya en-aut-mei=Atae kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=OkaTakashi en-aut-sei=Oka en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=MaedaYoshinobu en-aut-sei=Maeda en-aut-mei=Yoshinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= affil-num=1 en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=14 en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=15 en-affil=Department of Hematology, Imamura General Hospital kn-affil= affil-num=16 en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=17 en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=T-cell lymphoma kn-keyword=T-cell lymphoma en-keyword=Targeted therapies kn-keyword=Targeted therapies END start-ver=1.4 cd-journal=joma no-vol=10 cd-vols= no-issue=1 article-no= start-page=18550 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20201029 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Topoisomerase II beta targets DNA crossovers formed between distant homologous sites to induce chromatin opening en-subtitle= kn-subtitle= en-abstract= kn-abstract=Type II DNA topoisomerases (topo II) flip the spatial positions of two DNA duplexes, called G- and T- segments, by a cleavage-passage-resealing mechanism. In living cells, these DNA segments can be derived from distant sites on the same chromosome. Due to lack of proper methodology, however, no direct evidence has been described so far. The beta isoform of topo II (topo II beta) is essential for transcriptional regulation of genes expressed in the final stage of neuronal differentiation. Here we devise a genome-wide mapping technique (eTIP-seq) for topo II beta target sites that can measure the genomic distance between G- and T-segments. It revealed that the enzyme operates in two distinctive modes, termed proximal strand passage (PSP) and distal strand passage (DSP). PSP sites are concentrated around transcription start sites, whereas DSP sites are heavily clustered in small number of hotspots. While PSP represent the conventional topo II targets that remove local torsional stresses, DSP sites have not been described previously. Most remarkably, DSP is driven by the pairing between homologous sequences or repeats located in a large distance. A model-building approach suggested that topo II beta acts on crossovers to unknot the intertwined DSP sites, leading to chromatin decondensation. en-copyright= kn-copyright= en-aut-name=MiyajiMary en-aut-sei=Miyaji en-aut-mei=Mary kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FurutaRyohei en-aut-sei=Furuta en-aut-mei=Ryohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HosoyaOsamu en-aut-sei=Hosoya en-aut-mei=Osamu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SanoKuniaki en-aut-sei=Sano en-aut-mei=Kuniaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HaraNorikazu en-aut-sei=Hara en-aut-mei=Norikazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KuwanoRyozo en-aut-sei=Kuwano en-aut-mei=Ryozo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KangJiyoung en-aut-sei=Kang en-aut-mei=Jiyoung kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TatenoMasaru en-aut-sei=Tateno en-aut-mei=Masaru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TsutsuiKimiko M. en-aut-sei=Tsutsui en-aut-mei=Kimiko M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=TsutsuiKen en-aut-sei=Tsutsui en-aut-mei=Ken kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Molecular Genetics, Bioresource Science Branch, Center for Bioresources, Brain Research Institute, Niigata University kn-affil= affil-num=6 en-affil=Department of Molecular Genetics, Bioresource Science Branch, Center for Bioresources, Brain Research Institute, Niigata University kn-affil= affil-num=7 en-affil=Graduate School of Life Science, University of Hyogo kn-affil= affil-num=8 en-affil=Graduate School of Life Science, University of Hyogo kn-affil= affil-num=9 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=10 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Biochemistry kn-keyword=Biochemistry en-keyword=Molecular biology kn-keyword=Molecular biology END start-ver=1.4 cd-journal=joma no-vol=10 cd-vols= no-issue=1 article-no= start-page=18616 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20201029 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Capabilities of multi-pinhole SPECT with two stationary detectors for in vivo rat imaging en-subtitle= kn-subtitle= en-abstract= kn-abstract=We aimed to investigate the image quality of the U-SPECT5/CT E-Class a micro single-photon emission computed tomography (SPECT) system with two large stationary detectors for visualization of rat hearts and bones using clinically available Tc-99m-labelled tracers. Sensitivity, spatial resolution, uniformity and contrast-to-noise ratio (CNR) of the small-animal SPECT scanner were investigated in phantom studies using an ultra-high-resolution rat and mouse multi-pinhole collimator (UHR-RM). Point source, hot-rod, and uniform phantoms with Tc-99m-solution were scanned for high-count performance assessment and count levels equal to animal scans, respectively. Reconstruction was performed using the similarity-regulated ordered-subsets expectation maximization (SROSEM) algorithm with Gaussian smoothing. Rats were injected with similar to 100 MBq [Tc-99m]Tc-MIBI or similar to 150 MBq [Tc-99m]Tc-HMDP and received multi-frame micro-SPECT imaging after tracer distribution. Animal scans were reconstructed for three different acquisition times and post-processed with different sized Gaussian filters. Following reconstruction, CNR was calculated and image quality evaluated by three independent readers on a five-point scale from 1="very poor" to 5="very good". Point source sensitivity was 567 cps/MBq and radioactive rods as small as 1.2 mm were resolved with the UHR-RM collimator. Collimator-dependent uniformity was 55.5%. Phantom CNR improved with increasing rod size, filter size and activity concentration. Left ventricle and bone structures were successfully visualized in rat experiments. Image quality was strongly affected by the extent of post-filtering, whereas scan time did not have substantial influence on visual assessment. Good image quality was achieved for resolution range greater than 1.8 mm in bone and 2.8 mm in heart. The recently introduced small animal SPECT system with two stationary detectors and UHR-RM collimator is capable to provide excellent image quality in heart and bone scans in a rat using standardized reconstruction parameters and appropriate post-filtering. However, there are still challenges in achieving maximum system resolution in the sub-millimeter range with in vivo settings under limited injection dose and acquisition time. en-copyright= kn-copyright= en-aut-name=JanssenJan P. en-aut-sei=Janssen en-aut-mei=Jan P. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HoffmannJan V. en-aut-sei=Hoffmann en-aut-mei=Jan V. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KannoTakayuki en-aut-sei=Kanno en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NoseNaoko en-aut-sei=Nose en-aut-mei=Naoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=GrunzJan-Peter en-aut-sei=Grunz en-aut-mei=Jan-Peter kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OnoguchiMasahisa en-aut-sei=Onoguchi en-aut-mei=Masahisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ChenXinyu en-aut-sei=Chen en-aut-mei=Xinyu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=LapaConstantin en-aut-sei=Lapa en-aut-mei=Constantin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=BuckAndreas K. en-aut-sei=Buck en-aut-mei=Andreas K. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=HiguchiTakahiro en-aut-sei=Higuchi en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Nuclear Medicine, University Hospital W?rzburg kn-affil= affil-num=2 en-affil=Department of Nuclear Medicine, University Hospital W?rzburg kn-affil= affil-num=3 en-affil=Comprehensive Heart Failure Centre, University Hospital W?rzburg kn-affil= affil-num=4 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Diagnostic and Interventional Radiology, University Hospital W?rzburg kn-affil= affil-num=6 en-affil=Department of Quantum Medical Technology, Graduate School of Medical Sciences, Kanazawa University kn-affil= affil-num=7 en-affil=Comprehensive Heart Failure Centre, University Hospital W?rzburg kn-affil= affil-num=8 en-affil=Nuclear Medicine, Medical Faculty, University of Augsburg kn-affil= affil-num=9 en-affil=Department of Nuclear Medicine, University Hospital W?rzburg kn-affil= affil-num=10 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Biomarkers kn-keyword=Biomarkers en-keyword=Diagnostic markers kn-keyword=Diagnostic markers en-keyword=Medical research kn-keyword=Medical research en-keyword=Preclinical research kn-keyword=Preclinical research en-keyword=Translational research kn-keyword=Translational research END start-ver=1.4 cd-journal=joma no-vol=10 cd-vols= no-issue=1 article-no= start-page=18715 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20201030 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Risk of higher dose methotrexate for renal impairment in patients with rheumatoid arthritis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Renal impairment is a major concern in patients taking high-dose methotrexate (MTX) for malignancy, but it has not been fully explored in rheumatoid arthritis (RA) patients taking low-dose MTX. This study aimed to elucidate the dose-dependent effects of MTX on the renal function of patients with RA. We retrospectively reviewed 502 consecutive RA patients who were prescribed MTX for >= 1 year at Okayama University Hospital between 2006 and 2018. The primary outcome was the change in estimated glomerular filtration rate (eGFR) over 1 year. The association between MTX dosage (<8, 8-12, and >= 12 mg/week) and the change in eGFR was evaluated using multiple linear regression analysis with adjustment for possible confounding factors including age, sex, disease duration, body weight, comorbidity, baseline eGFR, concomitant treatment, and disease activity. Mean patient age was 63 years; 394 (78%) were female. Median disease duration was 77 months, while mean MTX dosage was 8.6 mg/week. The last 1-year change of eGFR (mean +/- SD) in patients treated with MTX<8 (n=186), 8-12 (n=219),>= 12 mg/week (n=97) decreased by 0.2 +/- 7.3, 0.6 +/- 8.6, and 4.5 +/- 7.9 mL/min/1.73 m(2)/year, respectively (p<0.0001). After adjustment for the confounding factors, MTX >= 12 mg/week was still correlated with a decrease in 1-year eGFR (beta-coefficient:-2.5; 95% confidence interval,-4.3 to-0.6; p=0.0089) in contrast to MTX 8-12 mg/week. Careful monitoring of renal function is required in patients with MTX >= 12 mg/week over the course of RA treatment regardless of disease duration. en-copyright= kn-copyright= en-aut-name=HayashiKeigo en-aut-sei=Hayashi en-aut-mei=Keigo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SadaKen-Ei en-aut-sei=Sada en-aut-mei=Ken-Ei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=AsanoYosuke en-aut-sei=Asano en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name= Hiramatsu AsanoSumie en-aut-sei= Hiramatsu Asano en-aut-mei=Sumie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YamamuraYuriko en-aut-sei=Yamamura en-aut-mei=Yuriko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OhashiKeiji en-aut-sei=Ohashi en-aut-mei=Keiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MorishitaMichiko en-aut-sei=Morishita en-aut-mei=Michiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=WatanabeHaruki en-aut-sei=Watanabe en-aut-mei=Haruki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NarazakiMariko en-aut-sei=Narazaki en-aut-mei=Mariko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MatsumotoYoshinori en-aut-sei=Matsumoto en-aut-mei=Yoshinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=WadaJun en-aut-sei=Wada en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Nephrology kn-keyword=Nephrology en-keyword=Rheumatology kn-keyword=Rheumatology END start-ver=1.4 cd-journal=joma no-vol=10 cd-vols= no-issue=1 article-no= start-page=19087 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20201105 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Cell cycle dependence of apoptosis photo-triggered using peptide-photosensitizer conjugate en-subtitle= kn-subtitle= en-abstract= kn-abstract=Investigation of the relevance between cell cycle status and the bioactivity of exogenously delivered biomacromolecules is hindered by their time-consuming cell internalization and the cytotoxicity of transfection methods. In this study, we addressed these problems by utilizing the photochemical internalization (PCI) method using a peptide/protein-photosensitizer conjugate, which enables immediate cytoplasmic internalization of the bioactive peptides/proteins in a light-dependent manner with low cytotoxicity. To identify the cell-cycle dependent apoptosis, a TatBim peptide-photosensitizer conjugate (TatBim-PS) with apoptotic activity was photo-dependently internalized into HeLa cells expressing a fluorescent ubiquitination-based cell cycle indicator (Fucci2). Upon irradiation, cytoplasmic TatBim-PS internalization exceeded 95% for all cells classified in the G(1), S, and G(2)/M cell cycle phases with no significant differences between groups. TatBim-PS-mediated apoptosis was more efficiently triggered by photoirradiation in the G(1)/S transition than in the G(1) and S/G(2)/M phases, suggesting high sensitivity of the former phase to Bim-induced apoptosis. Thus, the cell cycle dependence of Bim peptide-induced apoptosis was successfully investigated using Fucci2 indicator and the PCI method. Since PCI-mediated cytoplasmic internalization of peptides is rapid and does not span multiple cell cycle phases, the Fucci-PCI method constitutes a promising tool for analyzing the cell cycle dependence of peptides/protein functions. en-copyright= kn-copyright= en-aut-name=KimHyungjin en-aut-sei=Kim en-aut-mei=Hyungjin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=WatanabeSho en-aut-sei=Watanabe en-aut-mei=Sho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KitamatsuMizuki en-aut-sei=Kitamatsu en-aut-mei=Mizuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=WatanabeKazunori en-aut-sei=Watanabe en-aut-mei=Kazunori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OhtsukiTakashi en-aut-sei=Ohtsuki en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=2 en-affil=Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=3 en-affil=Department of Applied Chemistry, Kindai University kn-affil= affil-num=4 en-affil=Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=5 en-affil=Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= en-keyword=Biological techniques kn-keyword=Biological techniques en-keyword=Biotechnology kn-keyword=Biotechnology END start-ver=1.4 cd-journal=joma no-vol=11 cd-vols= no-issue=1 article-no= start-page=5627 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20201106 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Establishment of Neurospora crassa as a model organism for fungal virology en-subtitle= kn-subtitle= en-abstract= kn-abstract=The filamentous fungus Neurospora crassa is used as a model organism for genetics, developmental biology and molecular biology. Remarkably, it is not known to host or to be susceptible to infection with any viruses. Here, we identify diverse RNA viruses in N. crassa and other Neurospora species, and show that N. crassa supports the replication of these viruses as well as some viruses from other fungi. Several encapsidated double-stranded RNA viruses and capsid-less positive-sense single-stranded RNA viruses can be experimentally introduced into N. crassa protoplasts or spheroplasts. This allowed us to examine viral replication and RNAi-mediated antiviral responses in this organism. We show that viral infection upregulates the transcription of RNAi components, and that Dicer proteins (DCL-1, DCL-2) and an Argonaute (QDE-2) participate in suppression of viral replication. Our study thus establishes N. crassa as a model system for the study of host-virus interactions. The fungus Neurospora crassa is a model organism for the study of various biological processes, but it is not known to be infected by any viruses. Here, Honda et al. identify RNA viruses that infect N. crassa and examine viral replication and RNAi-mediated antiviral responses, thus establishing this fungus as a model for the study of host-virus interactions. en-copyright= kn-copyright= en-aut-name=HondaShinji en-aut-sei=Honda en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=Eusebio-CopeAna en-aut-sei=Eusebio-Cope en-aut-mei=Ana kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MiyashitaShuhei en-aut-sei=Miyashita en-aut-mei=Shuhei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YokoyamaAyumi en-aut-sei=Yokoyama en-aut-mei=Ayumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=AuliaAnnisa en-aut-sei=Aulia en-aut-mei=Annisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ShahiSabitree en-aut-sei=Shahi en-aut-mei=Sabitree kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KondoHideki en-aut-sei=Kondo en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SuzukiNobuhiro en-aut-sei=Suzuki en-aut-mei=Nobuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Faculty of Medical Sciences, University of Fukui kn-affil= affil-num=2 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=3 en-affil=Graduate School of Agricultural Science, Tohoku University kn-affil= affil-num=4 en-affil=Faculty of Medical Sciences, University of Fukui kn-affil= affil-num=5 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=6 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=7 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=8 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= en-keyword=Fungal biology kn-keyword=Fungal biology en-keyword=Virus?host interactions kn-keyword=Virus?host interactions END start-ver=1.4 cd-journal=joma no-vol=10 cd-vols= no-issue=1 article-no= start-page=19959 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20201117 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Follistatin expressed in mechanically-damaged salivary glands of male mice induces proliferation of CD49f(+) cells en-subtitle= kn-subtitle= en-abstract= kn-abstract=Salivary glands (SGs) are very important for maintaining the physiological functions of the mouth. When SGs regenerate and repair from various damages, including mechanical, radiological, and immune diseases, acinar and granular duct cells originate from intercalated duct cells. However, the recovery is often insufficient because of SGs' limited self-repair function. Furthermore, the precise repair mechanism has been unclear. Here, we focused on CD49f, one of the putative stem cell markers, and characterized CD49f positive cells (CD49f(+) cells) isolated from male murine SGs. CD49f(+) cells possess self-renewal ability and express epithelial and pluripotent markers. Compared to CD49f negative cells, freshly isolated CD49f(+) cells highly expressed inhibin beta A and beta B, which are components of activin that has anti-proliferative effects. Notably, an inhibitor of activin, follistatin was expressed in mechanically-damaged SGs, meanwhile no follistatin was expressed in normal SGs in vivo. Moreover, sub-cultured CD49f(+) cells highly expressed both Follistatin and a series of proliferative genes, expressions of which were decreased by Follistatin siRNA. These findings indicated that the molecular interaction between activin and follistatin may induce CD49f(+) cells proliferation in the regeneration and repair of mouse SGs. en-copyright= kn-copyright= en-aut-name=IkedaA. en-aut-sei=Ikeda en-aut-mei=A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YamamotoT. en-aut-sei=Yamamoto en-aut-mei=T. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MineshibaJ. en-aut-sei=Mineshiba en-aut-mei=J. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TakashibaS. en-aut-sei=Takashiba en-aut-mei=S. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Department of Periodontics and Endodontics, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Pathophysiology - Periodontal Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Hanamizuki Dental Clinic kn-affil= affil-num=4 en-affil=Department of Pathophysiology ? Periodontal Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= END start-ver=1.4 cd-journal=joma no-vol=10 cd-vols= no-issue=1 article-no= start-page=20698 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20201126 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Mirtazapine exerts astrocyte-mediated dopaminergic neuroprotection en-subtitle= kn-subtitle= en-abstract= kn-abstract=Mirtazapine, a noradrenergic and specific serotonergic antidepressant (NaSSA), is known to activate serotonin (5-HT) 1A receptor. Our recent study demonstrated that stimulation of astrocytic 5-HT1A receptors promoted astrocyte proliferation and upregulated antioxidative property in astrocytes to protect dopaminergic neurons against oxidative stress. Here, we evaluated the neuroprotective effects of mirtazapine against dopaminergic neurodegeneration in models of Parkinson's disease (PD). Mirtazapine administration attenuated the loss of dopaminergic neurons in the substantia nigra and increased the expression of the antioxidative molecule metallothionein (MT) in the striatal astrocytes of 6-hydroxydopamine (6-OHDA)-injected parkinsonian mice via 5-HT1A receptors. Mirtazapine protected dopaminergic neurons against 6-OHDA-induced neurotoxicity in mesencephalic neuron and striatal astrocyte cocultures, but not in enriched neuronal cultures. Mirtazapine-treated neuron-conditioned medium (Mir-NCM) induced astrocyte proliferation and upregulated MT expression via 5-HT1A receptors on astrocytes. Furthermore, treatment with medium from Mir-NCM-treated astrocytes protected dopaminergic neurons against 6-OHDA neurotoxicity, and these effects were attenuated by treatment with a MT-1/2-specific antibody or 5-HT1A antagonist. Our study suggests that mirtazapine could be an effective disease-modifying drug for PD and highlights that astrocytic 5-HT1A receptors may be a novel target for the treatment of PD. en-copyright= kn-copyright= en-aut-name=KikuokaRyo en-aut-sei=Kikuoka en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MiyazakiIkuko en-aut-sei=Miyazaki en-aut-mei=Ikuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KubotaNatsuki en-aut-sei=Kubota en-aut-mei=Natsuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MaedaMegumi en-aut-sei=Maeda en-aut-mei=Megumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KagawaDaiki en-aut-sei=Kagawa en-aut-mei=Daiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MoriyamaMasaaki en-aut-sei=Moriyama en-aut-mei=Masaaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SatoAsuka en-aut-sei=Sato en-aut-mei=Asuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MurakamiShinki en-aut-sei=Murakami en-aut-mei=Shinki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KitamuraYoshihisa en-aut-sei=Kitamura en-aut-mei=Yoshihisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=SendoToshiaki en-aut-sei=Sendo en-aut-mei=Toshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=AsanumaMasato en-aut-sei=Asanuma en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Clinical Pharmacy, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Clinical Pharmacy, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= END start-ver=1.4 cd-journal=joma no-vol=10 cd-vols= no-issue=1 article-no= start-page=20857 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20201130 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Lokiarchaeota archaeon schizorhodopsin-2 (LaSzR2) is an inward proton pump displaying a characteristic feature of acid-induced spectral blue-shift en-subtitle= kn-subtitle= en-abstract= kn-abstract=The photoreactive protein rhodopsin is widespread in microorganisms and has a variety of photobiological functions. Recently, a novel phylogenetically distinctive group named 'schizorhodopsin (SzR)' has been identified as an inward proton pump. We performed functional and spectroscopic studies on an uncharacterised schizorhodopsin from the phylum Lokiarchaeota archaeon. The protein, LaSzR2, having an all-trans-retinal chromophore, showed inward proton pump activity with an absorption maximum at 549 nm. The pH titration experiments revealed that the protonated Schiff base of the retinal chromophore (Lys188, pK(a)=12.3) is stabilised by the deprotonated counterion (presumably Asp184, pK(a)=3.7). The flash-photolysis experiments revealed the presence of two photointermediates, K and M. A proton was released and uptaken from bulk solution upon the formation and decay of the M intermediate. During the M-decay, the Schiff base was reprotonated by the proton from a proton donating residue (presumably Asp172). These properties were compared with other inward (SzRs and xenorhodopsins, XeRs) and outward proton pumps. Notably, LaSzR2 showed acid-induced spectral 'blue-shift' due to the protonation of the counterion, whereas outward proton pumps showed opposite shifts (red-shifts). Thus, we can distinguish between inward and outward proton pumps by the direction of the acid-induced spectral shift. en-copyright= kn-copyright= en-aut-name=KojimaKeiichi en-aut-sei=Kojima en-aut-mei=Keiichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YoshizawaSusumu en-aut-sei=Yoshizawa en-aut-mei=Susumu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HasegawaMasumi en-aut-sei=Hasegawa en-aut-mei=Masumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NakamaMasaki en-aut-sei=Nakama en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KuriharaMarie en-aut-sei=Kurihara en-aut-mei=Marie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KikukawaTakashi en-aut-sei=Kikukawa en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SudoYuki en-aut-sei=Sudo en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Atmosphere and Ocean Research Institute, The University of Tokyo kn-affil= affil-num=3 en-affil=Atmosphere and Ocean Research Institute, The University of Tokyo kn-affil= affil-num=4 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Faculty of Advanced Life Science, Hokkaido University kn-affil= affil-num=7 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=10 cd-vols= no-issue=1 article-no= start-page=21497 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20201209 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Effect of rhegmatogenous retinal detachment on preoperative and postoperative retinal sensitivities en-subtitle= kn-subtitle= en-abstract= kn-abstract=This retrospective study investigated foveal and perifoveal retinal sensitivities using microperimetry before and after surgery for rhegmatogenous retinal detachment (RRD). Consecutive patients with RRD who underwent vitrectomy or scleral buckling were included. Comprehensive ophthalmological examinations, including microperimetry and swept-source optical coherence tomography, were performed before and 6 months after surgery. Pre- and postoperative retinal sensitivities at the fovea and 4 perifoveal measurement points farthest from the fixation point, both vertically and horizontally (superior, inferior, nasal, and temporal) were examined. A total of 34 foveal and 136 perifoveal measurement points in 34 eyes of 34 patients were evaluated. The postoperative retinal sensitivity was significantly higher than the preoperative value at foveal and perifoveal points with (P<0.001 for both) and without (fovea: P=0.005, perifovea: P<0.001) RRD. The postoperative retinal sensitivity was significantly lower at foveal (P<0.01) and perifoveal (P<0.001) points with preoperative RRD than at points without preoperative RRD; furthermore, it was significantly better at points with ellipsoid zone (Ez) continuity than at points with Ez discontinuity (fovea: P<0.01, perifovea: P<0.001). RRD deteriorates retinal sensitivity, regardless of its presence or absence at the measurement point before surgery. Postoperative Ez continuity is important for good postoperative retinal sensitivity. en-copyright= kn-copyright= en-aut-name=NodaHiroshi en-aut-sei=Noda en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KimuraShuhei en-aut-sei=Kimura en-aut-mei=Shuhei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=Hosokawa MorizaneMio en-aut-sei=Hosokawa Morizane en-aut-mei=Mio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ShiodeYusuke en-aut-sei=Shiode en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=DoiShinichiro en-aut-sei=Doi en-aut-mei=Shinichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TakahashiKosuke en-aut-sei=Takahashi en-aut-mei=Kosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MatobaRyo en-aut-sei=Matoba en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KanzakiYuki en-aut-sei=Kanzaki en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=FujiwaraAtsushi en-aut-sei=Fujiwara en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MorizaneYuki en-aut-sei=Morizane en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= END start-ver=1.4 cd-journal=joma no-vol=10 cd-vols= no-issue=1 article-no= start-page=21578 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20201209 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Radiographic and clinical assessment of unidirectional porous hydroxyapatite to treat benign bone tumors en-subtitle= kn-subtitle= en-abstract= kn-abstract=Unidirectional porous hydroxyapatite (UDPHAp) was developed as an excellent scaffold with unidirectional pores oriented in the horizontal direction with interpore connections. The purpose of this study was to assess radiographic changes and clinical outcomes and complications following UDPHAp implantation to treat benign bone tumors. We retrospectively analyzed 44 patients treated with intralesional resection and UDPHAp implantation for benign bone tumors between 2010 and 2015. Clinical and radiographic findings were evaluated postoperatively at regular follow-up visits. The mean follow-up was 49 months. Radiographic changes were classified into five stages based on bone formation in the implanted UDPHAp according to Tamai's classification. All patients showed excellent bone formation inside and around implanted UDPHAp. Absorption of UDPHAp and bone marrow cavity remodeling was identified in 20 patients at a mean of 17 months postoperatively, and was significantly more common in young patients. Preoperative cortical thinning was completely regenerated in 26 of 31 patients on average 10 months after surgery. There were no cases of delayed wound healing, postoperative infection, or allergic reaction related to implanted UDPHAp. UDPHAp is a useful bone-filling substitute for treating benign bone tumor, and the use of this material has a low complication rate. en-copyright= kn-copyright= en-aut-name=KunisadaToshiyuki en-aut-sei=Kunisada en-aut-mei=Toshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HaseiJoe en-aut-sei=Hasei en-aut-mei=Joe kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=FujiwaraTomohiro en-aut-sei=Fujiwara en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NakataEiji en-aut-sei=Nakata en-aut-mei=Eiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YokooSuguru en-aut-sei=Yokoo en-aut-mei=Suguru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=DemiyaKoji en-aut-sei=Demiya en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=OzakiToshifumi en-aut-sei=Ozaki en-aut-mei=Toshifumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= END start-ver=1.4 cd-journal=joma no-vol=11 cd-vols= no-issue=1 article-no= start-page=1693 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=20210118 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Fibroblast activation protein targeted near infrared photoimmunotherapy (NIR PIT) overcomes therapeutic resistance in human esophageal cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=Cancer-associated fibroblasts (CAFs) have an important role in the tumor microenvironment. CAFs have the multifunctionality which strongly support cancer progression and the acquisition of therapeutic resistance by cancer cells. Near-infrared photoimmunotherapy (NIR-PIT) is a novel cancer treatment that uses a highly selective monoclonal antibody (mAb)-photosensitizer conjugate. We developed fibroblast activation protein (FAP)-targeted NIR-PIT, in which IR700 was conjugated to a FAP-specific antibody to target CAFs (CAFs-targeted NIR-PIT: CAFs-PIT). Thus, we hypothesized that the control of CAFs could overcome the resistance to conventional chemotherapy in esophageal cancer (EC). In this study, we evaluated whether EC cell acquisition of stronger malignant characteristics and refractoriness to chemoradiotherapy are mediated by CAFs. Next, we assessed whether the resistance could be rescued by eliminating CAF stimulation by CAFs-PIT in vitro and in vivo. Cancer cells acquired chemoradiotherapy resistance via CAF stimulation in vitro and 5-fluorouracil (FU) resistance in CAF-coinoculated tumor models in vivo. CAF stimulation promoted the migration/invasion of cancer cells and a stem-like phenotype in vitro, which were rescued by elimination of CAF stimulation. CAFs-PIT had a highly selective effect on CAFs in vitro. Finally, CAF elimination by CAFs-PIT in vivo demonstrated that the combination of 5-FU and NIR-PIT succeeded in producing 70.9% tumor reduction, while 5-FU alone achieved only 13.3% reduction, suggesting the recovery of 5-FU sensitivity in CAF-rich tumors. In conclusion, CAFs-PIT could overcome therapeutic resistance via CAF elimination. The combined use of novel targeted CAFs-PIT with conventional anticancer treatments can be expected to provide a more effective and sensible treatment strategy. en-copyright= kn-copyright= en-aut-name=KatsubeRyoichi en-aut-sei=Katsube en-aut-mei=Ryoichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NomaKazuhiro en-aut-sei=Noma en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OharaToshiaki en-aut-sei=Ohara en-aut-mei=Toshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NishiwakiNoriyuki en-aut-sei=Nishiwaki en-aut-mei=Noriyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KobayashiTeruki en-aut-sei=Kobayashi en-aut-mei=Teruki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KomotoSatoshi en-aut-sei=Komoto en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SatoHiroaki en-aut-sei=Sato en-aut-mei=Hiroaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KashimaHajime en-aut-sei=Kashima en-aut-mei=Hajime kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KatoTakuya en-aut-sei=Kato en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KikuchiSatoru en-aut-sei=Kikuchi en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=TazawaHiroshi en-aut-sei=Tazawa en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=KagawaShunsuke en-aut-sei=Kagawa en-aut-mei=Shunsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=ShirakawaYasuhiro en-aut-sei=Shirakawa en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=KobayashiHisataka en-aut-sei=Kobayashi en-aut-mei=Hisataka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=FujiwaraToshiyoshi en-aut-sei=Fujiwara en-aut-mei=Toshiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= affil-num=1 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=14 en-affil=Molecular Imaging Program, Center for Cancer Research, National Cancer Institute, US National Institutes of Health kn-affil= affil-num=15 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= END start-ver=1.4 cd-journal=joma no-vol=11 cd-vols= no-issue=1 article-no= start-page=2284 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=20210127 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Quantification of patellar tendon reflex using portable mechanomyography and electromyography devices en-subtitle= kn-subtitle= en-abstract= kn-abstract=Deep tendon reflexes are one of the main components of the clinical nervous system examinations. These assessments are inexpensive and quick. However, evaluation can be subjective and qualitative. This study aimed to objectively evaluate hyperreflexia of the patellar tendon reflex using portable mechanomyography (MMG) and electromyography (EMG) devices. This study included 10 preoperative patients (20 legs) who had a pathology that could cause bilateral patellar tendon hyperreflexia and 12 healthy volunteers (24 legs) with no prior history of neurological disorders. We attached MMG/EMG sensors onto the quadriceps and tapped the patellar tendon with maximal and constant force. Our results showed a significantly high amplitude of the root mean square (RMS) and low frequency of the mean power frequency (MPF) in the rectus femoris, vastus medialis, and vastus lateralis muscles in both EMG and MMG with both maximal and constant force. Especially in the patients with cervical and thoracic myelopathy, the receiver operating characteristic (ROC) curve for diagnosing hyperreflexia of the patellar tendon showed a moderate to very high area under the curve for all EMG-RMS, EMG-MPF, MMG-RMS, and MMG-MPF values. The use of EMG and MMG for objectively quantifying the patellar tendon reflex is simple and desirable for future clinical applications and could help diagnose neurological disorders. en-copyright= kn-copyright= en-aut-name=TsujiHironori en-aut-sei=Tsuji en-aut-mei=Hironori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MisawaHaruo en-aut-sei=Misawa en-aut-mei=Haruo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TakigawaTomoyuki en-aut-sei=Takigawa en-aut-mei=Tomoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TetsunagaTomoko en-aut-sei=Tetsunaga en-aut-mei=Tomoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YamaneKentaro en-aut-sei=Yamane en-aut-mei=Kentaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OdaYoshiaki en-aut-sei=Oda en-aut-mei=Yoshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=OzakiToshifumi en-aut-sei=Ozaki en-aut-mei=Toshifumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Orthopaedic Surgery, Dentistry, and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=2 en-affil=Department of Orthopaedic Surgery, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Orthopaedic Surgery, Kobe Red Cross Hospital kn-affil= affil-num=4 en-affil=Department of Orthopaedic Surgery, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Orthopaedic Surgery, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Orthopaedic Surgery, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Orthopaedic Surgery, Dentistry, and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= END start-ver=1.4 cd-journal=joma no-vol=11 cd-vols= no-issue=1 article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=20210304 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Exploratory classification of clinical phenotypes in Japanese patients with antineutrophil cytoplasmic antibody-associated vasculitis using cluster analysis en-subtitle= kn-subtitle= en-abstract= kn-abstract=A novel patient cluster in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) may be identified in Japan. We performed multiple correspondence and cluster analysis regarding 427 clinically diagnosed AAV patients excluding eosinophilic granulomatosis with polyangiitis. Model 1 included the ANCA phenotype, items of the Birmingham Vasculitis Activity Score, and interstitial lung disease; model 2 included serum creatinine (s-Cr) and C-reactive protein (CRP) levels with model 1 components. In seven clusters determined in model 1, the ANCA-negative (n=8) and proteinase 3-ANCA-positive (n=41) groups emerged as two distinct clusters. The other five myeloperoxidase-ANCA-positive clusters were characterized by ear, nose, and throat (ENT) (n=47); cutaneous (n=36); renal (n=256), non-renal (n=33); and both ENT and cutaneous symptoms (n=6). Four clusters in model 2 were characterized by myeloperoxidase-ANCA negativity (n=42), without s-Cr elevation (<1.3 mg/dL) (n=157), s-Cr elevation (1.3 mg/dL) with high CRP (>10 mg/dL) (n=71), or s-Cr elevation (>= 1.3 mg/dL) without high CRP (<= 10 mg/dL) (n=157). Overall, renal, and relapse-free survival rates were significantly different across the four clusters in model 2. ENT, cutaneous, and renal symptoms may be useful in characterization of Japanese AAV patients with myeloperoxidase-ANCA. The combination of s-Cr and CRP levels may be predictive of prognosis. en-copyright= kn-copyright= en-aut-name=WatanabeHaruki en-aut-sei=Watanabe en-aut-mei=Haruki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SadaKen-ei en-aut-sei=Sada en-aut-mei=Ken-ei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HarigaiMasayoshi en-aut-sei=Harigai en-aut-mei=Masayoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=AmanoKoichi en-aut-sei=Amano en-aut-mei=Koichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=DobashiHiroaki en-aut-sei=Dobashi en-aut-mei=Hiroaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TakasakiYoshinari en-aut-sei=Takasaki en-aut-mei=Yoshinari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=FujimotoShouichi en-aut-sei=Fujimoto en-aut-mei=Shouichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=AtsumiTatsuya en-aut-sei=Atsumi en-aut-mei=Tatsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=YamagataKunihiro en-aut-sei=Yamagata en-aut-mei=Kunihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=HommaSakae en-aut-sei=Homma en-aut-mei=Sakae kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=ArimuraYoshihiro en-aut-sei=Arimura en-aut-mei=Yoshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=MakinoHirofumi en-aut-sei=Makino en-aut-mei=Hirofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=Research Committee of Intractable Vasculitis Syndrome (JPVAS) & Research Committee of Intractable Renal Disease of the Ministry of Health, Labour, and Welfare of Japan en-aut-sei=Research Committee of Intractable Vasculitis Syndrome (JPVAS) & Research Committee of Intractable Renal Disease of the Ministry of Health, Labour, and Welfare of Japan en-aut-mei= kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= affil-num=1 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Rheumatology, Tokyo Women’s Medical University School of Medicine kn-affil= affil-num=4 en-affil=Department of Rheumatology and Clinical Immunology, Saitama Medical Center, Saitama Medical University kn-affil= affil-num=5 en-affil=Division of Hematology, Rheumatology and Respiratory Medicine, Department of Internal Medicine, Faculty of Medicine, Kagawa University kn-affil= affil-num=6 en-affil=Department of Internal Medicine and Rheumatology, Juntendo University School of Medicine kn-affil= affil-num=7 en-affil=Department of Hemovascular Medicine and Artificial Organs, Faculty of Medicine, University of Miyazaki kn-affil= affil-num=8 en-affil=Department of Rheumatology, Endocrinology and Nephrology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University kn-affil= affil-num=9 en-affil=Department of Nephrology, Faculty of Medicine, University of Tsukuba kn-affil= affil-num=10 en-affil=Department of Advanced and Integrated Interstitial Lung Diseases Research, School of Medicine, Toho University kn-affil= affil-num=11 en-affil=Department of Nephrology and Rheumatology, Kyorin University School of Medicine kn-affil= affil-num=12 en-affil=Okayama University kn-affil= affil-num=13 en-affil= kn-affil= END start-ver=1.4 cd-journal=joma no-vol=11 cd-vols= no-issue=1 article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=20210401 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Endoscopic resection is a suitable initial treatment strategy for oxyntic gland adenoma or gastric adenocarcinoma of the fundic gland type en-subtitle= kn-subtitle= en-abstract= kn-abstract=The aim of this study was to reveal the histological features of oxyntic gland adenomas and gastric adenocarcinoma of the fundic-gland type (GA-FG). We retrospectively examined the histological features of 126 lesions of oxyntic gland adenoma and/or GA-FG in 116 patients. The prevalence of oxyntic gland adenomas and GA-FG was approximately equal. The majority of the lesions were resected by endoscopic mucosal resection using a diathermic snare (EMR, n=42) or endoscopic submucosal dissection (ESD, n=72). Histologically, there were no lesions with invasion at the level of the muscularis propria or deeper, and lymphovascular invasion was present in 1.6%. Of the ESD and EMR specimens, there were no lesions that were positive for vertical margins. Among the eight GA-FG patients with deep (>= 500 mu m) submucosal invasion, six were treated with endoscopic resection alone, and no recurrence was documented. No patients died of the disease during the median follow-up period of 14.5 months. In conclusion, all lesions were confined to the mucosa or submucosa and were negative for vertical margins. Lymphovascular invasion was present in only 1.6% of the patients. Thus, we believe that endoscopic resection is a suitable initial treatment method for oxyntic gland adenoma and GA-FG. en-copyright= kn-copyright= en-aut-name=IwamuroMasaya en-aut-sei=Iwamuro en-aut-mei=Masaya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KusumotoChiaki en-aut-sei=Kusumoto en-aut-mei=Chiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NakagawaMasahiro en-aut-sei=Nakagawa en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KobayashiSayo en-aut-sei=Kobayashi en-aut-mei=Sayo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YoshiokaMasao en-aut-sei=Yoshioka en-aut-mei=Masao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=InabaTomoki en-aut-sei=Inaba en-aut-mei=Tomoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ToyokawaTatsuya en-aut-sei=Toyokawa en-aut-mei=Tatsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=HoriShinichiro en-aut-sei=Hori en-aut-mei=Shinichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TanakaShouichi en-aut-sei=Tanaka en-aut-mei=Shouichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MatsuedaKazuhiro en-aut-sei=Matsueda en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=TanakaTakehiro en-aut-sei=Tanaka en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=OkadaHiroyuki en-aut-sei=Okada en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Gastroenterology, Nippon Kokan Fukuyama Hospital kn-affil= affil-num=3 en-affil=Department of Internal Medicine, Hiroshima City Hospital kn-affil= affil-num=4 en-affil=Department of Internal Medicine, Fukuyama City Hospital kn-affil= affil-num=5 en-affil=Department of Internal Medicine, Okayama Saiseikai General Hospital kn-affil= affil-num=6 en-affil=Department of Gastroenterology, Kagawa Prefectural Central Hospital kn-affil= affil-num=7 en-affil=Department of Gastroenterology, Fukuyama Medical Center kn-affil= affil-num=8 en-affil=Department of Endoscopy, National Hospital Organization Shikoku Cancer Center kn-affil= affil-num=9 en-affil=Department of Gastroenterology, Iwakuni Clinical Center kn-affil= affil-num=10 en-affil=Department of Gastroenterology and Hepatology, Kurashiki Central Hospital kn-affil= affil-num=11 en-affil=Department of Pathology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= END start-ver=1.4 cd-journal=joma no-vol=11 cd-vols= no-issue=1 article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=20210407 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=En face image-based classification of diabetic macular edema using swept source optical coherence tomography en-subtitle= kn-subtitle= en-abstract= kn-abstract=This retrospective study was performed to classify diabetic macular edema (DME) based on the localization and area of the fluid and to investigate the relationship of the classification with visual acuity (VA). The fluid was visualized using en face optical coherence tomography (OCT) images constructed using swept-source OCT. A total of 128 eyes with DME were included. The retina was segmented into: Segment 1, mainly comprising the inner nuclear layer and outer plexiform layer, including Henle's fiber layer; and Segment 2, mainly comprising the outer nuclear layer. DME was classified as: foveal cystoid space at Segment 1 and no fluid at Segment 2 (n=24), parafoveal cystoid space at Segment 1 and no fluid at Segment 2 (n=25), parafoveal cystoid space at Segment 1 and diffuse fluid at Segment 2 (n=16), diffuse fluid at both segments (n=37), and diffuse fluid at both segments with subretinal fluid (n=26). Eyes with diffuse fluid at Segment 2 showed significantly poorer VA, higher ellipsoid zone disruption rates, and greater central subfield thickness than did those without fluid at Segment 2 (P<0.001 for all). These results indicate the importance of the localization and area of the fluid for VA in DME. en-copyright= kn-copyright= en-aut-name=FujiwaraAtsushi en-aut-sei=Fujiwara en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KanzakiYuki en-aut-sei=Kanzaki en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KimuraShuhei en-aut-sei=Kimura en-aut-mei=Shuhei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HosokawaMio en-aut-sei=Hosokawa en-aut-mei=Mio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ShiodeYusuke en-aut-sei=Shiode en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=DoiShinichiro en-aut-sei=Doi en-aut-mei=Shinichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TakahashiKosuke en-aut-sei=Takahashi en-aut-mei=Kosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MatobaRyo en-aut-sei=Matoba en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MorizaneYuki en-aut-sei=Morizane en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= END start-ver=1.4 cd-journal=joma no-vol=11 cd-vols= no-issue=1 article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=20210419 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Endonuclease increases efficiency of osteoblast isolation from murine calvariae en-subtitle= kn-subtitle= en-abstract= kn-abstract=Bone is a highly dynamic organ that undergoes remodeling equally regulated by osteoblast-mediated bone formation and osteoclast-mediated bone resorption. To clarify the regulation of osteoblastogenesis, primary murine osteoblasts are required for an in vitro study. Primary osteoblasts are isolated from neonatal calvariae through digestion with collagenase. However, the number of cells collected from one pup is not sufficient for further in vitro experiments, leading to an increase in the use of euthanized pups. We hypothesized that the viscosity of digested calvariae and digestion solution supplemented with collagenase results in cell clumping and reduction of isolated cells from bones. We simply added Benzonase, a genetically engineered endonuclease that shears all forms of DNAs/RNAs, in order to reduce nucleic acid-mediated viscosity. We found that addition of Benzonase increased the number of collected osteoblasts by three fold compared to that without Benzonase through reduction of viscosity. Additionally, Benzonase has no effect on cellular identity and function. The new osteoblast isolation protocol with Benzonase minimizes the number of neonatal pups required for an in vitro study and expands the concept that isolation of other populations of cells including osteocytes that are difficult to be purified could be modified by Benzonase. en-copyright= kn-copyright= en-aut-name=AsanoYosuke en-aut-sei=Asano en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MatsumotoYoshinori en-aut-sei=Matsumoto en-aut-mei=Yoshinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=La RoseRose, Jose en-aut-sei=La Rose en-aut-mei=Rose, Jose kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HeFang en-aut-sei=He en-aut-mei=Fang kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KatsuyamaTakayuki en-aut-sei=Katsuyama en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ZiyiWang en-aut-sei=Ziyi en-aut-mei=Wang kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TsujiShigetomo en-aut-sei=Tsuji en-aut-mei=Shigetomo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KamiokaHiroshi en-aut-sei=Kamioka en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=RottapelRobert en-aut-sei=Rottapel en-aut-mei=Robert kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=WadaJun en-aut-sei=Wada en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Princess Margaret Cancer Center, University Health Network, University of Toronto kn-affil= affil-num=4 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Orthodontics, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Orthodontics, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Orthodontics, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Princess Margaret Cancer Center, University Health Network, University of Toronto kn-affil= affil-num=10 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= END start-ver=1.4 cd-journal=joma no-vol=11 cd-vols= no-issue=1 article-no= start-page=10223 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=20210513 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Histidine-rich glycoprotein as a prognostic biomarker for sepsis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Various biomarkers have been proposed for sepsis; however, only a few become the standard. We previously reported that plasma histidine-rich glycoprotein (HRG) levels decreased in septic mice, and supplemental infusion of HRG improved survival in mice model of sepsis. Moreover, our previous clinical study demonstrated that HRG levels in septic patients were lower than those in noninfective systemic inflammatory response syndrome patients, and it could be a biomarker for sepsis. In this study, we focused on septic patients and assessed the differences in HRG levels between the non-survivors and survivors. We studied ICU patients newly diagnosed with sepsis. Blood samples were collected within 24 h of ICU admission, and HRG levels were determined using an enzyme-linked immunosorbent assay. Ninety-nine septic patients from 11 institutes in Japan were included. HRG levels were significantly lower in non-survivors (n=16) than in survivors (n=83) (median, 15.1 [interquartile ranges, 12.7-16.6] vs. 30.6 [22.1-39.6] mu g/ml; p<0.01). Survival analysis revealed that HRG levels were associated with mortality (hazard ratio 0.79, p<0.01), and the Harrell C-index (predictive power) for HRG was 0.90. These results suggested that HRG could be a novel prognostic biomarker for sepsis. en-copyright= kn-copyright= en-aut-name=KurodaKosuke en-aut-sei=Kuroda en-aut-mei=Kosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=IshiiKenzo en-aut-sei=Ishii en-aut-mei=Kenzo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MiharaYuko en-aut-sei=Mihara en-aut-mei=Yuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KawanoueNaoya en-aut-sei=Kawanoue en-aut-mei=Naoya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=WakeHidenori en-aut-sei=Wake en-aut-mei=Hidenori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MoriShuji en-aut-sei=Mori en-aut-mei=Shuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YoshidaMichihiro en-aut-sei=Yoshida en-aut-mei=Michihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NishiboriMasahiro en-aut-sei=Nishibori en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MorimatsuHiroshi en-aut-sei=Morimatsu en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Anesthesiology, Fukuyama City Hospital kn-affil= affil-num=3 en-affil=Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Pharmacology, Faculty of Medicine, Kindai University kn-affil= affil-num=6 en-affil=Department of Pharmacology, School of Pharmacy, Shujitsu University kn-affil= affil-num=7 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= END start-ver=1.4 cd-journal=joma no-vol=4 cd-vols= no-issue=1 article-no= start-page=76 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=20210524 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Halogen-sodium exchange enables efficient access to organosodium compounds en-subtitle= kn-subtitle= en-abstract= kn-abstract=With sodium being the most abundant alkali metal on Earth, organosodium compounds are an attractive choice for sustainable chemical synthesis. However, organosodium compounds are rarely used-and are overshadowed by organolithium compounds-because of a lack of convenient and efficient preparation methods. Here we report a halogen-sodium exchange method to prepare a large variety of (hetero)aryl- and alkenylsodium compounds including tri- and tetrasodioarenes, many of them previously inaccessible by other methods. The key discovery is the use of a primary and bulky alkylsodium lacking beta-hydrogens, which retards undesired reactions, such as Wurtz-Fittig coupling and beta-hydrogen elimination, and enables efficient halogen-sodium exchange. The alkylsodium is readily prepared in situ from neopentyl chloride and an easy-to-handle sodium dispersion. We believe that the efficiency, generality, and convenience of the present method will contribute to the widespread use of organosodium in organic synthesis, ultimately contributing to the development of sustainable organic synthesis by rivalling the currently dominant organolithium reagents. Halogen-sodium exchange reactions with neopentyl sodium provides access to a range of aryl and alkenyl organosodium compounds in situ, as an alternative to organolithium reagents. en-copyright= kn-copyright= en-aut-name=AsakoSobi en-aut-sei=Asako en-aut-mei=Sobi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TakahashiIkko en-aut-sei=Takahashi en-aut-mei=Ikko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NakajimaHirotaka en-aut-sei=Nakajima en-aut-mei=Hirotaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=IliesLaurean en-aut-sei=Ilies en-aut-mei=Laurean kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TakaiKazuhiko en-aut-sei=Takai en-aut-mei=Kazuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Division of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=RIKEN Center for Sustainable Resource Science kn-affil= affil-num=3 en-affil=Division of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=4 en-affil=RIKEN Center for Sustainable Resource Science kn-affil= affil-num=5 en-affil=Division of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=11 cd-vols= no-issue=1 article-no= start-page=11086 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=20210527 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Leucine-rich alpha-2 glycoprotein as a marker of mucosal healing in inflammatory bowel disease en-subtitle= kn-subtitle= en-abstract= kn-abstract=Leucine-rich alpha-2 glycoprotein (LRG) may be a novel serum biomarker for patients with inflammatory bowel disease. The association of LRG with the endoscopic activity and predictability of mucosal healing (MH) was determined and compared with those of C-reactive protein (CRP) and fecal markers (fecal immunochemical test [FIT] and fecal calprotectin [Fcal]) in 166 ulcerative colitis (UC) and 56 Crohn's disease (CD) patients. In UC, LRG was correlated with the endoscopic activity and could predict MH, but the performance was not superior to that of fecal markers (areas under the curve [AUCs] for predicting MH: LRG: 0.61, CRP: 0.59, FIT: 0.75, and Fcal: 0.72). In CD, the performance of LRG was equivalent to that of CRP and Fcal (AUCs for predicting MH: LRG: 0.82, CRP: 0.82, FIT: 0.70, and Fcal: 0.88). LRG was able to discriminate patients with MH from those with endoscopic activity among UC and CD patients with normal CRP levels. LRG was associated with endoscopic activity and could predict MH in both UC and CD patients. It may be particularly useful in CD. en-copyright= kn-copyright= en-aut-name=YasutomiEriko en-aut-sei=Yasutomi en-aut-mei=Eriko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=InokuchiToshihiro en-aut-sei=Inokuchi en-aut-mei=Toshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HiraokaSakiko en-aut-sei=Hiraoka en-aut-mei=Sakiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TakeiKensuke en-aut-sei=Takei en-aut-mei=Kensuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=IgawaShoko en-aut-sei=Igawa en-aut-mei=Shoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YamamotoShumpei en-aut-sei=Yamamoto en-aut-mei=Shumpei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=OhmoriMasayasu en-aut-sei=Ohmori en-aut-mei=Masayasu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OkaShohei en-aut-sei=Oka en-aut-mei=Shohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=YamasakiYasushi en-aut-sei=Yamasaki en-aut-mei=Yasushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KinugasaHideaki en-aut-sei=Kinugasa en-aut-mei=Hideaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=TakaharaMasahiro en-aut-sei=Takahara en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=HaradaKeita en-aut-sei=Harada en-aut-mei=Keita kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=FurukawaMasaki en-aut-sei=Furukawa en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=ItoshimaKouichi en-aut-sei=Itoshima en-aut-mei=Kouichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=OkadaKen en-aut-sei=Okada en-aut-mei=Ken kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=OtsukaFumio en-aut-sei=Otsuka en-aut-mei=Fumio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=TanakaTakehiro en-aut-sei=Tanaka en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=MitsuhashiToshiharu en-aut-sei=Mitsuhashi en-aut-mei=Toshiharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=KatoJun en-aut-sei=Kato en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=OkadaHiroyuki en-aut-sei=Okada en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= affil-num=1 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Department of Laboratory Medicine, Okayama University Hospital kn-affil= affil-num=14 en-affil=Department of Laboratory Medicine, Okayama University Hospital kn-affil= affil-num=15 en-affil=Department of Laboratory Medicine, Okayama University Hospital kn-affil= affil-num=16 en-affil=Department of Laboratory Medicine, Okayama University Hospital kn-affil= affil-num=17 en-affil=Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=18 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=19 en-affil=Department of Gastroenterology, Graduate School of Medicine, Chiba University kn-affil= affil-num=20 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= END start-ver=1.4 cd-journal=joma no-vol=11 cd-vols= no-issue=1 article-no= start-page=11883 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=20210604 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Enhancement of protein thermostability by three consecutive mutations using loop-walking method and machine learning en-subtitle= kn-subtitle= en-abstract= kn-abstract=We developed a method to improve protein thermostability, "loop-walking method". Three consecutive positions in 12 loops of Burkholderia cepacia lipase were subjected to random mutagenesis to make 12 libraries. Screening allowed us to identify L7 as a hot-spot loop having an impact on thermostability, and the P233G/L234E/V235M mutant was found from 214 variants in the L7 library. Although a more excellent mutant might be discovered by screening all the 8000 P233X/L234X/V235X mutants, it was difficult to assay all of them. We therefore employed machine learning. Using thermostability data of the 214 mutants, a computational discrimination model was constructed to predict thermostability potentials. Among 7786 combinations ranked in silico, 20 promising candidates were selected and assayed. The P233D/L234P/V235S mutant retained 66% activity after heat treatment at 60 degrees C for 30 min, which was higher than those of the wild-type enzyme (5%) and the P233G/L234E/V235M mutant (35%). en-copyright= kn-copyright= en-aut-name=YoshidaKazunori en-aut-sei=Yoshida en-aut-mei=Kazunori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KawaiShun en-aut-sei=Kawai en-aut-mei=Shun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=FujitaniMasaya en-aut-sei=Fujitani en-aut-mei=Masaya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KoikedaSatoshi en-aut-sei=Koikeda en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KatoRyuji en-aut-sei=Kato en-aut-mei=Ryuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=EmaTadashi en-aut-sei=Ema en-aut-mei=Tadashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Division of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Department of Basic Medicinal Sciences, Graduate School of Pharmaceutical Sciences, Nagoya University kn-affil= affil-num=3 en-affil=Department of Basic Medicinal Sciences, Graduate School of Pharmaceutical Sciences, Nagoya University kn-affil= affil-num=4 en-affil=Innovation Center, Amano Enzyme Inc. kn-affil= affil-num=5 en-affil=Department of Basic Medicinal Sciences, Graduate School of Pharmaceutical Sciences, Nagoya University kn-affil= affil-num=6 en-affil=Division of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=11 cd-vols= no-issue=1 article-no= start-page=11882 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=20210604 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Sarcopenia is associated with poor prognosis after chemoradiotherapy in patients with stage III non-small-cell lung cancer: a retrospective analysis en-subtitle= kn-subtitle= en-abstract= kn-abstract=We intended to investigate whether muscle and adipose masses were associated with prognosis among patients with stage III non-small-cell lung cancer (NSCLC) who were undergoing chemoradiotherapy (CCRT). We retrospectively explored data of patients with stage III NSCLC who underwent definitive CCRT (>= 60 Gy) between January 2004 and March 2018 at our hospital. We examined the relationship of overall survival (OS) with body mass index (BMI), skeletal muscle index (SMI), psoas muscle index (PMI), visceral adipose tissue index (VAI), subcutaneous adipose tissue index (SAI), and visceral-to-subcutaneous adipose tissue area ratio (VSR) using log-rank tests for the univariate analysis and Cox proportional hazard models for the multivariate analysis. Overall, 16, 32, and 12 patients had stage IIIA, IIIB, and IIIC NSCLC, respectively. The total radiotherapy dose ranged from 60 Gy/30 fractions to 66 Gy/33 fractions. In the univariate analysis, the performance status (PS), BMI, and SMI were associated with OS, whereas the PMI, VAI, SAI, and VSR were not. In the multivariate analysis, the PS and SMI were associated with OS. The hazard ratios and 95% confidence intervals were 2.91 and 1.28-6.64 for PS, and 2.36 and 1.15-4.85 for SMI, respectively. The 1, 3, and 5-year OS rates were 92.1%, 59.6%, and 51.0% in patients with high SMI, and 63.6%, 53.8%, and 17.9% in patients with low SMI, respectively. The SMI correlated with prognosis in our study population, whereas adipose mass did not. Therefore, sarcopenia should be considered while predicting the OS in such patients. en-copyright= kn-copyright= en-aut-name=KatsuiKuniaki en-aut-sei=Katsui en-aut-mei=Kuniaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OgataTakeshi en-aut-sei=Ogata en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SugiyamaSoichi en-aut-sei=Sugiyama en-aut-mei=Soichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YoshioKotaro en-aut-sei=Yoshio en-aut-mei=Kotaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KurodaMasahiro en-aut-sei=Kuroda en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HirakiTakao en-aut-sei=Hiraki en-aut-mei=Takao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KiuraKatsuyuki en-aut-sei=Kiura en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MaedaYoshinobu en-aut-sei=Maeda en-aut-mei=Yoshinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=ToyookaShinichi en-aut-sei=Toyooka en-aut-mei=Shinichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KanazawaSusumu en-aut-sei=Kanazawa en-aut-mei=Susumu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Proton Beam Therapy, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Radiology, Iwakuni Clinical Center kn-affil= affil-num=3 en-affil=Department of Radiology, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Radiology, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Radiological Technology, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= END start-ver=1.4 cd-journal=joma no-vol=11 cd-vols= no-issue=1 article-no= start-page=12298 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=20210610 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Extracellular vesicle-shuttled miRNAs as a diagnostic and prognostic biomarker and their potential roles in gallbladder cancer patients en-subtitle= kn-subtitle= en-abstract= kn-abstract=Circulating microRNAs (miRNAs) in serum extracellular vesicles (EVs) are a promising biomarker in cancer. We aimed to elucidate the serum EVs miRNA biomarkers to identify patients with gallbladder cancer (GBC) and to clarify their potential roles. One hundred nineteen serum EVs from GBC and non-GBC individuals were isolated by pure-EVs-yieldable size-exclusion chromatography, and then were analyzed using a comprehensive miRNAs array and RT-qPCR-based validation. The functional roles of the identified miRNAs were also investigated using GBC cell lines. Serum EVs miR-1246 and miR-451a were significantly upregulated and downregulated, respectively in GBC patients (P=0.005 and P=0.001), in line with their expression levels in cancer tissue according to an in silico analysis. The combination of CEA and CA19-9 with miR-1246 showed the highest diagnostic power (AUC, 0.816; Sensitivity, 72.0%; Specificity, 90.8%), and miR-1246 was an independent prognostic marker of GBC (Hazard ratio, 3.05; P=0.017) according to a Cox proportional hazards model. In vitro, miR-1246 promoted cell proliferation and invasion, while miR-451a inhibited cell proliferation and induced apoptosis with the targeting of MIF, PSMB8 and CDKN2D. Taken together, miR-1246 in serum EVs has potential application as a diagnostic and prognostic marker and miR-451a may be a novel therapeutic target in GBC. en-copyright= kn-copyright= en-aut-name=UetaEijiro en-aut-sei=Ueta en-aut-mei=Eijiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TsutsumiKoichiro en-aut-sei=Tsutsumi en-aut-mei=Koichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KatoHironari en-aut-sei=Kato en-aut-mei=Hironari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MatsushitaHiroshi en-aut-sei=Matsushita en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ShirahaHidenori en-aut-sei=Shiraha en-aut-mei=Hidenori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=FujiiMasakuni en-aut-sei=Fujii en-aut-mei=Masakuni kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MatsumotoKazuyuki en-aut-sei=Matsumoto en-aut-mei=Kazuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=HoriguchiShigeru en-aut-sei=Horiguchi en-aut-mei=Shigeru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=OkadaHiroyuki en-aut-sei=Okada en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science kn-affil= affil-num=2 en-affil=Department of Gastroenterology, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Gastroenterology, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Gastroenterology, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Gastroenterology, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Internal Medicine, Okayama Saiseikai General Hospital kn-affil= affil-num=7 en-affil=Department of Gastroenterology, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Gastroenterology, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science kn-affil= END start-ver=1.4 cd-journal=joma no-vol=11 cd-vols= no-issue=1 article-no= start-page=13125 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=20210623 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Reduced dose of PTCy followed by adjuvant alpha-galactosylceramide enhances GVL effect without sacrificing GVHD suppression en-subtitle= kn-subtitle= en-abstract= kn-abstract=Posttransplantation cyclophosphamide (PTCy) has become a popular option for haploidentical hematopoietic stem cell transplantation (HSCT). However, personalized methods to adjust immune intensity after PTCy for each patient's condition have not been well studied. Here, we investigated the effects of reducing the dose of PTCy followed by alpha -galactosylceramide (alpha -GC), a ligand of iNKT cells, on the reciprocal balance between graft-versus-host disease (GVHD) and the graft-versus-leukemia (GVL) effect. In a murine haploidentical HSCT model, insufficient GVHD prevention after reduced-dose PTCy was efficiently compensated for by multiple administrations of alpha -GC. The ligand treatment maintained the enhanced GVL effect after reduced-dose PTCy. Phenotypic analyses revealed that donor-derived B cells presented the ligand and induced preferential skewing to the NKT2 phenotype rather than the NKT1 phenotype, which was followed by the early recovery of all T cell subsets, especially CD4(+)Foxp3(+) regulatory T cells. These studies indicate that alpha -GC administration soon after reduced-dose PTCy restores GVHD-preventing activity and maintains the GVL effect, which is enhanced by reducing the dose of PTCy. Our results provide important information for the development of a novel strategy to optimize PTCy-based transplantation, particularly in patients with a potential relapse risk. en-copyright= kn-copyright= en-aut-name=NakamuraMakoto en-aut-sei=Nakamura en-aut-mei=Makoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MeguriYusuke en-aut-sei=Meguri en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=IkegawaShuntaro en-aut-sei=Ikegawa en-aut-mei=Shuntaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KondoTakumi en-aut-sei=Kondo en-aut-mei=Takumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SumiiYuichi en-aut-sei=Sumii en-aut-mei=Yuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=FukumiTakuya en-aut-sei=Fukumi en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=IwamotoMiki en-aut-sei=Iwamoto en-aut-mei=Miki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SandoYasuhisa en-aut-sei=Sando en-aut-mei=Yasuhisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SugiuraHiroyuki en-aut-sei=Sugiura en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=AsadaNoboru en-aut-sei=Asada en-aut-mei=Noboru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=EnnishiDaisuke en-aut-sei=Ennishi en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=TomidaShuta en-aut-sei=Tomida en-aut-mei=Shuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=Fukuda-KawaguchiEmi en-aut-sei=Fukuda-Kawaguchi en-aut-mei=Emi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=IshiiYasuyuki en-aut-sei=Ishii en-aut-mei=Yasuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=MaedaYoshinobu en-aut-sei=Maeda en-aut-mei=Yoshinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=MatsuokaKen-Ichi en-aut-sei=Matsuoka en-aut-mei=Ken-Ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= affil-num=1 en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=11 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=12 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital kn-affil= affil-num=13 en-affil=REGiMMUNE Corporation kn-affil= affil-num=14 en-affil=REGiMMUNE Corporation kn-affil= affil-num=15 en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=16 en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= END start-ver=1.4 cd-journal=joma no-vol=11 cd-vols= no-issue=1 article-no= start-page=13315 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=20210625 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=The gastrin-releasing peptide/bombesin system revisited by a reverse-evolutionary study considering Xenopus en-subtitle= kn-subtitle= en-abstract= kn-abstract=Bombesin is a putative antibacterial peptide isolated from the skin of the frog, Bombina bombina. Two related (bombesin-like) peptides, gastrin-releasing peptide (GRP) and neuromedin B (NMB) have been found in mammals. The history of GRP/bombesin discovery has caused little attention to be paid to the evolutionary relationship of GRP/bombesin and their receptors in vertebrates. We have classified the peptides and their receptors from the phylogenetic viewpoint using a newly established genetic database and bioinformatics. Here we show, by using a clawed frog (Xenopus tropicalis), that GRP is not a mammalian counterpart of bombesin and also that, whereas the GRP system is widely conserved among vertebrates, the NMB/bombesin system has diversified in certain lineages, in particular in frog species. To understand the derivation of GRP system in the ancestor of mammals, we have focused on the GRP system in Xenopus. Gene expression analyses combined with immunohistochemistry and Western blotting experiments demonstrated that GRP peptides and their receptors are distributed in the brain and stomach of Xenopus. We conclude that GRP peptides and their receptors have evolved from ancestral (GRP-like peptide) homologues to play multiple roles in both the gut and the brain as one of the 'gut-brain peptide' systems. en-copyright= kn-copyright= en-aut-name=HirookaAsuka en-aut-sei=Hirooka en-aut-mei=Asuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HamadaMayuko en-aut-sei=Hamada en-aut-mei=Mayuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=FujiyamaDaiki en-aut-sei=Fujiyama en-aut-mei=Daiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TakanamiKeiko en-aut-sei=Takanami en-aut-mei=Keiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KobayashiYasuhisa en-aut-sei=Kobayashi en-aut-mei=Yasuhisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OtiTakumi en-aut-sei=Oti en-aut-mei=Takumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KatayamaYukitoshi en-aut-sei=Katayama en-aut-mei=Yukitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SakamotoTatsuya en-aut-sei=Sakamoto en-aut-mei=Tatsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SakamotoHirotaka en-aut-sei=Sakamoto en-aut-mei=Hirotaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Ushimado Marine Institute (UMI), Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Ushimado Marine Institute (UMI), Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=3 en-affil=Ushimado Marine Institute (UMI), Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=4 en-affil=Ushimado Marine Institute (UMI), Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=5 en-affil=Ushimado Marine Institute (UMI), Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=6 en-affil=Ushimado Marine Institute (UMI), Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=7 en-affil=Ushimado Marine Institute (UMI), Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=8 en-affil=Ushimado Marine Institute (UMI), Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=9 en-affil=Ushimado Marine Institute (UMI), Graduate School of Natural Science and Technology, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=12 cd-vols= no-issue=1 article-no= start-page=4305 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=20210714 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Ultrafast olivine-ringwoodite transformation during shock compression en-subtitle= kn-subtitle= en-abstract= kn-abstract=Meteorites from interplanetary space often include high-pressure polymorphs of their constituent minerals, which provide records of past hypervelocity collisions. These collisions were expected to occur between kilometre-sized asteroids, generating transient high-pressure states lasting for several seconds to facilitate mineral transformations across the relevant phase boundaries. However, their mechanisms in such a short timescale were never experimentally evaluated and remained speculative. Here, we show a nanosecond transformation mechanism yielding ringwoodite, which is the most typical high-pressure mineral in meteorites. An olivine crystal was shock-compressed by a focused high-power laser pulse, and the transformation was time-resolved by femtosecond diffractometry using an X-ray free electron laser. Our results show the formation of ringwoodite through a faster, diffusionless process, suggesting that ringwoodite can form from collisions between much smaller bodies, such as metre to submetre-sized asteroids, at common relative velocities. Even nominally unshocked meteorites could therefore contain signatures of high-pressure states from past collisions. en-copyright= kn-copyright= en-aut-name=OkuchiTakuo en-aut-sei=Okuchi en-aut-mei=Takuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SetoYusuke en-aut-sei=Seto en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TomiokaNaotaka en-aut-sei=Tomioka en-aut-mei=Naotaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MatsuokaTakeshi en-aut-sei=Matsuoka en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=AlbertazziBruno en-aut-sei=Albertazzi en-aut-mei=Bruno kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HartleyNicholas J. en-aut-sei=Hartley en-aut-mei=Nicholas J. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=InubushiYuichi en-aut-sei=Inubushi en-aut-mei=Yuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KatagiriKento en-aut-sei=Katagiri en-aut-mei=Kento kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KodamaRyosuke en-aut-sei=Kodama en-aut-mei=Ryosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=PikuzTatiana A. en-aut-sei=Pikuz en-aut-mei=Tatiana A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=PurevjavNarangoo en-aut-sei=Purevjav en-aut-mei=Narangoo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=MiyanishiKohei en-aut-sei=Miyanishi en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=SatoTomoko en-aut-sei=Sato en-aut-mei=Tomoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=SekineToshimori en-aut-sei=Sekine en-aut-mei=Toshimori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=SuedaKeiichi en-aut-sei=Sueda en-aut-mei=Keiichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=TanakaKazuo A. en-aut-sei=Tanaka en-aut-mei=Kazuo A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=TangeYoshinori en-aut-sei=Tange en-aut-mei=Yoshinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=TogashiTadashi en-aut-sei=Togashi en-aut-mei=Tadashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=UmedaYuhei en-aut-sei=Umeda en-aut-mei=Yuhei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=YabuuchiToshinori en-aut-sei=Yabuuchi en-aut-mei=Toshinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=YabashiMakina en-aut-sei=Yabashi en-aut-mei=Makina kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=OzakiNorimasa en-aut-sei=Ozaki en-aut-mei=Norimasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= affil-num=1 en-affil=Institute for Integrated Radiation and Nuclear Science, Kyoto University kn-affil= affil-num=2 en-affil=Graduate School of Science, Kobe University kn-affil= affil-num=3 en-affil=Kochi Institute for Core Sample Research, Japan Agency for Marine-Earth Science and Technology (JAMSTEC) kn-affil= affil-num=4 en-affil=Institute for Open and Transdisciplinary Research Initiatives, Osaka University kn-affil= affil-num=5 en-affil=Graduate School of Engineering, Osaka University kn-affil= affil-num=6 en-affil=Graduate School of Engineering, Osaka University kn-affil= affil-num=7 en-affil=Japan Synchrotron Radiation Research Institute, kn-affil= affil-num=8 en-affil=Graduate School of Engineering, Osaka University kn-affil= affil-num=9 en-affil=Graduate School of Engineering, Osaka University kn-affil= affil-num=10 en-affil=Graduate School of Engineering, Osaka University kn-affil= affil-num=11 en-affil=Institute for Planetary Materials, Okayama University kn-affil= affil-num=12 en-affil=RIKEN SPring-8 Center kn-affil= affil-num=13 en-affil=Graduate School of Science, Hiroshima University kn-affil= affil-num=14 en-affil=Graduate School of Engineering, Osaka University kn-affil= affil-num=15 en-affil=RIKEN SPring-8 Center kn-affil= affil-num=16 en-affil=Graduate School of Engineering, Osaka University kn-affil= affil-num=17 en-affil=Japan Synchrotron Radiation Research Institute kn-affil= affil-num=18 en-affil=Japan Synchrotron Radiation Research Institute kn-affil= affil-num=19 en-affil=Institute for Integrated Radiation and Nuclear Science, Kyoto University kn-affil= affil-num=20 en-affil=Japan Synchrotron Radiation Research Institute kn-affil= affil-num=21 en-affil=Japan Synchrotron Radiation Research Institute kn-affil= affil-num=22 en-affil=Graduate School of Engineering, Osaka University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=13 cd-vols= no-issue=1 article-no= start-page=647 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230112 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Clinical characteristics of Campylobacter bacteremia: a multicenter retrospective study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Campylobacter species are the pathogens of the intestinal tract, which infrequently cause bacteremia. To reveal the clinical characteristics of Campylobacter bacteremia, we performed a retrospective, multicenter study. Patients diagnosed with Campylobacter bacteremia in three general hospitals in western Japan between 2011 and 2021 were included in the study. Clinical, microbiological, and prognostic data of the patients were obtained from medical records. We stratified the cases into the gastroenteritis (GE) and fever predominant (FP) types by focusing on the presence of gastrointestinal symptoms. Thirty-nine patients (24 men and 15 women) were included, with a median age of 57 years and bimodal distribution between those in their 20 s and the elderly. The proportion of GE and FP types were 21 (53.8%) and 18 (46.2%), respectively. Comparing these two groups, there was no significant difference in patient backgrounds in terms of sex, age, and underlying diseases. Campylobacter jejuni was exclusively identified in the GE type (19 cases, 90.5%), although other species such as Campylobacter fetus and Campylobacter coli were isolated in the FP type as well. Patients with the FP type underwent intravenous antibiotic therapy more frequently (47.6% vs. 88.9%), and their treatment (median: 5 days vs. 13 days) and hospitalization (median: 7 days vs. 21 days) periods were significantly longer. None of the patients died during the hospitalization. In summary, we found that nearly half of the patients with Campylobacter bacteremia presented with fever as a predominant manifestation without gastroenteritis symptoms. en-copyright= kn-copyright= en-aut-name=OtsukaYuki en-aut-sei=Otsuka en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HagiyaHideharu en-aut-sei=Hagiya en-aut-mei=Hideharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TakahashiMisa en-aut-sei=Takahashi en-aut-mei=Misa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=FukushimaShinnosuke en-aut-sei=Fukushima en-aut-mei=Shinnosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MaedaRuri en-aut-sei=Maeda en-aut-mei=Ruri kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SunadaNaruhiko en-aut-sei=Sunada en-aut-mei=Naruhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YamadaHaruto en-aut-sei=Yamada en-aut-mei=Haruto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KishidaMasayuki en-aut-sei=Kishida en-aut-mei=Masayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=FujitaKoji en-aut-sei=Fujita en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=OtsukaFumio en-aut-sei=Otsuka en-aut-mei=Fumio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Clinical Laboratory, Okayama City Hospital kn-affil= affil-num=8 en-affil=Department of General Internal Medicine, Okayama City Hospital kn-affil= affil-num=9 en-affil=Department of General Medicine and Infectious Disease, Tsuyama Chuo Hospital kn-affil= affil-num=10 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= END start-ver=1.4 cd-journal=joma no-vol=13 cd-vols= no-issue=1 article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230316 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Dexmedetomidine improves acute lung injury by activating autophagy in a rat hemorrhagic shock and resuscitation model en-subtitle= kn-subtitle= en-abstract= kn-abstract=Dexmedetomidine (DEX) can reduce lung injury in a hemorrhagic shock (HS) resuscitation (HSR) model in rats by inhibiting inflammation. Here, we aimed to investigate if these effects of DEX are due to autophagy activation. Therefore, we established HSR rat models and divided them into four groups. HS was induced using a blood draw. The rats were then resuscitated by reinjecting the drawn blood and saline. The rats were sacrificed 24 h after resuscitation. Lung tissues were harvested for histopathological examination, determination of wet/dry lung weight ratio, and detection of the levels of autophagy-related marker proteins LC3, P62, Beclin-1, and the ATG12-ATG5 conjugate. The morphological findings of hematoxylin and eosin staining in lung tissues and the pulmonary wet/dry weight ratio showed that lung injury improved in HSR + DEX rats. However, chloroquine (CQ), an autophagy inhibitor, abolished this effect. Detecting the concentration of autophagy-related proteins showed that DEX administration increased LC3, ATG12-ATG5, and Beclin-1 expression and decreased P62 expression. The expression levels of these proteins were similar to those in the HSR group after CQ + DEX administration. In summary, DEX induced autophagic activation in an HSR model. These findings suggest that DEX administration partially ameliorates HSR-induced lung injury via autophagic activation. en-copyright= kn-copyright= en-aut-name=LuYifu en-aut-sei=Lu en-aut-mei=Yifu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ShimizuHiroko en-aut-sei=Shimizu en-aut-mei=Hiroko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NakamuraRyu en-aut-sei=Nakamura en-aut-mei=Ryu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=LiYaqiang en-aut-sei=Li en-aut-mei=Yaqiang kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SakamotoRisa en-aut-sei=Sakamoto en-aut-mei=Risa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OmoriEmiko en-aut-sei=Omori en-aut-mei=Emiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TakahashiToru en-aut-sei=Takahashi en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MorimatsuHiroshi en-aut-sei=Morimatsu en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Anesthesiology and Resuscitology, Okayama University, Graduate School of Medicine, Dentistry, Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Anesthesiology and Resuscitology, Okayama University Medical School kn-affil= affil-num=3 en-affil=Department of Anesthesiology and Resuscitology, Okayama University, Graduate School of Medicine, Dentistry, Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Anesthesiology and Resuscitology, Okayama University, Graduate School of Medicine, Dentistry, Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Anesthesiology and Resuscitology, Okayama University, Graduate School of Medicine, Dentistry, Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Anesthesiology and Resuscitology, Okayama University, Graduate School of Medicine, Dentistry, Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Okayama Saidaiji Hospital kn-affil= affil-num=8 en-affil=Department of Anesthesiology and Resuscitology, Okayama University, Graduate School of Medicine, Dentistry, Pharmaceutical Sciences kn-affil= END