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WoS SCOPUS Document Type Document Title Abstract Authors Affiliation ResearcherID (WoS) AuthorsID (SCOPUS) Author Email(s) Journal Name JCR Abbreviation ISSN eISSN Volume Issue WoS Edition WoS Category JCR Year IF JCR (%) FWCI FWCI Update Date WoS Citation SCOPUS Citation Keywords (WoS) KeywordsPlus (WoS) Keywords (SCOPUS) KeywordsPlus (SCOPUS) Language Publication Stage Publication Year Publication Date DOI JCR Link DOI Link WOS Link SCOPUS Link
Article Method for evaluating segregation in self-consolidating concrete using electrical resistivity measurements Self-consolidating concrete requires a highly fluid binder with sufficient segregation resistance in the fresh mixture. However, careless mix proportioning with various chemical and mineral admixtures can cause instability among the components in the fresh state, including aggregate segregation. The fully or partially segregated mix expectedly exhibits low durability after it hardens. This study attempted to nondestructively evaluate the degree of static segregation in self-consolidating concrete. A column type test mold was fabricated, which allowed cross-sectional electrical resistivity to be measured in the top and bottom sections using a total of 24 electrodes. The electrical resistivity can sensitively evaluate the relative degree of segregation in concrete mixtures. The experimental results were also compared and discussed using the coarse aggregate segregation index obtained using the conventional method, that requires wet-sieving of self-consolidating concrete in the fresh state. (C) 2019 Elsevier Ltd. All rights reserved. Yim, Hong Jae; Bae, Young Hwan; Kim, Jae Hong Pusan Natl Univ, Dept Civil Engn, Busan 46241, South Korea; Kyungpook Natl Univ, Dept Construct & Disaster Prevent Engn, Sangju 37224, South Korea; Korea Adv Inst Sci & Technol, Dept Civil & Environm Engn, Daejeon 34141, South Korea Kim, Jae/F-7775-2011 57197297923; 57211355908; 56106288200 jae.kim@kaist.ac.kr; CONSTRUCTION AND BUILDING MATERIALS CONSTR BUILD MATER 0950-0618 1879-0526 232 SCIE CONSTRUCTION & BUILDING TECHNOLOGY;ENGINEERING, CIVIL;MATERIALS SCIENCE, MULTIDISCIPLINARY 2020 6.141 4.7 2.01 2025-06-25 35 39 Segregation; Self-consolidating concrete; Electrical resistivity; Square array electrode method CONDUCTIVITY Electrical resistivity; Segregation; Self-consolidating concrete; Square array electrode method Aggregates; Concrete aggregates; Concrete mixtures; Electric conductivity; Electrodes; Mixtures; Segregation (metallography); Aggregate segregations; Coarse aggregates; Conventional methods; Electrical resistivity measurements; Mineral admixtures; Segregation resistances; Self-consolidating concrete; Square array; Self compacting concrete English 2020 2020-01-30 10.1016/j.conbuildmat.2019.117283 바로가기 바로가기 바로가기 바로가기
Article Shear strength and interface friction characteristics of expandable foam grout The deterioration of buried pipes in urban areas leads to the formation of underground cavities, which may induce road subsidence. To fill these cavities, this study investigates the shear strength characteristics of expandable foam grout (EFG) and the interface between EFG and two types of sands. A series of direct shear tests is conducted using EFG specimens prepared under different conditions of curing time and unit weights of sand. After three days of curing, the shear stress curves of EFG and EFG-sand interface obtained at three normal stresses indicate brittle behavior and ductile behavior, respectively. Friction angles of the EFG increase with curing time, while those of the EFG-sand interface remain almost constant. The interface friction angles between the EFG and sands are smaller than or equal to the internal friction angles of the sands. Therefore, the shear strength of the EFG-surrounding soil interface should be given more attention than the high shear strength of the EFG, to fill underground cavities. (C) 2020 Elsevier Ltd. All rights reserved. Lee, Jong-Sub; Han, WooJin; Kim, Sang Yeob; Byun, Yong-Hoon Korea Univ, Sch Civil Environm & Architectural Engn, 145 Anam Ro, Seoul 136713, South Korea; Kyungpook Natl Univ, Sch Agr Civil & Bioind Engn, 80 Daehak Ro, Daegu 41566, South Korea; Kyungpook Natl Univ, Inst Agr Sci & Technol, 80 Daehak Ro, Daegu 41566, South Korea Han, WooJin/KLZ-1352-2024; Byun, Yong-Hoon/JKI-8441-2023; Lee, Jong-Sub/G-2752-2012 55690048400; 57191676149; 57202787920; 42761048000 yhbyun@knu.ac.kr; CONSTRUCTION AND BUILDING MATERIALS CONSTR BUILD MATER 0950-0618 1879-0526 249 SCIE CONSTRUCTION & BUILDING TECHNOLOGY;ENGINEERING, CIVIL;MATERIALS SCIENCE, MULTIDISCIPLINARY 2020 6.141 4.7 0.71 2025-06-25 18 19 Direct shear; Expansion; Flowable fill; Foam grout; Interface friction FLY-ASH; BEHAVIOR Direct shear; Expansion; Flowable fill; Foam grout; Interface friction Curing; Deterioration; Expansion; Friction; Grouting; Mortar; Sand; Shear stress; Direct shear; Flowable fill; Interface friction; Interface friction angle; Internal friction angle; Strength characteristics; Surrounding soils; Underground cavities; Shear strength English 2020 2020-07-20 10.1016/j.conbuildmat.2020.118719 바로가기 바로가기 바로가기 바로가기
Article Presynaptic PTPσ regulates postsynaptic NMDA receptor function through direct adhesion-independent mechanisms Synaptic adhesion molecules regulate synapse development and function. However, whether and how presynaptic adhesion molecules regulate postsynaptic NMDAR function remains largely unclear. Presynaptic LAR family receptor tyrosine phosphatases (LAR-RPTPs) regulate synapse development through mechanisms that include trans-synaptic adhesion; however, whether they regulate postsynaptic receptor functions remains unknown. Here we report that presynaptic PTP sigma, a LAR-RPTP, enhances postsynaptic NMDA receptor (NMDAR) currents and NMDAR-dependent synaptic plasticity in the hippocampus. This regulation does not involve trans-synaptic adhesions of PTP sigma, suggesting that the cytoplasmic domains of PTP sigma, known to have tyrosine phosphatase activity and mediate protein-protein interactions, are important. In line with this, phosphotyrosine levels of presynaptic proteins, including neurexin-1, are strongly increased in PTP sigma-mutant mice. Behaviorally, PTP sigma-dependent NMDAR regulation is important for social and reward-related novelty recognition. These results suggest that presynaptic PTP sigma regulates postsynaptic NMDAR function through trans-synaptic and direct adhesion-independent mechanisms and novelty recognition in social and reward contexts. Kim, Kyungdeok; Shin, Wangyong; Kang, Muwon; Lee, Suho; Kim, Doyoun; Kang, Ryeonghwa; Jung, Yewon; Cho, Yisul; Yang, Esther; Kim, Hyun; Bae, Yong Chul; Kim, Eunjoon Korea Adv Inst Sci & Technol, Dept Biol Sci, Daejeon, South Korea; Inst for Basic Sci Korea, Ctr Synapt Brain Dysfunct, Daejeon, South Korea; Kyungpook Natl Univ, Sch Dent, Dept Anat & Neurobiol, Daegu, South Korea; Korea Univ, Coll Med, Dept Anat, Seoul, South Korea; Korea Univ, Coll Med, Div Brain Korea 21, Biomed Sci, Seoul, South Korea Kim, Eunjoon/C-1566-2011; Kim, Hyongbum/D-5804-2019 56643307400; 56643997700; 57209347227; 57202691999; 55868319700; 57210116788; 57215853111; 23979595700; 57194107730; 55663909700; 56377838800; 57203240554 kime@kaist.ac.kr; ELIFE ELIFE 2050-084X 9 SCIE BIOLOGY 2020 8.146 4.8 0.89 2025-06-25 24 22 PROTEIN-TYROSINE-PHOSPHATASE; LONG-TERM POTENTIATION; ANTERIOR CINGULATE CORTEX; HIPPOCAMPAL CA2 REGION; MICE LACKING; TRANSSYNAPTIC ADHESION; SYNAPSE DEVELOPMENT; NEURONAL CIRCUITS; STRUCTURAL BASIS; NEURAL CIRCUITS Animals; Gene Expression Regulation; Mice; Mice, Transgenic; Neuroimaging; Open Field Test; Receptor-Like Protein Tyrosine Phosphatases, Class 2; Receptors, N-Methyl-D-Aspartate; Synapses; Synaptic Transmission; glutamate receptor; membrane protein; metabotropic receptor; n methyl dextro aspartic acid receptor; neurexin; phosphotyrosine; postsynaptic receptor; protein tyrosine phosphatase; n methyl dextro aspartic acid receptor; Ptprs protein, mouse; receptor like protein tyrosine phosphatase; animal cell; animal experiment; animal model; animal tissue; Article; brain electrophysiology; controlled study; electrophysiology; enzyme activity; excitatory postsynaptic potential; genetic transfection; hippocampus; immunoblotting; immunohistochemistry; immunoprecipitation; light-dark test; mass spectrometry; maze test; Morris water maze test; nerve cell plasticity; neuroimaging; nonhuman; open field test; phenotype; postsynaptic density; prepulse inhibition; protein expression; protein localization; protein phosphorylation; protein protein interaction; regulatory mechanism; rotarod test; signal transduction; synapse; synaptic potential; synaptic transmission; virus inhibition; Western blotting; Y-maze test; animal; gene expression regulation; genetics; metabolism; mouse; physiology; transgenic mouse English 2020 2020-03-06 10.7554/elife.54224 바로가기 바로가기 바로가기 바로가기
Article Selective inhibition of CDK7 reveals high-confidence targets and new models for TFIIH function in transcription CDK7 associates with the 10-subunit TFIIH complex and regulates transcription by phosphorylating the C-terminal domain (CTD) ofRNApolymerase II (RNAPII). Fewadditional CDK7 substrates are known. Here, using the covalent inhibitor SY-351 and quantitative phosphoproteomics, we identified CDK7 kinase substrates in human cells. Among hundreds of high-confidence targets, the vast majority are unique to CDK7 (i.e., distinct from other transcription-associated kinases), with a subset that suggest novel cellular functions. Transcription-associated factors were predominant CDK7 substrates, including SF3B1, U2AF2, and other splicing components. Accordingly, widespread and diverse splicing defects, such as alternative exon inclusion and intron retention, were characterized in CDK7-inhibited cells. Combined with biochemical assays, we establish that CDK7 directly activates other transcription-associated kinases CDK9, CDK12, and CDK13, invoking a "master regulator" role in transcription. We further demonstrate that TFIIH restricts CDK7 kinase function to the RNAPII CTD, whereas other substrates (e.g., SPT5 and SF3B1) are phosphorylated by the three-subunit CDK-activating kinase (CAK; CCNH, MAT1, and CDK7). These results suggest newmodels for CDK7 function in transcription and implicate CAK dissociation from TFIIH as essential for kinase activation. This straightforward regulatory strategy ensures CDK7 activation is spatially and temporally linked to transcription, and may apply toward other transcription-associated kinases. Rimel, Jenna K.; Poss, Zachary C.; Erickson, Benjamin; Maas, Zachary L.; Ebmeier, Christopher C.; Johnson, Jared L.; Decker, Tim-Michael; Yaron, Tomer M.; Bradley, Michael J.; Hamman, Kristin B.; Hu, Shanhu; Malojcic, Goran; Marineau, Jason J.; White, Peter W.; Brault, Martine; Tao, Limei; DeRoy, Patrick; Clavette, Christian; Nayak, Shraddha; Damon, Leah J.; Kaltheuner, Ines H.; Bunch, Heeyoun; Cantley, Lewis C.; Geyer, Matthias; Iwasa, Janet; Dowell, Robin D.; Bentley, David L.; Old, William M.; Taatjes, Dylan J. Univ Colorado, Dept Biochem, Boulder, CO 80303 USA; Univ Colorado, Dept Mol Cellular & Dev Biol, Boulder, CO 80309 USA; Univ Colorado, Sch Med, Dept Biochem & Mol Genet, Aurora, CO 80045 USA; Univ Colorado, Sch Med, UC Denver RNA Biosci Initiat, Aurora, CO 80045 USA; Univ Colorado, BioFrontiers Inst, Boulder, CO 80309 USA; Weill Cornell Med, Meyer Canc Ctr, New York, NY 10065 USA; Weill Cornell Med, Englander Inst Precis Med, New York, NY 10065 USA; Weill Cornell Med, Inst Computat Biomed, New York, NY 10065 USA; Weill Cornell Med, Dept Physiol & Biophys, New York, NY 10065 USA; Syros Pharmaceut, Cambridge, MA 02140 USA; Paraza Pharma Inc, Montreal, PQ H4S 1Z9, Canada; Univ Utah, Dept Biochem, Salt Lake City, UT 84112 USA; Univ Bonn, Inst Struct Biol, D-53127 Bonn, Germany; Kyungpook Natl Univ, Coll Agr & Life Sci, Sch Appl Biosci, Daegu 41566, South Korea ; Kaltheuner, Ines/IUQ-0999-2023; Bunch, Heeyoun/JAX-3215-2023; Bradley, Michael/F-6383-2012; Johnson, Jared/HNQ-1078-2023 57202347399; 36247833100; 35223105100; 57216789177; 6505934962; 35110556400; 56179120400; 57205282750; 57209912532; 57209908515; 56883443400; 25623366600; 55541280400; 7404090049; 7003772921; 57219773587; 37109582800; 57504593600; 57211554717; 57190121330; 57218343645; 56336812200; 35394495300; 7101696391; 55659004100; 7006596168; 57204298043; 6603575005; 7006861729 william.old@colorado.edu;taatjes@colorado.edu; GENES & DEVELOPMENT GENE DEV 0890-9369 1549-5477 34 21-22 SCIE CELL BIOLOGY;DEVELOPMENTAL BIOLOGY;GENETICS & HEREDITY 2020 11.361 4.8 3.1 2025-06-25 64 58 CDK12; CDK13; CDK7; CDK9; SF3B1; SILAC-MS; TFIIH; kinase inhibitor; splicing; transcription CARBOXY-TERMINAL DOMAIN; MESSENGER-RNA; KINASE; CANCER; PHOSPHORYLATION; PROTEIN; IDENTIFICATION; SPECIFICITY; EXPRESSION; SEQUENCE CDK12; CDK13; CDK7; CDK9; Kinase inhibitor; SF3B1; SILAC-MS; Splicing; TFIIH; Transcription Alternative Splicing; Cell Survival; Cyclin-Dependent Kinases; Enzyme Activation; HL-60 Cells; Humans; Models, Biological; Transcription Factor TFIIH; Transcription, Genetic; cyclin dependent kinase 12; cyclin dependent kinase 13; cyclin dependent kinase 7; cyclin dependent kinase 9; phosphotransferase inhibitor; RNA polymerase II; sy 351; transcription factor IIH; unclassified drug; CDK12 protein, human; cyclin dependent kinase; cyclin-dependent kinase-activating kinase; transcription factor IIH; alternative RNA splicing; Article; biochemical analysis; carboxy terminal sequence; controlled study; human; human cell; intron retention; phosphoproteomics; priority journal; protein function; RNA processing; SILAC labeling; splicing defect; transcription initiation; transcription regulation; biological model; cell survival; drug effect; enzyme activation; genetic transcription; genetics; HL-60 cell line; metabolism English 2020 2020-11-01 10.1101/gad.341545.120 바로가기 바로가기 바로가기 바로가기
Article Ag(I) ions working as a hole-transfer mediator in photoelectrocatalytic water oxidation on WO3 film Ag(I) is commonly employed as an electron scavenger to promote water oxidation. In addition to its straightforward role as an electron acceptor, Ag(I) can also capture holes to generate the high-valent silver species. Herein, we demonstrate photoelectrocatalytic (PEC) water oxidation and concurrent dioxygen evolution by the silver redox cycle where Ag(I) acts as a hole-transfer mediator. Ag(I) enhances the PEC performance of WO3 electrodes at 1.23 V vs. RHE with increasing O-2 evolution, while forming Ag(II) complexes ((AgNO3+)-N-II). Upon turning off both light and potential bias, the photocurrent immediately drops to zero, whereas O-2 evolution continues over similar to 10 h with gradual bleaching of the colored complexes. This phenomenon is observed neither in the Ag(I)-free PEC reactions nor in the photocatalytic (i.e., bias-free) reactions with Ag(I). This study finds that the role of Ag(I) is not limited as an electron scavenger and calls for more thorough studies on the effect of Ag(I). Jeon, Tae Hwa; Monllor-Satoca, Damian; Moon, Gun-hee; Kim, Wooyul; Kim, Hyoung-il; Bahnemann, Detlef W.; Park, Hyunwoong; Choi, Wonyong Pohang Univ Sci & Technol POSTECH, Div Environm Sci & Engn, Pohang 37673, South Korea; Sookmyung Womens Univ, Dept Chem & Biol Engn, Seoul 04310, South Korea; Yonsei Univ, Dept Civil & Environm Engn, Seoul 03722, South Korea; Leibniz Univ Hannover, Inst Tech Chem, Photocatalysis & Nanotechnol, Hannover, Germany; Kyungpook Natl Univ, Sch Energy Engn, Daegu 41566, South Korea; Univ Ra Mon Llull, Dept Analyt & Appl Chem, Inst Quim Sarria IQS, Sch Engn, Via Augusta 390, Barcelona 08017, Spain KIM, WOOYUL/GLT-3776-2022; Choi, Wonyong/F-8206-2010; Kim, Hyoung-il/D-1053-2014; Monllor-Satoca, Damián/B-2308-2013; Bahnemann, Detlef/G-3375-2012; Park, Hyunwoong/A-1247-2012; Moon, Gun-hee/A-3279-2017 37099787500; 22135331400; 41661921200; 23485589100; 57211720610; 7005878097; 7601565583; 7402516297 hwp@knu.ac.kr;wchoi@postech.edu; NATURE COMMUNICATIONS NAT COMMUN 2041-1723 11 1 SCIE MULTIDISCIPLINARY SCIENCES 2020 14.919 4.9 3.02 2025-06-25 91 87 ELECTROCHEMICAL OXIDATION; ARGENTIC SALTS; ACID-SOLUTION; SILVER; KINETICS; REDUCTION; STABILITY; NITRATE; CHARGE; PHOTOCATALYSIS nitrate; oxygen; silver; tungsten derivative; catalysis; catalyst; film; inorganic compound; ion; oxidation; Article; bleaching; catalyst; complex formation; controlled study; electrochemistry; electron spin resonance; mediator; oxidation; oxidation reduction reaction; oxygen evolution; photocatalysis; photooxidation; reduction (chemistry); steady state; surface plasmon resonance; surface property English 2020 2020-02-19 10.1038/s41467-020-14775-2 바로가기 바로가기 바로가기 바로가기
Article Astrocytic pyruvate dehydrogenase kinase-2 is involved in hypothalamic inflammation in mouse models of diabetes Hypothalamic inflammation plays an important role in disrupting feeding behavior and energy homeostasis as well as in the pathogenesis of obesity and diabetes. Here, we show that pyruvate dehydrogenase kinase (PDK)-2 plays a role in hypothalamic inflammation and its sequelae in mouse models of diabetes. Cell type-specific genetic ablation and pharmacological inhibition of PDK2 in hypothalamic astrocytes suggest that hypothalamic astrocytes are involved in the diabetic phenotype. We also show that the PDK2-lactic acid axis plays a regulatory role in the observed metabolic imbalance and hypothalamic inflammation in mouse primary astrocyte and organotypic cultures, through the AMPK signaling pathway and neuropeptidergic circuitry governing feeding behavior. Our findings reveal that PDK2 ablation or inhibition in mouse astrocytes attenuates diabetes-induced hypothalamic inflammation and subsequent alterations in feeding behavior. Hypothalamic inflammation is involved in the pathogenesis of diabetes. The underlying mechanisms are unclear. Here, the authors show that astrocytic PDK2 ablation or inhibition attenuates hypothalamic inflammation in mouse models of diabetes. Rahman, Md Habibur; Bhusal, Anup; Kim, Jae-Hong; Jha, Mithilesh Kumar; Song, Gyun Jee; Go, Younghoon; Jang, Il-Sung; Lee, In-Kyu; Suk, Kyoungho Kyungpook Natl Univ, Sch Med, Dept Biomed Sci, BK21 Plus KNU Biomed Convergence Program, Daegu, South Korea; Kyungpook Natl Univ, Sch Med, Dept Pharmacol, Daegu, South Korea; Johns Hopkins Univ, Dept Neurol, Baltimore, MD 21205 USA; Catholic Kwandong Univ, Dept Med Sci, Coll Med, Kangnung, South Korea; Catholic Kwandong Univ, Int St Marys Hosp, Translat Brain Res Ctr, Incheon, South Korea; Korea Inst Oriental Med, Korean Med Applicat Ctr, Daegu 41062, South Korea; Kyungpook Natl Univ, Sch Dent, Dept Pharmacol, Daegu 700412, South Korea; Kyungpook Natl Univ, Brain Sci & Engn Inst, Daegu 41944, South Korea; Kyungpook Natl Univ Hosp, Sch Med, Dept Internal Med, Daegu 700721, South Korea; Kyungpook Natl Univ, Res Inst Aging & Metab, Daegu 700721, South Korea ; Lee, In-Kyu/AAR-6374-2021; Rahman, Md Habibur/HMD-4572-2023 59607139800; 57200274141; 55926599800; 55553038000; 7402253055; 55455882000; 7102177910; 36071537600; 7005114595 ksuk@knu.ac.kr; NATURE COMMUNICATIONS NAT COMMUN 2041-1723 11 1 SCIE MULTIDISCIPLINARY SCIENCES 2020 14.919 4.9 1.62 2025-06-25 51 49 BETA/NF-KAPPA-B; FOOD-INTAKE; BLOOD-PRESSURE; AGRP NEURONS; LACTATE; BRAIN; OBESITY; INSULIN; GLUCOSE; OVERNUTRITION Animals; Astrocytes; Brain Diseases, Metabolic; Diabetes Mellitus; Disease Models, Animal; Feeding Behavior; Hypothalamus; Inflammation; Mice; Obesity; Pyruvate Dehydrogenase Acetyl-Transferring Kinase; Signal Transduction; glucose; hydroxymethylglutaryl coenzyme A reductase kinase; insulin; interleukin 1beta; interleukin 6; ketone body; lactic acid; leptin; messenger RNA; neuropeptide; neuropeptide Y; proopiomelanocortin; pyruvate dehydrogenase kinase 2; tumor necrosis factor; diabetes; enzyme; homeostasis; inhibition; numerical model; AMPK signaling; animal behavior; animal cell; animal experiment; animal model; animal tissue; Article; astrocyte; astrocyte culture; brain electrophysiology; brain slice; cerebrospinal fluid level; controlled study; data analysis software; diet-induced obesity; enzyme linked immunosorbent assay; enzyme phosphorylation; feeding behavior; food intake; gene overexpression; gliosis; glucose blood level; glycolysis; histopathology; hyperglycemia; hypothalamic slice; hypothalamic tissue; hypothalamus; immunohistochemistry; immunoregulation; insulin dependent diabetes mellitus; male; mediobasal hypothalamus; metabolic regulation; mouse; mRNA expression level; nervous system inflammation; non insulin dependent diabetes mellitus; nonhuman; primary culture; protein expression level; real time reverse transcription polymerase chain reaction; reverse transcription polymerase chain reaction; streptozotocin-induced diabetes mellitus; thermogenesis; upregulation; Western blotting; whole cell patch clamp; animal; astrocyte; cytology; diabetes mellitus; disease model; inflammation; metabolic encephalopathy; metabolism; obesity; pathology; signal transduction English 2020 2020-11-20 10.1038/s41467-020-19576-1 바로가기 바로가기 바로가기 바로가기
Editorial Material Can habitual exercise really increase serum concentrations of persistent organic pollutants? Lee, Yu-Mi; Lee, Duk-Hee Kyungpook Natl Univ, Sch Med, Dept Prevent Med, 680 Gukchaebosang Ro, Daegu 41944, South Korea; Kyungpook Natl Univ, Dept Biomed Sci, BK21 Plus KNU Biomed Convergence Program, Daegu, South Korea 57075191600; 57211851121 leedh@knu.ac.kr;lee_dh@knu.ac.kr; ENVIRONMENT INTERNATIONAL ENVIRON INT 0160-4120 1873-6750 140 SCIE ENVIRONMENTAL SCIENCES 2020 9.621 4.9 0 2025-06-25 1 1 OBESITY Adolescent; Child; Environmental Pollutants; Humans; Persistent Organic Pollutants; Pesticides; Plasma; Polychlorinated Biphenyls; liver enzyme; polychlorinated biphenyl; pesticide; polychlorinated biphenyl; biotransformation; body composition; body mass; body weight gain; body weight loss; circulation; concentration (parameter); enzyme activity; exercise; groups by age; health hazard; human; insulin resistance; Letter; lipolysis; lipophilicity; metabolism; obesity; persistent organic pollutant; priority journal; sex; validity; adolescent; chemistry; child; plasma; pollutant English 2020 2020-07 10.1016/j.envint.2020.105615 바로가기 바로가기 바로가기 바로가기
Article Cardio-centric hemodynamic management improves spinal cord oxygenation and mitigates hemorrhage in acute spinal cord injury Chronic high-thoracic and cervical spinal cord injury (SCI) results in a complex phenotype of cardiovascular consequences, including impaired left ventricular (LV) contractility. Here, we aim to determine whether such dysfunction manifests immediately post-injury, and if so, whether correcting impaired contractility can improve spinal cord oxygenation (SCO2), blood flow (SCBF) and metabolism. Using a porcine model of T2 SCI, we assess LV end-systolic elastance (contractility) via invasive pressure-volume catheterization, monitor intraparenchymal SCO2 and SCBF with fiberoptic oxygen sensors and laser-Doppler flowmetry, respectively, and quantify spinal cord metabolites with microdialysis. We demonstrate that high-thoracic SCI acutely impairs cardiac contractility and substantially reduces SCO2 and SCBF within the first hours post-injury. Utilizing the same model, we next show that augmenting LV contractility with the beta-agonist dobutamine increases SCO2 and SCBF more effectively than vasopressor therapy, whilst also mitigating increased anaerobic metabolism and hemorrhage in the injured cord. Finally, in pigs with T2 SCI survived for 12 weeks post-injury, we confirm that acute hemodynamic management with dobutamine appears to preserve cardiac function and improve hemodynamic outcomes in the chronic setting. Our data support that cardio-centric hemodynamic management represents an advantageous alternative to the current clinical standard of vasopressor therapy for acute traumatic SCI. Williams, Alexandra M.; Manouchehri, Neda; Erskine, Erin; Tauh, Keerit; So, Kitty; Shortt, Katelyn; Webster, Megan; Fisk, Shera; Billingsley, Avril; Munro, Alex; Tigchelaar, Seth; Streijger, Femke; Kim, Kyoung-Tae; Kwon, Brian K.; West, Christopher R. Univ British Columbia, Int Collaborat Repair Discoveries ICORD, Vancouver, BC, Canada; Univ British Columbia, Fac Med, Dept Cellular & Physiol Sci, Vancouver, BC, Canada; Kyungpook Natl Univ Hosp, Sch Med, Dept Neurosurg, Daegu, South Korea; Univ British Columbia, Vancouver Spine Surg Inst, Dept Orthopaed, Vancouver, BC, Canada ; West, Christopher/I-4677-2013 56390300700; 56685312300; 57193719210; 56899044200; 57194112871; 57194105837; 57214916693; 57212741152; 57219401906; 57219400822; 56610817600; 7801420947; 57201369790; 55851635600; 56232410100 chris.west@ubc.ca; NATURE COMMUNICATIONS NAT COMMUN 2041-1723 11 1 SCIE MULTIDISCIPLINARY SCIENCES 2020 14.919 4.9 0.81 2025-06-25 27 27 PORCINE MODEL; BLOOD-FLOW; CARDIOVASCULAR-DISEASE; NOREPINEPHRINE; DOBUTAMINE; METABOLISM; TRAUMA; SIZE Animals; Disease Models, Animal; Dobutamine; Female; Heart; Hemodynamics; Hemorrhage; Laser-Doppler Flowmetry; Molecular Chaperones; Norepinephrine; Regional Blood Flow; Respiratory Physiological Phenomena; Spinal Cord; Spinal Cord Injuries; Swine; Ventricular Dysfunction, Left; Suidae; Sus; dobutamine; noradrenalin; oxygen; chaperone; dobutamine; noradrenalin; cell component; injury; metabolism; metabolite; oxygenation; phenotype; anaerobic metabolism; animal experiment; animal tissue; Article; catheterization; continuous infusion; controlled study; drug efficacy; drug megadose; female; heart function; heart left ventricle endsystolic volume; heart muscle contractility; hemodynamic parameters; hemodynamics; laser Doppler flowmetry; metabolite; microdialysis; nonhuman; outcome assessment; oxygenation; porcine model; pressure volume curve; spinal cord; spinal cord blood flow; spinal cord hemorrhage; spinal cord injury; thoracic spinal cord; Yucatan micropig; animal; bleeding; blood flow; disease model; heart; heart left ventricle function; metabolism; pathology; pathophysiology; physiology; pig; respiratory function; spinal cord; spinal cord injury English 2020 2020-10-15 10.1038/s41467-020-18905-8 바로가기 바로가기 바로가기 바로가기
Article Enhanced succinic acid production by Mannheimia employing optimal malate dehydrogenase Succinic acid (SA), a dicarboxylic acid of industrial importance, can be efficiently produced by metabolically engineered Mannheimia succiniciproducens. Malate dehydrogenase (MDH) is one of the key enzymes for SA production, but has not been well characterized. Here we report biochemical and structural analyses of various MDHs and development of hyper-SA producing M. succiniciproducens by introducing the best MDH. Corynebacterium glutamicum MDH (CgMDH) shows the highest specific activity and least substrate inhibition, whereas M. succiniciproducens MDH (MsMDH) shows low specific activity at physiological pH and strong uncompetitive inhibition toward oxaloacetate (ki of 67.4 and 588.9 mu M for MsMDH and CgMDH, respectively). Structural comparison of the two MDHs reveals a key residue influencing the specific activity and susceptibility to substrate inhibition. A high-inoculum fed-batch fermentation of the final strain expressing cgmdh produces 134.25gL(-1) of SA with the maximum productivity of 21.3gL(-1)h(-1), demonstrating the importance of enzyme optimization in strain development. Malate dehydrogenase (MDH) is one of the key enzymes for succinic acid (SA) bioproduction. Here, the authors report biochemical and structural analyses of various MDHs to reveal amino acids influencing the specific activity and susceptibility to substrate inhibition, and achieve industrial-level SA production. Ahn, Jung Ho; Seo, Hogyun; Park, Woojin; Seok, Jihye; Lee, Jong An; Kim, Won Jun; Kim, Gi Bae; Kim, Kyung-Jin; Lee, Sang Yup Korea Adv Inst Sci & Technol KAIST, Metab & Biomol Engn Natl Res Lab, Dept Chem & Biomol Engn, Inst BioCentury,BK21 Plus Program, Daejeon 34141, South Korea; Korea Adv Inst Sci & Technol, Syst Metab Engn & Syst Healthcare Cross Generat C, Daejeon 34141, South Korea; Korea Adv Inst Sci & Technol, Bioinformat Res Ctr, Daejeon 34141, South Korea; Korea Adv Inst Sci & Technol, BioProc Engn Res Ctr, Daejeon 34141, South Korea; Kyungpook Natl Univ, Sch Life Sci, KNU Creat BioRes Grp, Daegu 41566, South Korea; Pohang Univ Sci & Technol, Pohang Accelerator Lab, Pohang, South Korea; Kyungpook Natl Univ, KNU Inst Microorganisms, Daegu 41566, South Korea Kim, Kyung-Jin/MVY-3405-2025; Kim, Wonjun/KDO-4306-2024; Lee, Sang Yup/C-1526-2011 57169290700; 57189697998; 57211680374; 57216545714; 57200389336; 57188820600; 57204761151; 55510867400; 57193960263 kkim@knu.ac.kr;leesy@kaist.ac.kr; NATURE COMMUNICATIONS NAT COMMUN 2041-1723 11 1 SCIE MULTIDISCIPLINARY SCIENCES 2020 14.919 4.9 4.16 2025-06-25 109 117 SUBSTRATE-INHIBITION; ESCHERICHIA-COLI; SACCHAROMYCES-CEREVISIAE; LACTATE-DEHYDROGENASE; ASPARTATE SHUTTLE; SUCCINICIPRODUCENS; MITOCHONDRIAL; FERMENTATION; CONSTRUCTION; REPLACEMENT Bacterial Proteins; Bioreactors; Corynebacterium glutamicum; Fermentation; Kinetics; Malate Dehydrogenase; Metabolic Engineering; Oxaloacetic Acid; Pasteurellaceae; Protein Conformation; Recombinant Proteins; Substrate Specificity; Succinic Acid; Corynebacterium glutamicum; Mannheimia; Mannheimia succiniciproducens; 2 oxoglutaric acid; acetate kinase; acetic acid; acetyl coenzyme A; ampicillin; chloramphenicol; citric acid; fumarate hydratase; fumarate reductase; fumaric acid; glucose; glycerol; glycerol 3 phosphate dehydrogenase; kanamycin; lactate dehydrogenase; lactic acid; lysine acetyltransferase; macrogol; malate dehydrogenase; malic acid; menaquinol oxidase (H+-transporting); oxaloacetic acid; phosphate acetyltransferase; phosphoenolpyruvate; phosphoenolpyruvate carboxylase; pyruvic acid; succinic acid; succinyl coenzyme A; unindexed drug; bacterial protein; malate dehydrogenase; recombinant protein; succinic acid; enzyme; enzyme activity; fermentation; optimization; organic acid; pH; physiological response; Actinobacillus succinogenes; Article; bacterial strain; biomass production; computer simulation; controlled study; Corynebacterium glutamicum; Cryptococcus neoformans; crystal structure; crystallization; electron transport; enzyme active site; enzyme activity; enzyme engineering; enzyme inhibition; enzyme kinetics; Escherichia coli; fed batch fermentation; gene overexpression; glucose intake; glucose transport; glycolysis; Haemophilus influenzae; interferometry; ion exchange chromatography; Mannheimia; Mannheimia succiniciproducens; Methylobacterium extorquens; Mycobacterium tuberculosis; nonhuman; nucleotide sequence; pH; Phycomyces blakesleeanus; polymerase chain reaction; Saccharomyces cerevisiae; thermodynamics; Yarrowia lipolytica; bioreactor; chemistry; enzyme specificity; enzymology; fermentation; genetics; kinetics; metabolic engineering; metabolism; Pasteurellaceae; protein conformation English 2020 2020-04-23 10.1038/s41467-020-15839-z 바로가기 바로가기 바로가기 바로가기
Article N-AS-triggered SPMs are direct regulators of microglia in a model of Alzheimer's disease Sphingosine kinase1 (SphK1) is an acetyl-CoA dependent acetyltransferase which acts on cyclooxygenase2 (COX2) in neurons in a model of Alzheimer's disease (AD). However, the mechanism underlying this activity was unexplored. Here we show that N-acetyl sphingosine (N-AS) is first generated by acetyl-CoA and sphingosine through SphK1. N-AS then acetylates serine 565 (S565) of COX2, and the N-AS-acetylated COX2 induces the production of specialized pro-resolving mediators (SPMs). In a mouse model of AD, microglia show a reduction in N-AS generation, leading to decreased acetyl-S565 COX2 and SPM production. Treatment with N-AS increases acetylated COX2 and N-AS-triggered SPMs in microglia of AD mice, leading to resolution of neuroinflammation, an increase in microglial phagocytosis, and improved memory. Taken together, these results identify a role of N-AS in the dysfunction of microglia in AD. Neuronal sphingosine kinase 1 (SphK1) acetylates COX2 which is needed for microglial phagocytosis activity, and release of pro-resolving mediators (SPMs) from neurons. Here the authors examine how SphK1-mediates COX2 acetylation, and how this leads to increased secretion of SPMs from neurons in the context of Alzheimer's disease models. Lee, Ju Youn; Han, Seung Hoon; Park, Min Hee; Song, Im-Sook; Choi, Min-Koo; Yu, Eunsoo; Park, Cheol-Min; Kim, Hee-Jin; Kim, Seung Hyun; Schuchman, Edward H.; Jin, Hee Kyung; Bae, Jae-sung Kyungpook Natl Univ, KNU Alzheimers Dis Res Inst, Daegu 41566, South Korea; Kyungpook Natl Univ, Sch Med, Cell & Matrix Res Inst, Dept Physiol, Daegu 41944, South Korea; Kyungpook Natl Univ, Dept Biomed Sci, BK21 Plus KNU Biomed Convergence Program, Daegu 41944, South Korea; Kyungpook Natl Univ, Coll Pharm, Daegu 41566, South Korea; Kyungpook Natl Univ, Res Inst Pharmaceut Sci, Daegu 41566, South Korea; Dankook Univ, Coll Pharm, Cheonan 31116, South Korea; Ulsan Natl Inst Sci & Technol UNIST, Dept Chem, Ulsan 44919, South Korea; Hanyang Univ, Dept Neurol, Coll Med, Seoul 04763, South Korea; Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, New York, NY 10029 USA; Kyungpook Natl Univ, Coll Vet Med, Dept Lab Anim Med, Daegu 41566, South Korea Kim, Hee-Jin/P-1903-2015; Park, Cheol-Min/G-2688-2010; Kim, Young/T-8521-2019; Bae, Jae-sung/AAM-8663-2021; KIM, Seung Hyun/T-5133-2017 56715493500; 57201661930; 55807755700; 7201564500; 8695781400; 57216737733; 19335557000; 58365187300; 55911799500; 7004364820; 8088145800; 35209510400 hkjin@knu.ac.kr;jsbae@knu.ac.kr; NATURE COMMUNICATIONS NAT COMMUN 2041-1723 11 1 SCIE MULTIDISCIPLINARY SCIENCES 2020 14.919 4.9 1.73 2025-06-25 54 41 RESOLVING LIPID MEDIATORS; INFLAMMATION; RESOLUTION; POLARIZATION; PATHOLOGY; PROTEIN; NAIVE Acetyl Coenzyme A; Acetylation; Alzheimer Disease; Animals; Anti-Inflammatory Agents; Brain; Cell Line; Cyclooxygenase 2; Disease Models, Animal; Humans; Male; Memory; Mice; Mice, Transgenic; Microglia; Mutagenesis; Neurons; Phagocytosis; Phosphotransferases (Alcohol Group Acceptor); Presenilin-1; Primary Cell Culture; Recombinant Proteins; Serine; Sphingosine; Mus; acetyl coenzyme A; acetylsalicylic acid; cyclooxygenase 2; cytochrome P450; gelatinase B; sphingosine; sphingosine kinase 1; acetyl coenzyme A; antiinflammatory agent; cyclooxygenase 2; N-acetylsphingosine; phosphotransferase; presenilin 1; presenilin 1, mouse; PTGS2 protein, human; Ptgs2 protein, mouse; recombinant protein; serine; sphingosine; Sphk1 protein, mouse; disease; induced response; model; nervous system disorder; adult; Alzheimer disease; animal cell; animal experiment; animal model; animal tissue; antiinflammatory activity; apoptosis; Article; astrocyte; behavior; binding affinity; binding assay; bioinformatics; carbon nuclear magnetic resonance; controlled study; crystal structure; degenerative disease; density gradient centrifugation; disease exacerbation; drug acetylation; enzyme activity; enzyme kinetics; enzyme linked immunosorbent assay; flow cytometry; gene expression; growth regulation; histology; hydrogen bond; immune response; immunofluorescence; lipidomics; liquid chromatography-mass spectrometry; live cell imaging; male; memory; microglia; molecular docking; mouse; multiple reaction monitoring; mutagenesis; nervous system inflammation; nonhuman; phagocytosis; phenotype; real time polymerase chain reaction; RNA extraction; RNA isolation; RNA sequence; specialized pre resolving mediator; synthesis; Western blotting; acetylation; Alzheimer disease; animal; brain; cell line; disease model; drug effect; genetics; human; immunology; metabolism; microglia; nerve cell; pathology; primary cell culture; transgenic mouse English 2020 2020-05-12 10.1038/s41467-020-16080-4 바로가기 바로가기 바로가기 바로가기
Article Precise capture and dynamic relocation of nanoparticulate biomolecules through dielectrophoretic enhancement by vertical nanogap architectures Toward the development of surface-sensitive analytical techniques for biosensors and diagnostic biochip assays, a local integration of low-concentration target materials into the sensing region of interest is essential to improve the sensitivity and reliability of the devices. As a result, the dynamic process of sorting and accurate positioning the nanoparticulate biomolecules within pre-defined micro/nanostructures is critical, however, it remains a huge hurdle for the realization of practical surface-sensitive biosensors and biochips. A scalable, massive, and non-destructive trapping methodology based on dielectrophoretic forces is highly demanded for assembling nanoparticles and biosensing tools. Herein, we propose a vertical nanogap architecture with an electrode-insulator-electrode stack structure, facilitating the generation of strong dielectrophoretic forces at low voltages, to precisely capture and spatiotemporally manipulate nanoparticles and molecular assemblies, including lipid vesicles and amyloid-beta protofibrils/oligomers. Our vertical nanogap platform, allowing low-voltage nanoparticle captures on optical metasurface designs, provides new opportunities for constructing advanced surface-sensitive optoelectronic sensors. Yu, Eui-Sang; Lee, Hyojin; Lee, Sun-Mi; Kim, Jiwon; Kim, Taehyun; Lee, Jongsu; Kim, Chulki; Seo, Minah; Kim, Jae Hun; Byun, Young Tae; Park, Seung-Chul; Lee, Seung-Yeol; Lee, Sin-Doo; Ryu, Yong-Sang Korea Inst Sci & Technol, Sensor Syst Res Ctr, Seoul 02792, South Korea; Seoul Natl Univ, Dept Elect & Comp Engn, Seoul 02792, South Korea; Korea Inst Sci & Technol, Ctr Biomat, Seoul 02792, South Korea; Korea Inst Sci & Technol, Clean Energy Res Ctr, Seoul 02792, South Korea; Korea Inst Machinery & Mat, Dept Nat Inspired Nanoconvergence Syst, Daejeon 34103, South Korea; Kyungpook Natl Univ, Sch Elect Engn, Daegu 41566, South Korea ; Seo, Minah/K-4997-2018; lee, sang/Q-4650-2019; Lee, Seungwoo/U-8056-2017; Ryu, Yong-Sang/AAI-3948-2020; Yu, Eui-Sang/GVR-7972-2022 56297930000; 35196276100; 36063914900; 57612765700; 59783064600; 58175758800; 55539260500; 25640297500; 57211615940; 7102768601; 54898973300; 55881869300; 34974364800; 55229727000 sidlee@plaza.snu.ac.kr;ysryu82@kist.re.kr; NATURE COMMUNICATIONS NAT COMMUN 2041-1723 11 1 SCIE MULTIDISCIPLINARY SCIENCES 2020 14.919 4.9 1.19 2025-06-25 48 50 FLOW; OLIGOMERS; MICROFLUIDICS; MANIPULATION; EXOSOMES; PEPTIDE Bacillus subtilis; Biocompatible Materials; Biosensing Techniques; Computer Simulation; Dimethylpolysiloxanes; Electrochemistry; Electrodes; Equipment Design; Fungi; Kinetics; Lipids; Materials Testing; Nanoparticles; Nanostructures; Nanotechnology; Osmosis; Reproducibility of Results; nanoparticle; baysilon; biomaterial; dimeticone; lipid; nanomaterial; nanoparticle; analytical method; equipment; molecular analysis; nanoparticle; precision; architecture; Article; drug delivery system; genetic recombination; impedance spectroscopy; local field potential; mathematical phenomena; nanofabrication; particle size; photon correlation spectroscopy; polarization; Raman spectrometry; refraction index; relaxation time; spectroscopy; stimulation; synapse vesicle; time lapse imaging; transmission electron microscopy; Bacillus subtilis; chemistry; computer simulation; electrochemistry; electrode; equipment design; fungus; genetic procedures; kinetics; materials testing; nanotechnology; osmosis; procedures; reproducibility English 2020 2020-06-04 10.1038/s41467-020-16630-w 바로가기 바로가기 바로가기 바로가기
Article Prediction-based highly sensitive CRISPR off-target validation using target-specific DNA enrichment CRISPR effectors, which comprise a CRISPR-Cas protein and a guide (g)RNA derived from the bacterial immune system, are widely used for target-specific genome editing. When the gRNA recognizes genomic loci with sequences that are similar to the target, deleterious mutations can occur. Off-target mutations with a frequency below 0.5% remain mostly undetected by current genome-wide off-target detection techniques. Here we report a method to effectively detect extremely small amounts of mutated DNA based on predicted off-target-specific amplification. In this study, we used various genome editors to induce intracellular genome mutations, and the CRISPR amplification method detected off-target mutations at a significantly higher rate (1.6 similar to 984 fold increase) than an existing targeted amplicon sequencing method. In the near future, CRISPR amplification in combination with genome-wide off-target detection methods will allow detection of genome editor-induced off-target mutations with high sensitivity and in a non-biased manner. Kang, Seung-Hun; Lee, Wi-jae; An, Ju-Hyun; Lee, Jong-Hee; Kim, Young-Hyun; Kim, Hanseop; Oh, Yeounsun; Park, Young-Ho; Jin, Yeung Bae; Jun, Bong-Hyun; Hur, Junho K.; Kim, Sun-Uk; Lee, Seung Hwan Kyung Hee Univ, Grad Sch, Dept Med, Seoul, South Korea; Korea Res Inst Biosci & Biotechnol KRIBB, Futurist Anim Resource & Res Ctr FARRC, Cheongju, South Korea; Konkuk Univ, Dept Biosci & Biotechnol, Seoul 143701, South Korea; Korea Univ Sci & Technol UST, KRIBB Sch Biosci, Dept Funct Genom, Daejeon, South Korea; Korea Res Inst Biosci & Biotechnol KRIBB, Natl Primate Res Ctr NPRC, Cheongju, South Korea; Kyungpook Natl Univ, Sch Life Sci & Biotechnol, BK21 Plus KNU Creat BioRes Grp, Daegu, South Korea; Korea Univ, Coll Life Sci & Biotechnol, Div Biotechnol, Seoul 02841, South Korea; Kyung Hee Univ, Coll Med, Dept Pathol, Seoul, South Korea; Kyung Hee Univ, Grad Sch, Dept Biomed Sci, Seoul, South Korea; Hanyang Univ, Coll Med, Dept Med Genet, Seoul, South Korea Kim, Sunuk/KJM-5211-2024; Hur, Junho/ADK-0757-2022; 김, 영현/HLH-3847-2023 57218162734; 57218165418; 57210789913; 57203736066; 54393408600; 57203630238; 57218169850; 56246852400; 35344928700; 35229652600; 35740323500; 8278891100; 57202327400 jh0210@gmail.com;sunuk@kribb.re.kr;lsh080390@kribb.re.kr; NATURE COMMUNICATIONS NAT COMMUN 2041-1723 11 1 SCIE MULTIDISCIPLINARY SCIENCES 2020 14.919 4.9 1.73 2025-06-25 54 48 NEXT-GENERATION; WEB TOOL; NUCLEASES; CPF1; SEQ; MUTAGENESIS; CLEAVAGE; CHOPCHOP; RARE Clustered Regularly Interspaced Short Palindromic Repeats; CRISPR-Cas Systems; DNA; Gene Editing; Humans; Mutation; RNA, Guide; Bacteria (microorganisms); DNA; guide RNA; detection method; DNA; genome; model validation; mutation; protein; amplicon; article; clustered regularly interspaced short palindromic repeat; editor; human; prediction; CRISPR Cas system; gene editing; genetics; mutation English 2020 2020-07-17 10.1038/s41467-020-17418-8 바로가기 바로가기 바로가기 바로가기
Article Switching from tenofovir disoproxil fumarate to tenofovir alafenamide in virologically suppressed patients with chronic hepatitis B: a randomised, double-blind, phase 3, multicentre non-inferiority study Background Treatment with tenofovir disoproxil fumarate has been associated with renal toxicity or reductions in bone mineral density, or both, in some patients with chronic hepatitis B virus (HBV) infection. Tenofovir alafenamide is a tenofovir prodrug with high intrahepatic concentrations of active drug and reduced systemic tenofovir exposures compared with tenofovir disoproxil fumarate. In patients with chronic HBV, tenofovir alafenamide has shown efficacy non-inferior to that of tenofovir disoproxil fumarate with improved renal and bone safety. With this non-inferiority study, we aimed to evaluate the efficacy and safety of tenofovir alafenamide in patients with HBV infection switching from tenofovir disoproxil fumarate who are virally suppressed. Methods Patients with chronic HBV infection who had been receiving tenofovir disoproxil fumarate for 48 weeks or more and who had HBV DNA less than the lower limit of quantification (LLOQ) for at least 12 weeks were recruited to this randomised, multicentre, double-blind, phase 3 non-inferiority study. Patients were randomly assigned in a 1:1 ratio to receive tenofovir alafenamide 25 mg once a day or to continue tenofovir disoproxil fumarate 300 mg once a day. The primary efficacy endpoint was loss of virological control, defined as the proportion of patients who received at least one dose of study drug who had HBV DNA of at least 20 IU/mL at week 48 by the modified US Food and Drug Administration (FDA) snapshot algorithm. Key safety endpoints were changes in hip and spine bone mineral density, estimated creatinine clearance by Cockcroft-Gault, and markers of bone turnover and renal tubular function. The study was powered for non-inferiority in efficacy of tenofovir alafenamide versus tenofovir disoproxil fumarate with a 4% margin. Investigators and patients were unaware of treatment allocation and on-treatment results. This trial is ongoing and is registered with ClinicalTrials.gov , number NCT02979613. Findings Participants in this study were enrolled between Dec 29,2016, and Oct 20,2017.541 patients were screened and 490 patients were randomly assigned to switch to tenofovir alafenamide or to stay on tenofovir disoproxil fumarate. Two patients assigned to receive tenofovir alafenamide did not receive treatment; thus the full analysis set for efficacy and safety analyses consisted of 243 patients in the tenofovir alafenamide group and 245 in the tenofovir disoproxil fumarate group. At week 48, one patient from each treatment group (both <1%) had HBV DNA of at least 20 IU/mL (difference in proportion 0.0%, 95% CI -1.9 to 2.0), thereby showing non-inferior efficacy of tenofovir alafenamide to tenofovir disoproxil fumarate. Patients who received tenofovir alafenamide had significantly increased bone mineral density at hip (mean change 0.66% [SD 2.08] vs -0.51% [SD 1.91]; difference in least square means 1.17% [95% CI 0.80 to 1.54; p<0.0001]) and at spine (mean change 1.74% [3.46] vs -0.11% [3.13]; difference in least square means 1.85% [1.24 to 2.46; p<0.0001]), creatinine clearance by Cockcroft-Gault relative to tenofovir disoproxil fumarate (median change 0.94 mL/min [IQR -4.47 to 6.24] vs -2.74 mL/min [-7.89 to 1.88]; p <0.0001), and improved markers of bone turnover and tubular function at week 48. The most common treatment-emergent adverse events were upper respiratory tract infection (18 [7%] of 243 patients in the tenofovir alafenamide group and 16 [7%] of 245 patients in the tenofovir disoproxil fumarate group) and nasopharyngitis (13 [5%] of 243 patients in the tenofovir alafenamide group and 12 [5%] of 245 patients in the tenofovir disoproxil fumarate group). The incidence of grade 3 and above adverse events and serious adverse events was low and similar between groups. No viral resistance was observed in patients who qualified for viral sequencing. Interpretation These findings suggest that tenofovir alafenamide can be substituted for tenofovir disoproxil fumarate in patients with HBV infection for improved safety without a loss of efficacy. Copyright (C) 2020 Elsevier Ltd. All rights reserved. Lampertico, Pietro; Buti, Maria; Fung, Scott; Ahn, Sang Hoon; Chuang, Wan-Long; Tak, Won Young; Ramji, Alnoor; Chen, Chi-Yi; Tam, Edward; Bae, Ho; Ma, Xiaoli; Flaherty, John F.; Gaggar, Anuj; Lau, Audrey; Liu, Yang; Wu, George; Suri, Vithika; Tan, Susanna K.; Subramanian, G. Mani; Trinh, Huy; Yoon, Seung-Kew; Agarwal, Kosh; Lim, Young-Suk; Chan, Henry L. Y. Univ Milan, Fdn IRCCS Ca Granda Osped, CRC AM&A Migliavacca Ctr Liver Dis, Div Gastroenterol & Hepatol,Maggiore Policlin, Milan, Italy; Hosp Gen Univ Vall dHebron, Barcelona, Spain; Toronto Gen Hosp, Toronto, ON, Canada; Yongsei Univ, Severance Hosp, Seoul, South Korea; Kaohsiung Med Univ, Kaohsiung Med Univ Hosp, Kaohsiung, Taiwan; Kyungpook Natl Univ, Kyungpook Natl Univ Hosp, Sch Med, Daegu, South Korea; Gastrointestinal Res Inst, Vancouver, BC, Canada; Chiayi Christian Hosp, Chiayi, Taiwan; LAIR Ctr, Vancouver, BC, Canada; Asian Pacific Liver Ctr, Los Angeles, CA USA; Med Coll Penn & Hahnemann Univ, Philadelphia, PA 19102 USA; Gilead Sci, Foster City, CA USA; Silicon Valley Res Inst, San Jose, CA USA; Catholic Univ Korea, Seoul, South Korea; Kings Coll Hosp London, London, England; Univ Ulsan, Asan Med Ctr, Coll Med, Seoul, South Korea; Chinese Univ Hong Kong, Hong Kong, Peoples R China Chan, Henry/B-9636-2008; Ahn, Sang Hoon/AFM-2603-2022; Wu, George/JCE-1302-2023; Agarwal, Kosh/ABH-8721-2020; Lim, Young-Suk/AFQ-5165-2022; Buti, MARIA/A-5327-2019; Lampertico, Pietro/J-8463-2018; Chuang, Wan-Long/C-9536-2009 7006770607; 7007153523; 7201970083; 7401989551; 57220662417; 7004074582; 6507797553; 7501967827; 56437380100; 56088528000; 56813955100; 7102825519; 6602353207; 56235673400; 57188678565; 57191504682; 57200392461; 57215085360; 57193563568; 7005816675; 7404036291; 7201380739; 25224923200; 25722700100 pietro.lampertico@unimi.it; LANCET GASTROENTEROLOGY & HEPATOLOGY LANCET GASTROENTEROL 2468-1253 5 5 SCIE GASTROENTEROLOGY & HEPATOLOGY 2020 18.486 4.9 5.24 2025-06-25 120 116 BONE-MINERAL DENSITY; FANCONI SYNDROME; KIDNEY TOXICITY; VIRUS INFECTION; EMTRICITABINE; LAMIVUDINE; SAFETY; ADULTS Adenine; Antiviral Agents; Bone Density; Creatinine; DNA, Viral; Double-Blind Method; Drug Substitution; Female; Hepatitis B virus; Hepatitis B, Chronic; Humans; Male; Middle Aged; Nasopharyngitis; Renal Insufficiency; Respiratory Tract Infections; Sustained Virologic Response; Tenofovir; alanine aminotransferase; tenofovir alafenamide; tenofovir disoproxil; adenine; antivirus agent; creatinine; GS-7340; tenofovir; virus DNA; Article; bipolar disorder; bone density; bone turnover; breast cancer; chronic hepatitis B; controlled study; creatinine clearance; diabetes mellitus; double blind procedure; drug efficacy; drug safety; dual energy X ray absorptiometry; Emtree; gastroenteritis; glomerulus filtration rate; headache; heart rupture; human; limb pain; limit of quantitation; liver cell carcinoma; major clinical study; melanoma; multicenter study; pancreatitis; phase 3 clinical trial; priority journal; randomized controlled trial; suicidal ideation; upper respiratory tract infection; wrist fracture; blood; chronic hepatitis B; clinical trial; drug effect; drug substitution; female; Hepatitis B virus; kidney failure; male; middle aged; respiratory tract infection; rhinopharyngitis; sustained virologic response English 2020 2020-05 10.1016/s2468-1253(19)30421-2 바로가기 바로가기 바로가기 바로가기
Article Universal light-guiding geometry for on-chip resonators having extremely high Q-factor By providing an effective way to leverage nonlinear phenomena in integrated devices, high-Q optical resonators have led to recent advances in on-chip photonics. However, developing fabrication processes to shape any new material into a resonator with extremely smooth surfaces on a chip has been an exceptionally challenging task. Here, we describe a universal method to implement ultra-high-Q resonators with any new material having desirable properties that can be deposited by physical vapor deposition. Using this method light-guiding cores with surface roughness on the molecular-scale are created automatically on pre-patterned substrates. Its efficacy has been verified using As2S3, a chalcogenide glass that has high-nonlinearity. The Q-factor of the As2S3 resonator so-developed approached the propagation loss record achieved in chalcogenide fibers which were limited by material losses. Owing to the boosted Q-factor, lasing by stimulated Brillouin scattering has been demonstrated with 100 times lower threshold power than the previous record. High-Q resonators are used to enhance nonlinear phenomena in photonics, but developing a fabrication process to shape a new material into a resonator is challenging and costly. Here, the authors present a method using vapour deposition on pre-patterned substrates to fabricate resonators with any new material. Kim, Dae-Gon; Han, Sangyoon; Hwang, Joonhyuk; Do, In Hwan; Jeong, Dongin; Lim, Ji-Hun; Lee, Yong-Hoon; Choi, Muhan; Lee, Yong-Hee; Choi, Duk-Yong; Lee, Hansuek Korea Adv Inst Sci & Technol KAIST, Dept Phys, Daejeon 34141, South Korea; Korea Adv Inst Sci & Technol KAIST, Grad Sch Nanosci & Technol, Daejeon 34141, South Korea; Daegu Gyeongbuk Inst Sci & Technol, Dept Robot Engn, Daegu 42988, South Korea; Kyungpook Natl Univ, Sch Elect Engn, Daegu 41566, South Korea; Australian Natl Univ, Laser Phys Ctr, Res Sch Phys, Canberra, ACT 2601, Australia Han, Sangyoon/JXM-0806-2024; Choi, Duk-Yong/E-6542-2013; Choi, Duk-Yong/KLE-3829-2024; Lee, Hansuek/G-2007-2015; Lee, Hansuek/HDL-6447-2022 57194633531; 56115439700; 57209586373; 15131461800; 57209569253; 57219620471; 57219622064; 7402093793; 57208480385; 14826492800; 37112322100 duk.choi@anu.edu.au;hansuek@kaist.ac.kr; NATURE COMMUNICATIONS NAT COMMUN 2041-1723 11 1 SCIE MULTIDISCIPLINARY SCIENCES 2020 14.919 4.9 2 2025-06-25 51 65 WAVE-GUIDES; CHALCOGENIDE arsenic derivative; glass; geometry; instrumentation; surface roughness; threshold; Article; drug efficacy; frequency; geometry; light; measurement precision; nanofabrication; nonlinear system; optical resonator; optics; phonon; photonics; physical vapor deposition; surface property English 2020 2020-11-23 10.1038/s41467-020-19799-2 바로가기 바로가기 바로가기 바로가기
Article Wnt-PLC-IP3-Connexin-Ca²⁺ axis maintains ependymal motile cilia in zebrafish spinal cord Ependymal cells (ECs) are multiciliated neuroepithelial cells that line the ventricles of the brain and the central canal of the spinal cord (SC). How ependymal motile cilia are maintained remains largely unexplored. Here we show that zebrafish embryos deficient in Wnt signaling have defective motile cilia, yet harbor intact basal bodies. With respect to maintenance of ependymal motile cilia, plc delta 3a is a target gene of Wnt signaling. Lack of Connexin43 (Cx43), especially its channel function, decreases motile cilia and intercellular Ca2+ wave (ICW) propagation. Genetic ablation of cx43 in zebrafish and mice diminished motile cilia. Finally, Cx43 is also expressed in ECs of the human SC. Taken together, our findings indicate that gap junction mediated ICWs play an important role in the maintenance of ependymal motile cilia, and suggest that the enhancement of functional gap junctions by pharmacological or genetic manipulations may be adopted to ameliorate motile ciliopathy. Ependymal cells are supporting cells in the central nervous system. Here the authors elucidate a signalling axis in zebrafish spinal cord ependymal cells that is important for motile cilia assembly and maintenance, demonstrating that it depends on intercellular propagation of calcium ions via connexin 43. Zhang, Jun; Chandrasekaran, Gopalakrishnan; Li, Wenting; Kim, Dong-Young; Jeong, In Young; Lee, So-Hyun; Liang, Ting; Bae, Jin Young; Choi, Isaac; Kang, Hyuno; Maeng, Jin-Soo; Kim, Myeong-Kyu; Lee, Taewon; Park, Seung Woo; Kim, Min Jung; Kim, Hyung-Seok; Ro, Hyunju; Bae, Yong Chul; Park, Hae-Chul; Choi, Eun Young; Choi, Seok-Yong Chonnam Natl Univ, Dept Biomed Sci, Med Sch, Hwasun 58128, South Korea; Chonnam Natl Univ, Ctr Creat Biomed Scientists, Hwasun 58128, South Korea; Chonnam Natl Univ, Grad Sch, Dept Mol Med, Hwasun 58128, South Korea; Univ Ulsan, Dept Biomed Sci, Coll Med, Seoul 05505, South Korea; Korea Univ, Dept Biomed Sci, Ansan 15355, South Korea; Kyungpook Natl Univ, Sch Dent, Dept Anat & Neurobiol, Daegu 41940, South Korea; Chungnam Natl Univ, Coll Biosci & Biotechnol, Dept Biol Sci, Daejeon 34134, South Korea; Korea Basic Sci Inst, Div Analyt Sci, Daejeon 34133, South Korea; Korea Food Res Inst, Res Grp Bioproc Engn, Wanju Gun 55365, South Korea; Korea Inst Chem Technol, Ctr Convergent Res Emerging Virus Infect, Daejeon 34114, South Korea; Chonnam Natl Univ, Dept Neurol, Med Sch, Gwangju 61469, South Korea; Korea Univ, Coll Sci & Technol, Div Appl Math Sci, Sejong 30019, South Korea; Yonsei Univ, Dept Internal Med, Coll Med, Seoul 03722, South Korea; Sookmyung Womens Univ, Dept Biol Sci, Seoul 04310, South Korea; Chonnam Natl Univ, Dept Forens Med, Med Sch, Hwasun 58128, South Korea ; Park, Seung/C-6989-2011; Chandrasekaran, Gopalakrishnan/Q-8652-2017; Kang, Hyuno/IUO-3103-2023; Kim, Chang Ki/JED-7215-2023; Lee, Seung/A-3743-2012; Kim, Min Jung/JXM-0046-2024; liang, ting/JFB-4960-2023; Choi, Seok-Yong/G-5516-2010 57211969440; 57209031495; 56844328300; 56136651500; 55566114400; 57195539189; 57216531834; 55268279500; 59438507600; 7404071328; 7003475758; 7406089822; 55501330600; 7501836373; 56984360900; 56739347400; 7005589399; 56377838800; 7601568789; 57214257711; 8399307200 choieun@ulsan.ac.kr;zebrafish@chonnam.ac.kr; NATURE COMMUNICATIONS NAT COMMUN 2041-1723 11 1 SCIE MULTIDISCIPLINARY SCIENCES 2020 14.919 4.9 1.4 2025-06-25 31 34 NEONATAL MICE LACKING; DRIVEN FLUID-FLOW; CALCIUM OSCILLATIONS; KUPFFERS VESICLE; SONIC-HEDGEHOG; CELLS; EXPRESSION; CONNEXIN43; LOCALIZATION; ACTIVATION Animals; Cell Differentiation; Cilia; Connexin 43; Connexins; Ependyma; Gap Junctions; Gene Expression Regulation, Developmental; Gene Knockout Techniques; Humans; Male; Mice; Mice, Knockout; Signal Transduction; Spinal Cord; Wnt Signaling Pathway; Zebrafish; Zebrafish Proteins; Danio rerio; Mus; calcium ion; connexin 43; firefly luciferase; green fluorescent protein; messenger RNA; proteinase K; Renilla luciferin 2 monooxygenase; transcription factor; connexin 43; gap junction protein; zebrafish protein; ablation; brain; cell; ciliate; cyprine; cyprinid; embryo; gene; genetic algorithm; genetic analysis; animal experiment; animal tissue; Article; cilium; confocal microscopy; controlled study; electron microscopy; embryo development; ependymoma; gap junction; gene expression; genetic manipulation; genotype; human; human cell; human tissue; immunofluorescence; immunohistochemistry; in situ hybridization; nonhuman; nutritional science; phenotype; polymerase chain reaction; protein expression; rhombencephalon; second cervical vertebra; signal transduction; spinal cord; transmission electron microscopy; Western blotting; Wnt signaling; zebra fish; animal; cell differentiation; cilium; embryology; ependyma; gene expression regulation; gene knockout; genetics; knockout mouse; male; metabolism; mouse; pathology; spinal cord; zebra fish English 2020 2020-04-20 10.1038/s41467-020-15248-2 바로가기 바로가기 바로가기 바로가기
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