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Hepatic angiotensin-converting enzyme 2 expression in metabolic dysfunction-associated steatotic liver disease and in patients with fatal cOVID-19

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World journal of Gastroenterology 2024年第31期30卷 3705-3716页

作者： Angus K jacobs Steven D Morley Kay Samuel Katie Morgan Lyndsey Boswell Timothy j Kendall David A Dorward jonathan A Fallowfield Peter c Hayes john N Plevris Hepatology Laboratory University of EdinburghEdinburgh EH164SBUnited Kingdom Scottish National Blood Transfusion Service Jack Copland CentreEdinburgh EH144BEUnited Kingdom Institute for Regeneration and Repair University of EdinburghEdinburgh EH164UUUnited Kingdom Edinburgh Pathology University of EdinburghEdinburgh EH164SBUnited Kingdom

BAcKGROUND Metabolic dysfunction-associated steatotic liver disease(MASLD),characterised by hepatic lipid accumulation,causes inflammation and oxidative stress accompanied by cell damage and *** injury(LI)is also frequently reported in patients hospitalised with coronavirus disease 2019(cOVID-19),while preexisting MASLD increases the risk of LI and the development of cOVID-19-associated *** of injury at the cellular level remain unclear,but it may be significant that severe acute respiratory syndrome coronavirus 2(SARS-coV-2)which causes cOVID-19,uses angiotensin-converting expression enzyme 2(AcE2),a key regulator of the‘anti-inflammatory’arm of the renin-angiotensin system,for viral attachment and host cell *** To determine if hepatic AcE2 levels are altered during progression of MASLD and in patients who died with severe *** AcE2 protein levels and localisation,and histological fibrosis and lipid droplet accumulation as markers of MASLD were determined in formalin-fixed liver tissue sections across the MASLD pathological spectrum(isolated hepatocellular steatosis,metabolic dysfunction-associated steatohepatitis(MASH)+/-fibrosis,end-stage cirrhosis)and in post-mortem tissues from patients who had died with severe cOVID-19,using AcE2 immunohistochemistry and haematoxylin and eosin and picrosirius red staining of total collagen and lipid droplet areas,followed by quantification using machine learning-based image pixel *** AcE2 staining is primarily intracellular and concentrated in the cytoplasm of centrilobular hepatocytes and apical membranes of bile duct ***,AcE2 protein levels are elevated in non-fibrotic MASH compared to healthy controls but not in the progression to MASH with fibrosis and in ***2 protein levels and histological fibrosis are not associated,but AcE2 and liver lipid droplet content are significantly correlated across the MASLD *** A

关键词： Metabolic dysfunction-associated steatotic liver disease Angiotensin-converting enzyme 2 Immunohistochemistry cOVID-19 cOVID-19-associated cholangiopathy

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cD4^(+)T cells produce IFN-I to license cDc1s for induction of cytotoxic T-cell activity in human tumors

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cellular & Molecular Immunology 2024年第4期21卷 374-392页

作者： Xin Lei Daniël c.de Groot Marij j.P.Welters Tom de Wit Ellen Schrama Hans van Eenennaam Saskia j.Santegoets Timo Oosenbrug Annemarthe van der Veen joris L.Vos charlotte L.Zuur Noel F.c.c.de Miranda Heinz jacobs Sjoerd H.van der Burg jannie Borst Yanling Xiao Department of Immunology Leiden University Medical CenterLeidenThe Netherlands Oncode Institute Leiden University Medical CenterLeidenThe Netherlands Department of Tumor Biology and Immunology The Netherlands Cancer InstituteAmsterdamThe Netherlands Department of Medical Oncology Oncode InstituteLeiden University Medical CenterLeidenThe Netherlands IMMIOS B.V. OssThe Netherlands Division of Medical Oncology The Netherlands Cancer InstituteAmsterdamThe Netherlands Department of Otorhinolaryngology Leiden University Medical center LeidenThe Netherlands Department of Pathology Leiden University Medical CenterLeidenThe Netherlands

cD4^(+)T cells can"help"or"license" conventional type 1 dendritic cells(cDc1s)to induce cD8^(+)cytotoxic T lymphocyte(cTL)anticancer responses,as proven in mouse *** recently identified cDc1s with a transcriptomic imprint of cD4^(+)T-cell help,specifically in T-cell-infiltrated human cancers,and these cells were associated with a good prognosis and response to PD-1-targeting ***,we delineate the mechanism of cDc1 licensing by cD4^(+)T cells in *** cD4^(+)T cells produce IFNβvia the STING pathway,which promotes MHc-I antigen(cross-)presentation by cDc1s and thereby improves their ability to induce cTL anticancer *** cooperation with cD40 ligand(L),IFNβalso optimizes the costimulatory and other functions of cDc1s required for cTL response ***-I-producing cD4^(+)T cells are present in diverse T-cell-infiltrated cancers and likely deliver“help”signals to cTLs locally,according to their transcriptomic profile and colocalization with“helped/licensed”cDcs and tumor-reactive cD8^(+)T *** agreement with this scenario,the presence of IFN-I-producing cD4^(+)T cells in the TME is associated with overall survival and the response to PD-1 checkpoint blockade in cancer patients.

关键词： cD4^(+)T-cell help cDc1 licensing IFN-I signaling cD40 costimulation (cross-)presentation cTL priming Tumor control

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用药点滴:双侧前段中毒性视神经病变与infliximab

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英国医学杂志中文版 2003年第3期6卷 153-153页

作者： Marcel P M ten Tusscher piet j c jacobs Michiel j W M Busch Linda de Graaf Willem L Diemont 曲冬懿 Department of Ophthalmology Laurentius Hospital 6043 CV Roermond Netherlands Maxima Medical Center 5631 BM Eindhoven Netherlands The Netherlands Pharmacovigilance Centre Lareb Goudsbloemvallei 7 5237 MH s-Hertogenbosch Netherlands

荷兰药物预警中心(Pharmacovigilance centre Lareb)最近接到了3例双眼视神经病变病例的报告。例1 男性,54岁,3次给予infliximab以治疗类风湿性关节炎,而后34天出现视物模糊。此外。

关键词：药物治疗双侧前段中毒性视神经病变 infliximab 药物不良反应类风湿性关节炎

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Performance and calibration of quark/gluon-jet taggers using 140 fb^(-1) of pp collisions at √s=13 TeV with the ATLAS detector

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chinese Physics c 2024年第2期48卷 1-25页

作者： G. Aad B. Abbott K. Abeling N.j. Abicht S.H. Abidi A. Aboulhorma H. Abramowicz H. Abreu Y. Abulaiti B.S. Acharya c. Adam Bourdarios L. Adamczyk S.V. Addepalli M.j. Addison j. Adelman A. Adiguzel T. Adye A.A. Affolder Y. Afik M.N. Agaras j. Agarwala A. Aggarwal c. Agheorghiesei A. Ahmad F. Ahmadov W.S. Ahmed S. Ahuja X. Ai G. Aielli A. Aikot M. Ait Tamlihat B. Aitbenchikh I. Aizenberg M. Akbiyik T.P.A. Åkesson A.V. Akimov D. Akiyama N.N. Akolkar K. Al Khoury G.L. Alberghi j. Albert P. Albicocco G.L. Albouy S. Alderweireldt M. Aleksa I.N. Aleksandrov c. Alexa T. Alexopoulos F. Alfonsi M. Algren M. Alhroob B. Ali H.M.j. Ali S. Ali S.W. Alibocus M. Aliev G. Alimonti W. Alkakhi c. Allaire B.M.M. Allbrooke j.F. Allen c.A. Allendes Flores P.P. Allport A. Aloisio F. Alonso c. Alpigiani M. Alvarez Estevez A. Alvarez Fernandez M. Alves cardoso M.G. Alviggi M. Aly Y. Amaral coutinho A. Ambler c. Amelung M. Amerl c.G. Ames D. Amidei S.P. Amor Dos Santos K.R. Amos V. Ananiev c. Anastopoulos T. Andeen j.K. Anders S.Y. Andrean A. Andreazza S. Angelidakis A. Angerami A.V. Anisenkov A. Annovi c. Antel M.T. Anthony E. Antipov M. Antonelli F. Anulli M. Aoki T. Aoki j.A. Aparisi Pozo M.A. Aparo L. Aperio Bella c. Appelt A. Apyan N. Aranzabal S.j. Arbiol Val c. Arcangeletti A.T.H. Arce E. Arena j-F. Arguin S. Argyropoulos j.-H. Arling O. Arnaez H. Arnold G. Artoni H. Asada K. Asai S. Asai N.A. Asbah j. Assahsah K. Assamagan R. Astalos S. Atashi R.j. Atkin M. Atkinson H. Atmani P.A. Atmasiddha K. Augsten S. Auricchio A.D. Auriol V.A. Austrup G. Avolio K. Axiotis G. Azuelos D. Babal H. Bachacou K. Bachas A. Bachiu F. Backman A. Badea P. Bagnaia M. Bahmani A.j. Bailey V.R. Bailey j.T. Baines L. Baines O.K. Baker E. Bakos D. Bakshi Gupta V. Balakrishnan R. Balasubramanian E.M. Baldin P. Balek E. Ballabene F. Balli L.M. Baltes W.K. Balunas j. Balz E. Banas M. Bandieramonte A. Bandyopadhyay S. Bansal L. Barak M. Barakat E.L. Barberio D. Barberis M. Barbero M.Z. Barel K.N. Barends T. Barillari M-S. Barisits T. Barklow P. Baron D.A. Baron Mo The ATLAS collaboration

The identification of jets originating from quarks and gluons,often referred to as quark/gluon tagging,plays an important role in various analyses performed at the Large Hadron collider,as Standard Model measurements and searches for new particles decaying to quarks often rely on suppressing a large gluon-induced *** paper describes the measurement of the efficiencies of quark/gluon taggers developed within the ATLAS collaboration,using √s=13 TeV proton–proton collision data with an integrated luminosity of 140 fb^(-1) collected by the ATLAS *** taggers with high performances in rejecting jets from gluon over jets from quarks are studied:one tagger is based on requirements on the number of inner-detector tracks associated with the jet,and the other combines several jet substructure observables using a boosted decision tree.A method is established to determine the quark/gluon fraction in data,by using quark/gluon-enriched subsamples defined by the jet *** in tagging efficiency between data and simulation are provided for jets with transverse momentum between 500 GeV and 2 TeV and for multiple tagger working points.

关键词： ATLAS jET QUARK GLUON TAGGING

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Fatty acid desaturation by stearoyl-coA desaturase-1 controls regulatory T cell differentiation and autoimmunity

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cellular & Molecular Immunology 2023年第6期20卷 666-679页

作者： Elien Grajchen Melanie Loix Paulien Baeten Beatriz F.côrte-Real Ibrahim Hamad Sam Vanherle Mansour Haidar jonas Dehairs jelle Y.Broos james M.Ntambi Robert Zimmermann Rolf Breinbauer piet Stinissen Niels Hellings Sanne G.S.Verberk Gijs Kooij Martin Giera johannes V.Swinnen Bieke Broux Markus Kleinewietfeld jerome j.A.Hendriks jeroen F.j.Bogie Department of Immunology and Infection Biomedical Research InstituteHasselt UniversityDiepenbeekBelgium University MS center Hasselt PeltBelgium Neuro-Immune connections and Repair Lab Department of Immunology and InfectionBiomedical Research InstituteHasselt UniversityDiepenbeekBelgium VIB Laboratory of Translational Immunomodulation VIB Center for Inflammation ResearchHasselt UniversityDiepenbeekBelgium Department of Oncology Laboratory of Lipid Metabolism and CancerLKI–Leuven Cancer InstituteKU Leuven-University of LeuvenLeuvenBelgium Department of Molecular cell Biology and Immunology Amsterdam University Medical CenterVrije Universiteit AmsterdamAmsterdam NeuroscienceMS Center AmsterdamAmsterdamThe Netherlands center for Proteomics and Metabolomics Leiden University Medical CenterLeidenThe Netherlands Department of Biochemistry Department of Nutritional SciencesUniversity of Wisconsin-MadisonMadisonUSA Institute of Molecular Biosciences University of GrazGrazAustria BioTechMed-Graz GrazAustria Institute of Organic chemistry Graz University of TechnologyGrazAustria cardiovascular Research Institute Maastricht Department of Internal MedicineMaastricht UniversityMaastrichtThe Netherlands

The imbalance between pathogenic and protective T cell subsets is a cardinal feature of autoimmune disorders such as multiple sclerosis(MS).Emerging evidence indicates that endogenous and dietary-induced changes in fatty acid metabolism have a major impact on both T cell fate and *** date,however,the molecular mechanisms that underlie the impact of fatty acid metabolism on T cell physiology and autoimmunity remain poorly ***,we report that stearoyl-coA desaturase-1(ScD1),an enzyme essential for the desaturation of fatty acids and highly regulated by dietary factors,acts as an endogenous brake on regulatory T-cell(Treg)differentiation and augments autoimmunity in an animal model of MS in a T cell-dependent *** by RNA sequencing and lipidomics analysis,we found that the absence of Scd1 in T cells promotes the hydrolysis of triglycerides and phosphatidylcholine through adipose triglyceride lipase(ATGL).ATGL-dependent release of docosahexaenoic acid enhanced Treg differentiation by activating the nuclear receptor peroxisome proliferator-activated receptor *** findings identify fatty acid desaturation by ScD1 as an essential determinant of Treg differentiation and autoimmunity,with potentially broad implications for the development of novel therapeutic strategies and dietary interventions for autoimmune disorders such as MS.

关键词： Regulatory T cells Autoimmunity Fatty acid metabolism Stearoyl-coA desaturase-1 Multiple sclerosis

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PERMEABILITY AND cONSOLIDATION OF SEDIMENT MIXTURES AS FUNcTION OF SAND cONTENT AND cLAY MINERALOGY

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International journal of Sediment Research 2007年第3期22卷 180-187页

作者： W. jacobs W. G. M. VAN KESTEREN j. c. WINTERWERP Ph. D candidate Delft University of Technology Delft the Netherlands M. Sc. WL|Delft Hydraulics the Netherlands Ms. c. Ph.D. Delft University of Technology and WL|Delft Hydraulics the Netherlands

The current study is the first step in a systematic experimental research on the erosion behaviour of sand-mud mixtures. It concerns the effect of a varying sand content and clay mineralogy on the porosity, structure, strength and permeability of artificially generated sediment mixtures. The permeability of a sediment mixture is an especially significant parameter concerning the type of erosion that occurs. It determines if the erosion of the bed is either a drained or an undrained process, respectively indicating surface erosion or mass erosion. Measurements on various mixtures concerning the consolidation coefficient and the permeability have been executed. Results show a distinct transition of behaviour between a sand-silt dominated network structure and a clay-water matrix. The occurrence of these two types of structures appears to depend on the porosity of the volume fraction of sand related to silt, which is, therefore, an important parameter concerning the type of erosion. Finally, the study provides a valuable data set that can be used as a reference for following stages of this research on the erosion behaviour of natural cohesive sediments.

关键词： cohesive sand-mud mixtures Erosion consolidation Permeability compressibility

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childhood cardiovascular Risk Factors and Adult cardiovascular Events

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四川生理科学杂志 2022年第2期44卷 53-53页

作者： David R jacobs jr From the Division of Epidemiology and community Health School of Public Health (D.R.J.) and the Department of Pediatrics University of Minnesota Medical School (A.R.S. J.S.) University of Minnesota Minneapolis the Division of Biostatistics and Epidemiology (j.G.W. N.Z.) and the Heart Institute (E.M.U.) Cincinnati Children's Hospital Medical Center and the Department of Pediatrics University of Cincinnati College of Medicine (J.G.W. N.Z. E.M.U.) - both in Cincinnati the Department of Pediatrics University of Colorado School of Medicine and Anschutz Medical Campus Children's Hospital Colorado - both in Aurora (S.R.D.) the center for Population Health Research (j.I. N.K. C.G.M. O.T.R.) the Research Center of Applied and Preventive Cardiovascular Medicine (J.I. N.K. C.G.M. O.T.R.) and the Departments of Medicine (M.J. J.S.A.V.) and Mathematics and Statistics (N.K.) University of Turku and the Center for Population Health Research (J.I. N.K. C.G.M. O.T.R.) the Division of Medicine (M.J. J.S.A.V.) and the Department of Clinical Physiology and Nuclear Medicine (O.T.R.) Turku University Hospital Turku and the Department of Clinical Chemistry Fimlab Laboratories and the Finnish Cardiovascular Research Center and the Faculty of Medicine and Health Technology Tampere University Tampere (T.L.) - all in Finland Menzies Institute for Medical Research University of Tasmania Hobart TAS (C.G.M. A.J.V. T.D.) and the Heart Research Group Murdoch Children's Research Institute Melbourne VIC (T.D.) - both in Australia the School of Public Health and Tropical Medicine Tulane University New Orleans (L.A.B.) the Department of Epidemiology College of Public Health University of Iowa Iowa City (T.L.B.) the Division of Public Health Sciences Wake Forest School of Medicine Winston-Salem NC (R.J.P.) and the Nuffield Department of Women's and Reproductive Health University of Oxford Oxford United Kingdom (T.D.).

Background:childhood cardiovascular risk factors predict subclinical adult cardiovascular disease,but links to clinical events are ***:In a prospective cohort study involving participants in the International childhood cardiovascular cohorts(i3c)consortium,we evaluated whether childhood risk factors(at the ages of 3 to 19 years)were associated with cardiovascular events in adulthood after a mean follow-up of 35 years.

关键词： cardiovascular cardiovascular childhood

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Docosahexaenoic acid suppresses arachidonic acid-induced proliferation of LS-174T human colon carcinoma cells

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World journal of Gastroenterology 2009年第9期15卷 1079-1084页

作者： piet Habbel Karsten H Weylandt Katja Lichopoj johannes Nowak Martin Purschke jing-Dong Wang cheng-Wei He Daniel c Baumgart jing X Kang Department of Medicine Massachusetts General Hospital and Harvard Medical School Boston MA 02114 United States Department of Medicine Division of Gastroenterology and Hepatology Charité Medical Center-Virchow-Hospital Medical School of the Humboldt-University of Berlin 13344 Berlin Germany

AIM:To investigate the impact of arachidonic acid (AA) and docosahexaenoic acid (DHA) and their combination on colon cancer cell ***:The LS-174T colon cancer cell line was used to study the role of the prostaglandin precursor AA and the omega-3 polyunsaturated fatty acid DHA on cell growth. cell viability was assessed in XTT assays. For analysis of cell cycle and cell death,flow cytometry and DAPI staining were applied. Expression of cyclooxygenase-2 (cOX-2),p21 and bcl-2 in cells incubated with AA or DHA was examined by real-time RT-PcR. Prostaglandin E2 (PGE2) generation in the presence of AA and DHA was measured using a ***:AA increased cell growth,whereas DHAreduced viability of LS 174T cells in a time-and dose-dependent manner. Furthermore,DHA down-regulated mRNA of bcl-2 and up-regulated p21. Interestingly,DHA was able to suppress AA-induced cell proliferation and significantly lowered AA-derived PGE2 formation. DHA also down-regulated cOX-2 expression. In addition to the effect on PGE2 formation,DHA directly reduced PGE2-induced cell proliferation in a dose-dependent manner. cONcLUSION:These results suggest that DHA can inhibit the pro-proliferative effect of abundant AA or PGE2.

关键词：二十二碳六烯酸人结肠癌细胞花生四烯酸诱导扫描仪 LS 酶联免疫吸附试验前列腺素E2 酸抑制

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Operations management for competitive advantage / Richard B. chase, Nicholas j. Aquilano, F. Robert jacobs. 9th ed.

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丛书名： The Irwin/McGraw-Hill series. Operations and decision sciences.

2001年

作者： Richard B. chase Nicholas j. Aquilano F. Robert jacobs.

来源：畅想之星图书光盘版（南... 评论

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Machine learning predictions of irradiation embrittlement in reactor pressure vessel steels

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npj computational Materials 2022年第1期8卷 795-805页

作者： Yu-chen Liu Henry Wu Tam Mayeshiba Benjamin Afflerbach Ryan jacobs josh Perry jerit George josh cordell jinyu Xia Hao Yuan Aren Lorenson Haotian Wu Matthew Parker Fenil Doshi Alexander Politowicz Linda Xiao Dane Morgan Peter Wells Nathan Almirall Takuya Yamamoto G.Robert Odette Materials Science and Engineering Department University of Wisconsin-MadisonMadisonWI53706USA Hierarchical Green-Energy Materials(Hi-GEM)Research center National Cheng Kung UniversityTainan70101TaiwanCHINA Materials Science and Engineering Department National Cheng Kung UniversityTainan70101TaiwanCHINA Mechanical Engineering Department University of CaliforniaSanta BarbaraCA93106USA

Irradiation increases the yield stress and embrittles light water reactor(LWR)pressure vessel *** this study,we demonstrate some of the potential benefits and risks of using machine learning models to predict irradiation hardening extrapolated to low flux,high fluence,extended life *** machine learning training data included the Irradiation Variable for lower flux irradiations up to an intermediate fluence,plus the Belgian Reactor 2 and Advanced Test Reactor 1 for very high flux irradiations,up to very high ***,the machine learning model predictions for the high fluence,intermediate flux Advanced Test Reactor 2 irradiations are superior to extrapolations of existing hardening *** successful extrapolations showed that machine learning models are capable of capturing key intermediate flux effects at high *** approaches,applied to expanded databases,could be used to predict hardening in LWRs under life-extension conditions.

关键词： life irradiation expanded

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