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Food Science and Human Wellness 2024年

作者： Yujia Chen Hanjiang Du Lei Wang Yueying Wang Zhangyu Du Dongbin Guo Li Wang Bingmei Wang Wei Li Department of Gastrocolorectal Surgery， General Surgery center， The First Hospital of Jilin university Faculty of medicine， international university of health and welfare Department of Gastric and Colorectal Surgery， Jilin Cancer Hospital College of Integrated Traditional Chinese and Western medicine， Changchun university of Chinese medicine clinical Medical College， Changchun university of Chinese medicine

Addressing the uncontrolled spread and increase in antibiotic resistance in methicillin-resistant Staphylococcus aureus （MRSA） will require new control strategies， particularly to improve the safety of food. Our results revealed the efficacy of Theaflavin-3，3'-digallate （TFBG）， which is a novel polyphenol derived from tea， in targeting the key regulatory protein MgrA in S. aureus. Through fluorescence anisotropy， we showed that the IC50of TFBG was 26.76 μg/mL. TFBG uniquely counters S. aureus by regulating its virulence factors and adhesion processes rather than by killing the bacteria directly. This compound alters the expression of key virulence factors and modulates the transcription levels of genes related to adhesion in S. aureus， ultimately reducing the bacteria’s ability to adhere to fibrinogen and its hemolytic activity. Our assays confirmed that TFBG directly interacts with the MgrA protein in MRSA， and we identified critical binding sites. Our in vivo studies highlighted the potent efficacy of TFBG. TFBG administration is an innovative approach to improve food safety by diminishing MRSA virulence and reducing its pathogenicity.

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Deleterious variants in RNF111 impair female fertility and induce premature ovarian insufficiency in humans and mice

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Science China(Life Sciences) 2024年第7期67卷 1325-1337页

作者： Chengcheng Song Yingying Qin Yan Li Bingyi Yang Ting Guo Wenqing Ma Dian Xu Keyan Xu Fangfang Fu Li Jin Yanhua Wu Shuyan Tang Xiaojun Chen Feng Zhang Obstetrics and Gynecology Hospital State Key Laboratory of Genetic EngineeringInstitute of Medical Genetics and GenomicsFudan UniversityShanghai 200011China Human Phenome Institute Zhangjiang Fudan International Innovation CenterFudan UniversityShanghai 201203China center for Reproductive medicine Cheeloo College of MedicineShandong UniversityJinan 250021China State Key Laboratory of Reproductive medicine and Offspring health Key Laboratory of Reproductive Endocrinology of Ministry of EducationNational Research Center for Assisted Reproductive Technology and Reproductive GeneticsShandong Key Laboratory of Reproductive MedicineShandong Provincial Clinical Research Center for Reproductive HealthShandong UniversityJinan 250021China Department of Obstetrics and Gynecology Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China National Demonstration center for Experimental Biology Education School of Life SciencesFudan UniversityShanghai 200433China Department of Gynecology the Tenth People’s Hospital of Tongji UniversityShanghai 200072China Soong Ching Ling Institute of Maternity and Child health International Peace Maternity and Child Health Hospital of China Welfare InstituteShanghai 200030China

Premature ovarian insufficiency(POI)is a heterogeneous female disorder characterized by the loss of ovarian function before the age of *** represents a significant detriment to female ***,the known POI-causative genes currently account for only a fraction of *** elucidate the genetic factors underlying POI,we conducted whole-exome sequencing on a family with three fertile POI patients and identified a deleterious missense variant in *** a subsequent replication study involving 1,030 POI patients,this variant was not only confirmed but also accompanied by the discovery of three additional predicted deleterious RNF111 *** variants collectively account for eight cases,representing 0.78%of the study cohort.A further study involving 500 patients with diminished ovarian reserve also identified two additional RNF111 ***,RNF111 encodes an E3 ubiquitin ligase with a regulatory role in the TGF-β/BMP signaling *** analysis revealed that RNF111/RNF111 is predominantly expressed in the oocytes of mice,monkeys,and *** further investigate the functional implications of RNF111 variants,we generated two mouse models:one with a heterozygous missense mutation(Rnf111+/M)and another with a heterozygous null mutation(Rnf111^(+/-)).Both mouse models exhibited impaired female fertility,characterized by reduced litter sizes and small ovarian ***,RNA-seq and quantitative proteomics analysis unveiled that Rnf111 haploinsufficiency led to dysregulation in female gonad development and negative regulation of the BMP signaling pathway within mouse *** conclusion,our findings strongly suggest that monoallelic deleterious variants in RNF111 can impair female fertility and induce POI in both humans and mice.

关键词： POI RNF111 female fertility ovarian reserve

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Utility of Goal Attainment Scaling(GAS)in evaluating a multicomponent exercise programme for community-dwelling pre-frail older adults

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Family medicine and Community health 2024年第1期12卷 36-44页

作者： Juan Fang Jianping Ren Jinjing Wang Xiantao Qiu Shiyan Zhang Shuang Yuan Liangfeng Wu Lin Xie Le Yu School of Public health Hangzhou Normal UniversityHangzhouZhejiangChina School of medicine Huzhou UniversityHuzhouZhejiangChina School of clinical medicine Hangzhou Normal UniversityHangzhouZhejiangChina Ziyang Street Community health Service center HangzhouZhejiangChina

Objectives This study aimed to investigate the effectiveness of Goal Attainment Scaling(GAS)in assessing an intervention for pre-frail senior ***,the study aimed to explain how the GAS goals were established based on the international Classification of Functioning,Disability and health(ICF)categories,including body function,activity and participation and environmental *** In this study,220 pre-frail older adults were randomly selected to participate in a controlled *** intervention group engaged in multicomponent exercise three times a week,once at a community health service location and twice at *** control group received advice on physical activity but did not have supervised *** in both groups selected individualised GAS goals from 23 goals developed based on ICF by focus group *** study used generalised estimating equations to analyse the differences between the *** The study included 144 participants,72 in the exercise group and 72 in the control *** top three individualised goals for all participants were vestibular functions(53.5%),pain management(43.1%)and lifting and carrying objects(31.9%).Both groups saw a significant increase in GAS scores at week 8 and week 24 of the intervention(p<0.05),but the exercise group showed a more significant improvement(p<0.05).The participants living alone were associated with lower postintervention improvements in the GAS *** contrast,the participants who were using a smartphone were likely to get higher postintervention improvements in the GAS *** GAS can be a valuable tool for setting and evaluating individualised and meaningful goals in body functions,activity and participation and environmental *** multicomponent exercise interventions can help pre-frail older adults achieve their expected goals as measured by the GAS.

关键词： meaningful goals lifting

CGG repeat expansion in LOC642361/NUTM2B-AS1 typically presents as oculopharyngodistal myopathy

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Journal of Genetics and Genomics 2024年第2期51卷 184-196页

作者： Yan Shi Chunyan Cao Yiheng Zeng Yuanliang Ding Long Chen Fuze Zheng Xuejiao Chen Fanggui Zhou Xiefeng Yang Jinjing Li Liuqing Xu Guorong Xu Minting Lin Hiroyuki Ishiura Shoji Tsuji Ning Wang Zhiqiang Wang Wan-Jin Chen Kang Yang Department of Neurology and Institute of Neurology of First Affiliated Hospital Institute of NeuroscienceFujian Key Laboratory of Molecular NeurologyFujian Medical UniversityFuzhouFujian 350005China Department of Neurology National Regional Medical CenterBinhai Campus of the First Affiliated HospitalFujian Medical UniversityFuzhouFujian 350212China The First Affiliated Hospital College of Clinical Medicine of Henan University of Science and TechnologyLuoyangHenan 471000China Department of Neurology Zhangzhou Municipal Hospital of Fujian Province and Zhangzhou Affiliated Hospital of Fujian Medical UniversityZhangzhouFujian 363000China Department of Neurology Jian'ou Municipal Hospital of Fujian ProvinceJian'ouFujian 353100China Department of Radiology First Affiliated Hospital of Fujian Medical UniversityFuzhouFujian 350005China Department of Neurology Graduate School of MedicineThe University of TokyoTokyo 113-8655Japan Department of Neurology Okayama University Graduate School of MedicineDentistry and Pharmaceutical SciencesOkayama 700-8558Japan Institute of Medical Genomics International University of Health and WelfareChiba 286-0048Japan

CGG repeat expansions in LOC642361/NUTM2B-AS1 have recently been identified as a cause of oculopharyngeal myopathy with ***,since only three patients from a single family were reported,it remains unknown whether their clinicopathological features are typical for CGG repeat expansions in LOC642361/***,using repeat-primed-polymerase chain reaction and long-read sequencing,we identify 12 individuals from 3 unrelated families with CGG repeat expansions in LOC642361/NUTM2B-AS1,typically presenting with oculopharyngodistal *** CGG repeat expansions range from 161 to 669 repeat *** of the patients present with ptosis,restricted eye movements,dysphagia,dysarthria,and diffuse limb muscle *** one patient shows T2-weighted hyperintensity in the cerebellar white matter surrounding the deep cerebellar nuclei on brain magnetic resonance *** biopsies from three patients show a myopathic pattern and rimmed *** of muscle biopsies suggest that CGG repeat expansions in LOC642361/NUTM2B-AS1 may deleteriously affect aggrephagic capacity,suggesting that RNA toxicity and mitochondrial dysfunction may contribute to *** study thus expands the phenotypic spectrum for the CGG repeat expansion of LOC642361/NUTM2B-AS1 and indicates that this genetic variant typically manifests as oculopharyngodistal myopathy with chronic myopathic changes with rimmed vacuoles and filamentous intranuclear inclusions in muscle fibers.

关键词： Oculopharyngeal myopathy with leukoencephalopathy Oculopharyngodistal myopathy CGG repeat expansion Rimmed vacuoles

DNA methylation clocks for estimating biological age in Chinese cohorts

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Protein & Cell 2024年第8期15卷 575-593页

作者： Zikai Zheng Jiaming Li Tianzi Liu Yanling Fan Qiao-Cheng Zhai Muzhao Xiong Qiao-Ran Wang Xiaoyan Sun Qi-Wen Zheng Shanshan Che Beier jiang Quan Zheng Cui Wang Lixiao Liu Jiale Ping Si Wang Dan-Dan Gao Jinlin Ye Kuan Yang Yuesheng Zuo Shuai Ma Yun-GuiYang Jig Qu Feng Zhang Peilin Jia Guang-Hui Liu Weiqi Zhang CAS Key Laboratory of Genomic and Precision medicine Beijing Institute of GenomicsChinese Academy of Sciences and China National Center for BioinformationBeijing 100101China university of Chinese Academy of Sciences Beijing 100049China CAS Key Laboratory of Computational Biology Shanghai Institute of Nutrition and HealthChinese Academy of SciencesShanghai 200031China Division of Orthopaedics Quzhou Affliated Hospital of Wenzhou Medical UniversityQuzhou 324000China The Joint Innovation center for Engineering in medicine Quzhou Affliated Hospital of Wenzhou Medical UniversityQuzhou 324000China Advanced Innovation center for Human Brain Protection and National Clinical Research Center for Geriatric DisordersXuanwu Hospital Capital Medical UniversityBeijing 100053China Aging Translational medicine center International Center for Aging and CancerXuanwu HospitalCapital Medical UniversityBeijing 100053China Aging Biomarker Consortium Beijing 100101China State Key Laboratory of Membrane Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China Key Laboratory of Organ Regeneration and Reconstruction Institute of ZoologyChinese Academy of SciencesBeijing 100101China nstitute for Stem Cell and Regeneration Chinese Academy of SciencesBeijing 100101China Beijing Institute for Stem Cell and Regenerative medicine Beijing 100101China State Key Laboratory of Stem Cell and Reproductive Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China National Genomics Data center Beijing Institute of GenomicsChinese Academy of Sciences and China National Center for BioinformationBeijing 100101China

Epigenetic clocks are accurate predictors of human chronological age based on the analysis of DNA methylation(DNAm)at specific CpG ***,a systematic comparison between DNA methylation data and other omics datasets has not yet been ***,available DNAm age predictors are based on datasets with limited ethnic *** address these knowledge gaps,we generated and analyzed DNA methylation datasets from two independent Chinese cohorts,revealing age-related DNAm ***,a DNA methylation aging clock(iCAS-DNAmAge)and a group of DNAm-based multi-modal clocks for Chinese individuals were developed,with most of them demonstrating strong predictive capabilities for chronological *** clocks were further employed to predict factors influencing aging *** DNAm aging clock,derived from multi-modal aging features(compositeAge-DNAmAge),exhibited a close association with multi-omics changes,lifestyles,and disease status,underscoring its robust potential for precise biological age *** findings offer novel insights into the regulatory mechanism of age-related DNAm changes and extend the application of the DNAm clock for measuring biological age and aging pace,providing the basis for evaluating aging intervention strategies.

关键词： DNA methylation aging clock aging age prediction

A single-nucleus transcriptomic atlas of primate liver aging uncovers the pro-senescence role of SREBP2 in hepatocytes

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Protein & Cell 2024年第2期15卷 98-120页

作者： Shanshan Yang Chengyu Liu Mengmeng Jiang Xiaoqian Liu Lingling Geng Yiyuan Zhang Shuhui Sun Kang Wang jian Yin Shuai Ma Si Wang Juan Carlos Izpisua Belmonte Weiqi Zhang Jing Qu Guang-Hui Liu Advanced Innovation center for Human Brain Protection and National clinical Research center for Geriatric Disorders Xuanwu Hospital Capital Medical UniversityBeijing 100053China State Key Laboratory of Membrane Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China Aging Translational medicine center International Center for Aging and CancerBeijing Municipal Geriatric Medical Research CenterXuanwu HospitalCapital Medical UniversityBeijing 100053China State Key Laboratory of Stem Cell and Reproductive Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China CAS Key Laboratory of Genomic and Precision medicine Beijing Institute of GenomicsChinese Academy of Sciences and China National Center for BioinformationBeijing 100101China Xuanwu Hospital Capital Medical university Beijing 100053China university of Chinese Academy of Sciences Beijing 100049China Institute for Stem Cell and Regeneration Chinese Academy of SciencesBeijing 100101China Beijing Institute for Stem Cell and Regenerative medicine Beijing 100101China Aging Biomarker Consortium Beijing 100101China Altos Labs Inc.San DiegoCA 94022USA

Aging increases the risk ofliver diseases and systemic susceptibility to aging-related ***,cell type-specific changes and the underlying mechanism of liver aging in higher vertebrates remain incompletely ***,we constructed the first single-nucleus transcriptomic landscape of primate liver aging,in which we resolved cell type-specific gene expression fluctuation in hepatocytes across three liver zonations and detected aberrant cell-cell interactions between hepatocytes and niche *** in-depth dissection of this rich dataset,we identifed impaired lipid metabolism and upregulation of chronic inflammation-related genes prominently associated with declined liver functions during *** particular,hyperactivated sterol regulatory element-binding protein(SREBP)signaling was a hallmark of the aged liver,and consequently,forced activation of SREBP2 in human primary hepatocytes recapitulated in vivo aging phenotypes,manifesting as impaired detoxification and accelerated cellular *** study expands our knowledge of primate liver aging and informs the development of diagnostics and therapeutic interventions for liver aging and associated diseases.

关键词： single-nucleus RNA sequencing liver hepatocytes aging senescence SREBP2

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Impact of pre-existing cardiometabolic diseases on metastatic cancer stage at diagnosis:a prospective multinational cohort study

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Cancer Communications 2024年第5期44卷 593-597页

作者： Anna Jansana Aviane Auguste Marina Kvaskoff Agnès Fournier Emma Fontvieille Laia Peruchet-Noray Carine Biessy Reynalda Cordova Kristina Elin Nielsen Petersen Anne Tjoneland Verena Katzke Rudolf Kaaks Fulvio Ricceri Salvatore Panico Paolo Contiero Maria-Jose Sánchez Jesus Castilla Marta Crous-Bou Alicia Heath Elom Kouassivi Aglago Elisabete Weiderpass Marc James Gunter Pietro Ferrari Elio Riboli Vivian Viallon Heinz Freisling international Agency for Research on Cancer(IARC-WHO) LyonFrance Paris-Saclay university University of Versailles-Saint-Quentin-en-YvelineUniversity Paris-SudFrench National Institute for Health and Medical Research(Inserm)Gustave Roussy“Exposome and Heredity”TeamCESPVillejuifFrance Department of Nutritional Sciences University of ViennaViennaAustria Danish Cancer Society Research center CopenhagenDenmark Department of Public health University of CopenhagenCopenhagenDenmark Division of Cancer Epidemiology German Cancer Research CentreHeidelbergGermany Department of clinical and Biological Sciences University of TurinTurinItaly Unit of Epidemiology Regional Health Service ASL TO3GrugliascoTurinItaly Department of clinical medicine and Surgery Federico II UniversityNaplesItaly Environmental Epidemiology Unit Istituto di Ricovero e Cura a Carattere Scientifico(IRCCS)-Istituto Nazionale dei TumoriMilanItaly Cancer Registry of Granada Institute for Biosanitary Research of Granada(ibs.GRANADA)GranadaSpain Epidemiology and Control of Chronic Diseases Group Epidemiology and Public Health Networking Biomedical Research CentreMadridSpain Navarra Public health Institute PamplonaSpain Unit of Nutrition and Cancer Cancer Epidemiology Research ProgramCatalan Institute of Oncology(ICO)-Bellvitge Biomedical Research Institute(IDIBELL)L’Hospitalet de LlobregatBarcelonaSpain Department of Epidemiology Harvard Tseng-Hsi Chan School of Public HealthBostonMassachusettsUSA Department of Epidemiology and Biostatistics School of Public HealthImperial College LondonSt Mary’s CampusNorfolk PlaceLondonUK

Owing to shared risk factors between cardiometabolic diseases(CMDs)and cancer,coupled with population aging,the lifetime risk of an individual developing cancer after a CMD is ***,biological mechanisms such as insulin resistance or inflammation may not only predispose individuals withCMDto an elevated risk of certain types of cancer but also to a diagnosis of cancer at an advanced stage[1,2].

关键词： diagnosis diseases cancer

CRL2^(APPBP2)-mediated TSPYL2 degradation counteracts human mesenchymal stem cell senescence

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Science China(Life Sciences) 2024年第3期67卷 460-474页

作者： Daoyuan Huang Qian Zhao Kuan Yang Jinghui Lei Ying Jing Hongyu Li Chen Zhang Shuai Ma Shuhui Sun Yusheng Cai Guibin Wang Jing Qu Weiqi Zhang Si Wang Guang-Hui Liu Advanced Innovation centerfor Human Brain Protection National Clinical Research Centerfor Geriatric DisordersXuanwu Hospital Capital Medical UniversityBeijing 100053China State Key Laboratory of Stem Cell and Reproductive Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China Aging Translational medicinecenter International Centerfor Aging and CancerBejing Municipal GeriatricMedical Research CenterXuanwu HospitalCapital Medical UniversityBeijing 100053China State Key Laboratory of Membrane Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China university of Chinese Academy of Sciences Beijing 100049China Beijing Institute for Stem Cell and Regenerative medicine Beijing100101China CAS Key Laboratory of Genomic and Precision medicine Bejing Institute of Genomics and China National Center for BioinformationChinese Academy of SciencesBeijing 100101China Institute for Stem Cell and Regeneration CASBeijing 100101China The Fifth People's Hospital of Chongqing Chongqing 400062China Sino-Danish Cllege University of Chinese Academy of SciencesBeijing101408China National Laboratory of Biomacromolecules CAS Center for Excelence in BiomacromoleculesInstitute of BiophysicsChinese Academy of SciencesBeijing100101China State Key Laboratory of Proteomics Beijing Proteome Research CenterNational Center for Protein Sciences(Beijing)Beijing Institute of LifeomicsBeijing 102206China

Cullin-RING E3 ubiquitin ligases(CRLs),the largest family of multi-subunit E3 ubiquitin ligases in eukaryotic cells,represent core cellular machinery for executing protein degradation and maintaining ***,we asked what roles Cullin proteins play in human mesenchymal stem cell(hMSC)homeostasis and *** this end,we conducted a comparative aging phenotype analysis by individually knocking down Cullin members in three senescence models:replicative senescent hMSCs,Hutchinson-Gilford Progeria Syndrome hMSCs,and Werner syndrome *** all family members,we found that CUL2 deficiency rendered hMSCs the most susceptible to *** investigate CUL2-specific underlying mechanisms,we then applied CRISPR/Cas9-mediated gene editing technology to generate CUL2-deficient human embryonic stem cells(hESCs).When we differentiated these into h MSCs,we found that CUL2 deletion markedly accelerates hMSC ***,we identified that CUL2 targets and promotes ubiquitin proteasome-mediated degradation of TSPYL2(a known negative regulator of proliferation)through the substrate receptor protein APPBP2,which in turn downregulates one of the canonical aging marker-P21^(waf1/cip1),and thereby delays *** work provides important insights into how CRL2^(APPBP2)-mediated TSPYL2 degradation counteracts hMSC senescence,providing a molecular basis for directing intervention strategies against aging and aging-related diseases.

关键词： Cullins stem cell senescence aging proteostasis ubiquitination APPBP2 TSPYL2

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Redefining pandemic preparedness:Multidisciplinary insights from the CERP modelling workshop in infectious diseases,workshop report

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Infectious Disease Modelling 2024年第2期9卷 501-518页

作者： Marta C.Nunes Edward Thommes Holger Fröhlich Antoine Flahault Julien Arino Marc Baguelin Matthew Biggerstaff Gaston Bizel-Bizellot Rebecca Borchering Giacomo Cacciapaglia Simon Cauchemez Alex Barbier--Chebbah Carsten Claussen Christine Choirat Monica Cojocaru Catherine Commaille-Chapus Chitin Hon Jude Kong Nicolas Lambert Katharina B.Lauer Thorsten Lehr Cédric Mahe Vincent Marechal Adel Mebarki Seyed Moghadas Rene Niehus Lulla Opatowski Francesco Parino Gery Pruvost Andreas Schuppert Rodolphe Thiébaut Andrea Thomas-Bachli Cecile Viboud Jianhong Wu Pascal Crépey PascalCrepey center of Excellence in Respiratory Pathogens(CERP) Hospices Civils de Lyon(HCL)and Centre International de Recherche en Infectiologie(CIRI)Équipe SantéPubliqueÉpidémiologie etÉcologieÉvolutive des Maladies Infectieuses(PHE3ID)Inserm U1111CNRS UMR5308ENS de LyonUniversitéClaude Bernard Lyon 1LyonFrance South African Medical Research Council Vaccines&Infectious Diseases Analytics Research UnitFaculty of Health SciencesUniversity of the WitwatersrandJohannesburgSouth Africa New Products and Innovation(NPI) Sanofi Vaccines(Global)TorontoOntarioCanada Department of Mathematics and Statistics University of GuelphGuelphOntarioCanada Fraunhofer Institute for Algorithms and Scientific Computing(SCAI) Department of BioinformaticsSchloss BirlinghovenSankt AugustinGermany university of Bonn Bonn-Aachen International Center for IT(b-it)BonnGermany Institute of Global health Faculty of MedicineUniversity of GenevaGenevaSwitzerland and Swiss School of Public HealthZürichSwitzerland Department of Mathematics University of ManitobaWinnipegManitobaCanada MRC Centre for Global Infectious Disease Analysis School of Public HealthImperial College LondonLondonUK Centre for Mathematical Modelling of Infectious Diseases Department of Infectious Disease EpidemiologyLondon School of Hygiene&Tropical MedicineLondonUK National center for Immunization and Respiratory Diseases(NCIRD) US Centers for Disease Control and Prevention(CDC)AtlantaGAUSA Departement of Computational Biology Departement of Global HealthInstitut PasteurParisFrance Institut de Physique des Deux Infinis de Lyon(IP2I) UMR5822IN2P3/CNRSUniversitéClaude Bernard Lyon 1VilleurbanneFrance Mathematical Modelling of Infectious Diseases Unit Institut PasteurUniversitéParis CitéUMR2000 CNRSParisFrance Decision and Bayesian Computation Institut PasteurUniversitéParis CitéCNRS UMR 3571France Fraunhofer-Institute for Translational medicine and Pharmacology HamburgGermany Institute of Global health Faculty of MedicineUniversity of

In July 2023,the center of Excellence in Respiratory Pathogens organized a two-day workshop on infectious diseases modelling and the lessons learnt from the Covid-19 *** report summarizes the rich discussions that occurred during the *** workshop participants discussed multisource data integration and highlighted the benefits of combining traditional surveillance with more novel data sources like mobility data,social media,and wastewater *** advancements were noted in the development of predictive models,with examples from various countries showcasing the use of machine learning and artificial intelligence in detecting and monitoring disease *** role of open collaboration between various stakeholders in modelling was stressed,advocating for the continuation of such partnerships beyond the pandemic.A major gap identified was the absence of a common international framework for data sharing,which is crucial for global pandemic ***,the workshop underscored the need for robust,adaptable modelling frameworks and the integration of different data sources and collaboration across sectors,as key elements in enhancing future pandemic response and preparedness.

关键词： Modelling Covid-19 Infectious diseases Pandemic preparedness Workshop

Expression of adhesion molecules on mature cholangiocytes in canal of Hering and bile ductules in wedge biopsy samples of primary biliary cirrhosis

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World Journal of Gastroenterology 2005年第28期11卷 4382-4389页

作者： Hiroaki Yokomori Masaya Oda Mariko Ogi Go Wakabayashi Shigeyuki Kawachi Kazunori Yoshimura Toshihiro Nagai Masaki Kitajima Masahiko Nomura Toshifumi Hibi Department of Internal medicine Kitasato Institute Medical center Hospital Saitama 364-8501Japan organized center of clinical medicine international university of health and welfare Tokyo 107-0052Japan Laboratory of Pathology Kitasato Institute Medical center Hospital Saitama 364-8501Japan Department of Surgery School of medicine Keio UniversityTokyo 160-0016Japan Physiology Saitama Medical School Saitama 350-0495Japan Electron Microscopy Laboratory School of medicine Keio UniversityTokyo 160-0016Japan Department of Internal medicine School of medicine Keio UniversityTokyo 160-0016Japan

AIM：To examine the expression of intercellular adhesion molecule-1 （ICAM-1） and lymphocyte function-associated antigen-1（LFA-1）expression on canals of Hering （COH）and bile ductules associated with the autoimmune process of bile duct destruction in primary biliary cirrhosis（PBC）．METHODS：Ten wedged liver biopsies of PBC（five cases each of stages 2 and 3）were studied. The liver specimens were processed for transmission electron microscopy. Immunohistochemistry was performed using anti-ICAM-1 and anti-LFA-1 mouse *** situ hybridization was done to examine the messenger RNA expression of ICAM-1 in ***-embedded sections using peptide nucleic acid probes and the catalyzed signal amplification （CSA）***-silver staining for electron microscopy was Derrormed using anti-ICAM and anti-LFA-1 mouse *** immunogold particles on epithelial cells of bileductules and cholangiocytes of CoH cells were counted and analyzed *** blotting was performed to confirm ICAM-1 protein expression．RESULTS：In liver tissues of PBC ***-stochemistry showed aberrant ICAM-1 expression on the plasma membrane of epithelial cells lining bile ductules，and also on mature cholangiocytes but not on hepatocytes in ***-1-positive lymphocytes were closely associated with epithelial cells in bile ***-1 expression at protein level was confirmed by Western *** situ hybridization demonstrated ICAM-1 mRNA expression in bile ductules and LFA-1 mRNA in lymphocytes infiltrating the *** immunoelectron microscopy，ICAM-1 was demonstrated on the basal suface of epithelial cells in bile ductules and on the luminal surfaces of cholangiocytes in damaged *** with intermediate morphology resembling progenitor cells in Coil were not labeled with ICAM-1 and LFA-1．CONCLUSION：De novo expression of ICAM-1 both on mature cholangiocytes in COH and epithelial cells in bile ductules in PBC implies that lymphocyte-indu

关键词： Primary biliary cirrhosis Canal of Hedng Small bile ductile ICAM-1 LFA-1 Immunohistochemistry Western blot Immunogold electron microscopyPrimary biliary cirrhosis Canal of Hedng Small bile ductile ICAM-1 LFA-1 Immunohistochemistry Western blot Immunogold electron microscopy