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Gut microbiota-derived metabolites as key mucosal barrier modulators in obesity

World Journal of Gastroenterology 2021年第33期27卷 5555-5565页

作者： Yan-Xia Wei Kui-Yang Zheng Yu-Gang Wang laboratory of infection and immunity Jiangsu Key Laboratory of Immunity and MetabolismDepartment of Pathogenic Biology and ImmunologyXuzhou Medical UniversityXuzhou 221004Jiangsu ProvinceChina

A significant breakthrough in the field of obesity research was the demonstration that an obese phenotype could be manipulated by modulating the gut *** important next step is to elucidate a human-relevant"map"of microbiota-host interactions that regulate the metabolic health of the *** improved understanding of this crosstalk is a prerequisite for optimizing therapeutic strategies to combat *** mucosal barrier dysfunction is an important contributor to metabolic diseases and has also been found to be involved in a variety of other chronic inflammatory conditions,including cancer,neurodegeneration,and *** mechanistic basis for intestinal barrier dysfunction accompanying metabolic disorders remains poorly *** the molecular and cellular modulators of intestinal barrier function will help devise improved strategies to counteract the detrimental systemic consequences of gut barrier *** in the composition and function of the gut microbiota,i.e.,dysbiosis,are thought to drive obesity-related pathogenesis and may be one of the most important drivers of mucosal barrier *** effects of the microbiota on the host are mediated by microbiota-derived *** this review,we focus on several relatively well-studied microbial metabolites that can influence intestinal mucosal homeostasis and discuss how they might affect metabolic *** design and use of microbes and their metabolites that are locally active in the gut without systemic side effects are promising novel and safe therapeutic modalities for metabolic diseases.

关键词： Obesity Metabolic diseases Microbiota Mucosal homeostasis Gut Microbial metabolites

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Nonconserved epitopes dominate reverse preexisting T cell immunity in COVID-19 convalescents

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Signal Transduction and Targeted Therapy 2024年第7期9卷 2984-2998页

作者： Xin Wang Jie Zhang Maoshun Liu Yuanyuan Guo Peipei Guo Xiaonan Yang Bingli Shang Min Li Jinmin Tian Ting Zhang Xi Wang Ronghua Jin Jikun Zhou George F.Gao Jun Liu department of Epidemiology School of Public HealthCheeloo College of MedicineShandong UniversityJinan 250012China NHC key laboratory of Biosafety Research Unit of Adaptive Evolution and Control of Emerging VirusesChinese Academy of Medical SciencesNational Institute for Viral Disease Control and PreventionChinese Center for Disease Control and Prevention(China CDC)Beijing 102206China Beijing key laboratory of Emerging Infectious Diseases Institute of Infectious DiseasesBeijing Ditan HospitalCapital Medical UniversityBeijing 100015China Beijing Institute of Infectious Diseases Beijing 100015China National Center for Infectious Diseases Beijing Ditan HospitalCapital Medical UniversityBeijing 100015P.R.China School of laboratory Medicine and Life Sciences Wenzhou Medical UniversityWenzhou 325035China School of Ophthalmology&Optometry Wenzhou Medical UniversityWenzhou 325027China Collaborative Innovation Centre of Regenerative Medicine and Medical BioResource Development and Application Co-constructed by the province and Ministry Guangxi Medical UniversityNanningGuangxi 530021China Shijiazhuang Fifth Hospital Shijiazhuang 050011China CAS key laboratory of Pathogen Microbiology and immunology Institute of MicrobiologyChinese Academy of Sciences(CAS)Beijing 100101China Savaid Medical School University of Chinese Academy of SciencesBeijing 100049China

The herd immunity against SARS-CoV-2 is continuously consolidated across the world during the ongoing ***,the potential function of the nonconserved epitopes in the reverse preexisting cross-reactivity induced by SARS-CoV-2 to other human coronaviruses is not well *** our research,we assessed T cell responses to both conserved and nonconserved peptides shared by SARS-CoV-2 and SARS-CoV,identifying cross-reactive CD8^(+)T cell epitopes using enzyme-linked immunospot and intracellular cytokine staining ***,in vitro refolding and circular dichroism were performed to evaluate the thermal stability of the HLA/peptide ***,single-cell T cell receptor reservoir was analyzed based on tetramer ***,we discovered that cross-reactive T cells targeting SARS-CoV were present in individuals who had recovered from COVID-19,and identified SARS-CoV-2 CD8^(+)T cell epitopes spanning the major structural antigens.T cell responses induced by the nonconserved peptides between SARS-CoV-2 and SARS-CoV were higher and played a dominant role in the cross-reactivity in COVID-19 ***-T cell reactivity was also observed within the identified series of CD8^(+)T cell *** representative immunodominant peptide pairs,although the HLA binding capacities for peptides from SARS-CoV-2 and SARS-CoV were similar,the TCR repertoires recognizing these peptides were *** results could provide beneficial information for the development of peptide-based universal vaccines against coronaviruses.

关键词： immunity conserved assessed

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DeBakey Type III Aortic Dissection Causing Bowel Necrosis: A Case Report

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Journal of Clinical and Nursing Research 2024年第8期8卷 159-162页

作者： Jinhu Kong Jiazheng Li Haiyang Hu Shangyun Pan Hongsheng Liu Clinical Medical College of Jining Medical University Jining 272067Shandong ProvinceChina department of Cardiac Intensive Medicine Affiliated Hospital of Jining Medical UniversityJining 272000Shandong ProvinceChina

Rationale:Aortic dissection is a life-threatening medical emergency associated with high morbidity and *** mesenteric malperfusion increases the surgical risk and mortality in patients with type B aortic *** DeBakey type III B patients involving most of the thoracoabdominal aorta,endovascular treatment to improve true lumen perfusion may have limited *** reperfusion on-time is *** concerns:A 38-year-old man was admitted with sudden severe upper abdominal *** CTA of the entire aorta revealed an aortic dissection with an entry tear in the descending aortic arch involving the celiac trunk,superior mesenteric artery,bilateral common iliac arteries and right external iliac artery,with thrombosis in the superior mesenteric ***:The patient was diagnosed with DeBakey type III aortic dissection with mesenteric artery *** chest CT showed the entry tear location and involvement of major *** confirmed partial blood flow in the superior mesenteric ***:The patient underwent endovascular aortic stent-graft implantation through the left femoral artery,covering the descending aortic arch and sealing the entry ***,the patient received intensive care,including ventilatory support,CRRT,anti-infection therapy,vasoactive drugs and lumbar cistern ***:Two weeks postoperatively,the patient developed massive black stools,indicative of intestinal obstruction and *** laparotomy revealed ischemic necrosis and rupture of the stomach,small intestine,and *** surgical efforts,the patient’s condition deteriorated,leading to death from severe infection,acid-base imbalance and multiple organ failure.

关键词： Abdominal pain Aortic dissection Arterial embolism Mesenteric artery

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OTUD5 promotes innate antiviral and antitumor immunity through deubiquitinating and stabilizing STING

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Cellular & Molecular immunology 2021年第8期18卷 1945-1955页

作者： Yunyun Guo Fei Jiang Lingli Kong Haifeng Wu Honghai Zhang Xiaorong Chen Jian Zhao Baoshan Cai Yanqi Li Chunhong Ma Fan Yi Lei Zhang Bingyu Liu Yi Zheng Lingqiang Zhang Chengjiang Gao key laboratory of infection and immunity of shandong province&department of immunology School of Biomedical SciencesShandong University250012JinanShandongPeople’s Republic of China department of Pharmacology School of Biomedical SciencesShandong University250012JinanShandongPeople’s Republic of China State key laboratory of Proteomics Beijing Proteome Research CenterNational Center for Protein Sciences(Beijing)Beijing Institute of Lifeomics100850BeijingPeople’s Republic of China

Stimulator of interferon genes(STING)is an adaptor protein that is critical for effective innate antiviral and antitumor *** activity of STING is heavily regulated by protein ubiquitination,which is fine-tuned by both E3 ubiquitin ligases and ***,we report that the deubiquitinase OTUD5 interacts with STING,cleaves its K48-linked polyubiquitin chains,and promotes its ***,knockout of OTUD5 resulted in faster turnover of STING and subsequently impaired type I IFN signaling following cytosolic DNA *** importantly,Lyz2-Cre Otud5^(fl/Y) mice and CD11-Cre Otud5^(fl/Y) mice showed more susceptibility to herpes simplex virus type 1(HSV-1)infection and faster development of melanomas than their corresponding control littermates,indicating that OTUD5 is indispensable for STING-mediated antiviral and antitumor *** data suggest that OTUD5 is a novel checkpoint in the cGAS-STING cytosolic DNA sensing pathway.

关键词： Antiviral innate immunity antitumor immunity STING deubiquitination OTUD5

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Impact of inhaled corticosteroid use on elderly chronic pulmonary disease patients with community acquired pneumonia

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Chinese Medical Journal 2024年第2期137卷 241-243页

作者： Xiudi Han Hong Wang Liang Chen Yimin Wang Hui Li Fei Zhou Xiqian Xing Chunxiao Zhang Lijun Suo Jinxiang Wang Guohua Yu Guangqiang Wang Xuexin Yao Hongxia Yu Lei Wang Meng Liu Chunxue Xue Bo Liu Xiaoli Zhu Yanli Li Ying Xiao Xiaojing Cui Lijuan Li Xuedong Liu Bin Cao department of Pulmonary and Critical Care Medicine Qingdao Municipal HospitalQingdaoShandong 266011China department of Nosocomial infection Qingdao Municipal HospitalQingdaoShandong 266011China department of Infectious Diseases Nanjing Lishui People’s HospitalNanjingJiangsu 211213China department of Pulmonary and Critical Care Medicine National Clinical Research Center of Respiratory DiseasesCenter for Respiratory DiseasesChina-Japan Friendship HospitalBeijing 100020China department of Respiratory Medicine Yan’an Hospital Affiliated to Kunming Medical UniversityKunmingYunnan 652199China department of Respiratory Medicine Beijing Huimin HospitalBeijing 100054China department of Pulmonary and Critical Care Medicine Zibo Municipal HospitalZiboShandong 255000China department of Respiratory Medicine Beijing Luhe HospitalCapital Medical UniversityBeijing 101149China department of Pulmonary and Critical Care Medicine Weifang No.2 People’s HospitalWeifangShandong 261599China department of Respiratory Medicine Shandong University Affiliated Qilu Hospital(Qingdao)QingdaoShandong 266035China department of Respiratory Medicine the 2nd Hospital of Beijing CorpsChinese Armed Police ForcesBeijing 100044China department of Infectious Disease Qingdao University Medical College Affiliated Yantai Yuhuangding HospitalYantaiShandong 100191China department of Respiratory Medicine Rizhao Chinese Medical Hospital Affiliated to Shandong Chinese Medical UniversityRizhaoShandong 276800China department of Respiratory Medicine Beijing Hospital of Traditional Chinese Medicine Affiliated to Capital Medical UniversityBeijing 100010China department of Occupational Medicine and Toxicology Beijing Chao-Yang HospitalCapital Medical UniversityBeijing 100020China

To the Editor:With an aging global population,the incidences of community-acquired pneumonia(CAP)and chronic obstructive pulmonary disease(COPD)have signicantly increased.[1]Previous studies have conrmed that COPD and asthma are independently associated with the prevalence of *** use of inhaled corticosteroid(ICS),the cornerstone of treatment for asthma,COPD with frequent acute exacerbations,and asthma-COPD overlap(ACO)may induce changes in the local lung microbiome and abnormal lung immunity,ultimately,causing a signicantly increased risk of ***,in cases of pneumonia,the effect of the use of ICS on CAP mortality remains *** data from one study favored the prior use of ICS,which was associated with a signicantly lower short-term mortality rate,[2]other studies have identied no impact on *** date,data on the impact of the use of ICS on mortality,prehospitalization or during hospitalization,are scarce,particularly in the older ***,this multicenter,retrospective study explored the association between the use of ICS during hospitalization and short-term mortality in older patients with CAP and those with chronic pulmonary disease(CPD).

关键词： pneumonia patients immunity

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Role of programmed cell death 4 in diseases: a double-edged sword

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Cellular & Molecular immunology 2017年第11期14卷 884-886页

作者： Yang Jiang Yufeng Jia Lining Zhang Hematology department The Second Hospital of Shandong UniversityJinanChina department of immunology and key laboratory of infection and immunity of shandong province Shandong University School of Basic Medical Sciences44 Wenhua Xi RoadJinan 250012China

The molecule of programmed cell death 4(PDCD4)is named based on its upregulation during *** is now known that PDCD4 is highly conserved during evolution and widely expressed in the immune cells and non-immune cells of humans and other ***4,as an inhibitor of gene transcription and translation,is very important in maintaining the normal function of cells.1,2 PDCD4 protein contains an N-terminal domain and two MA-3 domains in the central and C-terminal *** MA-3 domains can competitively bind to the translation initiation factor eIF4A with eIF4G to inhibit eIF4A activity and to impact the translation of specific mRNAs containing structured 5′-untranslated regions(5′UTRs).

关键词： PDCD4 death diseases

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The hepatic macrophage pool in NASH

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Cellular & Molecular immunology 2021年第8期18卷 2059-2060页

作者： Tixiao Wang Chunhong Ma key laboratory for Experimental Teratology of Ministry of Education Key Laboratory of Infection and Immunity of Shandong Provinceand Department of ImmunologySchool of Basic Medical SciencesCheeloo Medical College of Shandong UniversityJinanShandongChina Advanced Medical Research Institute Shandong UniversityJinanShandongChina

Nonalcoholic fatty liver disease(NAFLD)and its inflammatory subtype nonalcoholic steatohepatitis(NASH)are currently the most common chronic liver diseases worldwide and emerging risk factors for hepatocellular carcinoma.1 Numerous studies have demonstrated the critical involvement of hepatic macrophages,including resident Kupffer cells(KCs)and recruited monocyte-derived macrophages(MoMFs).

关键词： liver NAFLD NASH

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First small-molecule PROTACs for G protein-coupled receptors:inducing α1A-adrenergic receptor degradation

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Acta Pharmaceutica Sinica B 2020年第9期10卷 1669-1679页

作者： Zhenzhen Li Yuxing Lin Hui Song Xiaojun Qin Zhongxia Yu Zheng Zhang Gaopan Dong Xiang Li Xiaodong Shi Lupei Du Wei Zhao Minyong Li department of Medicinal Chemistry Key Laboratory of Chemical Biology(MOE)School of PharmacyShandong UniversityJinan 250012China department of immunology Key Laboratory of Infection and Immunity of Shandong ProvinceSchool of Basic Medical ScienceShandong UniversityJinan 250012China department of Chemistry University of South FloridaTampaFL 33620USA State key laboratory of Microbial Technology Shandong UniversityJinan 250100China

Proteolysis targeting chimeras(PROTACs)are dual-functional hybrid molecules that can selectively recruit an E3 ubiquitin ligase to a target protein to direct the protein into the ubiquitinproteasome system(UPS),thereby selectively reducing the target protein level by the ubiquitinproteasome ***,small-molecule PROTACs are gaining popularity as tools to desrade pathogenic ***,we present the first small-molecule PROTACs that can induce the alA-adrenergic receptor(α1 A-AR)degradation,which is also the first small-molecule PROTACs for G proteincoupled receptors(GPCRs)to our *** degradation inducers were developed through conjugation of knownα1-adrenergic receptors(α1-ARs)inhibitor prazosin and cereblon(CRBN)ligand pomalidomide through the different *** representative compound 9 c is proved to inhibit the proliferation of PC-3 cells and result in tumor growth regression,which highlighted the potential of our study as a new therapeutic strategy for prostate cancer.

关键词： Small-molecule PROTACs α1A-Adrenergic receptor Ubiquitylation Degradation Prostate cancer

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Monocyte-derived KCs(MoKCs)contribute to the KC pool in NASH

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Cellular & Molecular immunology 2021年第3期18卷 518-519页

作者： Yingchun Wang Lifen Gao key laboratory for Experimental Teratology of Ministry of Education Shandong Key Laboratory of Infection and Immunityand Department of ImmunologySchool of Basic Medical SciencesCheeloo College of MedicineShandong UniversityJinanShandong 250012P.R.China

Nonalcoholic fatty liver disease(NAFLD)is now recognized as the most common liver disease worldwide and has increasingly become a serious hazard to human *** consists of a spectrum of disease states ranging from simple steatosis to more severe disease termed nonalcoholic steatohepatitis(NASH),fibrosis,cirrhosis,and even hepatocellular carcinoma.

关键词： NAFLD liver NASH

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Development and Evaluation of a Promising Biomarker for Diagnosis of Latent and Active Tuberculosis infection

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Infectious Diseases & immunity 2024年第1期4卷 10-24页

作者： Cong Peng Fan Jiang Yinping Liu Yong Xue Peng Cheng Jie Wang Liang Wang Wenping Gong Hebei North University Zhangjiakou 075000Hebei ProvinceChina Beijing key laboratory of New Techniques of Tuberculosis Diagnosis and Treatment Senior Department of TuberculosisEighth Medical Center of PLA General HospitalBeijing 100091China department of Geriatrics Eighth Medical Center of PLA General HospitalBeijing 100091China Section of Health No.94804 Unit of the Chinese People's Liberation ArmyShanghai 200434China

Background:Diagnosing latent tuberculosis(TB)infection(LTBI)and active TB(ATB)is crucial for preventing disease progression and ***,current diagnostic tests have limitations in terms of accuracy and sensitivity,making it challenging to diagnose these different infection ***,this study intends to develop a promising biomarker for LTBI and ATB diagnosis to overcome the limitations of the current diagnostic ***:We developed a novelmultiepitope-based diagnostic biomarker(MEBDB)fromLTBI region of differentiation antigens using bioinformatics and *** responses induced byMEBDM were detected using enzyme-linked immunosorbent spot and cytometric bead *** study was conducted from April 2022 to December 2022 in the Seniordepartment of Tuberculosis at the 8thMedical Center of PLA General Hospital,*** samples were collected from participants with ATB,individuals with LTBI,and healthy controls(HCs).The diagnostic efficacy of MEBDB was evaluated using receiver operating characteristic ***:A novel MEBDB,designated as CP19128P,was ***19128P comprises 19 helper T lymphocyte epitopes,12 cytotoxic T lymphocyte epitopes,and 8 B-cell *** silico simulations demonstrated that CP19128P possesses strong affinity for Toll-like receptors and elicits robust innate and adaptive immune ***19128P generated significantly higher levels of tumor necrosis factor(TNF-α),interleukin 4(IL-4),and IL-10 in ATB patients(n=7)and LTBI(n=8)individuals compared with HCs(n=62)(P<0.001).Moreover,CP19128P-induced specific cytokines could be used to discriminate LTBI and ATB from healthy subjects with high sensitivity and *** IL-2 with IL-4 or TNF-α could differentiate LTBI from HCs(the area under the receiver operating characteristic curve[AUC],0.976[95% confidence interval[CI],0.934-1.000]or 0.986[0.956-1.000]),whereas combining IL-4 with IL-17A or TNF-α could differentiate ATB from

关键词： Tuberculosis Latent tuberculosis infection Active tuberculosis Multiepitope-based diagnostic biomarker Bioinformatics:Immunoinformatics

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