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FGF7 enhances the expression of ACE2 in human islet organoids aggravating SARS-CoV-2 infection

Signal Transduction and Targeted Therapy 2024年第5期9卷 2260-2274页

作者： Hao Meng Zhiying Liao Yanting Ji Dong Wang Yang Han Chaolin Huang Xujuan Hu Jingyi Chen Hengrui Zhang Zonghong Li Changliang Wang Hui Sun Jiaqi Sun Lihua Chen Jiaxiang Yin Jincun Zhao Tao Xu Huisheng Liu School of Biomedical Engineering Guangzhou Medical UniversityGuangzhou 511495 GuangdongChina Guangzhou national Laboratory Guangzhou 510320 GuangdongChina State key Laboratory of respiratory Disease National Clinical Research Center for Respiratory DiseaseGuangzhou Institute of Respiratory HealthThe First Affiliated Hospital of Guangzhou Medical UniversityGuangzhou 510120China center for Translational Medicine Wuhan Jinyintan HospitalWuhan 430023 HubeiChina School of Biomedical Sciences and Engineering South China University of TechnologyGuangzhou 510006 GuangdongChina

The angiotensin-converting enzyme 2(ACE2)is a primary cell surface viral binding receptor for SARS-CoV-2,so finding new regulatory molecules to modulate ACE2 expression levels is a promising strategy against *** the current study,we utilized islet organoids derived from human embryonic stem cells(hESCs),animal models and COVID-19 patients to discover that fibroblast growth factor 7(FGF7)enhances ACE2 expression within the islets,facilitating SARS-CoV-2 infection and resulting in impaired insulin *** hESC-derived islet organoids,we demonstrated that FGF7 interacts with FGF receptor 2(FGFR2)and FGFR1 to upregulate ACE2 expression predominantly inβ*** upregulation increases both insulin secretion and susceptibility ofβcells to SARS-CoV-2 *** FGFR counteracts the FGF7-induced ACE2 upregulation,subsequently reducing viral infection and replication in the ***,retrospective clinical data revealed that diabetic patients with severe COVID-19 symptoms exhibited elevated serum FGF7 levels compared to those with mild ***,animal experiments indicated that SARS-CoV-2 infection increased pancreatic FGF7 levels,resulting in a reduction of insulin concentrations in *** together,our research offers a potential regulatory strategy for ACE2 by controlling FGF7,thereby protecting islets from SARS-CoV-2 infection and preventing the progression of diabetes in the context of COVID-19.

关键词： ACE2 FGF7 islet

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Intranasal boosting with RBD-HR protein vaccine elicits robust mucosal and systemic immune responses

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Genes & diseases 2024年第4期11卷 327-339页

作者： Li Chen Wenyan Ren Hong Lei Jiayu Wang Haiying Que Dandan Wan Aqu Alu Dandan Peng Minyang Fu Weiqi Hong Yuhe Huang Xiangrong Song Guangwen Lu Xiawei Wei Laboratory of Aging research and Cancer Drug Target State Key Laboratory of Biotherapy and Cancer CenterNational Clinical Research Center for GeriatricsWest China HospitalSichuan UniversityChengduSichuan 610041China

The emergence of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)variants has decreased the efficacy of SARs-CoV-2 vaccines in containing coronavirus disease 2019(CoVID-19)over time,and booster vaccination strategies are urgently necessitated to achieve sufficient *** immunization can improvemucosal immunity,offer-ing protection against the infection and sustaining the spread of *** this study,an intranasal booster of the RBD-HR vaccine after two doses of the mRNA vaccine significantly increased the levels of specific binding antibodies in serum,nasal lavage fluid,and bronchoal-veolar lavage fluid compared with only two doses of mRNA *** intranasal boosting with the RBD-HR vaccine,the levels of serum neutralizing antibodies against prototype and variant strains of SARS-Cov-2 pseudoviruses weremarkedly higher than those in mice receiving mRNA vaccine alone,and intranasal boosting with the RBD-HR vaccine also inhibited the bind-ing of RBD to hACE2 ***,the heterologous intranasal immunization regimen promoted extensive memory T cell responses and activated CD103+dendritic cells in the respiratory mucosa,and potently enhanced the formation of T follicular helper cells and germinal center B cells in vital immune organs,including mediastinal lymph nodes,inguinal lymph nodes,and ***,these data infer that heterologous intranasal boosting with the RBD-HR vaccine elicited broad protective immunity against SARS-CoV-2 both locallyandsystemically.

关键词： Heterologous immunization Intranasal immunization mRNA vaccine SARS-CoV-2 Subunitprotein vaccine

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A High-Affinity Methyl-CpG-Binding Protein for Endonuclease-Free and Label-Free DNA Methyltransferase Activity Detection

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Journal of Analysis and Testing 2024年第3期8卷 327-334页

作者： Yang Bai Shulin Tan Yingsong Sheng Yueqing Gu Haiping Wu Baicun Li Yunlong Liu Department of Biomedical Engineering School of Engineering China Pharmaceutical University Department of clinical Pharmacy Jinling Hospital State Key Laboratory of Analytical Chemistry for Life Science & Jiangsu Key Laboratory of Molecular Medicine Medical School of Nanjing University School of Pharmaceutical Sciences Southern Medical University national center for respiratory Medicine Center of Respiratory Medicine China-Japan Friendship Hospital

DNA methyltransferase(MTase) activity detection has received increasing attention as a promising biomarker and therapeutic target. However, most of these detection methods rely on endonuclease digestion and signal groups ***, we present a novel platform for sensing DNA MTase activity that overcomes these limitations. Our approach is both endonuclease-free and label-free, utilizing a combination of a high-affinity streptavidin-methyl-CpG-binding domain(SA-MBD) protein and surface plasmon resonance(SPR) technology. The SA-MBD protein specifically recognizes a hairpin probe containing methylated CpG sites, which is treated with *** MTase. This recognition event generates a corresponding SPR response signal. The limit of detection is as low as 0.016 U/mL, owing to the high-a ffinity of the SA-MBD ***, we have demonstrated the feasibility of our method for *** MTase activity analysis in serum and inhibitor screening, which implies the potential prospects for biomedical research.

关键词： Biosensing DNA methyltransferase Inhibitor screening Methyl-CpG-binding protein Surface plasmon resonance

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Influenza and pneumococcal vaccination coverage and associated factors in patients hospitalized with acute exacerbations of COPD in China:Findings from real-world data

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Chinese Medical Journal 2024年第10期137卷 1179-1189页

作者： Ruoxi He Xiaoxia Ren Ke Huang Jieping Lei Hongtao Niu Wei Li Fen Dong Baicun Li Ye Wang Ting Yang Chen Wang School of Population Medicine and Public Health Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100730China Department of respiratory Medicine National Key Clinical SpecialtyBranch of National Clinical Research Center for Respiratory DiseaseXiangya HospitalCentral South UniversityChangshaHunan 410008China Department of Pulmonary and Critical Care Medicine Center of Respiratory MedicineChina-Japan Friendship HospitalBeijing 100029China Institute of respiratory Medicine Chinese Academy of Medical SciencesBeijing 100029China national center for respiratory Medicine Beijing 100029China national clinical research center for respiratory diseases Beijing 100029China Department of clinical research and Data Management Center of Respiratory MedicineChina-Japan Friendship HospitalBeijing 100029China

Background:Influenza and pneumococcal vaccination are a priority in patients with chronic obstructive pulmonary disease(COPD).However,limited information is available on vaccination coverage among patients with acute exacerbations of COPD(AECOPD)in *** study aimed to determine the rates and associated factors of influenza and pneumococcal vaccination in patients hospitalized with ***:Baseline data from a national,multicenter,hospital-based study that included adult inpatients with AECOPD between 2017 and 2021 were *** outcomes of interest were the influenza vaccination in the past year and the pneumococcal vaccination in the past 5 *** ensure national representativeness,rates were weighted according to the distribution of hospital levels and types enrolled in this *** Poisson regression based on mixed-effects models were used to determine the associated *** independent variables included the region and hospital features where the participants were located,sociodemographic characteristics(age,sex,rural/urban residence,education,etc.),and clinical indicators(COPD disease history,lung function parameters,comorbidities,etc.).The treatment profiles of the vaccinated and unvaccinated participants were ***:Of 6949 eligible participants,the weighted rates of influenza/pneumococcal,influenza,and pneumococcal vaccination were 2.72%(95%confidence interval[CI]:2.34%-3.10%),2.09%(95%CI:1.76%-2.43%),and 1.25%(95%CI:0.99%-1.51%),*** multivariable models,age≥60 years(60-69 years,odds ratio[OR]:1.90,95%CI:1.11-3.25;≥80 years,OR:2.00,95%CI:1.06-3.78),geographical regions(Northern China relative to Eastern China,OR:5.09,95%CI:1.96-13.21),urban residence(OR:1.69,95%CI:1.07-2.66),a higher education level(junior high school,OR:1.77,95%CI:1.21-2.58;senior high school or above,OR:2.61,95%CI:1.69-4.03),former smoking(OR:1.79,95%CI:1.15-2.79),and regular inhaled medication treatment(OR:3.28,95%CI:2.29-4.70)were

关键词： Chronic obstructive pulmonary disease Influenza Pneumococcal Vaccine AECOPD

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Asialoglycoprotein receptor 1 promotes SARS-CoV-2 infection of human normal hepatocytes

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Signal Transduction and Targeted Therapy 2024年第3期9卷 1199-1208页

作者： Xinyi Yang Xu Zheng Yuqi Zhu Xiaying Zhao Jun Liu Jiangna Xun Songhua Yuan Jun Chen Hanyu Pan Jinlong Yang Jing Wang Zhimin Liang Xiaoting Shen Yue Liang Qinru Lin Huitong Liang Min Li Fei Peng Daru Lu Jianqing Xu Hongzhou Lu Shibo Jiang Ping Zhao Huanzhang Zhu State key Laboratory of Genetic Engineering and Engineering research center of Gene Technology Ministry of EducationInstitute of GeneticsSchool of Life SciencesYiwu Research InstituteFudan UniversityShanghaiChina Department of Microbiology Faculty of Naval MedicineNaval Medical UniversityShanghai 200433China Scientific research center Shanghai Public Health Clinical CenterFudan UniversityShanghaiChina Department of Infectious diseases and Immunology Shanghai Public Health Clinical CenterFudan UniversityShanghaiChina Changzheng Hospital Naval Medical UniversityShanghaiChina key Laboratory of Medical Molecular Virology(MOE/NHC/CAMS) Shanghai Institute of Infectious Disease and BiosecuritySchool of Basic Medical SciencesFudan UniversityShanghaiChina Department of Infectious diseases and Nursing research Institution National Clinical Research Center for Infectious DiseasesThe Third People’s Hospital of ShenzhenShenzhenGuangdongChina

Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)causes multi-organ damage,which includes hepatic dysfunction,as observed in over 50%of COVID-19 *** I converting enzyme(peptidyl-dipeptidase A)2(ACE2)is the primary receptor for SARS-CoV-2 entry into host cells,and studies have shown the presence of intracellular virus particles in human hepatocytes that express ACE2,but at extremely low ***,we asked if hepatocytes might express receptors other than ACE2 capable of promoting the entry of SARS-CoV-2 into *** address this question,we performed a genome-wide CRISPR-Cas9 activation library screening and found that Asialoglycoprotein receptor 1(ASGR1)promoted SARS-CoV-2 pseudovirus infection of HeLa *** Huh-7 cells,simultaneous knockout of ACE2 and ASGR1 prevented SARS-CoV-2 pseudovirus *** the immortalized THLE-2 hepatocyte cell line and primary hepatic parenchymal cells,both of which barely expressed ACE2,SARSCoV-2 pseudovirus could successfully establish an ***,after treatment with ASGR1 antibody or siRNA targeting ASGR1,the infection rate significantly dropped,suggesting that SARS-CoV-2 pseudovirus infects hepatic parenchymal cells mainly through an ASGR1-dependent *** confirmed that ASGR1 could interact with Spike protein,which depends on receptor binding domain(RBD)and N-terminal domain(NTD).Finally,we also used Immunohistochemistry and electron microscopy to verify that SARS-CoV-2 could infect primary hepatic parenchymal *** inhibiting ASGR1 in primary hepatic parenchymal cells by siRNA,the infection efficiency of the live virus decreased ***,these findings indicate that ASGR1 is a candidate receptor for SARS-CoV-2 that promotes infection of hepatic parenchymal cells.

关键词： ACE2 infection glycoprotein

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Characterization of humoral immune responses against SARS-CoV-2 accessory proteins in infected patients and mouse model

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Virologica Sinica 2024年第3期39卷 414-421页

作者： Yuming Li Yanhong Tang Xiaoqian Wang Airu Zhu Dongdong Liu Yiyun He Hu Guo Jie Zheng Xinzhuo Liu Fengyu Chi Yanqun Wang Zhen Zhuang Zhaoyong Zhang Donglan Liu Zhao Chen Fang Li Wei Ran Kuai Yu Dong Wang Liyan Wen Jianfen Zhuo Yanjun Zhang Yin Xi Jingxian Zhao Jincun Zhao Jing Sun School of Public Health Shandong First Medical University&Shandong Academy of Medical SciencesJi'nan250117China key Laboratory of Emerging Infectious diseases in Universities of Shandong Shandong First Medical University&Shandong Academy of Medical SciencesJi'nan250117China State key Laboratory of respiratory Disease National Clinical Research Center for Respiratory DiseaseNational Center for Respiratory MedicineGuangzhou Institute of Respiratory HealthThe First Affiliated Hospital of Guangzhou Medical UniversityGuangzhouGuangdong510182China Hunan Provincial People's Hospital The First Affiliated Hospital of Hunan Normal UniversityHunan Normal UniversityChangsha410005China Guangzhou national Laboratory GuangzhouGuangdong510005China Shanghai Institute for Advanced Immunochemical Studies School of Life Science and TechnologyShanghai Tech UniversityShanghai201210China Institute for Hepatology National Clinical Research Center for Infectious DiseaseShenzhen Third People's HospitalThe Second Affiliated HospitalSchool of MedicineSouthern University of Science and TechnologyShenzhen518005China

Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),the causative agent of COVID-19,encodes several accessory proteins that have been shown to play crucial roles in regulating the innate immune ***,their expressions in infected cells and immunogenicity in infected humans and mice are still not fully *** study utilized various techniques such as luciferase immunoprecipitation system(LIPS),immunofluorescence assay(IFA),and western blot(WB)to detect accessory protein-specific antibodies in sera of COVID-19 *** antibodies to proteins 3a,3b,7b,8 and 9c can be detected by LIPS,but only protein 3a antibody was detected by IFA or *** against proteins 3a and 7b were only detected in ICU patients,which may serve as a marker for predicting disease ***,we investigated the expression of accessory proteins in SARS-CoV-2-infected cells and identified the expressions of proteins 3a,6,7a,8,and *** also analyzed their ability to induce antibodies in immunized mice and found that only proteins 3a,6,7a,8,9b and 9c were able to induce measurable antibody productions,but these antibodies lacked neutralizing activities and did not protect mice from SARS-CoV-2 *** findings validate the expression of SARS-CoV-2 accessory proteins and elucidate their humoral immune response,providing a basis for protein detection assays and their role in pathogenesis.

关键词： SARS-CoV-2 Accessory protein Humoral immune responses COVID-19 Mouse model

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Prevention and Treatment of Mycoplasma pneumoniae Requires Long-term Attention

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Infectious diseases & Immunity 2024年第2期4卷 58-60页

作者： Dawei Zhang Zhaomin Feng Quanyi Wang Department of Infectious diseases Fifth Medical Center of Chinese People's Liberation Army(PLA)General HospitalNational Clinical Research Center for Infectious DiseasesBeijing 100039China Beijing center for Disease Prevention and Control Beijing 100013China Beijing research center for respiratory Infectious diseases Beijing 100013China.

Mycoplasma pneumoniae is a major etiological agent of communityacquired pneumonia that accounts for 10%to 40%of communityacquired pneumonia and exhibits distinct cyclic epidemic patterns that recur at 3-to 7-year intervals,[1-4] Nonpharmaceutical interventions(NPIs)against coronavirus disease 2019(COVID-19)that were used by countries worldwide during the pandemic significantly reduced the prevalence of ***.[5]After the lifting of COVID-19 pandemic restrictions,*** gradually grew globally.[6]To provide a better understanding of the growth of *** in 2023,we explored the hazards,incidence,diagnosis,and antibiotic resistance of ***.

关键词： diagnosis pneumoniae lifting

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Measures of insulin resistance and beta cell function before and after treatment of HCV infection

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Virologica Sinica 2024年第4期39卷 667-674页

作者： Jizheng Chen Pan Qiu Tingfeng Zhao Haowei Jiang Kebinur Tursun Sulaiman Ksimu Xinwen Chen Qian Wang State key Laboratory of respiratory Disease National Clinical Research Center for Respiratory DiseaseGuangzhou Institute of Respiratory HealthThe First Affiliated Hospital of Guangzhou Medical UniversityGuangzhou510182China Jiangsu Province key Lab of Human Functional Genomics Department of Biochemistry and Molecular BiologyNanjing Medical UniversityNanjing210029China State key Laboratory of Virology Wuhan Institute of VirologyCenter for Biosafety Mega-ScienceChinese Academy of SciencesWuhan430071China Guangzhou Laboratory Guangzhou510005China The First Affiliated Hospital of Xinjiang Medical University Urumchi830054China

The association between chronic HCV infection and type 2 diabetes mellitus(T2DM)has been established;however,there is limited research onβ-cell function particularly in the pre-diabetic ***,we evaluated indices ofβ-cell function and insulin sensitivity across the spectrum from normal glucose tolerance to T2DMin individuals with and without chronic hepatitis C(CHC),and the effects of antiviral treatments on these variables.A total of 153 noncirrhotic,non-fibrotic CHC patients with a BMIclinical manifestations and complications.

关键词： Hepatitis C virus(HCV) Type 2 diabetes(T2DM) Beta cell(β-cell) Insulin secretion

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SARS-CoV-2 envelope protein impairs airway epithelial barrier function and exacerbates airway inflammation via increased intracellular Cl^(-)concentration

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Signal Transduction and Targeted Therapy 2024年第4期9卷 1745-1759页

作者： Jian-Bang Xu Wei-Jie Guan Yi-Lin Zhang Zhuo-Er Qiu Lei Chen Xiao-Chun Hou Junqing Yue Yu-Yun Zhou Jie Sheng Lei Zhao Yun-Xin Zhu Jing Sun Jincun Zhao Wen-Liang Zhou Nan-Shan Zhong State key Laboratory of respiratory Disease National Clinical Research Center for Respiratory DiseaseNational Center for Respiratory MedicineDepartment of Respiratory and Critical Care MedicineGuangzhou Institute of Respiratory HealthThe First Affiliated Hospital of Guangzhou Medical UniversityGuangzhouP.R.China Department of Thoracic Surgery Guangzhou Institute for Respiratory HealthThe First Affiliated Hospital of Guangzhou Medical UniversityGuangzhouP.R.China Guangzhou national Laboratory GuangzhouP.R.China School of Life Sciences Sun Yat-sen UniversityGuangzhouP.R.China Guangdong Provincial key Laboratory of Pharmaceutical Functional Genes School of Life SciencesSun Yat-sen UniversityGuangzhouP.R.China Department of Physiology School of Basic Medical SciencesGuangzhou Medical UniversityGuangzhouP.R.China

Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection disrupts the epithelial barrier and triggers airway *** envelope(E)protein,a core virulence structural component of coronaviruses,may play a role in this *** could interfere with transepithelial Cl^(-)transport via impairment of the cystic fibrosis transmembrane conductance regulator(CFTR),which modulates nuclear factor kB(NF-kB)***,the pathological effects of SARS-CoV-2 E protein on airway epithelial barrier function,Cl^(-)transport and the robust inflammatory response remain to be ***,we have demonstrated that E protein down-regulated the expression of tight junctional proteins,leading to the disruption of the airway epithelial *** addition,E protein triggered the activation of Toll-like receptor(TLR)2/4 and downstream c-Jun N-terminal kinase(JNK)signaling,resulting in an increased intracellular Cl^(-)concentration([Cl^(-)]_(i))via up-regulating phosphodiesterase 4D(PDE4D)expression in airway epithelial *** elevated[Cl^(-)]_(i);contributed to the heightened airway inflammation through promoting the phosphorylation of serum/glucocorticoid regulated kinase 1(SGK1).Moreover,blockade of SGK1 or PDE4 alleviated the robust inflammatory response induced by E ***,these findings provide novel insights into the pathogenic role of SARS-CoV-2 E protein in airway epithelial damage and the ongoing airway inflammation during SARS-CoV-2 infection.

关键词： airway inflammation elevated

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Sex Disparities in the Association of Blood Pressure Parameters and Arterial Sclerosis Risk

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Biomedical and Environmental Sciences 2024年第7期37卷 795-799页

作者： Dongdong Zhang Weiling Chen Minqi Gu Xi Li Yuying Wu Xueru Fu Ping Tang Fulan Hu Jing Li Xizhuo Sun Dongsheng Hu Ming Zhang Department of General Practice The Affiliated Luohu Hospital of Shenzhen University Medical SchoolShenzhen 518060GuangdongChina Department of Allergy and clinical Immunology State Key Laboratory of Respiratory DiseaseNational Clinical Research Center for Respiratory DiseaseGuangzhou Institute of Respiratory Healththe First Affiliated Hospital of Guangzhou Medical UniversityGuangzhou 510120GuangdongChina Department of Biostatistics and Epidemiology School of Public HealthShenzhen University Medical SchoolShenzhen 518060GuangdongChina

Cardiovascular disease(CVD)is the leading cause of death worldwide[1].Arterial sclerosis(AS)and hypertension are the main risk factors and pathological bases of *** pulse wave velocity(PWV)measurements could reflect early progression of *** on the structure-function properties of the vascular wall and hemodynamics,strong evidence suggests that any increase in blood pressure levels can mechanically impair the ability of the endothelium to maintain vascular homeostasis[2].High levels of blood pressure parameters,such as systolic blood pressure(SBP),diastolic blood pressure(DBP),pulse pressure(PP),and mean arterial pressure(MAP)have been identified as essential risk biomarkers for atherosclerosis.

关键词： Blood Arterial atherosclerosis

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