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Approach from the laboratory to the field: New strategies in the control of mosquito-borne infectious diseases

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Science China Life Sciences 2024年

作者： Ziqian Xu Lianpan Dai Jun Liu National Key laboratory of Intelligent Tracking and Forecasting for infectious diseases (NITFID) National Institute for Viral Disease Control and Prevention Chinese Center for Disease Control and Prevention CAS Key laboratory of Pathogen Microbiology and immunology Institute of Microbiology Chinese Academy of Sciences

Vector-borne viruses, transmitted among humans and animal hosts through bites of vectors such as mosquitoes and ticks,pose a great and ongoing threat to public health and biosafety (Yang et al., 2022).Among them, dengue virus-induced epidemics, have dramatically increased worldwide in recent decades. The report released by the World Health Organization (WHO) at the end of 2023 showed that dengue epidemic globally surged in2023, with the number of reported cases nearing a historical peak.

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Notch signaling pathway in cancer:from mechanistic insights to targeted therapies

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Signal Transduction and Targeted Therapy 2024年第6期9卷 2527-2563页

作者： Qingmiao Shi Chen Xue Yifan Zeng Xin Yuan Qingfei Chu Shuwen Jiang Jinzhi Wang Yaqi Zhang Danhua Zhu Lanjuan Li State Key laboratory for Diagnosis and Treatment of infectious diseases National Clinical Research Center for Infectious DiseasesNational Medical Center for Infectious DiseasesCollaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesThe First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China

Notch signaling,renowned for its role in regulating cell fate,organ development,and tissue homeostasis across metazoans,is highly conserved throughout *** Notch receptor and its ligands are transmembrane proteins containing epidermal growth factor-like repeat sequences,typically necessitating receptor-ligand interaction to initiate classical Notch signaling *** evidence indicates that the Notch signaling pathway serves as both an oncogenic factor and a tumor suppressor in various cancer *** of this pathway promotes epithelial-mesenchymal transition and angiogenesis in malignancies,closely linked to cancer proliferation,invasion,and ***,the Notch signaling pathway contributes to maintaining stem-like properties in cancer cells,thereby enhancing cancer *** regulatory role of the Notch signaling pathway in cancer metabolic reprogramming and the tumor microenvironment suggests its pivotal involvement in balancing oncogenic and tumor suppressive ***,the Notch signaling pathway is implicated in conferring chemoresistance to tumor ***,a comprehensive understanding of these biological processes is crucial for developing innovative therapeutic strategies targeting Notch *** review focuses on the research progress of the Notch signaling pathway in cancers,providing in-depth insights into the potential mechanisms of Notch signaling regulation in the occurrence and progression of ***,the review summarizes pharmaceutical clinical trials targeting Notch signaling for cancer therapy,aiming to offer new insights into therapeutic strategies for human malignancies.

关键词： Notch invasion involvement

Mitochondrial dysfunction: A promising therapeutic target for liver diseases

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Genes & diseases 2024年第3期11卷 324-337页

作者： Ping Chen Lichao Yao Mengqin Yuan Zheng Wang Qiuling Zhang Yingan Jiang Lanjuan Li Department of infectious diseases Renmin Hospital of Wuhan UniversityWuhanHubei 430060China State Key laboratory for Diagnosis and Treatment of infectious diseases National Clinical Research Center for Infectious DiseasesCollaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesThe First Affiliated HospitalCollege of MedicineZhejiang UniversityHangzhouZhejiang 310003China

The liver is an important metabolic and detoxification organ and hence demands a large amount of energy,which is mainly produced by the *** tissues of pa-tients with alcohol-related or non-alcohol-related liver diseases contain ultrastructural mito-chondrial lesions,mitochondrial DNA damage,disturbed mitochondrial dynamics,and compromised ATP *** of mitochondrial reactive oxygen species in-duces oxidative damage to mitochondrial proteins and mitochondrial DNA,decreases mito-chondrial membrane potential,triggers hepatocyte inflammation,and promotes programmed cell death,all of which impair liver *** DNA may be a poten-tial novel non-invasive biomarker of the risk of progression to liver cirrhosis and hepatocellular carcinoma in patients infected with the hepatitis B *** herein present a review of the mechanisms of mitochondrial dysfunction in the development of acute liver injury and chronic liver diseases,such as hepatocellular carcinoma,viral hepatitis,drug-induced liver injury,alcoholic liver disease,and non-alcoholic fatty liver *** review also discusses mito-chondrion-centric therapies for treating liver diseases.

关键词： Chronic diseases Liverdamage Mesenchymalstem cell Mitochondrial dysfunction Oxidativestress

Virus-like nanoparticle vaccines for inducing long-lasting immunity against infectious diseases

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National Science Review 2024年第4期11卷 13-15页

作者： Yi-Nan Zhang Sarah Auclair Jiang Zhu Department of Integrative Structural and Computational Biology The Scripps Research Institute Department of immunology and Microbiology The Scripps Research Institute

Prophylactic vaccines that can generate long-lasting protective immune responses are needed for many infectious diseases. Efficient vaccination requires vaccine antigens to be retained and presented to B cells in lymp...

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Activation of leukotriene B_(4)receptor 1 is a prerequisite for complement receptor 3-mediated antifungal responses of neutrophils

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Cellular & Molecular immunology 2024年第3期21卷 245-259页

作者： Yan Xin Sihan Xiong Linghong Zhou Xin Lin Institute for immunology and School of Medicine Tsinghua University100084BeijingChina Tsinghua University-Peking University Center for Life Sciences 100084BeijingChina Department of infectious diseases Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency ResponseNational Medical Center for Infectious DiseasesHuashan HospitalFudan UniversityShanghai200040China

Invasive fungal infections are life-threatening,and neutrophils are vital cells of the innate immune system that defend against *** role of LTA4H-LTB_(4)-BLT1 axis in regulation of neutrophil responses to fungal infection remains poorly ***,we demonstrated that the LTA4H-LTB_(4)-BLT1 axis protects the host against Candida albicans and Aspergillus fumigatus,but not Cryptococcus neoformans infection,by regulating the antifungal activity of *** results show that deleting Lta4h or Blt1 substantially impairs the fungal-specific phagocytic capacity of ***,defective activation of the spleen tyrosine kinase(Syk)and extracellular signal-related kinase(ERK1/2)pathways in neutrophils accompanies this ***,BLT1 regulates CR3-mediated,β-1,3-glucan-induced neutrophil phagocytosis,while a physical interaction with CR3 with slight influence on its dynamics is *** findings thus demonstrate that the LTA4H-LTB_(4)-BLT1 axis is essential for the phagocytic function of neutrophils in host antifungal immune response against Candida albicans and Aspergillus fumigatus.

关键词： LTA4H BLT1 Phagocytosis Complement receptor 3 Fungi

Human Placental Mesenchymal Stem Cells Relieve Primary Sclerosing Cholangitis via Upregulation of TGR5 in Mdr2^(-/-)Mice and Human Intrahepatic Cholangiocyte Organoid Models

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research 2024年第2期2023卷 355-372页

作者： Qigu Yao Wenyi Chen Yingduo Yu Feiqiong Gao Jiahang Zhou Jian Wu Qiaoling Pan Jinfeng Yang Lingling Zhou Jiong Yu Hongcui Cao Lanjuan Li State Key laboratory for the Diagnosis and Treatment of infectious diseases Cllaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesThe First Affliated HospitalZhejang University School of Medicine79 Qingchun Rd.Hangzhou 310003China National Clinical research Center for infectious diseases HangzhouChina Key laboratory of Diagnosis and Treatment of Aging and Physic-chemical Injury diseases of Zhejiang Province 79 Qingchun Rd.Hangzhou 310003China Jjinan Microecological Biomedicine Shandong laboratory Jinan 250117China

Primary sclerosing cholangitis(PSC)is a biliary disease accompanied by chronic inflammation of the liver and biliary *** stem cells(MSCs)are used to treat liver diseases because of their immune regulation and regeneration-promoting *** study was performed to explore the therapeutic potential of human placental MSCs(hP-MSCs)in PSC through the Takeda G protein-coupled receptor 5(TGR5)receptor *** tissues were collected from patients with PSC and healthy donors(n=4)for RNA sequencing and intrahepatic cholangiocyte organoid ***-MSCs were injected via the tail vein into Mdr2^(-/-),bile duct ligation(BDL),and 3,5-diethoxycarbonyl-1,4-dihydrocollidine(DDC)mouse models or co-cultured with organoids to confirm their therapeutic effect on biliary *** in bile acid metabolic profile were analyzed by liquid chromatography/tandem mass spectrometry(LC-MS/MS).Compared with healthy controls,liver tissues and intrahepatic cholangiocyte organoids from PSC patients were characterized by inflammation and cholestasis,and marked downregulation of bile acid receptor TGR5 ***-MSC treatment apparently reduced the inflammation,cholestasis,and fibrosis in Mdr2^(-/-),BDL,and DDC model *** activating the phosphatidylinositol 3 kinase/extracellular signal-regulated protein kinase pathway,hP-MSC treatment promoted the proliferation of cholangiocytes,and affected the transcription of downstream nuclear factorκB through regulation of the binding of TGR5 and Pellino3,thereby affecting the cholangiocyte inflammatory phenotype.

关键词： inflammation TGR5 Human

Hypertension and NAFLD risk:Insights from the NHANES 2017-2018 and Mendelian randomization analyses

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Chinese Medical Journal 2024年第4期137卷 457-464页

作者： Mengqin Yuan Jian He Xue Hu Lichao Yao Ping Chen Zheng Wang Pingji Liu Zhiyu Xiong Yingan Jiang Lanjuan Li Department of infectious diseases Renmin Hospital of Wuhan UniversityWuhanHubei 430000China Department of Gastroenterology Nanfang HospitalSouthern Medical UniversityGuangzhouGuangdong 510010China State Key laboratory for Diagnosis and Treatment of infectious diseases National Clinical Research Centre for Infectious DiseasesCollaborative Innovation Centre for Diagnosis and Treatment of Infectious DiseasesDepartment of Infectious DiseasesThe First Affiliated HospitalCollege of MedicineZhejiang UniversityHangzhouZhejiang 310000China

Background:Hypertension and non-alcoholic fatty liver disease(NAFLD)share several pathophysiologic risk factors,and the exact relationship between the two remains *** study aims to provide evidence concerning the relationship between hypertension and NAFLD by analyzing data from the National Health and Nutrition Examination Survey(NHANES)2017-2018 and Mendelian randomization(MR)***:Weighted multivariable-adjusted logistic regression was applied to assess the relationship between hypertension and NAFLD risk by using data from the NHANES ***,a two-sample MR study was performed using the genome-wide association study(GWAS)summary statistics to identify the causal association between hypertension,systolic blood pressure(SBP),diastolic blood pressure(DBP),and *** primary inverse variance weighted(IVW)and other supplementary MR approaches were conducted to verify the causal association between hypertension and *** analyses were adopted to confirm the robustness of the ***:A total of 3144 participants were enrolled for our observational study in *** multivariable-adjusted logistic regression analysis suggested that hypertension was positively related to NAFLD risk(odds ratio[OR]=1.677;95%confidence interval[CI],1.159-2.423).SBP≥130 mmHg and DBP≥80 mmHg were also significantly positively correlated with ***,hypertension was independently connected with liver steatosis(β=7.836[95%CI,2.334-13.338]).The results of MR analysis also supported a causal association between hypertension(OR=7.203[95%CI,2.297-22.587])and *** results were observed for the causal exploration between SBP(OR=1.024[95%CI,1.003-1.046]),DBP(OR=1.047[95%CI,1.005-1.090]),and *** sensitive analysis further confirmed the robustness and reliability of these findings(all P>0.05).Conclusion:Hypertension was associated with an increased risk of NAFLD.

关键词： Hypertension Non-alcoholic fatty liver disease National Health and Nutrition Examination Survey Mendelian randomization analysis Causality

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Impact of short-term ambient air pollution exposure on the risk of severe COVID-19

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Journal of Environmental Sciences 2024年第1期135卷 610-618页

作者： Baihuan Feng Jiangshan Lian Fei Yu Dan Zhang Weizhen Chen QiWang Yifei Shen Guoliang Xie Ruonan Wang Yun Teng Bin Lou Shufa Zheng Yida Yang Yu Chen Department of laboratory Medicine The First Affiliated HospitalZhejiang University School of MedicineHangzhou 310000China Key laboratory of Clinical In Vitro Diagnostic Techniques of Zhejiang Province Hangzhou 310000China Institute of laboratory Medicine Zhejiang UniversityHangzhou 310000China Department of infectious diseases The First Affiliated HospitalZhejiang University School of MedicineHangzhou 310000China State Key laboratory for Diagnosis and Treatment of infectious diseases National Clinical Research Center for Infectious DiseasesCollaborative Innovation Center for Diagnosis and Treatment of Infectious Diseasesthe First Affiliated HospitalZhejiang University School of MedicineHangzhou 310000China

Ecological studies suggested a link between air pollution and severe COVID-19 outcomes,while studies accounting for individual-level characteristics are *** the present study,we aimed to investigate the impact of short-term ambient air pollution exposure on disease severity among a cohort of 569 laboratory confirmed COVID-19 patients admitted to designated hospitals in Zhejiang province,China,from January 17 to March 3,2020,and elucidate the possible biological processes involved using *** with mild cases,severe cases had higher proportion of medical conditions as well as unfavorable results in most of the laboratory tests,and manifested higher air pollution exposure *** exposure to air pollutants was associated with increased risk of severe COVID-19 with odds ratio(OR)of 1.89(95%confidence interval(CI):1.01,3.53),2.35(95%CI:1.20,4.61),2.87(95%CI:1.68,4.91),and 2.01(95%CI:1.10,3.69)for PM_(2.5),PM_(10),NO_(2)and CO,*** for NO_(2)remained significant in two-pollutant models after adjusting for other *** analysis showed 884 differentially expressed genes which mainly were enriched in virus clearance related biological processes between patients with high and low NO_(2)exposure levels,indicating that compromised immune response might be a potential underlying mechanistic *** findings highlight the impact of shortterm air pollution exposure,particularly for NO_(2),on COVID-19 severity,and emphasize the significance in mitigating the COVID-19 burden of commitments to improve air quality.

关键词： Air pollution COVID-19 Severity Transcriptomics Immune response

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Astragaloside IV Alleviates Acute Liver Failure Induced by D-GalN/LPS by Upregulating Autophagy and Reducing Inflammation

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infectious Microbes & diseases 2024年第1期6卷 20-28页

作者： Meng Hong Wenwen Lian Ying Yang Zhi Chen State Key laboratory for Diagnosis and Treatment of infectious diseases National Clinical Research Center for Infectious DiseasesNational Medical Center for Infectious DiseasesCollaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesThe First Affiliated HospitalZhejiang University School of MedicineHangzhouChina

Acute liver failure(ALF)is a life-threatening condition that manifests in an extremely serious manner and progresses *** following study investigated the protective effect of astragaloside IV(AS-IV),a traditional Chinese drug,on ALF,and its underlying mechanisms,focusing on autophagy and inflammation *** were randomly divided into a saline group,a D-galactosamine and lipopolysac-charide(D-GalN/LPS)group and an AS-IV *** analysis,immunohistochemistry,cytometric bead array,high-throughput quantitative PCR,flow cytometry and Western analysis were used to assess inflammation and liver damage 5 hours after D-GalN/LPS *** IV treatment reduced mortality by alleviating D-GalN/LPS–induced hepatic damage and decreasing inflammation(decreasing Ly6c+monocyte levels,reducing inflammatory cytokines and increasing anti-inflammatory factors)as well as upregulating ***,PCR array was used to detect expression of autophagy-related genes,which demonstrated a Log2 fold change in gene expression between the AS-IV and D-GalN/LPS groups ranging from 1.19 to-3.53,with Tnfsf10 showing the largest alteration be-tween the two *** data suggest that AS-IV may alleviate ALF by upregulating autophagy and reducing inflammation,and it may therefore be an interesting drug for alleviating ALF.

关键词： astragaloside IV acute liver failure inflammation autophagy