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Dopamine Inhibits the Expression of Hepatitis B Virus Surface and e Antigens by Activating the JAK/STAT Pathway and Upregulating Interferon-stimulated Gene 15 Expression

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Journal of Clinical and Translational Hepatology 2024年第5期12卷 443-456页

作者： Xiaoquan Liu Xiuqing Pang Zhiping Wan Jinhua Zhao Zhiliang Gao Hong Deng Department of infectious diseases Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdongChina Guangdong Key Laboratory of Liver disease research Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhou GuangdongChina Key Laboratory of Tropical disease Control(Sun Yat-sen University) Ministry of EducationGuangzhouGuangdongChina

Background and Aims:Hepatitis B virus(HBV)infection is a major risk factor for cirrhosis and liver cancer,and its treatment continues to be *** previously demonstrated that a dopamine analog inhibited the packaging of pregenomic RNA into *** present study aimed to determine the effect of dopamine on the expressions of hepatitis B virus surface and e antigens(HBsAg and HBeAg,respectively)and to elucidate the underlying ***:We used dopamine-treated HBVinfected HepG2.2.15 and NTCP-G2 cells to monitor HBsAg and HBeAg expression *** analyzed interferon-stimulated gene 15(ISG15)expression in dopamine-treated *** knocked down ISG15 and then monitored HBsAg and HBeAg expression *** analyzed the expression of Janus kinase(JAK)/signal transducer and activator of transcription(STAT)pathway factors in dopamine-treated *** used dopamine hydrochloride-treated adeno-associated virus/HBV-infected mouse model to evaluate HBV DNA,HBsAg,and HBeAg *** virus was collected from HepAD38.7 cell culture ***:Dopamine inhibited HBsAg and HBeAg expression and upregulated ISG15 expression in HepG2.2.15 and HepG2-NTCP cell ***15 knockdown increased HBsAg and HBeAg expression in HepG2.2.15 ***-treated cells activated the JAK/STAT pathway,which upregulated ISG15 *** the adeno-associated virus-HBV murine infection model,dopamine downregulated HBsAg and HBeAg expression and activated the JAK-STAT/ISG15 ***:Dopamine inhibits the expression of HBsAg and HBeAg by activating the JAK/STAT pathway and upregulating ISG15 expression.

关键词： Hepatitis B virus Dopamine JAK-STAT/ISG15 axis HBV surface antigen HBV e antigen HepG2.2.15 cell line Human NTCP-expressing HepG2 cell line HepAD38 cell line

Inferring community transmission of SARS-CoV-2 in the united Kingdom using the ONS COVID-19 Infection Survey

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infectious disease Modelling 2024年第2期9卷 299-313页

作者： Ruth McCabe Gabriel Danelian Jasmina Panovska-Griffiths Christl A.Donnelly Department of Statistics University of OxfordUK National Institute for Health and Care research Health Protection research unit in Emerging and Zoonotic Infections UK united Kingdom Health Security Agency UK The Queen's College University of OxfordUK The Pandemic Sciences Institute University of OxfordUK MRC Centre for Global infectious disease Analysis Imperial College LondonUK

Key epidemiological parameters,including the effective reproduction number,,and the instantaneous growth rate,,generated from an ensemble of models,have been informing public health policy throughout the COVID-19 pandemic in the four nations of the united Kingdom of Great Britain and Northern Ireland(UK).However,estimation of these quantities became challenging with the scaling down of surveillance systems as part of the transition from the“emergency”to“endemic”phase of the *** Office for National Statistics(ONS)COVID-19 Infection Survey(CIS)provided an opportunity to continue estimating these parameters in the absence of other data *** used a penalised spline model fitted to the publicly-available ONS CIS test positivity estimates to produce a smoothed estimate of the prevalence of SARS-CoV-2 positivity over *** resulting fitted curve was used to estimate the“ONS-based”and across the four nations of the *** produced under this model are compared to government-published estimates with particular consideration given to the contribution that this single data stream can offer in the estimation of these *** on the nation and parameter,we found that up to 77%of the variance in the government-published estimates can be explained by the ONS-based estimates,demonstrating the value of this singular data stream to track the epidemic in each of the four *** additionally find that the ONS-based estimates uncover epidemic trends earlier than the corresponding government-published *** work shows that the ONS CIS can be used to generate key COVID-19 epidemiological parameters across the four UK nations,further underlining the enormous value of such population-level studies of *** is not intended as an alternative to ensemble modelling,rather it is intended as a potential solution to the aforementioned challenge faced by public health officials in the UK in early 2022.

关键词： Effective reproduction number Instantaneous growth rate SARS-CoV-2 COVID-19 ONS COVID-19 Infection Survey Surveillance

Diagnostic approaches for monkeypox virus

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iLABMED 2024年第1期2卷 6-13页

作者： Guohao Fan Jiahua Kuang Shengjie Zhang Yang Yang Yingxia Liu Hongzhou Lu Shenzhen Key Laboratory of Pathogen and Immunity Shenzhen Clinical Research Center for Infectious DiseaseState Key Discipline of Infectious DiseaseShenzhen Third People's HospitalSecond Hospital Affiliated to Southern University of Science and TechnologyShenzhenChina National Clinical research Center for infectious disease ShenzhenChina

Mpox(formerly Monkeypox)is a zoonotic infection caused by Monkeypox virus(MPXV).Since 2022,Mpox epidemics have occurred in many nonendemic countries and regions,leading the World Health Organization to declare a public health emergency of international *** the persistent transmission and evolution of MPXV,symptoms of Mpox have become milder,with some infections being *** addition,MPXV has become more ***,rapid and accurate diagnosis and screening of MPXV is vital to prevent and control MPXV ***,we review and summarize the technical details,application scenarios,and the advantages and disadvantages of MPXV‐specific diagnostic methods.

关键词： antigen diagnosis laboratory testing monkeypox virus specimens

Current status of liver transplantation for human immunodeficiency virus-infected patients in China's Mainland

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World Journal of Gastroenterology 2024年第14期30卷 1958-1962页

作者： Jian-Xin Tang Dong Zhao Department of Liver Surgery and Organ Transplantation Center Shenzhen Third People’s HospitalThe Second Affiliated Hospital of Southern University of Science and TechnologyNational Clinical Research Center for Infectious DiseaseShenzhen 518000Guangdong ProvinceChina

According to the report from the Chinese Center for disease Control and Prevention,the prevalence of human immunodeficiency virus(HIV)infection exceeded 1.2 million individuals by the year 2022,with an annual increase of about 80000 *** overall prevalence of hepatitis B surface antigen among individuals co-infected with HIV reached 13.7%,almost twice the rate of the general population in *** addition to the well-documented susceptibility to opportunistic infections and new malignancies,HIV infected patients frequently experience liver-related organ damage,with the liver and kidneys being the most commonly *** often leads to the development of end-stage liver and kidney ***,organ transplantation has emerged as an important part of active treatment for HIV infected ***,the curative effect is not *** infection has been considered a contraindication for organ *** the emergence of highly active anti-retroviral therapy in 1996,the once intractable replication of retrovirus was effectively *** prolonged survival,the failure of important organs has become the main cause of death among HIV ***,transplant centers worldwide have resu-med exploration of organ transplantation for HIV-infected individuals and reached a positive *** study provides an overview of the current landscape of HIV-positive patients receiving liver transplantation(LT)in main-land *** date,our transplant center has conducted LT for eight end-stage liver disease patients co-infected with HIV,and all but one,who died two months postoperatively due to sepsis and progressive multi-organ failure,have *** analysis with hepatitis B virus-infected patients during the same period revealed no statistically significant differences in acute rejection reactions,cytomegalovirus infection,bacteremia,pulmonary infections,acute kidney injury,new-onset cancers,or vascular and biliary co

关键词： Liver transplantation Human immunodeficiency virus Infection Hepatitis B virus End-stage liver disease China'Mainland

Infection and Genomic Characteristics of Campylobacter jejuni from a Patient Without Diarrhea—China,2018

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China CDC weekly 2024年第33期6卷 846-851,I0001-I0005页

作者： Xiangdong Yang Wen Wang Chajin Cui Binbin Yu Qing Zhang Yanhua Wang Ecological Medicine research Center National Key Laboratory of Intelligent Tracking and Forecasting for Infectious DiseasesNational Institute for Communicable Disease Control and PreventionChinese Center for Disease Control and PreventionBeijingChina Department of Zoonotic disease Control and Prevention Yunnan Institute of Endemic Diseases Control&PreventionDali Bai Autonomous PrefectureYunnan ProvinceChina Medical Laboratory Department Yunnan Luxi County People’s HospitalHonghe Hani-Yi Autonomous PrefectureYunnan ProvinceChina

What is already known about this topic?A 20-month-old boy was admitted to the hospital with a maximum temperature of 40°C and a single ***,blood culture detected Francisella tularensis(***)using the VITEK 2 Compact *** is added by this report?After incubation of the patient’s blood for 48 hours,the cultured strain was identified as Campylobacter jejuni,named L8,excluding *** the genome sequence of L8,we found a novel Type VI Secretion System(T6SS),of which the conserved C-terminal VgrG domain from positions 561 to 884 showed significant *** are the implications for public health practice?It should be underscored that relying solely on automatic bacterial identification instruments for accurate strain identification is ***,our study suggests that the potential effect of T6SS should be considered when studying the genetic features of a patient’s clinical phenotypes.

关键词： Campylobacter admitted culture

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

More common RNAemia in the early stage of severe SARS-CoV-2 BF.7.14 infections in pediatric patients

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Biosafety and Health 2024年第1期6卷 5-11页

作者： Yu Sun Runan Zhu Yang Pan Ri De Shuang Liu Liping Jia Bing Lv Xiaoyun Li Dongmei Chen Yao Yao Dong Qu Daitao Zhang Linqing Zhao Laboratory of Virology Bejing Key Laboratory of Etiology of Viral Diseases in ChildrenCapital Institute of PediatricsBejing 100020China Institute for infectious disease and Endemic disease Control Bejing Center for Disease Control and Prevention Beijing 100013China Department of Intensive Care unit Affiliated Children's Hospital of Capital Institute of PediatricsBeijing 100020China

The risk factors of severe infections in children during the severe acute respiratory syndrome coronavirus 2(SARS‐CoV‐2)outbreak in Beijing remain ***‐CoV‐2‐positive children admitted to the intensive care unit(ICU)with collected plasma specimens were enrolled and screened for common pathogens using capillary electrophoresis‐based multiplex PCR from December 12,2022,to January 24,*** SARS‐CoV‐2 subvariants were identified using next‐generation *** was positive for two(positive;P),one(suspicious;S),or no(negative;N)SARS‐CoV‐2 genes were classified as plasmatic RNA‐positive(RNAemia;P+S)or without RNAemia(N).Clinical and laboratory data of the enrolled cases were then collected and *** 34 enrolled children included 26 males and 24 younger than three *** were negative for other respiratory ***.7.14(18/29)was the predominant *** loads in respiratory specimens,hours from symptom onset to the first respiratory specimen collection(time‐variable),with comorbidities and BF.7.14 and BA.5.2 distributions were significantly different in P vs.N and RNAemia *** RNAemia *** most cases,the T lymphocyte ratios decreased,while the cytokine level and the B lymphocyte ratio *** time variables were 2.22±2.05 and 4.00±2.49 days in BF.7.14 and BA.5.2 infections,*** conclusion,SARS‐CoV‐2 was more likely to cause severe infections among males aged≤3 years old with comorbidities during the SARS‐CoV‐2 outbreak in Beijing,while RNAemia is more common in children at the early stage of severe BF.7.14 infections,and most had high cytokine levels and B‐cell activation.

关键词： Severe SARS‐CoV‐2 infection Pediatric patients Risk factor RNAemia BF.7.14

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

Stepping forward:T-cell redirecting bispecific antibodies in cancer therapy

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Acta Pharmaceutica Sinica B 2024年第6期14卷 2361-2377页

作者： Xiaojing Qin Wenjing Ning Han Liu Xue Liu Wenxin Luo Ningshao Xia State Key Laboratory of Vaccines for infectious diseases Xiang An Biomedicine LaboratorySchool of Public HealthXiamen UniversityXiamen 361102China National Institute of Diagnostics and Vaccine Development in infectious diseases State Key Laboratory of Molecular Vaccinology and Molecular DiagnosticsNational Innovation Platform for IndustryeEducation Integration in Vaccine Researchthe Research Unit of Frontier Technology of Structural Vaccinology of Chinese Academy of Medical SciencesXiamen UniversityXiamen 361102China

T cell-redirecting bispecific antibodies are specifically designed to bind to tumor-associated antigens,thereby engaging with CD3 on the T cell *** linkage between tumor cells and T cells actively triggers T cell activation and initiates targeted killing of the identified tumor *** antibodies have emerged as one of the most promising avenues within tumor ***,despite success in treating hematological malignancies,significant advancements in solid tumors have yet to be *** this review,we aim to address the critical challenges associated with T cellredirecting bispecific antibodies and explore novel strategies to overcome these obstacles,with the ultimate goal of expanding the application of this therapy to include solid tumors.

关键词： Bispecific antibody(BsAbs) T-cell redirecting BsAbs Tumor-associated antigens Toxicity Cytokine release syndrome Tumor microenvironment Cancer immunotherapy Combination therapy strategies