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Downregulation of Serum PTEN Expression in Mercury-Exposed Population and PI3K/AKT Pathway-Induced Inflammation

Biomedical and Environmental Sciences 2024年第4期37卷 354-366页

作者： MEI Peng DING En Min YIN Hao Yang DING Xue Xue WANG Huan WANG Jian Feng HAN Lei ZHANG Heng Dong ZHU Bao Li School of Public Health Nanjing Medical UniversityNanjing 210000JiangsuChina Institute of occupational Disease prevention Jiangsu Province Center for Disease Prevention and ControlNanjing 21000JiangsuChina Suzhou center for Disease prevention and Control Suzhou 215004JiangsuChina center for Global Health School of Public HealthNanjing Medical UniversityNanjing 210000JiangsuChina

Objective This study investigated the impact of occupational mercury(Hg) exposure on human gene transcription and expression, and its potential biological *** Differentially expressed genes related to Hg exposure were identified and validated using gene expression microarray analysis and extended validation. Hg-exposed cell models and PTEN lowexpression models were established in vitro using 293T cells. PTEN gene expression was assessed using qRT-PCR, and Western blotting was used to measure PTEN, AKT, and PI3K protein levels. IL-6 expression was determined by *** Combined findings from gene expression microarray analysis, bioinformatics, and population expansion validation indicated significant downregulation of the PTEN gene in the high-concentration Hg exposure group. In the Hg-exposed cell model(25 and 10 μmol/L), a significant decrease in PTEN expression was observed, accompanied by a significant increase in PI3K, AKT, and IL-6 ***, a low-expression cell model demonstrated that PTEN gene knockdown led to a significant decrease in PTEN protein expression and a substantial increase in PI3K, AKT, and IL-6 *** This is the first study to report that Hg exposure downregulates the PTEN gene, activates the PI3K/AKT regulatory pathway, and increases the expression of inflammatory factors, ultimately resulting in kidney inflammation.

关键词： PTEN occupational mercury exposure occupational health PI3K/AKT pathway 293T cell IL-6

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DNA vaccine prime and replicating vaccinia vaccine boost induce robust humoral and cellular immune responses against MERS-CoV in mice

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Virologica Sinica 2024年第3期39卷 490-500页

作者： Xiuli Shen Shuhui Wang Yanling Hao Yuyu Fu Li Ren Dan Li Wenqi Tang Jing Li Ran Chen Meiling Zhu Shuo Wang Ying Liu Yiming Shao National Key Laboratory of Intelligent Tracking and Forecasting for Infectious diseases National Center for AIDS/STD Control and PreventionChinese Center for Disease Control and PreventionBeijing 102206China Changping Laboratory Yard 28Science Park RoadChangping DistrictBeijing 102206China 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 HospitalSchool of MedicineZhejiang UniversityHangzhou 310003China

As of December 2022,2603 laboratory-identified Middle East respiratory syndrome coronavirus(MERS-CoV)infections and 935 associated deaths,with a mortality rate of 36%,had been reported to the World Health Organization(WHO).However,there are still no vaccines for MERS-CoV,which makes the prevention and control of MERS-CoV *** this study,we generated two DNA vaccine candidates by integrating MERS-CoV Spike(S)gene into a replicating Vaccinia Tian Tan(VTT)*** to homologous immunization with either vaccine,mice immunized with DNA vaccine prime and VTT vaccine boost exhibited much stronger and durable humoral and cellular immune *** immunized mice produced robust binding antibodies and broad neutralizing antibodies against the EMC2012,England1 and KNIH strains of ***-Boost immunization also induced strong MERS-S specific T cells responses,with high memory and poly-functional(CD107a-IFN-γ-TNF-α)effector CD8t T *** conclusion,the research demonstrated that DNA-Prime/VTT-Boost strategy could elicit robust and balanced humoral and cellular immune responses against *** study not only provides a promising set of MERS-CoV vaccine candidates,but also proposes a heterologous sequential immunization strategy worthy of further development.

关键词： MERS-CoV VTT vaccine DNA vaccine Humoral and cellular immune responses Prime/boost strategy

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Diagnosis,treatment,and Associated Factors Among Patients with HCV Infection—Jiangsu Province,China,2004–2020

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China CDC weekly 2024年第1期6卷 1-5,I0001-I0003页

作者： Dandan Yang Jing Lu Zhi Zhang Chuanwu Sun Zhuping Xu Yao Qi XiaoXia Liu Huan Ding Feifei Chai Zhengdong Zhang Baoli Zhu Department of Genetic Toxicology The Key Laboratory of Modern Toxicology of Ministry of EducationCenter for Global HealthSchool of Public HealthNanjing Medical UniversityNanjing CityJiangsu ProvinceChina Department of Sexually Transmitted diseases and AIDS Center for Disease Control and Prevention of Jiangsu ProvinceNanjing CityJiangsu ProvinceChina Department of Sexually Transmitted diseases and AIDS Center for Disease Control and Prevention of XuzhouXuzhou CityJiangsu ProvinceChina Department of Sexually Transmitted diseases and AIDS Center for Disease Control and Prevention of WuxiWuxi CityJiangsu ProvinceChina Department of Sexually Transmitted diseases and AIDS Center for Disease Control and Prevention of YanchengYancheng CityJiangsu ProvinceChina Department of Sexually Transmitted diseases and AIDS Center for Disease Control and Prevention of ZhenjiangZhenjiang CityJiangsu ProvinceChina.

What is already known on this topic?The global efforts to address the hepatitis C virus(HCV)are progressing,but there are still significant gaps in the diagnosis and treatment of HCV,leading to an increasing number of deaths related to *** is added by this report?An extensive investigation was conducted to assess HCV RNA diagnosis,treatment uptake,and associated factors among individuals infected with HCV within Jiangsu *** study encompassed a large geographical area and utilized a substantial sample *** are the implications for public health practice?Implementing focused interventions to improve the timely diagnosis of HCV RNA and increase the uptake of HCV treatment could effectively reduce the future burden of HCV-related health problems,deaths,and healthcare *** is essential for achieving the global target of eliminating hepatitis C.

关键词： diagnosis utilized Jiangsu

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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

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Knowledge Graph Enhanced Transformers for Diagnosis Generation of Chinese Medicine

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Chinese Journal of Integrative Medicine 2024年第3期30卷 267-276页

作者： WANG Xin-yu YANG Tao GAO Xiao-yuan HU Kong-fa School of Artificial Intelligence and Information Technology Nanjing University of Chinese MedicineNanjing210023China School of Information Management Nanjing UniversityNanjing210023China Jiangsu Collaborative Innovation center of Traditional Chinese Medicine in prevention and treatment of Tumor Nanjing210023China Jiangsu Province Engineering Research center of TCM Intelligence Health Service Nanjing210023China

Chinese medicine(CM)diagnosis intellectualization is one of the hotspots in the research of CM *** traditional CM intelligent diagnosis models transform the CM diagnosis issues into classification issues,however,it is difficult to solve the problems such as excessive or similar *** the development of natural language processing techniques,text generation technique has become increasingly *** this study,we aimed to establish the CM diagnosis generation model by transforming the CM diagnosis issues into text generation *** semantic context characteristic learning capacity was enhanced referring to Bidirectional Long Short-Term Memory(BILSTM)with Transformer as the backbone ***,the CM diagnosis generation model Knowledge Graph Enhanced Transformer(KGET)was established by introducing the knowledge in medical field to enhance the inferential *** KGET model was established based on 566 CM case texts,and was compared with the classic text generation models including Long Short-Term Memory sequence-to-sequence(LSTM-seq2seq),Bidirectional and Auto-Regression Transformer(BART),and Chinese Pre-trained Unbalanced Transformer(CPT),so as to analyze the model ***,the ablation experiments were performed to explore the influence of the optimized part on the KGET *** results of Bilingual Evaluation Understudy(BLEU),Recall-Oriented Understudy for Gisting Evaluation 1(ROUGE1),ROUGE2 and Edit distance of KGET model were 45.85,73.93,54.59 and 7.12,respectively in this *** with LSTM-seq2seq,BART and CPT models,the KGET model was higher in BLEU,ROUGE1 and ROUGE2 by 6.00–17.09,1.65–9.39 and 0.51–17.62,respectively,and lower in Edit distance by 0.47–*** ablation experiment results revealed that introduction of BILSTM model and prior knowledge could significantly increase the model ***,the manual assessment indicated that the CM diagnosis results of the KGET model used

关键词： Chinese medicine diagnosis knowledge graph enhanced transformer text generation

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Novel berberine derivatives as adjuvants in the battle against Acinetobacter baumannii: A promising strategy for combating multi-drug resistance

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Chinese Chemical Letters 2024年第10期35卷 360-366页

作者： Liping Zhao Xixi Guo Zhimeng Zhang Xi Lu Qingxuan Zeng Tianyun Fan Xintong Zhang Fenbei Chen Mengyi Xu Min Yuan Zhenjun Li Jiandong Jiang Jing Pang Xuefu You Yanxiang Wang Danqing Song Beijing Key Laboratory of Antimicrobial Agents Institute of Medicinal Biotechnology Chinese Academy of Medical Sciences and Peking Union Medical College State Key Laboratory for Infectious diseases prevention and Control Collaborative Innovation Center for Diagnosis and Treatment of Infectious DiseaseNational Institute for Communicable Disease Control and Prevention Chinese Center for Disease Control and Prevention

The development of resistance against most of the available antibiotics has made Acinetobacter baumannii(A. baumannii) a pathogen of high risk. In this study, thirty novel berberine derivatives are rationally designed, synthesized, and evaluated for their synergistic antibacterial activities against A. *** them, compound 2d shows the most potent synergetic effect to aztreonam against A. baumannii,including carbapenem-resistant and extended-spectrum β-lactamases-producing strains. Moreover, synergistic effects were observed for the combinations of 2d and different antibacterial used in clinical practices, indicating its potent broad-spectrum antibiotic-sensitizing effects against A. baumannii. The combination of 2d and aztreonam significantly improves the survival rates of G. mellonella larvae compared with aztreonam treatment alone. Mechanism studies indicate that 2d inhibits the drug efflux and iron acquisition of the bacteria by targeting the AdeB transporter protein, thus achieving a synergistic antimicrobial efficacy with different antibacterial agents. Therefore, berberine derivatives represent a new family of antimicrobial adjuvants against A. baumannii, with the advantage of dual-function antibacterial effect,and are worthy of further investigation.

关键词： Acinetobacter baumannii Berberine derivatives Efflux Iron acquisition Rational design Synergistic effect

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Knowledge,Attitude,and Practice Towards Mpox and Associated Factors Among HIV-Infected Individuals—Beijing Municipality,China,2023

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China CDC weekly 2024年第7期6卷 109-117,I0001,I0002页

作者： Yue Gu Ruiqi Ren Jing Han Wenqing Bai Yuanyuan Zhang Haoliang Liu Zhaohe Li Chao Li Rui Song Lei Zhou Chinese center for Disease Control and prevention BeijingChina National center for Infectious diseases Beijing Ditan HospitalCapital Medical UniversityBeijingChina Beijing Key Laboratory of Emerging Infectious diseases Institute of Infectious DiseasesBeijing Ditan HospitalCapital Medical UniversityBeijingChina nanjing Medical University Nanjing CityJiangsu ProvinceChina

Summary What is already known about this topic?Approximately 50%of patients with mpox are human immunodeficiency virus(HIV)-infected *** have shown that individuals with advanced HIV infection tend to have more severe... 详细信息

关键词： mortality Infect clinical

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Severe liver injury and clinical characteristics of occupational exposure to 2-amino-5-chloro-N,3-dimethylbenzamide: A case series

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Hepatobiliary & Pancreatic diseases International 2024年第2期23卷 186-194页

作者： Meng-Xiao Feng Hua Zou Yuan-Qiang Lu Department of Emergency Medicine The First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China Key Laboratory for Diagnosis and treatment of Aging and Physic-chemical Injury diseases of Zhejiang Province Hangzhou 310003China occupational Health and Radiation Protection Institute Zhejiang Provincial Center for Disease Control and PreventionHangzhou 310051China

Background:The 2-amino-5-chloro-N,3-dimethylbenzamide is a key intermediate in the synthesis of pesticides and ***,no literature currently exists on 2-amino-5-chloro-N,3-dimethylbenzamide poisoning in *** study aimed to reveal the health hazard of this chemical for humans and summarize the clinical characteristics of patients with occupational 2-amino-5-chloro-N,3-dimethylbenzamide ***:This observational study included four patients with 2-amino-5-chloro-N,3-dimethylbenzamide poisoning from June 2022 to July *** entire course of the incidents was described in *** 2-amino-5-chloro-N,3-dimethylbenzamide concentrations were detected by a mass ***-toxylin and eosin staining was performed to assess liver injury,and immunofluorescence was used to evaluate hepatic ***:The 2-amino-5-chloro-N,3-dimethylbenzamide powder(99%purity)entered the human body mainly via the skin and respiratory tract due to poor personal protective *** typical course of 2-amino-5-chloro-N,3-dimethylbenzamide poisoning was divided into latency,rash,fever,organic dam-age,and recovery phases in accordance with the clinical *** and fever may be the important premonitory symptoms for further organ *** chemical was detected in the blood of all patients and caused multiple organ injuries,predominantly liver injury,including kidney,myocardium,and *** patients recovered smoothly after comprehensive treatments,including artificial liver therapy,continuous renal replacement therapy,glucocorticoids,and other symptomatic and supportive *** patient survived by liver *** postoperative pathological findings of the removed liver showed acute liver failure,and immunofluorescence staining confirmed the abundance of mitophagy in residual ***:This study is the first to elaborate the clinical characteristics of patients with 2-amino-5-chloro-N,

关键词： 2-amino-5-chloro-N,3-dimethylbenzamide Poisoning Clinical characteristics Liver injury

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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

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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

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