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Gp78 regulates PMP22 and causes ER stress and autophagy in EV71-VP1-overexpressing mouse Schwann cells

BIOCELL 2024年第4期48卷 653-664页

作者： DANPING ZHU GUANGMING LIU KUAN FENG SUYUN LI DANDAN HU SIDA YANG PEIQING LI Pediatric Emergency Department Guangzhou Women and Children’s Medical CenterGuangzhou Medical UniversityGuangdong Provincial Clinical Research Center for Child HealthGuangzhouChina Department of Child health Care Guangzhou Women and Children’s Medical CenterGuangzhou Medical UniversityGuangdong Provincial Clinical Research Center for Child HealthGuangzhouChina Pediatric Neurology Department Guangzhou Women and Children’s Medical CenterGuangzhou Medical UniversityGuangdong Provincial Clinical Research Center for Child HealthGuangzhouChina

Background:During Enterovirus type 71(EV71)infection,the structural viral protein 1(VP1)activates endoplasmic reticulum(ER)stress associated with peripheral myelin protein 22(PMP22)accumulation and induces ***,the speciﬁc mechanism behind this process remains ***:In this research,we used the VP1-overexpressing mouse Schwann cells(SCs)models co-transfected with a PMP22 silencing or Autocrine motility factor receptor(AMFR/gp78)overexpressing vector to explore the regulation of gp78 on PMP22 and its relationship with autophagy and ***:The activity of gp78 could be inﬂuenced by EV71-VP1,leading to a decrease in the ubiquitination and degradation of PMP22,resulting in PMP22 accumulation in *** VP1-overexpressing mouse SCs,all three ER stress sensors,including pancreatic endoplasmic reticulum kinase(PERK),activating transcription factor 6(ATF6)and inositol-requiring enzyme 1(IRE1)and the related downstream signals(C/EBP-homologous protein(CHOP)and Caspase 12)were activated,as well as the ER-resident chaperone Glucose-regulated protein 78(GRP78).In addition,VP1 upregulated the autophagy marker Microtubule-associated protein 1 light chain 3 beta(LC3B),while PMP22 silencing or gp78 overexpression reversed the ***,PMP22 silencing or gp78 overexpression increased proliferation of EV71-VP1-transfected mouse ***:Gp78 could regulate PMP22 accumulation through ubiquitination degradation and cause ER stress and autophagy in EV71-VP1-overexpressing mouse ***,the gp78/PMP22/ER stress axis might emerge as a promising therapeutic target for myelin and neuronal damage induced by EV71 infection.

关键词： Enterovirus type 71 AMFR/gp78 PMP22 Autophagy Schwann cells

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Novel de novo TRPV4 mutation identified in a Chinese family with metatropic dysplasia inhibits chondrogenic differentiation

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Genes & Diseases 2024年第3期11卷 83-86页

作者： Ping Wei Weizhe Shi Tianying Nong Caixia Xian Xia Li Zhaohui Li Xin Li Jianping Wu Liyuan Shang Fulong Xu Yibo Xu Hongwen Xu Mingwei Zhu Guangzhou Institute of Pediatrics Guangzhou Women and Children's Medical CenterGuangzhou Medical UniversityGuangdong Provincial Clinical Research Center for Child HealthGuangzhouGuangdong 510623China Department of Pediatric Orthopedics Guangzhou Women and Children's Medical CenterGuangzhou Medical UniversityGuangdong Provincial Clinical Research Center for Child HealthGuangzhouGuangdong 510623China

Metatropicdysplasia(MD,MIM156530)is a rare congenital bone dysplasia primarily characterized by severe platyspondyly with long and wide vertebral bodies and dumbbell deformity of the tubular *** can be caused by heterozygous mutations in the gene encoding transient receptor potential vanilloid family member 4(TRPV4).We identifieda novel de novo mutation,c.2353T>C,in the TRPV4 gene,in a Chinese family with mild MD.

关键词： TRPV4 dysplasia congenital

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Development and validation of a novel non-invasive test for diagnosing nonalcoholic fatty liver disease in Chinese children

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World Journal of Pediatrics 2024年第4期20卷 413-421页

作者： Zhe-Wen Qin Qian-Nan Ren Hong-Xi Zhang Ya-Ru Liu Ke Huang Wei Wu Guan-Ping Dong Yan Ni Jun-Fen Fu Division of Endocrinology National Clinical Research Center for Child HealthNational Children’s Regional Medical CenterThe Children’s HospitalDepartment of EndocrinologyNational Clinical Research Center for Child HealthNational Children’s Regional Medical CenterThe Children’s HospitalZhejiang University School of MedicineHangzhou310052China

With the exploding prevalence of obesity,many children are at risk of developing nonalcoholic fatty liver *** anthropometric and laboratory parameters,our study aimed to develop a model to quantitatively evaluate liver fat content(LFC)in children with *** A well-characterized cohort of 181 children between 5 and 16 years of age were recruited to the study in the Endocrinology Department as the derivation *** external validation cohort comprised 77 *** assessment of liver fat content was performed using proton magnetic resonance *** and laboratory metrics were measured in all subjects.B-ultrasound examination was carried out in the external validation *** Kruskal-Wallis test,Spearman bivariate correlation analyses,univariable linear regressions and multivariable linear regression were used to build the optimal predictive *** The model was based on indicators including alanine aminotransferase,homeostasis model assessment of insulin resistance,triglycerides,waist circumference and Tanner *** adjusted R^(2)of the model was 0.589,which presented high sensitivity and specificity both in internal[sensitivity of 0.824,specificity of 0.900,area under curve(AUC)of 0.900 with a 95%confidence interval:0.783–1.000]and external validation(sensitivity of 0.918 and specificity of 0.821,AUC of 0.901 with a 95%confidence interval:0.818–0.984).Conclusions Our model based on five clinical indicators was simple,non-invasive,and inexpensive;it had high sensitivity and specificity in predicting LFC in ***,it may be useful for identifying children with obesity who are at risk for developing nonalcoholic fatty liver disease.

关键词： Biochemical markers Children Magnetic resonance spectroscopy Nonalcoholic fatty liver disease Pediatric obesity

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The characterization of protein lactylation in relation to cardiac metabolic reprogramming in neonatal mouse hearts

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Journal of Genetics and Genomics 2024年第7期51卷 735-748页

作者： Tongyu Zhang Yingxi Zhu Xiaochen Wang Danyang Chong Haiquan Wang Dandan Bu Mengfei Zhao Lei Fang Chaojun Li Ministry of Education Key Laboratory of Model Animals for Disease Study Model Animal Research CenterMedical School of Nanjing UniversityNational Resource Center for Mutant MiceNanjingJiangsu 210093China State Key Laboratory of Reproductive Medicine and Offspring health China International Joint Research Center on Environment and Human HealthCenter for Global HealthSchool of Public HealthGusu SchoolNanjing Medical UniversityNanjingJiangsu 211166China

In mammals,the neonatal heart can regenerate upon injury within a short time after birth,while adults lose this *** reprogramming has been demonstrated to be critical for cardiomyocyte proliferation in the neonatal ***,we reveal that cardiac metabolic reprogramming could be regulated by altering global protein *** performing 4D label-free proteomics and lysine lactylation(Kla)omics analyses in mouse hearts at postnatal days 1,5,and 7,2297 Kla sites from 980 proteins are identified,among which 1262 Kla sites from 409 proteins are *** clustering analysis reveals that the proteins with altered Kla sites are mainly involved in metabolic *** expression and Kla levels of proteins in glycolysis show a positive correlation while a negative correlation in fatty acid ***,we verify the Kla levels of several differentially modified proteins,including ACAT1,ACADL,ACADVL,PFKM,PKM,and ***,our study reports a comprehensive Kla map in the neonatal mouse heart,which will help to understand the regulatory network of metabolic reprogramming and cardiac regeneration.

关键词： Lactylation Metabolicrep rogramming Postnatal heart regeneration Cell proliferation

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Associations Between Active,Passive Smoking and the Risk of Nonalcoholic Fatty Liver Disease

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Journal of Clinical and Translational Hepatology 2024年第1期12卷 113-118页

作者： Xinyuan Ge Jing Lu Chengxiao Yu Wen Guo Ting Tian Xin Xu Yuqing Ding Jiaxin Gao Wei Zhao Xiaohua Zhou Qingqing Diao Hongxia Ma Qun Zhang Ci Song Hongbing Shen Department of Epidemiology China International Cooperation Center on Environment and Human HealthCenter for Global HealthSchool of Public HealthNanjing Medical UniversityNanjingJiangsuChina health Promotion center Jiangsu Province Hospital and the First Affiliated Hospital of Nanjing Medical UniversityNanjingJiangsuChina Research Units of Cohort Study on Cardiovascular Diseases and Cancers Chinese Academy of Medical SciencesBeijingChina Collaborative Innovation center for Cancer Personalized Medicine Nanjing Medical UniversityNanjingJiangsuChina

Nonalcoholic fatty liver disease(NAFLD)is the most common chronic liver disease with an estimated worldwide prevalence of 32.4%.1 The multisystem condition is related to an increased risk of liver-related and cardiovascular extrahepatic diseases.2 Smoking is the leading preventable risk factor for premature disability and *** NAFLD and smoking are both associated with the development of metabolic features,there has been increasing interest in testing the relationship between smoking and *** causal relevance of smoking to NAFLD incidence have been implicated in crosssectional and prospective cohort studies.3,4 However,previous studies mainly focused on the effect of active smoking,discussion on the influence of passive smoking on NAFLD will facilitate illustrating the association between smoking and *** conducted a national two-center cross-section study of active,passive smoking and NAFLD risk in Chinese and European *** design allowed us to(1)test for associations between active,passive smoking and NAFLD risk by sex and consolidate evidence for causality by estimating dose-response relationship,(2)identify mediated factors,and(3)resolve their possible interaction with smoking.

关键词： mortality cardiovascular passive

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Association of Thallium Exposure with Decreased Renal Function among Chinese Adults—China,2017-2018

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China CDC weekly 2024年第34期6卷 867-871,I0007-I0010页

作者： Zheng Zhang Miao Zhang Yingli Qu Feng Zhao Saisai Ji Zheng Li Bing Wu Chunxian Lyu Haocan Song Qi Sun Yawei Li Xu Zhang Xulin Zheng Yidan Qiu Zihan Lu Hui Fu Lanjing Xu Wenli Zhang Yufei Luo Fangyu Li Jiayi Cai Yuanduo Zhu Ying Zhu Zhaojin Cao Yuebin Lyu Xiaoming Shi China CDC Key Laboratory of Environment and Population health National Institute of Environmental HealthChinese Center for Disease Control and PreventionBeijingChina center for Global health School of Public HealthNanjing Medical UniversityNanjing CityJiangsu ProvinceChina Department of Big Data in health Science School of Public HealthZhejiang UniversityHangzhou CityZhejiang ProvinceChina Department of Occupational health and Environment health School of Public HealthAnhui Medical UniversityHefei CityAnhui ProvinceChina School of Public health China Medical UniversityShenyang CityLiaoning ProvinceChina National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases(NITFID) National Institute of Environmental HealthChinese Center for Disease Control and PreventionBeijingChina

Summary What is already known about this topic?Thallium(Tl)is significantly more toxic than heavy metals such as lead,cadmium,and ***,previous studies examining the relationship between Tl exposure and the risk of chr... 详细信息

关键词： Renal kidney mercury

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

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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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Prevalence of Anemia in Patients with Diabetes Mellitus:A Systematic Review and Meta-Analysis

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Biomedical and Environmental Sciences 2024年第1期37卷 96-107页

作者： Monireh Faghir-Ganji Narjes Abdolmohammadi Maryam Nikbina Alireza Amanollahi Alireza Ansari-Moghaddam Rozhan Khezri Hamidreza Baradaran Student Research Committee Iran University of Medical SciencesTehranIran Department of Epidemiology School of Public HealthIran University of Medical SciencesTehranIran Department of Epidemiology School of Public HealthTehran University of Medical SciencesTehranIran Department of Midwifery Shoushtar Faculty of Medical SciencesShoushtarIran Department of Epidemiology School of Public Health and SafetyShahid Beheshti University of Medical SciencesTehranIran Trauma and Injury Research center Iran University of Medical SciencesTehranIran health Promotion Research center Zahedan University of Medical SciencesZahedanIran Endocrine Research center Institute of Endocrinology and MetabolismIran University of Medical SciencesTehranIran

Objective Anemia is a common public health concern in patients with type 2 diabetes *** study aimed to identify the prevalence of anemia among patients with *** Electronic databases,including PubMed,Scopus,Web of Sciences,and Google Scholar,were searched systematically for studies published between 2010 and *** removing duplicates and inappropriate reports,the remaining manuscripts were reviewed and appraised using theNewcastleOttawa Scale(NOS)tool.A random-effects model was used to calculate the pooled estimates of the extracted data using Stata version *** of the studies was assessed using the Q *** A total of 51 articles containing information on 26,485 patients with diabetes were included in this *** articles were mainly from Asia(58.82%)and Africa(35.29%).The overall prevalence of anemia was 35.45%(95%CI:30.30–40.76),with no evidence of heterogeneity by *** the two continents with the highest number of studies,the prevalence of anemia in patients with diabetes was significantly higher in Asia[40.02;95%CI:32.72–47.54]compared to Africa[28.46;95%CI:21.90–35.50](P for heterogeneity=0.029).Moreover,there has been an increasing trend in the prevalence of anemia in patients with diabetes over time,from[15.28;95%CI:9.83–22.21]in 2012 to[40.70;95%CI:10.21–75.93]in *** Globally,approximately 4 in 10 patients with diabetes suffer from ***,routine anemia screening and control programs every 3 months might be useful in improving the quality of life of these patients.

关键词： Prevalence Diabetic foot Anemia Diabetes mellitus

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circRNAs deregulation in exosomes derived from BEAS-2B cells is associated with vascular stiffness induced by PM_(2.5)

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Journal of Environmental Sciences 2024年第3期137卷 527-539页

作者： Qingping Liu Yaling Zhang Bin Han Mengruo Wang Huaifang Hu Jie Ning Wentao Hu Meiyu Chen Yaxian Pang Yuanyuan Chen Lei Bao Yujie Niu Rong Zhang Department of Toxicology Hebei Medical UniversityShijiazhuang 050017China State Key Laboratory of Environment health(Incubation) Key Laboratory of Environment and HealthMinistry of EducationKey Laboratory of Environment and Health(Wuhan)Ministry of Environmental ProtectionSchool of Public HealthTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China China CDC Key Laboratory of Environment and Population health National Institute of Environmental HealthChinese Center for Disease Control and PreventionBeijing 100021China Occupational health and Environmental health Hebei Medical UniversityShijiazhuang 050017China Hebei Key Laboratory of Environment and Human health Hebei Medical UniversityShijiazhuang 050017China

As an environmental pollutant,ambient fine particulate matter (PM_(2.5)) was linked to cardiovascular *** molecular mechanisms underlying PM_(2.5)-induced extrapulmonary disease has not been elucidated *** this study the ambient PM_(2.5)exposure mice model we established was to explore adverse effects of vessel and potential ***-term PM_(2.5)exposure caused reduced lung function and vascular stiffness in *** chronic PM_(2.5)induced migration and epithelial-mesenchymal transition (EMT) phenotype in BEAS-2B *** PM_(2.5)treatment,the circRNAs and mRNAs levels of exosomes released by BEAS-2B cells were detected by competing endogenous RNA (ceRNA) array,which contained 1664 differentially expressed circRNAs (DE-circRNAs) and 308 differentially expressed m RNAs (DE-mRNAs).By bioinformatics analysis on host genes of DE-circRNAs,vascular diseases and some pathways related to vascular diseases including focal adhesion,tight junction and adherens junction were ***,ceRNA network was constructed,and DE-mRNAs in ceRNA network were conducted functional enrichment analysis by Ingenuity Pathway Analysis,which indicated that hsa_circ_0012627,hsa_circ_0053261and hsa_circ_0052810 were related to vascular endothelial ***,it was verified experimentally that Exo^(PM2.5)could induce endothelial dysfunction by increased endothelial permeability and decreased relaxation in *** present study,we investigated in-depth knowledge into the molecule events related to PM_(2.5) toxicity and pathogenesis of vascular diseases.

关键词： Fine particulate matter Vascular stiffness Exosome ceRNA microarray Endothelial dysfunction

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Development of a Proof-of-Concept Multi-Method Computer Simulation to Support Rural healthcare Disaster Preparedness Planning

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International Journal of Disaster Risk Science 2024年第3期15卷 346-358页

作者： Thomas A.Berg Kristina W.Kintziger Julie Suzuki Crumly Scott A.Lawson Carole R.Myers Tracey T.Stansberry College of Nursing University of Tennessee Knoxville Department of Environmental Agricultural and Occupational Health University of Nebraska Medical Center Public health and healthcare Oak Ridge Associated Universities

Due to a lack of resources, rural communities often face challenges when planning catastrophic events. This project involved applying systems thinking and model-based systems engineering to develop a proof-of-concept, multi-method computer simulation and then determining whether the simulation could be used to assess the efficacy of disaster planning approaches on health outcomes in rural communities, as a function of primary healthcare. The project focus was a rural or non-urban healthcare system experiencing a natural hazard. Both system dynamics and discrete event models were incorporated to represent subsystem operations, crucial disaster responses, as well as three key response systems: public health, emergency management, and healthcare. The subsystem models included several components: policies/procedures, communications,resources, exercises/drills/training, healthcare space and staff, and the flow of affected people into and through the *** combined simulation can serve as a first step to a more comprehensive approach to helping rural communities achieve more efficient and effective healthcare planning for disaster responses.

关键词： Computer simulation Disaster preparedness Model-based systems engineering Rural healthcare System dynamics model Systems thinking

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