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Sialyltransferase ST3GAL6 silencing reduces α2,3-sialylated glycans to regulate autophagy by decreasing HSPB8-BAG3 in the brain with hepatic encephalopathy

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2024年第6期25卷 485-498页

作者： Xiaocheng LI Yaqing XIAO Pengfei LI Yayun ZHU Yonghong GUO Huijie BIAN Zheng LI Laboratory for Functional Glycomics College of Life SciencesNorthwest UniversityXi’an 710069China National translational Science center for Molecular medicine Department of Cell BiologyFourth Military Medical UniversityXi’an 710032China Medical Experiment center Shaanxi University of Chinese MedicineXianyang 712046China The Infectious Disease Department Gongli HospitalPudong New AreaShanghai 200135China

End-stage liver diseases,such as cirrhosis and liver cancer caused by hepatitis B,are often combined with hepatic encephalopathy(HE);ammonia poisoning is posited as one of its main pathogenesis *** is closely related to autophagy,but the molecular mechanism of ammonia’s regulatory effect on autophagy in HE remains *** is an essential form of *** the nervous system,abnormal sialylation affects various physiological processes,such as neural development and synapse ***3 β-galactoside α2,3-sialyltransferase 6(ST3GAL6)is one of the significant glycosyltransferases responsible for addingα2,3-linked sialic acid to substrates and generating glycan *** found that the expression of ST3GAL6 was upregulated in the brains of mice with HE and in astrocytes after ammonia induction,and the expression levels of α2,3-sialylated glycans and autophagy-related proteins microtubule-associated protein light chain 3(LC3)and Beclin-1 were upregulated in ammonia-induced *** findings suggest that ST3GAL6 is related to autophagy in ***,we aimed to determine the regulatory relationship between ST3GAL6 and *** found that silencing ST3GAL6 and blocking or degrading α2,3-sialylated glycans by way of Maackia amurensis lectin-II(MAL-II)and neuraminidase can inhibit *** addition,silencing the expression of ST3GAL6 can downregulate the expression of heat shock proteinβ8(HSPB8)and Bcl2-associated athanogene 3(BAG3).Notably,the overexpression of HSPB8 partially restored the reduced autophagy levels caused by silencing ST3GAL6 *** results indicate that ST3GAL6 regulates autophagy through the HSPB8-BAG3 complex.

关键词： Hepatic encephalopathy Hyperammonemia Autophagy ST3β-galactosideα2,3-sialyltransferase 6(ST3GAL6) Heat shock proteinβ8(HSPB8)

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Phosphodiesterase 9 localization in cytoplasm and nucleus:the gateway to selective targeting in neuroprotection?

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Neural Regeneration Research 2025年第6期20卷 1701-1702页

作者： Giovanni Ribaudo Matteo Giannangeli Margrate Anyanwu Alessandra Gianoncelli Department of Molecular and translational medicine University of BresciaBresciaItaly

The umbrella term"neurodege ne rative disorders"(NDDs) refers to several conditions characterized by a progressive loss of structure and function of cells belonging to the nervous *** diseases affect more than 50million people *** disorders are characterized by sundry factors and pathophysiological mechanisms that a re challenging to be fully *** of these rely on cell signaling pathways to preserve homeostasis,involving second messengers such as cyclic adenosine monophosphate (cAMP)and cyclic guanosine 3',5'-monophosphate(cGMP).Their ability to control the duration and amplitude of the signaling cascade is given by the presence of several common and uncommon *** kinases A and G (PKA and PKG),phosphodiesterases (PDEs),and scaffold proteins are among them.

关键词： gateway homeostasis preserve

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Degeneration Directory:a multi-omics web resource for degenerative diseases

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Protein & Cell 2024年第5期15卷 385-392页

作者： Haoteng Yan Changfa Lu Chenyang Lan Si Wang Weiqi Zhang Zan He Jinghao Hu Jiaqi Ai Guang-Hui Liu Shuai Ma Yuanchun Zhou Jing Qu State Key Laboratory of Membrane Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China State Key Laboratory of Stem Cell and Reproductive Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China Key Laboratory of Organ Regeneration and Reconstruction Institute of ZoologyChinese Academy of SciencesBeijing 100101China Advanced Innovation center for Human Brain Protection and National Clinical Research Center for Geriatric DisordersXuanwu Hospital Capital Medical UniversityBeijing 100053China aging translational medicine center International Center for Aging and CancerBeijing Municipal Geriatric Medical Research CenterXuanwu HospitalCapital Medical UniversityBeijing 100053China Computer Network Information center Chinese Academy of SciencesBeijing 100190China The Fifth People’s Hospital of Chongqing Chongqing 400062China aging Biomarker Consortium Beijing 100101China CAS Key Laboratory of Genomic and Precision medicine Beijing Institute of GenomicsChinese Academy of Sciences and China National Center for BioinformationBeijing 100101China University of Chinese Academy of Sciences Beijing 100049China Sino-Danish College University of Chinese Academy of SciencesBeijing 101408China Beijing Institute for Stem Cell and Regenerative medicine Beijing 100101China Institute for Stem Cell and Regeneration Chinese Academy of SciencesBeijing 100101China

Background of *** degeneration refers to the gradual decline in organ function and structure deterioration that occurs during aging,which represents the greatest risk factor for various degenerative diseases,including cardiovascular diseases,neurodegenerative diseases,and osteoarthritis,etc.(aging Biomarker et al.,2023;Becker et al.,2018;Cai et al.,2022).

关键词： Directory web Becker

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DNA methylation clocks for estimating biological age in Chinese cohorts

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Protein & Cell 2024年第8期15卷 575-593页

作者： Zikai Zheng Jiaming Li Tianzi Liu Yanling Fan Qiao-Cheng Zhai Muzhao Xiong Qiao-Ran Wang Xiaoyan Sun Qi-Wen Zheng Shanshan Che Beier jiang Quan Zheng Cui Wang Lixiao Liu Jiale Ping Si Wang Dan-Dan Gao Jinlin Ye Kuan Yang Yuesheng Zuo Shuai Ma Yun-GuiYang Jig Qu Feng Zhang Peilin Jia Guang-Hui Liu Weiqi Zhang CAS Key Laboratory of Genomic and Precision medicine Beijing Institute of GenomicsChinese Academy of Sciences and China National Center for BioinformationBeijing 100101China University of Chinese Academy of Sciences Beijing 100049China CAS Key Laboratory of Computational Biology Shanghai Institute of Nutrition and HealthChinese Academy of SciencesShanghai 200031China Division of Orthopaedics Quzhou Affliated Hospital of Wenzhou Medical UniversityQuzhou 324000China The Joint Innovation center for Engineering in medicine Quzhou Affliated Hospital of Wenzhou Medical UniversityQuzhou 324000China Advanced Innovation center for Human Brain Protection and National Clinical Research Center for Geriatric DisordersXuanwu Hospital Capital Medical UniversityBeijing 100053China aging translational medicine center Intemational Center for Aging and CancerXuanwu HospitalCapital Medical UniversityBeijing 100053China aging Biomarker Consortium Beijing 100101China State Key Laboratory of Membrane Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China Key Laboratory of Organ Regeneration and Reconstruction Institute of ZoologyChinese Academy of SciencesBeijing 100101China nstitute for Stem Cell and Regeneration Chinese Academy of SciencesBeijing 100101China Beijing Institute for Stem Cell and Regenerative medicine Beijing 100101China State Key Laboratory of Stem Cell and Reproductive Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China National Genomics Data center Beijing Institute of GenomicsChinese Academy of Sciences and China National Center for BioinformationBeijing 100101China

Epigenetic clocks are accurate predictors of human chronological age based on the analysis of DNA methylation(DNAm)at specific CpG ***,a systematic comparison between DNA methylation data and other omics datasets has not yet been ***,available DNAm age predictors are based on datasets with limited ethnic *** address these knowledge gaps,we generated and analyzed DNA methylation datasets from two independent Chinese cohorts,revealing age-related DNAm ***,a DNA methylation aging clock(iCAS-DNAmAge)and a group of DNAm-based multi-modal clocks for Chinese individuals were developed,with most of them demonstrating strong predictive capabilities for chronological *** clocks were further employed to predict factors influencing aging *** DNAm aging clock,derived from multi-modal aging features(compositeAge-DNAmAge),exhibited a close association with multi-omics changes,lifestyles,and disease status,underscoring its robust potential for precise biological age *** findings offer novel insights into the regulatory mechanism of age-related DNAm changes and extend the application of the DNAm clock for measuring biological age and aging pace,providing the basis for evaluating aging intervention strategies.

关键词： DNA methylation aging clock aging age prediction

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Early-life famine exposure,adulthood obesity patterns,and risk of low-energy fracture

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Frontiers of medicine 2024年第1期18卷 192-203页

作者： Hongyan Qi Chunyan Hu Jie Zhang Lin Lin Shuangyuan Wang Hong Lin Xiaojing Jia Yuanyue Zhu Yi Zhang Xueyan Wu Mian Li Min Xu Yu Xu Tiange Wang Zhiyun Zhao Weiqing Wang Yufang Bi Meng Dai Yuhong Chen Jieli Lu Department of Endocrine and Metabolic Diseases Shanghai Institute of Endocrine and Metabolic DiseasesRuijin HospitalShanghai Jiao Tong University School of MedicineShanghai200025China Shanghai National Clinical Research center for Endocrine and Metabolic Diseases Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the People’s Republic of ChinaShanghai National Center for Translational MedicineRuijin HospitalShanghai Jiao Tong University School of MedicineShanghai200025China

Malnutrition in early life increases the risk of osteoporosis,but the association of early-life undernutrition combined with adulthood obesity patterns with low-energy fracture remains *** study included 5323 community-dwelling subjects aged⩾40 years from ***-life famine exposure was identified based on the participants’birth *** obesity was assessed using the body mass index(BMI),and abdominal obesity was evaluated with the waist-to-hip ratio(WHR).Low-energy fracture was defined as fracture occurring after the age of⩾40 typically caused by falls from standing height or *** to the nonexposed group,the group with fetal,childhood,and adolescence famine exposure was associated with an increased risk of fracture in women with odds ratios(ORs)and 95%confidence intervals(CIs)of 3.55(1.57–8.05),3.90(1.57–9.71),and 3.53(1.05–11.88),respectively,but not in *** interactions were observed between fetal famine exposure and general obesity with fracture among women(P for interaction=0.0008).Furthermore,compared with the groups with normal BMI and WHR,the group of women who underwent fetal famine exposure and had both general and abdominal obesity had the highest risk of fracture(OR,95%CI:3.32,1.17–9.40).These results indicate that early-life famine exposure interacts with adulthood general obesity and significantly increases the risk of low-energy fracture later in life in women.

关键词： famine obesity body mass index waist-to-hip ratio low-energy fracture

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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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Inflection Point Age in the Middle and Older Women—Jiangxi Province,China,2020-2022

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China CDC weekly 2024年第9期6卷 162-167页

作者： Shanlan Yang Langlang Zhang Helang Huang Jiaofeng Wang Lei Wu Zhijun Bao Shanghai Institute of Infectious Disease and Biosecurity Fudan UniversityShanghaiChina Department of Gerontology Huadong Hospital Affiliated to Fudan UniversityShanghai Key Laboratory of Clinical Geriatric MedicineResearch Center on Aging and MedicineFudan UniversityShanghaiChina Jiangxi Provincial Key Laboratory of Preventive medicine School of Public HealthNanchang UniversityNanchang CityJiangxi ProvinceChina

Summary What is already known about this topic?Previous studies have predominantly examined the micro-level aspects of women aging inflection points,while macro-level research using big data on the inflection points o... 详细信息

关键词： Middle Jiangxi currently

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Apoer2/Lrp8:the undercover cop of synaptic homeostasis

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Neural Regeneration Research 2024年第12期19卷 2563-2564页

作者： Gordon C.Werthmann Joachim Herz Department of Molecular Genetics and center for translational Neurodegeneration Research University of Texas Southwestern Medical Center at DallasDallasTXUSA Department of Neuroscience Department of Neurology University of Texas Southwestern Medical center at Dallas DallasTXUSA

Apolipoprotein E receptor 2(ApoER2)is a receptor for the protein ApoE,the most common genetic risk factor for late-onset Alzheimer's disease(AD).It is also a key modulator of syna ptic homeostasis,in part through its effect on the expression of neuronal genes including those implicated in AD and other neuropsychiatric *** this perspective,we highlight several genes affected by ApoER2 and its alternatively spliced forms and how aberrant expression can be rescued by the reintroduction of the ApoER2 intracellular domain in the mouse hippocampus.

关键词： homeostasis ApoE Alzheimer

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Opportunities and challenges of CD47-targeted therapy in cancer immunotherapy

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Oncology Research 2024年第1期32卷 49-60页

作者： QIUQIANG CHEN XUEJUN GUO WENXUE MA Key Laboratory for translational medicine The First Affiliated HospitalHuzhou University School of MedicineHuzhou313000China Department of Hematology Puyang Youtian General HospitalPuyang457001China Department of medicine Moores Cancer CenterSanford Stem Cell InstituteUniversity of California San DiegoLa JollaSan Diego92093USA

Cancer immunotherapy has emerged as a promising strategy for the treatment of cancer,with the tumor microenvironment(TME)playing a pivotal role in modulating the immune ***47,a cell surface protein,has been identified as a crucial regulator of the TME and a potential therapeutic target for cancer ***,the precise functions and implications of CD47 in the TME during immunotherapy for cancer patients remain incompletely *** comprehensive review aims to provide an overview of CD47’s multifaced role in TME regulation and immune evasion,elucidating its impact on various types of immunotherapy outcomes,including checkpoint inhibitors and CAR T-cell ***,CD47-targeted therapies offer a promising avenue for improving cancer treatment outcomes,especially when combined with other immunotherapeutic *** review also discusses current and potential CD47-targeted therapies being explored for cancer treatment and delves into the associated challenges and opportunities inherent in targeting *** the demonstrated effectiveness of CD47-targeted therapies,there are potential problems,including unintended effects on healthy cells,hematological toxicities,and the development if ***,further research efforts are warranted to fully understand the underlying mechanisms of resistance and to optimize CD47-targeted therapies through innovative combination approaches,ultimately improving cancer treatment ***,this comprehensive review highlights the significance of CD47 as a promising target for cancer immunotherapy and provides valuable insight into the challenges and opportunities in developing effective CD47-targeted therapies for cancer treatment.

关键词： CD47 Cancer immunotherapy CD47-targeted therapies Tumor microenvironment Macrophage Cancer cell Immune evasion Checkpoint inhibitors CAR T-cell therapy Cancer treatment outcomes

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Single-nucleus transcriptomics uncovers a geroprotective role of YAP in primate gingival aging

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Protein & Cell 2024年第8期15卷 612-632页

作者： Qinchao Hu Bin Zhang Yaobin Jing Shuai Ma Lei Hu jingyi Li Yandong Zheng Zijuan Xin Jianmin Peng Si Wang Bin Cheng Jing Qu Weiqi zhang Guang-Hui Liu Songlin Wang State Key Laboratory of Membrane Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China Hospital of Stomatology Guanghua School of StomatologyGuangdong Provincial Key Laboratory of StomatologySun Yat-sen UniversityGuangzhou 510060China Salivary Gland Disease center and Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction Beijing Laboratory of Oral Health and Beijing Stomatological HospitalCapital Medical UniversityBeijing 100050China Department of Biochemistry and Molecular Biology School of Basic Medical SciencesCapital Medical UniversityBeijing 100069China CAS Key Laboratory of Genomic and Precision medicine Beijing Institute of GenomicsChinese Academy of Sciences and China National Center for BioinformationBeijing 100101China State Key Laboratory of Stem Cell and Reproductive Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China Key Laboratory of Organ Regeneration and Reconstruction Institute of ZoologyChinese Academy of SciencesBeijing 100101China University of Chinese Academy of Sciences Beijing 100049China Institute for Stem Cell and Regeneration Chinese Academy of SciencesBeijing 100101China Beijing Institute for Stem Cell and Regenerative medicine Beijing 100101China Advanced Innovation center for Human Brain Protection and National Clinical Research center for Geriatric Disorders Xuanwu Hospital Capital Medical UniversityBeijing 100053China aging translational medicine center Intermational Center for Aging and CancerBeijing Municipal Geriatric Medical Research CenterXuan Wu HospitalCapital Medical UniversityBeijing 100053China Intemational center for aging and Cancer Hainan Medical UniversityHaikou 571199China aging Biomarker Consortium Beijing 100101China

aging has a profound impact on the gingiva and significantly increases its susceptibility to periodontitis,a worldwide prevalent inflammatory ***,a systematic characterization and comprehensive understanding of the regulatory mechanism underlying gingival aging is still ***,we systematically dissected the phenotypic characteristics of gingiva during aging in primates and constructed the first single-nucleus transcriptomic landscape of gingival aging,by which a panel of cell type-specific signatures were *** cells were identified as the most affected cell types by aging in the *** analyses pinpointed the crucial role of YAP in epithelial self-renew and homeostasis,which declined during aging in epithelial cells,especially in basal *** decline of YAP activity during aging was confrmed in the human gingival tissues,and downregulation of YAP in human primary gingival keratinocytes recapitulated the major phenotypic defects observed in the aged primate gingiva while overexpression of YAP showed rejuvenation *** work provides an in-depth understanding of gingival aging and serves as a rich resource for developing novel strategies to combat aging-associated gingival diseases,with the ultimate goal of advancing periodontal health and promoting healthy aging.

关键词： single-nucleus RNA-sequencing primate gingiva aging YAP

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