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Genetic analysis of transcription factors in dopaminergic neuronal development in Parkinson’s disease

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Chinese Medical Journal 2024年第4期137卷 450-456页

作者： Yuwen Zhao Lixia Qin Hongxu Pan Tingwei Song Yige Wang Xiaoxia Zhou Yaqin Xiang Jinchen Li Zhenhua Liu Qiying sun Jifeng Guo Xinxiang Yan Beisha Tang qian Xu Department of Neurology Xiangya HospitalCentral South UniversityChangshaHunan 410008China Department of Neurology The Second Xiangya HospitalCentral South UniversityChangshaHunan 410011China Bioinformatics Center National Clinical Research Center for Geriatric Disorders Xiangya HospitalCentral South UniversityChangshaHunan 410008China Department of Geriatrics Xiangya HospitalCentral South UniversityChangshaHunan 410008China Centre for Medical Genetics and Hunan Key Laboratory of Medical Genetics School of Life SciencesCentral South UniversityChangshaHunan 410008China Key Laboratory of Hunan Province in Neurodegenerative Disorders Central South UniversityChangshaHunan 410008China

Background:Genetic variants of dopaminergic transcription factor-encoding genes are suggested to be Parkinson’s disease(PD)risk factors;however,no comprehensive analyses of these genes in patients with PD have been ***,we aimed to genetically analyze 16 dopaminergic transcription factor genes in Chinese patients with ***:Whole-exome sequencing(WES)was performed using a Chinese cohort comprising 1917 unrelated patients with familial or sporadic early-onset PD and 1652 ***,whole-genome sequencing(WGS)was performed using another Chinese cohort comprising 1962 unrelated patients with sporadic late-onset PD and 1279 ***:We detected 308 rare and 208 rare protein-altering variants in the WES and WGS cohorts,***-based association analyses of rare variants suggested that MSX1 is enriched in sporadic late-onset ***,the significance did not pass the Bonferroni ***,72 and 1730 common variants were found in the WES and WGS cohorts,***,single-variant logistic association analyses did not identify significant associations between common variants and ***:Variants of 16 typical dopaminergic transcription factors might not be major genetic risk factors for PD in Chinese ***,we highlight the complexity of PD and the need for extensive research elucidating its etiology.

关键词： Parkinson’s disease Transcription factors Dopaminergic neurons Genetic Variants

Investigation of Nasal Mucosal IgA Responses in the Population Following COVID-19 Pandemic — China, September 2022–August 2023

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China CDC weekly 2024年第15期6卷 312-317,I0005页

作者： Boyang Li Lei Zhou Zhilong Chen Yanhan Wen qian Wang Tao Huang Si Chen Wei Wu Mengxuan Wang Lina sun Mifang Liang Shiwen Wang Ling Chen Qun Li National Institute for Viral Disease Control and Prevention Chinese Center for Disease Control and PreventionBeijingChina National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases Chinese Center for Disease Control and PreventionBeijingChina Xiamen United Institute of Respiratory Health Xiamen CityFujian ProvinceChina Guangzhou Laboratory Guangzhou CityGuangdong ProvinceChina State Key Laboratory of Respiratory Disease Guangzhou Institute of Respiratory HealthThe First Affiliated Hospital of Guangzhou Medical UniversityGuangzhou CityGuangdong ProvinceChina

What is already known about this topic?Mucosal IgA plays a crucial role in host immunity against respiratory *** studies suggest that it has the potential to mitigate the transmission of the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)Omicron ***,a comprehensive population-based analysis examining mucosal IgA levels following the winter 2022 wave of the coronavirus disease 2019(COVID-19)pandemic is yet to be *** is added by this report?In our study involving 3,421 participants,we documented IgA responses subsequent to SARS-CoV-2 infection.A significant proportion of individuals sustained increased levels of IgA for over six *** levels were also observed in individuals with prior infections who underwent asymptomatic reinfections,indicating an active production of IgA ***,individuals with multiple vaccinations or severe symptoms tended to display elevated IgA levels after *** are the implications for public health practice?IgA in the nasal mucosa is crucial for defense against SARS-CoV-2 *** insights can enhance our knowledge of immune responses following infection and have provided certain reference values for disease prevention and control strategies.

关键词： prevention sustained immunity

Artificial Nucleic Acid Tractor-Directed Simultaneous Depletion of Oncogenic Membrane Proteins Without Hijacking Proteolysis-Specific Actuator

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CCS Chemistry 2024年第2期6卷 439-449页

作者： Zhen Zou Songlan Pan qian Xue Ting Chen Ziyun Huang Bei Qing Pengfei Liu Conghui Zhao Yunlin sun Erhu Xiong Ronghua Yang Key Laboratory of Chemical Biology and Traditional Chinese Medicine Research Ministry of EducationCollege of Chemistry and Chemical EngineeringHunan Normal UniversityChangsha 410081 School of Chemistry and Chemical Engineering Hunan Provincial Key Laboratory of CytochemistryChangsha University of Science and TechnologyChangsha 410114 The Second Xiangya Hospital Central South UniversityChangsha 410011

Targeted protein degradation(TPD)is an emerging tool for degrading proteins of interest,which affords an attractive modality for cancer ***,the present TPD technologies must engage a proteolysis-specific actuator to initiate degradation of targeted proteins in the proteasome or ***,we report an artificial tractor that can induce endocytosis-mediated protein depletion without hijacking a proteolysis-specific *** this design,bispecific aptamer chimeras(BSACs)are established,which can bridge human epidermal growth factor receptor 2(ErbB-2),an important biomarker in a common important biomarker in cancer,with membrane proteins of *** advantage of the property of aptamer-induced endocytosis and digestion of ErbB-2,another membrane protein is translocated into the lysosome in a hitchhike-like manner,resulting in lysosomal proteolysis along with *** strategy frees the TPD from the fundamental limitation of proteolysis-specific actuator and allows simultaneous regulation of the quantity and function of two oncogenic receptors in a cell-type-specific manner,expanding the application scope of TPD-based therapeutics.

关键词： targeted protein degradation aptamer epidermal growth factor receptor 2 lysosome membrane proteins cancer therapy

A secure visualization platform for pathogenic genome analysis with an accurate reference database

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生物安全与健康(英文) 2024年第04期06卷 235-243页

作者： Fan Guomei Guo Chongye Zhang qian Liu Dongmei sun Qinglan Cui Zhigang Zhou Haijian Zhou Yuanchun Guo Zhibin Ma Juncai Wu Linhuan Microbial Resource and Big Data Center Institute of Microbiology Chinese Academy of Sciences Beijing China Chinese National Microbiology Data Center (NMDC) Beijing China National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases National Institute for Communicable Disease Control and Prevention Chinese Center for Disease Control and Prevention Beijing China Computer Network Information Center Chinese Academy of Sciences Beijing China State Key Laboratory of Microbial Resources Institute of Microbiology Chinese Academy of Sciences Beijing China

Investigating the genetic and developmental characteristics, infection transmission attributes, and epidemiological trends of pathogens using genomic data represents the foundation for pathogen surveillance and is a crucial prerequisite for guaranteeing global health security. To meet the analytical demands of research relating to pathogen prevention and control, we designed a secure visualization system capable of pathogen genome assembly, annotation, species identification, sequence typing, antibiotic resistance and virulence analysis, genomic mobile element and transferable resistance gene annotation, and phylogenetic tree reconstruction. For highly pathogenic organisms requiring complete data protection, we have developed a secure computing tool that utilizes a trusted execution environment, is combined with blockchain and privacy computing technologies, and is specifically designed for nucleotide basic local alignment search tool (BLASTn) comparison analysis. This technological advancement offers scientific support for in-depth investigations into pathogen transmission and epidemiological mechanisms, environmental adaptability, evolutionary trends, and immune evasion mechanisms, as well as the identification of new or emerging pathogen strains. This, in turn, aids efforts in infectious disease prevention, treatment, and research.

关键词： Pathogen surveillance One-stop analysis tools Sequence typing Horizontal transfer Secure computing

Non-coding RNAs in acute ischemic stroke:from brain to periphery

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Neural Regeneration Research 2025年第1期20卷 116-129页

作者： Shuo Li Zhaohan Xu Shiyao Zhang Huiling sun Xiaodan Qin Lin Zhu teng Jiang Junshan Zhou Fuling Yan Qiwen Deng Department of Neurology Nanjing First HospitalNanjing Medical UniversityNanjingJiangsu ProvinceChina Department of Neurology Zhongda HospitalSchool of MedicineSoutheast UniversityNanjingJiangsu ProvinceChina General Clinical Research Center Nanjing First HospitalNanjing Medical UniversityNanjingJiangsu ProvinceChina

Acute ischemic stroke is a clinical emergency and a condition with high morbidity,mortality,and *** predictive,diagnostic,and prognostic biomarkers and effective therapeutic targets for acute ischemic stroke remain *** innovations in high-throughput gene sequencing analysis,many aberrantly expressed non-coding RNAs(ncRNAs)in the brain and peripheral blood after acute ischemic stroke have been found in clinical samples and experimental *** expressed ncRNAs in the post-stroke brain were demonstrated to play vital roles in pathological processes,leading to neuroprotection or deterioration,thus ncRNAs can serve as therapeutic targets in acute ischemic ***,distinctly expressed ncRNAs in the peripheral blood can be used as biomarkers for acute ischemic stroke prediction,diagnosis,and *** particular,ncRNAs in peripheral immune cells were recently shown to be involved in the peripheral and brain immune response after acute ischemic *** this review,we consolidate the latest progress of research into the roles of ncRNAs(microRNAs,long ncRNAs,and circular RNAs)in the pathological processes of acute ischemic stroke–induced brain damage,as well as the potential of these ncRNAs to act as biomarkers for acute ischemic stroke prediction,diagnosis,and *** from this review will provide novel ideas for the clinical application of ncRNAs in acute ischemic stroke.

关键词： acute ischemic stroke apoptosis blood–brain barrier damage circular RNAs excitatory toxicity long non-coding RNAs microRNAs neuroinflammation non-coding RNAs oxidative stress

Serotonin receptor 2B induces visceral hyperalgesia in rat model and patients with diarrhea-predominant irritable bowel syndrome

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World Journal of Gastroenterology 2024年第10期30卷 1431-1449页

作者： Zheng-Yang Li Yu-Qing Mao qian Hua Yong-Hong sun Hai-Yan Wang Xuan-Guang Ye Jing-Xian Hu Ya-Jie Wang Miao Jiang Department of Gastroenterology Jinshan Hospital of Fudan UniversityShanghai 201508China Department of Gastroenterology Shanghai General HospitalShanghai Jiao Tong University School of MedicineShanghai 200080China Department of Gastroenterology Dalian Friendship HospitalDalian 116001Liaoning ProvinceChina Department of Pathology Jinshan Hospital of Fudan UniversityShanghai 201508China

BACKGROUND Serotonin receptor 2B(5-HT2B receptor)plays a critical role in many chronic pain *** possible involvement of the 5-HT2B receptor in the altered gut sensation of irritable bowel syndrome with diarrhea(IBS-D)was investigated in the present *** To investigate the possible involvement of 5-HT2B receptor in the altered gut sensation in rat model and patients with *** Rectosigmoid biopsies were collected from 18 patients with IBS-D and 10 patients with irritable bowel syndrome with constipation who fulfilled the Rome IV criteria and 15 healthy *** expression level of the 5-HT2B receptor in colon tissue was measured using an enzyme-linked immunosorbent assay and correlated with abdominal pain *** IBS-D rat model was induced by intracolonic instillation of acetic acid and wrap *** in visceral sensitivity and 5-HT2B receptor and transient receptor potential vanilloid type 1(TRPV1)expression were examined following 5-HT2B receptor antagonist *** in visceral sensitivity after administration of the TRPV1 antago-INTRODUCTION Irritable bowel syndrome(IBS)is a chronic functional bowel disorder characterized by recurrent abdominal pain with altered bowel habits that affects approximately 15%of the population worldwide[1].IBS significantly impacts the quality of life of *** the pathogenesis of IBS is not completely understood,the role of abnormal visceral sensitivity in IBS has recently emerged[2,3].5-Hydroxytryptamine(5-HT)is known to play a key role in the physiological states of the gastrointestinal *** 5-HT levels in IBS with diarrhea(IBS-D)patients were greater than those in healthy controls[4],suggesting a possible role of 5-HT in the pathogenesis of *** serotonin receptor 2(5-HT2 receptor)family comprises three subtypes:5-HT2A,5-HT2B,and *** 5-HT2 receptors exhibit 46%-50%overall sequence identity,and all of these receptors preferentially bind to Gq/

关键词： Diarrhea-predominant irritable bowel syndrome Serotonin receptor 2B Transient receptor potential vanilloid type-1 Visceral hypersensitivity Abdominal pain

Proteomic Stratification of Prognosis and Treatment Options for Small Cell Lung Cancer

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GENOMICS PROTEOMICS & BIOINFORMATICS 2024年第2期22卷 qzae033页

作者： Huo, Zitian Duan, Yaqi Zhan, Dongdong Xu, Xizhen Zheng, Nairen Cai, Jing sun, Ruifang Wang, Jianping Cheng, Fang Gao, Zhan Xu, Caixia Liu, Wanlin Dong, Yuting Ma, Sailong Zhang, qian Zheng, Yiyun Lou, Liping Kuang, Dong Chu, qian Qin, Jun Wang, Guoping Wang, Yi Huazhong Univ Sci & Technol Tongji Hosp Inst Pathol Tongji Med Coll Wuhan 430030 Peoples R China Huazhong Univ Sci & Technol Tongji Med Coll Sch Basic Med Dept Pathol Wuhan 430030 Peoples R China Huazhong Univ Sci & Technol Tongji Med Coll Tongji Hosp Natl Hlth CommissKey Lab Resp Dis Wuhan 430030 Peoples R China Beijing Pineal Diagnost Co Ltd Beijing 102206 Peoples R China Beijing Inst Life Beijing Proteome Res Ctr Natl Ctr Prot Sci Beijing State Key Lab Prote Beijing 102206 Peoples R China Huazhong Univ Sci & Technol Tongji Hosp Tongji Med Coll Dept Oncol Wuhan 430030 Peoples R China Chongqing Univ Posts & Telecommun Sch Bioinformat Chongqing Key Lab Big Data Bio Intelligence Chongqing 400065 Peoples R China Henan Univ Affiliated Hosp 1 Inst Pathol Kaifeng 475001 Peoples R China Shanxi Canc Hosp Dept Tumor Biobank Taiyuan 030013 Peoples R China

Small cell lung cancer (SCLC) is a highly malignant and heterogeneous cancer with limited therapeutic options and prognosis prediction models. Here, we analyzed formalin-fixed, paraffin-embedded (FFPE) samples of surgical resections by proteomic profiling, and stratified SCLC into three proteomic subtypes (S-I, S-II, and S-III) with distinct clinical outcomes and chemotherapy responses. The proteomic subtyping was an independent prognostic factor and performed better than current tumor-node-metastasis or Veterans Administration Lung Study Group staging methods. The subtyping results could be further validated using FFPE biopsy samples from an independent cohort, extending the analysis to both surgical and biopsy samples. The signatures of the S-II subtype in particular suggested potential benefits from immunotherapy. Differentially overexpressed proteins in S-III, the worst prognostic subtype, allowed us to nominate potential therapeutic targets, indicating that patient selection may bring new hope for previously failed clinical trials. Finally, analysis of an independent cohort of SCLC patients who had received immunotherapy validated the prediction that the S-II patients had better progression-free survival and overall survival after first-line immunotherapy. Collectively, our study provides the rationale for future clinical investigations to validate the current findings for more accurate prognosis prediction and precise treatments.

关键词： Small cell lung cancer Proteomics Prognosis Chemotherapy response Immunotherapy DOMAIN-LIKE PROTEIN PROTEOGENOMIC CHARACTERIZATION PRIMARY TUMOR EXPRESSION NECROPTOSIS LINES IDENTIFICATION ESTABLISHMENT CHEMOTHERAPY BIOMARKER

税收征管数字化抑制了企业高管在职消费吗?——来自金税三期工程的经验证据

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西部论坛 2024年第1期34卷 96-110页

作者：孙倩蚌埠工商学院财务与审计学院安徽蚌埠233010 厦门大学管理学院福建厦门361000

无论是在理论上还是在实践中,对企业高管超额在职消费的治理都是一个重要问题。以金税三期工程为代表的税收征管数字化,可以通过提高企业信息透明度和强化外部治理来压缩高管实施自利行为的操作空间,从而有效抑制高管在职消费。将金税... 详细信息

无论是在理论上还是在实践中,对企业高管超额在职消费的治理都是一个重要问题。以金税三期工程为代表的税收征管数字化,可以通过提高企业信息透明度和强化外部治理来压缩高管实施自利行为的操作空间,从而有效抑制高管在职消费。将金税三期系统分批上线作为一项准自然实验,采用沪深A股上市公司2010—2021年的数据,运用多期双重差分模型检验税收征管数字化对企业高管在职消费的影响,结果表明,金税三期工程的实施显著降低了企业高管在职消费水平。机制检验发现,税收征管数字化可以通过缓解信息不对称、抑制避税行为等路径来降低企业高管在职消费水平。异质性分析显示,税收征管数字化对高管在职消费的抑制作用在非国有企业、非四大会计师事务所审计企业、股权集中度较高企业、两职合一企业中更为显著。此外,税收征管数字化还可以弱化高管在职消费对企业业绩的负向影响。因此,政府在加快推进税收征管数字化的同时,要重视并充分发挥数字化监管的溢出效应,企业则应积极利用内外部数字化转型的契机实现高质量发展。

关键词：税收征管数字化金税三期高管在职消费信息不对称避税公司治理

数字经济背景下新职业群体的就业质量分析——以外卖骑手为例

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新视野 2024年第1期 95-102页

作者：孙茜河北经贸大学公共管理学院石家庄市050061

通过对外卖骑手就业质量的大样本实证统计,能够发现数字经济的就业创造效应对提升劳动者报酬、缩小城乡劳动者收入差距起到了关键的作用,绝大多数调查对象表示,在未来的职业规划中,愿意继续从事外卖骑手或相关岗位,并显示出具有新职业... 详细信息

通过对外卖骑手就业质量的大样本实证统计,能够发现数字经济的就业创造效应对提升劳动者报酬、缩小城乡劳动者收入差距起到了关键的作用,绝大多数调查对象表示,在未来的职业规划中,愿意继续从事外卖骑手或相关岗位,并显示出具有新职业群体特征的成长路径。外卖骑手在体面劳动这一评价维度上反映出较为积极的感知,尤其表现在物质条件、工作关系、就业环境公平性等方面。基于此,营造促进数字经济健康发展的政策环境和体制机制、重视数字经济对新职业群体技能要求的更新和结构性转换、引导大众解构对新职业群体的负面刻板印象、多方整合资源提供人文关怀、助力包容性数字社会建设等路径能够有效促进新职业群体的高质量充分就业。

关键词：数字经济高质量充分就业职业技能体面劳动