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

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 undertaken.Therefore,we aimed to genetically analyze 16 dopaminergic transcription factor genes in Chinese patients with PD.Methods:Whole-exome sequencing(WES)was performed using a Chinese cohort comprising 1917 unrelated patients with familial or sporadic early-onset PD and 1652 controls.Additionally,whole-genome sequencing(WGS)was performed using another Chinese cohort comprising 1962 unrelated patients with sporadic late-onset PD and 1279 controls.Results:We detected 308 rare and 208 rare protein-altering variants in the WES and WGS cohorts,respectively.Gene-based association analyses of rare variants suggested that MSX1 is enriched in sporadic late-onset PD.However,the significance did not pass the Bonferroni correction.Meanwhile,72 and 1730 common variants were found in the WES and WGS cohorts,respectively.Unfortunately,single-variant logistic association analyses did not identify significant associations between common variants and PD.Conclusions:Variants of 16 typical dopaminergic transcription factors might not be major genetic risk factors for PD in Chinese patients.However,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

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ZYX promotes invasion and metastasis of gastric cancer cells via WNK1/SNAI1axis

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Genes & Diseases 2024年第2期11卷 564-567页

作者： Yi Jiang Dongfang Xiang Xianmei Wen Mingmin He yan Qin Xiaoxue Yao Zexuan yan Xiuli Geng Yong Ren Xiongwei Cai Youhong Cui yan Wang Institute of Pathology and Southwest Cancer Center Southwest HospitalArmy Medical University (Third Military Medical University)Chongqing 400038China Department of Pathology General Hospital of Central Theater Command of PLAWuhanHubei 430070China Department of Obstetrics and Gynecology Southwest HospitalArmy Medical University (Third Military Medical University)Chongqing 400038China Department of Pharmacy The Hospital of 83rd Group of PLAXinxiangHenan 453000China Department of Gynecology Chongqing Health Center for Women and ChildrenWomen and Children's Hospital of Chongqing Medical UniversityChongqing 400013China

Gastric cancer(GC)is the third most common cause of cancer death globally and a large portion of patients are diagnosed at advanced stages with cancer invasion and metastasis1,2.However,the mechanisms underlying the invasion and metastasis of GC remain to be delineated.ZYX plays critical roles in cell mobility via cytoskeleton regulation in various cell types.3 In this study,we further reported that ZYX promoted migration,invasion,and metastasis of GC cells.Mechanistically,ZYX promoted WNK1 activation and SNAl1 up-regulation,inducing epithelial-mesenchymal transition(EMT)to enhance the mobility of GC cells.Inhibition of WNK1 impaired the mobility of GC cells.Therefore,ZYX/WNK1 could be potential therapeutic targets for GC treatment.

关键词： WNK1 invasion metastasis

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Rare TBK1 variants in patients with frontotemporal dementia and amyotrophic lateral sclerosis in a Chinese cohort

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Translational Neurodegeneration 2018年第1期7卷 346-351页

作者： Bin Jiao Qiying Sun Zhenhua Yuan Junling Wang Lin Zhou xinxiang yan Beisha Tang Lu Shen Department of Neurology Xiangya HospitalCentral South University87 Xiangya RdChangsha 410008China National Clinical Research Center for Geriatric Disorders Central South UniversityChangshaChina Key Laboratory of Hunan Province in Neurodegenerative Disorders Central South UniversityChangshaChina Department of Geriatrics Neurology Xiangya HospitalCentral South UniversityChangshaChina Parkinson’s Disease Center of Beijing Institute for Brain Disorders BeijingChina Collaborative Innovation Center for Brain Science ShanghaiChina Collaborative Innovation Center for Genetics and Development ShanghaiChina Key Laboratory of Organ Injury Aging and Regenerative Medicine of Hunan ProvinceChangshaChina

Background:The TANK-Binding Kinase 1(TBK1)gene has recently been identified as the third or fourth most frequent cause of frontotemporal dementia(FTD)and amyotrophic lateral sclerosis(ALS).The aim of this study was to assess the genetic contribution of TBK1 in a Chinese cohort.Methods:A total of 270 cases with ALS,FTD,or their combination were recruited into this study.All the coding exons of TBK1 and intron-exon boundaries were sequenced using Sanger sequencing.The frequency of TBK1 variants and the correlation with clinical phenotypes were analyzed.Results:A novel mutation(c.1959_1960insGT,p.E653fs)was identified in a sporadic case with semantic dementia,secondarily developing ALS.Another novel variant(c.2063_2064delTT,p.L688Rfs*14)was found in an ALS-FTD family.Totally,the TBK1 variants could only account for 0.7% of cases.Conclusions:This study enlarges the genetic and phenotypic spectrum of TBK1 mutation in a Chinese cohort.Our data indicates that TBK1 mutation is not a common cause for ALS and FTD in Chinese patients.

关键词： Amyotrophic lateral sclerosis Frontotemporal dementia TBK1 gene

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High-throughput fluorescent screening of thioredoxin reductase inhibitors to inhibit Mycobacterium tuberculosis

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Chinese Chemical Letters 2024年第3期35卷 358-362页

作者： Fei yan Xin Zhao Ruibo Li Xiuyan Han Qiulong yan Lei Feng Xiulan Xin Jingnan Cui Xiaochi Ma Second Affiliated Hospital Dalian Medical UniversityDalian 116044China State Key Laboratory of Fine Chemicals Dalian University of TechnologyDalian 116024China Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy Xuzhou Medical UniversityXuzhou 221004China School of Chemistry and Chemical Engineering Henan Normal UniversityXinxiang 453007China College of Bioengineering Beijing PolytechnicBeijing 100029China

Tuberculosis(TB)is a chronic infectious disease,which is caused by the pathogen Mycobacterium tuberculosis(Mtb)and reemerged as a global health risk with a significant proportion of multi-drug resistant and extensively drug resistant TB cases.It is very urgent to find some novel high-confidence drug targets in Mtb for discovering the effective anti-TB agents.Thioredoxin reductase(TrxR)has been identified to be a highly viable target for anti-TB drugs for its important role in protecting the pathogen from thiol-specific oxidizing stress,regulating intracellular dithiol/disulfide homeostasis and DNA replication and repair.In the present work,a near-infrared(NIR)fluorescent probe DDAT was developed for the detection of TrxR activity and used to high-throughput screen the TrxR inhibitors from natural products.Two screened TrxR inhibitors from Sappan Lignum and microbial metabolites that were further used to inhibit Mycobacterium tuberculosis.All the results indicate that DDAT is a practical fluorescent molecular tool for the discovery of potential anti-TB drugs.

关键词： Thioredoxin reductase NIR fluorescent probe Fluorescence imaging High-throughput screening inhibitors Inhibit Mycobacterium tuberculosis

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IRS Assisted UAV Communications against Proactive Eavesdropping in Mobile Edge Computing Networks

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工程与科学中的计算机建模(英文) 2024年第1期138卷 885-902页

作者： Ying Zhang Weiming Niu Leibing yan School of Electronic Information Engineering Henan Institute of TechnologyXinxiang453003China Houde College Henan Institute of TechnologyXinxiang453003China

In this paper,we consider mobile edge computing(MEC)networks against proactive eavesdropping.To maximize the transmission rate,IRS assisted UAV communications are applied.We take the joint design of the trajectory of UAV,the transmitting beamforming of users,and the phase shift matrix of IRS.The original problem is strong non-convex and difficult to solve.We first propose two basic modes of the proactive eavesdropper,and obtain the closed-form solution for the boundary conditions of the two modes.Then we transform the original problem into an equivalent one and propose an alternating optimization(AO)based method to obtain a local optimal solution.The convergence of the algorithm is illustrated by numerical results.Further,we propose a zero forcing(ZF)based method as sub-optimal solution,and the simulation section shows that the proposed two schemes could obtain better performance compared with traditional schemes.

关键词： Mobile edge computing(MEC) unmanned aerial vehicle(UAV) intelligent reflecting surface(IRS) zero forcing(ZF)

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RNA interference blocking the apoptosis in HEK293 cells induced by overexpression of alpha-synuclein

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Neural Regeneration Research 2009年第7期4卷 541-546页

作者： Tao Chen Beisha Tang Xiaoping Liao Guoqiang Wen xinxiang yan Jifeng Guo Yuhu Zhang Feng Ouyang Zhigang Long Li Cao Jing Li Department of Neurology People's Hospital of Hainan Province Haikou 570311 Hainan Province China Department of Neurology Xiangya Hospital Central South University Changsha 410008 Hunan Province China

BACKGROUND： Overexpression of α-synuclein can induce cell apoptosis. RNA interference （RNAi） may block specific gene function and cause gene silencing. OBJECTIVE： To construct a specific and effective RNAi plasmid for the α-synuclein gene and investigate if RNAi can block apoptosis in HEK293 cells, induced by overexpression of wild-type α-synuclein. DESIGN, TIME AND SETTING： A contrast experiment based on genetically engineered cytobiology was performed at the State Key Lab of Medical Genetics of China, Xiangya Medical College of Central South University, between October 2004 and October 2008. MATERIALS： HEK293 cells and pBSHH1 plasmid were provided by the State Key Lab of Medical Genetics of China; OligDNA sequence by Sagon Bioengineering Company, Shanghai; Lipofectamine 2000 by Invitrogen, USA; α-synuclein monoclonal antibody, Hoechst 33258, and MTT by Sigma, USA; Horseradish peroxidase-coupled goat anti-rat IgG by KPL, USA; FACSan flow cytometry by BD, USA. METHODS： Four target sites were used to construct hairpin RNA pBSHH1 vectors - pSYNi-1, pSYNi-2, pSYNi-3 and pSYNi-4 - which were cloned in the pBSHH1 plasmid. HEK293 cells were transfected using Lipofectamine 2000. In addition, a non-transfect group and a negative plasmid transfect group were established. The cultured HEK293 cells were processed as follows： transfection of blank plasmid （blank control group）, transfection of α-synuclein-pEGFP and RNAi negative vector （negative control group）, and transfection of α-synuclein-pEGFP and pSYNi-1 （transfection group）. Cells in all groups were transfected with Lipofectamine 2000 for 48 hours. MAIN OUTCOME MEASURES： Expression of α-synuclein mRNA and protein were detected by RT-PCR and Western blot. Cell morphology was observed under an inverted fluorescence microscope; cell viability was measured using MTT method; and cell apoptosis was determined with Annexin V-PE flow cytometry. RESULTS： α-synuclein mRNA and protein expressions were significantly decreased in the pSYNi-1 group when compared with the

关键词： RNA interference α-synuclein gene apoptosis

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Prenatal diagnosis of spinocerebellar ataxia type 3/Machado-Joseph disease in China's Mainland A case report

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Neural Regeneration Research 2011年第26期6卷 2047-2049页

作者： Lifang Lei Junling Wang Shen Zhang Hong Jiang Lu Shen Qian Xu xinxiang yan Yi Yuan Qian Pan Kun Xia Beisha Tang Department of Neurology Xiangya Hospital Central South University Changsha 410008 Hunan Province China Department of Neurology Xian-gya Third Hospital Central South University -Changsha 410013 Hunan Province China National Laboratory of Medical Genetics of China Changsha 410008 Hunan Province China

Spinocerebellar ataxia type 3/Machado-Joseph disease （SCA3/MJD） is a progressive, currently untreatable and ultimately fatal ataxic disorder that belongs to the group of neurological disorders known as CAG-repeat or polyglutamine diseases. Here, we present the first prenatal diagnosis of SCA3/MJD in China's Mainland in a woman who was known to carry an expanded CAG-trinucleotide repeat in the MJD1 gene. After evaluating motivation and psychological tolerance of the couple, amniocentesis was performed after 14 weeks of gestation. Polymerase chain reactions followed by T-vector cloning and direct sequencing were employed to evaluate the CAG-repeat number of the fetal MJD1 gene. We identified a truncated CAG expansion of 78 repeats in the MJD1 gene of the fetus compared with 81 repeats in his mother.

关键词： prenatal diagnosis spinocerebellar ataxia type 3/Machado-Joseph disease CAG-trinucleotide repeats genetic counseling

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Amlodipine inhibits the proliferation and migration of esophageal carcinoma cells through the induction of endoplasmic reticulum stress

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World Journal of Gastroenterology 2024年第4期30卷 367-380页

作者： yan-Min Chen Wen-Qian yang Cheng-Wei Gu Ying-Ying Fan Yu-Zhen Liu Bao-Sheng Zhao Department of Thoracic Surgery The First Affiliated Hospital of Xinxiang Medical UniversityWeihui 453100Henan ProvinceChina Department of Oncology The Affiliated HospitalHenan Polytechnic UniversityJiaozuo 454000Henan ProvinceChina Life Science Research Center The First Affiliated Hospital of Xinxiang Medical UniversityWeihui 453100Henan ProvinceChina Department of Gastroenterology The First Affiliated Hospital of Xinxiang Medical UniversityWeihui 453100Henan ProvinceChina

BACKGROUND L-type calcium channels are the only protein channels sensitive to calcium channel blockers,and are expressed in various cancer types.The Cancer Genome Atlas database shows that the mRNA levels of multiple L-type calcium channel subunits in esophageal squamous cell carcinoma tumor tissue are significantly higher than those in normal esophageal epithelial tissue.Therefore,we hypothesized that amlodipine,a long-acting dihydropyridine L-type calcium channel blocker,may inhibit the occurrence and development of esophageal cancer(EC).AIM To investigate the inhibitory effects of amlodipine on EC through endoplasmic reticulum(ER)stress.METHODS Cav1.3 protein expression levels in 50 pairs of EC tissues and corresponding paracancerous tissues were examined.Subsequently,the inhibitory effects of amlodipine on proliferation and migration of EC cells in vitro were detected using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide and Transwell assays.In vivo experiments were performed using murine xenograft model.To elucidate the underlying mechanisms,in vitro cell studies were performed to confirm that ER stress plays a role in inhibition proliferation and migration of EC cells treated with amlodipine.RESULTS The expression level of Cav1.3 in esophageal carcinoma was 1.6 times higher than that in paracancerous tissues.Amlodipine treatment decreased the viability of esophageal carcinoma cells in a dose-and time-dependent manner.In vivo animal experiments also clearly indicated that amlodipine inhibited the growth of EC tumors in mice.Additionally,amlodipine reduces the migration of tumor cells by inhibiting epithelial-mesenchymal transition(EMT).Mechanistic studies have demonstrated that amlodipine induces ER stress-mediated apoptosis and suppresses EMT.Moreover,amlodipine-induced autophagy was characterized by an increase in autophagy lysosomes and the accumulation of light chain 3B protein.The combination of amlodipine with the ER stress inhibitor 4-phenylbutyric acid further confirmed the role of

关键词： L-type calcium channel Amlodipine Esophageal cancer Autophagy Endoplasmic reticulum stress

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基于HS-SPME-GC-MS和化学计量学对不同产地红枣香气成分的分析

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食品工业科技 2024年第6期45卷 265-271页

作者：胡航伟张仁堂张楠楠梁辰游新侠孔欣欣朱玲闫信想刘云国郑州科技学院食品科学与工程学院河南郑州450064 山东农业大学食品科学与工程学院山东泰安271018 临沂大学生命科学学院山东临沂276000

为了比较不同产地红枣的挥发性风味特征,采用顶空固相微萃取结合气相色谱质谱技术对5个产地(新郑、灵宝、榆林、和田、德州)枣果的挥发性香气成分进行分析。结果表明:共鉴定出化合物51种,其中,新疆和田大枣中所含挥发性化合物的种类最... 详细信息

为了比较不同产地红枣的挥发性风味特征,采用顶空固相微萃取结合气相色谱质谱技术对5个产地(新郑、灵宝、榆林、和田、德州)枣果的挥发性香气成分进行分析。结果表明:共鉴定出化合物51种,其中,新疆和田大枣中所含挥发性化合物的种类最多。结合多元统计学分析,不同产地红枣的整体挥发性风味物质的差异得以很好区分。在满足预测变量重要性投影>1、P<0.05的条件下,从红枣样品中筛选出13种差异性特征香气物质,包括己酸甲酯、癸酸甲酯、己醛、苯甲醛等,赋予红枣独特的杏仁味、甜味、水果味。本研究结果明确了不同产地红枣香气品质的化学物质基础,为红枣产地溯源研究提供一种新思路,进一步对枣果资源的合理加工利用提供科学依据。

关键词：红枣化学计量学固相微萃取风味物质地理来源

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地铁杂散电流对变压器直流偏磁的影响分析

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电力科学与技术学报 2024年第1期39卷 134-143页

作者：周展帆严宇于艺盛倪砚茹程新翔喻锟曾祥君唐雨杭国网湖南省电力有限公司超高压变电公司湖南长沙410004 变电智能运检国网湖南省电力有限公司实验室湖南长沙410004 长沙理工大学电气与信息工程学院湖南长沙410114

地铁运行过程中泄漏的杂散电流引起地电位波动变化,易导致附近接地变压器出现直流偏磁现象。为解决此类问题,首先,建立了地铁运行等值电阻网络模型,实现杂散电流实时数值计算;然后,进一步推导了杂散电流场位方程,实现地铁机车运行时附... 详细信息

地铁运行过程中泄漏的杂散电流引起地电位波动变化,易导致附近接地变压器出现直流偏磁现象。为解决此类问题,首先,建立了地铁运行等值电阻网络模型,实现杂散电流实时数值计算;然后,进一步推导了杂散电流场位方程,实现地铁机车运行时附近大地电位空间分布的动态模拟;最后,基于杂散电流引起的大地电位分布结果与交流电网的等效直流电阻模型,实现接地变压器偏磁直流和励磁电流的数值计算,建立中性点直流量和波形畸变率偏移度评判指标,可有效评估变压器直流偏磁程度。仿真结果表明,机车运行工况及机车间距对变压器直流偏磁影响明显,制定合理的地铁运行策略可有效削弱附近变电站直流偏磁干扰。

关键词：地铁杂散电流地表电位变压器直流偏磁变压器中性点电流

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