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Identification of de novo Mutations in the Chinese Autism Spectrum Disorder Cohort via Whole-Exome Sequencing Unveils Brain Regions Implicated in Autism

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Neuroscience Bulletin 2023年第10期39卷 1469-1480页

作者： Bo Yuan Mengdi Wang Xinran wu Peipei Cheng Ran Zhang Ran Zhang Shunying Yu Jie Zhang Yasong Du xiaoqun Wang Zilong Qiu Songjiang Research Institute Songjiang HospitalShanghai Jiao Tong University School of MedicineShanghai 201600China Shanghai Mental Health Center Shanghai Jiao Tong University School of MedicineShanghai 200032China Institute of Neuroscience State Key Laboratory of NeuroscienceCAS Center for Excellence in Brain Science and Intelligence TechnologyShanghai Center for Brain Science and Brain-Inspired Intelligence TechnologyChinese Academy of SciencesShanghai 200032China Beijing Normal University Beijing 100875China Institute of Biophysics Chinese Academy of SciencesBeijing 100101China Institute of Science and Technology for Brain-Inspired Intelligence Fudan UniversityShanghai 200433China

Autism spectrum disorder(ASD)is a highly heritable neurodevelopmental disorder characterized by deficits in social interactions and repetitive *** hundreds of ASD risk genes,implicated in synaptic formation and transcriptional regulation,have been identified through human genetic studies,the East Asian ASD cohorts are still under-represented in genome-wide genetic ***,we applied whole-exome sequencing to 369 ASD trios including probands and unaffected parents of Chinese *** a joint-calling analytical pipeline based on GATK toolkits,we identified numerous de novo mutations including 55 high-impact variants and 165 moderate-impact variants,as well as de novo copy number variations containing known ASD-related ***,combined with single-cell sequencing data from the developing human brain,we found that the expression of genes with de novo mutations was specifically enriched in the pre-,post-central gyrus(PRC,PC)and banks of the superior temporal(BST)regions in the human *** further analyzing the brain imaging data with ASD and healthy controls,we found that the gray volume of the right BST in ASD patients was significantly decreased compared to healthy controls,suggesting the potential structural deficits associated with ***,we found a decrease in the seed-based functional connectivity between BST/PC/PRC and sensory areas,the insula,as well as the frontal lobes in ASD *** work indicated that combinatorial analysis with genome-wide screening,single-cell sequencing,and brain imaging data reveal the brain regions contributing to the etiology of ASD.

关键词： Autism Cohorts Whole-exome sequencing Single-cell sequencing

新阶段烟台市提升水生生物资源养护能力的思考

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渔业信息与战略 2024年第1期39卷 16-21页

作者：许丰杰吴红伟褚洪永周广军于炳礼周晓群烟台市海洋经济研究院山东烟台264003

水生生物资源养护工作是一项复杂的系统工程。多年来,烟台市坚持问题导向、系统治理,深入推进海岸带生态环境综合治理,持续加强水生生物增殖放流和海洋牧场建设,水生生物资源养护稳步发展、成效显著。但受人为开发活动、社会生产力水平... 详细信息

水生生物资源养护工作是一项复杂的系统工程。多年来,烟台市坚持问题导向、系统治理,深入推进海岸带生态环境综合治理,持续加强水生生物增殖放流和海洋牧场建设,水生生物资源养护稳步发展、成效显著。但受人为开发活动、社会生产力水平以及人们思想观念等因素影响,水生生物资源养护在科学性、全面性、系统性发展道路上仍有许多问题与不足,一定程度上阻碍了其健康可持续发展。立足新发展阶段,围绕新时代水生生物资源养护发展目标,系统分析烟台市水生生物资源养护现状及存在的主要问题,提出完善制度体系、应对气候变化、开展资源和生态环境保护、加强基础研究和开展宣传教育等意见措施,以期提升水生生物资源养护能力,推动海洋生态文明建设和海洋事业健康可持续发展。

关键词：水生生物资源养护生态环境保护增殖放流海洋牧场烟台市

Single-nucleus transcriptomic profiling of multiple organs in a rhesus macaque model of SARS-CoV-2 infection

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Zoological Research 2022年第6期43卷 1041-1062页

作者： Qiang Ma Wenji Ma Tian-Zhang Song Zhaobo wu Zeyuan Liu Zhenxiang Hu Jian-Bao Han Ling Xu Bo Zeng Bosong Wang Yinuo Sun Dan-Dan Yu Qian wu Yong-Gang Yao Yong-Tang Zheng xiaoqun Wang State Key Laboratory of Brain and Cognitive Science Institute of BiophysicsChinese Academy of SciencesBeijing 100101China University of Chinese Academy of Sciences Beijing 100049China Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common DiseasesKunming Institute of ZoologyChinese Academy of SciencesKunmingYunnan 650223China Kunming National High-Level Biosafety Research Center for Non-Human Primates Center for Biosafety Mega-ScienceKunming Institute of ZoologyChinese Academy of SciencesKunmingYunnan 650107China National Resource Center for Non-Human Primates National Research Facility for Phenotypic&Genetic Analysis of Model Animals(Primate Facility)Kunming Institute of ZoologyChinese Academy of SciencesKunmingYunnan 650107China LivzonBio Inc.ZhuhaiGuangdong 519045China State Key Laboratory of Cognitive Neuroscience and Learning Beijing Normal UniversityBeijing 100875China IDG/McGovern Institute for Brain Research Beijing Normal UniversityBeijing 100875China Advanced Innovation Center for Human Brain Protection Beijing Institute for Brain DisordersCapital Medical UniversityBeijing 100069China

Infection with severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) causes diverse clinical manifestations and tissue injuries in multiple ***, cellular and molecular understanding of SARS-CoV-2 infection-associated pathology and immune defense features in different organs remains incomplete. Here, we profiled approximately 77 000single-nucleus transcriptomes of the lung, liver,kidney, and cerebral cortex in rhesus macaques(Macaca mulatta) infected with SARS-CoV-2 and healthy controls. Integrated analysis of the multiorgan dataset suggested that the liver harbored the strongest global transcriptional alterations. We observed prominent impairment in lung epithelial cells, especially in AT2 and ciliated cells, and evident signs of fibrosis in fibroblasts. These lung injury characteristics are similar to those reported in patients with coronavirus disease 2019(COVID-19).Furthermore, we found suppressed MHC class I/II molecular activity in the lung, inflammatory response in the liver, and activation of the kynurenine pathway,which induced the development of an immunosuppressive microenvironment. Analysis of the kidney dataset highlighted tropism of tubule cells to SARS-CoV-2, and we found membranous nephropathy(an autoimmune disease) caused by podocyte dysregulation. In addition, we identified the pathological states of astrocytes and oligodendrocytes in the cerebral cortex, providing molecular insights into COVID-19-related neurological implications. Overall, our multi-organ single-nucleus transcriptomic survey of SARS-CoV-2-infected rhesus macaques broadens our understanding of disease features and antiviral immune defects caused by SARS-CoV-2 infection,which may facilitate the development of therapeutic interventions for COVID-19.

关键词： SARS-CoV-2 Rhesus macaque Animal model Single-nucleus RNA sequencing Antiviral immune defects Multiple organs

Ferrodifferentiation regulates neurodevelopment via ROS generation

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Science China(Life Sciences) 2023年第8期66卷 1841-1857页

作者： Shiyang Chang Peina Wang Yingying Han Qiang Ma Zeyuan Liu Suijuan Zhong Yufeng Lu Ruiguo Chen Le Sun Qian wu Guofen Gao xiaoqun Wang Yan-Zhong Chang Laboratory of Molecular Iron Metabolism Ministry of Education Key Laboratory of Molecular and Cellular BiologyHebei Key Laboratory of Animal PhysiologyBiochemistryand Molecular BiologyCollege of Life SciencesHebei Normal UniversityShijiazhuang 050024China College of Basic Medicine Hebei Medical UniversityShijiazhuang 050017China State Key Laboratory of Brain and Cognitive Science CAS Center for Excellence in Brain Science and Intelligence Technology(Shanghai)Institute of BiophysicsChinese Academy of Sciences(CAS)BNU IDG/McGovern Institute for Brain ResearchBeijing 100101China State Key Laboratory of Cognitive Neuroscience and Learning Beijing Normal UniversityBeijing 100875China Beijing Institute of Brain Disorders Laboratory of Brain DisordersMinistry of Science and TechnologyCollaborative Innovation Center for Brain DisordersCapital Medical UniversityBeijing 100069China

Iron is important for life,and iron deficiency impairs development,but whether the iron level regulates neural differentiation remains *** this study,with iron-regulatory proteins(IRPs)knockout embryonic stem cells(ESCs)that showed severe iron deficiency,we found that the Pax6-and Sox2-positive neuronal precursor cells and Tuj1 fibers in IRP1^(-/-)IRP2^(-/-)ESCs were significantly decreased after inducing neural ***,in vivo study showed that the knockdown of IRP1 in IRP2^(-/-)fetal mice remarkably affected the differentiation of neuronal precursors and the migration of *** findings suggest that low intracellular iron status significantly inhibits *** supplementing IRP1^(-/-)IRP2^(-/-)ESCs with iron,these ESCs could differentiate *** investigations revealed that the underlying mechanism was associated with an increase in reactive oxygen species(ROS)production caused by the substantially low level of iron and the downregulation of iron-sulfur cluster protein ISCU,which,in turn,affected the proliferation and differentiation of stem ***,the appropriate amount of iron is crucial for maintaining normal neural differentiation that is termed ferrodifferentiation.

关键词： IRPs ESCs iron differentiation neurodevelopment ROS

Neural stem cell and neurogenesis in mammalian brain

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Neural stem cell and neurogenesis in mammalian brain

中国神经科学学会第十届全国学术会议

作者： Qian wu Bai YE xiaoqun WANG Institute of Bipphysics Chinese Academic of Science

One of the most remarkable features in the evolution of the neocortex is the enormous increase in neuron number and the transformation of the lissencephalic cortex into the highly folded gyrencephalic cortex characteristic of *** development,this is established by the type of progenitor cells present in embryonic brain and in the number of neurogenic divisions they *** studies have shown that radial glial（RG） cells function as primary progemtors or neuronal stem cells（NSCs）.RG cells generate intermediate progenitor（IP） cells that migrate to the subventricular zone（SVZ） where they proliferate to increase neuron number in developing rodent *** the primate brain,the outer region of the SVZ（OSVZ） is massively *** recent studies revealed a new class of radial glia- like cells referred to as oRG（OSVZ radial glia） cells with characteristic monopolar morphology that populate the ***-lapse imaging reveals that the cells undergo self-renewing asymmetric divisions to generate neurons.

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构建外科同质化教学和考核体系的探索

中国继续医学教育 2024年第11期16卷 170-173页

作者：李明哲任晖胡雪延陈景耀王小群李剑锋吴文辉中山大学附属第七医院消化医学中心广东深圳518107

近年来,新建教学医院不断增加,医学生队伍也逐年增多。随着“新医科”教学理念的不断更新,新建医院临床教学面临巨大压力和挑战,尤其是外科临床教学常面临同质化不足的问题,这与师资团队的教育背景、教学经验等多方面因素有关。为解决... 详细信息

近年来,新建教学医院不断增加,医学生队伍也逐年增多。随着“新医科”教学理念的不断更新,新建医院临床教学面临巨大压力和挑战,尤其是外科临床教学常面临同质化不足的问题,这与师资团队的教育背景、教学经验等多方面因素有关。为解决外科临床教学师资同质化不足的问题,提升本科生教学质量,文章探索了构建外科同质化教学和考核体系的关键要素,搭建了外科学同质化教学平台,建立了同质化教学管理制度和教学评价体系,以外科学同质化教学平台为依托,建设了一支同质化外科带教师资队伍,进一步规范和完善了外科临床教学,提高了学校医学人才培养质量,为医学本科生“同质化”临床教学打下了坚实基础。

关键词：外科学临床教学同质化考核体系医学教育教学体系

Risk Assessment and Zoning of Winter Wheat Drought in Anhui Province

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Meteorological and Environmental Research 2013年第12期4卷 33-38页

作者： xiaoqun Ma Hongqun Zhang Xiaoyi Chen Wenyu wu Ying Xu Long Li Anhui Meteorological Institute /Anhui Key Laboratory of Atmospheric Science and Satellite Remote Sensing Xuancheng Meteorological Bureau

[Objective]The study aimed to assess and zone the drought risk of winter wheat in Anhui Province. [Method] The zoning factors were chosen from three aspects of disaster-causing factors,disaster-bearing bodies and environment conducive to drought,and then their data were standardized,rasterized and graded. Using analytic hierarchy process（ AHP）,we determined the weight of each index at various levels and then established the assessment models of drought intensity,sensitivity,vulnerability and resistance of winter wheat in the whole growth period and at heading and filling stage. Finally,the zoning map of drought risk for winter wheat in Anhui Province was obtained using the farmland data mask of Anhui Province. [Result]The drought risk of winter wheat in Anhui Province in the whole growth period and at heading and filling stage was divided into six grades,which reflected the distribution characteristics and regional difference of drought risk for winter wheat in Anhui Province. Drought risk was the maximum in the main producing areas of winter wheat in the north of Huaihe River,followed by the area along Huaihe River and the area between Yangtze River and Huaihe River,while the drought risk of winter wheat was very low in the south of Anhui Province. The drought risk of winter wheat was markedly affected by the sensitivity to drought,vulnerability and the drought resistance of winter wheat. [Conclusion] The research could provide scientific references for rational distribution of winter wheat and establishment of strategies for disaster prevention and mitigation.

关键词： Winter wheat Drought risk Sensitivity Vulnerability Disaster resistance Zoning China

NEURAL STEM CELL AND NEUROGENESIS IN THE EMBRYONIC NEOCORTEX

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NEURAL STEM CELL AND NEUROGENESIS IN THE EMBRYONIC NEOCORTEX

第二届全国发育生物学大会

作者： Rui Li Qian wu Le Sun xiaoqun Wang Institute of Biophysics Chinese Academic of Science

A hallmark of mammalian brain evolution is cortical expansion,which reflects an increase in the number of cortical *** development,this is established by the type of progenitor cells present in embryonic brain and in the number of neurogenic divisions they *** cells generate intermediate progenitor(IP)cells that migrate to the subventricular zone(SVZ)where they proliferate to increase neuron number in developing rodent *** the primate brain,the outer region of the SVZ(OSVZ)is massively *** studies revealed a new

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大跨度钢斜拉桥施工过程线形控制

同济大学学报（自然科学版） 2012年第9期40卷 1281-1286页

作者：吴杰罗晓群张其林同济大学土木工程学院上海200092

运用几何非线性分析理论,综合考虑斜拉索垂度效应、梁柱效应和大位移效应,对大跨钢斜拉桥施工过程线形控制进行数值模拟研究.采用多段短索桁架单元模拟长索的非线性效应,通过改变单元的无应力长度实现索的多次张拉.根据新增构件的不同... 详细信息

运用几何非线性分析理论,综合考虑斜拉索垂度效应、梁柱效应和大位移效应,对大跨钢斜拉桥施工过程线形控制进行数值模拟研究.采用多段短索桁架单元模拟长索的非线性效应,通过改变单元的无应力长度实现索的多次张拉.根据新增构件的不同激活方式,提出将施工过程模型分为切线安装、平行安装和建模位置安装3类,其中切线安装和平行安装用于施工过程分析,建模位置安装用于施工控制中的反拱分析.考虑几何非线性多次迭代计算安装线形,采用稀疏矩阵算法求解有限元方程.基于以上原理编制了大跨钢斜拉桥非线性分析及施工过程线形控制模拟软件BINAS,通过苏通大桥实例验证了该方法具有较好的计算精度和适用性.

关键词：斜拉桥线形控制施工过程几何非线性效应