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RhoGEF Trio Regulates Radial Migration of Projection Neurons via Its Distinct Domains

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Neuroscience Bulletin 2022年第3期38卷 249-262页

作者： Chengwen Wei Mengwen Sun Xiaoxuan Sun Hu Meng Qiongwei Li Kai Gao weihua yue Lifang Wang Dai Zhang Jun Li Peking University Sixth Hospital Peking University Institute of Mental HealthNHC Key Laboratory of Mental Health(Peking University)National Clinical Research Center for Mental Disorders(Peking University Sixth Hospital)Beijing100191China Peking-Tsinghua Center for Life Sciences Peking UniversityBeijing100871China PKU-IDG/McGovern Institute for Brain Research Peking UniversityBeijing100871China Chinese Institute for Brain Research Beijing100010China Institute for Brain Research and Rehabilitation(IBRR) Guangdong Key Laboratory of Mental Health and Cognitive ScienceSouth China Normal UniversityGuangzhou510631China

The radial migration of cortical pyramidal neurons(PNs)during corticogenesis is necessary for establishing a multilayered cerebral cortex.Neuronal migration defects are considered a critical etiology of neurodevelopmental disorders,including autism spectrum disorders(ASDs),schizophrenia,epilepsy,and intellectual disability(ID).TRIO is a high-risk candidate gene for ASDs and ID.However,its role in embryonic radial migration and the etiology of ASDs and ID are not fully understood.In this study,we found that the in vivo conditional knockout or in utero knockout of Trio in excitatory precursors in the neocortex caused aberrant polarity and halted the migration of late-born PNs.Further investigation of the underlying mechanism revealed that the interaction of the Trio N-terminal SH3 domain with Myosin X mediated the adherence of migrating neurons to radial glial fibers through regulating the membrane location of neuronal cadherin(N-cadherin).Also,independent or synergistic overexpression of RAC1 and RHOA showed different phenotypic recoveries of the abnormal neuronal migration by affecting the morphological transition and/or the glial fiber-dependent locomotion.Taken together,our findings clarify a novel mechanism of Trio in regulating N-cadherin cell surface expression via the interaction of Myosin X with its N-terminal SH3 domain.These results suggest the vital roles of the guanine nucleotide exchange factor 1(GEF1)and GEF2 domains in regulating radial migration by activating their Rho GTPase effectors in both distinct and cooperative manners,which might be associated with the abnormal phenotypes in neurodevelopmental disorders.

关键词： Trio Myosin X RhoGEF Neurodevelopmental disorder Radial migration

Fabrication of a High-Performance and Reusable Planar Face Mask in Response to the COVID-19 Pandemic

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Engineering 2022年第2期8卷 101-110页

作者： Shui Hu Hongchi Tian Shijia Zhang Dan Wang Guozhuo Gong weihua yue Keyang Liu Song Hong Rui Wang Qingqing Yuan Yonglai Lu Dong Wang Liqun Zhang Jianfeng Chen State Key Laboratory of Organic–Inorganic Composites Beijing University of Chemical TechnologyBeijing 100029China Dawn Polymer(Beijing)Technology Co. Ltd.Beijing 101599China Beijing Municipal Institute of Labor Protection Beijing 100054China Beijing Institute of Medical Device Testing Beijing 101111China School of Materials Design and Engineering Beijing Institute of Fashion TechnologyBeijing 100029China

The coronavirus disease 2019(COVID-19)pandemic has caused a surge in demand for face masks,with the massive consumption of masks leading to an increase in resource-related and environmental con-cerns.In this work,we fabricated meltblown polypropylene(mb-PP)-based high-performance planar face masks and investigated the effects of six commonly used disinfection methods and various mask-wearing periods on the reusability of these masks.The results show that,after three cycles of treatment using hot water at 70℃ for 30 min,which is one of the most scalable,user-friendly methods for viral disinfection,the particle filtration efficiency(PFE)of the mask remained almost unchanged.After mask wearing for 24 h and subsequent disinfection using the same treatment procedures,the PFE decreased to 91.3%;the average number of bacterial and fungal colonies was assessed to be 9.2 and 51.6 colony-forming units per gram(CFU∙g^(-1)),respectively;and coliform and pyogenic bacteria were not detected.Both the PFE and the microbial indicators are well above the standard for reusable masks after disinfection.Schlieren pho-tography was then used to assess the capabilities of used and disinfected masks during use;it showed that the masks exhibit a high performance in suppressing the spread of breathed air.

关键词： Mask Reusable Particle filtration efficiency Disinfection Schlieren photography

The Human MSI2 Gene is Associated with Schizophrenia in the Chinese Han Population

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Neuroscience Bulletin 2016年第3期32卷 239-245页

作者： Zhilin Luan Tianlan Lu Yanyan Ruan weihua yue Dai Zhang Advanced Institute for Medical Sciences Dalian Medical University The Sixth Hospital and Institute of Mental Health Peking University Key Laboratory of Mental Health Ministry of Health and National Clinical Research Center for Mental Disorders (Peking University)

It has been suggested that altered neurogenesis may be involved in the etiology of schizophrenia,so genes impacting on neurogenesis could be potential candidates for schizophrenia.A member of the Musashi family,the human MSI2 gene plays a substantial role in stem-cell maintenance,asymmetric division,and differentiation during neurogenesis.Our previous genome-wide association study（GWAS）implied an association of MSI2 with schizophrenia in a Han Chinese population.To further explore this association,three single-nucleotide polymorphisms（SNPs）,rs9892791,rs11657292,and rs1822381,were selected for a replication study involving 921 schizophrenia cases and 1244 controls.After rigorous Bonferroni correction,two of the SNPs（rs9892791 and rs11657292） displayed significant differences in allele and genotype distribution frequencies between the case and control groups.When our GWAS and replication samples were combined,the three MSI2 SNPs were all strongly associated with schizophrenia（rs9892791：allelic P = 1.07E-5;rs11657292：allelic P = 1.95E-12;rs1822381：allelic P = 1.44E-4）.These results indicate that the human MSI2 gene might be a susceptibility gene forschizophrenia and encourage future research on the functional relationship between this gene and schizophrenia.

关键词： Schizophrenia Neurogenesis Single-nucleotide polymorphism Musashi - MSI2

Abnormal Rich-Club Organization Associated with Compromised Cognitive Function in Patients with Schizophrenia and Their Unaffected Parents

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Neuroscience Bulletin 2017年第4期33卷 445-454页

作者： Xin Zhao Lin Tian Jun Yan weihua yue Hao Yan Dai Zhang Institute of Mental Health Peking University Sixth HospitalBeijing 100191China National Clinical Research Center for Mental Disorders andKey Laboratory of Mental Health(Ministry of Health) Peking UniversityBeijing 100191China Department of Psychiatry Wuxi Mental Health CenterNanjing Medical UniversityWuxi 214151China Wuxi Tongren International Rehabilitation Hospital Wuxi 214151China Peking University-Tsinghua University Joint Center for Life Sciences/PKU-IDG/McGovern Institute for Brain Research Peking UniversityBeijing 100871China

Schizophrenia is considered to be a disorder of brain connectivity, which might result from a disproportionally impaired rich-club organization. The rich-club is composed of highly interconnected hub regions that play crucial roles in integrating information between different brain regions. Few studies have yet investigated whether the structural rich-club organization is impaired in patients and their first-degree relatives. In this study, we established a weighted network model of white matter connections using diffusion tensor imaging of 19 patients and 39 unaffected parents, 22 young healthy controls for the patients, and 25 old healthy controls for the parents. Feeder edges between rich-club nodes and non-rich-club nodes were significantly decreased in both schizophrenic patients and their unaffected parents compared with controls.Furthermore, the feeder edges showed significant positive correlations with the scores in Category Fluency Test—animal naming in the unaffected parents. Specific feeder edges exhibited discriminative power with accuracy of 84.4% in distinguishing unaffected parents from old healthy controls. Our findings suggest that impaired richclub organization, especially impaired feeder edges, may be related to familial vulnerability to schizophrenia,possibly reflecting a genetic predisposition for schizophrenia.

关键词： Structural brain network Diffusion tensor imaging Rich-club Familial vulnerability Schizophrenia

P-Rex1 Overexpression Results in Aberrant Neuronal Polarity and Psychosis-Related Behaviors

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Neuroscience Bulletin 2019年第6期35卷 1011-1023页

作者： Qiongwei Li Lifang Wang Yuanlin Ma weihua yue Dai Zhang Jun Li Peking University Institute of Mental Health Peking University Sixth HospitalBeijing 100191China National Health Center Key Laboratory of Mental Health(Peking University) Beijing 100191China National Clinical Research Center for Mental Disorders Peking University Sixth HospitalBeijing 100191China Peking-Tsinghua Center for Life Sciences Peking UniversityBeijing 100871China PKU-IDG/McGovem Institute for Brain Research Peking UniversityBeijing 100871China

Neuronal polarity is involved in multiple developmental stages, including cortical neuron migration,multipolar-to-bipolar transition, axon initiation, apical/basal dendrite differentiation, and spine formation. All of these processes are associated with the cytoskeleton and are regulated by precise timing and by controlling gene expression. The P-Rex1(phosphatidylinositol-3,4,5-trisphosphate dependent Rac exchange factor 1) gene for example, is known to be important for cytoskeletal reorganization, cell motility, and migration. Deficiency of P-Rex1 protein leads to abnormal neuronal migration and synaptic plasticity, as well as autism-related behaviors.Nonetheless, the effects of P-Rex1 overexpression on neuronal development and higher brain functions remain unclear. In the present study, we explored the effect of P-Rex1 overexpression on cerebral development and psychosis-related behaviors in mice. In utero electroporation at embryonic day 14.5 was used to assess the influence of P-Rex1 overexpression on cell polarity and migration.Primary neuron culture was used to explore the effects of P-Rex1 overexpression on neuritogenesis and spine morphology. In addition, P-Rex1 overexpression in the medial prefrontal cortex(m PFC) of mice was used to assess psychosis-related behaviors. We found that P-Rex1 overexpression led to aberrant polarity and inhibited the multipolar-to-bipolar transition, leading to abnormal neuronal migration. In addition, P-Rex1 overexpression affected the early development of neurons, manifested as abnormal neurite initiation with cytoskeleton change,reduced the axon length and dendritic complexity, and caused excessive lamellipodia in primary neuronal culture.Moreover, P-Rex1 overexpression decreased the density of spines with increased height, width, and head area in vitro and in vivo. Behavioral tests showed that P-Rex1 overexpression in the mouse m PFC caused anxiety-like behaviors and a sensorimotor gating deficit. The appropriate P-Rex1 level plays a critical role in the developing cereb

关键词： P-Rex1 Neurodevelopment Polarity Lamellipodia Psychosis-related behavior

Progressive Grey Matter Volume Changes in Patients with Schizophrenia over 6 Weeks of Antipsychotic Treatment and Their Relationship to Clinical Improvement

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Neuroscience Bulletin 2018年第5期34卷 816-826页

作者： Xiao Zhang Yuyanan Zhang Jinmin Liao Sisi Jiang Jun Yan weihua yue Dai Zhang Hao Yan Peking University Sixth Hospital/Institute of Mental Health Beijing 100191 China Key Laboratory of Mental Health Ministry of Health (Peking University) and National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital) Beijing 100191 China Peking-Tsinghua Joint Center for Life Sciences and PKU IDG/McGovern Institute for Brain Research Peking University Beijing 100871 China

Cross-sectional and longitudinal studies have identified widespread and progressive grey matter volume （GMV） reductions in schizophrenia, especially in the frontal lobe. In this study, we found a progressive GMV decrease in the rostral medial frontal cortex （rMFC, including the anterior cingulate cortex） in the patient group during a 6-week follow-up of 40 patients with schizophrenia and 31 healthy controls well-matched for age, gender, and education. The higher baseline GMV in the rMFC predicted better improvement in the positive score on the Positive and Negative Syndrome Scale （PANSS）, and this might be related to the improved reality-monitoring. Besides, a higher baseline GMV in the posterior rMFC predicted better remission of general symptoms, and a lesser GMV reduction in this region was correlated with better remission of negative symptoms, probably associated with ameliorated self-referential pro- cessing and social cognition. Besides, a shorter disease course and higher educational level contributed to better improvement in the general psychopathological PANSS score, and a family history was negatively associated with improvement of the negative and total PANSS scores. These phenomena might be important for understanding the neuropathological mechanisms underlying the symp- toms of schizophrenia and for making clinical decisions.

关键词： Schizophrenia Grey matter volume Rostral medial frontal cortex Treatment response Biomarker

ZNF804A Variation May Affect Hippocampal-Prefrontal Resting-State Functional Connectivity in Schizophrenic and Healthy Individuals

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Neuroscience Bulletin 2018年第3期34卷 507-516页

作者： Yuyanan Zhang Hao Yan Jinmin Liao Hao Yu Sisi Jiang Qi Liu Dai Zhang weihua yue Institute of Mental Health Peking University Sixth HospitalBeijing 100191 China Key Laboratory of Mental Health Ministry of Health and National Clinical Research Center for Mental Disorders(Peking University) Beijing 100191 China Department of Psychiatry Jining Medical UniversityJining 272067 China Peking-Tsinglaua Joint Center for Life Sciences and PKUIDG/McGovern Institute for Brain Research Peking University Beijing 100871 China

The ZNF804 A variant rs1344706 has consistently been associated with schizophrenia and plays a role in hippocampal-prefrontal functional connectivity during working memory. Whether the effect exists in the resting state and in patients with schizophrenia remains unclear. In this study, we investigated the ZNF804 A polymorphism at rs1344706 in 92 schizophrenic patients and 99 healthy controls of Han Chinese descent, and used resting-state functional magnetic resonance imaging to explore the functional connectivity in the participants. We found a significant main effect of genotype on the resting-state functional connectivity（RSFC） between the hippocampus and the dorsolateral prefrontal cortex（DLPFC） in both schizophrenic patients and healthy controls. The homozygous ZNF804 A rs1344706 genotype（AA） conferred a high risk of schizophrenia, and also exhibited significantly decreased resting functional coupling between the left hippocampus and right DLPFC（F（2,165） = 13.43,P ／ 0.001）. The RSFC strength was also correlated with cognitive performance and the severity of psychosis in schizophrenia. The current findings identified the neural impact of the ZNF804 A rs1344706 on hippocampalprefrontal RSFC associated with schizophrenia.

关键词： Schizophrenia ZNF804A Imaging genetics Hippocampus Dorsolateral prefrontal cortex

Compromised small-world efficiency of structural brain networks in schizophrenic patients and their unaffected parents

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Neuroscience Bulletin 2015年第3期31卷 275-287页

作者： Hao Yan Lin Tian Qifeng Wang Qiang Zhao weihua yue Jun Yan Bing Liu Dai Zhang Peking University Six Hospital Peking University Institute of Mental Health Key Laboratory of Mental Health Ministry of Health (Peking University) LIAMA Center for Computational Medicine National Laboratory of Pattern Recognition Institute of Automation Chinese Academy of Sciences Department of Radiology The Third Hospital Peking University Peking-Tsinghua Center for Life Sciences PKU-IDG/Mc Govern Institute for Brain Research Peking University

Several lines of evidence suggest that efficient information integration between brain regions is disrupted in schizophrenia. Abnormalities in white matter tracts that interconnect brain regions may be directly relevant to this pathophysiological process. As a complex mental disorder with high heritability, mapping abnormalities in patients and their first- degree relatives may help to disentangle the risk factors for schizophrenia. We established a weighted network model of white matter connections using diffusion tensor imaging in 25 nuclear families with schizophrenic probands （19 patients and 41 unaffected parents） and two unrelated groups of normal controls （24 controls matched with patients and 26 controls matched with relatives）. The patient group showed lower global efficiency and local efficiency. The decreased regional efficiency was localized in hubs such as the bilateral frontal cortices, bilateral anterior cingulate cortices, and left precuneus. The global efficiency was negatively correlated with cognition scores derived from a 5-factor model of schizophrenic psychopathology.We also found that unaffected parents displayed decreased regional efficiency in the right temporal cortices, left supplementary motor area, left superior temporal pole, and left thalamus. The global efficiency tended to be lower in unaffected parents. Our data suggest that （1） the global efficiency loss in neuroanatomical networks may be associated with the cognitive disturbances in schizophrenia; and （2） genetic vulnerability to schizophrenia may influence the anatomical organization of an individual＇s brain networks.

关键词： network analysis diffusion tensorimaging tractography white matter small-worldarchitecture

运动干预对精神分裂症患者辅助治疗有效性和可行性的Meta分析

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中华行为医学与脑科学杂志 2024年第2期33卷 177-185页

作者：郭靖刘克菊廖云丹覃颖岳伟华滨州医学院应用心理学系烟台264009 北京大学深圳医院特诊心理科深圳518036 北京大学第六医院北京大学精神卫生研究所国家精神心理疾病临床医学研究中心(北京大学第六医院)国家卫生健康委员会精神卫生学重点实验室(北京大学)北京100191 贵州省第二人民医院精神科贵阳550000

目的系统评价辅助有氧运动干预在精神分裂症群体中的有效性和可行性。方法检索中国知网、维普、万方、中国生物医学文献数据库、PubMed、Cochrane Library、EMBASE和Web of Science数据库, 建库至2023年3月, 以获取与精神分裂症患者运... 详细信息

目的系统评价辅助有氧运动干预在精神分裂症群体中的有效性和可行性。方法检索中国知网、维普、万方、中国生物医学文献数据库、PubMed、Cochrane Library、EMBASE和Web of Science数据库, 建库至2023年3月, 以获取与精神分裂症患者运动干预相关的随机对照试验。以阳性与阴性症状量表(positive and negative symptom scale, PANSS)及其分量表作为主要结局指标, 阴性症状量表(scale for assessment of negative symptoms, SANS)、体质量指数(body mass index, BMI)等作为次要指标, 采用R 4.1.0和Stata 14.0进行Meta分析。结果共纳入47项研究, 涵盖3 139例精神分裂症患者。基于24项研究的网状Meta分析结果显示, 与其他干预措施相比, 辅助有氧运动干预可能是降低精神分裂症患者PANSS总分最有效的干预措施。与常规治疗相比, 有氧运动辅助治疗可改善患者的PANSS总评分(MD= -5.09, 95%CI:-5.90~-4.28)、SANS评分(MD=-12.17, 95%CI:-14.25~-10.10)以及BMI(MD= -1.59, 95%CI:-1.93~-1.25)。同时, 亚组分析结果显示, 干预持续2个月(MD=-6.12, 95%CI:-7.22~-5.02)和每周运动总时长在140~260 min(MD=-8.59, 95%CI:-12.93~-4.25)的效果更显著。对比试验组和对照组的依从性发现, 有氧运动干预联合常规治疗与单独常规治疗之间差异无统计学意义(P>0.05)。结论有氧运动干预辅助治疗是缓解精神分裂症患者症状的有效措施, 在住院患者中具有较好的依从性。

关键词：有氧运动干预精神分裂症 Meta分析阳性与阴性症状量表阴性症状