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Alzheimer’s disease early diagnostic and staging biomarkers revealed by large-scale cerebrospinal fluid and serum proteomic profiling

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The Innovation 2024年第1期5卷 118-126页

作者： Qing-Qing Tao Xue Cai Yan-Yan Xue Weigang Ge Liang Yue Xiao-Yan Li Rong-Rong Lin Guo-Ping Peng Wenhao Jiang Sainan Li Kun-Mu Zheng Bin Jiang Jian-Ping Jia Tiannan Guo Zhi-Ying Wu Department of Neurology and Research center of Neurology in the Second Affiliated Hospital and Key Laboratory of Medical Neurobiology of Zhejiang Province Zhejiang University School of MedicineHangzhou 310009China Liangzhu Laboratory Zhejiang UniversityHangzhou 311100China Westlake Laboratory of Life sciences and Biomedicine Key Laboratory of Structural Biology of Zhejiang ProvinceSchool of Life SciencesWestlake UniversityHangzhou 310024China Institute of Basic Medical sciences Westlake Institute for Advanced StudyHangzho 310024China Department of Neurology First Affiliated HospitalZhejiang University School of MedicineHangzhou 310009China Department of Neurology First Affiliated HospitalSchool of MedicineXiamen UniversityXiamen 361009China Innovation center for Neurological Disorders and Department of Neurology Xuanwu HospitalCapital Medical UniversityNational Clinical Research Center for Geriatric DiseasesBeijing 100053China MOE Frontier Science center for brain Science and brain-machine Integration School of Brain Science and Brain MedicineZhejiang UniversityHangzhou 310058China CAS center for Excellence in brain Science and Intelligence Technology Shanghai 200031China

Amyloid-b,tau pathology,and biomarkers of neurodegeneration make up the core diagnostic biomarkers of Alzheimer disease(AD).However,these proteins represent only a fraction of the complex biological processes underlying AD,and individuals with other brain diseases in which AD pathology is a comorbidity also test positive for these diagnostic *** ADspecific early diagnostic and disease staging biomarkers are *** this study,we performed tandem mass tag proteomic analysis of paired cerebrospinal fluid(CSF)and serum samples in a discovery cohort comprising 98 *** biomarkers were validated by parallel reaction monitoring–based targeted proteomic assays in an independent multicenter cohort comprising 288 *** quantified 3,238 CSF and 1,702 serum proteins in the discovery cohort,identifying 171 and 860 CSF proteins and 37 and 323 serum proteins as potential early diagnostic and staging biomarkers,*** the validation cohort,58 and 21 CSF proteins,as well as 12 and 18 serum proteins,were verified as early diagnostic and staging biomarkers,*** 19-protein CSF and an 8-protein serum biomarker panels were built by machine learning to accurately classify mild cognitive impairment(MCI)due to AD from normal cognition with areas under the curve of 0.984 and 0.881,*** 19-protein CSF biomarker panel also effectively discriminated patients with MCI due to AD from patients with other neurodegenerative ***,we identified 21 CSF and 18 serum stage-associated proteins re-flecting AD *** findings provide a foundation for developing bloodbased tests for AD screening and staging in clinical practice.

关键词： cerebrospinal Alzheimer fluid

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Association between the frontoparietal network,clinical symptoms and treatment response in individuals with untreated anorexia nervosa

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General Psychiatry 2024年第3期37卷 364-374页

作者： Qianqian He Hui Zheng Jialin Zhang Ling Yue Qing Kang Cheng Lian Lei Guo Yan Chen Yanran Hu Yuping Wang Sufang Peng Zhen Wang Qiang Liu Jue Chen Department of Clinical Psychology Shanghai Mental Health CenterShanghai Jiao Tong University School of MedicineShanghaiChina Department of Clinical Psychology Shanghai Pudong New Area Mental Health CenterTongji University School of MedicineShanghaiChina Shanghai Key Laboratory of Psychotic Disorders Brain Health InstituteNational Center for Mental DisordersShanghai Mental Health CenterShanghai Jiao Tong University School of MedicineShanghaiChina State Key Laboratory of cognitive Neuroscience and Learning and IDG/McGovern Institute for brain Research Bejing Normal UniversityBeijingChina

Background Anorexia nervosa(AN)has been characterised as a psychiatric disorder associated with increased ***,it remains difficult to predict treatment response in patients with *** cognitive abilities are known to be resistant to *** has been established that the frontoparietal control network(FPCN)is the direct counterpart of the executive control ***,the resting-state brain activity of the FPCN may serve as a biomarker to predict treatment response in *** The study aimed to investigate the association between resting-state functional connectivity(RSFC)of the FPCN,clinical symptoms and treatment response in patients with *** In this case-control study,79 female patients with AN and no prior treatment from the Shanghai Mental Health center and 40 matched healthy controls(HCs)were recruited from January 2015 to March *** participants completed the Questionnaire Versionof the Eating Disorder Examination(version 6.0)to assess the severity of their eating disorder ***,RSFC data were obtained from all participants at baseline by functional magnetic resonance *** with AN underwent routine outpatient treatment at the 4th and 12th week,during which time their clinical symptoms were evaluated using the same measures as at *** Among the 79 patients,40 completed the 4-week follow-up and 35 completed the 12-week *** RSFC from the right posterior parietal cortex(PPC)and dorsolateral prefrontal cortex(diPFC)increased in 79 patients with AN vs 40 HCs after controlling for depression and anxiety *** multiple linear regression,the RSFC of the PPC to the inferior frontal gyrus was found to be a significant factor for self-reported eating disorder symptoms at baseline and the treatment response to cognitive preoccupations about eating and body image,after controlling for age,age of onset and body mass *** RSFC in the dIPFC to the middle temporal gyrus and the

关键词： symptoms routine prevention

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Prediction of cell-cell communication patierns of dorsal root ganglion cells:single-cell RNA sequencing data analysis

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Neural Regeneration Research 2024年第6期19卷 1367-1374页

作者： Yanna Lian Cheng Wu Li Liu Xiangyao Li National Health Commission and Chinese Academy of Medical sciences Key Laboratory of Medical Neurobiology Ministry of Education Frontier Science Center for Brain Research and Brain-Machine IntegrationSchool of Brain Science and Brain MedicineZhejiang UniversityHangzhouZhejiang ProvinceChina International Institutes of Medicine the Fourth Affiliated Hospital of Zhejiang University School of MedicineYiwuZhejiang ProvinceChina Zhejiang University-University of Edinburgh Institute Zhejiang University School of MedicineZhejiang UniversityHainingZhejiang ProvinceChina Biomedical sciences College of Medicine and Veterinary MedicineThe University of EdinburghEdinburghUK Core Facilities of the School of Medicine Zhejiang UniversityHangzhouZhejiang ProvinceChina

Dorsal root ganglion neurons transmit peripheral somatic information to the central nervous system,and dorsal root ganglion neuron excitability affects pain *** root ganglion stimulation is a new approach for managing pain *** of the cell-cell communication among dorsal root ganglion cells may help in the development of new pain and itch management ***,we used the single-cell RNA-sequencing(scRNA-seq)database to investigate intercellular communication networks among dorsal root ganglion *** collected scRNA-seq data from six samples from three studies,yielding data on a total of 17,766 *** on genetic profiles,we identified satellite glial cells,Schwann cells,neurons,vascular endothelial cells,immune cells,fibroblasts,and vascular smooth muscle *** analysis revealed that eight types of dorsal root ganglion neurons mediated proprioceptive,itch,touch,mechanical,heat,and cold ***,we predicted several distinct forms of intercellular communication among dorsal root ganglion cells,including cell-cell contact,secreted signals,extracellular matrix,and neurotransmitter-mediated *** data mining predicted that Mrgpra3-positive neurons robustly express the genes encoding the adenosine Adora2b(A2B)receptor and glial cell line-derived neurotrophic factor family receptor alpha 1(GFRα-1).Our immunohistochemistry results confirmed the coexpression of the A2B receptor and GFRα-*** injection of the A2B receptor antagonist PSB-603 effectively prevented histamine-induced scratching behaviour in a dose-dependent *** results demonstrate the involvement of the A2B receptor in the modulation of itch ***,our findings provide insight into dorsal root ganglion cell-cell communication patterns and *** results should contribute to the development of new strategies for the regulation of dorsal root ganglion excitability.

关键词： cell-cell communications CellChat dorsal root ganglion scRNA-Seq database

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Peripheral Mechanism of Cancer-Induced Bone Pain

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Neuroscience Bulletin 2024年第6期40卷 815-830页

作者： Yachen Yang Wei Yang Ruofan Zhang Yanqing Wang Department of Integrative Medicine and Neurobiology School of Basic Medical SciencesShanghai Medical CollegeInstitute of Acupuncture ResearchInstitutes of Integrative MedicineFudan UniversityShanghai200032China Shanghai Key Laboratory of Acupuncture Mechanism and Acupoint Function Shanghai Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain ScienceInstitutes of Brain ScienceFudan UniversityShanghai200032China Zhongshan-Fudan Joint Innovation center Zhongshan528437China

Cancer-induced bone pain(CIBP)is a type of ongoing or breakthrough pain caused by a primary bone tumor or bone *** constitutes a specific pain state with distinct characteristics;however,it shares similarities with inflammatory and neuropathic *** present,although various therapies have been developed for this condition,complete relief from CIBP in patients with cancer is yet to be ***,it is urgent to study the mechanism underlying CIBP to develop efficient analgesic ***,we focused on the peripheral mechanism associated with the initiation of CIBP,which involves tissue injury in the bone and changes in the tumor microenvironment(TME)and dorsal root *** nerve–cancer and cancer–immunocyte cross-talk in the TME creates circumstances that promote tumor growth and metastasis,ultimately leading to *** peripheral mechanism of CIBP and current treatments as well as potential therapeutic targets are discussed in this review.

关键词： Cancer-induced bone pain Peripheral mechanism Tumor microenvironment Sensory nerve Immunocytes

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Status of biomarker development for frontotemporal dementia and amyotrophic lateral sclerosis

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Neural Regeneration Research 2024年第10期19卷 2117-2118页

作者： Yue Yang Qi Cheng Jianqun Gao Woojin Scott Kim brain and Mind Centre&School of Medical sciences The University of SydneySydneyNSWAustralia Department of Neurology and Neurophysiology Liverpool HospitalSydneyNSWAustralia Stroke and Neurology Research Group Ingham Institute for Applied Medical ResearchSydneyNSWAustralia Shanghai Key Laboratory of Anesthesiology and brain Functional Modulation ShanghaiChina Clinical Research center for Anesthesiology and Perioperative Medicine ShanghaiChina Translational Research Institute of brain and brain-Like Intelligence Shanghai Fourth People’s HospitalSchool of MedicineTongji UniversityShanghaiChina

Frontotemporal dementia(FTD) and amyotrophic lateral sclerosis(ALS) are neurodegenerative diseases that belong to the same disease spectrum,with overlapping of genetic and pathological *** mutations in TARDBP,C9ORF72,... 详细信息

关键词： amyotrophic sclerosis diseases

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Improving the electrical performances of InSe transistors by interface engineering

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Chinese Physics B 2024年第4期33卷 153-158页

作者：曹天俊郝松吴晨晨潘晨戴玉頔程斌梁世军缪峰 Institute of brain-Inspired Intelligence National Laboratory of Solid State MicrostructuresSchool of PhysicsCollaborative Innovation Center of Advanced MicrostructuresNanjing UniversityNanjing 210093China Institute of Interdisciplinary Physical sciences School of PhysicsNanjing University of Science and TechnologyNanjing 210014China

InSe has emerged as a promising candidate for next-generation electronics due to its predicted ultrahigh electrical ***,the efficacy of the InSe transistor in meeting application requirements is hindered due to its sensitivity to *** this study,we have achieved notable enhancement in the electrical performance of InSe transistors through interface *** engineered an InSe/h-BN heterostructure,effectively suppressing dielectric layer-induced ***,we successfully established excellent metal-semiconductor contacts using graphene ribbons as a buffer *** a methodical approach to interface engineering,our graphene/InSe/h-BN transistor demonstrates impressive on-state current,field-effect mobility,and on/off ratio at room temperature,reaching values as high as 1.1 mA/μm,904 cm^(2)·V^(-1)·s^(-1),and>10~6,*** computations corroborate that the graphene/InSe heterostructure shows significant interlayer charge transfer and weak interlayer interaction,contributing to the enhanced performance of InSe *** research offers a comprehensive strategy to elevate the electrical performance of InSe transistors,paving the way for their utilization in future electronic applications.

关键词： two-dimensional materials InSe van der Waals heterostructure electrical performances charge density difference

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Neural Circuitry Involving Substance P in Male Sexual Behavior

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Neuroscience Bulletin 2024年第4期40卷 544-546页

作者： Xinrong Wang Junqiang Zheng Han Xu Department of Neurobiology and Department of Neurology of the Second Affiliated Hospital and School of brain Science and brain Medicine Zhejiang University School of MedicineHangzhou310058China Nanhu brain-Computer Interface Institute Hangzhou311100China Liangzhu Laboratory MOE Frontier Science Center for Brain Science and Brain-machine IntegrationState Key Laboratory of Brain-Machine IntelligenceZhejiang UniversityHangzhou311121China NHC and CAMS Key Laboratory of Medical Neurobiology Zhejiang UniversityHangzhou310058China Lingang Laboratory Shanghai200031China

Male sexual behavior is an innate social behavior crucial for reproduction[1].Previous studies have identified several brain regions crucial for the control of both sexual and aggressive behaviors in ***,molecularly specified neural circuits that specifically control male sexual behavior remain *** with the inherently rewarding nature of sexual behavior,previous research has implicated the role of the dopamine system in regulating sexual desire[2].However,the interaction between reward and copulation at the circuit level remains largely ***,it is unclear if the associated neural pathways are specific in modulating sexual reward.

关键词： behavior neural specified

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Engineered AAV13 variants with enhanced transduction and confined spread

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Zoological Research 2024年第4期45卷 781-790页

作者： Neng-Song Luo Yu-Xiang Cai Zeng-Peng Han Xiao-Kai Sui Wen-Jia Yuan Zi-Lian Zhang Hao-Dong Guo Jie Wang Kun-Zhang Lin Fu-Qiang Xu Wuhan National Laboratory for Optoelectronics Huazhong University of Science and TechnologyWuhanHubei 430074China Shenzhen Key Laboratory of Viral Vectors for Biomedicine Shenzhen-Hong Kong Institute of Brain ScienceShenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhenGuangdong 518055China Key Laboratory of Magnetic Resonance in Biological Systems State Key Laboratory of Magnetic Resonance and Atomic and Molecular PhysicsNational Center for Magnetic Resonance in WuhanInnovation Academy for Precision Measurement Science and TechnologyChinese Academy of SciencesWuhanHubei 430071China Key Laboratory of Quality Control Technology for Virus-Based Therapeutics Guangdong Provincial Medical Products AdministrationNMPA Key Laboratory for Research and Evaluation of Viral Vector Technology in Cell and Gene Therapy Medicinal ProductsBrain Cognition and Brain Disease InstituteShenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhenGuangdong 518055China University of Chinese Academy of sciences Beijing 100049China Zhongnan Hospital Wuhan UniversityWuhanHubei 430072China brain Case Biotechnology Co. Ltd.ShenzhenGuangdong 518107China College of Life sciences Wuhan UniversityWuhanHubei 430072China center for Excellence in brain Science and Intelligence Technology Chinese Academy of SciencesShanghai 200031China

Precise targeting of specific regions within the central nervous system(CNS)is crucial for both scientific research and gene therapy in the context of brain ***-associated virus 13(AAV13)is known for its restricted diffusion range within the CNS,making it an ideal choice for precise labeling and administration within small brain ***,AAV13 mediates relatively low expression of target ***,we introduced specifically engineered modifications to the AAV13 capsid protein to enhance its transduction *** first constructed AAV13-YF by mutating tyrosine to phenylalanine on the surface of the AAV13 *** then inserted the 7m8 peptide,known to enhance cell transduction,into positions 587/588 and 585/586 of the AAV13 capsid,resulting in two distinct variants named AAV13-587-7m8 and AAV13-585-7m8,*** found that AAV13-YF exhibited superior in vitro infectivity in HEK293T cells compared to AAV13,while AAV13-587-7m8 and AAV13-585-7m8 showed enhanced CNS infection capabilities in C57BL/6 mice,with AAV13-587-7m8 infection retaining a limited spread *** modified AAV13 variants hold promising potential for applications in gene therapy and neuroscience research.

关键词： Adeno-associated virus 13 AAV13-YF AAV13-587-7m8 AAV13-585-7m8 transduction efficiency

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Enhanced Beta2-band Oscillations Denote Auditory Hallucination in Schizophrenia Patients and a Monkey Model of Psychosis

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Neuroscience Bulletin 2024年第3期40卷 325-338页

作者： Shuo Ma Tianzhen Chen Wenjun Jia Jie Liu Shihan Ding Puzhe Li Hong Gan Dapeng Zhang Shuxin Shao Mu-Ming Poo Min Zhao Bomin Sun Jian Jiang Department of Neurosurgery Ruijin HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai200020China Shanghai Mental Health center Shanghai Jiao Tong University School of MedicineShanghai200030China Shanghai center for brain Science and brain-inspired Technology Lingang LaboratoryShanghai201602China University of California at Berkeley BerkeleyCA94720USA School of Life Science and Technology ShanghaiTech UniversityShanghai201210China Institute of Neuroscience CAS Center for Excellence in Brain Science and Intelligence TechnologyCAS Key Laboratory of Primate NeurobiologyState Key Laboratory of NeuroscienceChinese Academy of SciencesShanghai200031China Shanghai center for brain Science and brain-Inspired Intelligence Technology Lingang LaboratoryShanghai201210China Fuyang Third People’s Hospital Fuyang Mental Health CenterFuyang236052China Shanghai Key Laboratory of Psychotic Disorders Shanghai200030China Institute of Psychological and Behavioral Science Shanghai Jiao Tong UniversityShanghai200030China Shanghai Quanlan Technology Co. LtdShanghai201602China

An electroencephalographic(EEG)signature of auditory hallucinations(AHs)is important for facilitating the diagnosis and treatment of AHs in *** recorded EEG from 25 schizophrenia patients with recurrent *** the period of AHs,EEG recordings exhibited significantly elevated beta2-band power in the temporal region,as compared to those recorded in the absence of AHs or during stimulation with verbal *** further generated methamphetamine-treated rhesus monkeys exhibiting psychosis-like behaviors,including repetitive sudden searching actions in the absence of external intrusion,suggesting the occurrence of *** EEG beta2-band power in the temporal region of these monkeys was enhanced immediately after methamphetamine treatment and positively correlated with the frequency of sudden searching ***,the enhancement of temporal beta2-band oscillations represents a signature for AHs in both patients and a monkey model of psychosis,and this monkey model can be used for developing closed-loop neuromodulation approaches for the treatment of refractory AHs in schizophrenia.

关键词： Schizophrenia Auditory hallucinations Non-human primate Methamphetamine Electroencephalography

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The ubiquitin codes in cellular stress responses

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Protein & Cell 2024年第3期15卷 157-190页

作者： Xiangpeng Sheng Zhixiong Xia Hanting Yang Ronggui Hu Key Laboratory of Systems Health Science of Zhejiang Province School of Life ScienceHangzhou Institute for Advanced StudyUniversity of Chinese Academy of SciencesHangzhou 310024China State Key Laboratory of Molecular Biology Shanghai Institute of Biochemistry and Cell BiologyCenter for Excellence in Molecular Cell ScienceChinese Academy of SciencesShanghai 200031China State Key Laboratory of Animal Disease Control Harbin Veterinary Research InstituteChinese Academy of Agricultural SciencesHarbin 150069China Department of Neurology State Key Laboratory of Medical NeurobiologyInstitute for Translational Brain ResearchMOE Frontiers Center for Brain ScienceZhongshan HospitalFudan UniversityShanghai 200032China

Ubiquitination/ubiquitylation,one of the most fundamental post-translational modifications,regulates almost every critical cellular process in *** evidence has shown that essential components of numerous biological processes undergo ubiquitination in mammalian cells upon exposure to diverse stresses,from exogenous factors to cellular reactions,causing a dazzling variety of functional *** forms of ubiquitin sig-nals generated by ubiquitylation events in specific milieus,known as ubiquitin codes,constitute an intrinsic part of myriad cellular stress *** ubiquitination events,leading to proteolytic turnover of the substrates or just switch in functionality,initiate,regulate,or supervise multiple cellular stress-associated responses,supporting adaptation,homeostasis recovery,and survival of the stressed *** this review,we attempted to summarize the crucial roles of ubiquitination in response to different environmental and intracellular stresses,while discussing how stresses modulate the ubiquitin *** review also updates the most recent advances in understanding ubiquitination machinery as well as different stress responses and discusses some important questions that may warrant future investigation.

关键词： ubiquitin E3 ligase environmental stresses intercellular stresses stress response homeostasis

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