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Single-nucleus transcriptomics uncovers a geroprotective role of YAP in primate gingival aging

Protein & Cell 2024年第8期15卷 612-632页

作者： Qinchao Hu Bin Zhang Yaobin Jing Shuai Ma Lei Hu jingyi Li Yandong Zheng Zijuan Xin Jianmin Peng Si Wang Bin Cheng Jing Qu Weiqi zhang Guang-Hui Liu Songlin Wang state key laboratory of Membrane Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China Hospital of Stomatology Guanghua School of StomatologyGuangdong Provincial Key Laboratory of StomatologySun Yat-sen UniversityGuangzhou 510060China Salivary Gland Disease Center and Beijing key laboratory of Tooth Regeneration and Function Reconstruction Beijing Laboratory of Oral Health and Beijing Stomatological HospitalCapital Medical UniversityBeijing 100050China Department of Biochemistry and Molecular Biology School of Basic Medical SciencesCapital Medical UniversityBeijing 100069China CAS key laboratory of Genomic and Precision Medicine Beijing Institute of GenomicsChinese Academy of Sciences and China National Center for BioinformationBeijing 100101China state key laboratory of Stem Cell and Reproductive Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China key laboratory of Organ Regeneration and Reconstruction Institute of ZoologyChinese Academy of SciencesBeijing 100101China University of Chinese Academy of sciences Beijing 100049China institute for Stem Cell and Regeneration Chinese Academy of SciencesBeijing 100101China Beijing institute for Stem Cell and Regenerative Medicine Beijing 100101China Advanced Innovation Center for Human brain Protection and National Clinical Research Center for Geriatric Disorders Xuanwu Hospital Capital Medical UniversityBeijing 100053China Aging Translational Medicine Center Intermational Center for Aging and CancerBeijing Municipal Geriatric Medical Research CenterXuan Wu HospitalCapital Medical UniversityBeijing 100053China Intemational Center for Aging and Cancer Hainan Medical UniversityHaikou 571199China Aging Biomarker Consortium Beijing 100101China

Aging has a profound impact on the gingiva and significantly increases its susceptibility to periodontitis,a worldwide prevalent inflammatory ***,a systematic characterization and comprehensive understanding of the regulatory mechanism underlying gingival aging is still ***,we systematically dissected the phenotypic characteristics of gingiva during aging in primates and constructed the first single-nucleus transcriptomic landscape of gingival aging,by which a panel of cell type-specific signatures were *** cells were identified as the most affected cell types by aging in the *** analyses pinpointed the crucial role of YAP in epithelial self-renew and homeostasis,which declined during aging in epithelial cells,especially in basal *** decline of YAP activity during aging was confrmed in the human gingival tissues,and downregulation of YAP in human primary gingival keratinocytes recapitulated the major phenotypic defects observed in the aged primate gingiva while overexpression of YAP showed rejuvenation *** work provides an in-depth understanding of gingival aging and serves as a rich resource for developing novel strategies to combat aging-associated gingival diseases,with the ultimate goal of advancing periodontal health and promoting healthy aging.

关键词： single-nucleus RNA-sequencing primate gingiva aging YAP

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Anisotropic metal–insulator transition in strained VO_(2)(B) single crystal

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Chinese Physics B 2024年第6期33卷 56-61页

作者：马泽成闫胜楠刘增霖徐涛陈繁强陈思成曹天俊孙立涛程斌梁世军缪峰 institute of brain-Inspired Intelligence National Laboratory of Solid State MicrostructuresSchool of PhysicsCollaborative Innovation Center of Advanced MicrostructuresNanjing UniversityNanjing 210093China SEU-FEI Nano-Pico Center Key Laboratory of MEMS of Ministry of EducationSoutheast UniversityNanjing 210096China institute of Interdisciplinary of Physical sciences School of ScienceNanjing University of Science and TechnologyNanjing 210094China

Mechanical strain can induce noteworthy structural and electronic changes in vanadium dioxide, imparting substantial scientific importance to both the exploration of phase transitions and the development of potential technological applications. Unlike the traditional rutile(R) phase, bronze-phase vanadium dioxide [VO_(2)(B)] exhibits an in-plane anisotropic structure. When subjected to stretching along distinct crystallographic axes, VO_(2)(B) may further manifest the axial dependence in lattice–electron interactions, which is beneficial for gaining insights into the anisotropy of electronic ***, we report an anisotropic room-temperature metal–insulator transition in single-crystal VO_(2)(B) by applying in-situ uniaxial tensile strain. This material exhibits significantly different electromechanical responses along two anisotropic *** reveal that such an anisotropic electromechanical response mainly arises from the preferential arrangement of a straininduced unidirectional stripe state in the conductive channel. This insulating stripe state could be attributed to the in-plane dimerization within the distorted zigzag chains of vanadium atoms, evidenced by strain-modulated Raman spectra. Our work may open up a promising avenue for exploiting the anisotropy of metal–insulator transition in vanadium dioxide for potential technological applications.

关键词： vanadium dioxide strain anisotropy electrical transport

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Ultrasensitive Mechanical Sensor Using Tunable Ordered Array of Metallic and Insulating states in Vanadium Dioxide

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Chinese Physics Letters 2024年第7期41卷 74-86页

作者：马泽成闫胜楠陈繁强戴玉頔刘增霖徐康徐涛童湛钦陈墨雨王利铮王鹏飞孙立涛程斌梁世军缪峰 institute of brain-Inspired Intelligence National Laboratory of Solid State MicrostructuresSchool of PhysicsCollaborative Innovation Center of Advanced MicrostructuresNanjing UniversityNanjing 210093China SEU-FEI Nano-Pico Center Key Laboratory of MEMS of Ministry of EducationSoutheast UniversityNanjing 210096China institute of Interdisciplinary of Physical sciences School of ScienceNanjing University of Science and TechnologyNanjing 210094China

Detecting tiny deformations or vibrations, particularly those associated with strains below 1%, is essential in various technological applications. Traditional intrinsic materials, including metals and semiconductors, face challenges in simultaneously achieving initial metallic state and strain-induced insulating state, hindering the development of highly sensitive mechanical sensors. Here we report an ultrasensitive mechanical sensor based on a strain-induced tunable ordered array of metallic and insulating states in the single-crystal bronze-phase vanadium dioxide [VO_(2)(B)] quantum material. It is shown that the initial metallic state in the VO_(2)(B) flake can be tuned to the insulating state by applying a weak uniaxial tensile strain. Such a unique property gives rise to a record-high gauge factor of above 607970, surpassing previous values by an order of magnitude, with excellent linearity and mechanical resilience as well as durability. As a proof-of-concept application, we use our proposed mechanical sensor to demonstrate precise sensing of the micro piece, gentle airflows and water droplets. We attribute the superior performance of the sensor to the strain-induced continuous metal-insulator transition in the single-crystal VO_(2)(B) flake, evidenced by experimental and simulation results. Our findings highlight the potential of exploiting correlated quantum materials for next-generation ultrasensitive flexible mechanical sensors, addressing critical limitations in traditional materials.

关键词： metallic durability hinder

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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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Identification of FOXO1 as a geroprotector in human synovium through single-nucleus transcriptomic profiling

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Protein & Cell 2024年第6期15卷 441-459页

作者： Feifei Liu Yi Lu Xuebao Wang Shuhui Sun Huize Pan Min Wang Zehua Wang Weiqi Zhang Shuai Ma Guoqiang Sun Qun Chu Si Wang Jing Qu Guang-Hui Liu state key laboratory of Membrane Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China Sports Medicine Department Beijing Jishuitan HospitalCapital Medical UniversityBeijing 100035China state key laboratory of Stem Cell and Reproductive Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China University of Chinese Academy of sciences Beijing 100049China institute for Stem Cell and Regeneration Chinese Academy of SciencesBeijing 100101China Beijing institute for Stem Cell and Regenerative Medicine Beijing 100101China National laboratory of Biomacromolecules Institute of BiophysicsChinese Academy of SciencesBeijing 100101China Division of Life sciences and Medicine School of Life SciencesUniversity of Science and Technology of ChinaHefei 230001China CAS key laboratory of Genomic and Precision Medicine Beijing Institute of GenomicsChinese Academy of Sciences and China National Center for BioinformationBeijing 100101China The Fifth People’s Hospital of Chongqing Chongqing 400062China Advanced Innovation Center for Human brain Protection and National Clinical Research Center for Geriatric Disorders Xuanwu Hospital Capital Medical UniversityBeijing 100053China Aging Translational Medicine Center International Center for Aging and CancerBeijing Municipal Geriatric Medical Research CenterXuanwu HospitalCapital Medical UniversityBeijing 100053China

The synovium,a thin layer of tissue that is adjacent to the joints and secretes synovial fluid,undergoes changes in aging that contribute to intense shoulder pain and other joint ***,the mechanism underlying human synovial aging remains poorly ***,we generated a comprehensive transcriptomic profile of synovial cells present in the subacromial synovium from young and aged *** delineating aging-related transcriptomic changes across different cell types and their associated regulatory networks,we identified two subsets of mesenchymal stromal cells(MSCs)in human synovium,which are lining and sublining MSCs,and found that angiogenesis and fibrosis-associated genes were upregulated whereas genes associated with cell adhesion and cartilage development were downregulated in aged ***,the specific cell-cell communications in aged synovium mirrors that of aging-related inflammation and tissue remodeling,including vascular hyperplasia and tissue *** particular,we identified forkhead box O1(FOXO1)as one of the major regulons for aging differentially expressed genes(DEGs)in synovial MSCs,and validated its downregulation in both lining and sublining MSC populations of the aged *** human FOXO1-depleted MSCs derived from human embryonic stem cells,we recapitulated the senescent phenotype observed in the subacromial synovium of aged *** data indicate an important role of FOXO1 in the regulation of human synovial ***,our study improves our understanding of synovial aging during joint degeneration,thereby informing the development of novel intervention strategies aimed at rejuvenating the aged joint.

关键词： FOXO1 degeneration inflammation

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Memristive switching in the surface of a charge-density-wave topological semimetal

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Science Bulletin 2024年第13期69卷 2042-2049页

作者： Jianwen Ma Xianghao Meng Binhua Zhang Yuxiang Wang Yicheng Mou Wenting Lin Yannan Dai Luqiu Chen Haonan Wang Haoqi Wu Jiaming Gu Jiayu Wang Yuhan Du Chunsen Liu Wu Shi Zhenzhong Yang Bobo Tian Lin Miao Peng Zhou Chun-Gang Duan Changsong Xu Xiang Yuan Cheng Zhang state key laboratory of Surface Physics and institute for Nanoelectronic Devices and Quantum Computing Fudan UniversityShanghai 200433China state key laboratory of Precision Spectroscopy East China Normal UniversityShanghai 200241China key laboratory of Computational Physical sciences(Ministry of Education) Institute of Computational Physical SciencesState Key Laboratory of Surface PhysicsDepartment of PhysicsFudan UniversityShanghai 200433China Shanghai Qi Zhi institute Shanghai 200030China School of Physics Southeast UniversityNanjing 211189China key laboratory of Polar Materials and Devices(Ministry of Education) Department of ElectronicsEast China Normal UniversityShanghai 200241China Shanghai Center of brain–inspired Intelligent Materials and Devices East China Normal UniversityShanghai 200241China state key laboratory of ASIC and System School of MicroelectronicsFudan UniversityShanghai 200433China Frontier institute of Chip and System Fudan UniversityShanghai 200433China Zhangjiang Fudan International Innovation Center Fudan UniversityShanghai 201210China School of Physics and Electronic Science East China Normal UniversityShanghai 200241China

Owing to the outstanding properties provided by nontrivial band topology,topological phases of matter are considered as a promising platform towards low-dissipation electronics,efficient spin-charge conversion,and topological quantum *** ferroelectricity in topological materials enables the non-volatile control of the quantum states,which could greatly facilitate topological electronic ***,ferroelectricity is generally incompatible with systems featuring metallicity due to the screening effect of free *** this study,we report the observation of memristive switching based on the ferroelectric surface state of a topological semimetal(TaSe_(4))*** find that the surface state of(TaSe_(4))2I presents out-of-plane ferroelectric polarization due to surface *** the combination of ferroelectric surface and charge-density-wave-gapped bulk states,an electric-switchable barrier height can be achieved in(TaSe_(4))2I-metal *** employing a multi-terminal-grounding design,we manage to construct a prototype ferroelectric memristor based on(TaSe_(4))2I with on/off ratio up to 103,endurance over 103 cycles,and good retention *** origin of the ferroelectric surface state is further investigated by first-principles calculations,which reveal an interplay between ferroelectricity and band *** emergence of ferroelectricity in(TaSe_(4))2I not only demonstrates it as a rare but essential case of ferroelectric topological materials,but also opens new routes towards the implementation of topological materials in functional electronic devices.

关键词： Topological semimetal Schottky barrier Surface ferroelectricity Memristor

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Comparative analysis of primate and pig cells reveals primate-specific PINK1 expression and phosphorylation

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Zoological Research 2024年第2期45卷 242-252页

作者： Xiu-Sheng Chen Rui Han Yan-Ting Liu Wei Huang Qi Wang Xin Xiong Ying Zhang Jian-Guo Zhao Shi-Hua Li Xiao-Jiang Li Wei-Li Yang Guangdong key laboratory of Non-human Primate Research Key Laboratory of CNS Regeneration(Ministry of Education)GHM Institute of CNS RegenerationJinan UniversityGuangzhouGuangdong 510632China state key laboratory of Stem Cell and Reproductive Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China Beijing institute for Stem Cell and Regenerative Medicine Beijing 100101China University of Chinese Academy of sciences Beijing 100049China

PTEN-induced putative kinase 1(PINK1),a mitochondrial kinase that phosphorylates Parkin and other proteins,plays a crucial role in mitophagy and protection against *** in PINK1 and Parkin can lead to loss of function and early onset Parkinson's ***,there is a lack of strong in vivo evidence in rodent models to support the theory that loss of PINK1 affects mitophagy and induces ***,PINK1 knockout pigs(Sus scrofa)do not appear to exhibit *** our recent work involving non-human primates,we found that PINK1 is selectively expressed in primate brains,while absent in rodent *** extend this to other species,we used multiple antibodies to examine the expression of PINK1 in pig *** contrast to tissues from cynomolgus monkeys(Macaca fascicularis),our data did not convincingly demonstrate detectable PINK1expression in pig *** of PINK1 in cultured pig cells did not result in altered Parkin and BAD phosphorylation,as observed in cultured monkey cells.A comparison of monkey and pig striatum revealed more PINK1-phosphorylated substrates in the monkey ***,PINK1 knockout in pigs did not lead to obvious changes in the phosphorylation of Parkin and *** findings provide new evidence that PINK1expression is specific to primates,underscoring the importance of non-human primates in investigating PINK1function and pathology related to PINK1 deficiency.

关键词： PINK1 Parkin Mitochondria Phosphorylation Non-human primates Pigs

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Comparative transcriptome analysis between rhesus macaques(Macaca mulatta) and crab-eating macaques(M. fascicularis)

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Zoological Research 2024年第2期45卷 299-310页

作者： Yu-Xiang Mao Yamei Li Zikun Yang Ning Xu Shilong Zhang Xuankai Wang Xiangyu Yang Qiang Sun Yafei Mao institute of Neuroscience State Key Laboratory of NeuroscienceCenter for Excellence in Brain Science&Intelligence TechnologyChinese Academy of SciencesShanghai 200031China Shanghai Center for brain Science and brain-Inspired Intelligence Technology Shanghai 201210China University of Chinese Academy of sciences Beijing 100049China key laboratory of Genetic Evolution&Animal Models Chinese Academy of SciencesKunmingYunnan 650201China Bio-X institutes Key Laboratory for the Genetics of Developmental and Neuropsychiatric DisordersMinistry of EducationShanghai Jiao Tong UniversityShanghai 200030China Zhiyuan College Shanghai Jiao Tong UniversityShanghai 200240China Center for Genomic Research International Institutes of MedicineFourth Affiliated HospitalZhejiang UniversityYiwuZhejiang 322000China

Understanding gene expression variations between species is pivotal for deciphering the evolutionary diversity in phenotypes. Rhesus macaques(Macaca mulatta, MMU)and crab-eating macaques(M. fascicularis, MFA) serve as crucial nonhuman primate biomedical models with different phenotypes. To date, however, large-scale comparative transcriptome research between these two species has not yet been fully explored. Here, we conducted systematic comparisons utilizing newly sequenced RNA-seq data from84 samples(41 MFA samples and 43 MMU samples)encompassing 14 common tissues. Our findings revealed a small fraction of genes(3.7%) with differential expression between the two species, as well as 36.5% of genes with tissue-specific expression in both macaques. Comparison of gene expression between macaques and humans indicated that 22.6% of orthologous genes displayed differential expression in at least two tissues. Moreover,19.41% of genes that overlapped with macaque-specific structural variants showed differential expression between humans and macaques. Of these, the FAM220A gene exhibited elevated expression in humans compared to macaques due to lineage-specific duplication. In summary,this study presents a large-scale transcriptomic comparison between MMU and MFA and between macaques and humans. The discovery of gene expression variations not only enhances the biomedical utility of macaque models but also contributes to the wider field of primate genomics.

关键词： Crab-eating macaques Rhesus macaques Comparative transcriptomics Biomedical models Nonhuman primates RNA-seq Duplicated genes

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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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brain-inspired artificial intelligence research: A review

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Science China(Technological sciences) 2024年第8期67卷 2282-2296页

作者： WANG GuoYin BAO HuaNan LIU Qun ZHOU TianGang WU Si HUANG TieJun YU ZhaoFei LU CeWu GONG YiHong ZHANG ZhaoXiang HE Sheng Chongqing key laboratory of Computational Intelligence Chongqing University of Posts and TelecommunicationsChongqing 400065China key laboratory of Cyberspace Big Data Intelligent Security Chongqing University of Posts and TelecommunicationsChongqing 400065China College of Computer and Information Science Chongqing Normal UniversityChongqing 401331China state key laboratory of brain and Cognitive Science Institute of BiophysicsChinese Academy of SciencesBeijing 100101China School of Psychological and Cognitive sciences Peking UniversityBeijing 100871China state key laboratory of Multimedia Information Processing School of Computer SciencePeking UniversityBeijing 100871China Department of Computer Science School of ElectronicsInformation and Electrical EngineeringShanghai Jiao Tong UniversityShanghai 200240China Faculty of Electronic and Information Engineering Xi’an Jiaotong UniversityXi’an 710049China The Center for Research on Intelligent Perception and Computing Institute of AutomationChinese Academy of SciencesBeijing 100190China institute of Biophysics Chinese Academy of SciencesBeijing 100101China

Artificial intelligence(AI) systems surpass certain human intelligence abilities in a statistical sense as a whole, but are not yet the true realization of these human intelligence abilities and behaviors. There are differences, and even contradictions, between the cognition and behavior of AI systems and humans. With the goal of achieving general AI, this study contains a review of the role of cognitive science in inspiring the development of the three mainstream academic branches of AI based on the three-layer framework proposed by David Marr, and the limitations of the current development of AI are explored and analyzed. The differences and inconsistencies between the cognition mechanisms of the human brain and the computation mechanisms of AI systems are analyzed. They are found to be the cause of the differences and contradictions between the cognition and behavior of AI systems and humans. Additionally, eight important research directions and their scientific issues that need to focus on braininspired AI research are proposed: highly imitated bionic information processing, a large-scale deep learning model that balances structure and function, multi-granularity joint problem solving bidirectionally driven by data and knowledge, AI models that simulate specific brain structures, a collaborative processing mechanism with the physical separation of perceptual processing and interpretive analysis, embodied intelligence that integrates the brain cognitive mechanism and AI computation mechanisms,intelligence simulation from individual intelligence to group intelligence(social intelligence), and AI-assisted brain cognitive intelligence.

关键词： artificial intelligence cognitive science brain science intelligence science large language model

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