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A Novel Retrograde AAV Variant for Functional Manipulation of Cortical Projection Neurons in Mice and Monkeys

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Neuroscience Bulletin 2024年第1期40卷 90-102页

作者： Yefei Chen Jingyi Wang Jing Liu Jianbang Lin Yunping Lin Jinyao Nie Qi Yue Chunshan Deng Xiaofei Qi Yuantao Li Ji Dai Zhonghua Lu Department of Anesthesiology Shenzhen Maternity and Child Healthcare HospitalThe First School of Clinical MedicineSouthern Medical UniversityShenzhen 518027China Shenzhen Technological Research center for Primate Translational Medicine Shenzhen Key Laboratory for Molecular Biology of Neural DevelopmentShenzhen-Hong Kong Institute of Brain ScienceShenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhen 518055China University of Chinese Academy of Sciences Beijing 100049China CAS Key Laboratory of brain Connectome and Manipulation the Brain Cognition and Brain Disease InstituteShenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhen 518055China Guangdong Provincial Key Laboratory of brain Connectome and Behavior the Brain Cognition and Brain Disease InstituteShenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhen 518055China Biomedical Research Institute Hubei University of MedicineShiyan 442000China Faculty of Life and Health Sciences Shenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhen 518055China

Retrograde adeno-associated viruses(AAVs)are capable of infecting the axons of projection neurons and serve as a powerful tool for the anatomical and functional characterization of neural ***,few retro-grade AAV capsids have been shown to offer access to cor-tical projection neurons across different species and enable the manipulation of neural function in non-human primates(NHPs).Here,we report the development of a novel retro-grade AAV capsid,AAV-DJ8R,which efficiently labeled cortical projection neurons after local administration into the striatum of mice and *** addition,intrastriatally injected AAV-DJ8R mediated opsin expression in the mouse motor cortex and induced robust behavioral ***,AAV-DJ8R markedly increased motor cortical neuron firing upon optogenetic light stimulation after viral delivery into the macaque *** data demonstrate the usefulness of AAV-DJ8R as an efficient retrograde tracer for cortical projection neurons in rodents and NHPs and indicate its suitability for use in conducting functional interrogations.

关键词： Retrograde AAV Capsid variant Cortical projection neuron Optogenetics Monkey

New‑Generation Ferroelectric AlScN Materials

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Nano-Micro Letters 2024年第11期16卷 88-118页

作者： Yalong Zhang Qiuxiang Zhu Bobo Tian Chungang Duan Key Laboratory of Polar Materials and Devices Ministry of EducationShanghai Center of Brain‑Inspired Intelligent Materials and DevicesDepartment of ElectronicsEast China Normal UniversityShanghai 200241People’s Republic of China Collaborative Innovation center of Extreme Optics Shanxi UniversityTaiyuan 030006ShanxiPeople’s Republic of China

Ferroelectrics have great potential in the field of nonvolatile memory due to programmable polarization states by external electric field in nonvolatile ***,complementary metal oxide semiconductor compatibility and uniformity of ferroelectric performance after size scaling have always been two thorny issues hindering practical application of ferroelectric memory *** emerging ferroelectricity of wurtzite structure nitride offers opportunities to circumvent the *** review covers the mechanism of ferroelectricity and domain dynamics in ferroelectric AlScN *** performance optimization of AlScN films grown by different techniques is summarized and their applications for memories and emerging in-memory computing are ***,the challenges and perspectives regarding the commercial avenue of ferroelectric AlScN are discussed.

关键词： AlScN Ferroelectrics Nonvolatile memory In-memory computing

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

Observing ferroelastic switching in Hf_(0.5)Zr_(0.5)O_(2) thin film

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Chinese Physics B 2024年第6期33卷 526-530页

作者：关赵王陶郑赟喆彭悦魏鹿奇张宇科阿卜力孜·麦提图尔荪黄家豪童文旖韩根全陈斌斌向平华段纯刚钟妮 Key Laboratory of Polar Materials and Devices Ministry of EducationShanghai Center of Brain-inspired Intelligent Materials and DevicesEast China Normal UniversityShanghai 200241China School of Microelectronics Xidian UniversityXi'an 710071China Collaborative Innovation center of Extreme Optics Shanxi UniversityTaiyuan 030006China

Hafnium zirconium oxides(HZO),which exhibit ferroelectric properties,are promising materials for nanoscale device fabrication due to their high complementary metal-oxide-semiconductor(CMOS) *** addition to piezoelectricity,ferroelectricity,and flexoelectricity,this study reports the observation of ferroelasticity using piezoelectric force microscopy(PFM) and scanning transmission electron microscopy(STEM).The dynamics of 90° ferroelastic domains in HZO thin films are investigated under the influence of an electric *** of the retentive domains is observed through repeated wake-up *** study presents a possibility of enhancing polarization in HZO thin films during wake-up processes.

关键词： HfO_(2)-based ferroelectrics ferroelasticity piezoelectric force microscopy(PFM)

Neural Stem Cell Competition

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Neuroscience Bulletin 2024年第2期40卷 277-279页

作者： Yanan Li Jie He State Key Laboratory of Neuroscience Institute of NeuroscienceCenter for Excellence in Brain Science and Intelligence TechnologyChinese Academy of SciencesShanghai 200031China University of Chinese Academy of Sciences Beijing 100049China

Cell competition is an adaptive surveillance mechanism to ensure the robustness of developmental outputs,maintain tissue integrity,and regulate tumor progression in multicellular organisms,which is highly conserved from invertebrates to vertebrates[1].At the cellular level,cell competition represents a non-cell-autonomous process in that cells can sense the fitness of their neighbors through cellular interactions,thereby eliminating low-fitness cells and expanding high-fitness counterparts,however,cells develop normally in homogenous populations.

关键词： thereby maintain eliminating

Neuroprotective effects of chaperone-mediated autophagy in neurodegenerative diseases

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Neural Regeneration Research 2024年第6期19卷 1291-1298页

作者： Qi Jia Jin Li Xiaofeng Guo Yi Li You Wu Yuliang Peng Zongping Fang Xijing Zhang Department of Anesthesiology and Perioperative Medicine and Department of Intensive Care Unit Xijing HospitalThe Fourth Military Medical UniversityXi’anShaanxi ProvinceChina Department of Critical Care Medicine Air Force Medical CenterBeijingChina Translational Research Institute of brain and brain-Like Intelligence Shanghai Fourth People’s HospitalSchool of MedicineTongji UniversityShanghaiChina

Chaperone-mediated autophagy is one of three types of autophagy and is characterized by the selective degradation of ***-mediated autophagy contributes to energy balance and helps maintain cellular homeostasis,while providing nutrients and support for cell ***-mediated autophagy activity can be detected in almost all cells,including *** to the extreme sensitivity of neurons to their environmental changes,maintaining neuronal homeostasis is critical for neuronal growth and ***-mediated autophagy dysfunction is closely related to central nervous system *** has been shown that neuronal damage and cell death are accompanied by chaperone-mediated autophagy *** certain conditions,regulation of chaperone-mediated autophagy activity attenuates *** this paper,we review the changes in chaperone-mediated autophagy in neurodegenerative diseases,brain injury,glioma,and autoimmune *** also summarize the most recent research progress on chaperone-mediated autophagy regulation and discuss the potential of chaperone-mediated autophagy as a therapeutic target for central nervous system diseases.

关键词： chaperone-mediated autophagy neurodegenerative disease neuronal homeostasis neuroprotection

Photonic neuromorphic architecture for tens-of-task lifelong learning

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Light(Science & Applications) 2024年第3期13卷 519-530页

作者： Yuan Cheng Jianing Zhang Tiankuang Zhou Yuyan Wang Zhihao Xu Xiaoyun Yuan Lu Fang Sigma Laboratory Department of Electronic EngineeringTsinghua UniversityBeijing 100084China Beijing National Research center for Information Science and Technology(BNRist) Beijing 100084China Institute for brain and Cognitive Science Tsinghua University(THUIBCS)Beijing 100084China

Scalable,high-capacity,and low-power computing architecture is the primary assurance for increasingly manifold and large-scale machine learning *** electronic artificial agents by conventional power-hungry processors have faced the issues of energy and scaling walls,hindering them from the sustainable performance improvement and iterative multi-task *** to another modality of light,photonic computing has been progressively applied in high-efficient neuromorphic ***,we innovate a reconfigurable lifelong-learning optical neural network(L2 ONN),for highly-integrated tens-of-task machine intelligence with elaborated algorithm-hardware *** from the inherent sparsity and parallelism in massive photonic connections,L2 ONN learns each single task by adaptively activating sparse photonic neuron connections in the coherent light field,while incrementally acquiring expertise on various tasks by gradually enlarging the *** multi-task optical features are parallelly processed by multi-spectrum representations allocated with different *** evaluations on freespace and on-chip architectures confirm that for the first time,L2 ONN avoided the catastrophic forgetting issue of photonic computing,owning versatile skills on challenging tens-of-tasks(vision classification,voice recognition,medical diagnosis,etc.)with a single ***,L2 ONN achieves more than an order of magnitude higher efficiency than the representative electronic artificial neural networks,and 14×larger capacity than existing optical neural networks while maintaining competitive performance on each individual *** proposed photonic neuromorphic architecture points out a new form of lifelong learning scheme,permitting terminal/edge AI systems with light-speed efficiency and unprecedented scalability.

关键词： life neural versatile

Regulatory Mechanisms for Transcriptional Bursting Revealed by an Event-Based Model

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Research 2024年第3期2023卷 217-231页

作者： Renje Wu Bangyan Zhou Wei Wang Feng Liu National Laboratory of Solid State Microstructures Department of Physicsand Collaborative Innovation Center of Advanced MicrostructuresNanjing UniversityNanjing 210093P.R.China Institute for brain Sciences Nanjing UniversityNanjing 210093P.R.China.

Gene transcription often occurs in discrete bursts, and it can be difficult to deduce the underlying regulatory mechanisms for transcriptional bursting with limited experimental data. Here, we categorize numerous states of single eukaryotic genes and identify 6 essential transcriptional events, each comprising a series of state transitions;transcriptional bursting is characterized as a sequence of 4 events, capable of being organized in various configurations, in addition to the beginning and ending events. By associating transcriptional kinetics with mean durations and recurrence probabilities of the events, we unravel how transcriptional bursting is modulated by various regulators including transcription factors. Through analytical derivation and numerical simulation, this study reveals key state transitions contributing to transcriptional sensitivity and specificity, typical characteristics of burst profiles, global constraints on intrinsic transcriptional noise, major regulatory modes in individual genes and across the genome, and requirements for fast gene induction upon stimulation. It is illustrated how biochemical reactions on different time scales are modulated to separately shape the durations and ordering of the events. Our results suggest that transcriptional patterns are essentially controlled by a shared set of transcriptional events occurring under specific promoter architectures and regulatory modes, the number of which is actually limited.

关键词： kinetics essentially constraints

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