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Glioma-derived ANXA1 suppresses the immune response to TLR3 ligands by promoting an anti-inflammatory tumor microenvironment

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Cellular & Molecular Immunology 2024年第1期21卷 47-59页

作者： Yu Zheng Haihui Jiang Naixue Yang Shaoping Shen Daosheng Huang Lemei Jia Jing Ling Longchen Xu Mingxiao Li Kefu Yu Xiaohui Ren Yong Cui Xun Lan Song Lin Xin Lin Institute for Immunology and School of Medicine Tsinghua UniversityBeijing100084China Department of Neurosurgery Beijing Tiantan HospitalCapital Medical UniversityChina.National Clinical Research Center for Neurological DiseasesCenter of Brain TumorBeijing Institute for Brain Disorders and Beijing Key Laboratory of Brain TumorBeijing100070China Department of Neurosurgery Peking University Third HospitalPeking UniversityBeijing100191China Tsinghua-Peking Center for Life Sciences Beijing100084China

A highly immunosuppressive tumor microenvironment(TME)and the presence of the blood‒brain barrier are the two major obstacles to eliciting an effective immune response in patients with high-grade glioma(HGG).Here,we tried to enhance the local innate immune response in relapsed HGG by intracranially injecting poly(I:C)to establish a robust antitumor immune response in this registered clinical trial(NCT03392545).During the follow-up,12/27(44.4%)patients who achieved tumor control concomitant with survival benefit were regarded as responders in our *** found that the T-cell receptor(TCR)repertoire in the TME was reshaped after poly(I:C)*** on the RNA-seq analysis of tumor samples,the expression of annexin A1(ANXA1)was significantly upregulated in the tumor cells of nonresponders,which was further validated at the protein *** vitro and in vivo experiments showed that ANXA1 could induce the production of M2-like macrophages and microglia via its surface receptor formyl peptide receptor 1(FPR1)to establish a Treg cell-driven immunosuppressive TME and suppress the antitumor immune response facilitated by poly(I:C).The ANXA1/FPR1 signaling axis can inhibit the innate immune response of glioma patients by promoting an anti-inflammatory and Treg-driven ***,ANXA1 could serve as a reliable predictor of response to poly(I:C),with a notable predictive accuracy rate of 92.3%.In light of these notable findings,this study unveils a new perspective of immunotherapy for gliomas.

关键词： glioma ANXA1 TLR3 poly(I:C) immunotherapy

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Control of defensive behavior by the nucleus of Darkschewitsch GABAergic neurons

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National Science Review 2024年第4期11卷 70-83页

作者： Huiying Zhao Jinrong Liu Yujin Shao Xiang Feng Binhan Zhao Li Sun Yijun Liu Linghui Zeng Xiao-ming Li Hongbin Yang Shumin Duan Yan-qin Yu Department of Neurology of Second Affiliated Hospital and School of brain Science and brain Medicine Zhejiang University School of Medicine Nanhu brain-Computer Interface Institute Liangzhu Laboratory MOE Frontier Science Center for Brain Science and Brain-Machine Integration State Key Laboratory of Brain-Machine Intelligence Zhejiang University NHC and CAMS Key Laboratory of Medical Neurobiology Zhejiang University Key Laboratory of Novel Targets and Drug Study for Neural Repair of Zhejiang Province School of Medicine Hangzhou City University

The nucleus of Darkschewitsch(ND), mainly composed of GABAergic neurons, is widely recognized as a component of the eye-movement controlling system. However, the functional contribution of ND GABAergic neurons(NDGABA) in animal behavior is largely unknown. Here, we show that NDGABA neurons were selectively activated by different types of fear stimuli, such as predator odor and foot *** and chemogenetic manipulations revealed that NDGABA neurons mediate freezing ***, using circuit-based optogenetic and neuroanatomical tracing methods, we identified an excitatory pathway from the lateral periaqueductal gray(l PAG) to the ND that induces freezing by exciting ND inhibitory outputs to the motor-related gigantocellular reticular nucleus, ventral part(Gi V). Together,these findings indicate the NDGABA population as a novel hub for controlling defensive response by relaying fearful information from the l PAG to Gi V, a mechanism critical for understanding how the freezing behavior is encoded in the mammalian brain.

关键词： nucleus of Darkschewitsch GABAergic population defensive behavior freezing neural circuitry

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Advances in brain tumor therapy: from molecular diagnostics to novel treatments

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Science China Life Sciences 2024年

作者： Junwen Zhang Ran Mu Fusheng Liu brain tumor Research Center Beijing Neurosurgical Institute Capital Medical University Department of Neurosurgery Beijing Tiantan Hospital Capital Medical University

With the rapid increase in incidence and mortality, brain tumors have become a major social, economic, and public health problem worldwide. According to the latest report from the International Agency for Research on Cancer (IARC),there are approximately 320,000 new cases and 250,000 deaths from brain and central nervous system (CNS) tumors each year. The incidence and mortality rates rank 19th and 12th among all cancers (Bray et al., 2024), respectively,and are particularly prevalent in East Asia, Western Europe, and South *** like San Marino, Denmark, and Norway have the highest age-standardized incidence rates, while Central Europe and tropical Latin America have the highest age-standardized mortality and disability-adjusted life-year (DALY) rates.

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Developmental Impairments of Synaptic Refinement in the Thalamus of a Mouse Model of Fragile X Syndrome

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Neuroscience Bulletin 2024年第4期40卷 439-450页

作者： Xiaotong Wu Yali Liu Xiaomeng Wang Lu Zheng Libiao Pan Hao Wang Department of Neurosurgery of Second Affiliated Hospital and School of brain Science and brain Medicine Key Laboratory for Biomedical Engineering of Education MinistryZhejiang University School of MedicineHangzhou310058China Nanhu brain-computer Interface Institute Hangzhou311100China NHC and CAMS Key Laboratory of Medical Neurobiology MOE Frontier Science Center for Brain Research and Brain Machine IntegrationKey Laboratory of Precise Treatment and Clinical Translational Research of Neurological DiseasesSchool of Brain Science and Brain MedicineZhejiang UniversityHangzhou310058China Lingang Laboratory Shanghai200031China

While somatosensory over-reactivity is a common feature of autism spectrum disorders such as fragile X syndrome(FXS),the thalamic mechanisms underlying this remain ***,we found that the developmental elimination of synapses formed between the principal nucleus of V(PrV)and the ventral posterior medial nucleus(VPm)of the somatosensory system was delayed in fragile X mental retardation 1 gene knockout(Fmr1 KO)mice,while the developmental strengthening of these synapses was *** showed excessive VGluT2 puncta in mutants at P12–13,but not at P7–8 or P15–16,confirming a delay in somatic pruning of PrV-VPm *** synaptic function was associated with a reduction in the frequency of quantal AMPA events,as well as developmental deficits in presynaptic vesicle size and *** results uncovered the developmental impairment of thalamic relay synapses in Fmr1 KO mice and suggest that a thalamic contribution to the somatosensory over-reactivity in FXS should be considered.

关键词： Fragile X syndrome Synaptic refinement VPm Sensory over-reactivity

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Microplastic exposure disturbs sleep structure,reduces lifespan,and decreases ovary size in Drosophila melanogaster

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Zoological Research 2024年第4期45卷 805-820页

作者： Wei Yan Zi-Jie Li Zi-Yi Lin Shu-Qin Ji William Ka Fai Tse Zhi-Qiang Meng Chang Liu Lei Li Shenzhen-Hong Kong Institute of brain Science Shenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhenGuangdong 518000China CAS Key Laboratory of brain Connectome and Manipulation the Brain Cognition and Brain Disease InstituteShenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhenGuangdong 518000China Laboratory of Developmental Disorders and Toxicology Center for Promotion of International Education and ResearchFaculty of AgricultureKyushu UniversityFukuokaFukuoka 819-0395Japan Shenzhen Key Laboratory of Drug Addiction the Brain Cognition and Brain Disease InstituteShenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhenGuangdong 518000China Guangdong Provincial Key Laboratory of brain Connectome and Behavior Brain Cognition and Brain Disease InstituteShenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhenGuangdong 518000China

The organ-specific toxicity resulting from microplastic(MP)exposure has been extensively explored,particularly concerning the gut,liver,testis,and ***,under natural conditions,these effects are not restricted to specific organs or *** whether MP exposure presents a systemic threat to an entire organism,impacting factors such as lifespan,sleep,and fecundity,is *** this study,we investigated the effects of dietary exposure to two different doses of MPs(1–5μm)using the terrestrial model organism Drosophila *** indicated that the particles caused gut damage and remained within the digestive *** MP exposure significantly shortened the lifespan of adult *** short-term exposure disrupted sleep patterns,increasing the length of daytime sleep ***,one week of MP exposure reduced ovary size,with a trend towards decreased egg-laying in mated *** MPs did not penetrate the brain or ovaries,transcriptome analysis revealed altered gene expression in these *** the ovary,Gene Ontology(GO)analysis indicated genotoxic effects impacting inflammation,circadian regulation,and metabolic processes,with significant impacts on extracellular structure-related *** the brain,GO analysis identified changes in pathways associated with proteolysis and carbohydrate ***,this study provides compelling evidence of the systemic negative effects of MP exposure,highlighting the urgent need to address and mitigate environmental MP pollution.

关键词： Microplastics Sleep Lifespan Reproduction Risk assessment Drosophila melanogaster

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Tuning the ferroelectricity of Hf0.5Zr0.5O2 with alloy electrodes

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Science China(Information Sciences) 2024年第8期67卷 321-330页

作者： Keqin LIU Bingjie DANG Zhiyu YANG Teng ZHANG Zhen YANG Jinxuan BAI Zelun PAN Ru HUANG Yuchao YANG Beijing Advanced Innovation Center for Integrated Circuits School of Integrated Circuits Peking University School of Electronic and Computer Engineering Peking University Center for brain Inspired Chips Institute for Artificial Intelligence Peking University Center for brain Inspired Intelligence Chinese Institute for Brain ResearchBeijing

Tuning ferroelectricity of Hf0.5Zr0.5O2is crucial for facilitating its practical applications in various fields, including in-memory and neuromorphic computing. Previous studies have revealed that the electrodes have a significant influence on ferroelectricity, and changing electrode materials can realize different but discrete ferroelectric polarization values. Here, we introduce an alloy-electrode method, in order to achieve gradual and accurate modulation of ferroelectric polarization, especially useful for matching the polarization charges at the interface of ferroelectric insulators and ferroelectric semiconductors. Au and W electrodes are chosen as baselines for realizing weak and strong ferroelectric polarization, where the intermediate states can be achieved by adjusting the ratio of metals in the Au-W alloy. To demonstrate the generality of this approach, the Cu-W alloy electrode is also realized for tuning ferroelectric polarization. The effect of alloy electrodes on device leakage current, endurance, and retention is evaluated. In addition, the temperature stability of ferroelectric capacitors is tested, where limited changes in both remnant polarization and coercive voltages are observed, showing the great potential of the ferroelectric hafnium oxide. Such gradual modulation of ferroelectric polarization could facilitate the application of Hf0.5Zr0.5O2in in-memory and neuromorphic computing.

关键词： ferroelectric hafnium oxide alloy electrode gradual modulation temperature stability

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State-sensitive convolutional sparse coding for potential biomarker identification in brain signals

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Science China(Information Sciences) 2024年第5期67卷 270-286页

作者： Puli WANG Yu QI Gang PAN College of Computer Science and Technology Zhejiang University State Key Laboratory of brain-Machine Intelligence Zhejiang University MOE Frontier Science Center for brain Science and brain-machine Integration Zhejiang University Affiliated Mental Health Center & Hangzhou Seventh People's Hospital Zhejiang University School of Medicine

The identification of prototypical waveforms, such as sleep spindles and epileptic spikes, is crucial for the diagnosis of neurological disorders. These prototypical waveforms are usually recurrently presented in certain brain states, serving as potential biomarkers for clinical evaluations. Convolutional sparse coding(CSC) approaches have demonstrated strength in identifying recurrent patterns in time-series. However,existing CSC approaches do not explicitly explore state-specific patterns, making it difficult to identify state-related biomarkers. To address this problem, we propose state-sensitive CSC to learn state-specific prototypical waveforms. Specifically, we model signals of a certain state with specific waveforms that only appear frequently in this state and background waveforms that are independent of states. Based on this,state-sensitive CSC separates state-specific waveforms from background ones explicitly by incorporating incoherence constraints into optimizations. Experiments with epilepsy brain signals demonstrate that our approach can effectively identify prototypical waveforms in pre-ictal states, providing potential biomarkers for seizure prediction. Our approach provides a promising tool for automatic biomarker candidate identification.

关键词： convolutional sparse coding prototypical waveforms state-specific dictionary biomarker identification neural signal processing

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Distinct clinical profiles and mutation landscapes of gliomas originating from the neocortex,mesocortex,and cerebellum

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Genes & Diseases 2024年第1期11卷 53-56页

作者： Ye Cheng Lei Zhang Xiaolong Wu Hiroaki Wakimoto Haoming Geng Yukui Wei Geng Xu Xinru Xiao Jie Bai Yaming Wang Zeliang Hu Leiming Wang Qingtang Lian Department of Neurosurgery Xuanwu HospitalCapital Medical UniversityBeijing 100053China brain tumor Research Center Massachusetts General HospitalDepartment of NeurosurgeryHarvard Medical SchoolBostonMA02134USA Department of Pathology Xuanwu HospitalCapital Medical UniversityBeijing 100053China

Gliomas originating from anatomically and developmentally distinct brain regions have different clinical ***,the molecular landscape underlying this difference remains *** analyzed key molecular mutations via sequencing and correlated them with clinical characteristics in 180 adult patients with gliomas originating from the neocortex,mesocortex,and *** of cerebellar origin had significantly longer survival than those of supratentorial origin,consistent with higher rates of mutation in key genes associated with supratentorial gliomas.

关键词： clinical cortex glioma

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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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Versatile strategies for adult neurogenesis:avenues to repair the injured brain

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Neural Regeneration Research 2024年第4期19卷 774-780页

作者： Junyi Zhao Siyu Liu Xianyuan Xiang Xinzhou Zhu The brain Cognition and brain Disease Institute(BCBDI) Shenzhen Institute of Advanced TechnologyChinese Academy of Sciences Faculty of Life and Health Sciences Shenzhen Institutes of Advanced TechnologyChinese Academy of Sciences Shenzhen-Hong Kong Institute of brain Science-Shenzhen Fundamental Research Institutions

brain injuries due to trauma or stroke are major causes of adult death and ***,few interventions are effective for post-injury repair of brain *** a long debate on whether endogenous neurogenesis actually happens in the adult human brain,there is now substantial evidence to support its *** neurogenesis is usually significantly stimulated by injury,the reparative potential of endogenous differentiation from neural stem/progenitor cells is usually ***,exogenous stem cell transplantation has shown promising results in animal models,but limitations such as poor long-term survival and inefficient neuronal differentiation make it still challenging for clinical ***,a high focus was placed on glia-to-neuron conversion under single-factor *** some inspiring results,the validity of this strategy is still *** this review,we summarize historical findings and recent advances on neurogenesis strategies for neurorepair after brain *** also discuss their advantages and drawbacks,as to provide a comprehensive account of their potentials for further studies.

关键词： adult neurogenesis glia-to-neuron conversion ischemic stroke neurogenic niche neuroinflammation stem cell transplantation traumatic brain injury

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