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Hypidone hydrochloride(YL-0919)ameliorates functional deficits after traumatic brain injury in mice by activating the sigma-1 receptor for antioxidation

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Neural Regeneration Research 2025年第8期20卷 2325-2336页

作者： Yafan Bai Hui Ma Yue Zhang Jinfeng Li Xiaojuan Hou Yixin Yang Guyan Wang Yunfeng Li Department of Anesthesiology Beijing Tongren HospitalCapital Medical UniversityBeijingChina beijing institute of basic medical Sciences BeijingChina Hebei North University ZhangjiakouHebei ProvinceChina beijing institute of Pharmacology and Toxicology State Key Laboratory of Toxicology and Medical CountermeasuresBeijing Key Laboratory of NeuropsychopharmacologyBeijingChina

Traumatic brain injury involves complex pathophysiological mechanisms,among which oxidative stress significantly contributes to the occurrence of secondary *** this study,we evaluated hypidone hydrochloride(YL-0919),a self-developed antidepressant with selective sigma-1 receptor agonist properties,and its associated mechanisms and targets in traumatic brain *** experiments to assess functional deficits were followed by assessment of neuronal damage through histological analyses and examination of blood-brain barrier permeability and brain ***,we investigated the antioxidative effects of YL-0919 by assessing the levels of traditional markers of oxidative stress in vivo in mice and in vitro in HT22 ***,the targeted action of YL-0919 was verified by employing a sigma-1 receptor antagonist(BD-1047).Our findings demonstrated that YL-0919 markedly improved deficits in motor function and spatial cognition on day 3 post traumatic brain injury,while also decreasing neuronal mortality and reversing blood-brain barrier disruption and brain ***,YL-0919 effectively combated oxidative stress both in vivo and in *** protective effects of YL-0919 were partially inhibited by *** results indicated that YL-0919 relieved impairments in motor and spatial cognition by restraining oxidative stress,a neuroprotective effect that was partially reversed by the sigma-1 receptor antagonist ***-0919 may have potential as a new treatment for traumatic brain injury.

关键词： antidepressant drug blood-brain barrier cognitive function hypidone hydrochloride(YL-0919) neurological function nuclear factor-erythroid 2 related factor 2 oxidative stress sigma-1 receptor superoxide dismutase traumatic brain injury

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Epigenetic regulation of the inflammatory response in stroke

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Neural Regeneration Research 2025年第11期20卷 3045-3062页

作者： Jingyi Liang Fei Yang Zixiao Li Qian Li School of basic medical Sciences Capital Medical UniversityBeijingChina Department of Neurobiology School of Basic Medical SciencesCapital Medical UniversityBeijingChina Laboratory for Clinical Medicine Beijing Key Laboratory of Neural Regeneration and RepairCapital Medical UniversityBeijingChina Department of Neurology Beijing Tiantan HospitalCapital Medical UniversityBeijingChina China National Clinical Research Center for Neurological Diseases Beijing Tiantan HospitalCapital Medical UniversityBeijingChina National Center for Healthcare Quality Management in Neurological Diseases Beijing Tiantan HospitalCapital Medical UniversityBeijingChina Chinese institute for Brain Research BeijingChina Research Unit of Artificial Intelligence in Cerebrovascular Disease Chinese Academy of Medical SciencesBeijingChina beijing Engineering Research Center of Digital Healthcare for Neurological Diseases BeijingChina Department of Biochemistry and Molecular Biology School of Basic Medical SciencesCapital Medical UniversityBeijingChina beijing Key Laboratory of Cancer Invasion and Metastasis Research Capital Medical UniversityBeijingChina

Stroke is classified as ischemic or hemorrhagic,and there are few effective treatments for either *** mechanisms play a critical role in secondary brain injury following a stroke,which manifests as cytokine release,blood–brain barrier disruption,neuronal cell death,and ultimately behavioral *** the inflammatory response has been shown to mitigate this cascade of events in experimental stroke ***,in clinical trials of anti-inflammatory agents,longterm immunosuppression has not demonstrated significant clinical benefits for *** may be attributable to the dichotomous roles of inflammation in both tissue injury and repair,as well as the complex pathophysiologic inflammatory processes in *** acute harmful inflammatory responses or inducing a phenotypic shift from a pro-inflammatory to an anti-inflammatory state at specific time points after a stroke are alternative and promising therapeutic *** agents that can modulate inflammation requires a detailed understanding of the inflammatory processes of ***,epigenetic reprogramming plays a crucial role in modulating post-stroke inflammation and can potentially be exploited for stroke *** this review,we summarize current findings on the epigenetic regulation of the inflammatory response in stroke,focusing on key signaling pathways including nuclear factor-kappa B,Janus kinase/signal transducer and activator of transcription,and mitogen-activated protein kinase as well as inflammasome *** also discuss promising molecular targets for stroke *** evidence to date indicates that therapeutic targeting of the epigenetic regulation of inflammation can shift the balance from inflammation-induced tissue injury to repair following stroke,leading to improved post-stroke outcomes.

关键词： DNA methylation histone modification intracerebral hemorrhage ischemic stroke neuroinflammation neuroprotection non-coding RNA RNA methylation subarachnoid hemorrhage treatment

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Lipid droplets in the nervous system:involvement in cell metabolic homeostasis

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Neural Regeneration Research 2025年第3期20卷 740-750页

作者： Yuchen Zhang Yiqing Chen Cheng Zhuang Jingxuan Qi Robert Chunhua Zhao Jiao Wang School of Life Sciences Shanghai UniversityShanghaiChina School of Medicine Shanghai UniversityShanghaiChina institute of basic medical Sciences Chinese Academy of medical Sciences School of Basic MedicinePeking Union Medical CollegeBeijingChina Center of Excellence in Tissue Engineering Chinese Academy of Medical SciencesBeijingChina beijing Key Laboratory of New Drug Development and Clinical Trial of Stem Cell Therapy BeijingChina

Lipid droplets serve as primary storage organelles for neutral lipids in neurons,glial cells,and other cells in the nervous *** droplet formation begins with the synthesis of neutral lipids in the endoplasmic ***,lipid droplets were recognized for their role in maintaining lipid metabolism and energy homeostasis;however,recent research has shown that lipid droplets are highly adaptive organelles with diverse functions in the nervous *** addition to their role in regulating cell metabolism,lipid droplets play a protective role in various cellular stress ***,lipid droplets exhibit specific functions in neurons and glial *** of lipid droplet formation leads to cellular dysfunction,metabolic abnormalities,and nervous system *** review aims to provide an overview of the role of lipid droplets in the nervous system,covering topics such as biogenesis,cellular specificity,and ***,it will explore the association between lipid droplets and neurodegenerative *** the involvement of lipid droplets in cell metabolic homeostasis related to the nervous system is crucial to determine the underlying causes and in exploring potential therapeutic approaches for these diseases.

关键词： Alzheimer's disease lipid droplet biogenesis lipid droplets lipid metabolism nervous system neurodegenerative disorders oxidative stress Parkinson's disease

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The complex roles of m^(6)A modifications in neural stem cell proliferation, differentiation, and self-renewal and implications for memory and neurodegenerative diseases

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Neural Regeneration Research 2025年第6期20卷 1582-1598页

作者： Yanxi Li Jing Xue Yuejia Ma Ke Ye Xue Zhao Fangliang Ge Feifei Zheng Lulu Liu Xu Gao Dayong Wang Qing Xia Department of Biochemistry and Molecular Biology College of Basic Medical SciencesHarbin Medical UniversityHarbinHeilongjiang ProvinceChina College of basic medical Sciences Harbin Medical UniversityHarbinHeilongjiang ProvinceChina basic medical institute Heilongjiang Academy of Medical SciencesHarbinHeilongjiang ProvinceChina Key Laboratory of Heilongjiang Province for Genetically Modified Animals Harbin Medical UniversityHarbinHeilongjiang ProvinceChina Translational Medicine Research and Cooperation Center of Northern China Heilongjiang Academy of Medical SciencesHarbinHeilongjiang ProvinceChina Dongzhimen Hospital Beijing University of Chinese MedicineBeijingChina

N6-methyladenosine(m^(6)A), the most prevalent and conserved RNA modification in eukaryotic cells, profoundly influences virtually all aspects of mRNA metabolism. mRNA plays crucial roles in neural stem cell genesis and neural regeneration, where it is highly concentrated and actively involved in these processes. Changes in m^(6)A modification levels and the expression levels of related enzymatic proteins can lead to neurological dysfunction and contribute to the development of neurological diseases. Furthermore, the proliferation and differentiation of neural stem cells, as well as nerve regeneration, are intimately linked to memory function and neurodegenerative diseases. This paper presents a comprehensive review of the roles of m^(6)A in neural stem cell proliferation, differentiation, and self-renewal, as well as its implications in memory and neurodegenerative diseases. m^(6)A has demonstrated divergent effects on the proliferation and differentiation of neural stem cells. These observed contradictions may arise from the time-specific nature of m^(6)A and its differential impact on neural stem cells across various stages of development. Similarly, the diverse effects of m^(6)A on distinct types of memory could be attributed to the involvement of specific brain regions in memory formation and recall. Inconsistencies in m^(6)A levels across different models of neurodegenerative disease, particularly Alzheimer's disease and Parkinson's disease, suggest that these disparities are linked to variations in the affected brain regions. Notably, the opposing changes in m^(6)A levels observed in Parkinson's disease models exposed to manganese compared to normal Parkinson's disease models further underscore the complexity of m^(6)A's role in neurodegenerative processes. The roles of m^(6)A in neural stem cell proliferation, differentiation, and self-renewal, and its implications in memory and neurodegenerative diseases, appear contradictory. These inconsistencies may be a

关键词： Alzheimer's disease cell self-renewal central nervous system memory microglia nerve regeneration neurodegenerative diseases neurogenesis RNA methylation

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Boosting bidirectional sulfur conversion enabled by introducing boron-doped atoms and phosphorus vacancies in Ni2P for lithium-sulfur batteries

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Journal of Energy Chemistry 2025年第1期100卷 760-769页

作者： Lin Peng Yu Bai Hang Li Meixiu Qu Zhenhua Wang Kening Sun Advanced Research institute of Multidisciplinary Science Beijing Institute of Technology beijing Key Laboratory of Chemical Power Source and Green Catalysis School of Chemistry and Chemical Engineering Beijing Institute of Technology

Lithium-sulfur （Li-S） batteries have gained great attention due to the high theoretical energy density and low cost,yet their further commercialization has been obstructed by the notorious shuttle effect and sluggish redox ***,we supply a strategy to optimize the electron structure of Ni2P by concurrently introducing B-doped atoms and P vacancies in Ni2P （Vp-B-Ni2P）,thereby enhancing the bidirectional sulfur *** study indicates that the simultaneous introduction of B-doped atoms and P vacancies in Ni2P causes the redistribution of electron around Ni atoms,bringing about the upward shift of d-band center of Ni atoms and effective d-p orbital hybridization between Ni atoms and sulfur species,thus strengthening the chemical anchoring for lithium polysulfides （LiPSs） as well as expediting the bidirectional conversion kinetics of sulfur ***,theoretical calculations reveal that the incorporation of B-doped atoms and P vacancies in Ni2P selectively promotes Li2S dissolution and nucleation ***,the Li-S batteries with Vp-B-Ni2P-separators present outstanding rate ability of 777 m A h g-1at 5 C and high areal capacity of 8.03 mA h cm-2under E/S of 5μL mg-1and sulfur loading of 7.20 mg *** work elucidates that introducing heteroatom and vacancy in metal phosphide collaboratively regulates the electron structure to accelerate bidirectional sulfur conversion.

关键词： Lithium sulfur batteries

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High-dose dexamethasone regulates microglial polarization via the GR/JAK1/STAT3 signaling pathway after traumatic brain injury

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Neural Regeneration Research 2025年第9期20卷 2611-2623页

作者： Mengshi Yang Miao Bai Yuan Zhuang Shenghua Lu Qianqian Ge Hao Li Yu Deng Hongbin Wu Xiaojian Xu Fei Niu Xinlong Dong Bin Zhang Baiyun Liu beijing Tiantan Hospital Capital Medical UniversityBeijingChina Department of Neurology The First Hospital of Tsinghua UniversityBeijingChina Department of Neurotrauma and beijing Key Laboratory of Central Nervous System Injury Beijing Neurosurgical InstituteCapital Medical UniversityBeijingChina Department of Critical Care Medicine Beijing Tiantan HospitalCapital Medical UniversityBeijingChina Center for Nerve Injury and Repair Beijing Institute of Brain DisordersChina National Clinical Research Center for Neurological DiseasesBeijingChina

Although microglial polarization and neuroinflammation are crucial cellular responses after traumatic brain injury,the fundamental regulatory and functional mechanisms remain insufficiently *** potent anti-inflammato ry agents,the use of glucoco rticoids in traumatic brain injury is still controversial,and their regulatory effects on microglial polarization are not yet *** the present study,we sought to determine whether exacerbation of traumatic brain injury caused by high-dose dexamethasone is related to its regulatory effects on microglial polarization and its mechanisms of *** vitro cultured BV2 cells and primary microglia and a controlled cortical impact mouse model were used to investigate the effects of dexamethasone on microglial ***,dexamethasone,RU486(a glucocorticoid receptor antagonist),and ruxolitinib(a Janus kinase 1 antagonist)were ***-sequencing data obtained from a C57BL/6 mouse model of traumatic brain injury were used to identify potential targets of *** Morris water maze,quantitative reverse transcription-polymerase chain reaction,western blotting,immunofluorescence and confocal microscopy analysis,and TUNEL,Nissl,and Golgi staining were performed to investigate our ***-throughput sequencing results showed that arginase 1,a marker of M2 microglia,was significantly downregulated in the dexamethasone group compared with the traumatic brain injury group at3 days post-traumatic brain *** dexamethasone inhibited M1 and M2 microglia,with a more pronounced inhibitory effect on M2microglia in vitro and in *** receptor plays an indispensable role in microglial polarization after dexamethasone treatment following traumatic brain ***,glucocorticoid receptor activation increased the number of apoptotic cells and neuronal death,and also decreased the density of dendritic spines.A possible downstream receptor signaling mechanism is th

关键词： apoptosis BV2 microglia dexamethasone glucocorticoid receptor glucocorticoids innate immune system microglial polarization neuroinflammation primary microglia traumatic brain injury

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Multi-layer multi-pass friction rolling additive manufacturing of Al alloy:Toward complex large-scale high-performance components

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International Journal of Minerals,Metallurgy and Materials 2025年第2期32卷 425-438页

作者： Haibin Liu Run Hou Chenghao Wu Ruishan Xie Shujun Chen College of Mechanical&Energy Engineering Beijing University of TechnologyBeijing 100124China Chongqing Research institute of beijing University of Technology Chongqing 401121China

At present,the emerging solid-phase friction-based additive manufacturing technology,including friction rolling additive man-ufacturing(FRAM),can only manufacture simple single-pass *** this study,multi-layer multi-pass FRAM-deposited alumin-um alloy samples were successfully prepared using a non-shoulder tool *** material flow behavior and microstructure of the over-lapped zone between adjacent layers and passes during multi-layer multi-pass FRAM deposition were studied using the hybrid 6061 and 5052 aluminum *** results showed that a mechanical interlocking structure was formed between the adjacent layers and the adja-cent passes in the overlapped center *** friction and rolling of the tool head led to different degrees of lateral flow and plastic deformation of the materials in the overlapped zone,which made the recrystallization degree in the left and right edge zones of the over-lapped zone the highest,followed by the overlapped center zone and the non-overlapped *** tensile strength of the overlapped zone exceeded 90%of that of the single-pass deposition *** is proved that although there are uneven grooves on the surface of the over-lapping area during multi-layer and multi-pass deposition,they can be filled by the flow of materials during the deposition of the next lay-er,thus ensuring the dense microstructure and excellent mechanical properties of the overlapping *** multi-layer multi-pass FRAM deposition overcomes the limitation of deposition width and lays the foundation for the future deposition of large-scale high-performance components.

关键词： aluminum alloy additive manufacturing solid-state friction stir welding multi-layer multi-pass

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Prominent cycling reversibility and kinetics enabled by CaTiO3 protective layer on Zn metal for aqueous Zn-ion batteries

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Journal of Energy Chemistry 2025年第1期100卷 245-258页

作者： Gaeun Lee Yong Nam Ahn Seongjoon So Chanwoo Park Jong-Seong Bae Taehyun Park Il Tae Kim Jaehyun Hur School of Chemical Biological and Battery Engineering Gachon University Seongnam Busan Center Korea Basic Science Institute

Aqueous Zn-ion batteries （AZIBs） have received considerable attention owing to their various advantages such as safety,low cost,simple battery assembly conditions,and high ionic ***,they still suffer from serious problems,including uncontrollable dendrite growth,corrosion,hydrogen evolution reaction （HER） from water decomposition,electrode passivation,and unexpected *** creation of a uniform artificial nanocrystal layer on the Zn anode surface is a promising strategy for resolving these ***,we propose the use of a perovskite CaTiO3（CTO） protective layer on Zn（CTO@Zn） as a promising approach for improving the performance of *** CTO artificial layer provides an efficient pathway for Zn ion diffusion towards the Zn metal because of the high dielectric constant （εr=180） and ferroelectric characteristics that enable the alignment of dipole moments and redistribute the Zn2+ions in the CTO *** avoiding the direct contact of the Zn anode with the electrolyte solution,the uneven dendrite growth,corrosion,parasitic side reactions,and HER are mitigated,while CTO retains its mechanical and chemical robustness during ***,CTO@Zn demonstrates an improved lifespan in a symmetric cell configuration compared with bare ***@Zn shows steady overpotential （～68 m V） for 1500 h at 1 mA cm-2/0.5 mA h cm-2,excelling bare ***,when paired with the V2O5-C cathode,the CTO@Zn//V2O5-C full battery delivers 148.4 mA h g-1（based on the mass of the cathode） after 300 *** study provides new insights into Zn metal anodes and the development of high-performance AZIBs.

关键词： Artificial layer Dielectric constant Zn metal anode Zinc aqueous battery

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High-energy-density lithium manganese iron phosphate for lithium-ion batteries: Progresses, challenges, and prospects

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Journal of Energy Chemistry 2025年第1期100卷 1-17页

作者： Bokun Zhang Xiaoyun Wang Shuai Wang Yan Li Libo Chen Handong Jiao Zhijing Yu Jiguo Tu State Key Laboratory of Advanced Metallurgy University of Science and Technology Beijing Research institute for Intelligent Wearable Systems The Hong Kong Polytechnic University institute of Advanced Structure Technology Beijing Institute of Technology

The soaring demand for smart portable electronics and electric vehicles is propelling the advancements in high-energy–density lithium-ion *** manganese iron phosphate (LiMnxFe1-xPO4) has garnered significant attention as a promising positive electrode material for lithium-ion batteries due to its advantages of low cost,high safety,long cycle life,high voltage,good high-temperature performance,and high energy *** LiMnxFe1-xPO4has made significant breakthroughs in the past few decades,there are still facing great challenges in poor electronic conductivity and Li-ion diffusion,manganese dissolution affecting battery cycling performance,as well as low tap *** review systematically summarizes the reaction mechanisms,various synthesis methods,and electrochemical properties of LiMnxFe1-xPO4to analyze reaction processes accurately and guide material ***,the main challenges currently faced are concluded,and the corresponding various modification strategies are discussed to enhance the reaction kinetics and electrochemical performance of LiMnxFe1-xPO4,including multi-scale particle regulation,heteroatom doping,surface coating,as well as microscopic morphology ***,in view of the current research challenges faced by intrinsic reaction processes,kinetics,and energy storage applications,the promising research directions are *** importantly,it is expected to provide key insights into the development of high-performance and stable LiMnxFe1-xPO4materials,to achieve practical energy storage requirements.

关键词： Lithium manganese iron phosphate High energy density Lithium-ion batteries Reaction mechanism Tap density

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Repetitive traumatic brain injury–induced complement C1–related inflammation impairs long-term hippocampal neurogenesis

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Neural Regeneration Research 2025年第3期20卷 821-835页

作者： Jing Wang Bing Zhang Lanfang Li Xiaomei Tang Jinyu Zeng Yige Song Chao Xu Kai Zhao Guoqiang Liu Youming Lu Xinyan Li Kai Shu Department of Neurosurgery Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei ProvinceChina Department of Neurosurgery Shanxi Bethune HospitalShanxi Academy of Medical SciencesTongji Shanxi HospitalThird Hospital of Shanxi Medical UniversityTaiyuanShanxi ProvinceChina Department of Pathophysiology School of Basic Medicine and Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei ProvinceChina institute for Brain Research Wuhan Center of Brain ScienceHuazhong University of Science and TechnologyWuhanHubei ProvinceChina Department of Graduate Student Chongqing Medical UniversityChongqingChina Department of basic Medicine School of Medical ScienceHubei University for NationalitiesEnshiHubei ProvinceChina Department of Anatomy School of Basic Medicine and Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei ProvinceChina

Repetitive traumatic brain injury impacts adult neurogenesis in the hippocampal dentate gyrus,leading to long-term cognitive ***,the mechanism underlying this neurogenesis impairment remains *** this study,we established a male mouse model of repetitive traumatic brain injury and performed long-term evaluation of neurogenesis of the hippocampal dentate gyrus after repetitive traumatic brain *** results showed that repetitive traumatic brain injury inhibited neural stem cell proliferation and development,delayed neuronal maturation,and reduced the complexity of neuronal dendrites and *** with repetitive traumatic brain injuryalso showed deficits in spatial memory ***,following repetitive traumatic brain injury,neuroinflammation was enhanced in the neurogenesis microenvironment where C1q levels were increased,C1q binding protein levels were decreased,and canonical Wnt/β-catenin signaling was *** inhibitor of C1 reversed the long-term impairment of neurogenesis induced by repetitive traumatic brain injury and improved neurological *** findings suggest that repetitive traumatic brain injury–induced C1-related inflammation impairs long-term neurogenesis in the dentate gyrus and contributes to spatial memory retrieval dysfunction.

关键词： complement C1 dendrite dentate gyrus hippocampus neural stem cell neurogenesis neuroinflammation neurological function neuron traumatic brain injury

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