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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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可再生型高价碘试剂亚碘酰二内酯在高效醇氧化中的应用研究

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化学学报 2015年第10期73卷 1002-1006页

作者：宋爱茹张弛南开大学元素有机化学国家重点实验室天津化学化工协同创新中心天津300071 天津师范大学天津市水资源与水环境重点实验室天津300387

利用商品化的高价碘试剂亚碘酰二内酯(Iodosodilactone)作为最终氧化剂,配合催化量的氮氧自由基2,2,6,6-四甲基哌啶-1-氧自由基(TEMPO)和当量的4-二甲氨基吡啶(DMAP)所组成的反应体系可以将含有不同官能团的伯醇快速高效地氧化为相应的... 详细信息

利用商品化的高价碘试剂亚碘酰二内酯(Iodosodilactone)作为最终氧化剂,配合催化量的氮氧自由基2,2,6,6-四甲基哌啶-1-氧自由基(TEMPO)和当量的4-二甲氨基吡啶(DMAP)所组成的反应体系可以将含有不同官能团的伯醇快速高效地氧化为相应的醛且不会发生过度氧化;将反应体系中的催化剂换为空间位阻较小的氮氧自由基1-甲基-2-金刚烷氮氧自由基(1-Me-AZADO)则可以将仲醇高效地氧化为相应的酮.值得指出的是,反应结束后Iodosodilactone的还原态2-碘-间苯二甲酸和DMAP可以通过简单的过滤及酸碱中和处理进行回收,Iodosodilactone的再生可通过用次氯酸钠/盐酸体系氧化2-碘-间苯二甲酸来高效实现.

关键词：亚碘酰二内酯可再生型高价碘试剂醇氧化氮氧自由基

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Mechanism of inflammatory response and therapeutic effects of stem cells in ischemic stroke:current evidence and future perspectives

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Neural Regeneration Research 2025年第1期20卷 67-81页

作者： Yubo Wang Tingli Yuan Tianjie Lyu Ling zhang Meng Wang Zhiying He Yongjun Wang Zixiao Li Vascular Neurology Department of NeurologyBeijing Tiantan HospitalCapital Medical UniversityBeijingChina China National Clinical Research Center for Neurological Diseases Beijing Tiantan HospitalCapital Medical UniversityBeijingChina Shanghai Engineering Research Center of Stem Cells Translational Medicine ShanghaiChina National Center for Healthcare Quality Management in Neurological Diseases Beijing Tiantan HospitalCapital Medical UniversityBeijingChina Institute for Regenerative Medicine Shanghai East HospitalSchool of Life Sciences and TechnologyTongji UniversityShanghaiChina 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

Ischemic stroke is a leading cause of death and disability worldwide,with an increasing trend and tendency for onset at a younger ***,in particular,bears a high burden of stroke *** recent years,the inflammatory response after stroke has become a research hotspot:understanding the role of inflammatory response in tissue damage and repair following ischemic stroke is an important direction for its *** review summarizes several major cells involved in the inflammatory response following ischemic stroke,including microglia,neutrophils,monocytes,lymphocytes,and ***,we have also highlighted the recent progress in various treatments for ischemic stroke,particularly in the field of stem cell ***,understanding the complex interactions between inflammation and ischemic stroke can provide valuable insights for developing treatment strategies and improving patient *** cell therapy may potentially become an important component of ischemic stroke treatment.

关键词： cell therapy immune cell inflammatory ischemic stroke stem cell

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Characteristic changes in astrocyte properties during astrocyte-to-neuron conversion induced by NeuroD1/Ascl1/Dlx2

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Neural Regeneration Research 2025年第6期20卷 1801-1815页

作者： Qing He Zhen Wang Yuchen Wang Mengjie Zhu Zhile Liang Kanghong zhang Yuge Xu Gong Chen GHM Institute of CNS Regeneration Jinan UniversityGuangzhouGuangdong ProvinceChina

Direct in vivo conversion of astrocytes into functional new neurons induced by neural transcription factors has been recognized as a potential new therapeutic intervention for neural injury and degenerative disorders. However, a few recent studies have claimed that neural transcription factors cannot convert astrocytes into neurons, attributing the converted neurons to pre-existing neurons mis-expressing transgenes. In this study, we overexpressed three distinct neural transcription factors––NeuroD1, Ascl1, and Dlx2––in reactive astrocytes in mouse cortices subjected to stab injury, resulting in a series of significant changes in astrocyte properties. Initially, the three neural transcription factors were exclusively expressed in the nuclei of astrocytes. Over time, however, these astrocytes gradually adopted neuronal morphology, and the neural transcription factors was gradually observed in the nuclei of neuron-like cells instead of astrocytes. Furthermore,we noted that transcription factor-infected astrocytes showed a progressive decrease in the expression of astrocytic markers AQP4(astrocyte endfeet signal), CX43(gap junction signal), and S100β. Importantly, none of these changes could be attributed to transgene leakage into preexisting neurons. Therefore, our findings suggest that neural transcription factors such as NeuroD1, Ascl1, and Dlx2 can effectively convert reactive astrocytes into neurons in the adult mammalian brain.

关键词： aquaporin-4 Ascl1 astrocyte cortex Dlx2 gap junction glia-to-neuron conversion neural regeneration NeuroD1 reprogramming

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Spontaneous Orientation Polarization of Anisotropic Equivalent Dipoles Harnessed by Entropy Engineering for Ultra‑Thin Electromagnetic Wave Absorber

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Nano-Micro Letters 2025年第1期17卷 424-438页

作者： Honghan Wang Xinyu Xiao Shangru Zhai Chuang Xue Guangping Zheng Deqing zhang Renchao Che Junye Cheng Liaoning Key Lab of Lignocellulose Chemistry and BioMaterials Liaoning Collaborative Innovation Center for Lignocellulosic BiorefinerySchool of Light Industry and Chemical EngineeringDalian Polytechnic UniversityDalian 116034People’s Republic of China School of Life Science and Biotechnology Dalian University of TechnologyDalian 116024People’s Republic of China Department of Mechanical Engineering Hong Kong Polytechnic UniversityHung HomKowloonHong Kong 999077People’s Republic of China School of Materials Science and Engineering Qiqihar UniversityQiqihar 161006People’s Republic of China Laboratory of Advanced Materials Shanghai Key Lab of Molecular Catalysis and Innovative MaterialsAcademy for Engineering&TechnologyFudan UniversityShanghai 200438People’s Republic of China Department of Materials Science Shenzhen MSU-BIT UniversityShenzhen 517182People’s Republic of China

The synthesis of carbon supporter/nanoscale high-entropy alloys(HEAs)electromagnetic response composites by carbothermal shock method has been identified as an advanced strategy for the collaborative competition engineering of conductive/dielectric *** migration modes within HEAs as manipulated by the electronegativity,valence electron configurations and molar proportions of constituent elements determine the steady state and efficiency of equivalent ***,enlightened by skin-like effect,a reformative carbothermal shock method using carbonized cellulose paper(CCP)as carbon supporter is used to preserve the oxygencontaining functional groups(O·)of carbonized cellulose fibers(CCF).Nucleation of HEAs and construction of emblematic shell-core CCF/HEAs heterointerfaces are inextricably linked to carbon metabolism induced by O·.Meanwhile,the electron migration mode of switchable electronrich sites promotes the orientation polarization of anisotropic equivalent *** virtue of the reinforcement strategy,CCP/HEAs composite prepared by 35%molar ratio of Mn element(CCP/HEAs-Mn_(2.15))achieves efficient electromagnetic wave(EMW)absorption of−51.35 dB at an ultra-thin thickness of 1.03 *** mechanisms of the resulting dielectric properties of HEAs-based EMW absorbing materials are elucidated by combining theoretical calculations with experimental characterizations,which provide theoretical bases and feasible strategies for the simulation and practical application of electromagnetic functional devices(e.g.,ultra-wideband bandpass filter).

关键词： High-entropy alloys Carbothermal shock Switchable electron migration modes Emblematic shell-core heterointerfaces Ultra-thin thickness

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Study on the hydrogen absorption properties of a YGdTbDyHo rare-earth high-entropy alloy

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International Journal of Minerals,Metallurgy and Materials 2025年第1期32卷 127-135页

作者： Tongyue Li Ziliang Xie Wenjiao Zhou Huan Tong Dawen Yang Anjia zhang Yuan Wu Xiping Song State Key Laboratory for Advanced Metals and Materials University of Science and Technology BeijingBeijing 100083China Whole Win(Beijing)Materials Sci.&Tech.Co. Ltd.Beijing 100083China

This study investigated the microstructure and hydrogen absorption properties of a rare-earth high-entropy alloy(HEA),*** indicated that the YGdTbDyHo alloy had a microstructure of equiaxed grains,with the alloy elements distributed *** hydrogen absorption,the phase structure of the HEA changed from a solid solution with an hexagonal-close-packed(HCP)structure to a high-entropy hydride with an faced-centered-cubic(FCC)structure without any secondary phase *** alloy demonstrated a maximum hydrogen storage capacity of 2.33 H/M(hydrogen atom/metal atom)at 723 K,with an enthalpy change(ΔH)of-141.09 kJ·mol^(-1)and an entropy change(ΔS)of-119.14 J·mol^(-1)·K^(-1).The kinetic mechanism of hydrogen absorption was hydride nucleation and growth,with an apparent activation energy(E_(a))of 20.90 kJ·mol^(-1).Without any activation,the YGdTbDyHo alloy could absorb hydrogen quickly(180 s at 923 K)with nearly no incubation period *** reason for the obtained value of 2.33 H/M was that the hydrogen atoms occupied both tetrahedral and octahedral *** results demonstrate the potential application of HEAs as a high-capacity hydrogen storage material with a large H/M ratio,which can be used in the deuterium storage field.

关键词： rare-earth high-entropy alloy hydrogen absorption capacity pressure–composition–temperature curves kinetics

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AAV2-PDE6B restores retinal structure and function in the retinal degeneration 10 mouse model of retinitis pigmentosa by promoting phototransduction and inhibiting apoptosis

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Neural Regeneration Research 2025年第8期20卷 2408-2419页

作者： Ruiqi Qiu Mingzhu Yang Xiuxiu Jin Jingyang Liu Weiping Wang Xiaoli zhang Jinfeng Han Bo Lei Henan Eye Hospital Henan Provincial People’s HospitalPeople’s Hospital of Zhengzhou UniversityZhengzhouHenan ProvinceChina Eye Institute Henan Academy of Innovations in Medical ScienceZhengzhouHenan ProvinceChina Branch of National Clinical Research Center for Ocular Disease Henan Provincial People’s HospitalZhengzhouHenan ProvinceChina Academy of Medical Science Zhengzhou UniversityZhengzhouHenan ProvinceChina

Retinitis pigmentosa is a group of inherited diseases that lead to retinal degeneration and photoreceptor cell ***,there is no effective treatment for retinitis pigmentosa caused by PDE6B ***-associated virus(AAV)-mediated gene therapy is a promising strategy for treating retinitis *** aim of this study was to explore the molecular mechanisms by which AAV2-PDE6B rescues retinal *** do this,we injected retinal degeneration 10(rd10)mice subretinally with AAV2-PDE6B and assessed the therapeutic effects on retinal function and structure using dark-and light-adapted electroretinogram,optical coherence tomography,and ***-independent acquisition-mass spectrometry-based proteomic analysis was conducted to investigate protein expression levels and pathway enrichment,and the results from this analysis were verified by real-time polymerase chain reaction and western ***2-PDE6B injection significantly upregulated PDE6βexpression,preserved electroretinogram responses,and preserved outer nuclear layer thickness in rd10 *** expressed proteins between wild-type and rd10 mice were closely related to visual perception,and treating rd10 mice with AAV2-PDE6B restored differentially expressed protein expression to levels similar to those seen in wild-type *** Encyclopedia of Genes and Genome analysis showed that the differentially expressed proteins whose expression was most significantly altered by AAV2-PDE6B injection were enriched in phototransduction ***,the phototransductionrelated proteins Pde6α,Rom1,Rho,Aldh1a1,and Rbp1 exhibited opposite expression patterns in rd10 mice with or without AAV2-PDE6B ***,Bax/Bcl-2,p-ERK/ERK,and p-c-Fos/c-Fos expression levels decreased in rd10 mice following AAV2-PDE6B *** data suggest that AAV2-PDE6B-mediated gene therapy promotes phototransduction and inhibits apoptosis by inhibiting the ERK signaling pathway and upr

关键词： apoptosis AAV2-PDE6B ERK1/2 gene therapy phototransduction proteomics rd10 retinitis pigmentosa

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Exosomes originating from neural stem cells undergoing necroptosis participate in cellular communication by inducing TSC2 upregulation of recipient cells following spinal cord injury

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Neural Regeneration Research 2025年第11期20卷 3273-3286页

作者： Shiming Li Jianfeng Li Guoliang Chen Tao Lin Penghui zhang Kuileung Tong Ningning Chen Shaoyu Liu Shenzhen Key Laboratory of Bone Tissue Repair and Translational Research Department of Orthopedic SurgeryThe Seventh Affiliated HospitalSun Yat-sen UniversityShenzhenGuangdong ProvinceChina Department of Orthopedic Surgery The First Affiliated Hospital of Jinan UniversityGuangzhouGuangdong ProvinceChina Department of Orthopedics and Traumatology Zhujiang HospitalSouthern Medical UniversityGuangzhouGuangdong ProvinceChina Department of Orthopedic Surgery The Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdong ProvinceChina Department of Orthopedic Surgery The First Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdong ProvinceChina

We previously demonstrated that inhibiting neural stem cells necroptosis enhances functional recovery after spinal cord *** exosomes are recognized as playing a pivotal role in neural stem cells exocrine function,their precise function in spinal cord injury remains *** investigate the role of exosomes generated following neural stem cells necroptosis after spinal cord injury,we conducted singlecell RNA sequencing and validated that neural stem cells originate from ependymal cells and undergo necroptosis in response to spinal cord ***,we established an in vitro necroptosis model using neural stem cells isolated from embryonic mice aged 16-17 days and extracted *** results showed that necroptosis did not significantly impact the fundamental characteristics or number of *** sequencing of exosomes in necroptosis group identified 108 differentially expressed messenger RNAs,104 long non-coding RNAs,720 circular RNAs,and 14 microRNAs compared with the control *** of a competing endogenous RNA network identified the following hub genes:tuberous sclerosis 2(Tsc2),solute carrier family 16 member 3(Slc16a3),and forkhead box protein P1(Foxp1).Notably,a significant elevation in TSC2 expression was observed in spinal cord tissues following spinal cord ***2-positive cells were localized around SRY-box transcription factor 2-positive cells within the injury ***,in vitro analysis revealed increased TSC2 expression in exosomal receptor cells compared with other *** assessment of cellular communication following spinal cord injury showed that Tsc2 was involved in ependymal cellular communication at 1 and 3 days post-injury through the epidermal growth factor and midkine signaling *** addition,Slc16a3 participated in cellular communication in ependymal cells at 7 days post-injury via the vascular endothelial growth factor and macrophage migration inhibitory factor signaling

关键词： cellular communication competing endogenous RNA exosomes Foxp1 necroptosis neural stem cells Slc16a3 spinal cord injury transcriptome sequencing Tsc2

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Transforming growth factor-beta 1 enhances discharge activity of cortical neurons

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Neural Regeneration Research 2025年第2期20卷 548-556页

作者： Zhihui Ren Tian Li Xueer Liu Zelin zhang Xiaoxuan Chen Weiqiang Chen Kangsheng Li Jiangtao Sheng Department of Microbiology and Immunology Guangdong Provincial Key Laboratory of Infectious Diseases and Molecular ImmunopathologyShantou University Medical CollegeShantouGuangdong ProvinceChina Department of Neurosurgery First Affiliated Hospital of Shantou University Medical CollegeShantouGuangdong ProvinceChina

Transforming growth factor-beta 1(TGF-β1)has been extensively studied for its pleiotropic effects on central nervous system *** neuroprotective or neurotoxic effects of TGF-β1 in specific brain areas may depend on the pathological process and cell types ***-gated sodium channels(VGSCs)are essential ion channels for the generation of action potentials in neurons,and are involved in various neuroexcitation-related ***,the effects of TGF-β1 on the functional properties of VGSCs and firing properties in cortical neurons remain *** this study,we investigated the effects of TGF-β1 on VGSC function and firing properties in primary cortical neurons from *** found that TGF-β1 increased VGSC current density in a dose-and time-dependent manner,which was attributable to the upregulation of Nav1.3 *** VGSC current density and Nav1.3 expression were significantly abolished by preincubation with inhibitors of mitogen-activated protein kinase kinase(PD98059),p38 mitogen-activated protein kinase(SB203580),and Jun NH2-terminal kinase 1/2 inhibitor(SP600125).Interestingly,TGF-β1 significantly increased the firing threshold of action potentials but did not change their firing rate in cortical *** findings suggest that TGF-β1 can increase Nav1.3 expression through activation of the ERK1/2-JNK-MAPK pathway,which leads to a decrease in the firing threshold of action potentials in cortical neurons under pathological ***,this contributes to the occurrence and progression of neuroexcitatory-related diseases of the central nervous system.

关键词： central nervous system cortical neurons ERK firing properties JNK Nav1.3 p38 transforming growth factor-beta 1 traumatic brain injury voltage-gated sodium currents

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Salsolinol as an RNA m~6A methylation inducer mediates dopaminergic neuronal death by regulating YAP1 and autophagy

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Neural Regeneration Research 2025年第3期20卷 887-899页

作者： Jianan Wang Yuanyuan Ran Zihan Li Tianyuan Zhao Fangfang zhang Juan Wang Zongjian Liu Xuechai Chen Beijing International Science and Technology Cooperation Base for Antiviral Drugs College of Chemistry and LifeBeijing University of TechnologyBeijingChina Department of Rehabilitation Beijing Rehabilitation HospitalCapital Medical UniversityBeijingChina

Salsolinol(1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline,Sal)is a catechol isoquinoline that causes neurotoxicity and shares structural similarity with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine,an environmental toxin that causes Parkinson's ***,the mechanism by which Sal mediates dopaminergic neuronal death remains *** this study,we found that Sal significantly enhanced the global level of N~6-methyladenosine(m~6A)RNA methylation in PC12 cells,mainly by inducing the downregulation of the expression of m~6A demethylases fat mass and obesity-associated protein(FTO)and alk B homolog 5(ALKBH5).RNA sequencing analysis showed that Sal downregulated the Hippo signaling *** m~6A reader YTH domain-containing family protein 2(YTHDF2)promoted the degradation of m~6A-containing Yes-associated protein 1(YAP1)mRNA,which is a downstream key effector in the Hippo signaling ***,downregulation of YAP1 promoted autophagy,indicating that the mutual regulation between YAP1 and autophagy can lead to *** findings reveal the role of Sal on m~6A RNA methylation and suggest that Sal may act as an RNA methylation inducer mediating dopaminergic neuronal death through YAP1 and *** results provide greater insights into the neurotoxic effects of catechol isoquinolines compared with other studies and may be a reference for assessing the involvement of RNA methylation in the pathogenesis of Parkinson's disease.

关键词： ALKBH5 autophagy FTO Hippo pathway m~6A Parkinson's disease RNA methylation salsolinol YAP1 YTHDF2

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