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Mutual regulation of microglia and astrocytes after Gas6 inhibits spinal cord injury

Neural Regeneration Research 2025年第2期20卷 557-573页

作者： Jiewen Chen Xiaolin Zeng Le Wang Wenwu Zhang Gang Li Xing Cheng Peiqiang Su Yong Wan Xiang Li Department of Spine Surgery The First Affiliated HospitalSun Yat-sen UniversityGuangzhouGuangdong ProvinceChina guangdong Province key laboratory of Orthopedics and Traumatology GuangzhouGuangdong ProvinceChina

Invasive inflammation and excessive scar formation are the main reasons for the difficulty in repairing nervous tissue after spinal cord *** and astrocytes play key roles in the spinal cord injury micro-environment and share a close ***,the mechanisms involved remain *** this study,we found that after spinal cord injury,resting microglia(M0)were polarized into pro-inflammatory phenotypes(MG1 and MG3),while resting astrocytes were polarized into reactive and scar-forming *** expression of growth arrest-specific 6(Gas6)and its receptor Axl were significantly down-regulated in microglia and astrocytes after spinal cord *** vitro experiments showed that Gas6 had negative effects on the polarization of reactive astrocytes and pro-inflammatory microglia,and even inhibited the cross-regulation between *** further demonstrated that Gas6 can inhibit the polarization of reactive astrocytes by suppressing the activation of the Yes-associated protein signaling ***,in turn,inhibited the polarization of pro-inflammatory microglia by suppressing the activation of the nuclear factor-κB/p65 and Janus kinase/signal transducer and activator of transcription signaling *** vivo experiments showed that Gas6 inhibited the polarization of pro-inflammatory microglia and reactive astrocytes in the injured spinal cord,thereby promoting tissue repair and motor function ***,Gas6 may play a role in the treatment of spinal cord *** can inhibit the inflammatory pathway of microglia and polarization of astrocytes,attenuate the interaction between microglia and astrocytes in the inflammatory microenvironment,and thereby alleviate local inflammation and reduce scar formation in the spinal cord.

关键词： astrocytes Axl cell polarization Gas6 Hippo signal inflammatory micro-environment intercellular interaction microglia single-cell sequencing spinal cord injury

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Inhibiting ceramide synthase 5 expression in microglia decreases neuroinflammation after spinal cord injury

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Neural Regeneration Research 2025年第10期20卷 2955-2968页

作者： Wei Zhang Yubao Lu Ruoqi Shen Yingjie Wu Chenrui Liu Xingxing Fang Liangming Zhang Bin Liu Limin Rong Department of Spine Surgery The Third Affiliated HospitalSun Yat-sen UniversityGuangzhouGuangdong ProvinceChina National Medical Products Administration(NMPA)key laboratory for Quality Research and Evaluation of Cell Products GuangzhouGuangdong ProvinceChina guangdong Provincial Center for Quality Control of Minimally Invasive Spine Surgery GuangzhouGuangdong ProvinceChina guangdong Provincial Center for Engineering and Technology Research of Minimally Invasive Spine Surgery GuangzhouGuangdong ProvinceChina

Microglia,the resident monocyte of the central nervous system,play a crucial role in the response to spinal cord ***,the precise mechanism remains *** investigate the molecular mechanisms by which microglia regulate the neuroinflammatory response to spinal cord injury,we performed single-cell RNA sequencing dataset analysis,focusing on changes in microglial *** found that the MG1 subpopulation emerged in the acute/subacute phase of spinal cord injury and expressed genes related to cell pyroptosis,sphingomyelin metabolism,and neuroinflammation at high ***,we established a mouse model of contusive injury and performed intrathecal injection of siRNA and molecular inhibitors to validate the role of ceramide synthase 5 in the neuroinflammatory responses and pyroptosis after spinal cord ***,we established a PC12-BV2 cell co-culture system and found that ceramide synthase 5 and pyroptosis-associated proteins were highly expressed to induce the apoptosis of neuron *** ceramide synthase 5 expression in a mouse model of spinal cord injury effectively reduced ***,ceramide synthase 5-induced pyroptosis was dependent on activation of the NLRP3 signaling *** ceramide synthase 5 expression in microglia in vivo reduced neuronal apoptosis and promoted recovery of neurological ***2g7 formed a“bridge”between sphingolipid metabolism and ceramide synthase 5-mediated cell death by inhibiting the NLRP3 signaling ***,these findings suggest that inhibiting ceramide synthase 5 expression in microglia after spinal cord injury effectively suppressed microglial pyroptosis mediated by NLRP3,thereby exerting neuroprotective effects.

关键词： ceramide synthase 5 gasdermin D microglia neuroinflammation NLRP3 nuclear factor kappa B Pla2g7 pyroptosis sphingomyelin metabolism spinal cord injury

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Glutamatergic CYLD deletion leads to aberrant excitatory activity in the basolateral amygdala:association with enhanced cued fear expression

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Neural Regeneration Research 2025年第11期20卷 3259-3272页

作者： Huidong Li Faqin Li Zhaoyi Chen Erwen Wu Xiaoxi Dai Danni Li Haojie An Shiyi Zeng Chunyan Wang Li Yang Cheng Long School of Life sciences South China Normal UniversityGuangzhouGuangdong ProvinceChina School of Life sciences Guangzhou UniversityGuangzhouGuangdong ProvinceChina guangdong Provincial key laboratory of Major Obstetric Diseases The Third Affiliated Hospital of Guangzhou Medical UniversityGuangzhouGuangdong ProvinceChina South China Normal University-Panyu Central Hospital Joint laboratory of Translational Medical Research Panyu Central HospitalGuangzhouGuangdong ProvinceChina

Neuronal activity,synaptic transmission,and molecular changes in the basolateral amygdala play critical roles in fear ***(CYLD)is a deubiquitinase that negatively regulates the nuclear factor kappa-B *** is well studied in non-neuronal cells,yet underinvestigated in the brain,where it is highly *** studies have shown involvement of CYLD in the remodeling of glutamatergic synapses,neuroinflammation,fear memory,and anxiety-and autism-like ***,the precise role of CYLD in glutamatergic neurons is largely ***,we first proposed involvement of CYLD in cued fear *** next constructed transgenic model mice with specific deletion of Cyld from glutamatergic *** results show that glutamatergic CYLD deficiency exaggerated the expression of cued fear in only male ***,loss of CYLD in glutamatergic neurons resulted in enhanced neuronal activation,impaired excitatory synaptic transmission,and altered levels of glutamate receptors accompanied by over-activation of microglia in the basolateral amygdala of male ***,our study suggests a critical role of glutamatergic CYLD in maintaining normal neuronal,synaptic,and microglial *** may contribute,at least in part,to cued fear expression.

关键词： basolateral amygdala cued fear expression cylindromatosis deubiquitinase glutamate receptor 1 glutamatergic neuron microglial activation N-methyl-D-aspartate receptor 1 neuronal activation synaptic transmission

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Storage time affects the level and diagnostic efficacy of plasma biomarkers for neurodegenerative diseases

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Neural Regeneration Research 2025年第8期20卷 2373-2381页

作者： Lifang Zhao Mingkai Zhang Qimeng Li Xuemin Wang Jie Lu Ying Han Yanning Cai Department of Clinical Biobank Xuanwu HospitalCapital Medical UniversityBeijingChina Beijing Geriatric Medical Research Center BeijingChina Department of Neurology Xuanwu HospitalCapital Medical UniversityBeijingChina Department of Radiology and nuclear Medicine Xuanwu HospitalCapital Medical UniversityBeijingChina Beijing key laboratory of Magnetic Resonance Imaging and Brain Informatics BeijingChina key laboratory of Neurodegenerative diseases Ministry of EducationBeijingChina School of Biomedical Engineering Hainan UniversityHaikouHainan ProvinceChina Center of Alzheimer’s Disease Beijing Institute for Brain DisordersBeijingChina National Clinical Research Center for Geriatric Diseases BeijingChina Institute of Biomedical Engineering Shenzhen Bay LaboratoryGaoke Innovation CenterShenzhenGuangdong ProvinceChina Department of Neurobiology Xuanwu HospitalCapital Medical UniversityBeijingChina

Several promising plasma biomarker proteins,such as amyloid-β(Aβ),tau,neurofilament light chain,and glial fibrillary acidic protein,are widely used for the diagnosis of neurodegenerative ***,little is known about the long-term stability of these biomarker proteins in plasma samples stored at-80°*** aimed to explore how storage time would affect the diagnostic accuracy of these biomarkers using a large *** samples from 229 cognitively unimpaired individuals,encompassing healthy controls and those experiencing subjective cognitive decline,as well as 99 patients with cognitive impairment,comprising those with mild cognitive impairment and dementia,were acquired from the Sino Longitudinal Study on Cognitive Decline *** samples were stored at-80°C for up to 6 years before being used in this *** results showed that plasma levels of Aβ42,Aβ40,neurofilament light chain,and glial fibrillary acidic protein were not significantly correlated with sample storage ***,the level of total tau showed a negative correlation with sample storage ***,in individuals without cognitive impairment,plasma levels of total protein and tau phosphorylated protein threonine 181(p-tau181)also showed a negative correlation with sample storage *** was not observed in individuals with cognitive ***,we speculate that the diagnostic accuracy of plasma p-tau181 and the p-tau181 to total tau ratio may be influenced by sample storage ***,caution is advised when using these plasma biomarkers for the identification of neurodegenerative diseases,such as Alzheimer's ***,in cohort studies,it is important to consider the impact of storage time on the overall results.

关键词： Alzheimer’s disease amyloid-β diagnostic ability glial fibrillary acidic protein neurodegeneration neurofilament light chain plasma biomarkers single molecule array storage time tau

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Altered 3D genome reorganization mediates precocious myeloid differentiation of aged hematopoietic stem cells in inflammation

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science China Life sciences 2025年

作者： Xinyu Cui Yu Dong Qiang Zhan Yixin Huang Qianshu Zhu Zihao Zhang Guang Yang Liping Wang Shijun Shen Jia Zhao Zhiyi Lin Jiatong Sun Zhongqu Su Yihan Xiao Chuyu Zhang Yuwei Liang Lu Shen Lichen Ji Xuguang Zhang Jiqing Yin Hong Wang Zhiyang Chen Zhenyu Ju Cizhong Jiang Rongrong Le Shaorong Gao Clinical and Translational Research Center of Shanghai First Maternity & Infant Hospital Frontier Science Center for Stem Cells School of Life Sciences and Technology Tongji University key laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education Orthopaedic Department of Tongji Hospital School of Life Sciences and Technology Tongji University key laboratory of Regenerative Medicine of Ministry of Education Institute of Aging and Regenerative Medicine Department of Developmental & Regenerative Medicine College of Life Science and Technology Jinan University Shandong key laboratory of Animal Bioengineering and Disease Prevention College of Animal Science and Technology Shandong Agricultural University Department of Joint Surgery Shanghai East Hospital Tongji University School of Medicine Shanghai Institute of Nutrition and Health Chinese Academy of Sciences

Inflammation is a driving force of hematopoietic stem cells(HSCs) aging, causing irreversible exhaustion of functional HSCs. However, the underlying mechanism of HSCs erosion by inflammatory insult remains poorly understood. Here, we find that transient LPS exposure primes aged HSCs to undergo accelerated differentiation at the expense of self-renewal, leading to depletion of HSCs. Meanwhile, the central regulator nuclear factor kappa B(NF-κB) mediating functional impairment by inflammation insult induces differential transcriptional response in aged HSCs compared with young HSCs, with precocious activation of myeloid lineage genes. Altered compartmentalization and chromatin loop formation are associated with aging-related differential transcriptional response in HSCs upon lipopolysaccharide(LPS)stimulation. Mechanistically, enhancer and promoter regions of myeloid lineage genes in aged HSCs are more accessible and display more rapid and prominent CTCF occupancy upon LPS stimulation. Our study provides comprehensive resources for the three-dimensional(3D)genome structure of HSCs and sheds light into the ordered genome organization and the associated transcriptome signature underlying HSCs aging.

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Approach the Gell-Mann–Okubo Formula with Machine Learning

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Chinese Physics Letters 2022年第11期39卷 6-11页

作者： Zhenyu Zhang Rui Ma Jifeng Hu Qian Wang guangdong Provincial key laboratory of nuclear science Institute of Quantum MatterSouth China Normal UniversityGuangzhou 510006China guangdong-Hong Kong Joint laboratory of Quantum Matter Southern Nuclear Science Computing CenterSouth China Normal UniversityGuangzhou 510006China

Machine learning is a novel and powerful technology and has been widely used in various science *** demonstrate a machine-learning-based approach built by a set of general metrics and rules inspired by *** advantages of physical constraints,such as dimension identity,symmetry and generalization,we succeed to approach the Gell-Mann-Okubo formula using a technique of symbolic *** approach can effectively find explicit solutions among user-defined observables,and can be extensively applied to studying exotic hadron spectrum.

关键词： spectrum symmetry generalization

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Massless limit of transport theory for massive Fermions

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Chinese Physics C 2020年第10期44卷 137-141页

作者： Xingyu Guo guangdong Provincial key laboratory of nuclear science Institute of Quantum MatterSouth China Normal UniversityGuangzhou 510006China

We studied the m=0 limit of different components of Wigner functions for massive fermions. Comparingwith the chiral kinetic theory, we separated the vanishing and non-vanishing parts of vector and axial-vector components,up to the first order of . Then, we discussed the possible physical meaning of the vanishing and non-vanishingparts and their different behaviors at thermal equilibrium.

关键词： spin quantum kinetic theory mass correction

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Hadron productions and jet substructures associated with Z^(0)/γ in Pb+Pb collisions at the LHC

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science China(Physics,Mechanics & Astronomy) 2023年第12期66卷 77-89页

作者： Shan-Liang Zhang Hongxi Xing Ben-Wei Zhang key laboratory of Atomic and Subatomic Structure and Quantum Control(MOE) Guangdong Basic Research Center of Excellence for Structure and Fundamental Interactions of MatterInstitute of Quantum MatterSouth China Normal UniversityGuangzhou 510006China guangdong-Hong Kong Joint laboratory of Quantum Matter Guangdong Provincial Key Laboratory of Nuclear ScienceSouthern Nuclear Science Computing CenterSouth China Normal UniversityGuangzhou 510006China guangdong-Hong Kong Joint laboratory of Quantum Matter Southern Nuclear Science Computing CenterSouth China Normal UniversityGuangzhou 510006China Institute of Particle Physics and key laboratory of Quarks and Lepton Physics(MOE) Central China Normal UniversityWuhan 430079China

We carry out a detailed study of medium modifications on Z^(0)/γ+hadron correlations as well as jet substructures in association with Z^(0)/γ in Pb+Pb collisions with √S_(NN)=5.02TeV at the *** utilize the linear Boltzmann transport(LBT)model to simulate the jet-medium interactions and medium response,and an extended cluster hadronization model to investigate the nonperturbative transition of quarks and gluons into final hadrons in heavy-ion *** hadronization effect,we can well describe Z^(0)/γ+hadrons correlations and Z^(0)/γ-tagged jet substructures in both p+p and Pb+Pb collisions *** modification on jet profile and jet fragmentation functions indicate that particles carrying a large fraction of the jet momentum are generally closely aligned with the jet axis,whereas low-momentum particles are observed to have a much broader angular distribution relative to jet axis in Pb+Pb collisions due to jet-medium *** particular,we find that Z^(0)/γ-tagged hadron correlations are sensitive to the soft particles from the dense medium and medium response,while jet-substructures show weak dependence on those soft hadrons with only a fraction of them falling inside the jet area.

关键词： relativistic heavy-ion collisions jet quenching hadronization jet substructures

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Dissociation of J/ψin hot medium and magnetic field

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Chinese Physics C 2022年第9期46卷 232-236页

作者： Da Teng Xingyu Guo guangdong Provincial key laboratory of nuclear science Institute of Quantum MatterSouth China Normal UniversityGuangzhou 510006China guangdong-Hong Kong Joint laboratory of Quantum Matter Southern Nuclear Science Computing CenterSouth China Normal UniversityGuangzhou 510006China

Charmonium dissociation is an important probe of the quark–gluon plasma medium in heavy-ion *** magnetic field produced in non-central collisions can affect the charmonia and their *** study the cc bound state in magnetic field and at finite temperature using the Schrodinger *** find that below the dissociation temperature,both the magnetic field and momentum of the charmonia affect the formation or dissociation of the bound state,forming a non-trivial structure.

关键词： Schrodinger equation magnetic field charmonium

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Production of X_(eses)in heavy ion collisions

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Chinese Physics C 2023年第5期47卷 1-5页

作者：胡元元张辉 guangdong Provincial key laboratory of nuclear science Institute of Quantum MatterSouth China Normal UniversityGuangzhou 510006China guangdong-Hong Kong Joint laboratory of Quantum Matter Southern Nuclear Science Computing CenterSouth China Normal UniversityGuangzhou 510006China

The yields of X_(cscs)with its two possible configurations,i.e.,the hadronic molecular state and tetraquark state,for Pb-Pb collisions at√sNN=5.02 TeV is studied.A volume effect is found from the centrality distribution of X_(cscs),which could help to distinguish the inner structure of X_(cscs).We also show the rapidity and the transverse momentum distributions of X_(cscs) production as well as its elliptic flow coefficient as a function of the transverse momentum.

关键词： heavy ion collision exotic hadron hadronic molecular state tetraquark state

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