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A core scientific problem in the treatment of central nervous system diseases:newborn neurons

Neural Regeneration Research 2024年第12期19卷 2588-2601页

作者： Peng Hao Zhaoyang Yang Kwok-Fai So xiaoguang li Department of Neurobiology School of Basic Medical SciencesCapital Medical UniversityBeijingChina Guangdong-HongKong-Macao Institute of CNS Regeneration Ministry of Education CNS Regeneration Collaborative Joint LaboratoryJinan UniversityGuangzhouGuangdong ProvinceChina Bioland Laboratory(Guangzhou Regenerative Medicine and Health Guangdong Laboratory) GuangzhouGuangdong ProvinceChina Department of Ophthalmology and State Key Laboratory of Brain and Cognitive Sciences The University of Hong KongHong Kong Special Administration RegionChina Center for Brain Science and Brain-Inspired Intelligence Guangdong-Hong Kong-Macao Greater Bay AreaGuangzhouGuangdong ProvinceChina Co-innovation Center of Neuroregeneration Nantong UniversityNantongJiangsu ProvinceChina Department of Biomedical Engineering School of Biological Science and Medical EngineeringBeihang UniversityBeijingChina

It has long been asserted that failure to recover from central nervous system diseases is due to the system's intricate structure and the regenerative incapacity of adult *** over recent decades,numerous studies have established that endogenous neurogenesis occurs in the adult central nervous system,including humans'.This has challenged the long-held scientific consensus that the number of adult neurons remains constant,and that new central nervous system neurons cannot be created or ***,we present a comprehensive overview of the alterations and regulatory mechanisms of endogenous neurogenesis following central nervous system injury,and describe novel treatment strategies that to rget endogenous neurogenesis and newborn neurons in the treatment of central nervous system *** nervous system injury frequently results in alterations of endogenous neurogenesis,encompassing the activation,proliferation,ectopic migration,diffe rentiation,and functional integration of endogenous neural stem *** of the unfavorable local microenvironment,most activated neural stem cells diffe rentiate into glial cells rather than ***,the injury-induced endogenous neurogenesis response is inadequate for repairing impaired neural *** have attempted to enhance endogenous neurogenesis using various strategies,including using neurotrophic factors,bioactive materials,and cell reprogramming *** alone or in combination,these therapeutic strategies can promote targeted migration of neural stem cells to an injured area,ensure their survival and diffe rentiation into mature functional neurons,and facilitate their integration into the neural *** can integration re plenish lost neurons after central nervous system injury,by improving the local *** regulating each phase of endogenous neurogenesis,endogenous neural stem cells can be harnessed to promote effective regeneration of newborn ***

关键词： bioactive materials brain trauma endogenous neurogenesis hippocampal dentate gyrus neural stem cells neurotrophic factors newborn neurons spinal cord injury stroke subventricular zone

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The advantages of multi-level omics research on stem cell-based therapies for ischemic stroke

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Neural Regeneration Research 2024年第9期19卷 1998-2003页

作者： Yiqing Wang Chuheng Chang Renzhi Wang xiaoguang li Xinjie Bao 4+4 Doctor Medical Program Chinese Academy of Medical Sciences&Peking Union Medical CollegeBeijingChina Department of Neurosurgery Peking Union Medical College HospitalPeking Union Medical CollegeChinese Academy of Medical SciencesBeijingChina Beijing Key Laboratory for Biomaterials and Neural Regeneration School of Biological Science and Medical EngineeringBeihang UniversityBeijingChina Department of Neurobiology School of Basic Medical SciencesCapital Medical UniversityBeijingChina

Stem cell transplantation is a potential therapeutic strategy for ischemic stroke. However, despite many years of preclinical research, the application of stem cells is still limited to the clinical trial stage. Although stem cell therapy can be highly beneficial in promoting functional recovery, the precise mechanisms of action that are responsible for this effect have yet to be fully elucidated. Omics analysis provides us with a new perspective to investigate the physiological mechanisms and multiple functions of stem cells in ischemic stroke. Transcriptomic, proteomic, and metabolomic analyses have become important tools for discovering biomarkers and analyzing molecular changes under pathological conditions. Omics analysis could help us to identify new pathways mediated by stem cells for the treatment of ischemic stroke via stem cell therapy, thereby facilitating the translation of stem cell therapies into clinical use. In this review, we summarize the pathophysiology of ischemic stroke and discuss recent progress in the development of stem cell therapies for the treatment of ischemic stroke by applying multi-level omics. We also discuss changes in RNAs, proteins, and metabolites in the cerebral tissues and body fluids under stroke conditions and following stem cell treatment, and summarize the regulatory factors that play a key role in stem cell therapy. The exploration of stem cell therapy at the molecular level will facilitate the clinical application of stem cells and provide new treatment possibilities for the complete recovery of neurological function in patients with ischemic stroke.

关键词： ischemic stroke mesenchymal stem cells metabolomics multilevel omics neural stem/progenitor cells neuroinflammation pathophysiology proteomics stem cell therapy transcriptomes

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Visualizing Wallerian degeneration in the corticospinal tract after sensorimotor cortex ischemia in mice

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Neural Regeneration Research 2024年第3期19卷 636-641页

作者： Jiao Mu liufang Hao Zijue Wang Xuyang Fu Yusen li Fei Hao Hongmei Duan Zhaoyang Yang xiaoguang li Beijing Key Laboratory for Biomaterials and Neural Regeneration School of Biological Science and Medical EngineeringBeihang UniversityBeijingChina Department of Neurobiology School of Basic Medical SciencesCapital Medical UniversityBeijingChina

Stroke can cause Wallerian degeneration in regions outside of the brain,particularly in the corticospinal *** investigate the fate of major glial cells and axons within affected areas of the corticospinal tract following stroke,we induced photochemical infarction of the sensorimotor cortex leading to Wallerian degeneration along the full extent of the corticospinal *** first used a routine,sensitive marker of axonal injury,amyloid precursor protein,to examine Wallerian degeneration of the corticospinal *** antibody to amyloid precursor protein mapped exclusively to proximal axonal segments within the ischemic cortex,with no positive signal in distal parts of the corticospinal tract,at all time *** improve visualization of Wallerian degeneration,we next utilized an orthograde virus that expresses green fluorescent protein to label the corticospinal tract and then quantitatively evaluated green fluorescent protein-expressing *** this approach,we found that axonal degeneration began on day 3 post-stroke and was almost complete by 7 days after *** addition,microglia mobilized and activated early,from day 7 after stroke,but did not maintain a phagocytic state over ***,astrocytes showed relatively delayed mobilization and a moderate response to Wallerian ***,no anterograde degeneration of spinal anterior horn cells was observed in response to Wallerian degeneration of the corticospinal *** conclusion,our data provide evidence for dynamic,pathogenic spatiotemporal changes in major cellular components of the corticospinal tract during Wallerian degeneration.

关键词： corticospinal tract green fluorescent protein microglia spinal anterior horn cells stroke virus trace Wallerian degeneration

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Chitosan-based thermosensitive hydrogel with long-term release of murine nerve growth factor for neurotrophic keratopathy

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Neural Regeneration Research 2024年第3期19卷 680-686页

作者： Jie Wu Yulei Huang Hanrui Yu Kaixiu li Shifeng Zhang Guoqing Qiao Xiao liu Hongmei Duan Yifei Huang Kwok-Fai So Zhaoyang Yang xiaoguang li liqiang Wang Department of Ophthalmology the Third Medical CenterChinese PLA General HospitalBeijingChina The PLA Medical College Department of NephrologyChinese PLA Institute of NephrologyState Key Laboratory of Kidney DiseasesNational Clinical Research Center for Kidney DiseasesBeijingChina Department of Ophthalmology Hainan Hospital of Chinese PLA General HospitalSanyaHainan ProvinceChina Medical School of Chinese PLA BeijingChina Department of Neurobiology School of Basic Medical SciencesCapital Medical UniversityBeijingChina Guangdong-Hongkong-Macao Institute of CNS Regeneration Ministry of Education CNS Regeneration Collaborative Joint LaboratoryJinan UniversityGuangzhouGuangdong ProvinceChina Bioland Laboratory(Guangzhou Regenerative Medicine and Health Guangdong Laboratory) GuangzhouGuangdong ProvinceChina Department of Ophthalmology and State Key Laboratory of Brain and Cognitive Sciences The University of Hong KongHong Kong Special Administrative RegionChina Center for Brain Science and Brain-Inspired Intelligence Guangdong-Hong Kong-Macao Greater Bay AreaGuangzhouGuangdong ProvinceChina Co-innovation Center of Neuroregeneration Nantong UniversityNantongJiangsu ProvinceChina School of Engineering Medicine Beijing Key Laboratory for Biomaterials and Neural RegenerationBeihang UniversityBeijingChina Beijing International Cooperation Bases for Science and Technology on Biomaterials and Neural Regeneration Beijing Advanced Innovation Center for Big Data-Based Precision MedicineBeihang UniversityBeijingChina

Neurotrophic keratopathy is a persistent defect of the corneal epithelium,with or without stromal ulceration,due to corneal nerve deficiency caused by a variety of *** treatment options for neurotrophic keratopathy are *** this study,an ophthalmic solution was constructed from a chitosan-based thermosensitive hydrogel with long-term release of murine nerve growth factor(CTH-mNGF).Its effectiveness was evaluated in corneal denervation(CD)mice and patients with neurotrophic *** the preclinical setting,CTH-mNGF was assessed in a murine corneal denervation ***-mNGF was transparent,thermosensitive,and ensured sustained release of mNGF for over 20 hours on the ocular surface,maintaining the local mNGF concentration around 1300 pg/mL in *** denervation mice treated with CTH-mNGF for 10 days showed a significant increase in corneal nerve area and total corneal nerve length compared with non-treated and CTH treated mice.A subsequent clinical trial of CTH-mNGF was conducted in patients with stage 2 or 3 neurotrophic *** received topical CTH-mNGF twice daily for 8 *** sodium images,Schirmer’s test,intraocular pressure,Cochet-Bonnet corneal perception test,and best corrected visual acuity were *** total,six patients(total of seven eyes)diagnosed with neurotrophic keratopathy were *** 8 weeks of CTH-mNGF treatment,all participants showed a decreased area of corneal epithelial defect,as stained by ***,six out of seven eyes had fluorescence staining scores<***,best corrected visual acuity,intraocular pressure,Schirmer’s test and Cochet-Bonnet corneal perception test results showed no significant *** increase in corneal nerve density was observed by in vivo confocal microscopy after 8 weeks of CTH-mNGF treatment in three out of seven *** study demonstrates that CTH-mNGF is transparent,thermosensitive,and has sustained-release *** effecti

关键词： chitosan corneal reinnervation murine nerve growth factor neurotrophic keratopathy thermosensitive hydrogel

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Activation of endogenous neurogenesis and angiogenesis by basic fibroblast growth factor-chitosan gel in an adult rat model of ischemic stroke

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Neural Regeneration Research 2024年第2期19卷 409-415页

作者： Hongmei Duan Shulun li Peng Hao Fei Hao Wen Zhao Yudan Gao Hui Qiao Yiming Gu Yang Lv Xinjie Bao Kin Chiu Kwok-Fai So Zhaoyang Yang xiaoguang li Department of Neurobiology School of Basic Medical SciencesCapital Medical UniversityBeijingChina Beijing Key Laboratory for Biomaterials and Neural Regeneration School of Engineering MedicineBeihang UniversityBeijingChina Department of Epidemiology and Statistics School of Public Health and ManagementNingxia Medical UniversityYinchuanNingxia Hui Autonomous RegionChina Department of Physical Education Capital University of Economics and BusinessmBeijingChina Department of Neurosurgery Peking Union Medical College HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina Department of Psychology State Key Lab of Brain and Cognitive SciencesThe University of Hong KongHong Kong Special Administration RegionChina Guangdong-Hongkong-Macao Institute of CNS Regeneration Ministry of Education CNS Regeneration Collaborative Joint LaboratoryJinan UniversityGuangzhouGuangdong ProvinceChina Bioland Laboratory(Guangzhou Regenerative Medicine and Health Guangdong Laboratory) GuangzhouGuangdong ProvinceChina Department of Ophthalmology and State Key Laboratory of Brain and Cognitive Sciences The University of Hong KongHong Kong Special Administration RegionChina Center for Brain Science and Brain-Inspired Intelligence Guangdong-Hong Kong-Macao Greater Bay AreaGuangzhouGuangdong ProvinceChina Co-innovation Center of Neuroregeneration Nantong UniversityNantongJiangsu ProvinceChina Department of Biomedical Engineering School of Biological Science and Medical EngineeringBeihang UniversityBeijingChina

Attempts have been made to use cell transplantation and biomaterials to promote cell proliferation,differentiation,migration,and survival,as well as angiogenesis,in the context of brain ***,whether bioactive materials can repair the damage caused by ischemic stroke by activating endogenous neurogenesis and angiogenesis is still *** this study,we applied chitosan gel loaded with basic fibroblast growth factor to the stroke cavity 7 days after ischemic stroke in *** gel slowly released basic fibroblast growth factor,which improved the local microenvironment,activated endogenous neural stem/progenitor cells,and recruited these cells to migrate toward the penumbra and stroke cavity and subsequently differentiate into neurons,while enhancing angiogenesis in the penumbra and stroke cavity and ultimately leading to partial functional *** study revealed the mechanism by which bioactive materials repair ischemic strokes,thus providing a new strategy for the clinical application of bioactive materials in the treatment of ischemic stroke.

关键词： adult endogenous neurogenesis angiogenesis basic fibroblast growth factor-chitosan gel chitosan functional recovery ischemic stroke neural stem cell newborn neuron

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Clinical and molecular significance of homologous recombination deficiency positive non-small cell lung cancer in Chinese population:An integrated genomic and transcriptional analysis

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Chinese Journal of Cancer Research 2024年第3期36卷 282-297页

作者： Yifei Wang Yidan Ma Lei He Jun Du xiaoguang li Peng Jiao Xiaonan Wu Xiaomao Xu Wei Zhou li Yang Jing Di Changbin Zhu liming Xu Tianlin Sun lin li Dongge liu Zheng Wang Department of Pathology Department of Minimally Invasive Tumor Therapies Center Department of Thoracic Surgery Department of Oncology Department of Respiratory and Critical Care Medicine Beijing HospitalNational Center of GerontologyInstitute of Geriatric MedicineChinese Academy of Medical SciencesBeijing 100730China Amoy Diagnostics Co. Ltd.Xiamen 361027China

Objective:The clinical significance of homologous recombination deficiency(HRD)in breast cancer,ovarian cancer,and prostate cancer has been established,but the value of HRD in non-small cell lung cancer(NSCLC)has not been fully *** study aimed to systematically analyze the HRD status of untreated NSCLC and its relationship with patient prognosis to further guide clinical ***:A total of 355 treatment-naïve NSCLC patients were retrospectively *** status was assessed using the AmoyDx Genomic Scar Score(GSS),with a score of≥50 considered ***,transcriptomic,tumor microenvironmental characteristics and prognosis between HRD-positive and HRDnegative patients were ***:Of the patients,25.1%(89/355)were *** to HRD-negative patients,HRDpositive patients had more somatic pathogenic homologous recombination repair(HRR)mutations,higher tumor mutation burden(TMB)(Plifications in PI3K pathway and cell cycle genes,MET and MYC in epidermal growth factor receptor(EGFR)/anaplastic lymphoma kinase(ALK)mutant NSCLC,and more PIK3CA and AURKA in EGFR/ALK wild-type ***-positive NSCLC displayed higher tumor proliferation and immunosuppression ***-negative NSCLC showed activated signatures of major histocompatibility complex(MHC)-II,interferon(IFN)-γand effector memory CD8+T ***-positive patients had a worse prognosis and shorter progressionfree survival(PFS)to targeted therapy(first-and third-generation EGFR-TKIs)(P=0.042).Additionally,HRDpositive,EGFR/ALK wild-type patients showed a numerically lower response to platinum-free immunotherapy ***:Unique genomic and transcriptional characteristics were found in HRD-positive *** prognosis and poor response to EGFR-TKIs and immunotherapy were observed in HRD-positive *** study highlights potential actionable alterations in HRD

关键词： Non-small cell lung cancer homologous recombination deficiency genetic alterations transcriptional analysis tumor microenvironment prognosis

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Passive activity enhances residual control ability in patients with complete spinal cord injury

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Neural Regeneration Research 2025年第8期20卷 2337-2347页

作者： Yanqing Xiao Mingming Gao Zejia He Jia Zheng Hongming Bai Jia-Sheng Rao Guiyun Song Wei Song xiaoguang li Beijing Key Laboratory for Biomaterials and Neural Regeneration Beijing Advanced Innovation Center for Biomedical EngineeringSchool of Biological Science and Medical EngineeringBeihang UniversityBeijingChina Department of Rehabilitation Evaluation China Rehabilitation Research CenterBeijingChina Cardiac Center Beijing Children’s HospitalCapital Medical UniversityBeijingChina The State Key Laboratory of Virtual Reality Technology and Systems Beihang UniversityBeijingChina Department of Rehabilitation Engineering China Rehabilitation Science InstituteBeijingChina

Patients with complete spinal cord injury retain the potential for volitional muscle activity in muscles located below the spinal injury ***,because of prolonged inactivity,initial attempts to activate these muscles may not effectively engage any of the remaining neurons in the descending pathway.A previous study unexpectedly found that a brief clinical round of passive activity significantly increased volitional muscle activation,as measured by surface *** this study,we further explored the effect of passive activity on surface electromyographic signals during volitional control tasks among individuals with complete spinal cord *** patients with chronic complete thoracic spinal cord injury were *** electromyography data from eight major leg muscles were acquired and compared before and after the passive activity *** results indicated that the passive activity led to an increased number of activated volitional muscles and an increased frequency of *** the cumulative root mean square of surface electromyography amplitude for volitional control of movement showed a slight increase after passive activity,the difference was not statistically *** findings suggest that brief passive activity may enhance the ability to initiate volitional muscle activity during surface electromyography tasks and underscore the potential of passive activity for improving residual motor control among patients with motor complete spinal cord injury.

关键词： complete spinal cord injury cycle training epidural electrical stimulation motor training passive activity physiological state spinal cord circuit surface electromyography volitional control task

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教育失配经历对企业雇佣决策的影响:来自简历投递实验和在线招聘职位的证据

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管理世界 2024年第4期40卷 121-137页

作者：李晓光西安交通大学人文社会科学学院

伴随我国高等教育扩张进程,劳动力市场中的教育失配现象日渐凸显。本文聚焦高学历者的教育失配经历对企业雇佣决策的影响,通过区分纵向失配和横向失配,分别从劳动力供给侧和需求侧来检验教育失配经历对雇佣决策产生的异质性后果。实证... 详细信息

伴随我国高等教育扩张进程,劳动力市场中的教育失配现象日渐凸显。本文聚焦高学历者的教育失配经历对企业雇佣决策的影响,通过区分纵向失配和横向失配,分别从劳动力供给侧和需求侧来检验教育失配经历对雇佣决策产生的异质性后果。实证数据来自2023年中国在线联合调查实验项目,该项目通过抓取在线招聘职位和实施简历投递实验来加强因果推断(样本量为37273份)。实验结果表明:第一,教育失配经历对雇佣决策的影响呈现高度异质性。相较于纵向匹配,纵向失配者的简历回应率显著更低,反映出纵向失配潜藏着疤痕效应。相比于横向匹配,横向失配者的简历回应率显著更高,并且主要由横向高配者所驱动,由此揭示出横向高配具有赋能效应。第二,供给侧的性别因素、学校层级和前职公司,显著调节着失配经历对雇佣决策的影响。第三,需求侧的组织产权类型、岗位要求和城市环境,也会显著调节失配经历对雇佣决策的效应。本文揭示出教育失配经历对企业雇佣决策的异质性后果,对于加强高学历者就业质量和推动经济社会高质量发展具有重要意义。

关键词：教育匹配过度教育雇佣决策简历投递实验在线招聘职位

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基于双阶段元学习的小样本中医舌色域自适应分类方法

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电子与信息学报 2024年第3期46卷 986-994页

作者：卓力张雷贾童瑶李晓光张辉北京工业大学计算智能与智能系统北京重点实验室北京100124 北京工业大学信息学部北京100124

舌色是中医(TCM)望诊最关注的诊察特征之一。在实际应用中,通过一台设备采集到的舌象数据训练得到的舌色分类模型应用于另一台设备时,由于舌象数据分布特性不一致,分类性能往往急剧下降。为此,该文提出一种基于双阶段元学习的小样本中... 详细信息

舌色是中医(TCM)望诊最关注的诊察特征之一。在实际应用中,通过一台设备采集到的舌象数据训练得到的舌色分类模型应用于另一台设备时,由于舌象数据分布特性不一致,分类性能往往急剧下降。为此,该文提出一种基于双阶段元学习的小样本中医舌色域自适应分类方法。首先,设计了一种双阶段元学习训练策略,从源域有标注样本中提取域不变特征,并利用目标域的少量有标注数据对网络模型进行微调,使得模型可以快速适应目标域的新样本特性,提高舌色分类模型的泛化能力并克服过拟合。接下来,提出了一种渐进高质量伪标签生成方法,利用训练好的模型对目标域的未标注样本进行预测,从中挑选出置信度高的预测结果作为伪标签,逐步生成高质量的伪标签。最后,利用这些高质量的伪标签,结合目标域的有标注数据对模型进行训练,得到舌色分类模型。考虑到伪标签中含有噪声问题,采用了对比正则化函数,可以有效抑制噪声样本在训练过程中产生的负面影响,提升目标域舌色分类准确率。在两个自建中医舌色分类数据集上的实验结果表明,在目标域仅提供20张有标注样本的情况下,舌色分类准确率达到了91.3%,与目标域有监督的分类性能仅差2.05%。

关键词：中医舌色分类小样本域自适应双阶段元学习

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族际网络的形成机制和社会效应——基于中国西部地区的实证发现

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西南民族大学学报（人文社会科学版） 2024年第2期45卷 20-33页

作者：李晓光郭小弦西安交通大学人文学院社会学系陕西西安710049 西安交通大学实证社会科学研究所陕西西安710049

聚焦中国西部地区族际网络的形成机制及其社会效应。通过对中国西部社会经济变迁调查数据开展实证分析,并使用倾向值匹配方法加强因果推断,最终得到两个结论:第一,族际网络的形成机制中,空间聚居、民族文化、家庭结构和个体特征发挥着... 详细信息

聚焦中国西部地区族际网络的形成机制及其社会效应。通过对中国西部社会经济变迁调查数据开展实证分析,并使用倾向值匹配方法加强因果推断,最终得到两个结论:第一,族际网络的形成机制中,空间聚居、民族文化、家庭结构和个体特征发挥着重要影响;第二,族际网络具有丰富的社会效应,可以优化社会资本和促进民族团结。无论族际聊天还是族际友谊,这种跨越民族边界的社会交往,可以显著扩大网络规模、提高网络顶端、增加网络差异和提升网络均值,由此优化个体社会资本,并显著促进民族团结。未来民族工作需要关注空间聚居和民族文化对族际网络的潜在制约,并且充分发挥族际网络所蕴含的社会效应。

关键词：族际网络族际交往社会资本民族团结

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