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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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Regression analysis and its application to oil and gas exploration:A case study of hydrocarbon loss recovery and porosity prediction,China

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Energy Geoscience 2024年第4期5卷 240-252页

作者： Yang li xiaoguang li Mingyu Guo Chang Chen Pengbo Ni Zijian Huang liaohe Oilfield CNPCPanjinLiaoning124010China Tianjin Company of China National Offshore Oil Corporation Tianjin300452China China-France Bohai Geoservices Co. Ltd.Tianjin300450China Panjin Zhonglu Oil and Gas Technology Service Co. Ltd.PanjinLiaoning124000China

In oil and gas exploration,elucidating the complex interdependencies among geological variables is *** study introduces the application of sophisticated regression analysis method at the forefront,aiming not just at predicting geophysical logging curve values but also innovatively mitigate hydrocarbon depletion observed in geochemical *** a rigorous assessment,we explore the efficacy of eight regression models,bifurcated into linear and nonlinear groups,to accommodate the multifaceted nature of geological *** linear model suite encompasses the Standard Equation,Ridge Regression,Least Absolute Shrinkage and Selection Operator,and Elastic Net,each presenting distinct *** Standard Equation serves as a foundational benchmark,whereas Ridge Regression implements penalty terms to counteract overfitting,thus bolstering model robustness in the presence of *** Least Absolute Shrinkage and Selection Operator for variable selection functions to streamline models,enhancing their interpretability,while Elastic Net amalgamates the merits of Ridge Regression and Least Absolute Shrinkage and Selection Operator,offering a harmonized solution to model complexity and *** the nonlinear front,Gradient Descent,Kernel Ridge Regression,Support Vector Regression,and Piecewise Function-Fitting methods introduce innovative *** Descent assures computational efficiency in optimizing solutions,Kernel Ridge Regression leverages the kernel trick to navigate nonlinear patterns,and Support Vector Regression is proficient in forecasting extremities,pivotal for exploration risk *** Piecewise Function-Fitting approach,tailored for geological data,facilitates adaptable modeling of variable interrelations,accommodating abrupt data trend *** analysis identifies Ridge Regression,particularly when augmented by Piecewise Function-Fitting,as superior in recouping hydrocarbon losses,and underscoring it

关键词： Regression analysis Oil and gas exploration Multiple linear regression model Nonlinear regression model Hydrocarbon loss recovery Porosity prediction

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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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Ultralow operating voltage for energy conversion performance in Hf_(1-x)Zr_(x)O_(2) thin films

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Journal of Materiomics 2024年第6期10卷 1206-1213页

作者： Ying Hou Baoyuan Wang Zhen Luo Xinzhe Du Zijian Wang Yi Fang xiaoguang li School of Physics East China University of Science and TechnologyShanghai200237China State Key Laboratory of Powder Metallurgy Central South UniversityChangsha410083China Hefei National Research Center for Physical Sciences at the Microscale Department of Physics and CAS Key Laboratory of Strongly-Coupled Quantum Matter PhysicsUniversity of Science and Technology of ChinaHefei230026China

Emerging ferroelectric and antiferroelectric HfO_(2)-based thin films are attractive candidates for energy conversion and storage applications. In this work, the polar phase transformation between tetragonal and orthorhombic phases associated with ferroelectric or antiferroelectric behaviors is utilized to manipulate the electrocaloric cooling and energy storage performances in Zr-doped, woken up HfO_(2) ultrathin films. A giant electrocaloric temperature change of up to 11.85 K in Hf_(0.5)Zr_(0.5)O_(2) with the morphotropic phase boundary (MPB) state and a high energy storage density of 39.34 J/cm3 in the tetragonal phase-dominant Hf0.25Zr0.75O2 system are obtained. More interestingly, contrary to overdoping and excessive electric fields, an appropriate Zr concentration of 0.5 and an applicable driving field of 1.91 MV/cm are desired for the electrocaloric effect, resulting in an ultralow operating voltage as low as 1.3 V in this 6.8 nm thick Hf_(0.5)Zr_(0.5)O_(2) film. These findings illustrate that the structural design strategy is a visible method for achieving optimal energy-related behaviors and highlight the great possibilities for building future energy-related devices.

关键词： HfO_(2)-based films Morphotropic phase boundary state Electrocaloric cooling Energy storage

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A flexible Hf_(0.5)Zr_(0.5)O_(2) thin film with highly robust ferroelectricity

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Journal of Materiomics 2024年第1期10卷 210-217页

作者： Xiang Zhou Haoyang Sun Jiachen li Xinzhe Du He Wang Zhen Luo Zijian Wang Yue lin Shengchun Shen Yuewei Yin xiaoguang li Hefei National Research Center for Physical Sciences at the Microscale Department of Physicsand CAS Key Laboratory of Strongly-Coupled Quantum Matter PhysicsUniversity of Science and Technology of ChinaHefei230026China Collaborative Innovation Center of Advanced Microstructures Nanjing210093China

Flexible hafnia-based ferroelectric memories are arousing much interest with the ever-growing demands for nonvolatile data storage in wearable electronic ***,high-quality flexible Hf_(0.5)Zr_(0.5)O_(2)membranes with robust ferroelectricity were fabricated on inorganic pliable mica substrates via an atomic layer deposition *** flexible Hf_(0.5)Zr_(0.5)O_(2) thin membranes with a thickness of∼8 nm exhibit a high remanent polarization of∼16μC/cm^(2),which possess very robust polarization switching endurance(>10^(10) cycles,two orders of magnitude better than reported flexible HfO_(2)-based films)and superior retention ability(expected>10 years).In particular,stable ferroelectric polarization as well as excellent endurance and retention performance show negligible degradations under 6 mm radius bending conditions or after 10^(4) bending cycles with a 6 mm bending *** results mark a crucial step in the development of flexible hafnium oxide-based ferroelectric memories for wearable electronic devices.

关键词： Ferroelectric polarization Hf_(0.5)Zr_(0.5)O_(2) Flexibility Mica Atomic layer deposition

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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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