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Neuronal autophagy aggravates microglial inflammatory injury by downregulating CX3CL1/fractalkine after ischemic stroke

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Neural Regeneration Research 2019年第2期14卷 280-288页

作者： hong-yun he Lu Ren Tao Guo Yi-Hao Deng Department of Basic Medicine Medical School Kunming University of Science and Technology

Ischemic stroke often induces excessive neuronal autophagy, resulting in brain damage; meanwhile, inflammatory responses stimulated by ischemia exacerbate neural injury. However, interactions between neuronal autophagy and microglial inflammation following ischemic stroke are poorly understood. CX3CL1/fractalkine, a membrane-bound chemokine expressed on neurons, can suppress microglial inflammation by binding to its receptor CX3CR1 on microglia. In the present study, to investigate whether autophagy could alter CX3CL1 expression on neurons and consequently change microglial inflammatory activity, middle cerebral artery occlusion(MCAO) was established in Sprague-Dawley rats to model ischemic stroke, and tissues from the ischemic penumbra were obtained to evaluate autophagy level and microglial inflammatory activity. MCAO rats were administered 3-methyladenine(autophagy inhibitor) or Tat-Beclin 1(autophagy inducer). Western blot assays were conducted to quantify expression of Beclin-1, nuclear factor kappa Bp65(NF-κB), light chain 3B(LC3B), and CX3CL1 in ischemic penumbra. Moreover, immunofluorescence staining was performed to quantify numbers of LC3B-, CX3CL1-, and Iba-1-positive cells in ischemic penumbra. In addition, enzyme linked immunosorbent assays were utilized to analyze concentrations of tumor necrosis factor alpha(TNF-α), interleukin 6(IL-6), interleukin 1 beta(IL-1β), and prostaglandin E2(PGE2). A dry/wet weight method was used to detect brain water content, while 2,3,5,-triphenyltetrazolium chloride staining was utilized to measure infarct volume. The results demonstrated that autophagy signaling(Beclin-1 and LC3B expression) in penumbra was prominently activated by MCAO, while CX3CL1 expression on autophagic neurons was significantly reduced and microglial inflammation was markedly activated. However, after inhibition of autophagy signaling with 3-methyladenine, CX3CL1 expression on neurons was obviously increased, whereas Iba-1 and NF-κB expression was

关键词： nerve regeneration ischemic stroke neuronal autophagy microglial inflammation CX3CL1 autophagic neurons autophagy induction autophagy inhibition neural regeneration

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Enriched environment boosts the post-stroke recovery of neurological function by promoting autophagy

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Neural Regeneration Research 2021年第5期16卷 813-819页

作者： Yi-Hao Deng Ling-Ling Dong Yong-Jie Zhang Xiao-Ming Zhao hong-yun he Department of Basic Medicine Medical SchoolKunming University of Science and TechnologyKunmingYunnan ProvinceChina

Autophagy is crucial for maintaining cellular homeostasis,and can be activated after ischemic *** also participates in nerve injury and *** purpose of this study was to investigate whether an enriched environment has neuroprotective effects through affecting autophagy.A Sprague-Dawley rat model of transient ischemic stroke was prepared by occlusion of the middle cerebral artery followed by *** week after surgery,these rats were raised in either a standard environment or an enriched environment for 4 successive *** enriched environment increased Beclin-1 expression and the LC3-II/LC3-I ratio in the autophagy/lysosomal pathway in the penumbra of middle cerebral artery-occluded *** environment-induced elevations in autophagic activity were mainly observed in *** environment treatment also promoted the fusion of autophagosomes with lysosomes,enhanced the lysosomal activities of lysosomal-associated membrane protein 1,cathepsin B,and cathepsin D,and reduced the expression of ubiquitin and *** 4 weeks of enriched environment treatment,neurological deficits and neuronal death caused by middle cerebral artery occlusion/reperfusion were significantly alleviated,and infarct volume was significantly *** findings suggest that neuronal autophagy is likely the neuroprotective mechanism by which an enriched environment promotes recovery from ischemic *** study was approved by the Animal Ethics Committee of the Kunming University of Science and Technology,China(approval No.5301002013855)on March 1,2019.

关键词： autophagy brain central nervous system factor injury pathways protection regeneration repair stroke

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Autophagy Elicits Neuroprotection at the Subacute Phase of Transient Cerebral Ischaemia but Has Few Effects on Neurological Outcomes After Permanent Ischaemic Stroke in Rats

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Current Medical Science 2021年第4期41卷 803-814页

作者： Tao GUO Yi-hao DENG Ling-ling DONG Lu REN hong-yun he Department of Basic Medicine Medical SchoolKunming University of Science and TechnologyKunming 650500China

Objective Autophagy was prominently activated by cerebral *** study was to investigate the exact role of autophagy in ischaemic *** Two rat models of transient middle cerebral artery occlusion(tMCAO)and permanent MCAO(pMCAO)were *** brain tissues in the penumbra were obtained to observe the dynamic variations of autophagy activity with Beclin1 and LC3 antibodies by Western *** the characteristic time points,when autophagy activity was markedly elevated or reduced,the autophagy activation signaling was intervened with rapamycin and 3-methyladenine,***,key proteins in the autopahgic/lysosomal pathway were detected with the antibodies of LC3,p62,ubiquitin,LAMP-1 and cathepsin ***,TTC staining,neurological score and immunofluorescence were performed to evaluate brain infarct volume,neurological deficit and neuron survival,*** Both Beclin1 and LC3 expression levels were remarkably altered at 6 h,12 h,2 days and 7 days after ***,the dynamic changes of autophagy activity following pMCAO were identical to those after *** autophagy induction nor autophagy inhibition was able to ameliorate the pMCAO-induced neurological injury due to lysosomal dysfunction,as indicated by low levels of LAMP-1 and cathepsin B,accompanied with the accumulation of LC3-II,ubiquitin and insoluble ***,autophagy induction elicited overt neuroprotection at 2 and 7 days after tMCAO,and this neuroprotection might be elicited by the enhancement of autophagy *** Our study suggests that autophagy confers neuroprotection at the subacute phase of tMCAO but has few effects on neurological outcomes after pMCAO.

关键词： permanent cerebral stroke transient cerebral ischaemia autophagy induction autophagy inhibition neuroprotection

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Dynamic changes in neuronal autophagy and apoptosis in the ischemic penumbra following permanent ischemic stroke

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Neural Regeneration Research 2016年第7期11卷 1108-1114页

作者： Yi-hao Deng hong-yun he Li-qiang Yang Peng-yue Zhang Department of Human Anatomy and Histoembryology Medical SchoolKunming University of Science and Technology

The temporal dynamics of neuronal autophagy and apoptosis in the ischemic penumbra following stroke remains ***,in this study,we investigated the dynamic changes in autophagy and apoptosis in the penumbra to provide insight into potential therapeutic targets for *** adult Sprague-Dawley rat model of permanent ischemic stroke was prepared by middle cerebral artery *** autophagy and apoptosis in the penumbra post-ischemia were evaluated by western blot assay and immunofluorescence staining with antibodies against LC3-Ⅱ and cleaved caspase-3,*** of both LC3-Ⅱ and cleaved caspase-3 in the penumbra gradually increased within 5 hours ***,levels of both proteins declined,especially LC3-Ⅱ.The cerebral infarct volume increased slowly 1–4 hours after ischemia,but subsequently increased rapidly until 5 hours after *** severity of the neurological deficit was positively correlated with infarct ***3-Ⅱ and cleaved caspase-3 levels were high in the penumbra within 5 hours after ischemia,and after that,levels of these proteins decreased at different ***3-Ⅱ levels were reduced to a very low level,but cleaved caspase-3 levels remained high 72 hours after *** results indicate that there are temporal differences in the activation status of the autophagic and apoptotic *** suggests that therapeutic targeting of these pathways should take into consideration their unique temporal dynamics.

关键词： neuronal autophagy permanent infarct deficit caspase neurological targeting occlusion unclear

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The detection, extraction and parameter estimation of extreme-mass-ratio inspirals with deep learning

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Science China(Physics,Mechanics & Astronomy) 2025年第1期Mechanics & Astronomy) .卷 86-96页

作者： Qianyun yun Wen-Biao Han Yi-Yang Guo he Wang Minghui Du Hangzhou Institute for Advanced Study University of Chinese Academy of Sciences Shanghai Astronomical Observatory Chinese Academy of Sciences School of Physics and Astronomy Shanghai Jiao Tong University School of Astronomy and Space Science University of Chinese Academy of Sciences Taiji Laboratory for Gravitational Wave Universe (Beijing/Hangzhou) University of Chinese Academy of Sciences Lanzhou Center for Theoretical Physics Key Laboratory of Theoretical Physics of Gansu Province Key Laboratory of Quantum Theory and Applications of MoE Lanzhou University Institute of Theoretical Physics & Research Center of Gravitation Lanzhou University International Centre for Theoretical Physics Asia-Pacific (ICTP-AP) University of Chinese Academy of Sciences (UCAS) Center for Gravitational Wave Experiment National Microgravity Laboratory Institute of Mechanics Chinese Academy of Sciences

One of the primary goals of space-borne gravitational wave detectors is to detect and analyze extreme-mass-ratio inspirals(EMRIs). This task is particularly challenging because EMRI signals are complex, lengthy, and faint. In this work, we introduce a2-layer convolutional neural network(CNN) approach to detect EMRI signals for space-borne detectors, achieving a true positive rate(TPR) of 96.9% at a 1% false positive rate(FPR) for signal-to-noise ratio(SNR) from 50 to 100. Especially, the key intrinsic parameters of EMRIs such as the mass, spin of the supermassive black hole(SMBH) and the initial eccentricity of the orbit can also be inferred directly by employing a neural network. The mass and spin of the SMBH can be determined at 99% and 92% respectively. This will greatly reduce the parameter spaces and computing cost for the following Bayesian parameter *** model also has a low dependency on the accuracy of the waveform model. This study underscores the potential of deep learning methods in EMRI data analysis, enabling the rapid detection of EMRI signals and efficient parameter estimation.

关键词： gravitational wave EMRIs deep-learing

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Regulation and function of endoplasmic reticulum autophagy in neurodegenerative diseases

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Neural Regeneration Research 2025年第1期20卷 6-20页

作者： Xiu-yun Zhao De-En Xu Ming-Lei Wu Ji-Chuan Liu Zi-Ling Shi Quan-hong Ma Department of Neurology and Clinical Research Center of Neurological Disease the Second Affiliated Hospital of Soochow UniversitySuzhouJiangsu ProvinceChina Institute of Neuroscience&Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases Soochow UniversitySuzhouJiangsu ProvinceChina Department of Neurology Jiangnan University Medical CenterWuxiJiangsu ProvinceChina

The endoplasmic reticulum,a key cellular organelle,regulates a wide variety of cellular *** reticulum autophagy,one of the quality control systems of the endoplasmic reticulum,plays a pivotal role in maintaining endoplasmic reticulum homeostasis by controlling endoplasmic reticulum turnover,remodeling,and *** this review,we briefly describe the endoplasmic reticulum quality control system,and subsequently focus on the role of endoplasmic reticulum autophagy,emphasizing the spatial and temporal mechanisms underlying the regulation of endoplasmic reticulum autophagy according to cellular *** also summarize the evidence relating to how defective or abnormal endoplasmic reticulum autophagy contributes to the pathogenesis of neurodegenerative *** summary,this review highlights the mechanisms associated with the regulation of endoplasmic reticulum autophagy and how they influence the pathophysiology of degenerative nerve *** review would help researchers to understand the roles and regulatory mechanisms of endoplasmic reticulum-phagy in neurodegenerative disorders.

关键词： autophagy endoplasmic reticulum endoplasmic reticulum autophagy endoplasmic reticulum quality control system endoplasmic reticulum receptors endoplasmic reticulum-associated degradation neurodegeneration neurodegenerative disease selective autophagy unfolded protein response

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3D Printing of Tough Hydrogel Scaffolds with Functional Surface Structures for Tissue Regeneration

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Nano-Micro Letters 2025年第2期17卷 18-45页

作者： Ke Yao Gaoying hong Ximin Yuan Weicheng Kong Pengcheng Xia Yuanrong Li Yuewei Chen Nian Liu Jing he Jue Shi Zihe Hu Yanyan Zhou Zhijian Xie Yong he State Key Laboratory of Fluid Power and Mechatronic Systems School of Mechanical EngineeringZhejiang UniversityHangzhou 310027People’s Republic of China Liangzhu Laboratory Zhejiang UniversityHangzhou 310027People’s Republic of China Key Laboratory of 3D Printing Process and Equipment of Zhejiang Province College of Mechanical EngineeringZhejiang UniversityHangzhou 310027People’s Republic of China Stomatology Hospital School of StomatologyZhejiang University School of MedicineHangzhou 310027People’s Republic of China State Key Laboratory of Advanced Welding and Joining Harbin Institute of TechnologyHarbin 150001People’s Republic of China Institute of Digital Medicine Nanjing First HospitalNanjing Medical UniversityNanjing 210006People’s Republic of China

Hydrogel scaffolds have numerous potential applications in the tissue engineering ***,tough hydrogel scaffolds implanted in vivo are seldom reported because it is difficult to balance biocompatibility and high mechanical *** by Chinese ramen,we propose a universal fabricating method(printing-P,training-T,cross-linking-C,PTC&PCT)for tough hydrogel scaffolds to fill this ***,3D printing fabricates a hydrogel scaffold with desired structures(P).Then,the scaffold could have extraordinarily high mechanical properties and functional surface structure by cycle mechanical training with salting-out assistance(T).Finally,the training results are fixed by photo-cross-linking processing(C).The tough gelatin hydrogel scaffolds exhibit excellent tensile strength of 6.66 MPa(622-fold untreated)and have excellent ***,this scaffold possesses functional surface structures from nanometer to micron to millimeter,which can efficiently induce directional cell ***,this strategy can produce bionic human tissue with mechanical properties of 10 kPa-10 MPa by changing the type of salt,and many hydrogels,such as gelatin and silk,could be improved with PTC or PCT *** experiments show that this scaffold can effectively promote the new generation of muscle fibers,blood vessels,and nerves within 4 weeks,prompting the rapid regeneration of large-volume muscle loss injuries.

关键词： 3D printing Tough hydrogel scaffold Functional surface structure Tissue regeneration Biomaterials

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Au掺杂Fe_3O_4纳米粒子酶传感器的制备及其应用于有机磷农药检测的研究

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化学学报 2007年第20期65卷 2303-2308页

作者：闵红曲云鹤李晓华谢宗红卫银银金利通华东师范大学化学系上海200062

合成了金掺杂的四氧化三铁纳米粒子(Au-Fe3O4),以壳聚糖为交联剂,制备了电流型乙酰胆碱酯酶(AChe)生物传感器,并将其应用于有机磷农药(OPs)的检测.实验表明,Au-Fe3O4纳米粒子具有良好的生物兼容性,能够有效地促进电子传递,修饰了Au-Fe3O... 详细信息

合成了金掺杂的四氧化三铁纳米粒子(Au-Fe3O4),以壳聚糖为交联剂,制备了电流型乙酰胆碱酯酶(AChe)生物传感器,并将其应用于有机磷农药(OPs)的检测.实验表明,Au-Fe3O4纳米粒子具有良好的生物兼容性,能够有效地促进电子传递,修饰了Au-Fe3O4纳米粒子的酶传感器,响应速度快,检测灵敏度高,稳定性好;固定在传感器上的乙酰胆碱酯酶有良好的酶动力学响应,其表观米氏常数(KMapp)为10.3mmol/L.利用有机磷农药对乙酰胆碱酯酶的抑制作用,以硫代乙酰胆碱(ATCh)为底物,对有机磷农药敌敌畏进行了检测,检测限达到4.0×10-13mol/L.

关键词： Au-Fe3O4 乙酰胆碱酯酶有机磷农药敌敌畏

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Drosophila models used to simulate human ATP1A1 gene mutations that cause Charcot-Marie-Tooth type 2 disease and refractory seizures

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Neural Regeneration Research 2025年第1期20卷 265-276页

作者： Yao Yuan Lingqi Yu Xudong Zhuang Dongjing Wen Jin he Jingmei hong Jiayu Xie Shengan Ling Xiaoyue Du Wenfeng Chen Xinrui Wang Institute of Life Sciences College of Biological Science and EngineeringFuzhou UniversityFuzhouFujian ProvinceChina NHC Key Laboratory of Technical Evaluation of Fertility Regulation for Non-human Primate(Fujian Maternity and Child health Hospital) FuzhouFujian ProvinceChina Medical Research Center Fujian Maternity and Child Health HospitalCollege of Clinical Medicine for Obstetrics&Gynecology and PediatricsFujian Medical UniversityFuzhouFujian ProvinceChina Department of Neurology and Institute of Neurology of The First Affiliated Hospital Institute of Neuroscienceand Fujian Key Laboratory of Molecular NeurologyFujian Medical UniversityFuzhouFujian ProvinceChina

Certain amino acids changes in the human Na^(+)/K^(+)-ATPase pump,ATPase Na^(+)/K^(+)transporting subunit alpha 1(ATP1A1),cause Charcot-Marie-Tooth disease type 2(CMT2)disease and refractory *** develop in vivo models to study the role of Na^(+)/K^(+)-ATPase in these diseases,we modified the Drosophila gene homolog,Atpα,to mimic the human ATP1A1 gene mutations that cause *** located within the helical linker region of human ATP1A1(I592T,A597T,P600T,and D601F)were simultaneously introduced into endogenous Drosophila Atpαby CRISPR/Cas9-mediated genome editing,generating the Atpα^(TTTF)*** addition,the same strategy was used to generate the corresponding single point mutations in flies(Atpα^(I571T),Atpα^(A576T),Atpα^(P579T),and Atpα^(D580F)).Moreover,a deletion mutation(Atpα^(mut))that causes premature termination of translation was generated as a positive *** these alleles,we found two that could be maintained as homozygotes(Atpα^(I571T)and Atpα^(P579T)).Three alleles(Atpα^(A576T),Atpα^(P579)and Atpα^(D580F))can form heterozygotes with the Atpαmut *** found that the Atpαallele carrying these CMT2-associated mutations showed differential phenotypes in *** heterozygous for Atpα^(TTTF)mutations have motor performance defects,a reduced lifespan,seizures,and an abnormal neuronal *** Drosophila models will provide a new platform for studying the function and regulation of the sodium-potassium pump.

关键词： ATP1A1 Atpα bang-sensitive paralysis Charcot-Marie-Tooth disease type 2 CRISPR/Cas9 homology-directed repair Na^(+)/K^(+)-ATPase point mutation seizures sodium pump

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Sex-dependent alterations in extracellular vesicles linking chronic spinal cord injury to brain neuroinflammation and neurodegeneration

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Neural Regeneration Research 2025年第2期20卷 483-484页

作者： yun Li Junfang Wu Department of Anesthesiology&Shock Trauma and Anesthesiology Research(STAR)CenterUniversity of Maryland School of MedicineBaltimoreMDUSA

Traumatic spinal cord injury(SCI)is a devastating exogenous injury with long-lasting consequences and a leading cause of death and disability *** in assistive technology,rehabilitative interventions,and the ability to identify and intervene in secondary conditions have significantly increased the long-term survival rate of SCI patients,with some people even living well into their seventh or eighth *** survival changes have led neurotrauma researchers to examine how SCI interacts with brain *** health and epidemiological data showed that patients with long-term SCI can have a lower life expectancy and quality of life,along with a higher risk of comorbidities and complications.

关键词： alterations inflammation injury

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