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Mitophagy in acute central nervous system injuries:regulatory mechanisms and therapeutic potentials

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Neural Regeneration Research 2025年第9期20卷 2437-2453页

作者： Siyi Xu Junqiu jia Rui mao Xiang Cao Yun Xu Department of Neurology Nanjing Drum Tower HospitalClinical College of Jiangsu UniversityNanjingJiangsu ProvinceChina Department of Neurology Nanjing Drum Tower HospitalChinese Academy of Medical Science&Peking Union Medical CollegeNanjingJiangsu ProvinceChina Department of Neurology Nanjing Drum Tower HospitalAffiliated Hospital of Medical SchoolNanjing UniversityNanjingJiangsu ProvinceChina State Key Laboratory of Pharmaceutical Biotechnology and Institute of Translational Medicine for Brain Critical Diseases Nanjing UniversityNanjingJiangsu ProvinceChina jiangsu Key Laboratory for Molecular Medicine Medical School of Nanjing UniversityNanjingJiangsu ProvinceChina Nanjing Neurology Medical Center NanjingJiangsu ProvinceChina

Acute central nervous system injuries,including ischemic stro ke,intracerebral hemorrhage,subarachnoid hemorrhage,traumatic brain injury,and spinal co rd injury,are a major global health *** optimal therapies and improving the long-term neurological functions of patients with acute central nervous system injuries are urgent *** are susceptible to damage after acute central nervous system injury,and this leads to the release of toxic levels of reactive oxygen species,which induce cell ***,a selective form of autophagy,is crucial in eliminating redundant or damaged mitochondria during these *** evidence has highlighted the significant role of mitophagy in acute central nervous system *** this review,we provide a comprehensive overview of the process,classification,and related mechanisms of *** also highlight the recent developments in research into the role of mitophagy in various acute central nervous system injuries and drug therapies that regulate *** the final section of this review,we emphasize the potential for treating these disorders by focusing on mitophagy and suggest future research paths in this area.

关键词： autophagy intracerebral hemorrhage ischemic stroke mitochondria mitochondrial biogenesis mitochondrial quality control mitophagy spinal cord injury subarachnoid hemorrhage traumatic brain injury

AAV mediated carboxyl terminus of Hsp70 interacting protein overexpression mitigates the cognitive and pathological phenotypes of APP/PS1 mice

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Neural Regeneration Research 2025年第1期20卷 253-264页

作者： Zhengwei Hu Jing Yang Shuo Zhang Mengjie Li Chunyan Zuo Chengyuan mao Zhongxian Zhang Mibo tang Changhe Shi Yuming Xu Department of Neurology The First Affiliated Hospital of Zhengzhou UniversityZhengzhou UniversityZhengzhouHenan ProvinceChina Academy of Medical Sciences of Zhengzhou University ZhengzhouHenan ProvinceChina NHC Key Laboratory of Prevention and treatment of Cerebrovascular Diseases The First Affiliated Hospital of Zhengzhou UniversityZhengzhou UniversityZhengzhouHenan ProvinceChina Henan Key Laboratory of Cerebrovascular Diseases The First Affiliated Hospital of Zhengzhou UniversityZhengzhou UniversityZhengzhouHenan ProvinceChina Institute of Neuroscience Zhengzhou UniversityZhengzhouHenan ProvinceChina Sino-British Research Centre for Molecular Oncology National Centre for International Research in Cell and Gene TherapySchool of Basic Medical SciencesAcademy of Medical SciencesZhengzhou UniversityZhengzhouHenan ProvinceChina Department of Gerontology The First Affiliated Hospital of Zhengzhou UniversityZhengzhou UniversityZhengzhouHenan ProvinceChina

The E3 ubiquitin ligase,carboxyl terminus of heat shock protein 70(Hsp70)interacting protein(CHIP),also functions as a co-chaperone and plays a crucial role in the protein quality control *** this study,we aimed to investigate the neuroprotective effect of overexpressed CHIP on Alzheimer’s *** used an adeno-associated virus vector that can cross the blood-brain barrier to mediate CHIP overexpression in APP/PS1 mouse *** overexpression significantly ameliorated the performance of APP/PS1 mice in the Morris water maze and nest building tests,reduced amyloid-βplaques,and decreased the expression of both amyloid-βand phosphorylated *** also alleviated the concentration of microglia and astrocytes around *** APP/PS1 mice of a younger age,CHIP overexpression promoted an increase in ADAM10 expression and inhibitedβ-site APP cleaving enzyme 1,insulin degrading enzyme,and neprilysin *** of HSP70 and HSP40,which have functional relevance to CHIP,were also *** nuclei transcriptome sequencing in the hippocampus of CHIP overexpressed mice showed that the lysosomal pathway and oligodendrocyte-related biological processes were up-regulated,which may also reflect a potential mechanism for the neuroprotective effect of *** research shows that CHIP effectively reduces the behavior and pathological manifestations of APP/PS1 ***,overexpression of CHIP could be a beneficial approach for the treatment of Alzheimer’s disease.

关键词： adeno-associated virus Alzheimer’s disease APP/PS1 mice carboxyl terminus of Hsp70 interacting protein gene therapy

Inhibition of the NLRP3 inflammasome attenuates spiral ganglion neuron degeneration in aminoglycoside-induced hearing loss

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Neural Regeneration Research 2025年第10期20卷 3025-3039页

作者： jia Fang Zhuangzhuang Li Pengjun Wang Xiaoxu Zhang Song mao Yini Li Dongzhen Yu Xiaoyan Li Yazhi Xing Haibo Shi Shankai Yin Department of Otolaryngology Head and Neck Surgery Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of MedicineOtolaryngology Institute of Shanghai Jiao Tong UniversityShanghai Key Laboratory of Sleep Disordered BreathingShanghaiChina Department of Otorhinolaryngology-Head and Neck Surgery Shanghai Children’s HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghaiChina

Aminoglycosides are a widely used class of antibacterials renowned for their effectiveness and broad antimicrobial ***,their use leads to irreversible hearing damage by causing apoptosis of hair cells as their direct *** addition,the hearing damage caused by aminoglycosides involves damage of spiral ganglion neurons upon *** investigate the mechanisms underlying spiral ganglion neuron degeneration induced by aminoglycosides,we used a C57BL/6J mouse model treated with *** found that the mice exhibited auditory deficits following the acute loss of outer hair *** ganglion neurons displayed hallmarks of pyroptosis and exhibited progressive degeneration over *** profiling of these neurons showed significant upregulation of genes associated with inflammation and immune response,particularly those related to the NLRP3 *** of the canonical pyroptotic pathway in spiral ganglion neurons was observed,accompanied by infiltration of macrophages and the release of proinflammatory *** intervention targeting NLRP3 using Mcc950 and genetic intervention using NLRP3 knockout ameliorated spiral ganglion neuron degeneration in the injury *** findings suggest that NLRP3 inflammasome-mediated pyroptosis plays a role in aminoglycoside-induced spiral ganglion neuron *** of this pathway may offer a potential therapeutic strategy for treating sensorineural hearing loss by reducing spiral ganglion neuron degeneration.

关键词： degeneration hearing loss macrophages Mcc950 neuroinflammation NLRP3 inflammasome ototoxicity pyroptosis sensorineural hearing loss spiral ganglion neuron

Deciphering fungal metabolon coupling tandem inverse-electrondemand Diels-Alder reaction and semipinacol rearrangement for the biosynthesis of spiro polycyclic alkaloids

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Science China Chemistry 2025年第01期 288-296页

作者： Shuai Liu Wen-Qiang Xu Ying-Tong Di Man-Cheng tang Ding-Kang Chen Ming-Ming Cao Yao-Wen Chang Hong-Yu tang Chun-mao Yuan Jun-Bo Yang Zhi-Li Zuo Han Guo Zi-Fei Xu Ying Zeng Yun-Dong Wu Xiao-jiang Hao Key Laboratory of Phytochemistry and Natural Medicines (Chinese Academy of Sciences) Kunming Institute of Botany Chinese Academy of Sciences University of Chinese Academy of Sciences Lab of Computational Chemistry and Drug Design State Key Laboratory of Chemical Oncogenomics Peking University Shenzhen Graduate School Shenzhen Bay Laboratory State Key Laboratory of Microbial Metabolism School of Life Sciences & Biotechnology Shanghai Jiao Tong University State Key Laboratory of Functions and Applications of Medicinal Plants Guizhou Medical University Molecular Biology Experimental Center Germplasm Bank of Wild Species in Southwest China Kunming Institute of Botany Chinese Academy of Sciences Yunnan Key Laboratory for Wild Plant Resources Kunming Institute of Botany Chinese Academy of Sciences Research Unit of Chemical Biology of Natural Anti-Virus Products Chinese Academy of Medical Sciences

In the intricate process of natural product biosynthesis, a metabolon can enhance metabolic flux by associating sequential enzymes. A fungal metabolon, comprising of flavin-dependent monooxygenase Spe F and P450 monooxygenase Spe G, is identified in the biosynthesis of spiro polycyclic alkaloids(+)-notoamide B and its diastereomer(+)-versicolamide B. Using notoamide E as a substance, Spe F/Spe G metabolon can control the stereoselectivity of its 2,3-epoxidation, followed by hydrogen atom ion at C-17 to generate reactive epoxide tau-m A with dienyl iminium unit. Subsequently,(+)-notoamide B and(+)-versicolamide B are produced via tandem nonenzymatic inverse-electron-demand Diels-Alder reaction and semipinacol rearrangement. This provides the first example of metabolon in the biosynthesis of spiro-prenylated indole alkaloids.

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Development of high-strength,low-cost wrought Mg–2.0 mass% Zn alloy with high Mn content

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Progress in Natural Science:Materials International 2016年第6期26卷 630-635页

作者： Fusheng.Pan jianjun mao Gen Zhang Aitao tang jia She College of Materials Science and Engineering Chongqing University National Engineering Research Center for Magnesium Alloys Chongqing University Chongqing Research Center for Advanced Materials Chongqing Academy of Science and Technology Science and Technology on Reactor System Design Technology Laboratory Nuclear Power Institute of China

Mg–Zn–Mn-based alloys have received considerable attention because of their high creep resistance, strength,and good corrosion resistance. The alloying element Mn in Mg–Zn-based alloys is commonly less than 1 wt%. In the present study, the effect of high Mn content(1 wt% and 2 wt%) on the microstructures and mechanical properties of Mg–2Zn–0.3Sr extruded alloy was investigated. The results revealed that the high Mn content significantly increased the ultimate tensile strength, tensile yield strength, compress yield strength, and yield asymmetry of the alloy without affecting its ductility. The dynamically recrystallized(DRXed) grains of Mg–2Zn–0.3Sr were remarkably refined because of the large amount of fine Mn precipitates in the homogenized alloy. The improved strengths were mainly attributed to the fine DRXed grains according to the Hall–Petch effect and to the large amount of spherical and Mn precipitates through the precipitation and dispersion strengthening. The fine DRXed grains and numerous Mn precipitates effectively suppressed the extension twining, substantially enhanced the compress yield strength, and resulted in improved anisotropy.

关键词： Magnesium alloy Mg–Zn alloy Microstructure Ultra-fine grains Second phase Mechanical properties

Evaluation Model and Method of Margin in Electromagnetic Environmental Effects for Complex Systems

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Chinese Journal of Electronics 2021年第1期30卷 171-179页

作者： tang Shiping mao Junfa Key Laboratory of Ministry of Education of Design and Electromagnetic Compatibility of High Speed Electronic System Shanghai Jiao Tong University Research Center for Electromagnetic Environmental Effects Southeast University

Margin is an important index in the control of Electromagnetic environmental effects(E3) and Electromagnetic compatibility(EMC) design for *** to define and verify the E3 margins of complex systems such as ships and airplanes is a difficult problem.A new method of system-level E3 margin evaluation is proposed. Based on the theory of fault tree, the evaluation model of system-level margin is *** complex system function is transformed into the equipment and subsystem that affect the function, and the relationship between margin of system-level and equipment is established. The change from margin of equipment to system-level margin is realized. According to the action process of Electromagnetic environment(EME), the verification and evaluation methods of EME domain, response domain and effect domain are put forward. The margin calculation formula of EME domain and typical electromagnetic energy coupling response are deduced. The problem of margin evaluation for equipment under different input parameters is solved. A typical application example is given. The verification test scheme is designed. The methods of electromagnetic energy radiation and injection are adopted. The system-level margin is analyzed by the data obtained from the effective test verification. The results show that the model and method are reasonable and feasible.

关键词： effect domain evaluation methods fault trees typical electromagnetic energy coupling response E3 margin evaluation response domain margin calculation formula ships EME domain complex systems Electromagnetic environmental effects electromagnetic compatibility system-level margin evaluation model complex system function

Synchronization of noise-perturbed optical systems with multiple time delays

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Chinese Physics B 2012年第2期21卷 187-192页

作者： tang mao-Ning School of Science Huzhou UniversityHuzhou 313000China

In this paper, complete synchronization and generalized synchronization between two unidirectionally coupled optical systems with multiple time delays and noise perturbation are investigated. Sufficient conditions for both complete synchronization and generalized synchronization are rigorously established. Numerical simulations fully support the theoretical results. The effect of parameter mismatch on the quality of synchronization is also explored.

关键词： synchronization noise time delayt

Microwave sintering of Ca_(0.6)La_(0.2667)TiO_3 microwave dielectric ceramics

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International Journal of Minerals,Metallurgy and Materials 2012年第3期19卷 245-251页

作者： jia-mao Li Tai Qiu College of Materials Science and Engineering Nanjing University of Technology Nanjing 210009 China School of Materials Science and Engineering Anhui University of Technology Ma＇anshan 243002 China

Ca0.6La0.2667TiO3 ceramics were prepared by conventional and microwave sintering techniques and their sinterability, microstructure, and microwave dielectric properties were investigated in detail for comparison. Densified Ca0.6La0.E667TiO3 ceramics were obtained by microwave sintering at 1350℃ for 30 min and by conventional sintering at 1450℃ for 4 h. An unusual phenomenon was found that some larger grains （grain size range： 8-10 pan） inclined to assemble in one area but some smaller ones （grain size range： 2-4 μm） inclined to gather in another area in the microwave sintered ceramics. The microwave dielectric properties of Ca0.6La0.2667TiO3 ceramics prepared by micro- wave sintering at 1350℃ were as follows＂ dielectric constant （er） = 119.6, quality factor （Qf） = 17858.5 GHz, and temperature coefficient of resonant fi＇equency （rf）= 155.5 ppm/℃. In contrast, the microwave dielectric properties of the ceramics prepared by conventional sintering at 1450℃ were er = 117.4, Qf= 13375 GHz, and rf= 217.2 ppm/℃.

关键词： pcrovskite microwave sintering microstructure dielectric properties

Modular assembly of Co4-thiacalix[4]arene units and Keggin-type SiW12O40 for visible-light photothermal conversion

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Tungsten 2025年第1期 112-119页

作者： jia-Hui Li Qing Zhao Dong-Ao mao Kun Zhou Bao-Kuan Chen Yan-Feng Bi School of Petrochemical Engineering Liaoning Petrochemical University

The construction of metal-organic coordination clusters（MCCs） using modular secondary building units is an important method for preparing functional *** this study,two new MCCs modularly assembled from Keggin-type {SiW12O40}H4TC4A=p-tert-Butylthiacalix[4]arene(SiW12) units and thiacalixarene-supported Co4-thiacalix[4]arene(Co4-TC4A polynuclear second-building units（PSBUs,H4TC4A=p-tert-Butylthiacalix[4]arene） are *** two MCCs,abbreviated as Co4-SiW12and Co8-SiW12,were structurally characterized by single-crystal X-ray *** Co4-SiW12is a supramolecular structure involving cation-anion interactions between Co4-TC4A PSBUs and ***8-SiW12features "barbell-like" shapes with two Co4-TC4A coordinatively linked to a Keggin-type SiW12unit on opposite via W-O_t-Co *** coordination of Co4-TC4A to SiW12in Co8-SiW12resulted in significantly improved photothermal conversion performances compared with Co4-SiW12and pure SiW12or ***-gap determination and photophysical analysis combined with density functional theory calculations indicated the binding mode between Co4-TC4A PSBUs and SiW12,which considerably influences the way of electron transport and the conversion ability of visible light to heat.

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