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Achieving superior strength-ductility synergy in a heterostructured magnesium alloy via low-temperature extrusion and low-temperature annealing

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Journal of Materials Science & technology 2023年第32期163卷 32-44页

作者： H.Wang d.t.zhang C.Qiu W.W.zhang d.L.Chen Guangdong Key Laboratory for Advanced Metallic Materials Processing and Forming National Engineering Research Center of Near-net-shape Forming for Metallic MaterialsSouth China University of TechnologyGuangzhou 510640China department of Mechanical and Industrial Engineering Toronto Metropolitan University(formerly Ryerson University)350 Victoria StreetTorontoON M5B 2K3Canada

A low-alloyed Mg-1.2Zn-0.1Ca(wt.%)alloy was fabricated via low-temperature extrusion and annealing at 250℃for different times(10,30,and 90 min)to attain heterostructures with different fine-grained fractions,focusing on the effect of heterostructure on the mechanical *** dynamic recrystallization(RX)occurred during extrusion at 150℃,and a lamellar structure consisting of fine RX grains and coarse unRX grains was *** subsequent annealing promoted static RX in the as-extruded alloy,leading to an increased fine-grained fraction from 67%to 95%.Meanwhile,the co-segregation of Zn and Ca atoms impeded the migration of grain boundaries,thus achieving a fine grain size of 0.8–1.6μ*** sample annealed for 10 min with a fine-grained fraction of 73%and an average RX grain size of 0.9μm exhibited a superior combination of high yield strength(305 MPa)and good ductility(20%).In comparison,an excellent elongation of 30%was achieved in the alloy with a nearly fully-RXed microstructure and an average grain size of 1.6μm after 90 min annealing,despite a lower yield strength of 228 *** unRX grains,the hard orientation with(01–10)parallel to the extrusion direction and high-density dislocations made it more difficult to deform compared with the RX grains,thus producing hetero-deformation induced(HdI)*** fine grains and high-density dislocations,HdI strengthening is the key to achieving the superior mechanical properties of the low-alloyed Mg alloy.

关键词： Low-alloyed magnesium alloy Low-temperature extrusion Annealing Heterostructure Mechanical properties

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Glucocorticoid receptor signaling in the brain and its involvement in cognitive function

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Neural Regeneration Research 2025年第9期20卷 2520-2537页

作者： Chonglin Su taiqi Huang Meiyu zhang Yanyu zhang Yan Zeng Xingxing Chen Brain Science and Advanced technology Institute Hubei Province Key Laboratory of Occupational Hazard Identification and ControlSchool of MedicineWuhan University of Science and TechnologyWuhanHubei ProvinceChina

the hypothalamic-pituitary-adrenal axis regulates the secretion of glucoco rticoids in response to environmental *** the brain,a nuclear receptor transcription fa ctor,the glucocorticoid recepto r,is an important component of the hypothalamicpituitary-a d renal axis's negative feedback loop and plays a key role in regulating cognitive equilibrium and *** glucoco rticoid receptor influences cognitive processes,including glutamate neurotransmission,calcium signaling,and the activation of brain-derived neurotrophic factor-mediated pathways,through a combination of genomic and non-genomic *** interactions within the central nervous system can alter the expression and activity of the glucocorticoid receptor,there by affecting the hypothalamic-pituitary-a d renal axis and stress-related cognitive *** appropriate level of glucocorticoid receptor expression can improve cognitive function,while excessive glucocorticoid receptors or long-term exposure to glucoco rticoids may lead to cognitive *** with cognitive impairment-associated diseases,such as Alzheimer's disease,aging,depression,Parkinson's disease,Huntington's disease,stroke,and addiction,often present with dysregulation of the hypothalamic-pituitary-adrenal axis and glucocorticoid receptor *** review provides a comprehensive overview of the functions of the glucoco rticoid receptor in the hypothalamic-pituitary-a d renal axis and cognitive *** emphasizes that appropriate glucocorticoid receptor signaling fa cilitates learning and memory,while its dysregulation can lead to cognitive *** provides clues about how glucocorticoid receptor signaling can be targeted to ove rcome cognitive disability-related disorders.

关键词： brain-derived neurotrophic factor calcium signaling glucocorticoid receptor glucocorticoid glutamate transmission hypothalamic-pituitary-adrenal axis long-term potentiation neurocognitive disorders neuroplasticity stress

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Subretinal fibrosis secondary to neovascular age-related macular degeneration:mechanisms and potential therapeutic targets

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Neural Regeneration Research 2025年第2期20卷 378-393页

作者： Jingxiang zhang Xia Sheng Quanju ding Yujun Wang Jiwei Zhao Jingfa zhang department of Ophthalmology People’s Hospital of Huangdao DistrictQingdaoShandong ProvinceChina department of Urology People’s Hospital of Huangdao DistrictQingdaoShandong ProvinceChina department of Ophthalmology Shanghai General Hospital(Shanghai First People’s Hospital)Shanghai Jiao Tong University School of MedicineShanghaiChina National Clinical Research Center for Eye diseases Shanghai Key Laboratory of Ocular Fundus DiseasesShanghai Engineering Center for Visual Science and PhotomedicineShanghai Engineering Center for Precise Diagnosis and Treatment of Eye DiseasesShanghaiChina

Subretinal fibrosis is the end-stage sequelae of neovascular age-related macular *** causes local damage to photoreceptors,retinal pigment epithelium,and choroidal vessels,which leads to permanent central vision loss of patients with neovascular age-related macular *** pathogenesis of subretinal fibrosis is complex,and the underlying mechanisms are largely ***,there are no effective treatment options.A thorough understanding of the pathogenesis of subretinal fibrosis and its related mechanisms is important to elucidate its complications and explore potential *** current article reviews several aspects of subretinal fibrosis,including the current understanding on the relationship between neovascular age-related macular degeneration and subretinal fibrosis;multimodal imaging techniques for subretinal fibrosis;animal models for studying subretinal fibrosis;cellular and non-cellular constituents of subretinal fibrosis;pathophysiological mechanisms involved in subretinal fibrosis,such as aging,infiltration of macrophages,different sources of mesenchymal transition to myofibroblast,and activation of complement system and immune cells;and several key molecules and signaling pathways participating in the pathogenesis of subretinal fibrosis,such as vascular endothelial growth factor,connective tissue growth factor,fibroblast growth factor 2,platelet-derived growth factor and platelet-derived growth factor receptor-β,transforming growth factor-βsignaling pathway,Wnt signaling pathway,and the axis of heat shock protein 70-toll-like receptors 2/*** review will improve the understanding of the pathogenesis of subretinal fibrosis,allow the discovery of molecular targets,and explore potential treatments for the management of subretinal fibrosis.

关键词： choroidal neovascularization epithelial-mesenchymal transition mesenchymal transition myofibroblast neovascular age-related macular degeneration submacular fibrosis subretinal fibrosis therapeutic targets transforming growth factor-β vascular endothelial growth factor

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targeting Epac2 and GluA3-containing AMPARs:a novel therapeutic strategy for Alzheimer's disease

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Neural Regeneration Research 2025年第11期20卷 3223-3224页

作者： tong zhang Martina Schmidt department of Molecular Pharmacology Groningen Research Institute of PharmacyUniversity of GroningenGroningenThe Netherlands School of Pharmacy Tianjin Medical UniversityTianjinChina

Alzheimer's disease(Ad)is a neurodegenerative disease that manifests progressive decline in memory and *** the early stage of Ad,memory retrieval is impaired preceding memory acquisition and consolidation(Roy et al.,2016).Prior to the onset of symptoms,pathological amyloid-β(Aβ)plagues and tau protein tangles accumulate in extracellular and intracellular spaces,respectively,leading to *** these hallmark pathologies,Aβ is proposed to be the primary etiology by triggering a cascade of pathogenic events,including neuroinflammation,oxidative stress,tau hyperphosphorylation,synaptic/neuronal dysfunction,and neuronal death(zhang et al.,2023b).

关键词： Alzheimer impaired Aβ

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Small extracellular vesicles derived from cerebral endothelial cells with elevated microRNA 27a promote ischemic stroke recovery

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Neural Regeneration Research 2025年第1期20卷 224-233页

作者： Yi zhang Zhongwu Liu Michael Chopp Michael Millman Yanfeng Li Pasquale Cepparulo Amy Kemper Chao Li Li zhang Zheng Gang zhang department of Neurology Henry Ford HospitalDetroitMIUSA department of Physics Oakland UniversityRochesterMIUSA department of Pathology Henry Ford HospitalDetroitMIUSA division of Pharmacology Department of NeuroscienceReproductive and Dentistry SciencesSchool of MedicineUniversity of Naples“Federico Ⅱ”NaplesItaly

Axonal remodeling is a critical aspect of ischemic brain repair processes and contributes to spontaneous functional *** previous in vitro study demonstrated that exosomes/small extracellular vesicles(sEVs)isolated from cerebral endothelial cells(CEC-sEVs)of ischemic brain promote axonal growth of embryonic cortical neurons and that microRNA 27a(miR-27a)is an elevated miRNA in ischemic *** the present study,we investigated whether normal CEC-sEVs engineered to enrich their levels of miR-27a(27a-sEVs)further enhance axonal growth and improve neurological outcomes after ischemic stroke when compared with treatment with non-engineered CEC-sEVs.27a-sEVs were isolated from the conditioned medium of healthy mouse CECs transfected with a lentiviral miR-27a expression *** EVs isolated from CECs transfected with a scramble vector(Scra-sEVs)were used as a *** male mice were subjected to permanent middle cerebral artery occlusion and then were randomly treated with 27a-sEVs or *** array of behavior assays was used to measure neurological *** with treatment of ischemic stroke with Scra-sEVs,treatment with 27a-sEVs significantly augmented axons and spines in the peri-infarct zone and in the corticospinal tract of the spinal grey matter of the denervated side,and significantly improved neurological *** vitro studies demonstrated that CEC-sEVs carrying reduced miR-27a abolished 27a-sEV-augmented axonal *** analysis revealed that 27a-sEVs systemically administered preferentially localized to the pre-synaptic active zone,while quantitative reverse transcription-polymerase chain reaction and Western Blot analysis showed elevated miR-27a,and reduced axonal inhibitory proteins Semaphorin 6A and Ras Homolog Family Member A in the peri-infarct *** of the Clathrin-dependent endocytosis pathway substantially reduced neuronal internalization of *** data provide evidence that 27a-sEVs have

关键词： axonal remodeling cerebral endothelial cells exosomes miR-27a mitochondria Semaphorin 6A small extracellular vesicles stroke

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Gamma-glutamyl transferase 5 overexpression in cerebrovascular endothelial cells improves brain pathology,cognition,and behavior in APP/PS1 mice

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Neural Regeneration Research 2025年第2期20卷 533-547页

作者： Yanli zhang tian Li Jie Miao Zhina zhang Mingxuan Yang Zhuoran Wang Bo Yang Jiawei zhang Haiting Li Qiang Su Junhong Guo department of Neurology First Hospital of Shanxi Medical UniversityTaiyuanShanxi ProvinceChina department of Neurology Sixth Hospital of Shanxi Medical University(General Hospital of Tisco)TaiyuanShanxi ProvinceChina department of Physiology Key Laboratory of Cellular PhysiologyMinistry of EducationShanxi Medical UniversityTaiyuanShanxi ProvinceChina department of Hernia and Abdominal Wall Surgery Shanxi Bethune HospitalShanxi Academy of Medical SciencesTongji Shanxi HospitalThird Hospital of Shanxi Medical UniversityTaiyuanShanxi ProvinceChina department of Laboratory Medicine of Fenyang College Shanxi Medical UniversityFenyangShanxi ProvinceChina

In patients with Alzheimer’s disease,gamma-glutamyl transferase 5(GGt5)expression has been observed to be downregulated in cerebrovascular endothelial ***,the functional role of GGt5 in the development of Alzheimer’s disease remains *** study aimed to explore the effect of GGt5 on cognitive function and brain pathology in an APP/PS1 mouse model of Alzheimer’s disease,as well as the underlying *** observed a significant reduction in GGt5 expression in two in vitro models of Alzheimer’s disease(Aβ_(1-42)-treated hCMEC/d3 and bEnd.3 cells),as well as in the APP/PS1 mouse ***,injection of APP/PS1 mice with an adeno-associated virus encoding GGt5 enhanced hippocampal synaptic plasticity and mitigated cognitive ***,increasing GGt5 expression in cerebrovascular endothelial cells reduced levels of both soluble and insoluble amyloid-βin the brains of APP/PS1 *** effect may be attributable to inhibition of the expression ofβ-site APP cleaving enzyme 1,which is mediated by nuclear factor-kappa *** findings demonstrate that GGt5 expression in cerebrovascular endothelial cells is inversely associated with Alzheimer’s disease pathogenesis,and that GGt5 upregulation mitigates cognitive deficits in APP/PS1 *** findings suggest that GGt5 expression in cerebrovascular endothelial cells is a potential therapeutic target and biomarker for Alzheimer’s disease.

关键词： Alzheimer’s disease amyloid-β APP/PS1 mice cerebrovascular endothelial cells cognitive deficits gamma-glutamyl transferase 5 neurovascular unit nuclear factor‐kappa B synaptic plasticity β-site APP cleaving enzyme 1

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Loss-of-function mutations of microRNA-142-3p promote ASH1L expression to induce immune evasion and hepatocellular carcinoma progression

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World Journal of Gastroenterology 2025年第1期31卷 126-145页

作者： Xing-Hui Yu Yan Xie Jian Yu Kun-Ning zhang Zhou-Bo Guo di Wang Zhao-Xian Li Wei-Qi zhang Yu-Ying tan Li zhang Wen-tao Jiang School of Medicine Nankai UniversityTianjin 300192China tianjin Key Laboratory of Molecular diagnosis and treatment of Liver Cancer Tianjin First Center HospitalTianjin 300192China department of Liver transplantation Tianjin First Center HospitalTianjin 300192China First Central Clinical School Tianjin Medical UniversityTianjin 300192China

BACKGROUNd Hepatocellular carcinoma(HCC)has been a pervasive malignancy throughout the world with elevated *** therapeutic targets are beneficial to treat and predict the ***,the exact molecular mechanisms leading to the progression of HCC are still *** has shown that the microRNA-142-3p level decreases in HCC,whereas bioinformatics analysis of the cancer genome atlas database shows the ASH1L expression increased among liver tumor *** this paper,we will explore the effects and mechanisms of microRNA-142-3p and ASH1L affect the prognosis of HCC patients and HCC cell bioactivity,and the association between *** to investigate the effects and mechanisms of microRNA-142-3p and ASH1L on the HCC cell bioactivity and prognosis of HCC *** In this study,we grouped HCC patients according to their immunohistochemistry results of ASH1L with pathological tissues,and retrospectively analyzed the prognosis of HCC ***,explored the roles and mechanisms of microRNA-142-3p and ASH1L by cellular and animal experiments,which involved the following experimental methods:Immunohistochemical staining,western blot,quantitative real-time-polymerase chain reaction,flow cytometric analysis,tumor xenografts in nude mice,*** statistical methods involved in this study contained t-test,one-way analysis of variance,theχ^(2)test,the Kaplan-Meier approach and the log-rank *** In this study,we found that HCC patients with high expression of ASH1L possess a more recurrence rate as well as a decreased overall survival ***1L promotes the tumorigenicity of HCC and microRNA-142-3p exhibits reduced expression in HCC tissues and interacts with ASH1L through targeting the ASH1L 3′untranslated ***,microRNA-142-3p promotes apoptosis and inhibits proliferation,invasion,and migration of HCC cell lines in vitro via *** the exploration mechanism,we found ASH1L may promote an immunosuppressive mi

关键词： Hepatocellular carcinoma MicroRNA-142-3p ASH1L Immune evasion tumor immune microenvironment Apoptosis

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Autophagy-targeting modulation to promote peripheral nerve regeneration

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Neural Regeneration Research 2025年第7期20卷 1864-1882页

作者： Yan Chen Hongxia deng Nannan zhang department of Obstetrics and Gynecology West China Second HospitalSichuan UniversityChengduSichuan ProvinceChina Key Laboratory of Birth defects and Women and Children’s diseases Ministry of EducationSichuan UniversityChengduSichuan ProvinceChina Laboratory of Reproductive Endocrinology and Reproductive Regulation Sichuan UniversityChengduSichuan ProvinceChina National Center for Birth defect Monitoring West China Second University HospitalSichuan UniversityChengduSichuan ProvinceChina

Nerve regeneration following traumatic peripheral nerve injuries and neuropathies is a complex process modulated by diverse factors and intricate molecular *** studies have focused on factors that stimulate axonal outgrowth and myelin ***,recent studies have highlighted the pivotal role of autophagy in peripheral nerve regeneration,particularly in the context of traumatic ***,autophagy-targeting modulation has emerged as a promising therapeutic approach to enhancing peripheral nerve *** current understanding suggests that activating autophagy facilitates the rapid clearance of damaged axons and myelin sheaths,thereby enhancing neuronal survival and mitigating injury-induced oxidative stress and *** actions collectively contribute to creating a favorable microenvironment for structural and functional nerve regeneration.A range of autophagyinducing drugs and interventions have demonstrated beneficial effects in alleviating peripheral neuropathy and promoting nerve regeneration in preclinical models of traumatic peripheral nerve *** review delves into the regulation of autophagy in cell types involved in peripheral nerve regeneration,summarizing the potential drugs and interventions that can be harnessed to promote this *** hope that our review will offer novel insights and perspectives on the exploitation of autophagy pathways in the treatment of peripheral nerve injuries and neuropathies.

关键词： autophagy autophagy related genes Charcot–Marie–tooth diseases diabetic peripheral neuropathy metformin myelination peripheral nerve injury Schwann cells sciatic nerve Wallerian degeneration

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the dopaminergic system and Alzheimer's disease

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Neural Regeneration Research 2025年第9期20卷 2495-2512页

作者： Yuhan zhang Yuan Liang Yixue Gu International Medical College Chongqing Medical UniversityChongqingChina College of Pharmacy Chongqing Medical UniversityChongqingChina department of Neurology The First Affiliated Hospital of Chongqing Medical UniversityChongqing Key Laboratory of NeurologyChongqingChina

Alzheimer's disease is a common neurodegenerative disorder in older *** its prevalence,its pathogenesis remains unclea *** addition to the most widely accepted causes,which in clude excessive amyloid-beta aggregation,tau hyperphosphorylation,and deficiency of the neurotransmitter acetylcholine,numerous studies have shown that the dopaminergic system is also closely associated with the occurrence and development of this *** is a crucial catecholaminergic neurotransmitter in the human ***-associated treatments,such as drugs that target dopamine receptor d and dopamine analogs,can improve cognitive function and alleviate psychiatric symptoms as well as ameliorate other clinical *** r,therapeutics targeting the dopaminergic system are associated with various adverse reactions,such as addiction and exacerbation of cognitive *** review summarizes the role of the dopaminergic system in the pathology of Alzheimer's disease,focusing on currently available dopamine-based therapies for this disorder and the common side effects associated with dopamine-related *** aim of this review is to provide insights into the potential connections between the dopaminergic system and Alzheimer's disease,thus helping to clarify the mechanisms underlying the condition and exploring more effective therapeutic options.

关键词： adverse drug reaction Alzheimer's disease catecholamine dopamine receptor dopamine receptor heterodimers dopaminergic system neurodegenerative disease neurotransmitter signaling pathways traditional Chinese medicine treatment

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the emerging role of nitric oxide in the synaptic dysfunction of vascular dementia

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Neural Regeneration Research 2025年第2期20卷 402-415页

作者： Xiaorong zhang Zhiying Chen Yinyi Xiong Qin Zhou Ling-Qiang Zhu dan Liu department of Pathology Affiliated Hospital of Jiujiang UniversityJiujiangJiangxi ProvinceChina Jiujiang Clinical Precision Medicine Research Center JiujiangJiangxi ProvinceChina Center for Cognitive Science and transdisciplinary Studies Jiujiang UniversityJiangxi ProvinceChina department of Neurology Affiliated Hospital of Jiujiang UniversityJiujiangJiangxi ProvinceChina department of Rehabilitation Affiliated Hospital of Jiujiang UniversityJiujiangJiangxi ProvinceChina department of Pathophysiology School of Basic MedicineTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei ProvinceChina

With an increase in global aging,the number of people affected by cerebrovascular diseases is also increasing,and the incidence of vascular dementia-closely related to cerebrovascular risk-is increasing at an epidemic ***,few therapeutic options exist that can markedly improve the cognitive impairment and prognosis of vascular dementia *** in Alzheimer’s disease and other neurological disorders,synaptic dysfunction is recognized as the main reason for cognitive *** oxide is one of the ubiquitous gaseous cellular messengers involved in multiple physiological and pathological processes of the central nervous ***,nitric oxide has been implicated in regulating synaptic plasticity and plays an important role in the pathogenesis of vascular *** review introduces in detail the emerging role of nitric oxide in physiological and pathological states of vascular dementia and summarizes the diverse effects of nitric oxide on different aspects of synaptic dysfunction,neuroinflammation,oxidative stress,and blood-brain barrier dysfunction that underlie the progress of vascular ***,we propose that targeting the nitric oxide-sGC-cGMP pathway using certain specific approaches may provide a novel therapeutic strategy for vascular dementia.

关键词： endoplasmic reticulum stress endothelial nitric oxide synthase gene therapy nitric oxide NO-sGC-cGMP pathway synaptic dysfunction vascular dementia

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