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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

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

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 j.nhong 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

Three-dimensional matrix for lithium metal anode for next-generation rechargeable batteries: Structure design and interface engineering

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journal of Energy Chemistry 2019年第6期28卷 167-168页

作者： long Kong Qiang zhang Beij.ng Key Laboratory of Green Chemical Reaction Engineering and Technology Department of Chemical Engineering Tsinghua University

The next-generation batteries with very high energy/power densities, affordable cost, safe operation are of paramount importance to electric vehicles and grid-scale storage. Lithium (Li) metal anode paired with conversion reaction cathodes (sulfur and oxygen) is regarded as a Holy Grail research because such battery system can employ earth-abundant elements and afford 3?5 times higher energy density than current lithium ion batteries (3500 Wh kg^-1 for lithium-oxygen batteries and 2600 Wh kg^-1 for lithium-sulfur batteries)[1].

关键词： Lithium metal anode Carbon nanofibers nitrogen doped carbon nanomaterials Dendrite formation Electrochemical energy storage

Simulated effects of interactions between ocean acidification,marine organism calcification, and organic carbon export on ocean carbon and oxygen cycles

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Science China Earth Sciences 2018年第6期61卷 804-822页

作者： Han zhang long CAO Department of Atmospheric Sciences School of Earth Sciences Zhejiang University

Ocean acidification caused by oceanic uptake of anthropogenic carbon dioxide(CO_2) tends to suppress the calcification of some marine organisms. This reduced calcification then enhances surface ocean alkalinity and increases oceanic CO_2 uptake, a process that is termed calcification feedback. On the other hand, decreased calcification also reduces the export flux of calcium carbonate(Ca CO_3), potentially reducing Ca CO_3-bound organic carbon export flux and CO_2 uptake, a process that is termed ballast feedback. In this study, we incorporate a range of different parameterizations of the links between organic carbon export, calcification, and ocean acidification into an Earth system model, in order to quantify the long-term effects on oceanic CO_2 uptake that result from calcification and ballast feedbacks. We utilize an intensive CO_2 emission scenario to drive the model in which an estimated fossil fuel resource of 5000 Pg C is burnt out over the course of just a few centuries. Simulated results show that, in the absence of both calcification and ballast feedbacks, by year 3500, accumulated oceanic CO_2 uptake is2041 Pg C. Inclusion of calcification feedback alone increases the simulated uptake by 629 Pg C(31%), while the inclusion of both calcification and ballast feedbacks increase simulated uptake by 449–498 Pg C(22–24%), depending on the parameter values used in the ballast feedback scheme. These results indicate that ballast effect counteracts calcification effect in oceanic CO_2 uptake. Ballast effect causes more organic carbon to accumulate and decompose in the upper ocean, which in turn leads to decreased oxygen concentration in the upper ocean and increased oxygen at depths. By year 2600, the inclusion of ballast effect would decrease oxygen concentration by 11% at depth of ca. 200 m in tropics. Our study highlights the potentially critical effects of interactions between ocean acidification, marine organism calcification, and Ca CO3-bound organic carbon

关键词： Ocean carbon cycle Ocean acidification Carbon cycle modeling Carbon cycle-climate feedback

A functional tacrolimus-releasing nerve wrap for enhancing nerve regeneration following surgical nerve repair

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neural Regeneration Research 2025年第1期20卷 291-304页

作者： Simeon C.Daeschler Katelyn j.W.So Konstantin Feinberg Marina Manoraj j.nny Cheung j.nnifer zhang Kaveh Mirmoeini jPaul Santerre Tessa Gordon Gregory HBorschel SickKids Research Institute Neuroscience and Mental Health ProgramTorontoONCanada Institute of Biomaterials and Biomedical Engineering University of TorontoTorontoONCanada Indiana University School of Medicine IndianapolisINUSA Division of Plastic and Reconstructive Surgery the Hospital for Sick ChildrenTorontoONCanada Translational Biology and Engineering Program Ted Rogers Centre for Heart ResearchInstitute of Biomedical EngineeringFaculty of DentistryUniversity of TorontoTorontoONCanada

Axonal regeneration following surgical nerve repair is slow and often incomplete,resulting in poor functional recovery which sometimes contributes to lifelong ***,there are no FDA-approved therapies available to promote nerve *** accelerates axonal regeneration,but systemic side effects presently outweigh its potential benefits for peripheral nerve *** authors describe herein a biodegradable polyurethane-based drug delivery system for the sustained local release of tacrolimus at the nerve repair site,with suitable properties for scalable production and clinical application,aiming to promote nerve regeneration and functional recovery with minimal systemic drug *** is encapsulated into co-axially electrospun polycarbonate-urethane nanofibers to generate an implantable nerve wrap that releases therapeutic doses of bioactive tacrolimus over 31 *** and drug loading are adjustable for applications in small and large caliber nerves,and the wrap degrades within 120 days into biocompatible *** released from the nerve wrap promotes axon elongation in vitro and accelerates nerve regeneration and functional recovery in preclinical nerve repair models while off-target systemic drug exposure is reduced by 80%compared with systemic *** its surgical suitability and preclinical efficacy and safety,this system may provide a readily translatable approach to support axonal regeneration and recovery in patients undergoing nerve surgery.

关键词： biodegradable local drug delivery nerve injury nerve regeneration nerve wrap tacrolimus

Frequency Domain Fatigue Evaluation on SCR Girth-Weld Based on Structural Stress

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China Ocean Engineering 2024年第2期38卷 255-270页

作者： zhang long ZHAO Tian-feng College of Safety and Ocean Engineering China University of Petroleum(Beijing)Beijing 102249China

The Steel Catenary Riser(SCR)is a vital component for transporting oil and gas from the seabed to the floating *** harsh environmental conditions and complex platform motion make the SCR’s girth-weld prone to fatigue *** structural stress fatigue theory and Master S-n curve method provide accurate predictions for the fatigue damage on the welded joints,which demonstrate significant potential and compatibility in multi-axial and random fatigue ***,we propose a new frequency fatigue model subjected to welded joints of SCR under multiaxial stress,which fully integrates the mesh-insensitive structural stress and frequency domain random process and transforms the conventional welding fatigue technique of SCR into a spectrum analysis technique utilizing structural ***,a full-scale FE model of SCR with welds is established to obtain the modal structural stress of the girth weld and the frequency response function(FRF)of modal coordinate,and a biaxial fatigue evaluation about the girth weld of the SCR can be achieved by taking the effects of multi-load correlation and pipe-soil interaction into *** research results indicate that the frequency-domain fatigue results are aligned with the time-domain results,meeting the fatigue evaluation requirements of the SCR.

关键词： SCR girth weld random vibration self(cross)power spectrum structural stress method biaxial fatigue damage

Exercise preconditioning alleviates ischemia-induced memory deficits by increasing circulating adiponectin

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neural Regeneration Research 2025年第5期20卷 1445-1454页

作者： Meifeng Zheng Borui zhang Sonata S Y Yau Kwok-Fai So Li zhang Haining Ou Department of Rehabilitation Medicine Guangzhou Medical UniversityGuangzhouGuangdong ProvinceChina Department of Rehabilitation Medicine The Fifth Clinical College of Guangzhou Medical UniversityGuangzhouGuangdong ProvinceChina Key Laboratory of CnS Regeneration(Ministry of Education) Guangdong-Hong Kong-Macao Institute of CNS RegenerationJinan UniversityGuangzhouGuangdong ProvinceChina Department of Rehabilitation Sciences The Hong Kong Polytechnic UniversityHong Kong Special Administrative RegionChina State Key Laboratory of Brain and Cognitive Science Li Ka Shing Faculty of MedicineThe University of Hong KongHong Kong Special Administrative RegionChina Center for Exercise and Brain Science School of PsychologyShanghai University of SportShanghaiChina neuroscience and neurorehabilitation Institute University of Health and Rehabilitation SciencesQingdaoShandong ProvinceChina

Cerebral ischemia is a major health risk that requires preventive approaches in addition to drug *** exercise enhances neurogenesis and synaptogenesis,and has been widely used for functional rehabilitation after *** this study,we determined whether exercise training before disease onset can alleviate the severity of cerebral *** also examined the role of exercise-induced circulating factors in these *** mice were subjected to 14 days of treadmill exercise training before surgery for middle cerebral artery *** found that this exercise pre-conditioning strategy effectively attenuated brain infarct area,inhibited gliogenesis,protected synaptic proteins,and improved novel object and spatial memory *** analysis showed that circulating adiponectin plays a critical role in these preventive effects of *** activation of adiponectin receptors by Adipo Ron mimicked the effects of exercise,while inhibiting receptor activation abolished the exercise *** summary,our results suggest a crucial role of circulating adiponectin in the effects of exercise pre-conditioning in protecting against cerebral ischemia and supporting the health benefits of exercise.

关键词： adiponectin cerebral ischemia exercise pre-conditioning hippocampus memory function middle cerebral artery occlusion prefrontal cortex synaptic proteins treadmill exercise

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 Tianj.n 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