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Targeting epigenetic mechanisms in amyloid-β-mediated Alzheimer’s pathophysiology:unveiling therapeutic potential

Neural Regeneration Research 2025年第1期20卷 54-66页

作者： Jennie Z.li Nagendran Ramalingam shaomin li Ann Romney Center for Neurologic Diseases Brigham and Women’s Hospital and Harvard Medical SchoolBostonMAUSA

Alzheimer’s disease is a prominent chronic neurodegenerative condition characterized by a gradual decline in memory leading to *** evidence suggests that Alzheimer’s disease is associated with accumulating various amyloid-βoligomers in the brain,influenced by complex genetic and environmental *** memory and cognitive deficits observed during the prodromal and mild cognitive impairment phases of Alzheimer’s disease are believed to primarily result from synaptic *** life,environmental factors can lead to enduring changes in gene expression and the emergence of brain *** changes,known as epigenetic modifications,also play a crucial role in regulating the formation of synapses and their adaptability in response to neuronal *** this context,we highlight recent advances in understanding the roles played by key components of the epigenetic machinery,specifically DNA methylation,histone modification,and microRNAs,in the development of Alzheimer’s disease,synaptic function,and activity-dependent synaptic ***,we explore various strategies,including enriched environments,exposure to non-invasive brain stimulation,and the use of pharmacological agents,aimed at improving synaptic function and enhancing long-term potentiation,a process integral to epigenetic ***,we deliberate on the development of effective epigenetic agents and safe therapeutic approaches for managing Alzheimer’s *** suggest that addressing Alzheimer’s disease may require distinct tailored epigenetic drugs targeting different disease stages or pathways rather than relying on a single drug.

关键词： Alzheimer’s disease DNA methylation enriched environments histone modification microRNAs non-invasive brain stimulation synaptic plasticity

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Potential role and therapeutic implications of glutathione peroxidase 4 in the treatment of Alzheimer's disease

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Neural Regeneration Research 2025年第3期20卷 613-631页

作者： Yanxin shen Guimei Zhang Chunxiao Wei Panpan Zhao Yongchun Wang Mingxi li li sun Department of Neurology and Neuroscience Center The First Hospital of Jilin UniversityJilin UniversityChangchunJilin ProvinceChina Cognitive Impairment Center Department of NeurologyThe First Hospital of Jilin UniversityJilin UniversityChangchunJilin ProvinceChina

Alzheimer's disease is an age-related neurodegenerative disorder with a complex and incompletely understood pathogenesis. Despite extensive research, a cure for Alzheimer's disease has not yet been found. Oxidative stress mediates excessive oxidative responses, and its involvement in Alzheimer's disease pathogenesis as a primary or secondary pathological event is widely accepted. As a member of the selenium-containing antioxidant enzyme family, glutathione peroxidase 4 reduces esterified phospholipid hydroperoxides to maintain cellular redox homeostasis. With the discovery of ferroptosis, the central role of glutathione peroxidase 4 in anti-lipid peroxidation in several diseases, including Alzheimer's disease, has received widespread attention. Increasing evidence suggests that glutathione peroxidase 4 expression is inhibited in the Alzheimer's disease brain, resulting in oxidative stress, inflammation, ferroptosis, and apoptosis, which are closely associated with pathological damage in Alzheimer's disease. several therapeutic approaches, such as small molecule drugs, natural plant products, and non-pharmacological treatments, ameliorate pathological damage and cognitive function in Alzheimer's disease by promoting glutathione peroxidase 4 expression and enhancing glutathione peroxidase 4 activity. Therefore, glutathione peroxidase 4 upregulation may be a promising strategy for the treatment of Alzheimer's disease. This review provides an overview of the gene structure, biological functions, and regulatory mechanisms of glutathione peroxidase 4, a discussion on the important role of glutathione peroxidase 4 in pathological events closely related to Alzheimer's disease, and a summary of the advances in small-molecule drugs, natural plant products, and non-pharmacological therapies targeting glutathione peroxidase 4 for the treatment of Alzheimer's disease. Most prior studies on this subject used animal models, and relevant clinical studies are lacking. Future clinica

关键词： apoptosis ferroptosis inflammation lipid peroxidation natural plant products neurodegenerative disorder neuroprotection oxidative stress small-molecule drugs

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The autophagy-lysosome pathway:a potential target in the chemical and gene therapeutic strategies for Parkinson’s disease

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Neural Regeneration Research 2025年第1期20卷 139-158页

作者： Fengjuan Jiao lingyan Meng Kang Du Xuezhi li school of Mental Health Jining Medical UniversityJiningShandong ProvinceChina shandong Collaborative Innovation Center for Diagnosis Treatment and Behavioral Interventions of Mental DisordersInstitute of Mental HealthJining Medical UniversityJiningShandong ProvinceChina

Parkinson’s disease is a common neurodegenerative disease with movement disorders associated with the intracytoplasmic deposition of aggregate proteins such asα-synuclein in *** one of the major intracellular degradation pathways,the autophagy-lysosome pathway plays an important role in eliminating these *** evidence has shown that upregulation of the autophagy-lysosome pathway may contribute to the clearance ofα-synuclein aggregates and protect against degeneration of dopaminergic neurons in Parkinson’s ***,multiple genes associated with the pathogenesis of Parkinson’s disease are intimately linked to alterations in the autophagy-lysosome ***,this pathway appears to be a promising therapeutic target for treatment of Parkinson’s *** this review,we briefly introduce the machinery of ***,we provide a description of the effects of Parkinson’s disease–related genes on the autophagy-lysosome ***,we highlight the potential chemical and genetic therapeutic strategies targeting the autophagy–lysosome pathway and their applications in Parkinson’s disease.

关键词： autophagy chemical therapy gene therapy Parkinson’s disease α-synuclein

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Hydrogen sulfide reduces oxidative stress in Huntington's disease via Nrf2

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Neural Regeneration Research 2025年第6期20卷 1776-1788页

作者： Zige Jiang Dexiang liu Tingting li Chengcheng Gai Danqing Xin Yijing Zhao Yan song Yahong Cheng Tong li Zhen Wang Department of Physiology School of Basic Medical SciencesCheeloo College of MedicineShandong UniversityJinanShandong ProvinceChina Department of Medical Psychology and Ethics School of Basic Medicine SciencesCheeloo College of MedicineShandong UniversityJinanShandong ProvinceChina Department of Neurosurgery surgery Qingdao Municipal HospitalQingdaoShandong ProvinceChina

The pathophysiology of Huntington's disease involves high levels of the neurotoxin quinolinic acid. Quinolinic acid accumulation results in oxidative stress, which leads to neurotoxicity. However, the molecular and cellular mechanisms by which quinolinic acid contributes to Huntington's disease pathology remain unknown. In this study, we established in vitro and in vivo models of Huntington's disease by administering quinolinic acid to the PC12 neuronal cell line and the striatum of mice, respectively. We observed a decrease in the levels of hydrogen sulfide in both PC12 cells and mouse serum, which was accompanied by down-regulation of cystathionine β-synthase, an enzyme responsible for hydrogen sulfide production. However, treatment with NaHs(a hydrogen sulfide donor) increased hydrogen sulfide levels in the neurons and in mouse serum, as well as cystathionine β-synthase expression in the neurons and the mouse striatum, while also improving oxidative imbalance and mitochondrial dysfunction in PC12 cells and the mouse striatum. These beneficial effects correlated with upregulation of nuclear factor erythroid 2-related factor 2 expression. Finally, treatment with the nuclear factor erythroid 2-related factor 2inhibitor ML385 reversed the beneficial impact of exogenous hydrogen sulfide on quinolinic acid-induced oxidative stress. Taken together, our findings show that hydrogen sulfide reduces oxidative stress in Huntington's disease by activating nuclear factor erythroid 2-related factor 2,suggesting that hydrogen sulfide is a novel neuroprotective drug candidate for treating patients with Huntington's disease.

关键词： apoptosis cystathionine-β-synthase nuclear factor erythroid 2-related factor 2 Huntington's disease hydrogen sulfide mitochondrion neuroplasticity oxidative stress quinolinic acid reactive oxygen species

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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

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Interpretable Machine Learning Method for Compressive strength Prediction and Analysis of Pure Fly Ash-based Geopolymer Concrete

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Journal of Wuhan University of Technology(Materials science) 2025年第1期40卷 65-78页

作者： sHI Yuqiong li Jingyi ZHANG Yang li li Key Laboratory of Agricultural soil and Water Engineering in Arid and semiarid Areas of Ministry of Education Northwest A&F Uni-versityYangling 712100China College of Water Resources and Architectural Engineering Northwest A&F UniversityYangling 712100China Chongqing Key Laboratory of Public Big Data security Technology Chongqing 401420China Chongqing College of Mobile Communication Chongqing 401520China Department of Civil and Environmental Engineering The Hong Kong Polytechnic UniversityHung HomKowloonHong KongChina National Rail Transit Electrification and Automation Engineering Technology Research Center(Hong Kong Branch) The Hong Kong Polytechnic UniversityKowloonHung HomHong KongChina

In order to study the characteristics of pure fly ash-based geopolymer concrete(PFGC)conveniently,we used a machine learning method that can quantify the perception of characteristics to predict its compressive *** this study,505 groups of data were collected,and a new database of compressive strength of PFGC was *** order to establish an accurate prediction model of compressive strength,five different types of machine learning networks were used for comparative *** five machine learning models all showed good compressive strength prediction performance on *** them,R2,MsE,RMsE and MAE of decision tree model(DT)are 0.99,1.58,1.25,and 0.25,*** R2,MsE,RMsE and MAE of random forest model(RF)are 0.97,5.17,2.27 and 1.38,*** two models have high prediction accuracy and outstanding generalization *** order to enhance the interpretability of model decision-making,we used importance ranking to obtain the perception of machine learning model to 13 *** 13 variables include chemical composition of fly ash(siO_(2)/Al_(2)O_(3),si/Al),the ratio of alkaline liquid to the binder,curing temperature,curing durations inside oven,fly ash dosage,fine aggregate dosage,coarse aggregate dosage,extra water dosage and sodium hydroxide *** temperature,specimen ages and curing durations inside oven have the greatest influence on the prediction results,indicating that curing conditions have more prominent influence on the compressive strength of PFGC than ordinary Portland cement *** importance of curing conditions of PFGC even exceeds that of the concrete mix proportion,due to the low reactivity of pure fly ash.

关键词： machine learning pure fly ash geopolymer compressive strength feature perception

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On the existence of solutions for prescribing fractional Q-curvature problem on s~n

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Acta Mathematica sinica,English series 2025年

作者： Yan li Zhongwei TANG College of science China University of Petroleum(Beijing) school of Mathematical sciences Laboratory of Mathematics and Complex Systems MOEBeijing Normal University

The aim of this paper is to investigate the existence of solutions to the prescribing fractional Q-curvature problem on s~n under some reasonable assumption of the Laplacian sign at the critical point of prescribing curvature function K. Due to the lack of compactness, we choose to return to the basic elements of variational theory and study the deformation along the flow lines. The novelty of the paper is that we obtain the existence without assuming any symmetry and periodicity on K. In addition,to overcome the loss of compactness for high-order operator problem, we need more delicate estimates with the second order cases.

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Revisiting cerebral endothelial cells in Alzheimer’s disease

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Neural Regeneration Research 2025年第10期20卷 2911-2912页

作者： Amira s.Hanafy Department of Neurosurgery University Hospital BonnBonnGermany

Alzheimer’s disease(AD)is the most common neurodegenerative disorder characterized by slow and progressive decline of cognitive and memory *** only approximately 5%of the cases,AD is familial,as often predisposed by genetic mutations(Hoogmartens et al.,2021),while sporadic AD accounts for approximately 95%of the *** amyloid cascade hypothesis is one of the fundamental hypotheses put out to explain AD pathogenesis as dysregulated homeostasis of amyloid-β(Aβ)peptides that leads to the accumulation of Aβplaques in the parenchyma,an anatomical hallmark of AD.

关键词： Alzheimer Aβ cerebral

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Manufacture the conducting polymer with light

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science China Chemistry 2025年第1期68卷 8-9页

作者： Yang li Tianyu li Yan Ji Baoguang liu College of Electronic and Optical Engineering & College of Flexible Electronics (Future Technology) Nanjing University of Posts & Telecommunications

Poly(3,4-ethylenedioxythiophene) (PEDOT), heralded as the “king” of conducting polymers, is esteemed in bioelectronics for its mixed electronic and ionic conductivity, mechanical properties compatible with biological tissues, tunable healing ability and stability in diverse environments [1]. Based on additive manufacturing of three-dimensional structures,PEDOT realizes the implementation in the efficient production of flexible bioelectronics, the construction of intricate electrode-neural implantations, and the development of smart brain-computer-interfaces [2].

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A Wind Tunnel Experimental study on the Wake Characteristics of a Horizontal Axis Wind Turbine

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Journal of Thermal science 2025年第1期34卷 145-158页

作者： GUO Xingduo li Yinran li Rennian MA Yulong WEI Kui College of Energy and Power Engineering Lanzhou University of Technology Key Laboratory of Fluid Machinery and systems Gansu Provincial Technology Centre for Wind Turbines

The characteristics of wind turbine wakes are influenced by multiple factors,including the atmospheric boundary layer(ABL) wind and wind turbine operating conditions(e.g.,tip speed ratio and yaw angle).In this study,two types of ABL winds with different velocity gradients and turbulence intensities are generated in a wind tunnel through configurations of spires,baffles,and various numbers of roughness elements.A wind turbine with a rotor diameter of 0.8 m and a hub height of 0.6 m is tested under varying tip speed ratios,yaw angles,and ABL wind *** results indicate that the streamwise velocity deficit in the near-wake region becomes more pronounced with an increase in the tip speed ratio,while the far-wake velocity deficit remains largely unaffected by changes in the tip speed *** the yaw angle increases,the wake deflection becomes more prominent and the wake narrows;the offset of the wake center at various downstream positions grows linearly,reaching a maximum value of approximately half the rotor ***,the turbulence level and influence range in the wake region are reduced when the turbine is *** ABL wind conditions,high turbulence intensity in the incoming flow accelerates wake recovery,and the Reynolds stress at different lateral positions tends to become consistent with increasing longitudinal ***,turbulence has a significant impact on the meandering characteristics of the wind turbine wake,with greater fluctuations in the wake center observed under higher turbulence ***,this study provides insights that could inform the optimal operation of wind farms.

关键词： horizontal axis wind turbine turbulence wind tunnel experiment wind turbine wake

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