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

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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

Research status and prospects of the fractal analysis of metal material surfaces and interfaces

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International Journal of Minerals,Metallurgy and materials 2025年第1期32卷 20-38页

作者： Qinjin Dai Xuefeng liu Xin ma Shaojie Tian Qinghe Cui Beijing Advanced Innovation Center for materials Genome Engineering University of Science and Technology BeijingBeijing 100083China Beijing laboratory of Metallic materials and Processing for Modern Transportation University of Science and Technology BeijingBeijing 100083China laboratory for Advanced materials Processing of Ministry of Education University of Science and Technology BeijingBeijing 100083China School of Mechanical and Electrical Engineering Xinjiang Institute of EngineeringUrumqi 830023China

As a mathematical analysis method,fractal analysis can be used to quantitatively describe irregular shapes with self-similar or self-affine *** analysis has been used to characterize the shapes of metal materials at various scales and *** methods make it difficult to quantitatively describe the relationship between the regular characteristics and properties of metal material surfaces and ***,fractal analysis can be used to quantitatively describe the shape characteristics of metal materials and to establish the quantitative relationships between the shape characteristics and various properties of metal *** the perspective of two-dimensional planes and three-dimensional curved surfaces,this paper reviews the current research status of the fractal analysis of metal precipitate interfaces,metal grain boundary interfaces,metal-deposited film surfaces,metal fracture surfaces,metal machined surfaces,and metal wear *** relationship between the fractal dimensions and properties of metal material surfaces and interfaces is *** from three perspectives of fractal analysis,namely,research scope,image acquisition methods,and calculation methods,this paper identifies the direction of research on fractal analysis of metal material surfaces and interfaces that need to be *** is believed that revealing the deep influence mechanism between the fractal dimensions and properties of metal material surfaces and interfaces will be the key research direction of the fractal analysis of metal materials in the future.

关键词： metal material surfaces and interfaces fractal analysis fractal dimension homogeneity

Polyethylene glycol has immunoprotective effects on sciatic allografts, but behavioral recovery and graft tolerance require neurorrhaphy and axonal fusion

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Neural Regeneration Research 2025年第4期20卷 1192-1206页

作者： Tyler A.Smith liwen zhou Cameron l.Ghergherehchi Michelle Mikesh Cathy z.Yang Haley O.Tucker JuliAnne Allgood Jared S.Bushman George D.Bittner Department of Molecular Biosciences University of Texas at AustinAustinTXUSA Department of Neuroscience University of Texas at AustinAustinTXUSA Division of Pharmaceutical Sciences University of WyomingLaramieWYUSA

Behavioral recovery using(viable)peripheral nerve allografts to repair ablation-type(segmental-loss)peripheral nerve injuries is delayed or poor due to slow and inaccurate axonal ***,such peripheral nerve allografts undergo immunological rejection by the host immune *** contrast,peripheral nerve injuries repaired by polyethylene glycol fusion of peripheral nerve allografts exhibit excellent behavioral recovery within weeks,reduced immune responses,and many axons do not undergo Wallerian *** relative contribution of neurorrhaphy and polyethylene glycol-fusion of axons versus the effects of polyethylene glycol per se was unknown prior to this *** hypothesized that polyethylene glycol might have some immune-protective effects,but polyethylene glycol-fusion was necessary to prevent Wallerian degeneration and functional/behavioral *** examined how polyethylene glycol solutions per se affect functional and behavioral recovery and peripheral nerve allograft morphological and immunological responses in the absence of polyethylene glycol-induced axonal ***-type sciatic nerve injuries in outbred Sprague–Dawley rats were repaired according to a modified protocol using the same solutions as polyethylene glycol-fused peripheral nerve allografts,but peripheral nerve allografts were loose-sutured(loose-sutured polyethylene glycol)with an intentional gap of 1–2 mm to prevent fusion by polyethylene glycol of peripheral nerve allograft axons with host *** to negative control peripheral nerve allografts not treated by polyethylene glycol and in contrast to polyethylene glycol-fused peripheral nerve allografts,animals with loose-sutured polyethylene glycol peripheral nerve allografts exhibited Wallerian degeneration for all axons and myelin degeneration by 7 days postoperatively and did not recover sciatic-mediated behavioral functions by 42 days *** morphological signs of rejection,such as col

关键词： allograft rejection axotomy macrophage myelin nerve repair polyethylene glycol(PEG) sciatic nerve T cell transplantation Wallerian degeneration

Recombinant chitinase-3-like protein 1 alleviates learning and memory impairments via M2 microglia polarization in postoperative cognitive dysfunction mice

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Neural Regeneration Research 2025年第9期20卷 2727-2736页

作者： Yujia liu Xue Han Yan Su Yiming zhou Minhui Xu Jiyan Xu zhengliang ma Xiaoping Gu Tianjiao Xia Department of Anesthesiology Nanjing Drum Tower HospitalAffiliated Hospital of Medical SchoolNanjing UniversityNanjingJiangsu ProvinceChina Medical School Nanjing UniversityNanjingJiangsu ProvinceChina Jiangsu Key laboratory of Molecular Medicine Nanjing UniversityNanjingJiangsu ProvinceChina State Key laboratory of Pharmaceutical Biotechnology Nanjing UniversityNanjingJiangsu ProvinceChina Department of Anesthesiology Zhongshan HospitalFudan UniversityShanghaiChina

Postoperative cognitive dysfunction is a seve re complication of the central nervous system that occurs after anesthesia and surgery,and has received attention for its high incidence and effect on the quality of life of *** date,there are no viable treatment options for postoperative cognitive *** identification of postoperative cognitive dysfunction hub genes could provide new research directions and therapeutic targets for future *** identify the signaling mechanisms contributing to postoperative cognitive dysfunction,we first conducted Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses of the Gene Expression Omnibus GSE95426 dataset,which consists of mRNAs and long non-coding RNAs differentially expressed in mouse hippocampus3 days after tibial *** dataset was enriched in genes associated with the biological process"regulation of immune cells,"of which Chill was identified as a hub ***,we investigated the contribution of chitinase-3-like protein 1 protein expression changes to postoperative cognitive dysfunction in the mouse model of tibial fractu re *** were intraperitoneally injected with vehicle or recombinant chitinase-3-like protein 124 hours post-surgery,and the injection groups were compared with untreated control mice for learning and memory capacities using the Y-maze and fear conditioning *** addition,protein expression levels of proinflammatory factors(interleukin-1βand inducible nitric oxide synthase),M2-type macrophage markers(CD206 and arginase-1),and cognition-related proteins(brain-derived neurotropic factor and phosphorylated NMDA receptor subunit NR2B)were measured in hippocampus by western *** with recombinant chitinase-3-like protein 1 prevented surgery-induced cognitive impairment,downregulated interleukin-1βand nducible nitric oxide synthase expression,and upregulated CD206,arginase-1,pNR2B,and brain-derived neurotropic factor expr

关键词： Chil1 hippocampus learning and memory M2 microglia neuroinflammation postoperative cognitive dysfunction(POCD) recombinant CHI3l1

Decreased levels of phosphorylated synuclein in plasma are correlated with poststroke cognitive impairment

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Neural Regeneration Research 2025年第9期20卷 2598-2610页

作者： Yi Wang Yuning li Yakun Gu Wei ma Yuying Guan Mengyuan Guo Qianqian Shao Xunming Ji Jia liu Department of Clinical laboratory Beijing Bo’ai HospitalChina Rehabilitation Research CenterCapital Medical UniversityBeijingChina Beijing Institute of Brain Disorders Laboratory of Brain DisordersMinistry of Science and TechnologyCollaborative Innovation Center for Brain DisordersBeijing Advanced Innovation Center for Big Data-based Precision MedicineCapital Medical UniversityBeijingChina Department of Neurosurgery Xuanwu HospitalCapital Medical UniversityBeijingChina

Poststro ke cognitive impairment is a major secondary effect of ischemic stroke in many patients;however,few options are available for the early diagnosis and treatment of this *** aims of this study were to(1)determine the specific relationship between hypoxic andα-synuclein during the occur of poststroke cognitive impairment and(2)assess whether the serum phosphorylatedα-synuclein level can be used as a biomarker for poststro ke cognitive *** found that the phosphorylatedα-synuclein level was significantly increased and showed pathological aggregation around the cerebral infa rct area in a mouse model of ischemic *** addition,neuronalα-synuclein phosphorylation and aggregation were observed in the brain tissue of mice subjected to chronic hypoxia,suggesting that hypoxia is the underlying cause ofα-synuclein-mediated pathology in the brains of mice with ischemic *** phosphorylatedα-synuclein levels in patients with ischemic stroke were significantly lower than those in healt hy subjects,and were positively correlated with cognition levels in patients with ischemic ***,a decrease in serum high-density lipoprotein levels in stroke patie nts was significantly correlated with a decrease in phosphorylatedα-synuclein *** ischemic stroke mice did not show significant cognitive impairment or disrupted lipid metabolism 14 days after injury,some of them exhibited decreased cognitive function and reduced phosphorylatedα-synuclein *** together,our results suggest that serum phosphorylatedα-synuclein is a potential biomarker for poststroke cognitive impairment.

关键词： biomarker high-density lipoprotein ischemic stroke phosphorylatedα-synuclein poststroke cognitive impairment

Synergetic deformation mechanisms in an Mg-zn-Y-zr alloy with intragranular lPSO structures

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Journal of magnesium and Alloys 2023年第5期11卷 1754-1768页

作者： z.z.Peng X.H.Shao z.M.liang D.l.Wang l.W.Wang X.l.ma Hebei Key laboratory of material Near-Net Forming Technology School of Materials Science and EngineeringHebei University of Science and TechnologyShijiazhuang 050018China Shenyang National laboratory for materials Science Institute of Metal ResearchChinese Academy of Sciences72 Whenua RoadShenyang 110016China

Deformation kink is one of the important strengthening mechanisms of the long-period-stacking-ordered(lPSO)phase containing magnesium(Mg)alloys,while the deformation twin is generally *** optimize the mechanical properties of lPSO containing Mg alloy by simultaneously exciting kink and twin,we successfully prepared the Mg-zn-Y-zr alloy featuring intragranular lPSO phase and free grain boundary lPSO phase by *** unraveled the corresponding strengthening and toughening mechanisms through transmission electron microscopy characterization and theoretical *** high strength and good plasticity of the homogenized alloy benefit from the synergistic deformation mechanism of multiple kinking and twining in the *** the activation of kinking and twinning depends on the thicknesses of lPSO lamellae and their relative *** results may shed light on optimizing the design of Mg alloys regulating the microstructure of lPSO phases.

关键词： Mg alloy lPSO distribution Kink Twin Transmission electron microscopy

Evolution of the Microstructure and Strength in the Nugget zone of Friction Stir Welded SiCp/Al-Cu-Mg Composite

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Journal of materials Science & Technology 2014年第1期30卷 54-60页

作者： D.Wang B.l.Xiao Q.z.Wang z.Y.ma Shenyang National laboratory for materials Science Institute of Metal ResearchChinese Academy of Sciences University of Science and Technology of China

A 6 mm-thick SiCp/2009AI composite plate was successfully joined by friction stir welding （FSW） using an ultrahard material tool to investigate the evolution of the microstructure and the strength in the nugget zone （Nz）. While some SiC particles were broken up during FSW, most of them rotated in the matrix. large compound particles on the interfaces were broken off during FSW, whereas the amorphous layer and small compound particles remained on the interfaces. The dynamically recrystallized AI grains nucleated on the surface of fractured SiC particles during FSW, forming nano-sized grains around the SiC particles. The yield strength of the Nz decreased slightly due to the variation in the size, shape, and distribution of the SiC particles. The clean interfaces were beneficial to the load transfer between SiC particles and AI matrix and then increased the ultimate tensile strength of the Nz.

关键词： Metal-matrix composites Friction stir welding Microstructure Mechanical properties

Microstructure evolution and hot deformation behavior of carbon nanotube reinforced 2009Al composite with bimodal grain structure

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Journal of materials Science & Technology 2021年第11期70卷 73-82页

作者： K.ma z.Y.liu S.Bi X.X.zhang B.l.Xiao z.Y.ma Shi-changxu Innovation Center for Advanced materials Institute of Metal ResearchChinese Academy of ScienceShenyang110016China School of materials Science and Engineering University of Science and Technology of China72 Wenhua RoadShenyang110016China School of materials Science and Engineering Guilin University of TechnologyGuilin541004China

The hot deformation behaviors of the bimodal carbon nanotube reinforced 2009Al(CNT/2009Al)composite were studied by establishing processing map and characterizing the microstructure *** results indicate that the grain size in the ultra-fine grained zones was stable during hot deformation,while the coarse grained zones were elongated with their long axis directions tending to be perpendicular to the compression *** temperature with high strain rate(lTHR),as well as high temperature with low strain rate(HTlR)could increase the length/width ratio of the coarse grained ***,lTHR and HTlR could cause the instable *** instable deformation at lTHR was induced by severe intragranular plastic deformation and the localized shear crack,while the instable deformation at HTlR resulted from the more deformation component at the coarse grained zones,and the micro-pore initiation due to CNT re-agglomeration at the boundaries between the coarse and the ultra-fine grained zones.

关键词： Carbon nanotube Bimodal Aluminum matrix composite Hot deformation Processing map

Effect of Carbon Nanotube Orientation on Mechanical Properties and Thermal Expansion Coefficient of Carbon Nanotube-Reinforced Aluminum matrix Composites

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Acta Metallurgica Sinica(English letters) 2014年第5期27卷 901-908页

作者： z.Y.liu B.l.Xiao W.G.Wang z.Y.ma School of materials Science and Engineering Dalian University of Technology Shenyang National laboratory for materials Science Institute of Metal ResearchChinese Academy of Sciences School of Mechanical Engineering Liaoning Shihua University

Carbon nanotube-reinforced 2009Al （CNT/2009Al） composites with randomly oriented CNTs and aligned CNTs were fabricated by friction stir processing （FSP） and FSP-rolling, respectively. The CNT/2009A1 composites with aligned CNTs showed much better tensile properties at room temperature and elevated temperature compared with those with the randomly oriented CNTs, which is mainly attributed to larger equivalent aspect ratio of the CNTs and avoidance of preferential fracture problems. However, much finer grain size was not beneficial to obtaining high strength above 473 K. The aligned CNTs resulted in tensile anisotropy, with the best tensile properties being achieved along the direction of CNT aligning. As the off-axis angle increased, the tensile properties were reduced due to the weakening of the load transfer ability. Furthermore, aligned CNTs resulted in much lower coefficient of thermal expansion compared with randomly oriented CNTs.

关键词： Carbon nanotubes Metal matrix composites Mechanical properties Coefficient of thermalexpansion Friction stir processing