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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

Effects of aggregate size distribution and carbon nanotubes on the mechanical properties of cemented gangue backfill samples under true triaxial compression

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International Journal of Minerals,Metallurgy and Materials 2025年第2期32卷 311-324页

作者： Qian Yin Fan Wen Zhigang Tao hai Pu Tianci Deng Yaoyao meng Qingbin meng hongwen Jing Bo meng Jiangyu Wu state Key Laboratory of Intelligent Construction and healthy Operation and Maintenance of Deep Underground Engineering China University of Mining and TechnologyXuzhou 221116China state Key Laboratory of Mining Response and Disaster Prevention and Control in Deep Coal Mines Anhui University of Science and TechnologyHuainan 232001China state Key Laboratory for Geomechanics&Deep Underground Engineering China University of Mining and Technology(Beijing)Beijing 100083China Key Laboratory of Xinjiang Coal Resources Green Mining Ministry of EducationXinjiang Institute of EngineeringUrumqi 830023China

The mechanical behavior of cemented gangue backfill materials(CGBMs)is closely related to particle size distribution(PsD)of aggregates and properties of cementitious ***,the true triaxial compression tests,CT scanning,sEM,and EDs tests were conducted on cemented gangue backfill samples(CGBss)with various carbon nanotube concentrations(P_(CNT))that satisfied fractal theory for the PsD of *** mechanical properties,energy dissipations,and failure mechanisms of the CGBss under true triaxial compression were systematically *** results indicate that appropriate carbon nanotubes(CNTs)effectively enhance the mechanical properties and energy dissipations of CGBss through micropore filling and microcrack bridging,and the optimal effect appears at P_(CNT)of 0.08wt%.Taking PsD fractal dimension(D)of 2.500 as an example,compared to that of CGBs without CNT,the peak strength(σ_(p)),axial peak strain(ε_(1,p)),elastic strain energy(Ue),and dissipated energy(U_(d))increased by 12.76%,29.60%,19.05%,and90.39%,***,excessive CNTs can reduce the mechanical properties of CGBss due to CNT agglomeration,manifesting a decrease inρ_(p),ε_(1,p),and the volumetric strain increment(Δε_(v))when P_(CNT)increases from 0.08wt%to 0.12wt%.Moreover,the addition of CNTs improved the integrity of CGBs after macroscopic failure,and crack extension in CGBss appeared in two modes:detour and pass through the ***σ_(p)and U_(d)firstly increase and then decrease with increasing D,and porosity shows the opposite ***ε_(1,p)andΔε_(v)are negatively correlated with D,and CGBs with D=2.150 has the maximum deformation parameters(ε_(1,p)=0.05079,Δε_(v)=0.01990)due to the frictional slip effect caused by coarse *** increasing D,the failure modes of CGBss are sequentially manifested as oblique shear failure,"Y-shaped"shear failure,and conjugate shear failure.

关键词： cemented gangue backfill materials particle size distribution true triaxial compression test carbon nanotubes mechanical properties failure modes

Progress of research in the application of ultrasound technology for the treatment of Alzheimer’s disease

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Neural Regeneration Research 2025年第10期20卷 2823-2837页

作者： Qiuquan Cai Lianghui meng Meina Quan Ling Wang Jing Ren Chenguang Zheng Jiajia Yang Dong Ming Academy of Medical Engineering and Translational Medicine Tianjin UniversityTianjinChina Innovation Center for Neurological Disorders Xuanwu HospitalCapital Medical UniversityBeijingChina Brain-Computer Interaction and human-Machine Fusion haihe Laboratory Tianjin UniversityTianjinChina Tianjin Key Laboratory of Brain science and Neural Engineering Tianjin UniversityTianjinChina

Alzheimer’s disease is a common neurodegenerative disorder defined by decreased reasoning abilities,memory loss,and cognitive *** presence of the blood-brain barrier presents a major obstacle to the development of effective drug therapies for Alzheimer’s *** use of ultrasound as a novel physical modulation approach has garnered widespread attention in recent *** a safe and feasible therapeutic and drug-delivery method,ultrasound has shown promise in improving cognitive *** article provides a summary of the application of ultrasound technology for treating Alzheimer’s disease over the past 5 years,including standalone ultrasound treatment,ultrasound combined with microbubbles or drug therapy,and magnetic resonance imaging-guided focused ultrasound *** is placed on the benefits of introducing these treatment methods and their potential *** found that several ultrasound methods can open the blood-brain barrier and effectively alleviate amyloid-βplaque *** believe that ultrasound is an effective therapy for Alzheimer’s disease,and this review provides a theoretical basis for future ultrasound treatment methods.

关键词： Alzheimer’s disease blood-brain barrier drugs magnetic resonance imaging-guided focused ultrasound microbubbles scanning ultrasound ultrasound ultrasound stimulation

Neuroinflammation as a therapeutic target in huntington's disease

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Neural Regeneration Research 2025年第3期20卷 817-818页

作者： Andrea Kwakowsky Thulani h.Palpagama Center for Brain Research and Department of Anatomy and Medical Imaging Faculty of Medical and Health SciencesUniversity of AucklandAucklandNew Zealand Pharmacology and Therapeutics School of MedicineGalway Neuroscience CentreUniversity of GalwayGalwayIreland

In 1872, George huntington presented his essay “On Chorea” to the Meigs and Mason Academy of Medicine and, in doing so, detailed a disease that would later bear his name. huntington's disease(hD) is a genetic, neurodegenerative disease that manifests as the loss of motor control,cognitive impairment,and mood and psychiatric changes in paents.

关键词： huntington inflammation Medicine

Glial response in the midcingulate cortex in huntington’s disease

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Neural Regeneration Research 2025年第1期20卷 207-208页

作者： Thulani h.Palpagama Andrea Kwakowsky Center for Brain Research and Department of Anatomy and Medical Imaging Faculty of Medical and Health SciencesUniversity of AucklandAucklandNew Zealand Pharmacology and Therapeutics School of MedicineGalway Neuroscience CenterUniversity of GalwayGalwayIreland

huntington’s disease(hD)is a genetic disease characterized by the progressive degeneration of the striatum and *** can present with a variety of symptoms that can broadly be classified into motor symptoms,inclusive of choreatic movements and rigidity,mood and psychiatric symptoms,such as depression and apathy,and cognitive symptoms,such as cognitive *** causal mutation underlying hD results from an expansion of a CAG repeat sequence on the IT15 gene,resulting in the formation and accumulation of a mutant huntingtin protein.

关键词： huntington degeneration cortex

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

Emerging structures and dynamic mechanisms ofγ-secretase for Alzheimer’s disease

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Neural Regeneration Research 2025年第1期20卷 174-180页

作者： Yinglong Miao Michael s.Wolfe Computational Medicine Program and Department of Pharmacology University of North Carolina–Chapel HillChapel HillNCUSA Department of Medicinal Chemistry University of KansasLawrenceKSUSA

γ-secretase,called“the proteasome of the membrane,”is a membrane-embedded protease complex that cleaves 150+peptide substrates with central roles in biology and medicine,including amyloid precursor protein and the Notch family of cell-surface *** inγ-secretase and amyloid precursor protein lead to early-onset familial Alzheimer’s disease.γ-secretase has thus served as a critical drug target for treating familial Alzheimer’s disease and the more common late-onset Alzheimer’s disease as ***,critical gaps remain in understanding the mechanisms of processive proteolysis of substrates,the effects of familial Alzheimer’s disease mutations,and allosteric modulation of substrate cleavage byγ-*** this review,we focus on recent studies of structural dynamic mechanisms ofγ-*** mechanisms,including the“Fit-stay-Trim,”“sliding-Unwinding,”and“Tilting-Unwinding,”have been proposed for substrate proteolysis of amyloid precursor protein byγ-secretase based on all-atom molecular dynamics *** an incorrect registry of the Notch1 substrate was identified in the cryo-electron microscopy structure of Notch1-boundγ-secretase,molecular dynamics simulations on a resolved model of Notch1-boundγ-secretase that was reconstructed using the amyloid precursor protein-boundγ-secretase as a template successfully capturedγ-secretase activation for proper cleavages of both wildtype and mutant Notch,being consistent with biochemical experimental *** approach could be potentially applied to decipher the processing mechanisms of various substrates byγ-*** addition,controversy over the effects of familial Alzheimer’s disease mutations,particularly the issue of whether they stabilize or destabilizeγ-secretase-substrate complexes,is ***,an outlook is provided for future studies ofγ-secretase,including pathways of substrate binding and product release,effects of modulators on familial Alzheimer’s disease mutations

关键词： Alzheimer’s disease amyloid precursor protein cryo-EM structures drug design intramembrane proteolysis molecular dynamics Notch

Near-perfect replication on amorphous alloys through active force modulation based on machine learning/neural network parameter prediction

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science China(Physics,Mechanics & Astronomy) 2025年第1期Mechanics & Astronomy) .卷 181-191页

作者： senkuan meng Zheng Wang Ruisong Zhu Ruijie Liu Jiang Ma Lina hu Weihua Wang Key Laboratory for Liquid-solid structural Evolution and Processing of Materials (Ministry of Education) School of Materials Science and Engineering Shandong University College of Mechatronics and Control Engineering Shenzhen University songshan Lake Materials Laboratory Institute of Physics Chinese Academy of Sciences

As a microforming technique, micro/nano-structural replication possesses advantages of high precision and efficiency. With the remarkable superplasticity in the supercooled liquid region, amorphous alloys or metallic glasses(MGs) are regarded as ideal materials for miniature fabrication. however, due to the intrinsic metastable nature of supercooled liquids, the design of imprinting processes for MGs poses a challenge. In the past, process parameters have largely relied on trial-and-error *** this work, a low-frequency active force modulation system is employed to apply a stable, precise, and real-time feedback stress field for imprinting of MG samples. Low-frequency vibrations can facilitate the filling of microstructures on the template surface by reducing the effective viscosity of the supercooled liquid. With the dataset composed of orthogonal experiments, a machine learning strategy based on back-propagation(BP) neural networks was utilized to construct a 3D parameter space for temperature, stress, and time, and to predict the corresponding filling ratio. Furthermore, the optimal combination of imprinting process parameters was identified, and its filling ratio was experimentally validated to reach as high as 0.94. The near-perfect replication of microstructures confirms the superiority of the active force modulation system and the data-driven strategy of machine learning-assisted parameter design. At the same time, this one-step microforming process provides a new approach to addressing the accuracy-cost trade-off dilemma in precision manufacturing.

关键词： metallic glass amorphous alloy microforming imprinting machine learning

Complementary roles of glial cells in generating region-specific neuroinflammatory responses and phagocytosis in Parkinson’s disease

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Neural Regeneration Research 2025年第10期20卷 2917-2918页

作者： Leyre Ayerra Maria s.Aymerich Universidad de Navarra Facultad de CienciasDepartamento de Bioquímica y GenéticaPamplonaSpain CIMA-Universidad de Navarra PamplonaSpain IdisNA Instituto de Investigación Sanitaria de NavarraPamplonaSpain

Neuroinflammation is associated with Parkinson’s disease:Reactive gliosis and neuroinflammation are hallmarks of Parkinson’s disease(PD),a multisystem neurodegenerative disorder characterized by a progressive loss of dopaminergic *** has long been considered a mere consequence of neuronal loss,but whether it promotes PD or is a key player in disease progression remains to be *** leukocyte antigen.

关键词： inflammation leukocyte generating