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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

Bioelectronic medicine in modulation of cortical spreading depolarization and beyond

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Neural Regeneration Research 2025年第2期20卷 481-482页

作者： Khaled Alok Timothy g.White Chunyan Li Department of Neurosurgery Donald and Barbara Zucker School of Medicine at Hofstra/NorthwellHempsteadNYUSA Translational Brain Research Laboratory The Feinstein Institutes for Medical ResearchManhassetNYUSA

Bioelectronic interventions,specifically trigeminal nerve st imulat ion(TNs),have attracted considerable attention in conditions where cortical spreading depolarizations(CsDs)accompanied by compromised cerebral perfusion may exacerbate neurological *** pharmacological interventions have demonstrated initial potential in addressing CsDs,a standardized treatment approach has not yet been *** objective of this perspective is to explore emerging bioelectronic methodologies for addressing CsDs,particularly emphasizing TNs,and to underscore TNs’s capacity to enhance neurovascular coupling and cerebral perfusion.

关键词： cerebral perfusion electronic

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

Understanding activity of butyrate at a cellular level

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Neural Regeneration Research 2025年第8期20卷 2323-2324页

作者： Prapti Chakraborty Angela s.Laird Macquarie University Motor Neuron Disease Research Centre Macquarie Medical SchoolFaculty of MedicineHealth and Human SciencesMacquarie UniversitySydneyAustralia

Butyrate is a short-chain fatty acid of four carbons in length that is a by-product produced by the microbial fermentation of dietary fiber and undigested carbohydrates within the *** the years,butyrate has attracted ... 详细信息

关键词： carbons butyrate fiber

Microglial dysfunction and genetic risk for neurodegenerative disease

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Neural Regeneration Research 2025年第5期20卷 1401-1402页

作者： Debra s.MacDonald Jay Penney Department of Biomedical sciences AVCUniversity of Prince Edward IslandCharlottetownPECanada

Neurodegenerative disorders such as Alzheimer's and Parkinson's diseases a re increasing in prevalence as world populations *** tremendous progress has been made,our understanding of the mechanisms that underlie the development of these diseases remains far from com *** troubling,despite the growing emotional and financial toll being to ken by neurodegenerative disorders,existing treatment options are limited almost exclusively to those that help manage symptoms but that lack the ability to alter the progression of the disease(Liu et al.,2022).

关键词： degenerative diseases

Chemotherapy for cholangiocarcinoma:An update

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World Journal of gastrointestinal Oncology 2013年第7期5卷 171-176页

作者： Natalia Ramírez-Merino santiago Ponce Aix Hernán cortés-Funes Department of Medical Oncology Clinica La Luz28003 MadridSpain

Cholangiocarcinomas(bile duct cancers) are a heterogeneous group of malignancies arising from the epithelial cells of the intrahepatic,perihilar and extrahepatic bile *** diagnosed with cholangiocarcinoma must be evaluated by a multidisciplinary team and be treated with individualized *** of all,it is very important to define the potential resectability of the tumor because surgery is the main therapeutic option for these ***,cholangiocarcinomas have a very poor *** 5 year survival rate is 5%-10%.In cases with a potentially curative surgery,5 year survival rates of 25%-30% are ***,it is necessary to increase the cure rate from surgery,exploring the survival benefit of any adjuvant *** is difficult to clarify the role of adjuvant treatment in localized and locally advanced *** are limited data and the role of adjuvant chemotherapy/chemoradiation in patients with resected biliary tract cancer is poorly *** most relevant studies in the adjuvant setting are one from Japan,the well known EsPAC-3 and BILCAP from the United Kingdom and a *** show the results of these *** to medical oncology guidelines,postoperative adjuvant therapy is widely recommended for all patients with intrahepatic or extrahepatic cholangiocarcinoma who have microscopically positive resection margins,as well as for those with a complete resection but node-positive *** trials are *** locally advanced cholangiocarcinoma setting includes a heterogeneous mix of patients:(1) patients who have had surgery but with macroscopic residual disease;(2) patients with locally recurrent disease after potentially curative treatment;and(3) patients with locally unresectable disease at *** these patients,surgery is not an option and chemoradiation therapy can prolong overall survival and provide control of symptoms due to local tumor ***,no neoadjuv

关键词： Chemotherapy Cholangiocarcinoma Review Oncology gemcitabine

A comprehensive investigation on nonlinear vibration and bending characteristics of bio-inspired helicoidal laminated composite structures

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Applied Mathematics and Mechanics(English Edition) 2025年第1期46卷 81-100页

作者： s.sAURABH R.KIRAN D.sINgH R.VAIsH V.s.CHAUHAN school of Mechanical and Materials Engineering Indian Institute of Technology Mandi

Bio-inspired helicoidal composite laminates, inspired by the intricate helical structures found in nature, present a promising frontier for enhancing the mechanical properties of structural designs. Hence, this study provides a comprehensive investigation into the nonlinear free vibration and nonlinear bending behavior of bio-inspired composite plates. The inverse hyperbolic shear deformation theory(IHsDT) of plates is employed to characterize the displacement field, with the incorporation of green-Lagrange nonlinearity. The problem is modeled using the C0finite element method(FEM), and an in-house code is developed in the MATLAB environment to solve it numerically. Various helicoidal layup configurations including helicoidal recursive(HR), helicoidal exponential(HE), helicoidal semi-circular(Hs), linear helicoidal(LH), and Fibonacci helicoidal(FH)with different layup sequences and quasi-isotropic configurations are studied. The model is validated, and parametric studies are conducted. These studies investigate the effects of layup configurations, side-to-thickness ratio, modulus ratios, boundary conditions, and loading conditions at different load amplitudes on the nonlinear vibration and nonlinear bending behaviors of bio-inspired composite plates. The results show that the laminate sequence exerts a substantial impact on both nonlinear natural frequencies and nonlinear bending behaviors. Moreover, this influence varies across different side-to-thickness ratios and boundary conditions of the bio-inspired composite plate.

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semantic segmentation of Lumbar Vertebrae Using Meijering U-Net(MU-Net)on spine Magnetic Resonance Images

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Computer Modeling in Engineering & sciences 2025年第1期142卷 733-757页

作者： Lakshmi s V V shiloah Elizabeth Darmanayagam sunil Retmin Raj Cyril Department of Computer science and Engineering College of Engineering GuindyAnna UniversityChennai600025India Department of Information Technology Madras Institute of TechnologyAnna UniversityChrompetChennai600044India

Lower back pain is one of the most common medical problems in the world and it is experienced by a huge percentage of people *** to its ability to produce a detailed view of the soft tissues,including the spinal cord,nerves,intervertebral discs,and vertebrae,Magnetic Resonance Imaging is thought to be the most effective method for imaging the *** semantic segmentation of vertebrae plays a major role in the diagnostic process of lumbar *** is difficult to semantically partition the vertebrae in Magnetic Resonance Images from the surrounding variety of tissues,including muscles,ligaments,and intervertebral discs.U-Net is a powerful deep-learning architecture to handle the challenges of medical image analysis tasks and achieves high segmentation *** work proposes a modified U-Net architecture namely MU-Net,consisting of the Meijering convolutional layer that incorporates the Meijering filter to perform the semantic segmentation of lumbar vertebrae L1 to L5 and sacral vertebra ***-colour mask images were generated and used as ground truth for training the *** work has been carried out on 1312 images expanded from T1-weighted mid-sagittal MRI images of 515 patients in the Lumbar spine MRI Dataset publicly available from Mendeley *** proposed MU-Net model for the semantic segmentation of the lumbar vertebrae gives better performance with 98.79%of pixel accuracy(PA),98.66%of dice similarity coefficient(DsC),97.36%of Jaccard coefficient,and 92.55%mean Intersection over Union(mean IoU)metrics using the mentioned dataset.

关键词： Computer aided diagnosis(CAD) magnetic resonance imaging(MRI) semantic segmentation lumbar vertebrae deep learning U-Net model

Predicting Maximum Lifespan Limits at Mean Menopausal Age

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Journal of Mathematical Research with Applications 2025年第1期 133-142页

作者： M.sUMATHI s.ANTONY CARLA Department of Mathematics N.M.S.S.Vellaichamy Nadar College Research scholar (Part-time) Madurai Kamaraj University

The age at which a woman enters natural menopause has also been associated to death from any cause. Menopause is a natural component of aging that happens between the ages of 45 and 55, with the average menopausal age being 51. Previous research has revealed the age at which women reach menopause, but there is no evidence to support the link between menopause and longevity. We made a study in assessing the limits of maximum lifespan at menopausal age in our previous article. In this paper, we aim to predict the maximum lifespan of women at mean menopausal age.

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