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Deciphering the mechanobiology of microglia in traumatic brain injury with advanced microsystems

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Neural Regeneration Research 2025年第8期20卷 2304-2306页

作者： Anthony Procès sylvain Gabriele Univ.Grenoble Alpes InsermU1216Grenoble Institut des NeurosciencesGrenobleFrance Mechanobiology&Biomaterials Group CIRMAPResearch Institute for BiosciencesUniversity of MonsMonsBelgium

Advanced microsystems in traumatic brain injury research:Traumatic brain injury(TBI)results from a mechanical insult to the brain,leading to neuronal and axonal damage and subsequently caus.ng a secondary *** minutes ... 详细信息

关键词： traumatic injury damage

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 us.ng 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 process.ng 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

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

The effects of nutrients on stream invertebrates:a regional estimation by generalized propensity score

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Ecological Processes 2018年第1期7卷 218-230页

作者： Zutao Ouyang s.ng s.qian Richard Becker Jiquan Chen Center for Global Change and Earth Observations Michigan State University1405 S.Harrison RoadEast LansingMI 48823USA Department of Environmental sciences University of Toledo2801 West Bancroft StreetToledoOH 43606USA

Introduction:The effects of nutrients on stream conditions within individual streams or small areas have been studied extensively,but the same effects over a large region have rarely been examined due to the difficulty of applying large-scale manipulative *** this study,we estimated the causal effects of nutrients within the Western United states on invertebrate richness,an important biological indicator of stream conditions,by us.ng observational ***:We used the generalized propensity score method to avoid the common problem of statistical inference us.ng observational data,i.e.,correlation established based on observational data does not imply a causal relationship because the effects of confounding factors are not properly ***:Our analysis showed a subsidy-stress relationship between nutrients and invertebrate taxon richness in the whole Western United states and in its *** magnitude of the relationship varies among these subecoregions,suggesting a varying nitrogen effect on macroinvertebrates due,in large part,to the varying natural and anthropogenic conditions from ecoregion to ***,our analysis confirmed that causal estimation results us.ng regression can be sensitive to the imbalance of confounding ***:stratifying data into ecoregions with relatively homogeneous environmental conditions or adjusting data by generalized propensity score can improve the balance of confounding factors,thereby allowing more reliable causal inference of nutrient *** respond to the same nutrient levels differently across different site conditions.

关键词： Nutrient criteria Water quality Environmental management Ecoregion

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 increas.ng 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

A pan-cancer fingerprint:common molecular denominators of the human tumor microenvironment

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signal Transduction and Targeted Therapy 2021年第12期6卷 3371-3372页

作者： susanna s.ng sonia Leonardelli Michael Hölzel Institute of Experimental Oncology University Hospital BonnUniversity of Bonn53127 BonnGermany

In a recent study published in Cancer Cell,Bagaev et *** a pan-cancer tumor microenvironment(TME)classification that can be predictive of response to immune checkpoint inhibitor(ICI)therapy.1 The authors presented a detailed visualization that can be generated for each tumor,which combines the 29 functional gene expression signatures(Fges)used to subtype the TME with targetable genomic *** the compartments and pathways within the TME could aid decision-making in patient-specific treatment of cancer,especially in the context of immunotherapies.2 The increas.ng use of ICIs have shown promis.ng clinical outcomes in several cancer ***,response to treatment is heterogenous and often results in immune-related adverse events.3 Therefore,efforts are focused on the development of prognostic tools to predict response to *** analysis of 468 melanoma patients resulted in grouping of the TME into four major subsets based on manually curated Fges.

关键词： cancer alterations

A Causality-guided statistical Approach for Modeling Extreme Mei-yu Rainfall Based on Known Large-scale Modes——A Pilot study

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Advances in Atmospheric sciences 2022年第11期39卷 1925-1940页

作者： Kelvin s.ng Gregor C.LECKEBUsCH Kevin I.HODGEs school of Geography Earth and Environmental SciencesUniversity of BirminghamBirmingham B152TTUnited Kingdom Department of Meteorology and NCAs University of ReadingReading RG66BBUnited Kingdom

Extreme Mei-yu rainfall(MYR)can cause catastrophic impacts to the economic development and societal welfare in *** significant improvements have been made in climate models,they often struggle to simulate local-to-regional extreme rainfall(e.g.,MYR).Yet,large-scale climate modes(LsCMs)are relatively well represented in climate *** there exists a close relationship between MYR and various LsCMs,it might be possible to develop causality-guided statistical models for MYR prediction based on *** statistical models could then be applied to climate model simulations to improve the representation of MYR in climate *** this pilot study,it is demonstrated that skillful causality-guided statistical models for MYR can be constructed based on known *** relevancy of the selected predictors for statistical models are found to be consistent with the *** importance of temporal resolution in constructing statistical models for MYR is also shown and is in good agreement with the *** results demonstrate the reliability of the causality-guided approach in studying complex circulation systems such as the East Asian summer monsoon(EAsM).some limitations and possible improvements of the current approach are *** application of the causality-guided approach opens up a new possibility to uncover the complex interactions in the EAsM in future studies.

关键词： extreme rainfall Mei-yu front causality-guided approach large-scale climate modes

Incorporation of a nanotechnology-based additive in cementitious products for clay stabilisation

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Journal of Rock Mechanics and Geotechnical Engineering 2020年第5期12卷 1056-1069页

作者： E.U.Eyo s.ng’ambi s.J.Abbey school of Energy Construction and EnvironmentFaculty of EngineeringEnvironment and ComputingCoventry UniversityCoventryUK Faculty of Environment and Technology Department of Geography and Environmental ManagementCivil Engineering ClusterUniversity of the West of EnglandBristolUK

The mechanical performances and water retention characteristics of clays,stabilised by partial substitution of cement with by-products and inclusion of a nanotechnology-based additive called RoadCem(RC),are studied in this *** unconfined compression tests and one-dimensional oedometer swelling were performed after 7 d of curing to understand the influence of addition of 1%of RC material in the stabilised soils with the cement partially replaced by 49%,59%and 69%of ground granulated blast furnace slag(GBBs)or pulverised fuel ash(PFA).The moisture retention capacity of the stabilised clays was also explored us.ng the soil-water retention curve(sWRC)from the measured *** confirmed an obvious effect of the use of RC with the obtained strength and swell properties of the stabilised clays suitable for road application at 50%replacement of *** outcome is associated with the in-depth and penetrating hydration of the cementitious materials by the RC and water which results in the production of needle-like matrix with interlocking filaments e a phenomenon referred to as the‘wrapping’*** the other hand,the sWRC used to describe the water holding capacity and corresponding swell mechanism of clays stabilised by a proportion of RC showed a satisfactory *** moisture retention of the RC-modified clays was initially higher but reduced subsequently as the saturation level increased with decreas.ng *** phenomenon confirmed that clays stabilised by including the RC are water-proof in nature,thus ensuring reduced porosity and suction even at reduced water ***,the stabilised clays with the combination of cement,GGBs and RC showed a better performance compared to those with the PFA included.

关键词： Cement Ground granulated blast furnace slag(GBBs) Fly ash RoadCem(RC) swell stabilisation Unconfined compressive strength soil-water retention curve(sWRC)