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Impacts of PI3K/protein kinase B pathway activation in reactive astrocytes: from detrimental effects to protective functions

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neural Regeneration Research 2025年第4期20卷 1031-1041页

作者： Ramón Pérez-núñez María Fernanda González Ana María Avalos Lisette Leyton Cellular Communication Laboratory Programa de Biología Celular y MolecularCenter for Studies on ExerciseMetabolism and Cancer(CEMC)Instituto de Ciencias Biomédicas(ICBM)Facultad de MedicinaUniversidad de ChileSantiagoChile Advanced Center for Chronic Diseases(ACCDiS) Faculty of Chemical and Pharmaceutical Sciences&Faculty of MedicineUniversidad de ChileSantiagoChile Instituto de Ciencias Biomédicas Facultad de Ciencias de la SaludUniversidad Autónoma de ChileSantiagoChile

Astrocytes are the most abundant type of glial cell in the central nervous *** injury and inflammation,astrocytes become reactive and undergo morphological and functional *** on their phenotypic classification as A1 or A2,reactive astrocytes contribute to both neurotoxic and neuroprotective responses,***,this binary classification does not fully capture the diversity of astrocyte responses observed across different diseases and *** analysis has revealed that reactive astrocytes have a complex landscape of gene expression profiles,which emphasizes the heterogeneous nature of their *** actively participate in regulating central nervous system inflammation by interacting with microglia and other cell types,releasing cytokines,and influencing the immune *** phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT)signaling pathway is a central player in astrocyte reactivity and impacts various aspects of astrocyte behavior,as evidenced by in silico,in vitro,and in vivo *** astrocytes,inflammatory cues trigger a cascade of molecular events,where nuclear factor-κB serves as a central mediator of the pro-inflammatory ***,we review the heterogeneity of reactive astrocytes and the molecular mechanisms underlying their *** highlight the involvement of various signaling pathways that regulate astrocyte reactivity,including the PI3K/AKT/mammalian target of rapamycin(mTOR),αvβ3 integrin/PI3K/AKT/connexin 43,and notch/PI3K/AKT *** targeting the inactivation of the PI3K/AKT cellular signaling pathway to control reactive astrocytes and prevent central nervous system damage,evidence suggests that activating this pathway could also yield beneficial *** dual function of the PI3K/AKT pathway underscores its complexity in astrocyte reactivity and brain function *** review emphasizes the importance of employing astrocyte-exclusive models to underst

关键词： inflammation integrins neuroprotective neurotoxic phosphatidylinositol 3-kinase reactive astrocytes signal transduction Thy-1(CD90)

Dendritic spine degeneration:a primary mechanism in the aging process

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neural Regeneration Research 2025年第6期20卷 1696-1698页

作者： Gonzalo Flores Leonardo Aguilar-Hernández Fernado García-Dolores Humberto nicolini Andrea Judith vázquez-Hernández Hiram Tendilla-Beltrán Instituto de Fisiología Benemérita Universidad Autónoma de Puebla(BUAP)PueblaMexico Instituto de Ciencias Forenses(InCIFO) Tribunal Superior de Justicia de la Ciudad de México(TSJCDMX).Mexico CityMexico Instituto nacional de Medicina Genómica(InMEGEn) Mexico CityMexico

Recent reports suggest that aging is not solely a physiological process in living beings;instead, it should be considered a pathological process or disease(Amorim et al., 2022). Consequently, this process involves a wide range of factors, spanning from genetic to environmental factors, and even includes the gut microbiome(GM)(Mayer et al., 2022). All these processes coincide at some point in the inflammatory process, oxidative stress, and apoptosis, at different degrees in various organs and systems that constitute a living organism(Mayer et al., 2022;AguilarHernández et al., 2023).

关键词： aging process stress

Brain-derived neurotrophic factor signaling in the neuromuscular junction during developmental axonal competition and synapse elimination

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neural Regeneration Research 2025年第2期20卷 394-401页

作者： Josep Tomàs víctor Cilleros-Mañé Laia Just-Borràs Marta Balanyà-Segura Aleksandra Polishchuk Laura nadal Marta Tomàs Carolina Silvera-Simón Manel M.Santafé Maria A.Lanuza Unitat d’Histologia i neurobiologia(UHneurob) Facultat de Medicina i Ciències de la SalutUniversitat Rovira i VirgiliReusSpain

During the development of the nervous system,there is an overproduction of neurons and *** competition between neighboring nerve endings and synapses performing different activity levels leads to their elimination or *** have extensively studied the involvement of the brain-derived neurotrophic factor-Tropomyosin-related kinase B receptor neurotrophic retrograde pathway,at the neuromuscular junction,in the axonal development and synapse elimination process versus the synapse *** purpose of this review is to describe the neurotrophic influence on developmental synapse elimination,in relation to other molecular pathways that we and others have found to regulate this *** particular,we summarize our published results based on transmitter release analysis and axonal counts to show the different involvement of the presynaptic acetylcholine muscarinic autoreceptors,coupled to downstream serine-threonine protein kinases A and C(PKA and PKC)and voltage-gated calcium channels,at different nerve endings in developmental *** dynamic changes that occur simultaneously in several nerve terminals and synapses converge across a postsynaptic site,influence each other,and require careful studies to individualize the mechanisms of specific *** describe an activity-dependent balance(related to the extent of transmitter release)between the presynaptic muscarinic subtypes and the neurotrophin-mediated TrkB/p75nTR pathways that can influence the timing and fate of the competitive interactions between the different axon *** downstream displacement of the PKA/PKC activity ratio to lower values,both in competing nerve terminals and at postsynaptic sites,plays a relevant role in controlling the elimination of supernumerary ***,calcium entry through L-and P/Q-subtypes of voltage-gated calcium channels(both channels are present,together with the n-type channel in developing nerve terminals)contributes to red

关键词： acetylcholine release adenosine receptors axonal competition brain-derived neurotrophic factor calcium channels motor end-plate muscarinic acetylcholine receptors postnatal synapse elimination serine kinases tropomyosin-related kinase receptorB

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

Malpractice or masterful practice?navigating vicarious liability in healthcare

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World Journal of Clinical Cases 2025年第2期13卷 10-13页

作者： Satvik n Pai naveen Jeyaraman Madhan Jeyaraman Swaminathan Ramasubramanian Department of Orthopaedics PES University Institute of Medical Sciences and ResearchBengaluru 560100KarnatakaIndia Department of Orthopaedics ACS Medical College and HospitalDr MGR Educational and Research InstituteChennai 600077Tamil NaduIndia Department of Orthopaedics Government Medical CollegeOmandurar Government EstateChennai 600002Tamil NaduIndia

In the intricate landscape of healthcare,vicarious liability looms large,shaping the responsibilities and actions of healthcare practitioners and administrators *** by a poignant scenario of a medication error,this article navigates the complexities of vicarious liability in *** explains the legal basis and ramifications of this theory,emphasizing its importance in fostering responsibility,protecting patient welfare,and easing access to *** paper explores the practical effects of vicarious responsibility on day-to-day operations,leadership practices,and decision-making processes via the eyes of senior consultants,junior doctors,and hospital *** comprehensive insights and real-world examples,it underscores the imperative of fostering a culture of accountability,communication,and quality care to navigate the intricate web of liabilities inherent in modern healthcare.

关键词： vicarious liability Healthcare Responsibility Litigation Patient welfare

An SPH Framework for Earthquake-Induced Liquefaction Hazard Assessment of Geotechnical Structures

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Computer Modeling in Engineering & Sciences 2025年第1期142卷 251-277页

作者： Sourabh Mhaski G.v.Ramana Department of Civil Engineering Indian Institute of Technology DelhiNew Delhi110016India

Earthquake-induced soil liquefaction poses significant risks to the stability of geotechnical structures *** understanding of the liquefaction triggering,and the post-failure large deformation behaviour is essential for designing resilient *** present study develops a Smoothed Particle Hydrodynamics(SPH)framework for earthquake-induced liquefaction hazard assessment of geotechnical *** coupled flowdeformation behaviour of soils subjected to cyclic loading is described using the PM4Sand model implemented in a three-phase,single-layer SPH framework.A staggered discretisation scheme based on the stress particle SPH approach is adopted to minimise numerical inaccuracies caused by zero-energy modes and tensile ***,non-reflecting boundary conditions for seismic analysis of semi-infinite soil domains using the SPH method are *** numerical framework is employed for the analysis of cyclic direct simple shear test,seismic analysis of a level ground site,and liquefaction-induced failure of the Lower San Fernando *** agreement for liquefaction triggering and post-failure behaviour demonstrates that the SPH framework can be utilised to assess the effect of seismic loading on field-scale geotechnical *** present study also serves as the basis for future advancements of the SPH method for applications related to earthquake geotechnical engineering.

关键词： Earthquake seismic liquefaction stress particle PM4Sand smoothed particle hydrodynamics(SPH)

Gate-Dependent nonlinear Hall Effect at Room Temperature in Topological Semimetal GeTe

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Chinese Physics Letters 2023年第7期40卷 63-67页

作者： n.n.Orlova A.v.Timonina n.n.Kolesnikov E.v.Deviatov Institute of Solid State Physics of the Russian Academy of Sciences ChernogolovkaMoscow District2 Academician Ossipyan str.142432Russia

We experimentally investigate nonlinear Hall effect as zero-frequency and second-harmonic transverse voltage responses to ac electric current for topological semimetal GeTe.A thick single-crystal GeTe flake is placed on the Si/SiO_(2) substrate,where the p-doped Si layer serves as a gate *** confirm that electron concentration is not gate-sensitive in thick GeTe flakes due to the gate field screening by bulk *** contrast,by transverse voltage measurements,we demonstrate that the nonlinear Hall effect shows pronounced dependence on the gate electric field at room *** the nonlinear Hall effect is a direct consequence of a Berry curvature dipole in topological media,our observations indicate that Berry curvature can be controlled by the gate electric *** experimental observation can be understood as a result of the known dependence of giant Rashba splitting on the external electric field in *** possible applications,the zero-frequency gate-controlled nonlinear Hall effect can be used for the efficient broad-band rectification.

关键词： temperature. field. curvature

Performance Analysis of Thermoacoustic Refrigerator of 10 W Cooling Power Made up of Poly-vinyl-Chloride for Different Parallel Plate Stacks by Using Helium as a Working Fluid

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Journal of Thermal Science 2021年第6期30卷 2037-2055页

作者： n v Shivakumara BHEEMSHA Arya Department of Mechanical Engineering BMS College of EngineeringBengaluru 560019India Department of Mechanical Engineering Government PolytechnicChannasandraBengaluru 560067India

Refrigerants are usually provided in the conventional refrigeration system although the refrigerants produce Chlorofluorocarbons(CFCs)and Hydro-chlorofluorocarbons(HCFCs),which are hazardous to the ***,these disadvantages can be overcome by using air or inert gas in the thermoacoustic refrigeration *** the present experimental work,helium is used as a working gas with an operating pressure range of 0.2 MPa to 1.0 MPa in order to study the performance of thermoacoustic refrigerator(TAR)which is fabricated using Poly-vinyl-Chloride(PvC).The parallel plate stacks with different porosity ratios have been considered to study the performance of *** temperature difference between the hot and cold heat exchanger and acoustic dynamic pressure were recorded by using Bruel and Kjaer data acquisition system under different operating *** effect of different operating parameters such as operating frequency(200 Hz to 600 Hz),cooling load(2 W to 10 W)and drive ratio(0.6%to 1.6%)have also been considered to study the performance of *** TAR also modeled in DeltaEC software and the results are compared with the experimental outcomes and found to be in good *** experimental results show that-2.1℃is the lowest temperature measured at cold heat exchanger by achieving the highest temperature difference of about 32.9℃.An improvement is around 36%as compared to that of previous experiments that used aluminium *** highest Coefficient of Performance(COP)and the Relative Coefficient of Performance(COPR)are found to be 2.024 and 0.217,respectively.

关键词： thermoacoustic refrigerator parallel plate stack porosity ratio temperature difference COP COPR

Ordered exponential and its features in Yang-Mills effective action

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Communications in Theoretical Physics 2023年第8期75卷 119-127页

作者： A v Ivanov n v Kharuk St.Petersburg Department of Steklov Mathematical Institute of Russian Academy of Sciences 27 FontankaSt.Petersburg 191023Russia Leonhard Euler International Mathematical Institute 10 Pesochnaya nab.St.Petersburg 197022Russia

In this paper,we discuss some non-trivial relations for ordered exponentials on smooth Riemannian *** an example of application,we study the dependence of the four-dimensional quantum Yang–Mills effective action on the special gauge transformation with respect to the background ***,we formulate some open questions about a structure of divergences for a special type of regularization in the presence of the background field formalism.

关键词： Yang-Mills effective action ordered exponential heat kernel Green's function short-distance asymptotics cutoff regularization Synge's world function