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Impacts of PI3K/protein kin.s. 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 lan.s.ape 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 cytokin.s.and influencing the immune *** phosphoin.s.tide 3-kin.s.(PI3K)/protein kin.s. B(AKT)signaling pathway is a central player in astrocyte reactivity and impacts various aspects of astrocyte behavior,as evidenced by in.s.lico,in vitro,and in vivo *** astrocytes,inflammatory cues trigger a cascade of molecular even.s.where nuclear factor-κB serves as a central mediator of the pro-inflammatory ***,we review the heterogeneity of reactive astrocytes and the molecular mechan.s.s 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 phosphatidylin.s.tol 3-kin.s. reactive astrocytes signal transduction Thy-1(CD90)

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sex differences in aging and injured brain

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neural Regeneration Research 2025年第10期20卷 2901-2902页

作者： Jordan n.Williamson Yuan Yang University of Illinois Urbana-Champaign Grainger College of EngineeringDepartment of BioengineeringUrbanaILUSA Carle Foundation Hospital Stephenson Family Clinical Research InstituteClinical Imaging Research CenterUrbanaILUSA University of Illinois Urbana-Champaign Beckman Institute for Advanced Science and TechnologyUrbanaILUSA northwestern University Department of Physical Therapy and Human Movement SciencesChicagoILUSA

Background:The prevalence,age of onset,and symptomatology of traumatic brain injury,stroke,and neurodegenerative diseases(such as Alzheimer’s disease(AD),Parkinson.s.disease,amyotrophic lateral sclerosis,and Huntington.s.disease)differ substantially between males and *** higher prevalence of these brain disorders has been attributed to females having a greater longevity compared with *** one of the greatest risk factors of acquired brain injury(such as stroke,traumatic brain injury caused by fall)and neurodegenerative disease is age.

关键词： Huntington prevalence traumatic

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Astrocytes, reactive astrogliosis, and glial scar formation in traumatic brain injury

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neural Regeneration Research 2025年第4期20卷 973-989页

作者： María Belén Cieri Alberto Javier Ramos Laboratorio de neuropatología Molecular IBCN UBA-CONICETFacultad de MedicinaUniversidad de Buenos AiresBuenos AiresArgentina

Traumatic brain injury is a global health crisis,causing significant death and disability *** that follows traumatic brain injury has serious consequences for neuronal survival and cognitive impairmen.s.with astrocytes involved in this *** traumatic brain injury,astrocytes rapidly become reactive,and astrogliosis propagates from the injury core to distant brain *** astroglial proteins are downregulated near the traumatic brain injury core,while pro-inflammatory astroglial gen.s.are *** altered gene expression is considered a pathological remodeling of astrocytes that produces serious consequences for neuronal survival and cognitive *** addition,glial scar formed by reactive astrocytes is initially necessary to limit immune cell infiltration,but in the long term impedes axonal reconnection and functional *** therapeutic strategies for traumatic brain injury are focused on preventing acute ***,cannabinoids,progesterone,beta-blockers,and cerebrolysin demonstrate neuroprotective benefits but most of them have not been.s.udied in the context of *** this review,we discuss the cell signaling pathways activated in reactive astrocytes following traumatic brain injury and we discuss some of the potential new strategies aimed to modulate astroglial responses in traumatic brain injury,especially using cell-targeted strategies with miRn.s.or lncRnA,viral vectors,and repurposed drugs.

关键词： astrocyte glial scar innate immunity neuroinflammation stab injury Toll-like receptors

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Making bridges between preclinical and clinical insights into age-related cognitive decline

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neural Regeneration Research 2025年第8期20卷 2321-2322页

作者： David VC Brito Clévio nóbrega Algarve Biomedical Center-Research Institute(ABC-RI) Campus GambelasFaroPortugal Algarve Biomedical Center-(ABC) Campus GambelasFaroPortugal Faculty of Medicine and Biomedical sciences(FMCB) University of AlgarveGambelas CampusFaroPortugal

With people living longer,the societal impact of age-related cognitive decline is becoming more pronounced(Crimmins,2015).Thus,it is increasingly important to comprehend the cognitive shifts linked to aging-whether th... 详细信息

关键词： bridges becoming insight

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Amyloid-beta pathology-induced nan.s.ale synaptic disruption:the case of the GABA_B-GIRK assembly

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neural Regeneration Research 2025年第5期20卷 1409-1410页

作者： Rafael Lujan Alejandro Martín-Belmonte sergi Ferré Francisco Ciruela synaptic structure Laboratory Instituto de Biomedicina de la UCLM(IB-UCLM)Departamento de Ciencias MédicasInstituto de Investigación en Salud de Castilla-La Mancha(IDISCAM)Facultad de MedicinaUniversidad Castilla-La ManchaCampus BiosanitarioC/AlmansaAlbaceteSpain Integrative neurobiology section National Institute on Drug AbuseIntramural Research ProgramNational Institutes of HealthBaltimoreMDUSA Pharmacology Unit Department of Pathology and Experimental TherapeuticsSchool of Medicine and Health SciencesInstitute of NeurosciencesUniversity of BarcelonaNeuropharmacology&Pain GroupNeuroscience ProgramBellvitge Institute for Biomedical ResearchL’Hospitalet de LlobregatSpain

Alzheimer's disease (AD) is characterized by an imbalance between excitatory and inhibitory brain networks,leading to aberrant homeostatic synaptic *** has progressively been recognized as syna ptopathy and syna ptic dysfunction has been identified as a key component of its pathogen.s.s (schirinzi et al.,2020).syna ptic dysfunction is believed to precede synapse loss,a primary biological correlate of cognitive decline in AD,inevita bly associated with neuronal death.

关键词： Alzheimer pathology

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Clinical,laboratory,and therapeutic differences between immunoglobulin E-mediated and non-immunoglobulin E-mediated cow’s milk protein allergy in children

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World Journal of Clinical Pediatrics 2025年第1期14卷 78-92页

作者： Hasan M Isa Marwa J Abdulnabi nawra s n.s.r Fatema n Lahmda noor M AlAnsari Zahra H Isa Afaf M Mohamed Department of Pediatrics Salmaniya Medical ComplexManama 26671Bahrain Department of Pediatrics Arabian Gulf UniversityManama 26671Bahrain Faculty of Medicine Mansoura UniversityMansoura 35516Egypt Public Health Directorate Ministry of HealthManama 26671Bahrain

BACKGROUnD Although breast milk is ideal for newborns,in.s.me cases,it is replaced with cow’s milk,which contains proteins that increase the risk of cow’s milk protein allergy(CMPA).AIM To evaluate CMPA prevalence in Bahrain and compare clinical characteristics of children with immunoglobulin E(IgE)-and non-IgE-mediated *** This retrospective cohort study examined children with CMPA diagn.s.d at the pediatric gastroenterology outpatient clinic of the salmaniya Medical Complex,Bahrain,between 2014 and 2022,and assessed CMPA *** presentations,laboratory findin.s.dietary modifications,and outcomes were compared between children with IgE-mediated and non-IgE-mediated *** variables were compared using Fisher’s exact test or Pearson.s.2 test,whereas continuous variables were compared using student’s t-test or the Mann-Whitney U *** Of 8332 patien.s.6022(72.3%)adhered to their *** them,618(10.3%)were suggested of having CMPA and 595(96.3%)were included;CMPA prevalence was 2%.Most patien.s.were Bahraini(93.8%)and males(55.3%).non-IgE-mediated type accounted for 77.3%cases and IgE-mediated type,22.7%.IgE-mediated CMPA presented more in boys(P=0.030),and later in life(5.1 months±4.5 months vs 4.2 months±4.2 months,P=0.016,95%CI:0.08-1.73),had more associated diseases(Pnd presented with more cutaneous(P=0.024)and respiratory(P=0.003)manifestations,severe symptoms[rash/dry skin(P=0.031),facial swelling/angioedema(P=0.003),failure to thrive(P=0.013),apparent life-threatening event(Pnd positive physical findin.s.P=0.002)than non-IgE-mediated *** patien.s.were exclusively fed cow milk formula(50.3%).The amino acid-based formula(AAF)was most prescribed(60.5%)with no difference between the two types(P=0.173).Although breastfeeding was recommended to 49.6%,only 8.2%were exclusively ***-mediated CMPA was associated with a longer follow-up duration than non-IgE-mediated CMPA(17.3 months±14.0 mo

关键词： Children Milk allergy Immunoglobulin E Breastfeeding Infant formula Bahrain

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site index determination using a time series of airborne laser scanning data

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Forest Ecosystems 2025年第01期 93-103页

作者： Maria ?sn.s.Moan Ole Martin Bollan.s.s svetlana saarela Terje Gobakken Erik n.s.et Hans Ole ?rka Lennart noordermeer Faculty of Environmental sciences and natural Resource Management Norwegian University of Life Sciences

site index (sI) is determined from the top height development and is a proxy for forest productivity,defined as the expected top height for a given.s.ecies at a certain index *** norway,an index age of 40 years is *** using bi-temporal airborne laser scanning (ALs) data,sI can be determined using models estimated from sI observed on field plots (the direct approach) or from predicted top heights at two poin.s.in time (the height differential approach).Time series of ALs data may enhance sI determination compared to conventional methods used in operational forest inventory by providing more detailed information about the top height *** used longitudinal data comprising spatially consistent field and ALs data collected from training plots in 1999,2010,and 2022 to determine sI using the direct and height differential approaches using all combinations of years and performed an external *** also evaluated the use of data *** of root mean.s.uare error obtained from external validation were in the ranges of 16.3%–21.4%and 12.8%–20.6%of the mean fieldregistered sI for the direct approach and the height differential approach,*** were no statistically significant effects of time series length or the number of poin.s.in time on the obtained *** assimilation did not result in any substantial improvement in the obtained *** a time series of ALs data did not yield greater accuracies compared to using only two poin.s.in time,a larger proportion of the study area could be used in ALs-based determination of sI when a time series was *** was because areas that were unsuitable for sI determination between two poin.s.in time could be subject to sI determination based on data from another part of the time series.

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A novel Reliable and Trust Objective Function for RPL-Based IoT Routing Protocol

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Computers, Materials & Continua 2025年第2期82卷 3467-3497页

作者： Mariam A.Alotaibi sami s.Alwakeel Aasem n.Alyahya Department of Computer Engineering College of Computer ScienceKing Saud UniversityRiyadh11543Saudi Arabia Department of Computer science and Information Technology Shaqra UniversityShaqra11961Saudi Arabia

The Internet of Thin.s.(IoT) integrates diverse devices into the Internet infrastructure, including sensors, meters, and wearable devices. Designing efficient IoT networks with these heterogeneous devices requires the selection of appropriate routing protocols, which is crucial for maintaining high Quality of service (Qos). The Internet Engineering Task Force’s Routing Over Low Power and Lossy networks (IETF ROLL) working group developed the IPv6 Routing Protocol for Low Power and Lossy networks (RPL) to meet these needs. While the initial RPL standard focused on.s.ngle-metric route selection, ongoing research explores enhancing RPL by incorporating multiple routing metrics and developing new Objective Functions (OFs). This paper introduces a novel Objective Function (OF), the Reliable and secure Objective Function (RsOF), designed to enhance the reliability and trustworthin.s. of parent selection at both the node and link levels within IoT and RPL routing protocols. The RsOF employs an adaptive parent node selection mechan.s. that incorporates multiple metrics, including Residual Energy (RE), Expected Transmission Count (ETX), Extended RPL node Trustworthin.s. (ERnT), and a novel metric that measures node failure rate (nFR). In this mechan.s., nodes with a high nFR are excluded from the parent selection process to improve network reliability and stability. The proposed RsOF was evaluated using random and grid topologies in the Cooja simulator, with tests conducted across small, medium, and large-scale networks to examine the impact of varying node densities. The simulation results indicate a significant improvement in network performance, particularly in terms of average latency, packet acknowledgment ratio (PAR), packet delivery ratio (PDR), and Control Message Overhead (CMO), compared to the standard Minimum Rank with Hysteresis Objective Function (MRHOF).

关键词： IoT LLns RPL objective function OF MRHOF OF0 routing metrics reliability trustworthin.s.

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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-thickn.s. 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-thickn.s. ratios and boundary conditions of the bio-inspired composite plate.

关键词： bio-inspired composite plate finite element method (FEM) Green-Lagrange helicoidal inverse hyperbolic shear deformation theory (IHsDT) nonlinear O322

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Exploring the therapeutic potential of glucagon-like peptide 1agon.s.s in metabolic disorders

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World Journal of Gastroenterology 2025年第4期31卷 169-175页

作者： Adrián Cortés-Martín Julio Plaza-Diaz Promoting Fitn.s. and Health Through Physical Activity Research Group Sport and Health University Research InstituteUniversity of GranadaGranada 18016AndalusiaSpain school of Health sciences Universidad Internacional de La RiojaLogroño 26006La RiojaSpain

This article commen.s.on the work by soresi and *** authors have stated that one of the most novel and promising treatmen.s.for metabolic dysfunction-associated steatotic liver disease(MAsLD)is the use of glucagon-like peptide 1 receptor agon.s.s,especially when used in combination ***,despite their notable efficacy,these drugs were not initially designed to target MAsLD *** a groundbreaking development,the Food and Drug Admin.s.ration has recently approved resmetirom,the first treatment specifically aimed at reducing liver fibrosis in metabolic-associated ***,an orally admin.s.ered,liver-directed thyroid hormone beta-selective agon.s.,acts directly on intrahepatic pathways,enhancing its therapeutic potential and marking the beginning of a new era in the treatment of ***,the integration of lifestyle modifications into liver disease management is an essential component that should be considered and *** incorporating dietary changes and regular physical exercise into treatment,patien.s.may achieve improved outcomes,reducing the need for pharmacological interventions and/or improving treatment *** a complement to medical therapies,lifestyle factors should not be overlooked in the broader strategy for managing MAsLD.

关键词： Glucagon-like peptide 1 agon.s.s Liver diseases Metabolic dysfunction.s.ociated steatotic liver disease Metabolic health Pharmacotherapy Diet Gut microbiome Physical exercise Lifestyle non-alcoholic fatty liver disease

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