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Unlocking hypoglycemia–associated brain microvascular dysfunction:critical insights from proteomic analysis

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Neural Regeneration Research 2025年第6期20卷 1707-1708页

作者： siva s.V.p.sakamuri Anil sakamuri Department of Chemistry Auburn University at MontgomeryMontgomeryALUSA Vascular Biology Center and Department of Medicine Medical College of Georgia at Augusta UniversityAugustaGAUSA

Hypoglycemia-a critical complication linked to worsened brain function in diabetic subjects:Hypoglycemia is characterized by a decline in circulatory glucose levels below sta nda rd physiological *** hypoglycemia,classified as level 1 hypoglycemia,is defined by blood glucose levels below 70 mg/dL and can be effectively addressed through carbohydrate *** hypoglycemia,denoted by blood glucose levels less than 54 mg/dL,poses a life-threatening risk if left *** with type 1 and type 2 diabetes undergoing insulin treatment are particularly susceptible to hypoglycemia due to impaired counterregulatory mechanisms.

关键词： impaired intake critical

s1p: the elixir of life for naive T cells

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Cellular & Molecular Immunology 2018年第7期15卷 657-659页

作者： Michaël pérès Anne Montfort Nathalie Andrieu-Abadie Céline Colacios Bruno ségui INsERM UMR1037 Centre de Recherches en Cancérologie de ToulouseToulouse 31037France Facultéde pharmacie UniversitéToulouse III Paul-SabatierToulouse 31062France Laboratoire d’hématologie CHU de ToulouseToulouse 31059France Equipe Labellisée Ligue Contre Le Cancer Toulouse 31037France Correspondence:Professor B SéguiPhDINSERMUMR1037 CRCTCentre de Recherches en Cancérologie de Toulouse2 avenue Hubert CurienToulouse 31037France

During their life,T cells are constantly circulating throughout the ***-1-phosphate(s1p),a sphingolipid metabolite,triggers T cell egress from the thymus and secondary lymphoid organs(sLO)into the lymph and the *** phenomenon is dependent on the s1p gradient between lymphoid organs(including thymus and sLO)and the lymphatic and blood vessels,which exhibit low,intermediate and high s1p levels,respectively.T cells follow the s1p gradient via the engagement of the G-protein-coupled receptor s1p receptor 1(s1p1)expressed on T cells.1 s1p production is regulated by various sphingolipid-metabolizing *** sphingosine kinases 1 and 2(sKs),encoded by sphk1 and sphk2,phosphorylate the sphingosine(sph)into ***,s1p can be dephosphorylated to sph by s1p phosphatases 1 and 2,encoded by sgpp1 and ***,s1p can be irreversibly degraded by the s1p Lyase(spL),encoded by sgpl1,into phosphoethanolamine and hexadecenal.

关键词： organs al. lymphoid

small molecule inhibitor DDQ-treated hippocampal neuronal cells show improved neurite outgrowth and synaptic branching

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Neural Regeneration Research 2025年第9期20卷 2624-2632页

作者： Jangampalli Adi pradeepkiran priyanka Rawat Arubala p.Reddy Erika Orlov pHemachandra Reddy Department of Internal Medicine Texas Tech University Health Sciences CenterLubbockTXUSA Department of Nutritional sciences College of Human SciencesTexas Tech UniversityLubbockTXUSA Department of pharmacology&Neuroscience Texas Tech University Health Sciences CenterLubbockTXUSA Department of Neurology Texas Tech University Health Sciences CenterLubbockTXUSA Department of speech Language and Hearing SciencesTexas Tech University Health Sciences CenterLubbockTXUSA Department of public Health Texas Tech University Health Sciences CenterLubbockTXUSA

The process of neurite outgrowth and branching is a crucial aspect of neuronal development and *** and dendrites,sometimes referred to as neurites,are extensions of a neuron's cellular body that are used to start *** we explored the effects of diethyl(3,4-dihydroxyphenethylamino)(quinolin-4-yl)methylphosphonate(DDQ)on neurite developmental features in HT22 neuronal *** this work,we examined the protective effects of DDQ on neuronal processes and synaptic outgrowth in differentiated HT22cells expressing mutant Tau(mTau)*** investigate DDQ chara cteristics,cell viability,biochemical,molecular,western blotting,and immunocytochemistry were *** outgrowth is evaluated through the segmentation and measurement of neural *** neural processes can be seen and measured with a fluorescence microscope by manually tracing and measuring the length of the neurite *** neuronal processes can be observed and quantified with a fluorescent microscope by manually tracing and measuring the length of the neuronal ***-treated mTau-HT22 cells(HT22 cells transfected with cDNA mutant Tau)were seen to display increased levels of synaptophysin,MAp-2,andβ-***,we confirmed and noted reduced levels of both total and p-Tau,as well as elevated levels of microtubule-associated protein 2,β-tubulin,synaptophysin,vesicular acetylcholine transporter,and the mitochondrial biogenesis protein-pe roxisome prolife rator-activated receptor-gamma coactivator-1α.In mTa u-expressed HT22 neurons,we observed DDQ enhanced the neurite characteristics and improved neurite development through increased synaptic *** findings conclude that mTa u-HT22(Alzheimer's disease)cells treated with DDQ have functional neurite developmental chara *** key finding is that,in mTa u-HT22 cells,DDQ preserves neuronal structure and may even enhance nerve development function with mTa u inhibition.

关键词： diethyl(3 4-dihydroxyphenethylamino)(quinolin-4-yl)methylphosphonate(DDQ) hippocampal neuronal cells HT22 neurite outgrowth neuronal development small molecule

Multi-exponential model to describe pressure-dependent p-and s-wave velocities and its use to estimate the crack aspect ratio

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Journal of Rock Mechanics and Geotechnical Engineering 2022年第2期14卷 385-395页

作者： Mihály Dobróka Norbert péter szabó Tünde Edit Dobróka Mátyás Krisztián Baracza Department of Geophysics University of MiskolcMiskolc-Egyetemváros3515Hungary MTA-ME Geoengineering Research Group University of MiskolcMiskolc-Egyetemváros3515Hungary Research Institute of Applied Earth sciences University of MiskolcMiskolc-Egyetemváros3515Hungary

We present new quantitative model describing the pressure dependence of acoustic p-and s-wave *** that a variety of individual mechanisms or defects(such as cracks,pore collapse and grain crushing)can contribute to the pressure-dependent change of the wave velocity,we order a characteristic pressure to all of them and allow a series of exponential terms in the description of the(pand s-waves)velocity-pressure *** estimate the parameters of the multi-exponential rock physical model in inversion procedures using laboratory measured p-and s-wave velocity *** is known,the conventional damped least squares method gives acceptable results only when one or two individual mechanisms are *** the number of exponential terms leads to highly nonlinear ill-posed inverse *** to this reason,we develop the spectral inversion method(sIM)in which the velocity amplitudes(the spectral lines in the characteristic pressure spectrum)are only considered as *** characteristic pressures(belonging to the velocity amplitudes)are excluded from the set of inversion unknowns,instead,they are defined in a set of fixed positions equidistantly distributed in the actual interval of the independent variable(pressure).Through this novel linear inversion method,we estimate the parameters of the multi-exponential rock physical model using laboratory measured p-and s-wave velocity *** characteristic pressures are related to the closing pressures of cracks which are described by well-known rock mechanical relationships depending on the aspect ratio of elliptical *** gives the possibility to estimate the aspect ratios in terms of the characteristic pressures.

关键词： Multi-exponential rock physical model spectral inversion method(sIM) Crack aspect ratio Characteristic pressures

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

spastin and alsin protein interactome analyses begin to reveal key canonical pathways and suggest novel druggable targets

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Neural Regeneration Research 2025年第3期20卷 725-739页

作者： Benjamin R.Helmold Angela Ahrens Zachary Fitzgerald p.Hande Ozdinler Department of Neurology Feinberg School of MedicineNorthwestern UniversityChicagoILUSA Center for Molecular Innovation and Drug Discovery Center for Developmental TherapeuticsChemistry of Life Processes InstituteNorthwestern UniversityEvanstonILUSA Mesulam Center for Cognitive Neurology and Alzheimer’s Disease Feinberg School of MedicineNorthwestern UniversityChicagoILUSA Feinberg school of Medicine Les Turner ALS Center at Northwestern UniversityChicagoILUSA

Developing effective and long-term treatment strategies for rare and complex neurodegenerative diseases is challenging. One of the major roadblocks is the extensive heterogeneity among patients. This hinders understanding the underlying disease-causing mechanisms and building solutions that have implications for a broad spectrum of patients. One potential solution is to develop personalized medicine approaches based on strategies that target the most prevalent cellular events that are perturbed in patients. Especially in patients with a known genetic mutation, it may be possible to understand how these mutations contribute to problems that lead to neurodegeneration. protein–protein interaction analyses offer great advantages for revealing how proteins interact, which cellular events are primarily involved in these interactions, and how they become affected when key genes are mutated in patients. This line of investigation also suggests novel druggable targets for patients with different mutations. Here, we focus on alsin and spastin, two proteins that are identified as “causative” for amyotrophic lateral sclerosis and hereditary spastic paraplegia, respectively, when mutated. Our review analyzes the protein interactome for alsin and spastin, the canonical pathways that are primarily important for each protein domain, as well as compounds that are either Food and Drug Administration–approved or are in active clinical trials concerning the affected cellular pathways. This line of research begins to pave the way for personalized medicine approaches that are desperately needed for rare neurodegenerative diseases that are complex and heterogeneous.

关键词： ALs2 alsin amyotrophic lateral sclerosis hereditary spastic paraplegia neurodegenerative diseases personalized medicine precision medicine protein interactome protein-protein interactions spAsT spastin

Machine learning applications in healthcare clinical practice and research

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World Journal of Clinical Cases 2025年第1期13卷 16-21页

作者： Nikolaos-Achilleas Arkoudis stavros p papadakos Research Unit of Radiology and Medical Imaging School of MedicineNational and Kapodistrian University of AthensAthens 11528Greece 2^(nd)Department of Radiology “Attikon”General University HospitalMedical SchoolNational and Kapodistrian University of AthensChaidari 12462Greece Department of Gastroenterology Laiko General HospitalNational and Kapodistrian University of AthensAthens 11527Greece

Machine learning(ML)is a type of artificial intelligence that assists computers in the acquisition of knowledge through data analysis,thus creating machines that can complete tasks otherwise requiring human *** its various applications,it has proven groundbreaking in healthcare as well,both in clinical practice and *** this editorial,we succinctly introduce ML applications and present a study,featured in the latest issue of the World Journal of Clinical *** authors of this study conducted an analysis using both multiple linear regression(MLR)and ML methods to investigate the significant factors that may impact the estimated glomerular filtration rate in healthy women with and without non-alcoholic fatty liver disease(NAFLD).Their results implicated age as the most important determining factor in both groups,followed by lactic dehydrogenase,uric acid,forced expiratory volume in one second,and *** addition,for the NAFLD-group,the 5th and 6th most important impact factors were thyroid-stimulating hormone and systolic blood pressure,as compared to plasma calcium and body fat for the NAFLD+***,the study's distinctive contribution lies in its adoption of ML methodologies,showcasing their superiority over traditional statistical approaches(herein MLR),thereby highlighting the potential of ML to represent an invaluable advanced adjunct tool in clinical practice and research.

关键词： Machine Learning Artificial Intelligence Clinical practice Research Glomerular filtration rate Non-alcoholic fatty liver disease Medicine

Enhanced entropy generation and heat transfer characteristics of magnetic nano-encapsulated phase change materials in latent heat thermal energy storage systems

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Applied Mathematics and Mechanics(English Edition) 2024年第6期45卷 1051-1070页

作者： p.s.REDDY p.sREEDEVI Department of Mathematics Rajeev Gandhi Memorial College of Engineering and TechnologyNandyal 518501India

The objective of the current study is to investigate the importance of entropy generation and thermal radiation on the patterns of velocity,isentropic lines,and temperature contours within a thermal energy storage device filled with magnetic nanoencapsulated phase change materials(NEpCMs).The versatile finite element method(FEM)is implemented to numerically solve the governing *** effects of various parameters,including the viscosity parameter,ranging from 1 to 3,the thermal conductivity parameter,ranging from 1 to 3,the Rayleigh parameter,ranging from 102 to 3×10^(2),the radiation number,ranging from 0.1 to 0.5,the fusion temperature,ranging from 1.0 to 1.2,the volume fraction of NEpCMs,ranging from 2%to 6%,the stefan number,ranging from 1 to 5,the magnetic number,ranging from 0.1 to 0.5,and the irreversibility parameter,ranging from 0.1 to 0.5,are examined in detail on the temperature contours,isentropic lines,heat capacity ratio,and velocity ***,the heat transfer rates at both the cold and hot walls are analyzed,and the findings are presented *** results indicate that the time taken by the NEpCMs to transition from solid to liquid is prolonged inside the chamber region as the fusion temperatureθf ***,the contours of the heat capacity ratio Cr decrease with the increase in the stefan number ste.

关键词： volume fraction of nano-encapsulated phase change material(NEpCM) radiation stefan number heat capacity ratio entropy generation

semi-solid moulding:Competition to cast and machine from forging in making automotive complex components

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中国有色金属学会会刊：英文版 2010年第S3期20卷 1042-1047页

作者： s.p.MIDsON Aluminium Complex Components Inc 2211 South Jason StreetDenverColorado 80223USA

The very latest technique for impeller manufacture is called semi-solid moulding(ssM).Cummins Turbo Technologies Limited,together with Aluminum Complex Components Inc,developed ssM compressor wheels as a way of achieving cost and durability performance somewhere between that of cast and machined from solid(MFs) aluminium alloy *** results show ssM material has a superior microstructure and mechanical properties over cast and comparable to MFs *** testing including durability testing,using accelerated speed cycle tests,proves ssM compressor wheels emerge as being significantly more durable than cast equivalents and approaching that of MFs *** challenges for semi-solid processing in manufacture of other complex components and other materials in automotive industry in terms of both cost and durability are also discussed.

关键词： aluminum alloys semi-solid moulding durability automotive complex component turbocharger compressor wheel