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Inflammasome links traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease

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Neural Regeneration Research 2025年第6期20卷 1644-1664页

作者： Gabriela Seplovich Yazan Bouchi Juan Pablo de Rivero Vaccari Jennifer c.Munoz Pareja Andrew Reisner Laura Blackwell Yehia Mechref Kevin K.Wang J.Adrian Tyndall Binu Tharakan Firas Kobeissy Department of Surgery Morehouse School of MedicineAtlantaGAUSA Department of Neurobiology Center for NeurotraumaMultiomics&Biomarkers(CNMB)Neuroscience InstituteMorehouse School of MedicineAtlantaGAUSA Department of Neurological Surgery and the Miami Project to cure Paralysis University of Miami Miller School of MedicineMiamiFLUSA Division of Pediatric critical care Department of PediatricsUniversity of Miami Miller School of MedicineMiamiFLUSA Department of Pediatrics Emory UniversityAtlantaGAUSA Department of Neurosurgery Children’s Healthcare of AtlantaAtlantaGAUSA Department of chemistry and Biochemistry Texas Tech UniversityLubbockTXUSA Morehouse School of Medicine AtlantaGAUSA

Traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease are three distinct neurological disorders that share common pathophysiological mechanisms involving neuroinflammation. One sequela of neuroinflammation includes the pathologic hyperphosphorylation of tau protein, an endogenous microtubule-associated protein that protects the integrity of neuronal cytoskeletons. Tau hyperphosphorylation results in protein misfolding and subsequent accumulation of tau tangles forming neurotoxic aggregates. These misfolded proteins are characteristic of traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease and can lead to downstream neuroinflammatory processes, including assembly and activation of the inflammasome complex. Inflammasomes refer to a family of multimeric protein units that, upon activation, release a cascade of signaling molecules resulting in caspase-induced cell death and inflammation mediated by the release of interleukin-1β cytokine. One specific inflammasome, the NOD-like receptor protein 3, has been proposed to be a key regulator of tau phosphorylation where it has been shown that prolonged NOD-like receptor protein 3 activation acts as a causal factor in pathological tau accumulation and spreading. This review begins by describing the epidemiology and pathophysiology of traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease. Next, we highlight neuroinflammation as an overriding theme and discuss the role of the NOD-like receptor protein 3 inflammasome in the formation of tau deposits and how such tauopathic entities spread throughout the brain. We then propose a novel framework linking traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease as inflammasomedependent pathologies that exist along a temporal continuum. Finally, we discuss potential therapeutic targets that may intercept this pathway and ultimately minimize long-term neurological decline.

关键词： Alzheimer's disease caspase-1 chronic traumatic encephalopathy inflammasomes neurodegeneration neuroinflammation NLRP1 NLRP3 pyroptosis tauopathy traumatic brain injury

Silk-based nerve guidance conduits with macroscopic holes modulate the vascularization of regenerating rat sciatic nerve

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Neural Regeneration Research 2025年第6期20卷 1789-1800页

作者： carina Hromada Patrick Heimel Markus Kerbl LászlóGál Sylvia Nürnberger Barbara Schaedl James Ferguson Nicole Swiadek Xavier Monforte Johannes c.Heinzel Antal Nógrádi Andreas H.Teuschl-Woller David Hercher Department Life Science Engineering University of Applied Sciences Technikum WienViennaAustria Austrian cluster for Tissue Regeneration ViennaAustria Ludwig Boltzmann Institute for Traumatology The Research Center in Cooperation with AUVAViennaAustria University clinic of Dentistry Medical University of ViennaViennaAustria Department of Plastic Reconstructive and Aesthetic SurgeryLandesklinikum Wiener Neustadt2700 Wiener NeustadtAustria Department of Anatomy Histology and EmbryologyAlbert Szent-Györgyi Medical SchoolUniversity of SzegedSzegedHungary Medical University of Vienna Department of Orthopedics and Trauma SurgeryDevision of Trauma SurgeryViennaAustria Department of Hand- PlasticReconstructive and Burn SurgeryBG Unfallklinik TuebingenUniversity of TuebingenTuebingenGermany

Peripheral nerve injuries induce a severe motor and sensory deficit. Since the availability of autologous nerve transplants for nerve repair is very limited, alternative treatment strategies are sought, including the use of tubular nerve guidance conduits(tNGcs). However, the use of tNGcs results in poor functional recovery and central necrosis of the regenerating tissue, which limits their application to short nerve lesion defects(typically shorter than 3 cm). Given the importance of vascularization in nerve regeneration, we hypothesized that enabling the growth of blood vessels from the surrounding tissue into the regenerating nerve within the tNGc would help eliminate necrotic processes and lead to improved regeneration. In this study, we reported the application of macroscopic holes into the tubular walls of silk-based tNGcs and compared the various features of these improved silk^(+) tNGcs with the tubes without holes(silk^(–) tNGcs) and autologous nerve transplants in an 8-mm sciatic nerve defect in rats. Using a combination of micro-computed tomography and histological analyses, we were able to prove that the use of silk^(+) tNGcs induced the growth of blood vessels from the adjacent tissue to the intraluminal neovascular formation. A significantly higher number of blood vessels in the silk^(+) group was found compared with autologous nerve transplants and silk^(–), accompanied by improved axon regeneration at the distal coaptation point compared with the silk^(–) tNGcs at 7 weeks postoperatively. In the 15-mm(critical size) sciatic nerve defect model, we again observed a distinct ingrowth of blood vessels through the tubular walls of silk^(+) tNGcs, but without improved functional recovery at 12 weeks postoperatively. Our data proves that macroporous tNGcs increase the vascular supply of regenerating nerves and facilitate improved axonal regeneration in a short-defect model but not in a critical-size defect model. This study suggests that further optimizatio

关键词： axon regeneration blood vessel functional recovery macroporous nerve lesion peripheral nerve repair sciatic nerve silk-based nerve guidance conduit vascularization

Hepatitis c Virus, Insulin Resistance, and Steatosis

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Journal of clinical and Translational Hepatology 2016年第1期4卷 66-75页

作者： Dominik Kralj Lucija Virovi(c) Juki(c) Sanja Stojsavljevi(c) Marko Duvnjak Martina Smoli(c) Ines Bili(c) (c)ur(c)i(c) Department of Gastroenterology and Hepatology Sisters of Charity University Hospital Center Zagreb Croatia Department of Pharmacology Faculty of Medicine University of Osijek Osijek Croatia Department of Pharmacology Faculty of MedicineUniversity of Osijek Department of Endocrinology and metabolism disorders University Hospital Center Osijek Osijek Croatia

Hepatitis c virus (HcV) is one of the main causes of liver disease *** steatosis is a common finding in many hepatic and extrahepatic disorders,the most common being metabolic syndrome (MS).Overtime,it has been shown that the frequent coexistence of these two conditions is not coincidental,since many epidemiological,clinical,and experimental studies have indicated HcV to be strongly associated with liver steatosis and numerous metabolic ***,we present an overview of publications that provide clinical evidence of the metabolic effects of HcV and summarize the available data on the pathogenetic mechanisms of this *** has been shown that HcV infection can induce insulin resistance (IR) in the liver and peripheral tissues through multiple *** research has suggested that HcV interferes with insulin signaling both directly and indirectly,inducing the production of several proinflammatory *** replication,assembly,and release from hepatocytes require close interactions with lipid droplets and host *** modulation of lipid metabolism in host cells can induce hepatic steatosis,which is more pronounced in patients with HcV genotype *** risk of steatosis depends on several viral factors (including genotype,viral load,and gene mutations) and host features (visceral obesity,type 2 diabetes mellitus,genetic predisposition,medication use,and alcohol consumption).HcV-related IR and steatosis have been shown to have a remarkable clinical impact on the prognosis of HcV infection and quality of life,due to their association with resistance to antiviral therapy,progression of hepatic fibrosis,and development of hepatocellular ***,HcV-induced IR,oxidative stress,and changes in lipid and iron metabolism lead to glucose intolerance,arterial hypertension,hyperuricemia,and atherosclerosis,resulting in increased cardiovascular mortality.

关键词： Hepatitis c virus Metabolic syndrome Insulin resistance Steatosis

Influence of B4c and ZrB2 reinforcements on microstructural,mechanical and wear behaviour of AA 2014 aluminium matrix hybrid composites

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Defence Technology（防务技术） 2024年第10期40卷 242-254页

作者： Ramesh Babu R Rajendran c Saiyathibrahim A Rajkumar Velu Department of Mechanical Engineering Karpagam Institute of TechnologyCoimbatore 641105India Department of Mechanical Engineering Sri Krishna College of Engineering and TechnologyCoimbatore 641008India Department of Mechanical Engineering Indian Institute of Technology JammuJammu and Kashmir 181221India

considering their affordability and high strength-to-weight ratio,lightweight aluminium alloys are the subject of intensive research aimed at improving their properties for use in the aerospace *** research effort aims to develop novel hybrid composites based on AA 2014 alloy through the use of liquid metallurgy stir casting to reinforce dual ceramic particles of Zirconium Diboride(ZrB_(2))and Boron carbide(B4c).The weight percentage(wt%)of ZrB_(2) was varied(0,5,10,and 15),while a constant 5 wt%of B4c was maintained during this *** as-cast samples have been assessed using an Optical Microscope(OM)and a Scanning Electron Microscope(SEM)with Energy Dispersive Spectroscopy(EDS).The properties such as hardness,tensile strength,and wear characteristics of stir cast specimens were assessed to examine the impact of varying weight percentages of reinforcements in AA 2014 *** particular,dry sliding wear behaviour was evaluated considering varied loads using a pin-on-disc *** the weight%of ZrB_(2) grew and B4c was incorporated,hybrid composites showed higher hardness,tensile strength,and wear ***,the incorporation of a cumulative reinforcement consisting of 15 wt%ZrB_(2) and 5 wt%B4c resulted in a significant 31.86%increase in hardness and a 44.1%increase in tensile strength compared to AA 2014 *** addition,it has been detected that wear resistance of hybrid composite pin(containing 20 wt%cumulative reinforcement)is higher than that of other stir cast wear test pins during the whole range of applied *** surfaces of tensile specimens showed ductile fracture in the AA 2014 matrix and mixed mode for hybrid *** surfaces obtained employing higher applied load indicated abrasive wear with little plastic deformation for hybrid composites and dominant adhesive wear for matrix ***,the superior mechanical and tribological performance of hybrid composites can be attributed to dual reinforcement pa

关键词： AA 2014 alloy Stir casting Hybrid composite Hardness Tensile strength Specific wear rate

c_c(X)Spaces with X Locally compact

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Acta Mathematica Sinica,English Series 2007年第9期23卷 1593-1600页

作者： J.c.FERRANDO S.MOLL centro de Investigación Operativa Universidad Miquel Hernández Departamento de Matemática Aplicada Universidad Politécnica

In this paper, we show, among other results, that if X is a [separable] locally compact space X [satisfying the first countability axiom] then the space cc （X） has countable tightness [if and only if it has bounding tightness] if and only if it is Frechet-Urysohn, if and only if cc （X） contains a dense （LM） subspace and if and only if X is a-compact.

关键词： Frechet-Urysohn space countable [bounding] tightness (LM)-space

Fabrication and Properties of SiB6-B4c with Phenolic Resin as a carbon Source

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Journal of Materials Science & Technology 2008年第1期24卷 102-104页

作者： G. c.Hwang J.Matsushita United Graduate School of Science and Engineering Tokai University 1117 Kitakaname Hiratsuka 259-12921 Japan

Si-B-c ceramic composites were synthesized using SiB-6,B-4c,and phenolic resin as a carbon source by pressureless sintering in an Ar ***,the Si-B-c ceramic composites were fabricated to determine their potential for applications as high hardness and high temperature *** X-ray diffraction patterns of sintered bodies of SiB-6-B-4c with carbonized phenolic resin can be seen that SiB-6 and c changed to B-4c and *** this study,it is obtained that carbonized phenolic resin is good addition material as a reaction material comparing to carbon powder at 1683 K for 1 h by pressureless sintering in an Ar atmosphere.

关键词： Silicon boride Boron carbide Phenolic resin

Finite element analysis of the effect of interlayer on interfacial stress transfer in layered graphene nanocomposites

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Journal of Materials Science & Technology 2019年第6期35卷 1147-1152页

作者： c.c.Roach Y.c.Lu Department of Mechanical Engineering University of Kentucky

Understanding the roles of interlayers in reinforcement efficiencies by layered graphene is very important in order to produce strong and light graphene based nanocomposites. The present paper uses the finite element method to evaluate the interfacial strain transfers and reinforcement efficiencies in layered graphene-polymer composites. Results indicate that the presence of compliant interlayers in layered graphene plays significant roles in the transfers of strain/stress from matrix to graphene and subsequently the reinforcement effectiveness of layered graphene. In general, the magnitude of shear strain transferred onto the rigid graphene decreases as the thickness of the interlayer increases. This trend becomes insignificant as the graphene becomes sufficiently large(s>25,000). The shear strain at the interface of graphene-matrix is also greatly influenced by the interlayer modulus. A stiffer interlayer would result in a higher shear strain transferred on the graphene. The performance of the interlayers is further affected by the property of the composite and the architecture of the layered graphene stack. If a composite contains more graphene phase, the efficiency of reinforcement by a layered graphene becomes improved. If a graphene stack contains more interlayers, the effectiveness of reinforcement at the edges of the graphene becomes negatively affected.

关键词： Interlayer Layered graphene Nanocomposites Interfacial stress transfer Finite element method

Analytical modeling of effect of interlayer on effective moduli of layered graphene-polymer nanocomposites

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Journal of Materials Science & Technology 2017年第8期33卷 827-833页

作者： c.c.Roach Y.c.Lu Department of Mechanical Engineering University of KentuckyLexingtonKY 40506-0503USA

Nanocomposites enhanced with two-dimensional, layered graphene fillers are a new class of engineering materials that exhibit superior properties and characteristics to composites with conventional ***, the roles of ＂interlayers＂ in layered graphene fillers have yet to be fully explored. This paper examines the effect of interlayers on mechanical properties of layered graphene polymer *** an effective filler, the fundamental properties（in-plane Young＇s modulus E（L1）, out-of-plane Young＇s modulus E（L2）; shear modulus G（L12）, major Poisson＇s ratio V（L12）） of the layered graphene were computed by using the Arridge＇s lamellar model. The effects of interlayers on effective moduli of layered graphene epoxy composites were examined through the Tandon-Weng model. The properties of the interlayer show noticeable impact on elastic properties of the composites, particular the out-of-plane properties（Young＇s modulus E2 and shear modulus G（12））. The interlayer spacing is seen to have much great influence on properties of the composites. As the interlayer spacing increases from 0.34 nm to 2 nm, all elastic properties of the composites have been greatly decreased.

关键词： Interlayer Layered graphene Nanocomposite Effective moduli

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日冕开放磁场中的慢激波

中国科学（A辑） 1989年第11期20卷 1178-1186页

作者：胡友秋祝中伟 A.J.Hundhause T.E.holzer B.c.Low 中国科学技术大学地球和空间科学系美国大气研究中心高山天文台

日冕物质喷发的观测速度常低于Alfven波速的估计值而高于背景日冕声速,这表明日冕质量喷发可能在日冕中形成慢激波.本文假定日冕物质喷发由冕底的磁通量喷发所驱动,对它在开放磁场中形成的慢激波进行数值模拟。结果表明,慢激波纬度范围... 详细信息

日冕物质喷发的观测速度常低于Alfven波速的估计值而高于背景日冕声速,这表明日冕质量喷发可能在日冕中形成慢激波.本文假定日冕物质喷发由冕底的磁通量喷发所驱动,对它在开放磁场中形成的慢激波进行数值模拟。结果表明,慢激波纬度范围有限,外形平坦;一快波与慢激波共存并发生相互作用。快波使背景磁场发生偏转从而在慢激波前方引起稀疏,两侧引起压缩。快波的这些效应对慢激波的位,形和特征具有重要影响。

关键词：磁流体力学磁场激波太阳