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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

Status and prospects for symmetric organic redox flow batteries

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Journal of Energy chemistry 2025年第1期100卷 125-143页

作者： Md Al Raihan c.Adam Dyker Department of chemistry University of New Brunswick

As environmental concerns from fossil fuel consumption intensify, large-scale energy storage becomes imperative for the integration of renewable sources like wind, hydro, and solar with the electrical *** flow batteries, particularly those employing organic molecules, are positioned as a key technology for this purpose. This review explores the growing field of symmetric organic redox flow batteries(ORFBs) within this context. Unlike traditional asymmetric designs based on unique active materials for each electrode, symmetric ORFBs involve a single bipolar species for both electrodes. This review highlights the benefits of a symmetric design, and categorizes five distinct classes of organic bipolar molecules used in both aqueous and non-aqueous solvents. By providing a comprehensive overview of their cell cycling and performance characteristics, the strengths and weaknesses of the diverse categories of bipolar molecules are highlighted for both solvent systems, as are opportunities for future development. This should guide new research directions and advance the development of practical symmetric ORFBs.

关键词： Redox flow battery Symmetric battery Organic battery Aqueous electrolyte Non-aqueous electrolyte

Acquired sensorineural hearing loss,oxidative stress,and microRNAs

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Neural Regeneration Research 2025年第9期20卷 2513-2519页

作者： Desmond A.Nunez Ru c.Guo Division of Otolaryngology–Head&Neck Surgery Department of SurgeryFaculty of MedicineThe University of British ColumbiaVancouverBCCanada Division of Otolaryngology–Head&Neck Surgery Gordon&Leslie Diamond Health Care CentreVancouver General HospitalVancouverBCCanada Faculty of Medicine–The University of British columbia VancouverBCCanada

Hearing loss is the third leading cause of human ***-related hearing loss,one type of acquired sensorineural hearing loss,is largely responsible for this escalating global health ***-induced,ototoxic,and idiopathic sudden sensorineural are other less common types of acquired hearing *** etiology of these conditions is complex and multi-fa ctorial involving an interplay of genetic and environmental *** stress has recently been proposed as a likely linking cause in most types of acquired sensorineural hearing *** non-coding RNA sequences known as microRNAs(miRNAs)have increasingly been shown to play a role in cellular hypoxia and oxidative stress responses including promoting an apoptotic *** hair cell death is a central histopathological finding in sensorineural hearing *** these cells do not regenerate in humans,it underlies the irreversibility of human age-related hearing *** EMBASE,Ovid MEDLINE,Web of Science core collection,and *** databases over the period August 1,2018 to July 31,2023 were searched with"hearing loss,""hypoxamiRs,""hypoxia,""microRNAs,""ischemia,"and"oxidative stress"text words for English language primary study publications or registered clinical *** red clinical trials known to the senior author we re also assessed.A total of 222studies were thus *** excluding duplicates,editorials,retra ctions,secondary research studies,and non-English language articles,39 primary studies and clinical trials underwent full-text *** resulted in 11 animal,in vitro,and/or human subject journal articles and 8 registered clinical trial database entries which form the basis of this narrative *** miR-34a and miR-29b levels increase with age in *** miRNAs were demonstrated in human neuroblastoma and murine cochlear cell lines to target Sirtuin 1/peroxisome proliferato r-activated receptor gamma coactivator-1-alpha(SIRT1/P Gc-1α),SIRT

关键词： hearing loss hypoxia microRNAs oxidative stress sensorineural

Multiple sclerosis is at a checkpoint: advancing the program

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Neural Regeneration Research 2025年第3期20卷 811-812页

作者： Brandon c.Smith Jessica L.Williams Department of Neurosciences Lerner Research InstituteCleveland ClinicClevelandOHUSA Department of Biological Geologicaland Environmental SciencesCleveland State UniversityClevelandOHUSA

Multiple sclerosis(MS) is a chronic inflammatory and demyelinating disease of the central nervous system(cNS). Patients with MS experience sensory and motor function loss due to myelin and/or axon damage perpetuated b... 详细信息

关键词： Hauser sclerosis damage

Genomic analysis uncovers functional variation in the c-terminus of anthocyanin-activating MYB transcription factors

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Horticulture Research 2021年第1期8卷 885-898页

作者： Jessica A.Rodrigues Richard V.Espley andrew c.Allan The New Zealand Institute for Plant and Food Research Limited 120 Mount Albert RoadSandringhamAuckland 1025New Zealand School of Biological Sciences University of Auckland3A Symonds StAuckland 1010New Zealand

MYB transcription factors regulate diverse aspects of plant development and secondary metabolism,often by partnering in transcriptional regulatory ***,we harness genomic resources to identify novel MYBs,thereby producing an updated eudicot MYB phylogeny with revised relationships among subgroups as well as new information on sequence variation in the disordered c-terminus of anthocyanin-activating ***®and hidden Markov model scans of gene annotations identified a total of 714 MYB transcription factors across the genomes of four crops that span the eudicots:apple,grape,kiwifruit and *** model-based phylogenetic inference identified novel members of previously defined subgroups,and the function of specific anthocyanin-activating subgroup 6 members was assayed transiently in tobacco *** conservation within subgroup 6 highlighted one previously described and two novel short linear motifs in the disordered c-terminal *** novel motifs have a mix of hydrophobic and acidic residues and are predicted to be relatively ordered compared with flanking protein *** of motifs with the Eukaryotic Linear Motif database suggests roles in protein–protein *** of motifs and their flanking regions from strong anthocyanin activators into weak activators,and vice versa,affected *** conclude that,although the MYB c-terminal sequence diverges greatly even within MYB clades,variation within the c-terminus at and near relatively ordered regions offers opportunities for exploring MYB function and developing superior alleles for plant breeding.

关键词： phylogeny metabolism thereby

Interactions of complement proteins c1q and factor H with lipid A and Escherichia coli:further evidence that factor H regulates the classical complement pathway

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Protein & cell 2011年第4期2卷 320-332页

作者： Lee Aun Tan andrew c.Yang Uday Kishore Robert B.Sim Medical Research council Immunochemistry Unit Department of BiochemistryUniversity of OxfordSouth Parks RoadOxford OX13QUUK Present address:Department of Immunology Faculty of MedicineImperial College LondonHammersmith HospitalDu Cane RoadLondon W120NNUK St Peter’s college New Inn Hall St.Oxford OX12DLUK Present address:SUNY Downstate college of Medicine 450 Clarkson Avenue BrooklynNY 11203USA Weatherall Institute of Molecular Medicine John Radcliffe HospitalUniversity of OxfordHeadingtonOxford OX39DSUK Present address:center for Infection Immunity and Disease MechanismsBiosciencesSchool of Health Sciences and Social CareBrunel UniversityUxbridge UB83PH West LondonUK Present address:Department of Pharmacology University of OxfordMansfield RoadOxford OX13QTUK

Proteins of the complement system are known to interact with many charged *** recently characterized binding of c1q and factor H to immobilized and liposomal anionic *** H inhibited c1q binding to anionic phospholipids,suggesting a role for factor H in regulating activation of the complement classical pathway by anionic *** extend this finding,we examined interactions of c1q and factor H with lipid A,a well-characterized activator of the classical *** report that c1q and factor H both bind to immobilized lipid A,lipid A liposomes and intact Escherichia coli *** H competes with c1q for binding to these ***,increasing the factor H:c1q molar ratio in serum diminished c4b fixation,indicating that factor H diminishes classical pathway *** recombinant forms of the cterminal,globular heads of c1q A,B and c chains bound to lipid A and *** in a manner qualitatively similar to native c1q,confirming that c1q interacts with these targets via its globular head *** observations reinforce our proposal that factor H has an additional complement regulatory role of down-regulating classical pathway activation in response to certain *** is distinct from its role as an alternative pathway *** suggest that under physiological conditions,factor H may serve as a downregulator of bacterially-driven inflammatory responses,thereby finetuning and balancing the inflammatory response in infections with Gram-negative bacteria.

关键词： complement lipid A bacteria factor H c1q

Inaccuracies in the history of a well-known introduction:a case study of the Australian House Sparrow(Passer domesticus)

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chinese Birds 2016年第2期7卷 95-109页

作者： Samuel c.andrew Simon c.Griffith Department of Biological Sciences Macquarie University

Background:Modern ecosystems contain many invasive species as a result of the activity of acclimatisation societies that operated in the second half of the nineteenth century,and these species provide good opportunities for studying invasion ***,to gain insight into the ecological and genetic mechanisms that determine the rate of colonization and adaptation to new environments,we need a good understanding of the history of the introduced species,and a knowledge of the source population,timing,and number of individuals introduced is particularly ***,any inaccuracies in the history of an introduction will affect subsequent assumptions and ***:Focusing on a single well-known species,the House Sparrow(Passer domesticus),we have documented the introduction into Australia using primary sources(*** records and newspaper articles).Results:Our revised history differs in a number of significant ways from previous *** evidence indicates that the House Sparrow was not solely introduced from source populations in England but also from Germany and most strikingly also from India—with the latter birds belonging to a different *** also clarify the distinction between the number released and the number of founders,due to pre-release captive breeding programs,as well as identifying inaccuracies in a couple of well-cited sources with respect to the range expansion of the introduced ***:Our work suggests that caution is required for those studying introductions using the key sources of historical information and ideally should review original sources of information to verify the accuracy of published accounts.

关键词： Acclimatisation Bottlenecks Propagule size Range expansion Hybridisation

Ultra‑Transparent and Multifunctional IZVO Mesh Electrodes for Next‑Generation Flexible Optoelectronics

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Nano-Micro Letters 2025年第1期17卷 293-309页

作者： Kiran A.Nirmal Tukaram D.Dongale Atul c.Khot chenjie Yao Nahyun Kim Tae Geun Kim School of Electrical Engineering Korea UniversityAnam‑ro 145Seongbuk‑guSeoulRepublic of Korea computational Electronics and Nanoscience Research Laboratory School of Nanoscience and BiotechnologyShivaji UniversityKolhapur 416004India

Mechanically durable transparent electrodes are essential for achieving long-term stability in flexible optoelectronic ***,they are crucial for applications in the fields of energy,display,healthcare,and soft *** meshes represent a promising alternative to traditional,brittle,metal oxide conductors due to their high electrical conductivity,optical transparency,and enhanced mechanical *** this paper,we present a simple method for fabricating an ultra-transparent conducting metal oxide mesh electrode using selfcracking-assisted *** this method,we produced an electrode with ultra-transparency(97.39%),high conductance(Rs=21.24Ωsq^(−1)),elevated work function(5.16 eV),and good mechanical *** also evaluated the effectiveness of the fabricated electrodes by integrating them into organic photovoltaics,organic light-emitting diodes,and flexible transparent memristor devices for neuromorphic computing,resulting in exceptional device *** addition,the unique porous structure of the vanadium-doped indium zinc oxide mesh electrodes provided excellent flexibility,rendering them a promising option for application in flexible optoelectronics.

关键词： Self-cracking template Vanadium-doped indium zinc oxide mesh Organic solar cells Organic light-emitting diodes Flexible transparent memory

PI3K-AKT-mTOR signaling in prostate cancer progression and androgen deprivation therapy resistance

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Asian Journal of Andrology 2014年第3期16卷 378-386页

作者： Merritt P Edlind andrew c Hsieh Perelman School of Medicine University of Pennsylvania Philadelphia PA USA Division of Hematology/Oncology and Department of Internal Medicine University of California San Francisco CA USA.

Prostate cancer （Pca） is the second most common malignancy among men in the world. castration-resistant prostate cancer （cRPc） is the lethal form of the disease, which develops upon resistance to first line androgen deprivation therapy （ADT）. Emerging evidence demonstrates a key role for the PI3K-AKT-mTOR signaling axis in the development and maintenance of cRPc. This pathway, which is deregulated in the majority of advanced Pcas, serves as a critical nexus for the integration of growth signals with downstream cellular processes such as protein synthesis, proliferation, survival, metabolism and differentiation, thus providing mechanisms for cancer cells to overcome the stress associated with androgen deprivation. Furthermore, preclinical studies have elucidated a direct connection between the PI3K-AKT-mTOR and androgen receptor （AR） signaling axes, revealing a dynamic interplay between these pathways during the development of ADT resistance. Thus, there is a clear rationale for the continued clinical development of a number of novel inhibitors of the PI3K pathway, which offer the potential of blocking cRPc growth and survival. In this review, we will explore the relevance of the PI3K-AKT-mTOR pathway in Pca progression and castration resistance in order to inform the clinical development of specific pathway inhibitors in advanced Pca. In addition, we will highlight current deficiencies in our clinical knowledge, most notably the need for biomarkers that can accurately predict for response to PI3K pathway inhibitors.

关键词： androgen receptor cRPc kinase inhibitors mTOR prostate cancer PI3K resistance