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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

Canonical and noncanonical Wnt signaling: Multilayered mediators, signaling mechanisms and major signaling crosstalk

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Genes & Diseases 2024年第1期11卷 103-134页

作者： kevin Qin Michael Yu Jiaming Fan Hongwei Wang Piao Zhao Guozhi Zhaoo Wei Zeng Connie Chen Yonghui Wang Annie Wang Zander Schwartz Jeffrey Hong Lily Song William Wagstaff Rex C.Haydon Hue H.Luu Sherwin H.Ho Jason Strelzow Russell R.Reid Tong-Chuan He Lewis L.Shi Chicago Medical School Rosalind Franklin University of Medicine and ScienceNorth ChicagoIL 60064USA Molecular Oncology Laboratory Department of Orthopaedic Surgery and Rehabilitation MedicineThe University of Chicago Medical CenterChicagoIL 60637USA Ministry of Education Key Laboratory of Diagnostic Medicine and Department of Clinical BiochemistryThe School of Laboratory MedicineChongqing Medical UniversityChongqing 400016China Departments of Orthopaedic Surgery and Urology The First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China Department of Interventional Neurology The First Dongguan Affiliated HospitalGuangdong Medical UniversityDongguanGuangdong 523475China Department of Clinical Laboratory Medicine Shanghai Jiaotong University School of MedicineShanghai 200000China School of Biomedical Engineering Vanderbilt UniversityNashvilleTN 37235USA Laboratory of Craniofacial Biology and Development Department of Surgery Section of Plastic SurgeryThe University of Chicago Medical CenterChicagoIL 60637USA

Wnt signaling plays a major role in regulating cell proliferation and *** Wnt ligands are a family of 19 secreted glycoproteins that mediate their signaling effects via binding to Frizzled receptors and LRP5/6 coreceptors and transducing the signal either throughβ-catenin in the canonical pathway or through a series of other proteins in the nonca-nonical *** of the individual components of both canonical and noncanonical Wnt signaling have additional functions throughout the body,establishing the complex interplay between Wnt signaling and other signaling *** crosstalk between Wnt signaling and other pathways gives Wnt signaling a vital role in many cellular and organ ***-regulation of this system has been implicated in many diseases affecting a wide array of organ systems,including cancer and embryological defects,and can even cause embryonic *** complexity of this system and its interacting proteins have made Wnt signaling a target for many therapeutic ***,both stimulatory and inhibitory treatments come with potential risks that need to be *** review synthesized much of the current knowl-edge on the Wnt signaling pathway,beginning with the history of Wnt *** thoroughly described the different variants of Wnt signaling,including canonical,noncanonical Wnt/PCP,and the noncanonical Wnt/Ca2+*** description involved each of its components and their involvement in other cellular ***,this review explained the various other pathways and processes that crosstalk with Wnt signaling.

关键词： β-catenin Canonical Wnt Noncanonical Wnt Signal transduction Signaling crosstalk

Tensorial tomographic Fourier ptychography with applications to muscle tissue imaging

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Advanced Photonics 2024年第2期6卷 50-60页

作者： Shiqi Xu Xi Yang Paul Ritter Xiang Dai Kyung Chul Lee Lucas Kreiss kevin C.Zhou Kanghyun Kim Amey Chaware Jadee Neff Carolyn Glass Seung Ah Lee Oliver Friedrich Roarke Horstmeyer Duke University DurhamNorth CarolinaUnited States Friedrich-Alexander University ErlangenGermany UC San Diego La JollaCaliforniaUnited States Yonsei University SeoulRepublic of Korea UC Berkeley BerkeleyCaliforniaUnited States Duke University Medical Center DurhamNorth CarolinaUnited States

We report tensorial tomographic Fourier ptychography(T^(2)oFu),a nonscanning label-free tomographic microscopy method for simultaneous imaging of quantitative phase and anisotropic specimen information in *** upon Fourier ptychography,a quantitative phase imaging technique,T^(2)oFu additionally highlights the vectorial nature of *** imaging setup consists of a standard microscope equipped with an LED matrix,a polarization generator,and a polarization-sensitive *** tensors of anisotropic samples are computationally recovered from polarized intensity measurements across three *** demonstrate T^(2)oFu’s efficiency through volumetric reconstructions of refractive index,birefringence,and orientation for various validation samples,as well as tissue samples from muscle fibers and diseased heart *** reconstructions of healthy muscle fibers reveal their 3D fine-filament structures with consistent ***,we demonstrate reconstructions of a heart tissue sample that carries important polarization information for detecting cardiac amyloidosis.

关键词： computational imaging three-dimensional imaging phase retrieval microscopy polarization-sensitive imaging labelfree imaging

Mixed ion and electron transport theory and application in solid oxide conductors

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International Journal of Minerals,Metallurgy and Materials 2022年第4期29卷 870-875页

作者： kevin Huang Department of Mechanical engineering University of South CarolinaColumbiaSC 292201USA

Mixed ions and electron conductors(MIECs)are an important family of electrocatalysts for electrochemical devices,such as reversible solid oxide cells,rechargeable metal-air batteries,and oxygen transport *** ionic and electronic transports in these materials play a key role in electrocatalytic *** in-depth fundamental understanding of the transport phenomena is critically needed to develop better *** this brief review,we introduced generic ionic and electronic transport theory based on irreversible thermodynamics and applied it to practical oxide-based materials with oxygen vacancies and electrons/holes as the predominant *** oxide systems,namely CeO_(2)-based and La CrO_(3)-based materials,are selected as case studies to illustrate the utility of the transport theory in predicting oxygen partial pressure distribution across MIECs,electrochemical electronic/ionic leakage currents,and the effects of external load current on the leakage currents.

关键词： irreversible thermodynamics diffusivity charge neutrality electrochemical potential electrostatic potential

Surgical Treatment of Osteonecrosis of the Femoral Head Using Minimally Invasive Surgical Drilling and Cancellous Grafting at Brazzaville University Hospital

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Open Journal of Orthopedics 2024年第2期14卷 122-132页

作者： kevin Parfait Bienvenu Bouhelo-Pam Marius Monka Arnauld Sledje Wilfrid Bilongo Bouyou Regis Perry Massouama Paul Yèlai Ikounga Roger Bertrand Sah Mbou Armand Moyikoua Department of Orthopaedic surgery and Traumatology University Hospital of Brazzaville Brazzaville Republic of the Congo Faculty of Health Sciences Marien N’GOUABI University Brazzaville Republic of the Congo

Introduction: Osteonecrosis of the femoral head (ONTF) is a debilitating condition. Several treatments have been proposed with controversial results. The aim of our study was to evaluate treatment by surgical drilling coupled with in situ cancellous grafting. Materials and methods: Our study was a case-control study conducted at Brazzaville University Hospital from 1st January 2018 to 31 December 2023. It compared two groups of patients with ONTF: non-operated (13 patients, 20 hips) and operated (22 patients, 35 hips). We used the visual digital scale (VDS) for pain assessment, the Merle D’Aubigne-Postel (MDP) scoring system for clinical and functional assessment, and the evolution of necrosis. Results: The group of non-operated patients had a mean age of 35.69 ± 3.4 years, no improvement in pain with an EVN above seven at the last recoil and a mean global MDP score falling from 12.7 before offloading to 10.13 at one year. The group of patients operated on had a mean age of 37.86 ± 7.02 years, a significant reduction in pain (p = 0.00004) and a significantly increased MDP score (p = 0.0034). A comparison of the two groups of patients showed significant stabilization of the necrotic lesions in the operated patients (p = 0.00067), with better satisfaction in the same group. Conclusion: Surgical drilling combined with grafting in the treatment of early-stage ONTF has improved progress in our series. The technique is reproducible and less invasive. It has made it possible to delay unfavorable progression and, consequently, hip replacement surgery.

关键词： Hip Osteonecrosis of the Femoral Head Conservative Treatment Surgical Drilling Bone Grafting

Treatment of Synovial Cysts in Relation to the Tibial Tunnel of Anterior Cruciate Ligament Grafts by Filling the Tunnel with Acrylic Cement

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Surgical Science 2024年第4期15卷 289-298页

作者： Saint Luc Mungina Sedou Charlène Tshitala Mbombo Yannick Toko Kiama kevin Ndangi Ezechiel Nkodia Dieudonné Mwangala Rossyl Kivudi Dominique Saragaglia Luc Mokassa Bakumobatane Department of Surgery University Clinics of Kinshasa Faculty of Medicine University of Kinshasa Kinshasa Democratic Republic of Congo Matete General Reference Hospital Kinshasa Democratic Republic of Congo Department of Orthopedic Surgery Osteoarthritis Surgery and Sports Tromatology at the Grenoble Hospital and University Center Grenoble France National Border Hygiene Program Kinshasa Democratic Republic of Congo

Introduction: Synovial cyst of the tibial tunnel in connection with anterior cruciate ligament (ACL) reconstruction is a rare but particularly troublesome complication. Medical treatment is often doomed to failure, and surgical treatment usually consists of excising the cyst and filling the tunnel with bone. The aim of this study was to evaluate the results of filling the tunnel with acrylic cement. Hypothesis: Filling the tibial bone tunnel with acrylic cement should eliminate communication between the joint cavity and the pre-tibial surface and prevent cyst recurrence. Patients and Methods: This retrospective series is composed of 13 patients, 9 men and 4 women, mean age 48.5 years (31 to 64) operated on between 2011 and 2019 for an intra- and extraosseous synovial cyst consecutive to the tibial tunnel of an ACL graft. Between 1983 and 2016, 12 of the patients had had a bone graft without bone block fixation (DI-DT or Mac Intosh) and one patient, a bone-bone transplant (KJ). The cyst was of variable size, located on the anteromedial aspect of the proximal end of the tibia, and often painful, warranting consultation. At the time of the initial operation, 9 patients had undergone meniscectomies (6 medial, 2 lateral, 1 double). In 7 knees, there were 7 cartilage lesions in the femorotibial and/or patellofemoral compartments (one stage 1 lesion, 2 stage 2 lesions, 4 stage 3 lesions, and no stage 4 lesions). Only 2 knees had neither cartilage nor meniscus lesions. After curettage of the bone tunnel /− removal of the non-resorbed or PEEK interference screw, the tunnel was filled with acrylic cement /− reinforced with a ligament staple to prevent expulsion. All patients underwent regular follow-up consultations until recovery. Results: At a maximum follow-up of 8 years, only 1 cyst recurred, representing a 7.69% failure rate. It was reoperated with another technique, which involved filling the tibial bone tunnel with bone graft taken from a half-bank head. After recovery

关键词： Arthro-Synovial Cyst Tibial Tunnel ACL Graft Filling Acrylic Cement

Multistage Off-Line Permutation Packet Routing on a Mesh:An Approach with Elementary Mathematics

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Journal of Computer Science & Technology 2009年第1期24卷 175-180页

作者： kevin Chiew School of Information Systems Singapore Management University80 Stamford RoadSingapore 178902

Various methods have been proposed for off-line permutation packet routing on a mesh. One of the methods is known as multistage routing, in which the first stage is crucial. For the first stage of routing, the previous study normally converts it to a problem of graph theory and proves the existence of solutions. However, there is a lack of simple algorithms to the first stage of routing. This article presents an explicit and simple approach for the first stage of routing based on elementary mathematics.

关键词： permutation packet routing explicit algorithm

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地球科学的大数据、数字孪生与水文学

水利信息化 2024年第4期 99-100页

作者： Tiffany C.Vance Thomas Huang kevin A.Butler 包鑫如(编译) 不详

地球科学是研究地球物理、化学和生物系统及其相互作用的庞大而复杂的领域。随着基于地球和卫星的传感器数量和分辨率的提高,地球科学数据的体量呈爆炸式增长,这些数据有助于我们探索地球的复杂现象和变化过程,并推动数据分析、可视化... 详细信息

地球科学是研究地球物理、化学和生物系统及其相互作用的庞大而复杂的领域。随着基于地球和卫星的传感器数量和分辨率的提高,地球科学数据的体量呈爆炸式增长,这些数据有助于我们探索地球的复杂现象和变化过程,并推动数据分析、可视化等技术的发展。将地球科学中的大数据定义为对地球系统开展多种观测和模拟而得到的大量、多样且不断积累的复杂数据,这些数据的分析与应用不仅需要大量可用的计算资源,还需要先进的技术和工具。随着大数据和人工智能的应用与发展,用于发现、分析和可视化大数据的技术和工具不断涌现,如Google Earth Engine,Apache Science Data Analytic Platform,The Pangeo Project等,这些平台具有广泛的地理空间数据和计算能力,显著提升了对地球系统的认知水平。

关键词：大数据人工智能地球科学传感器数量复杂数据地理空间数据 Apache 计算能力

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Determination of contact parameters for discrete element method simulations of granular systems

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Particuology 2008年第6期6卷 521-528页

作者： kevin Francis Malone Institute of Particle Science and Engineering University of Leeds

Both linear-spring-dashpot （LSD） and non-linear Hertzian-spring-dashpot （HSD） contact models are commonly used for the calculation of contact forces in Discrete Element Method （DEM） simulations of granular systems. Despite the popularity of these models, determination of suitable values for the contact parameters of the simulated particles such as stiffness, damping coefficient, coefficient of restitution, and simulation time step, is not altogether obvious. In this work the relationships between these contact parameters for a model system where a particle impacts on a flat base are examined. Recommendations are made concerning the determination of these contact parameters for use in DEM simulations.

关键词： Discrete Element Method (DEM) Linear-spring--dashpot model Non-linear Hertzian-spring-dashpot model Contact parameters