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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

soluble epoxide hydrolase:a next-generation drug target for Alzheimer's disease and related dementias

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Neural Regeneration Research 2025年第9期20卷 2585-2586页

作者： andrew Gregory Chengyun Tang Fan Fan Department of Physiology Medical College of GeorgiaAugusta UniversityAugustaGAUSA

Alzheimer's disease(AD)and Alzheimer's diseaserelated dementias(ADRD)represent a significant public health challenge,with projections indicating a substantial increase in affected individuals due to the aging global *** the World Health Organization,AD/ADRD has affected more than 55 million individuals worldwide,with an additional 10 million cases diagnosed each year.

关键词： Alzheimer population drug

A hybrid tracking control strategy for an unmanned underwater vehicle aided with bioinspired neural dynamics

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IET Cyber-systems and Robotics 2022年第3期4卷 153-162页

作者： Zhe Xu Tao Yan simon X.Yang s.andrew Gadsden school of Engineering University of GuelphGuelphOntarioCanada Department of Mechanical Engineering McMaster UniversityHamiltonOntarioCanada

Tracking control has been a vital research topic in *** paper presents a novel hybrid control strategy for an unmanned underwater vehicle(UUV)based on a bio-inspired neural dynamics *** enhanced backstepping kinematic control strategy is first developed to avoid sharp velocity jumps and provides smooth velocity commands relative to conventional ***,a novel sliding mode control is proposed,which is capable of providing smooth and continuous torque commands free from *** comparative studies,the proposed combined hybrid control strategy has ensured control signal smoothness,which is critical in real‐world applications,especially for a UUV that needs to operate in complex underwater environments.

关键词： backstepping bioinspired neural dynamics sliding mode control unmanned underwater vehicle

A functional tacrolimus-releasing nerve wrap for enhancing nerve regeneration following surgical nerve repair

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Neural Regeneration Research 2025年第1期20卷 291-304页

作者： simeon C.Daeschler Katelyn J.W.so Konstantin Feinberg Marina Manoraj Jenny Cheung jennifer Zhang Kaveh Mirmoeini JPaul santerre Tessa Gordon Gregory HBorschel sickKids Research Institute Neuroscience and Mental Health ProgramTorontoONCanada Institute of Biomaterials and Biomedical Engineering University of TorontoTorontoONCanada Indiana University school of Medicine IndianapolisINUSA Division of Plastic and Reconstructive surgery the Hospital for Sick ChildrenTorontoONCanada Translational Biology and Engineering Program Ted Rogers Centre for Heart ResearchInstitute of Biomedical EngineeringFaculty of DentistryUniversity of TorontoTorontoONCanada

Axonal regeneration following surgical nerve repair is slow and often incomplete,resulting in poor functional recovery which sometimes contributes to lifelong ***,there are no FDA-approved therapies available to promote nerve *** accelerates axonal regeneration,but systemic side effects presently outweigh its potential benefits for peripheral nerve *** authors describe herein a biodegradable polyurethane-based drug delivery system for the sustained local release of tacrolimus at the nerve repair site,with suitable properties for scalable production and clinical application,aiming to promote nerve regeneration and functional recovery with minimal systemic drug *** is encapsulated into co-axially electrospun polycarbonate-urethane nanofibers to generate an implantable nerve wrap that releases therapeutic doses of bioactive tacrolimus over 31 *** and drug loading are adjustable for applications in small and large caliber nerves,and the wrap degrades within 120 days into biocompatible *** released from the nerve wrap promotes axon elongation in vitro and accelerates nerve regeneration and functional recovery in preclinical nerve repair models while off-target systemic drug exposure is reduced by 80%compared with systemic *** its surgical suitability and preclinical efficacy and safety,this system may provide a readily translatable approach to support axonal regeneration and recovery in patients undergoing nerve surgery.

关键词： biodegradable local drug delivery nerve injury nerve regeneration nerve wrap tacrolimus

Anodic dissolution of metals in ionic liquids

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Progress in Natural science:Materials International 2015年第6期25卷 595-602页

作者： andrew P.Abbott Gero Frisch jennifer Hartley Wrya O.Karim Karl s.Ryder Chemistry Department University of Leicester TU Bergakademie Freiberg Institut fu?r Anorganische Chemie

The anodic dissolution of metals is an important topic for battery design,material finishing and metal *** liquids are being used in all of these areas but the research on the anodic dissolution is relatively few in these *** study investigates the behaviour of 9 metals in an ionic liquid [C;mim][Cl] and a deep eutectic solvent,Ethaline,which is a 1:2 mol ratio mixture of choline chloride and ethylene *** is shown that for the majority of metals studied a quasi-passivation of the metal surface occurs,primarily due to the formation of insoluble films on the electrode *** behaviour of most metals is different in [C;mim][Cl] to that in Ethaline due in part to the differences in *** formation of passivating salt films can be decreased with stirring or by increasing the electrolyte temperature,thereby increasing ligand transport to the electrode surface.

关键词： Ionic liquid Deep eutectic solvent speciation Electropolishing Passivation

synthesis and crystal structure of a neodymium coordination polymer with 2,6-anthraquinonedisulfonate

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Particuology 2010年第3期8卷 221-224页

作者： jennifer L. Nicholls John Bacsa andrew M. Fogg Department of Chemistry University of Liverpool Crown Street Liverpool L69 7ZD United Kingdom

The coordination polymer, （Nd（H2O）5）2（2,6-AQDs）3.2H2O where 2,6-AQDs = 2,6- anthraquinonedisulfonate, has been synthesised via a hydrothermal route. structurally, it consists of layers of monomeric Nd polyhedra which are linked by 2,6-AQDs anions forming a polymeric, three-dimensional network. Each Nd atom is nine coordinate, bonding to five water molecules and to four oxygen atoms from four 2,6-AODs anions which in turn pillar the layers by bridging two Nd atoms in one layer, and coordinating to a single Nd in the other.

关键词： Lanthanide Layered materials sulfonate Coordination polymer

Esophageal dilations in eosinophilic esophagitis: A single center experience

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World Journal of Gastroenterology 2014年第28期20卷 9549-9555页

作者： andrew Ukleja jennifer shiroky Amitesh Agarwal Daniela Allende Department of Gastroenterology Cleveland Clinic Florida the University of Texas Medical Branch at Galveston Cleveland Clinic

AIM: To diagnose the clinical and histologic features that may be associated with or predictive of the need for dilation and dilation related complications; examine the safety of dilation in patients with eosinophilic... 详细信息

关键词： Balloon dilation Dysphagia Esophagus disorder Esophageal stricture Esosinophilic esophagitis

Endoscopic ultrasound sedation in the United Kingdom: Is life without propofol tolerable?

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World Journal of Gastroenterology 2017年第3期23卷 560-562页

作者： jennifer Anne Campbell andrew James Irvine andrew Derek Hopper Department of Gastroenterology Royal Hallamshire HospitalSheffield S10 2JFUnited Kingdom

There is compelling evidence to support the quality,cost effectiveness and safety profile of non-anesthesiologist-administered propofol for endoscopic ultrasound (EUs). However in the United Kingdom, it is recommended that the administration and monitoring of propofol sedation for endoscopic procedures should be the responsibility of a dedicated and appropriately trained anaesthetist only. The majority of United Kingdom EUs procedures are performed with opiate and benzodiazepine sedation rather than anaesthetist led propofol lists due to anaesthetist resource availability. We sought to prospectively determine the tolerability and safety of EUs with benzodiazepine and opiate sedation in single United Kingdom centre. Two hundred consecutive patients undergoing either EUs or oesophago-gastroduodenoscopy (OGD) with conscious sedation were prospectively recruited with a 1:1 enrolment ratio. Patients completed questionnaires pre and post procedure detailing anticipated and actual pain experienced on a 1-10 visual analogue scale. Demographics, procedure duration, sedation doses and willingness to repeat the procedure were also recorded. EUs procedures lasted significantly longer than OGDs(15 min vs 6 min, P s no difference in anticipated pain scores between the groups(EUs 3.37/10 vs OGD 3.47/10, P = 0.46). Pain scores indicated EUs was better tolerated than OGD(1.16/10 vs 1.88/10, P = 0.03) although higher doses of sedation were used for EUs procedures. There were no complications identified in either group. We feel our study demonstrates that the tolerability of EUs with opiate and benzodiazepine sedation is acceptable.

关键词： sedation Endoscopy Tolerability Propofol Endoscopic ultrasound

Associations with pancreatic exocrine insufficiency:An United Kingdom single-centre study

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World Journal of Clinical Cases 2021年第31期9卷 9469-9480页

作者： Benjamin M shandro Joshua Chen jennifer Ritehnia andrew Poullis Department of Gastroenterology St George's University Hospitals NHS Foundation TrustLondon SW170QTUnited Kingdom

BACKGROUND Pancreatic exocrine insufficiency(PEI)is said to be associated with numerous conditions both within and outside the gastrointestinal(GI)*** majority of research has been concerned with conditions that reduce the volume of functioning pancreatic tissue or prevent adequate drainage to the small bowel,such as chronic pancreatitis,cystic fibrosis,pancreatic cancer and pancreatic ***,the evidence base supporting an association with extrapancreatic conditions,such as coeliac disease,diabetes mellitus and congestive cardiac failure,is *** To strengthen the evidence base by studying all previously reported associations with PEI in a large cohort of *** A single-centre retrospective study was *** gastroenterology outpatients tested for PEI with faecal elastase-1(FE1)were identified and information retrieved from the electronic patient *** was defined as FE1s used to handle missing *** logistic regression was used to study which presenting symptoms predicted *** logistic regression was used to explore the relationship between all previously reported associations and *** Of 1027 patients were included.182 patients(17.7%)were diagnosed with ***[odds ratios(OR):2.51,95%confidence intervals(CI):1.58-3.98]and weight loss(OR:1.49,95%CI:1.08-2.06)were the only presenting symptoms that predicted *** pancreatitis(OR:7.98,95%CI:3.95-16.15),pancreatic cancer(OR:6.58,95%CI:1.67-25.98),upper GI surgery(OR:2.62,95%CI:1.32-5.19),type 2 diabetes(OR:1.84,95%CI:1.18-2.87),proton pump inhibitor therapy(OR:1.87,95%CI:1.25-2.80)and Asian ethnicity(OR:2.11,95%CI:1.30-3.42)were significantly associated with PEI in the multivariable *** of the other historically reported associations with PEI were significant after adjustment for the other variable

关键词： Exocrine pancreatic insufficiency Chronic pancreatitis Pancreatic elastase steatorrhoea Proton pump inhibitors