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Targeting TrkB–PSD-95 coupling to mitigate neurological disorders

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Neural Regeneration Research 2025年第3期20卷 715-724页

作者： Xin Yang Yu-Wen Alvin Huang john Marshall Department of Molecular Biology Cell Biology and BiochemistryBrown UniversityProvidenceRIUSA Department of Neurology Warren Alpert Medical School of Brown UniversityProvidenceRIUSA Center for Translational Neuroscience Robert J.and Nancy D.Carney Institute for Brain Science and Brown Institute for Translational ScienceBrown UniversityProvidenceRIUSA

Tropomyosin receptor kinase B(TrkB)signaling plays a pivotal role in dendritic growth and dendritic spine formation to promote learning and *** activity-dependent release of brain-derived neurotrophic factor at synapses binds to pre-or postsynaptic TrkB resulting in the strengthening of synapses,reflected by long-term ***,the association of postsynaptic density protein-95 with TrkB enhances phospholipase Cγ-Ca^(2+)/calmodulin-dependent protein kinaseⅡand phosphatidylinositol 3-kinase-mechanistic target of rapamycin signaling required for long-term *** this review,we discuss TrkB-postsynaptic density protein-95 coupling as a promising strategy to magnify brain-derived neurotrophic factor signaling towards the development of novel therapeutics for specific neurological disorders.A reduction of TrkB signaling has been observed in neurodegenerative disorders,such as Alzheimer's disease and Huntington's disease,and enhancement of postsynaptic density protein-95 association with TrkB signaling could mitigate the observed deficiency of neuronal connectivity in schizophrenia and *** with brain-derived neurotrophic factor is problematic,due to poor pharmacokinetics,low brain penetration,and side effects resulting from activation of the p75 neurotrophin receptor or the truncated TrkB.T1 *** TrkB agonists and antibodies that activate TrkB are being intensively investigated,they cannot distinguish the multiple human TrkB splicing isoforms or cell type-specific *** TrkB–postsynaptic density protein-95 coupling provides an alternative approach to specifically boost TrkB signaling at localized synaptic sites versus global stimulation that risks many adverse side effects.

关键词： Angelman syndrome autism brain-derived neurotrophic factor depression neurodegenerative disorder neurodevelopmental disorder postsynaptic density protein-95 synaptic plasticity TrkB

Cascade degradation and electrocatalytic upcycling of waste poly(ethylene terephthalate)to valued products

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Nano Research 2025年第1期18卷 76-93页

作者： Xin Li Zirui Jiang Zongkui Kou john Wang Shiyou Zheng School of Materials and Chemistry University of Shanghai for Science and TechnologyShanghai 200093China School of Materials Science and Engineering Wuhan University of TechnologyWuhan 430070China Department of Materials Science and Engineering National University of SingaporeSingapore 117574Singapore

The global annual production of poly(ethylene terephthalate)(PET)has reached 82 million tons,yet only a small fraction(less than 20%)is *** ultra-slow degradation rate of PET results in the accumulation of PET waste in the environment,causing serious plastic pollution and posing severe challenges to *** response,great efforts have been directed toward developing a cascade degradation and electrocatalytic upcycling strategy,which serves as a“waste-towealth”*** strategy involves electro-reforming PEThydrolyzed intermediates or using PET pyrolyzed products as electrocatalysts to generate high-value *** review provides an overview of the state-of-the-art strategies for the“degradation-electrocatalytic upcycling(De-eUp)”of PET ***,an introduction to the strategy is provided,categorizing it into two main frameworks:“pyrolysis-electrocatalytic upcycling”and“hydrolysis-electrocatalytic upcycling”.The section on“pyrolysis-electrocatalytic upcycling”delves into the degradation methods for designing derived carbon nanomaterials and their utilization as high-performance ***“hydrolysis-electrocatalytic upcycling”section discusses recent advancements in electro-reforming of PET hydrolyzed intermediates for the production of C_(1) and C_(2) *** review concludes by examining the challenges and future prospects in developing an efficient and economical PET upcycling *** is anticipated that this review will stimulate further progress in plastic waste valorization.

关键词： poly(ethylene terephthalate)waste electrocatalytic upcycling pyrolysis hydrolysis ethylene glycol oxidation reaction

A spotlight on dosage and subject selection for effective neuroprotection: exploring the central role of mitochondria

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Neural Regeneration Research 2025年第4期20卷 1081-1082页

作者： john Mitrofanis Jonathan Stone Michael R.Hamblin Pierre Magistretti Alim-Louis Benabid Glen Jeffery Fonds Clinatec UniversitéGrenoble AlpesGrenobleFrance School of Medical Science University of SydneySydneyAustralia Faculty of Health Sciences University of JohannesburgJohannesburgSouth Africa King Abdullah University of Science and Technology ThuwalSaudi Arabia Institute of Ophthalmology University College LondonLondonUK

Neurons are notoriously vulnerable cell *** the slightest change in their internal and/or external environments will cause much distress and dysfunction,leading often to their death.A range of pathological conditions,including stroke,head trauma,and neurodegenerative disease,can generate stress in neurons,affecting their survival and proper *** most neural pathologies,mitochondria become dysfunctional and this plays a pivotal role in the process of cell *** challenge over the last few decades has been to develop effective interventions that improve neuronal homeostasis under pathological *** interventions,often referred to as disease-modifying or neuroprotective,have,however,proved frustratingly elusive,at both preclinical and,in particular,clinical *** this perspective,we highlight two factors that we feel are key to the development of effective neuroprotective *** are:firstly,the choice of dose of intervention and method of application,and secondly,the selection of subjects,whether they be patients or the animal model.

关键词： protective dosage distress

Future of non-invasive graft evaluation:A systematic review of proteomics in kidney transplantation

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World Journal of Transplantation 2025年第1期15卷 135-149页

作者： Eleni Avramidou Konstantina Psatha Kallisti St john Georgios Tsoulfas Michalis Aivaliotis Department of Transplantation Surgery Center for Research and Innovation in Solid Organ TransplantationAristotle University of ThessalonikiSchool of MedicineThessaloniki 54642Greece Laboratory of Medical Biology-Genetics School of MedicineAristotle University of ThessalonikiThessaloniki 54124Greece Functional Proteomics and Systems Biology(FunPATh) Center for Interdisciplinary Research and Innovation(CIRI-AUTH)Thessaloniki GR-57001Greece Laboratory of Biological Chemistry School of MedicineAristotle University of ThessalonikiThessaloniki 54124Greece

BACKGROUND Despite the developments in the field of kidney transplantation,the already existing diagnostic techniques for patient monitoring are considered *** biomarkers that can be derived from modern approaches of proteomic analysis of liquid biopsies(serum,urine)represent a promising innovation in the monitoring of kidney transplant *** To investigate the diagnostic utility of protein biomarkers derived from proteomics approaches in renal allograft *** A systematic review was conducted in accordance with PRISMA guidelines,based on research results from the PubMed and Scopus *** primary focus was on evaluating the role of biomarkers in the non-invasive diagnosis of transplant-related *** criteria included protein biomarkers and urine and blood samples,while exclusion criteria were language other than English and the use of low resolution and sensitivity *** selected research articles,were categorized based on the biological sample,condition and methodology and the significantly and reproducibly differentiated proteins were manually selected and *** and network analysis of the selected proteins was *** In 17 included studies,58 proteins were studied,with the cytokine CXCL10 being the most *** pathways related to immune response and fibrosis have shown to be *** of biomarkers for the assessment of renal damage as well as the prediction of short-term and long-term function of the graft were ***,all studies have shown satisfactory diagnostic accuracy of proteins alone or in combination with conventional methods,as far as renal graft assessment is *** Our review suggests that protein biomarkers,evaluated in specific biological fluids,can make a significant contribution to the timely,valid and non-invasive assessment of kidney graft.

关键词： Proteomics Kidney transplantation Graft evaluation Non-invasive diagnosis Kidney graft function

Prof. john Chabot: working hard and asking important questions, but also keeping focused

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Hepatobiliary Surgery and Nutrition 2020年第2期9卷 269-270页

作者： john Chabot 不详

Expert's introduction *** Chabot(Figure 1)received his medical degree from Dartmouth College School of Medicine and completed a residency in General Surgery at Columbia Presbyterian Medical Center and a fellowship in Surgery at Dartmouth-Hitchcock Medical *** joined New York-Presbyterian/Columbia in 1983 and has since become Professor of Surgery and Executive Director of the Pancreas Center and Chief of Gastrointestinal/Endocrine ***’s clinical interest is focused on the prevention,treatment,and cure of cancers involving the gastrointestinal tract(especially pancreatic cancer)and other areas of surgical oncology such as the surgical treatment of thyroid cancer and mesothelioma of the *** has published extensively in leading medical journals including Pancreas,Journal of Clinical Oncology,Journal of Gastrointestinal Surgery,and other notable *** also actively leads Columbia Doctors in responding to the challenges associated with rapid innovation,advancing technology,and the highly informed *** has received numerous awards during his career,including the Jerry Gliklich Practitioner of the Year Award,Teaching Award in Surgery for Excellence in Teaching and Mentoring,and has been named multiple times as one of New York Magazine’s Top Doctors.

关键词： Surgery prevention Figure

Mixing of powders and granular materials by mechanical means——A perspective

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Particuology 2012年第4期10卷 397-427页

作者： john Bridgwater Department of Chemical Engineering and Biotechnology University of CambridgePembroke StreetCambridge CB2 3RAUK Laboratory for Simulation and Modeling of Particulate Systems School of Materials Science and EngineeringThe University of New South WalesSydneyNSW 2052Australia

When engineers and scientists encounter the mixing of powders, they enter a subject where it is often difficult to find bearings. This perspective seeks to address this need by setting out the state of prac- tice. It then considers the growing momentum in the area following advances in computation and in measurement that became significant in the 1990s. The mixing of powders and granular materials is of central importance for the quality and performance of a wide range of products. However, process design and operation are very difficult, being largely based on judgement rather than science. There are not even tabulated data to tell how the quality of mixtures depends on mixer selection. Design depends on experience and insight, not science. There are no sound scale-up laws for a given equipment type, largely because particle size needs to be included in any dimensional analysis. Design is not possible by applying physical principles. There is no reliable equation to describe the flow of single component powders, let alone multi-component mixtures. In most cases, measurement has been difficult because the materials are optically opaque. Work in the research literature has been questionable because the results obtained for mixture sampling are affected by sample size. Recently, modern experimental techniques and modelling work have provided a good deal of infor- mation on the behaviour of many of the pieces of equipment, though these have been small in size and often confined to materials of a single size. However, the studies have enhanced knowledge of physical behaviour. For example, for a wide range of equipment when operating at lower velocities, mixing is determined by the number of revolutions of the mixer, not the time. Observations of flow structure have led to a few specific models that should scale with equipment size. Measurement techniques are slowly becoming more effective in giving internal flow patterns and in measuring powder composition. For cohe

关键词： PerspectivePowder mixingMixing of granular materialsCurrent designMixture qualityMixing mechanismsExperiments and computationsResearch trendsOpportunities for advanceSegregationCohesion

Optical monitoring of particle aggregates

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Journal of Environmental Sciences 2009年第1期21卷 2-7页

作者： john Gregory Department of Civil Environmental and Geomatic EngineeringUniversity College London

Methods for monitoring particle aggregation are briefly reviewed. Most of the techniques are based on some form of light scattering and may be greatly dependent on the optical properties of aggregates, which are not generally known. As fractal aggregates grow larger their density can become very low and this has important practical consequences for light scattering. For instance, the scattering coefficient may be much less than for solid objects, which means that the aggregates can appear much smaller than their actual size by a light transmission method. Also, for low-density objects, a high proportion of the scattered light energy is within a small angle of the incident beam, which may also be relevant for measurements with aggregates. Using the ＂turbidity fluctuation＂ technique as an example, it is shown how the apparent size of hydroxide flocs depends mainly on the included impurity particles, rather than the hydroxide precipitate itself. Results using clay suspensions with hydrolyzing coagulants and polymeric floceulants under different string conditions are discussed.

关键词： monitoring method flocculation turbidity fluctuation

SERVICE VALUE NETWORKS:INTO PRACTICE

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Journal of Systems Science and Systems Engineering 2007年第4期16卷 414-423页

作者： john HAMILTON Director of E-Business James Cook UniversityCairns4870Australia

Modeling a business to match its customer perceived （and customer desired） outcomes, remains an on-going task. This paper considers shows how a service value networks （SVNs） approach may be engaged to model, and deliver, understanding of the front-end business and its direct engagement with its immediate （or front-end） customers. These front-end customers may be either：（1） its off-line, in-store customers - engaging directly with the business sales staff （or representative）, or-（2） its on-line, virtual customers - engaging with the business via internet or remote access. In this situation, both the business, and the customer draw upon their respective viewpoints, and both sides influence the interaction. External to these business and customer influences are additional factors that capture the immediate and broader global effects - termed environmental effects. These three business-customer engagement areas of influence are captured by a SVN SEM approach. Without a business-customer encounter of some kind the likelihood of a services business, and a prospecting customer, successfully engaging in an exchange process is reduced. This exchange may be a physical, and/or services exchange, and/or an information and/or ideas exchange. To the business, this encounter is, in effect, a trade, and as a result, the business targets acquiring an economic exchange that will ultimately deliver a net positive economic outcome. To the customer, external and internal information feeds, servicing, perceived value, and satisfaction, are key encounter drivers. SVNs offers a new way to understand the business-customer encounter, and to then utilize this acquired knowledge to either：（1） build a strategic management model, or （2） reengineer its business networks, and to then create a re-positioned, more customer-aligned business operation - one that is capable of delivering win - win, competitive business-customer solutions.

关键词： Service value networks alignment structural equation modeling

Interfacial assembly of two-dimensional MXenes

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Journal of Energy Chemistry 2021年第9期30卷 417-434页

作者： Chuanfang(john)Zhang Laboratory for Functional Polymers Swiss Federal Laboratories for Materials Science and Technology(Empa)ETH DomainUberlandstrasse 129CH-8600 DubendorfSwitzerland

Two-dimensional(2D) transition metal carbides, carbonitrides and nitrides, known as MXenes, are emerging quickly at the frontiers of 2D materials world. Their exotic properties such as the highest electrical conductivity among all solution-processed 2 D materials, the best electromagnetic interference shielding performance outperforming that of copper or aluminum at a nanoscale thickness, as well as the highest volumetric capacitance for pseudocapacitors, have been attracting extensive fundamental research and applications. Their unique surface chemistries, that is, hydrophilic groups terminated on the surface of MXenes after etching and delamination, enable plenty of opportunities for assembling into MXene building blocks. Particularly, assembling at liquid–liquid, liquid–solid, liquid–air, and solid–solid interfaces allows the efficient fabrication of various structures, including MXene surfactants, MXene heterostructures, MXene transparent films. Interfacial assembly of MXenes is of significance in unveiling more versatilities of MXenes as well as impacts on novel MXene-based architectures, based on which enhanced performance of devices is achieved. As such, this review focuses on the interfacial assembly of MXenes, explaining mechanisms behind various assembling and providing classical examples for corresponding interfacial assembling techniques. Applications of these as-assembled architectures are also discussed in brief. We believe this review may shed light on the interfacial chemistry of MXenes, thus guiding more efficient fabrication of MXene-based functional films/coatings/electrodes/devices.

关键词： Interfacial assembly MXene Interfacial tension Crosslinking Heterostructures