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Targeting TrkB–PSD-95 coupling to mitigate neurological disorders

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

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Influence of second phase precipitates on mechanical and in-vitro corrosion behaviour of Mg-4Zn-0.5Ca-0.8Mn alloy in optimum homogenized conditions

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Journal of Magnesium and Alloys 2023年第4期11卷 1343-1366页

作者： Darothi Bairagi Partha duley Manas Paliwal Sumantra Mandal Department of Metallurgical and Materials Engineering Indian Institute of Technology Kharagpur721302India

The present study investigates the mechanical and in-vitro corrosion behavior of Mg-4Zn-0.5Ca-0.8Mn alloy in optimum homogenized *** optimization of the homogenization parameters has been carried out employing thermodynamic calculations and kinetic *** model utilizes the inter-diffusivity of the solute elements and predicts that∼6–24 h of homogenization at 633 K effectively redistributes the elements in the Mg *** on the insights obtained from the simulations,the as-cast Mg-4Zn-0.5Ca-0.8Mn alloy was subjected to homogenization heat treatment process for 6–*** microstructural study through optical microscopy and scanning electron microscopy(SEM)revealed that the interconnected network of second phase precipitates substantially dissolve within 24 h,implying adequate ***,fine Mg-Zn based precipitates with varied morphology and phase fractions also evolved during homogenization treatment,as confirmed through SEM and transmission electron *** the 12 h homogenized specimen,the highest fraction of uniformly dispersed fine precipitates resulted in the highest strength(∼225 MPa).On the other hand,a substantial disruption in coarse precipitate network and lower aspect ratio of fine Mg-Zn precipitates led to the highest ductility(∼8%)in this *** the 24 h homogenized specimen,the ductility reduced marginally owing to higher aspect ratio of fine *** immersion and electrochemical tests(viz.,potentiodynamic polarization and electrochemical impedance spectroscopy)carried out in Hank’s solution revealed that the 24 h homogenized specimen exhibits the best corrosion *** least fraction of Ca_(2)Mg_(6)Zn_(3)phase with maximum disruption in interconnectivity,in combination with a small fraction of fine equilibrium MgZn_(2)precipitates,resulted in suppression of localized corrosion in this *** promotes the formation of the most stable and compact product layer over the specimen,result

关键词： Mg alloy Thermodynamic-kinetic calculation Homogenization EIS Passive film

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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

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Adaption of a commercial lipase kit to measure bile salt-stimulated lipase in human milk

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Food Bioscience 2022年第6期50卷 210-215页

作者： Jie Zhang john.a.duley David M.Cowley Paul N.Shaw Nidhi Bansal School of Agriculture and Food Science The University of QueenslandSt Lucia4072Australia School of Pharmacy The University of QueenslandWoolloongabba4102Australia Mater Research Institute The University of QueenslandSouth Brisbane4101Australia

A highly sensitive,fluorometric method for measuring activities of two major lipases in milk,lipoprotein lipase(LPL)and bile salt-stimulated lipase(BSSL)is *** milk LPL showed linear activity from 65 to 347 U/L(U=1μmol/min)and the quantification limit was theoretically about 65 U/*** human milk BSSL,the linear range was from 10 to 267 U/L and the quantification limit was 18 U/*** mean LPL and BSSL activities were 409±13 U/L and 5263±132 U/L,*** corresponded well to the values reported in *** residual LPL and BSSL activities were reduced dramatically to 21%,and 2%,respectively,when the milk was heated to 55°C;heating to 50°C caused only nominal reductions of LPL and BSSL(activities remaining∼82%and 87%,respectively).No BSSL activity was detected in cow,camel,goat milk or in infant formula.

关键词： Milk Lipoprotein lipase Bile salt-dependent lipase Holder pasteurisation Infant formula Thermal pasteurisation

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Resistive Switching Memory of TiO2 Nanowire Networks Grown on Ti Foil by a Single Hydrothermal Method

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Nano-Micro Letters 2017年第2期9卷 23-31页

作者： Ming Xiao Kevin P.Musselman Walter W.duley Norman Y.Zhou Centre for Advanced Materials Joining University of WaterlooWaterlooON N2L 3G1Canada Waterloo Institute of Nanotechnology University of WaterlooWaterlooON N2L 3G1Canada Department of Mechanics and Mechatronics Engineering University of WaterlooWaterlooON N2L 3G1Canada Department of Physics and Astronomy University of WaterlooWaterlooON N2L 3G1Canada

The resistive switching characteristics of TiO_2 nanowire networks directly grown on Ti foil by a single-step hydrothermal technique are discussed in this paper. The Ti foil serves as the supply of Ti atoms for growth of the TiO_2 nanowires, making the preparation straightforward. It also acts as a bottom electrode for the device. A top Al electrode was fabricated by e-beam evaporation process. The Al/TiO_2 nanowire networks/Ti device fabricated in this way displayed a highly repeatable and electroforming-free bipolar resistive behavior with retention for more than 10~4 s and an OFF/ON ratio of approximately 70. The switching mechanism of this Al/TiO_2 nanowire networks/Ti device is suggested to arise from the migration of oxygen vacancies under applied electric field. This provides a facile way to obtain metal oxide nanowire-based Re RAM device in the future.

关键词： TiO2 nanowire networks Resistive switching memory Ti foil Hydrothermal process Al electrode

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Femtosecond laser irradiation induced heterojunctions between carbon nanofibers and silver nanowires for a flexible strain sensor

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Journal of Materials Science & Technology 2021年第25期84卷 139-146页

作者： Jiayun Feng Yanhong Tian Sumei Wang Ming Xiao Zhuang Hui Chunjin Hang Walter W.duley Y.Norman Zhou State Key Laboratory of Advanced Welding and Joining Harbin Institute of TechnologyHarbin150001China Centre for Advanced Materials Joining University of WaterlooWaterlooOntarioN2L 3G1Canada Laser Micro/Nano-Fabrication Laboratory School of Mechanical EngineeringBeijing Institute of TechnologyBeijing100081China Beijing Key Laboratory of Materials Utilization of Nonmetallic Minerals and Solid Wastes National Laboratory of Mineral MaterialsSchool of Materials Science and TechnologyChina University of GeosciencesBeijing100083China Department of Physics and Astronomy University of WaterlooWaterlooOntarioN2L 3G1Canada

We report the direct joining of carbon nanofibers(CNFs)to silver nanowire(Ag NWs)by controlled irradiation with femtosecond(fs)laser *** separate types of nano-junction dependent on joint geometry,laser fluence and irradiation time are identified in irradiated *** one type of junction,the tip of an Ag NW is melted and flows to form a bond with an adjacent *** second type of junction occurs without significant heating of the Ag NW and involves the softening and flow of carbon in the CNF in response to the transfer of plasmonic energy from the Ag NW into the *** in a T-type joint configuration can be of either kind depending on the relative orientation of the incident optical field and the long axis of the Ag *** simulations were used to explore this effect for different joint geometries and laser *** electrical properties of a heterojunction involving a single Ag NW-CNF structure have been measured,and it is found that the junction resistance can be reduced by six orders of magnitude after laser ***,we have investigated the properties of a strain sensor based on an Ag NW-CNF hybrid nanowire network and find that this device can exhibit high *** sensitivity occurs as nano-junctions induced by fs laser irradiation greatly reduces the initial *** laser-based technique for direct nanojoining of CNF and Ag NWs may enable the design of robust nanowire structures for application in a variety of new devices.

关键词： Nanojoining Carbon nanofiber Silver nanowire Femtosecond laser Strain sensor

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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

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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

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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

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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

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