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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 memory.The 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 potentiation.Postsynaptically,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 potentiation.In 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 depression.Treatment 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 isoform.Although TrkB agonists and antibodies that activate TrkB are being intensively investigated,they cannot distinguish the multiple human TrkB splicing isoforms or cell type-specific functions.Targeting 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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A four-band index for both liquid and solid water and its applications in the Aral Sea Basin

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Science China Earth Sciences 2024年第3期67卷 769-788页

作者： Bing YUE Xi CHEN Saibo LI Zhengping DU john WILSON Junhui YANG Yimen JIAO Shuangyan huang Chenghu ZHOU Xinjiang Institute of Ecology and Geography Chinese Academy of SciencesUrumqi 830011China College of Resources and Environment University of Chinese Academy of SciencesBeijing 100049China Institute of Geographical Sciences and Natural Resources Research Chinese Academy of SciencesBeijing 100101China Spatial Sciences Institute University of Southern CaliforniaLos AngelesCA 90089-0374USA

Various investigations have been conducted to analyze the water-coverage area of the Aral Sea and the Aral Sea Basin(ASB). However, the investigations incorporated considerable uncertainty and the used water indices had misclassification problem, which made different research groups present different results. Thus we first ascertain the boundaries of the ASB, the Syr and Amu river basins as well as their upper, middle and lower reaches. Then a four-band index for both liquid and solid water(ILSW) is proposed to address the misclassification problems of the classic water indices. ILSW is calculated by using the reflectance values of the green, red, near infrared, and thermal infrared bands, which combines the normalized difference water index(NDWI) and land surface temperature(LST) together. Validation results show that the ILSW water index has the highest accuracy by far in the Aral Sea Basin. Our results indicate that annual average decline of the water-coverage area was 963 km^(2) in the southern Aral Sea, whereas the northern Aral Sea has experienced little change. In the meanwhile, permanent ice and snow in upper reach of ASB has retreated considerably. Annual retreating rates of the permanent ice and snow were respectively 6233and 3841 km^(2) in upper reaches of Amu river basin(UARB) and Syr river basin(USRB). One of major reasons is that climate has become warmer in ASB. The climate change has caused serious water deficit problem. The water deficit had an increasing trend since the 1990s and its increasing rates was 3.778 billion m^(3) yearly on average. The total water deficit was 76.967 billion m^(3) on average in the whole area of ASB in the 2010s. However, up reaches of Syr river basin(USRB), a component area of ASB, had water surplus of 25.461 billion m^(3). These conclusions are useful for setting out a sustainable development strategy in ASB.

关键词： Aral Sea Basin Syr river basin Amu river basin Water indices Water-coverage area Water deficit Climate change

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Investigation and mitigation of Mott neuronal oscillation fluctuation in spiking neural network

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Science China(Information Sciences) 2024年第2期67卷 291-301页

作者： Lindong WU Zongwei WANG Lin BAO Linbo SHAN Zhizhen YU Yunfan YANG Shuangjie ZHANG Guandong BAI Cuimei WANG john ROBERTSON Yuan WANG Yimao CAI Ru huang School of Integrated Circuits Peking University Beijing Advanced Innovation Center for Integrated Circuits State Key Laboratory of Information Photonics and Optical Communications Beijing University of Posts and Telecommunications Department of Engineering University of Cambridge

Mott devices, featuring low hardware cost and high energy efficiency, have been demonstrated as a key oscillatory element in artificial neurons to enable spiking neural networks(SNNs) such as conversionbased SNNs(CSNNs). However, there will be inevitably non-ideal fluctuation in the oscillation behavior,causing the accuracy degradation of networks. In this paper, we investigate the Mott neuronal oscillation fluctuation(NOF) through experiments and modeling. The results show that the NOF phenomenon conforms to Gaussian distribution and originates from thermal fluctuation induced switching voltage variations. We construct a two-layer CSNN for image recognition tasks to study the NOF effect and propose the activation function boundary(AFB) method to strengthen the stability of the network. The results indicate that AFB can improve the accuracy of CSNN by up to 15.5% by tightening output distribution.

关键词： Mott neuron oscillation fluctuation variation-aware Mott neuronal model conversion-based spiking neural network activation function boundary

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Gas-phase synthesis of Ti_(2)CCl_(2) enables an efficient catalyst for lithiumsulfur batteries

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The Innovation 2024年第1期5卷 33-40页

作者： Maoqiao Xiang Zihan Shen Jie Zheng Miao Song Qiya He Yafeng Yang Jiuyi Zhu Yuqi Geng Fen Yue Qinghua Dong Yu Ge Rui Wang Jiake Wei Weiliang Wang Haiming huang Huigang Zhang Qingshan Zhu Chuanfang john Zhang State Key Laboratory of Multiphase Complex Systems Institute of Process EngineeringChinese Academy of SciencesBeijing 100190China School of Chemical Engineering University of the Chinese Academy of SciencesBeijing 100049China Innovation Academy for Green Manufacture Chinese Academy of SciencesBeijing 100190China China Nuclear Power Engineering Co. Ltd.117 West Third Ring RoadNorth SectionBeijing 100840China College of Materials Science&Engineering Sichuan UniversityChengdu 610065China State Key Laboratory of Catalysis Dalian Institute of Chemical PhysicsChinese Academy of SciencesDalian 116023China School of Physics Guangdong Province Key Laboratory of Display Material and TechnologyCenter for Neutron Science and TechnologySun Yat-sen UniversityGuangzhou 510275China Solid State Physics&Material Research Laboratory School of Physics and Materials ScienceGuangzhou UniversityGuangzhou 510006China

MXenes have aroused intensive enthusiasm because of their exotic properties and promising applications.However,to date,they are usually synthesized by etching technologies.Developing synthetic technologies provides more opportunities for innovation and may extend unexplored applications.Here,we report a bottom-up gas-phase synthesis of Cl-terminated MXene(Ti_(2)CCl_(2)).The gas-phase synthesis endows Ti_(2)CCl_(2) with unique surface chemistry,high phase purity,and excellent metallic conductivity,which can be used to accelerate polysulfide conversion kinetics and dramatically prolong the cyclability of Li-S batteries.In-depth mechanistic analysis deciphers the origin of the formation of Ti_(2)CCl_(2) and offers a paradigm for tuning MXene chemical vapor deposition.In brief,the gas-phase synthesis transforms the synthesis of MXenes and unlocks the hardly achieved potentials of MXenes.

关键词： synthesis phase lithium

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Car-following strategy of intelligent connected vehicle using extended disturbance observer adjusted by reinforcement learning

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CAAI Transactions on Intelligence Technology 2024年第2期9卷 365-373页

作者： Ruidong Yan Penghui Li Hongbo Gao Jin huang Chengbo Wang School of Traffic and Transportation The Beijing Jiaotong UniversityBeijingChina Department of Automation School of Information Science and TechnologyUniversity of Science and Technology of ChinaHefeiChina School of Vehicle and Mobility The Tsinghua UniversityBeijingChina Liverpool Logistics Offshore and Marine Research Institute(LOOM)Liverpool John Moores UniversityLiverpoolUK

Disturbance observer-based control method has achieved good results in the carfollowing scenario of intelligent and connected vehicle(ICV).However,the gain of conventional extended disturbance observer(EDO)-based control method is usually set manually rather than adjusted adaptively according to real time traffic conditions,thus declining the car-following performance.To solve this problem,a car-following strategy of ICV using EDO adjusted by reinforcement learning is proposed.Different from the conventional method,the gain of proposed strategy can be adjusted by reinforcement learning to improve its estimation accuracy.Since the“equivalent disturbance”can be compensated by EDO to a great extent,the disturbance rejection ability of the carfollowing method will be improved significantly.Both Lyapunov approach and numerical simulations are carried out to verify the effectiveness of the proposed method.

关键词： adaptive system autonomous vehicle intelligent control

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ROS Balance Autoregulating Core-Shell CeO_(2)@ZIF-8/Au Nanoplatform for Wound Repair

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Nano-Micro Letters 2024年第8期16卷 341-361页

作者： Xi Zhou Quan Zhou Zhaozhi He Yi Xiao Yan Liu Zhuohang huang Yaoji Sun Jiawei Wang Zhengdong Zhao Xiaozhou Liu Bin Zhou Lei Ren Yu Sun Zhiwei Chen Xingcai Zhang The Higher Educational Key Laboratory for Biomedical Engineering of Fujian Province Research Center of Biomedical Engineering of XiamenDepartment of BiomaterialsCollege of MaterialsXiamen UniversityXiamen 361005People’s Republic of China Department of Electronic Science Fujian Provincial Key Laboratory of Plasma and Magnetic Resonance ResearchSchool of Electronic Science and EngineeringXiamen UniversityXiamen 361005People’s Republic of China john A Paulson School of Engineering and Applied Sciences Harvard UniversityCambridgeMA 02138USA Department of Otorhinolaryngology Union Hospital of Tongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430022People’s Republic of China NO.1 Middle School Affiliated to Central China Normal University Wuhan 430223People’s Republic of China

Reactive oxygen species(ROS)plays important roles in living organisms.While ROS is a double-edged sword,which can eliminate drug-resistant bacteria,but excessive levels can cause oxidative damage to cells.A core–shell nanozyme,Ce O_(2)@ZIF-8/Au,has been crafted,spontaneously activating both ROS generating and scavenging functions,achieving the multifaceted functions of eliminating bacteria,reducing inflammation,and promoting wound healing.The Au Nanoparticles(NPs)on the shell exhibit high-efficiency peroxidase-like activity,producing ROS to kill bacteria.Meanwhile,the encapsulation of Ce O_(2) core within ZIF-8 provides a seal for temporarily limiting the superoxide dismutase and catalase-like activities of Ce O_(2) nanoparticles.Subsequently,as the ZIF-8 structure decomposes in the acidic microenvironment,the Ce O_(2) core is gradually released,exerting its ROS scavenging activity to eliminate excess ROS produced by the Au NPs.These two functions automatically and continuously regulate the balance of ROS levels,ultimately achieving the function of killing bacteria,reducing inflammation,and promoting wound healing.Such innovative ROS spontaneous regulators hold immense potential for revolutionizing the field of antibacterial agents and therapies.

关键词： Metal-organic framework(MOF) Reactive oxygen species(ROS) Cerium dioxide Au nanoparticles Wound healing

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An In Vitro Investigation of Pulmonary Alveolar Macrophage Cytotoxicity Introduced by Fibrous and Grainy Mineral Dusts

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Acta Geologica Sinica(English Edition) 2006年第4期80卷 589-596页

作者： DONG Faqin DENG Jianjun WU Fengchun PU Xiaoyong john huang FENG Qiming HE Xiaochun Institute of Mineral Materials andApplication Southwest University of Science and Technology Mianyang Sichuan 621002 China Clinical Laboratory Fourth People＇s Hospital ofMianyang Mianyang Sichuan 621000 China Department of Clinical Laboratory Third Military Medical University Chongqing 400038 China Central Analytical Facility Laurentian University Sudbury Ontario P3E 2C6 Canada

In order to study the damage mechanism of mineral dusts on the pulmonary alveolar macrophage （AM）, the changes in their death ratio, malandialdthyde （MDA） content and activities of lactate dehydrogenase （LDH） and superoxide dismutase （SOD） were measured, and the technique of cell culture in vitro was used to investigate the cytotoxicity of six mineral dusts （twelve crystal habits） from twelve mineral deposits. The results show that woUastonite and clinoptilolite have no AM cytotoxicity, while other fibrous and grainy mineral dusts damage pulmonary AM in various degrees. The cytotoxicity of fibrous mineral dusts was greater than that of the grainy ones, and the cytotoxicity of dusts was positively correlated with the active OH- content in dusts, but not necessarily so with its SiO2 content. The high pH values produced by dust was unfavorable for the survival of cells and the dusts with low bio-resistance were safe for cells. The content of variable valence elements in dusts might influence their cytotoxicity and the surface charge of dusts was not a stable factor for their toxicity. It is demonstrated that the shape of mineral dusts was one of the factors affecting cytotoxicity, and that the cytotoxicity of mineral dusts depends mainly on their properties.

关键词： grainy mineral fibrous mineral dust pulmonary alveolar macrophage cytotoxicity

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异形矿物粉尘巨噬细胞毒性研究

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生物医学工程学杂志 2006年第4期23卷 848-851页

作者：董发勤邓建军蒲小允 john huang 西南科技大学矿物材料及其应用研究所绵阳621010 四川省绵阳市第四人民医院绵阳621000 第三军医大学重庆400038 The Central Analytical Facility Laurentian UniversitySudburyOntarioCanada P3E 2C6

为研究粉尘样品对兔肺泡巨噬细胞(AM)产生的不同毒性,探讨巨噬细胞受损的机制,采用体外细胞培养技术,观测兔肺泡巨噬细胞死亡率,丙二醛(M DA)、乳酸脱氢酶(LDH)及超氧化物歧化酶(SOD)的活性及变化。结果表明,沸石、硅灰石无细胞毒性,而... 详细信息

为研究粉尘样品对兔肺泡巨噬细胞(AM)产生的不同毒性,探讨巨噬细胞受损的机制,采用体外细胞培养技术,观测兔肺泡巨噬细胞死亡率,丙二醛(M DA)、乳酸脱氢酶(LDH)及超氧化物歧化酶(SOD)的活性及变化。结果表明,沸石、硅灰石无细胞毒性,而其它的纤维状及颗粒状矿物粉尘则表现出不同程度的细胞毒性。纤维状矿物尘对AM毒性大于颗粒状矿物,毒性程度与粉尘中的活性OH-含量正相关,但并不一定与S iO2含量相关。粉尘所形成的高pH值不利于细胞的生存,低生物持久性的粉尘对人体是安全的。粉尘中变价元素的含量可能影响其毒性。表面电位是粉尘毒性的非稳定因素。矿物尘的微形态是影响其毒性的因素之一,而矿物尘的毒性主要依赖于其特性。

关键词：粒状矿物纤维状矿物粉尘肺泡巨噬细胞细胞毒性

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Materials-oriented integrated design and construction of structures in civil engineering—A review

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Frontiers of Structural and Civil Engineering 2022年第1期16卷 24-44页

作者： Xing MING john C.huang Zongjin LI Institute of Applied Physics and Materials Engineering University of MacaoMacao SAR 999078China CHC Engineering LLCFairfaxVA 20030USA

Design is a goal-oriented planning activity for creating products,processes,and systems with desired functions through specifications.It is a decision-making exploration:the design outcome may vary greatly depending on the designer’s knowledge and philosophy.Integrated design is one type of design philosophy that takes an interdisciplinary and holistic approach.In civil engineering,structural design is such an activity for creating buildings and infrastructures.Recently,structural design in many countries has emphasized a performance-based philosophy that simultaneously considers a structure’s safety,durability,serviceability,and sustainability.Consequently,integrated design in civil engineering has become more popular,useful,and important.Material-oriented integrated design and construction of structures(MIDCS)combine materials engineering and structural engineering in the design stage:it fully utilizes the strengths of materials by selecting the most suitable structural forms and construction methodologies.This paper will explore real-world examples of MIDCS,including the realization of MIDCS in timber seismic-resistant structures,masonry arch structures,long-span steel bridges,prefabricated/on-site extruded light-weight steel structures,fiber-reinforced cementitious composites structures,and fiber-reinforced polymer bridge decks.Additionally,advanced material design methods such as bioinspired design and structure construction technology of additive manufacturing are briefly reviewed and discussed to demonstrate how MIDCS can combine materials and structures.A unified strengthdurability design theory is also introduced,which is a human-centric,interdisciplinary,and holistic approach to the description and development of any civil infrastructure and includes all processes directly involved in the life cycle of the infrastructure.Finally,this paper lays out future research directions for further development in the field.

关键词： integrated design and construction fiber-reinforced concrete fiber-reinforced polymer light-weight steel structures digital fabrication composites

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Adenoviral-mediated localized CTLA-4Ig gene expression induces long-term allograft pancreas survival and donor-specific immune tolerance in rats

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Journal of Medical Colleges of PLA(China) 2008年第6期23卷 313-323页

作者： Chen Xianhua john huang Health Branch Southwest Hospital Third Military Medical University Chongqing 400038 China Department of Medicine University of California San Francisco CA 94143-0780 USA

T cell activation following alloantigen recognition plays a critical role in the development of the rejection in all solid organ, tissue and cell transplantation. A recombinant molecule, cytotoxic T lymphocyte antigen 4 antibody (CTLA-4Ig), is known to induce to T-cell into "anergy" by blocking the costimulatory B7-CD28 interaction. Either systemic or localized administration of CTLA-Ig has been shown to prolong allograft survival and induce donor-specific tolerance in some transplant models. In this study, we characterized the expression and immunosuppressive effectiveness of adenoviral-mediated CTLA-4Ig gene transfer. We demonstrated transduction of the allografts with AdCTLA-4Ig resulted in localized expression, permanent graft survival and stable donor-specific tolerance. In addition, by performing simultaneous dual-organ transplantation, we targeted on immunosuppression through a local expression of CTLA-4Ig via adenoviral-mediated gene transfer into pancreatic allografts.

关键词：细胞毒素抗原免疫抑制耐性糖尿病基因转移

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