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Establishment of human cerebral organoid systems to model early neural development and assess the central neurotoxicity of environmental toxins

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Neural Regeneration Research 2025年第1期20卷 242-252页

作者： Daiyu Hu Yuanqing Cao Chenglin Cai Guangming Wang Min Zhou Luying Peng Yantao Fan Qiong lai Zhengliang Gao Fundamental Research Center Shanghai Yangzhi Rehabilitation Hospital(Shanghai Sunshine Rehabilitation Center)School of MedicineTongji UniversityShanghaiChina Institute of Geriatrics(Shanghai University) Affiliated Nantong Hospital of Shanghai University(The Sixth People’s Hospital of Nantong)Shanghai University School of MedicineNantongJiangsu ProvinceChina Shanghai Engineering Research Center of Organ Repair Shanghai University School of MedicineShanghaiChina key Laboratory of Arrhythmias Ministry of EducationShanghai East HospitalSchool of MedicineTongji UniversityShanghaiChina

Human brain development is a complex process,and animal models often have significant *** address this,researchers have developed pluripotent stem cell-derived three-dimensional structures,known as brain-like organoids,to more accurately model early human brain development and *** enable more consistent and intuitive reproduction of early brain development,in this study,we incorporated forebrain organoid culture technology into the traditional unguided method of brain organoid *** involved embedding organoids in matrigel for only 7 days during the rapid expansion phase of the neural epithelium and then removing them from the matrigel for further cultivation,resulting in a new type of human brain organoid *** cerebral organoid system replicated the temporospatial characteristics of early human brain development,including neuroepithelium derivation,neural progenitor cell production and maintenance,neuron differentiation and migration,and cortical layer patterning and formation,providing more consistent and reproducible organoids for developmental modeling and toxicology *** a proof of concept,we applied the heavy metal cadmium to this newly improved organoid system to test whether it could be used to evaluate the neurotoxicity of environmental *** organoids exposed to cadmium for 7 or 14 days manifested severe damage and abnormalities in their neurodevelopmental patterns,including bursts of cortical cell death and premature *** exposure caused progressive depletion of neural progenitor cells and loss of organoid integrity,accompanied by compensatory cell proliferation at ectopic *** convenience,flexibility,and controllability of this newly developed organoid platform make it a powerful and affordable alternative to animal models for use in neurodevelopmental,neurological,and neurotoxicological studies.

关键词： cadmium cell death cell proliferation cortical development environmental toxins neural progenitor cells neurogenesis neurotoxicology organoids stem cells

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onequilibrium Dynamical Phase Transition of a Three—Dimensional kinetic Heisenberg Spin System

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Chinese Physics Letters 2002年第9期19卷 1344-1346页

作者：邵元智 J.k.L.lai 等 DepartmentofPhysics ZhongshanUniversityGuangzhou510275 DepartmentofPhysicsandMaterialsScience CityUniversityofHongKongKowloonHongKong

We systematically investigate the dynamical response of a three-dimensional kinetic isotropic Heisenberg spin system (HSS) to an external driving field by Monte Carlo numerical simulation. The dynamical response of the isotropic HSS differs obviously from those of the anisotropic Ising spin system in which no real stable ordered state and relevant dynamical phase transition were observed in the kinetic HSS. There is a threshold time after which the magnetization m(t) in the HSS driven by a symmetrical external field always tends asymptotically to a disorder state regardless of the initial state of the system. The threshold time depends on the reduced temperature T/TC of the investigated spin system, amplitude H0 and frequency of the external field, i.e.τ = CωαH0-β(T/TC)-γ. C is a constant equal to 0.0302 for a three-dimensional lattice and exponents α = 1.18±0.01, β = 1.81±0.01 and γ = 1.68±0.01.

关键词： kinetics

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Parallelized volumetric fluorescence microscopy with a reconfigurable coded incoherent light-sheet array

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Light(Science & Applications) 2020年第1期9卷 1914-1924页

作者： Yu-Xuan Ren Jianglai Wu Queenie T.k.lai Hei Ming lai Dickson M.D.Siu Wutian Wu kenneth k.Y.Wong kevin k.Tsia Department of Electrical and Electronic Engineering The University of Hong KongPokfulam RoadHong KongSAR 999077China Department of Physics University of CaliforniaBerkeleyCA 94720USA School of Biomedical Sciences Li Ka Shing Faculty of MedicineThe University of Hong KongHong KongSAR 999077China Department of Psychiatry Faculty of MedicineThe Chinese University of Hong KongHong KongSAR 999077China GHM Institute of CNS Regeneration Jinan University601 Huangpu Avenue WestGuangzhou 510632China Re-Stem Biotechnology Suzhou 215007China

Parallelized fluorescence imaging has been a long-standing pursuit that can address the unmet need for a comprehensive three-dimensional(3D)visualization of dynamical biological processes with minimal ***,the available approaches are limited to incomplete parallelization in only two dimensions or sparse sampling in three *** hereby develop a novel fluorescence imaging approach,called coded light-sheet array microscopy(CLAM),which allows complete parallelized 3D imaging without mechanical *** the concept of an“infinity mirror”,CLAM generates a light-sheet array with controllable sheet density and degree of ***,CLAM circumvents the common complications of multiple coherent light-sheet generation in terms of dedicated wavefront engineering and mechanical dithering/***,the encoding of multiplexed optical sections in CLAM allows the synchronous capture of all sectioned images within the imaged *** demonstrate the utility of CLAM in different imaging scenarios,including a light-scattering medium,an optically cleared tissue,and microparticles in fluidic *** can maximize the signal-to-noise ratio and the spatial duty cycle,and also provides a further reduction in photobleaching compared to the major scanning-based 3D imaging *** flexible implementation of CLAM regarding both hardware and software ensures compatibility with any light-sheet imaging modality and could thus be instrumental in a multitude of areas in biological research.

关键词： scattering light mirror

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HIGHER-ORDER DUALITY FOR A CLASS OF NONDIFFERENTIABLE MULTIOBJECTIVE PROGRAMMING PROBLEMS INVOLVING GENERALIZED TYPE I AND RELATED FUNCTIONS

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Journal of Systems Science & Complexity 2011年第5期24卷 883-891页

作者： S. k. MISHRA Shouyang WANG kin keung lai Department of Mathematics Faculty of Science Banaras Hindu University Varanasi 221005 India Institute of Systems Science Academy of Mathematics and Systems Science Chinese Academy of Sciences Beijing 100190 China Department of Management Sciences City University of Hong Kong Tat Chee Avenue Hong Kong China

This paper extends the class of generalized type I functions introduced by Aghezzaf and Hachimi（2000） to the context of higher-order case and formulate a number of higher-order duals to a non-differentiable multi-objective programming problem and establishes higher-order duality results under the higher-order generalized type I functions introduced in the present paper, A special case that appears repeatedly in the literature is that the support function is the square root of a positive semi-definite quadratic form. This and other special cases can be readily generated from these results.

关键词： Generalized convexity higher order duality non-differentiable nonlinear programming support function.

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Tunable Reactive Wetting of Sn on Microporous Cu Layer

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Journal of Materials Science & Technology 2012年第4期28卷 379-384页

作者： Qingquan lai Lei Zhang Cai Chen J.k.Shang Shenyang National Laboratory for Materials Science Institute of Metal ResearchChinese Academy of SciencesShenyang110016China

Wetting of microporous Cu layer by liquid Sn resulted in contact angles from 0 to 33 deg., tunable by varying wetting temperature and porous microstructure. The wetting was dominated by the interracial metallurgical r... 详细信息

关键词： Wetting Porous material Soldering

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knowledge-driven decision analytics for commercial banking

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Journal of Management Analytics 2020年第2期7卷 209-230页

作者： k.S.Law Fu-lai Chung Department of Computing Hong Kong Polytechnic UniversityHong KongChina

Although the corporate relationship manager seems to be the key enabler in commercial banking,the personal relationship sales model is not a sustainable model for the paradigm shift in digital financial *** this research,we propose a knowledge-driven decision analytics approach to improve the decision ***,most of the corporate client documents processed in banks are not well-structured and the traditional analysis approach does not consider the document structure,which carries rich semantic *** propose a document structure-based text representation approach with incorporating auxiliary information in the predictive analytics of unstructured data to improve the performance in the document classification *** proposed approach significantly outperforms the traditional whole document approach which does not take into considerations of the document *** the proposed approach,knowledge can be effectively and efficiently used for business decisions and planning to improve the competitive advantage and substantiality of banks.

关键词： document classification information retrieval informatics document structure analysis auxiliary information

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Recent advancement of flow-induced piezoelectric vibration energy harvesting techniques:principles,structures,and nonlinear designs

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Applied Mathematics and Mechanics(English Edition) 2022年第7期43卷 959-978页

作者： Dongxing CAO Junru WANG Xiangying GUO S.k.lai Yongjun SHEN Faculty of Materials and Manufacturing Beijing University of TechnologyBeijing 100124China Beijing key Laboratory of Nonlinear Vibrations and Strength of Mechanical Structures Beijing 100124China School of Automation Beijing Information Science and Technology UniversityBeiing 100192China Department of Civil and Environmental Engineering The Hong Kong Polytechnic UniversityKowloonHong KongChina Hong kong Branch of National Rail Transit Electrification and Automation Engineering Technology Research Center The Hong Kong Polytechnic UniversityKowloonHong KongChina State key Laboratory of Mechanical Behavior and System Safety of Traffic Engineering Structures Shijiazhuang Tiedao UniversityShijiazhuang 050043China

Energy harvesting induced from flowing fluids(e.g.,air and water flows)is a well-known process,which can be regarded as a sustainable and renewable energy *** addition to traditional high-efficiency devices(e.g.,turbines and watermills),the micro-power extracting technologies based on the flow-induced vibration(FIV)effect have sparked great concerns by virtue of their prospective applications as a self-power source for the microelectronic devices in recent *** article aims to conduct a comprehensive review for the FIV working principle and their potential applications for energy ***,various classifications of the FIV effect for energy harvesting are briefly introduced,such as vortex-induced vibration(VIV),galloping,flutter,and wake-induced vibration(WIV).Next,the development of FIV energy harvesting techniques is reviewed to discuss the research works in the past three *** application of hybrid FIV energy harvesting techniques that can enhance the harvesting performance is also ***,the nonlinear designs of FIV-based energy harvesters are reported in this study,e.g.,multi-stability and limit-cycle oscillation(LCO)***,advanced FIV-based energy harvesting studies for fluid engineering applications are briefly ***,conclusions and future outlook are summarized.

关键词： vibration-driven energy harvesting flow-induced vibration(FIV) piezoelectric approach nonlinear design

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Activation of human fibroblast-like synoviocytes by uric acid crystals in rheumatoid arthritis

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Cellular & Molecular Immunology 2011年第6期8卷 469-478页

作者： Da P Chen Chun k Wong lai S Tam Edmund k Li Christopher Wk Lam Department of Chemical Pathology The Chinese University of Hong KongPrince of Wales HospitalShatinNTHong KongChina Department of Clinical Laboratory Children’s Hospital of Chongqing Medical UniversityChongqingChina Department of Medicine and Therapeutics The Chinese University of Hong KongPrince of Wales HospitalNgan Shing StreetShatinNTHong KongChina Macao Institute for Applied Research in Medicine and Health Macao University of Science and TechnologyAvenida Wai LongTaipaMacaoChina

Hyperuricemia-mediated uric acid crystal formation may cause joint inflammation and provoke the destruction of joints through the activation of inflammasome-mediated innate immune ***,the immunopathological effects and underlying intracellular regulatory mechanisms of uric acid crystal-mediated activation of fibroblast-like synoviocytes(FLS)in rheumatoid arthritis(RA)have not been ***,we investigated the in vitro effects of monosodium urate crystals,alone or in combination with the inflammatory cytokines tumor-necrosis factor(TNF)-a or interleukin(IL)-1b,on the activation of human FLS from RA patients and normal control subjects and the underlying intracellular signaling mechanisms of treatment with these *** urate crystals were able to significantly increase the release of the inflammatory cytokine IL-6,the chemokine CXCL8 and the matrix metalloproteinase(MMP)-1 from both normal and RA-FLS(all P,0.05).Moreover,the additive or synergistic effect on the release of IL-6,CXCL8 and MMP-1 from both normal and RA-FLS was observed following the combined treatment with monosodium urate crystals and TNF-a or *** experiments showed that the release of the measured inflammatory cytokine,chemokine and MMP-1 stimulated by monosodium urate crystals were differentially regulated by the intracellular activation of extracellular signal-regulated kinase and c-Jun N-terminal kinase pathways but not the p38 mitogen-activated protein kinase *** results therefore provide a new insight into the uric acid crystal-activated immunopathological mechanisms mediated by distinct intracellular signal transduction pathways leading to joint inflammation in RA.

关键词： cytokines fibroblast-like synoviocytes rheumatoid arthritis signal transduction uric acid

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Exploring the synergy of the eyebrain connection:neuromodulation approaches for neurodegenerative disorders through transcorneal electrical stimulation

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Neural Regeneration Research 2024年第10期19卷 2097-2098页

作者： Antara Verma Stephen k.Agadagba Leanne lai-Hang Chan Department of Electrical Engineering City University of Hong KongKowloonHong Kong Special Administrative RegionChina Centre for Eye and Vision Research Ltd. Hong Kong Special Administrative RegionChina Pennsylvania State University University ParkPAUSA

The connection and interaction between the eye and the brain are crucial to understanding brain disorders(Marchesi et al.,2021).Both the eye and the brain have a limited regenerative capacity as there are few progenitor cells,and nerve cells do not ***,neurodegeneration implicates irreversible damage to the central nervous system,as observed in several neurodegenerative diseases(Marchesi et al.,2021).

关键词： stimulation degenerative

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Nanocarrier-mediated siRNA delivery:a new approach for the treatment of traumatic brain injury-related Alzheimer's disease

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Neural Regeneration Research 2025年第9期20卷 2538-2555页

作者： Jie Jin Huajing Zhang Qianying Lu Linqiang Tian Sanqiao Yao Feng lai Yangfan Liang Chuanchuan Liu Yujia Lu Sijia Tian Yanmei Zhao Wenjie Ren Institute of Disaster and Emergency Medicine Tianjin UniversityTianjinChina key Laboratory for Disaster Medicine Technology TianjinChina Henan Medical key Laboratory for Research of Trauma and Orthopedics The Third Affiliated Hospital of Xinxiang Medical UniversityXinxiangHenan ProvinceChina Clinical Medical Center of Tissue Engineering and Regeneration Xinxiang Medical UniversityXinxiangHenan ProvinceChina Institutes of Health Central Plain Xinxiang Medical UniversityXinxiangHenan ProvinceChina School of Public Health Xinxiang Medical UniversityXinxiangHenan ProvinceChina

Traumatic brain injury and Alzheimer's disease share pathological similarities,including neuronal loss,amyloid-βdeposition,tau hyperphosphorylation,blood-brain barrier dysfunction,neuroinflammation,and cognitive ***,traumatic brain injury can exacerbate Alzheimer's disease-like pathologies,potentially leading to the development of Alzheimer's *** offer a potential solution by facilitating the delive ry of small interfering RNAs across the blood-brain barrier for the targeted silencing of key pathological genes implicated in traumatic brain injury and Alzheimer's disease.U nlike traditional approaches to neuro regeneration,this is a molecula r-targeted strategy,thus avoiding non-specific drug *** review focuses on the use of nanocarrier systems for the efficient and precise delive ry of siRNAs,discussing the advantages,challenges,and future *** principle,siRNAs have the potential to target all genes and non-targetable protein s,holding significant promise for treating various *** the various therapeutic approaches currently available for neurological diseases,siRNA gene silencing can precisely"turn off"the expression of any gene at the genetic level,thus radically inhibiting disease progression;however,a significant challenge lies in delivering siRNAs across the blood-brain *** have received increasing attention as an innovative drug delive ry tool fo r the treatment of brain *** are considered a potential therapeutic strategy with the advantages of being able to cross the blood-brain barrier,targeted drug delivery,enhanced drug stability,and multifunctional *** use of nanoparticles to deliver specific modified siRNAs to the injured brain is gradually being recognized as a feasible and effective *** this strategy is still in the preclinical exploration stage,it is expected to achieve clinical translation in the future,creating a new field of molecular tar

关键词： blood-brain barrier cognitive dysfunction exosomes gene silencing immunotherapy inorganic nanomaterials liposome nanoparticles neuroinflammation polymer nanoparticles stem cells

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