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N, N-dimethyltryptamine, a natural psychedelic, rapidly improves spatial memory and hippocampal longterm potentiation: a potential rapid-acting therapy for dementia-associated wandering

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中国药理学与毒理学杂志 2023年第7期37卷 489-490页

作者： CHENG Dan LEI Zhuogui Benjamin Chun-Kit TONG Catherine Kin CHIU LI Ying king-ho cheung ZHANG Zhangjin School of Chinese Medicine the University of HongKong Department of Neuroscience City University of HongKong School of Chinses Medicine and Mr. and Mrs. Ko Chi Ming Centre for Parkinson’s Disease Research HongKong Baptist University Department of Psychology LKS Faculty of Medicine the University of HongKong Department of Chinese Medicine the University of Hong Kong-Shenzhen Hospital

There is no fast-acting treatment strategies against Alzheimer′s disease(AD), in particular dementia-related wandering. N, N-dimethyltryptamine(DMT) is a natural psychedelic that may have rapid-onset nootropic effects. In this study, 5 × FAD transgenic mice which recapitulated amyloid neuropathological features of AD received one single injection of 6 or 12 mg · kg-1DMT and tested at 0.5, 1, and 2 h thereafter in Y-maze for spatial memory. 5×FAD transgenic mice exhibited pronounced decreases in time spent, number entered, and distance travelled in the novel arm of Y-maze. DMT at 12 mg · kg-1partially or completely reversed the three behavioral indices at multiple time points, up to 2 h post injection. The rapid-onset behavioral improvement was consistent with pharmacokinetic analysis of DMT, showing approximately 30 min to reach the maximum concentration in the brain tissue. The transgenic mice also displayed dramatically impaired hippocampal long-term potentiation(LTP), an electrophysiological feature of memory formation and consolidation. DMT potently enhanced LTP and restored intracellular calcium activity, expression and phosphorylation of calcium/calmodulin-dependent protein kinase Ⅱ(CaMKⅡ) and AMPA-type glutamate receptor1(GluR1), the two key calcium-activated mediators involved in LTP induction. Adenosine triphosphate(ATP)is purinergic signalling molecules that are involved in LTP induction and maintenance. DMT rapidly increased mitochondrial ATP dynamics in in vivo and in vitro *** results suggest that DMT rapidly improve spatial memory and hippocampal LTP by restoring the CaMKⅡ-GluR1 signaling pathway and mitochondrial ATP production. It may be served as a fast-acting nootropic agent for the treatment of AD in particular wandering.

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Attenuation of Capacitative Calcium Entry by γ-secretase Cleavage of Stromal Interaction Molecule 1 as a Pathogenic Mechanism for Familial Alzheimer's Disease

Attenuation of Capacitative Calcium Entry by γ-secretase Cl...

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第四届全国痴呆与认知障碍学术研讨会及高级讲授班

作者： Benjamin Chun-Kit Tong king-ho cheung Department of Physiology LKS Faculty of MedicineUniversity of Hong Kong University of hong Kong Shenzhen Institute of Research and Innovation

Abnormalγ-secretase cleavage of amyloid precursor protein(APP)to amyloid beta(Aβ)has been shown to play an important role in Alzheimer’s disease(AD)pathogenesis.γ-secretase is a multimeric intramembranous protease that cleaves various type-I transmembrane *** presenilin-1(PS1)being the catalytic core ofγ-secretase,many FAD-linked PS1 mutations enhance proteolytic activity that

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Fe65-engineered neuronal exosomes encapsulating corynoxine-B ameliorate cognition and pathology of Alzheimer’s disease

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Signal Transduction and Targeted Therapy 2023年第11期8卷 5481-5494页

作者： Ashok Iyaswamy Abhimanyu Thakur Xin-Jie Guan Senthilkumar Krishnamoorthi Tsz Yan Fung Kejia Lu Isha Gaurav Zhijun Yang Cheng-Fu Su Kwok-Fai Lau Kui Zhang Roy Chun-Laam Ng Qizhou Lian king-ho cheung Keqiang Ye Huanhuan Joyce Chen Min Li Mr.&Mrs.Ko Chi-Ming Centre for Parkinson’s Disease Research School of Chinese MedicineHong Kong Baptist UniversityHong Kong SARChina Pritzker School of Molecular Engineering The University of ChicagoChicagoILUSA Ben May Department for Cancer Research The University of ChicagoChicagoILUSA School of Chinese Medicine Hong Kong Baptist UniversityHong Kong SARChina School of Life Sciences The Chinese University of Hong KongHong Kong SARChina Division of Neuroscience School of Biological SciencesFaculty of BiologyMedicine and HealthManchester Academic Health Science CentreUniversity of ManchesterManchesterUnited Kingdom Department of Medicine Li Ka Shing Faculty of MedicineThe University of Hong KongPok Fu LamHong Kong SARChina Prenatal Diagnostic Center and Cord Blood Bank Guangzhou Women and Children’s Medical CenterGuangzhou Medical UniversityGuangzhouChina HKUMed Laboratory of Cellular Therapeutics the University of Hong KongPok Fu LamHong Kong SARChina Faculty of Life and Health Sciences Shenzhen Institutes of Advanced TechnologyChinese Academy of SciencesShenzhenChina

Alzheimer’s disease(AD)is a neurodegenerative disorder characterized by the predominant impairment of neurons in the hippocampus and the formation of amyloid plaques,hyperphosphorylated tau protein,and neurofibrillary tangles in the *** overexpression of amyloid-βprecursor protein(APP)in an AD brain results in the binding of APP intracellular domain(AICD)to Fe65 protein via the C-terminal Fe65-PTB2 interaction,which then triggers the secretion of amyloid-βand the consequent pathogenesis of ***,targeting the interaction between APP and Fe65 can offer a promising therapeutic approach for ***,exosome,a type of extracellular vesicle with diameter around 30–200 nm,has gained much attention as a potential delivery tool for brain diseases,including AD,due to their ability to cross the blood–brain barrier,their efficient uptake by autologous cells,and their ability to be surface-modified with target-specific receptor ***,the engineering of hippocampus neuron cell-derived exosomes to overexpress Fe65,enabled the development of a novel exosome-based targeted drug delivery system,which carried Corynoxine-B(Cory-B,an autophagy inducer)to the APP overexpressed-neuron cells in the brain of AD *** Fe65-engineered HT22 hippocampus neuron cell-derived exosomes(Fe65-EXO)loaded with Cory-B(Fe65-EXO-Cory-B)hijacked the signaling and blocked the natural interaction between Fe65 and APP,enabling APP-targeted delivery of ***,Fe65-EXO-Cory-B induced autophagy in APP-expressing neuronal cells,leading to amelioration of the cognitive decline and pathogenesis in AD mice,demonstrating the potential of Fe65-EXO-Cory-B as an effective therapeutic intervention for AD.

关键词： Alzheimer gained loaded

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Self-synchronization of reinjected droplets for highefficiency droplet pairing and merging

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Microsystems & Nanoengineering 2023年第2期9卷 181-192页

作者： Lang Nan Tianjiao Mao ho cheung Shum Advanced Biomedical Instrumentation Centre Hong Kong Science ParkShatinNew TerritoriesHong KongChina Department of Mechanical Engineering The University of Hong KongPokfulam RoadHong KongChina

Droplet merging serves as a powerful tool to add reagents to moving droplets for biological and chemical ***,unsynchronized droplet pairing impedes high-effciency ***,we develop a microfluidic design for the self-synchronization of reinjected droplets.A periodic increase in the hydrodynamic resistance caused by droplet blocking a T-junction enables automatic pairing of *** inducing spacing,the paired droplets merge downstream under an electric *** blockage-based design can achieve a 100%synchronization efficiency even when the mismatch rate of droplet frequencies reaches 10%.Over 98%of the droplets can still be synchronized at nonuniform droplet sizes and fluctuating reinjection flow ***,the droplet pairing ratio can be adjusted flexibly for on-demand sample *** this system,we merge two groups of droplets encapsulating enzyme/substrate,demonstrating its capacity to conduct multi-step *** also combine droplet sorting and merging to coencapsulate single cells and single beads,providing a basis for high-efficiency single-cell *** expect that this system can be integrated with other droplet manipulation systems for a broad range of chemical and biological applications.

关键词： field merge spacing

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A Versatile Flow-Profile Engineering Method in the Stokes Flow Regime for Complex-Shaped Flows

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Engineering 2021年第5期7卷 655-662页

作者： Zhenyu Yang Lang Nan ho cheung Shum Department of Mechanical Engineering The University of Hong KongHong Kong 999077China

Flow profiles are frequently engineered in microfluidic channels for enhanced mixing,reaction control,and material ***,flow profiles are engineered by inducing inertial secondary flow to redistribute the streams,which can hardly be reproduced in microfluidic environments with negligible inertial *** employed symmetric channel structures also limit the variety of achievable flow ***,each of the flow profiles specifically corresponds to a strictly defined flow condition and cannot be generalized to other flow *** address these issues,we present a systematic method to engineer the flow profile using inertialess secondary *** flow is manipulated in the Stokes regime by deploying a cascaded series of microsteps with various morphologies inside a microchannel to shape the flow *** tuning the shapes of the microsteps,arbitrary outflow profiles can be customized.A numerical profile-transformation program is developed for rapid prediction of the output profiles of arbitrary sequences of predefined *** proposed method allows the engineering of stable flow profiles,including asymmetric ones,over a wide range of flow conditions for complex microfluidic environmental prediction and design.

关键词： Microfluidics Flow profile Stokes flow Hydrodynamic focusing Flow shaping

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A transcription assay for EWS oncoproteins in Xenopus oocytes

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Protein & Cell 2010年第10期1卷 927-934页

作者： king Pan Ng Felix cheung Kevin A.W.Lee Department of Biology The Hong Kong University of Science and TechnologyClear Water BayKowloon Hong KongChina

Aberrant chromosomal fusion of the Ewing's sarcoma oncogene(EWS)to several different cellular partners produces the Ewing's family of oncoproteins(EWSfusion-proteins,EFPs)and associated tumors(EFTs).EFPs are potent transcriptional activators,dependent on the N-terminal region of EWS(the EWS-activationdomain,EAD)and this function is thought to be central to EFT oncogenesis and *** EFPs are promising therapeutic targets,but detailed molecular studies will be pivotal for exploring this *** studies have so far largely been restricted to intact mammalian cells while recent evidence has indicated that a mammalian cell-free transcription system may not support bona fide EAD ***,the lack of manipulatable assays for the EAD presents a significant barrier to *** Xenopus laevis oocytes we describe a plasmid-based micro-injection assay that supports efficient,bona fide EAD transcriptional activity and hence provides a new vehicle for molecular dissection of the EAD.

关键词： EWS/ATF1 Ewing's sarcoma microinjection Xenopus oocytes transcription EWS-activation domain

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A novel adjustable multiple cross-hexagonal search algorithm for fast block motion estimation

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Journal of Zhejiang University-Science A(Applied Physics & Engineering) 2007年第8期8卷 1304-1310页

作者： XIE Chun-lai cheung Chun-ho LIU Wei-zhong Department of Electronic Science and Technology Huazhong University of Science and Technology Wuhan 430074 China hong Kong Institute of Technology Hong Kong China

In this paper,we propose a novel adjustable multiple cross-hexagonal search(AMCHS) algorithm for fast block motion estimation. It employs adjustable multiple cross search patterns(AMCSP) in the first step and then uses half-way-skip and half-way-stop technique to determine whether to employ two hexagonal search patterns(HSPs) subsequently. The AMCSP can be used to find small motion vectors efficiently while the HSPs can be used to find large ones accurately to ensure prediction quality. Simulation results showed that our proposed AMCHS achieves faster search speed,and provides better distortion performance than other popular fast search algorithms,such as CDS and CDHS.

关键词： Motion estimation Fast search algorithm Adjustable search patterns Threshold strategy Hexagonal search pattern

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Multi-element analysis by ArF laser excited atomic fluorescence of laser ablated plumes： Mechanism and applications

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Frontiers of physics 2012年第6期7卷 670-678页

作者： Yue Cai Po-Chun Chu Sut Kam ho Nai-ho cheung Department of Physics Hong Kong Baptist University Kowloon Tong Hong Kong China Faculty of Science and Technology University of Macao Macao China

A new multi-element analysis technique based on laser-excited atomic fluorescence was reviewed. however, the one-wavelength-one-transition constraint was overcome. Numerous elements were induced to fluoresce at a single excitation wavelength of 193 nm. This was possible provided that the analytes were imbedded in dense plumes, such as those produced by pulsed laser ablation. The underlying mechanism of the technique was explained and corroborated. Analytical applications to metals, plastics, ceramics and their composites were discribed. Detection limits in the ng/g range and mass limits of atto moles were demonstrated. Several real-world problems, including the analysis of paint coating for trace lead, the non-destructive analysis of potteries and ink, the chemical profiling of electrode plastic interfaces, and the analysis of ingestible lead colloids were discussed.

关键词： laser-excited atomic fluorescence (LEAF) argon fluoride laser laser plume spectroscopy multi-element analysis

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Oil-mediated high-throughput generation and sorting of water-in-water droplets

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Microsystems & Nanoengineering 2020年第1期6卷 484-493页

作者： Lang Nan Yang Cao Shuai Yuan ho cheung Shum Department of Mechanical Engineering The University of Hong KongPokfulam RoadHong KongChina Department of Electrical and Electronic Engineering The University of Hong KongPokfulam RoadHong KongChina

Aqueous two-phase system(ATPS)droplets have demonstrated superior compatibility over conventional water-in-oil droplets for various biological ***,the ultralow interfacial tension hampers efficient and stable droplet generation,limiting further development and more extensive use of such ***,we present a simple strategy to employ oil as a transient medium for ATPS droplet *** methods based on passive flow focusing and active pico-injection are demonstrated to generate water-water-oil double emulsions,achieving a high generation frequency of~2.4 *** evaporation of the oil to break the double emulsions,the aqueous core can be released to form uniform-sized water-in-water ***,this technique can be used to fabricate aqueous microgels,and the introduction of the oil medium enables integration of droplet sorting to produce single-cell-laden hydrogels with a harvest rate of over 90%.We believe that the demonstrated high-throughput generation and sorting of ATPS droplets represent an important tool to advance droplet-based tissue engineering and single-cell analyses.

关键词： limiting sized compatibility

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Gas marbles: ultra-long-lasting and ultra-robust bubbles formed by particle stabilization

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Frontiers of Chemical Science and Engineering 2022年第11期16卷 1681-1687页

作者： Xuxin Zhao Kunling Yang Zhou Liu ho cheung Shum Tiantian Kong College of Chemistry and Environmental Engineering Shenzhen UniversityShenzhen 518000China Department of Mechanical Engineering University of Hong KongHong KongChina Advanced Biomedical Instrumentation Centre Hong KongChina Department of Biomedical Engineering School of MedicineShenzhen UniversityShenzhen 518000China Department of Urology The Institute of Translational MedicineThe First Affiliated Hospital of Shenzhen UniversityShenzhen Second People’s HospitalShenzhen 518000China

Bubbles and foams are ubiquitous in daily life and industrial *** their dynamic behaviors is of key importance for foam manufacturing processes in food packaging,cosmetics and *** bubbles are inherently fragile and transient;enhancing their robustness and shelf lives is an ongoing *** rupture can be attributed to liquid evaporation,thin film drainage and the nuclei of environmental *** by particle-stabilized interfaces in Pickering emulsions,armored bubbles and liquid marble,bubbles are protected by an enclosed particle-entrapping liquid thin film,and the resultant soft object is termed gas *** gas marble exhibits mechanical strength orders of magnitude higher than that of soap bubbles when subjected to overpressure and underpressure,owing to the compact particle monolayer straddling the surface liquid *** using a water-absorbent glycerol solution,the resulting gas marble can persist for 465 d in normal atmospheric *** particle-stabilizing approach not only has practical implications for foam manufacturing processes but also can inspire the new design and fabrication of functional biomaterials and biomedicines.

关键词： bubble particles interfaces armored bubble liquid marble gas marble Pickering emulsion

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