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Regulation of cytohesins by their interactors in the nervous system

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Neural Regeneration Research 2023年第10期18卷 2186-2187页

作者： Yuqi Zhai King To Leung kwok-fai lau School of Life Sciences Faculty of ScienceThe Chinese University of Hong KongHong Kong Special Administrative RegionChina

Adenosine diphosphate ribosylation factors(ARFs) are small GTP-binding proteins of the Ras superfamily which are involved in membrane trafficking and actin cytoskeleton *** other small GTPases,their functions are attributed to the cycling of ARF between GTP(active) and GDP (inactive) states through the actions of guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins,respectively.

关键词： Adenosine cycling attributed

FE65:a hub for neurodevelopment

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Neural Regeneration Research 2024年第9期19卷 1883-1884页

作者： Yuqi Zhai laura Lok-Haang Ng Dennis Dik-Long Chau kwok-fai lau School of Life Sciences Faculty of ScienceThe Chinese University of Hong KongHong Kong Special Administrative RegionChina

FE65,initially identified as a binding partner of amyloid precursor protein(APP),is an adaptor protein enriched in the brain and regulated during ***65 belongs to the FE65 protein *** family is comprised of three memb... 详细信息

关键词： family development partner

Emerging roles of the neural adaptor FE65 in neurite outgrowth

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Neural Regeneration Research 2018年第12期13卷 2085-2086页

作者： Wen Li Wai Wa Ray Chan Jacky Chi Ki Ngo kwok-fai lau Shenzhen Institute of Advanced Technology Chinese Academy of Sciences School of Life Sciences Chinese University of Hong Kong

The brain is the third largest organ in the human body and consists of over80 billion neurons（Herculano-Houzel,2009）.Neurons are interconnected by neurite to form a complex neural network that allows the communicati... 详细信息

关键词： FE Emerging roles of the neural adaptor FE65 in neurite outgrowth GEF

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

Roles of the Y chromosome genes in human cancers

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Asian Journal of Andrology 2015年第3期17卷 373-380页

作者： Tatsuo Kido Yun-fai Chris lau Division of Cell and Developmental Genetics Department of Medicine Veterans Affairs Medical Center Institute for Human Genetics University of California San Francisco California 94121 USA

Male and female differ genetically by their respective sex chromosome composition, that is, XY as male and XX as female. Although both X and Y chromosomes evolved from the same ancestor pair of autosomes, the Y chromosome harbors male-specific genes, which play pivotal roles in male sex determination, germ cell differentiation, and masculinization of various tissues. Deletions or translocation of the sex-determining gene, SRY, from the Y chromosome causes disorders of sex development （previously termed as an intersex condition） with dysgenic gonads. failure of gonadal development results not only in infertility, but also in increased risks of germ cell tumor （GCT）, such as gonadoblastoma and various types of testicular GCT. Recent studies demonstrate that either loss of Y chromosome or ectopic expression of Y chromosome genes is closely associated with various male-biased diseases, including selected somatic cancers. These observations suggest that the Y-linked genes are involved in male health and diseases in more frequently than expected. Although only a small number of protein-coding genes are present in the male-specific region of Y chromosome, the impacts of Y chromosome genes on human diseases are still largely unknown, due to lack of in vivo models and differences between the Y chromosomes of human and rodents. In this review, we highlight the involvement of selected Y chromosome genes in cancer development in men.

关键词： germ cell tumors RBMY, Y-linked somatic cancers TSPY Y chromosome

Battle of the sexes: contrasting roles of testis-specific protein Y-encoded (TSPY) and TSPX in human oncogenesis

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Asian Journal of Andrology 2019年第3期21卷 260-269页

作者： Yun-fai Chris lau Yunmin Li Tatsuo Kido Division of Cell and Developmental Genetics Department of Medicine VA Medical Center and Institute for Human Genetics University of California San Francisco CA 94121 USA

The Y-located testis-specific protein Y-encoded (TSPY) and its X-homologue TSPX originated from the same ancestral gene, but act as a proto-oncogene and a tumor suppressor gene, respectively. TSPY has specialized in male-specific functions, while TSPX has assumed the functions of the ancestral gene. Both TSPY and TSPX harbor a conserved SET/NAP domain, but are divergent at flanking structures. Specifically, TSPX contains a C-terminal acidic domain, absent in TSPY. They possess contrasting properties, in which TSPY and TSPX, respectively, accelerate and arrest cell proliferation, stimulate and inhibit cyclin B-CDK1 phosphorylation activities, have no effect and promote proteosomal degradation of the viral HBx oncoprotein, and exacerbate and repress androgen receptor (AR) and constitutively active AR variant, such as AR-V7, gene transactivation. The inhibitory domain has been mapped to the carboxyl acidic domain in TSPX, truncation of which results in an abbreviated TSPX exerting positive actions as TSPY. Transposition of the acidic domain to the C-terminus of TSPY results in an inhibitory protein as intact TSPX. Hence, genomic mutations/aberrant splicing events could generate TSPX proteins with truncated acidic domain and oncogenic properties as those for TSPY. Further, TSPY is upregulated by AR and AR-V7 in ligand-dependent and ligand-independent manners, respectively, suggesting the existence of a positive feedback loop between a Y-located proto-oncogene and male sex hormone/receptors, thereby amplifying the respective male oncogenic actions in human cancers and diseases. TSPX counteracts such positive feedback loop. Hence, TSPY and TSPX are homologues on the sex chromosomes that function at the two extremes of the human oncogenic spectrum.

关键词： androgen receptor AR-V7 cell cycle regulation cyclin B-CDK1 oncogene sex chromosomes sex differences TSPX TSPY tumor suppressor

Spreadsheet quality assurance:a literature review

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Frontiers of Computer Science 2024年第2期18卷 61-82页

作者： Pak-Lok POON Man fai lau Yuen Tak YU Sau-Fun TANG School of Engineering and Technology Central Queensland UniversityMelbourne 3000Australia Department of Computing Technologies Swinburne University of TechnologyHawthorn 3122Australia Department of Computer Science City University of Hong KongHong Kong SAR 999077China The Royal Victorian Eye and Ear Hospital East Melbourne 3002Australia

Spreadsheets are very common for information processing to support decision making by both professional developers and non-technical end ***,business intelligence and artificial intelligence are increasingly popular in the industry nowadays,where spreadsheets have been used as,or integrated into,intelligent or expert systems in various application ***,it has been repeatedly reported that faults often exist in operational spreadsheets,which could severely compromise the quality of conclusions and decisions based on the *** a view to systematically examining this problem via survey of existing work,we have conducted a comprehensive literature review on the quality issues and related techniques of spreadsheets over a 35.5-year period(from January 1987 to June 2022)for target journals and a 10.5-year period(from January 2012 to June 2022)for target *** other findings,two major ones are:(a)Spreadsheet quality is best addressed throughout the whole spreadsheet life cycle,rather than just focusing on a few specific stages of the life cycle.(b)Relatively more studies focus on spreadsheet testing and debugging(related to fault detection and removal)when compared with spreadsheet specification,modeling,and design(related to development).As prevention is better than cure,more research should be performed on the early stages of the spreadsheet life *** by our comprehensive review,we have identified the major research gaps as well as highlighted key research directions for future work in the area.

关键词： decision support system end-user computing end-user programming Excel spreadsheet

Large-area perovskite films for PV applications:A perspective from nucleation and crystallization

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Journal of Energy Chemistry 2021年第8期30卷 626-641,I0013页

作者： Yuanhang Yang Zexu Xue Long Chen Cho fai Jonathan lau Zhiping Wang Key Lab of Artificial Micro-and Nano-Structures of Ministry of Education of China School of Physics and TechnologyWuhan UniversityWuhan 430072China Canadian Solar Inc. Suzhou 215129China School of Microelectronics Wuhan UniversityWuhan 430072China

Perovskite solar cells(PSCs)have attracted significant research interest due to the rapid rise in ***,a large efficiency gap still exists between laboratory-based small devices and industrialoriented large-scale *** of the main reasons for the efficiency losses is the degraded quality and morphology of the deposited large-area films,which is closely associated with crystallization *** this review,we discuss the nucleation and crystallization processes in solution and vaporbased up-scaling deposition methods for large-area perovskite *** review recent scientific achievements and technical developments that have been made in the field of large-area *** present the existing problems that limit the performance of large devices and extensively discuss the key influencing parameters from the perspective of nucleation and crystallization over large *** review highlights the importance of crystallization control in up-scaling fabrications and presents promising strategies towards large-area perovskite-based optoelectronic devices.

关键词： Large area Perovskite solar cells Nucleation Crystallization Solution and vacuum processes

A new osteogenic protein isolated from Dioscorea opposita Thunb accelerates bone defect healing through the mTOR signaling axis

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Bioactive Materials 2023年第9期27卷 429-446页

作者： John Akrofi Kubi Augustine Suurinobah Brah Kenneth Man Chee Cheung Yin lau Lee Kai-fai Lee Stephen Cho Wing Sze Wei Qiao Kelvin Wai-kwok Yeung Department of Orthopaedics and Traumatology Li Ka Shing Faculty of MedicineThe University of Hong Kong(HKU)Hong Kong S.A.R.PR China Shenzhen Key Laboratory for Innovative Technology in Orthopaedic Trauma HKU-Shenzhen HospitalShenzhen518053PR China Department of Obstetrics and Gynaecology Li Ka Shing Faculty of MedicineHKU21 Sassoon RoadHong Kong S.A.RPR China Shenzhen Key Laboratory of Fertility Regulation Reproductive Medicine CenterHKU-Shenzhen HospitalShenzhenPR China Department of Biology Faculty of ScienceHong Kong Baptist UniversityKowloon TongHong Kong S.A.RPR China Golden Meditech Center for NeuroRegeneration Sciences Hong Kong Baptist UniversityKowloon TongHong Kong S.A.RPR China Applied Oral Sciences and Community Dental Care Faculty of DentistryHong Kong S.A.RPR China

Delayed bone defect repairs lead to severe health and socioeconomic impacts on patients. Hence, there are increasing demands for medical interventions to promote bone defect healing. Recombinant proteins such as BMP-2 have been recognized as one of the powerful osteogenic substances that promote mesenchymal stem cells (MSCs) to osteoblast differentiation and are widely applied clinically for bone defect repairs. However, recent reports show that BMP-2 treatment has been associated with clinical adverse side effects such as ectopic bone formation, osteolysis and stimulation of inflammation. Here, we have identified one new osteogenic protein, named ‘HKUOT-S2’ protein, from Dioscorea opposita Thunb. Using the bone defect model, we have shown that the HKUOT-S2 protein can accelerate bone defect repair by activating the mTOR signaling axis of MSCs-derived osteoblasts and increasing osteoblastic biomineralization. The HKUOT-S2 protein can also modulate the transcriptomic changes of macrophages, stem cells, and osteoblasts, thereby enhancing the crosstalk between the polarized macrophages and MSCs-osteoblast differentiation to facilitate osteogenesis. Furthermore, this protein had no toxic effects in vivo. We have also identified HKUOT-S2 peptide sequence TKSSLPGQTK as a functional osteogenic unit that can promote osteoblast differentiation in vitro. The HKUOT-S2 protein with robust osteogenic activity could be a potential alternative osteoanabolic agent for promoting osteogenesis and bone defect repairs. We believe that the HKUOT-S2 protein may potentially be applied clinically as a new class of osteogenic agent for bone defect healing.

关键词： Dioscorea spp protein Mesenchymal stem cells(MSCs) Osteoblast differentiation Bone mineral density(BMD) Bone defect repair mTOR signaling pathway