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Insect Science 2023年第3期30卷 758-770页

作者： Jianing Yang Di Wang Hui Liu Lin Wang Ling Jin Virpi Ahola Chongren Xu Rongjiang Wang School of Life Sciences Peking UniversityBejingChina Department of Biosciences University of HelsinkiHelsinkiFinland ming wai lau centre for reparative medicine Karolinska InstituteHong KongChina

Temperature is one of the most important environmental factors that affect organisms,especially ectotherms,due to its effects on protein *** the general rules that govern thermostability changes in proteins to adapt high-temperature environments is ***,we report the amino acid substitutions of phosphoglucose isomerase(PGI)related to thermostability in the Glanville fritillary butterfly(Melitaea cinxia,Lepidoptera:Nymphalidae).The PGI encoded by the most common allele in *** in the Chinese population(G3-PGI),which is more thermal tolerant,is more stable under heat stress than that in the Finnish population(D1-PGI).There are 5 amino acid substitutions between G3-PGI and ***-directed mutagenesis revealed that the combination of amino acid substitutions of H35Q,M49T,and I64V may increase PGI *** substitutions alter the 3D structure to increase the interaction between 2 monomers of *** molecular dynamics simulations,it was found that the amino acid at site 421 is more stable in G3-PGI,confining the motion of theα-helix 420-441 and stabilizing the interaction between 2 PGI *** strategy for hightemperature adaptation through these 3 amino acid substitutions is also adopted by other butterfly species(Boloria eunomia,Aglais urticae,Colias erate,and Polycaena lua)concurrent with *** in the Tianshan Mountains of China,i.e.,convergent evolution in butterflies.

关键词： amino acid substitution biochemical adaptation convergent evolution Glanville fritillary butterfly phosphoglucose isomerase thermostability

A near-infrared plasma membrane-specific AIE probe for fluorescence lifetime imaging of phagocytosis

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Science China Chemistry 2022年第5期65卷 979-988页

作者： ming-Yu Wu Jong-Kai Leung Chuen Kam Tsu Yu Chou Jia-Li Wang Xueqian Zhao Shun Feng Sijie Chen ming wai lau centre for reparative medicine Karolinska InstitutetHong KongChina Sichuan Engineering Research Center for Biomimetic Synthesis of Natural Drugs School of Life Science and EngineeringSouthwest Jiaotong UniversityChengdu 610031China

Phagocytosis is a biological process that plays a key role in host defense and tissue *** approaches for real-time imaging of phagocytosis are highly desired but ***,an AIE-active near-infrared fluorescent probe,named TBTCP,was developed for fluorescence lifetime imaging of *** could selectively label the cell plasma membrane with fast staining,wash-free process,high signal-to-background ratio,and excellent *** membrane statuses under different osmolarities as well as macrophage phagocytosis of bacteria or large silica particles in early stages could be reported by the fluorescence lifetime changes of *** with current fluorescence imaging methods,which target the bioenvironmental changes in the late phagocytosis stage,this approach detects the changes in the cell membrane,thus giving a faster response to *** article provides a functional tool to report the phagocytic dynamics of macrophages which may greatly contribute to the studies of phagocytic function-related diseases.

关键词： fluorescence lifetime imaging phagocytosis plasma membrane aggregation-induced emission near-infrared

A Highly Efficient Aggregation-induced Emission Photosensitizer for Photodynamic Combat of Multidrug-resistant Bacteria

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Chemical Research in Chinese Universities 2021年第1期37卷 150-156页

作者： ZOU Qian WANG Jia-Li WU ming-Yu KAM LEE Sin-Ying FENG Shun CHEN Sijie School of Life Science and Engineering Southwest Jiaotong UniversityChengdu610031P.R.China ming wai lau centre for reparative medicine Karolinska InstitutetHong KongP.R.China

With the antibiotic abuse and the resulting increased antibiotic resistance,the bacterial infection has posed a serious threat to human *** therapy is an effective tool for treating localized and superficial *** is a promising approach for the treatment of superbugs and with minimal risk of induced antibiotic ***,an isoquinolinium-based photosensitizer,LIQ-TPE,with aggregation-induced emission properties is designed and *** is with high 1O2 generation efficiency and shows efficient antibacterial performance towards both Gram-negative and Gram-positive bacteria,and even methicillin-resistant Staphylococcus aureus(MRSA).LIQ-TPE thus shows great promise as an effective antimicrobial agent to combat the menace of multi-drug resistant bacteria.

关键词： Aggregation-induced emission Photosensitizer Isoquinolinium Photodynamic antibiosis

An AIE-active probe for efficient detection and high-throughput identification of outer membrane vesicles

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聚集体(英文)

聚集体(英文) 2023年第4期4卷 111-121页

作者： Fei Wang Po-Yu Ho Chuen Kam Quanzhi Yang Jinzhao Liu Weiping Wang Engui Zhao Sijie Chen ming wai lau centre for reparative medicine Karolinska InstitutetHong KongP.R.China Laboratory of Molecular Engineering and Nanomedicine Dr.Li Dak-Sum Research CentreThe University of Hong KongHong KongP.R.China School of Science Harbin Institute of TechnologyShenzhenHIT Campus of University TownShenzhenGuangdongP.R.China

Rapid detection and quantification of outer membrane vesicle(OMV)are of both scientific value and clinical ***,limited tools are available for investigations of ***,we report a novel fluorescent probe with aggregation-induced emission(AIE)characteristics,namely,OEO-TPE-MEM(OTM),for OMV *** emits faintly in an aqueous medium,but its fluorescence could be effectively turned on upon interacting with bacteria bodies and OMVs produced by Gram-negative ***,OTM could provide quantitative information on bacterial membrane remodeling and OMV secretion and be applied to high-throughput screening of OMV-inducing *** study presents a powerful AIE probe for imaging and quantitative analysis of bacteria envelop and derived OMVs,which might be applied for evaluating research and clinical antimicrobial materials in future studies.

关键词： aggregation-induced emission antibiotics bacteria fluorescent probe outer membrane vesicle

Mechanistic connotations of restriction of intramolecular motions(RIM)

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National Science Review 2021年第6期8卷 10-13页

作者： Yujie Tu Zheng Zhao Jacky W.Y.Lam Ben Zhong Tang Department of Chemistry Hong Kong Branch of Chinese National Engineering Research Center for Tissue Restoration and ReconstructionInstitute for Advanced Study and Department of Chemical and Biological EngineeringThe Hong Kong University of Science and Technology Center for Aggregation-Induced Emission SCUT-HKUST Joint Research InstituteState Key Laboratory of Luminescent Materials and DevicesSouth China University of Technology AIE Institute Guangzhou Development District ming wai lau centre for reparative medicine Karolinska Institutet

Molecules are all in constant motions,which influence their properties. For example, in photophysics, the light emission behavior of a luminogen is determined by its electronic and nuclear motions in the excited state. Flexible molecular motions usually favor nonradiative decay along with the transformation of excited-state energy to other forms such as thermal energy. Therefore,the restriction of intramolecular motions(RIM) is commonly adopted to achieve luminescent materials with high emission brightness.

关键词： AGGREGATION-INDUCED EMISSION CONICAL INTERSECTION

Mutation-independent gene knock-in therapy targeting 5′UTR for autosomal dominant retinitis pigmentosa

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Signal Transduction and Targeted Therapy 2023年第4期8卷 1361-1363页

作者： Duc Anh Hoang Baoshan Liao Zongli Zheng Wenjun Xiong Department of Biomedical Sciences City University of Hong KongHong KongChina Key Laboratory of Biochip Technology Biotech and Health CentreShenzhen Research Institute of City University of Hong KongShenzhenChina TUNG Biomedical Sciences centre City University of Hong KongHong KongChina ming wai lau centre for reparative medicine Karolinska InstitutetHong KongChina These authors contributed equally:Duc Anh HoangBaoshan Liao

Dear Editor,Retinitis pigmentosa(RP)is an inherited photoreceptor degeneration disease with high genetic heterogeneity(>90 disease-causing genes according to RetNet:https://***/RetNet/***).Taking a single RP disease gene RHO as an example,there are more than two hundred loss-of-function and gain-of-function mutations identified.1 While gene supplementation therapy has emerged as the most promising treatment for autosomal recessive RP(arRP)and X-linked RP(ClinicalTrials identifier:NCT01482195,NCT03328130,NCT03116113,NCT03252847,NCT03316560),therapeutic approaches to treat autosomal dominant RP(adRP)fall behind due to the low efficiency to disrupt mutant alleles specifically and a broad spectrum of the gain-of-function mutations.

关键词： autosomal degeneration identifier

Genetic evidence for asymmetric blocking of higher-order chromatin structure by CTCF/cohesin

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Protein & Cell 2019年第12期10卷 914-920页

作者： Yujia Lu Jia Shou Zhilian Jia Yonghu Wu Jinhuan Li Ya Guo Qiang Wu MOE Key Lab of Systems Biomedicine Center for Comparative BiomedicineState Key Lab of Oncogenes and Related GenesShanghai Cancer InstituteJoint International Research Laboratory of Metabolic&Developmental SciencesInstitute of Systems BiomedicineXin Hua HospitalShanghai Jiao Tong UniversityShanghai 200240China Present address:ming wai lau centre for reparative medicine Karolinska InstitutetHong KongChina MRC London Institute of Medical Sciences Imperial College LondonLondon W120NNUK

Dear Editor,Similar to higher-order folding of polypeptide chains into functional proteins,linear DNA molecules are spatially folded in a hierarchical and dynamic manner into three-dimensional(3D)functional chromatin structures in eukaryotic nuclei(Huang and Wu,2016;Rowley and Corces,2018).This dynamic folding is closely related to many nuclear processes such as DNA replication and repair,chromosomal translocation,recombination,and segregation,as well as RNA transcription,splicing,and *** particular,dynamic long-distance chromatin looping interactions,which result in close spatial contacts between distal enhancers and target promoters,are thought to play a role in controlling precise spatiotemporal as well as cell-type specific gene expression during animal development(Rowley and Corces,2018).Mammalian genomes contain numerous noncoding regulatory elements that regulate these dynamic long-distance chromatin looping interactions.

关键词： asymmetric precise chains

Three-dimensional (3D) hydrogel serves as a platform to identify potential markers of chondrocyte dedifferentiation by combining RNA sequencing

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Bioactive Materials 2021年第9期6卷 2914-2926页

作者： Yang Ling Weiyuan Zhang Peiyan Wang Wanhua Xie Wei Yang Dong-An Wang Changjiang Fan Institute for Translational medicine The Affiliated Hospital of Qingdao UniversityCollege of MedicineQingdao UniversityQingdao266021ShandongPR China Department of Human Anatomy Histology and Embryology School of Basic MedicineCollege of MedicineQingdao UniversityQingdao266071ShandongPR China School of Basic medicine College of MedicineQingdao UniversityQingdao266071ShandongPR China The Precise medicine Center Shenyang Medical CollegeShenyang110034LiaoningPR China Department of Biomedical Engineering City University of Hong KongKowloonHong KongChina Shenzhen Research Institute City University of Hong KongShenzhen Hi-tech Industrial ParkShenzhenGuangdong518057PR China Karolinska Institute ming wai lau centre for reparative medicine HKSTPSha TinHong KongChina

Dedifferentiation of chondrocyte greatly restricts its function and application,however,it is poorly understood except a small number of canonical *** non-cell-adhesive property endows polysaccharide hydrogel with the ability to maintain chondrocyte phenotype,which can serve as a platform to identify new molecular markers and therapeutic targets of chondrocyte *** this study,the high-throughput RNA sequencing(RNA-seq)was first performed on articular chondrocytes at primary(P0)and passage 1(P1)stages to explore the global alteration of gene expression along with chondrocyte ***,several potential marker genes,such as PFKFB3,KDM6B,had been identified via comparatively analyzing their expression in P0 and P1 chondrocytes as well as in 3D constructs(***-laden alginate hydrogel and HA-MA hydrogel)at both mRNA and protein ***,the changes in cellular morphology and enriched pathway of differentially expressed genes during chondrocyte dedifferentiation was studied in *** study developed the use of hydrogel as a platform to investigate chondrocyte dedifferentiation;the results provided new molecular markers and potential therapeutic targets of chondrocyte dedifferentiation.

关键词： Chondrocyte dedifferentiation Hydrogel Gene expression RNA sequencing

Cancer-associated histone mutation H2BG53D disrupts DNA–histone octamer interaction and promotes oncogenic phenotypes

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Signal Transduction and Targeted Therapy 2020年第1期5卷 2230-2233页

作者： Yi Ching Esther Wan Tsz Chui Sophia Leung Dongbo Ding Xulun Sun Jiaxian Liu Lina Zhu Tze Zhen Evangeline Kang Du Yang Yuchen Zhang Jitian Zhang Chengmin Qian Michael Shing Yan Huen Qing Li Maggie Zi Ying Chow Zongli Zheng Junhong Han Ajay Goel Xin Wang Toyotaka Ishibashi Kui ming Chan Department of Biomedical Sciences City University of Hong KongHong KongChina Key Laboratory of Biochip Technology Biotech and Health CentreShenzhen Research Institute of City University of Hong KongShenzhenChina Division of Life Science Hong Kong University of Science and TechnologyHong KongChina State Key Laboratory of Protein and Plant Gene Research School of Life Sciences and Peking-Tsinghua Center for Life SciencesPeking UniversityPekingChina School of Biomedical Sciences The University of Hong KongHong KongChina ming wai lau centre for reparative medicine Karolinska InstitutetHong KongChina State Key Laboratory of Biotherapy and Cancer Center West China HospitalWest China Medical SchoolSichuan UniversitySichuanChina Department of Molecular Diagnostics and Experimental Therapeutics Beckman Research Institute at City of Hope Comprehensive Cancer CenterDuarteCAUSA

Dear Editor,Recent studies from us and others have deciphered the clinical relevance of a variety of oncohistones1 in different *** H3K27M and H3K36M mutant histones exert dominant-negative effects on methylation levels of histone H3K27 and H3K36 on wildtype histone protein in pediatric brain cancers2–4 and chondroblastoma,5,6 *** contrast to H3K27M and H3K36M that act in trans to cause global reduction of methylation at the respective residues,the H3G34 mutations,including H3G34V/R and H3G34W/L found in pediatric high-grade glioma and giant cell tumor of the bone,affect the H3K36 methylation in cis and alter the H3K36 methylation on the nucleosome containing the H3G34 mutation(s).

关键词： Cancer clinical pediatric

An Aggregation-Induced Emission Optical Highlighter for the Studies of Endoplasmic Reticulum-Lipid Droplet Content Dynamics

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CCS Chemistry 2022年第2期4卷 515-525页

作者： Engui Zhao Chuen Kam ming-Yu Wu Erjing Wang Jiawei Wang Ben Zhong Tang Sijie Chen School of Science School of Electronics and Information EngineeringHarbin Institute of TechnologyShenzhenHIT Campus of University TownShenzhen 518055 ming wai lau centre for reparative medicine Karolinska InstitutetHong Kong 999077 Overseas Expertise Introduction Center for Discipline Innovation(D18025) Collaborative Innovation Center for Advanced Organic Chemical Materials Co-Constructed by the Province and MinistrySchool of Material Science and EngineeringHubei UniversityWuhan 430062 Department of Chemistry The Hong Kong Branch of Chinese National Engineering Research Center for Tissue Restoration and ReconstructionSCUT-HKUST Joint Research InstituteInstitute for Advanced StudyDepartment of Chemical and Biological EngineeringThe Hong Kong University of Science and TechnologyClear Water BayKowloonHong Kong 999077 Shenzhen Institute of Molecular Aggregate Science and Engineering School of Science and EngineeringGuangdong of Electronic and Information EngineeringThe Chinese University of Hong KongShenzhen2001 Longxiang BoulevardLonggang DistrictShenzhen CityGuangdong 518172

The lipid droplet(LD)is a dynamic organelle responsible for lipid storage and metabolism that plays important roles in maintaining lipid ***,limited strategies are available for tracking the LD content *** this contribution,we report a novel fluorescent probe,TPEAmAl,for real-time LD content dynamics ***-AmAl is LD-specific,but emits faintly due to its intramolecular *** photoactivation,it undergoes a photocyclodehydrogenation reaction and shows a large fluorescence ***,it can be used for highlighting selected LDs with high spatial *** measuring the fluorescence changes in the distal region,the lipid content exchange efficiency can be *** our experiment,LD content exchange rate differences between nascent and mature LDs as well as cells with normal and deficient LD budding machinery are *** probe expands the fluorescence-based toolbox for LD content dynamics studies.

关键词： aggregation-induced emission lipid droplet-ER content dynamics optical highlighter photoactivation