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Inhibition of the CDK9-cyclin T1 protein-protein interaction as a new approach against triple-negative breast cancer

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Acta Pharmaceutica Sinica B 2022年第3期12卷 1390-1405页

作者： Sha-Sha Cheng Yuan-Qing Qu Jia Wu Guan-Jun Yang Hao Liu Wanhe Wang Qi Huang Feng Chen Guodong Li chun-Yuen wong Vincent Kam wai wong Dik-Lung Ma chung-Hang Leung Institute of Chinese Medical Sciences and State Key Laboratory of Quality Research in Chinese Medicine University of MacaoMacao 999078China Dr.Neher’s Biophysics Laboratory for Innovative Drug Discovery State Key Laboratory of Quality Research in Chinese MedicineMacao University of Science and TechnologyMacao 999078China State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products Ningbo UniversityKow loon TongHong Kong 999077China Laboratory of Biochemistry and Molecular Biology School of Marine SciencesNingbo UniversityNingbo 315211China Department of Chemistry Hong Kong Baptist UniversityNingbo 315211China Institute of Medical Research Northwestern Polytechnical UniversityXi'an 710072China Department of Chemistry City University of Hong KongHong Kong 999077China Department of Biomedical Sciences Faculty of Health SciencesUniversity of MacaoMacao 999078China

Cyclin-dependent kinase 9(CDK9) activity is correlated with worse outcomes of triplenegative breast cancer(TNBC) patients. The heterodimer between CDK9 with cyclin T1 is essential for maintaining the active state of the kinase and targeting this protein-protein interaction(PPI) may offer promising avenues for selective CDK9 inhibition. Herein, we designed and generated a library of metal complexes bearing the 7-chloro-2-phenylquinoline CN ligand and tested their activity against the CDK9cyclin T1 PPI. Complex 1 bound to CDK9 via an enthalpically-driven binding mode, leading to disruption of the CDK9-cyclin T1 interaction in vitro and in cellulo. Importantly, complex 1 showed promising anti-metastatic activity against TNBC allografts in mice and was comparably active compared to cisplatin. To our knowledge, 1 is the first CDK9-cyclin T1 PPI inhibitor with anti-metastatic activity against TNBC. Complex 1 could serve as a new platform for the future design of more efficacious kinase inhibitors against cancer, including TNBC.

关键词： Metal complex Kinase inhibitor Protein-protein interaction Epigenetics Triple-negative breast cancer Metastasis

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Effects of biochar on soil water retention curves of compacted clay during wetting and drying

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Biochar 2022年第1期4卷 1117-1130页

作者： James Tsz Fung wong Ka Lai Chow Xun Wen Chen Charles Wang wai Ng Ming Hung wong Department of Civil and Environmental Engineering The Hong Kong University of Science and TechnologyClear Water BayKowloonHong KongSARChina Department of Geography Hong Kong Baptist UniversityKowloon TongHong KongSARChina Consortium on Health EnvironmentEducation and Research(CHEER)Department of Science and Environmental StudiesThe Education University of Hong KongTai PoHong KongSARChina Guangdong Provincial Key Laboratory of Soil and Groundwater Pollution Control School of Environmental Science and EngineeringSouthern University of Science and TechnologyShenzhen 518055China State Environmental Protection Key Laboratory of Integrated Surface Water Groundwater Pollution Control School of Environmental Science and EngineeringSouthern University of Science and TechnologyShenzhen 518055China

Compacted clay possesses a low water permeability and has been widely used in geo-environmental facilities such as landfill cover *** studies revealed the potential applications of compacted biochar-amended clay(BAC)as an alternative landfill cover ***,the effects of biochar on the soil water retention curves(SWRCs)of clay at low suction are not *** study can help fill this knowledge gap by measuring the wetting and drying SWRCs of clay and BAC(20%biochar).Soils were compacted in instrumented soil columns and subjected to a wetting and drying cycle,and soil water content and suction were measured along with the soil *** was saturated faster when compared with *** drying,the soil water content of clay at 65 mm depth dropped to almost zero,while about 5%of water was retained in *** showed that biochar increased the soil water retention capacity of compacted clay upon *** showed that biochar-clay composite possesses a higher soil water retention capacity at a low soil suction range(<1000 kPa)compared with clay *** revealed the benefits of using compacted biochar-clay composite as a hydraulic barrier to minimize desiccation-induced cracks and potentially promote its serviceability,especially in arid and semi-arid *** composite is also a carbon sink material that can reduce landfill gas emissions and pollutant leaching.

关键词： Soil amendment Biochar-clay composite Soil carbon Soil suction Soil depth

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Virtual reality based multiple life skill training for intellectual disability:A multicenter randomized controlled trial

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Engineered Regeneration 2022年第2期3卷 121-130页

作者： James chung-wai Cheung Ming Ni Andy Yiu-Chau Tam Tim Tin-chun Chan Alyssa Ka-Yan Cheung Ocean Yu-Hong Tsang Chi-Bun Yip Wing-Kai Lam Duo wai-Chi wong Department of Biomedical Engineering Faculty of EngineeringThe Hong Kong Polytechnic UniversityHong Kong 999077China Research Institute for Smart Ageing The Hong Kong Polytechnic UniversityHong Kong 999077China Jockey Club Smart Ageing Hub Department of Biomedical EngineeringFaculty of EngineeringThe Hong Kong Polytechnic UniversityHong Kong 999077China Department of Orthopaedics Pudong New Area People’s Hospital Affiliated to Shanghai Jiaotong UniversityShanghai 201299China Social Service Department Yan Chai HospitalHong Kong 999077China C2 Innovations and Research Limited Hong Kong 999077China Department of Kinesiology Shenyang Sport UniversityShenyang 110102China Sports Information and External Affairs Centre Hong Kong Sports InstituteHong Kong 999077China

Life skill-based training is essential for intellectual disabled individuals to regain autonomy and social *** reality(VR)could deliver a nascent application that is more engaging and *** objective of this study was to evaluate the training effects of the VR-based multiple life skill training program on life skill perfor-mance,self-efficacy,memory,cognitive and behavioral functions via a multicenter randomized controlled trial.A total of 145 intellectual disabled participants were recruited for a randomized controlled trial with three in-tervention arms:VR(n=42);traditional(n=53);and control(n=50).The life skill tasks for the interventions included 1)grocery shopping,2)cooking,and 3)kitchen *** measures were performance scores for the three tasks,self-efficacy scale,digit span score,and Frontal Assessment Battery score,graded by blinded ***-after effects of each group were evaluated using separated Wilcoxon Signed-rank *** sig-nificantly improved cooking,cleaning performance,and memory span,while traditional training significantly improved shopping,cooking,and cleaning *** generalized estimating equation evaluated effects between groups adjusted for age,gender and intelligence quotient(IQ).VR had significantly larger improvement effects in cooking and cleaning than the control group and memory span compared to traditional training and controls *** appeared to be a significant confounder on the training *** work may consider developing artificial intelligence to customize programs depending on IQ level.

关键词： Mental retardation Intellectual development X-reality Immersive rehabilitation Metaverse

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Chronic ulcerative gastroduodenitis as a first gastrointestinal manifestation of Hermansky-Pudlak syndrome in a 10-year-old child

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World Journal of Gastroenterology 2008年第18期14卷 2939-2941页

作者： Anselm Chi-wai Lee Kin-Hung Poon Wing-Hong Lo Lap-Gate wong Department of Pediatrics & Adolescent Medicine Tuen Mun Hospital New Territories Hong Kong 999077 China Department of Clinical Pathology Tuen Mun Hospital New Territories Hong Kong 999077 China

A 10-year-old Chinese boy who had a history of congenital thrombocytopathy presented with severe iron deficiency anemia secondary to chronic gastric inflammation and duodenal ulcerations. Subtle oculocutaneous albinism led to the finding of diminished dense bodies in the platelets under electron microscopy, hence the diagnosis of Hermansky-Pudlak syndrome (HPS). Biopsies from the stomach and duodenum revealed a lymphocytic infiltration in the submucosa, but H pylori infection was absent. The gastroduodenitis responded to the treatment with omeprazole while iron deficiency anemia was corrected by oral iron therapy. HPS is a rare cause of congenital bleeding disorder with multisystemic manifestations. Upper gastrointestinal involvement is rare and should be distinguished from a mere manifestation of the bleeding diathesis.

关键词： Albinism Duodenal ulceration Hermansky-Pudlak syndrome Inflammatory bowel disease Thrombocytopathy

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Genetically modified foods in China and the United States:A primer of regulation and intellectual property protection

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Food Science and Human Wellness 2016年第3期5卷 124-140页

作者： Alice Yuen-Ting wong Albert wai-Kit Chan Albert wai-Kit Chan Intellectual Property Limited Hong Kong Special Administrative Region United States-China Intellectual Property Institute New YorkUSA Law Offices of Albert wai-Kit Chan PLLCNew YorkUSA

Food is a basic and personal necessity to *** of food is a prime factor to consider apart from nutrition,quality and *** modified(GM)foods first came on the market in *** safety,transparency and traceability ofGMfoods are still under hot ***,the market of GM foods is huge and *** affairs and intellectual property(IP)are two critical factors affecting the development and commercial success of a food *** article will take a look at the GM food technology and regulatory framework for GM foods in China and the United *** article will also discuss the unique patent issues and non-patent IP tools for safeguarding the technology in these two countries.

关键词： property modified attractive

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Design of AIEgen-based porphyrin for efficient heterogeneous photocatalytic hydrogen evolution Special Collection:Aggregation-Induced Processes and Functions

Aggregate

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Aggregate 2023年第5期4卷 199-206页

作者： Govardhana Babu Bodedla Muhammad Imran Jianzhang Zhao Xunjin Zhu wai-Yeung wong Department of Applied Biology&Chemical Technology and Research Institute for Smart Energy The Hong Kong Polytechnic UniversityHong KongP.R.China The Hong Kong Polytechnic University Shenzhen Research Institute ShenzhenP.R.China Department of Chemistry Hong Kong Baptist UniversityHong KongP.R.China State Key Laboratory of Fine Chemicals and School of Chemical Engineering Dalian University of TechnologyDalianP.R.China

Tetraphenylethylene(TPE)-conjugated porphyrin TPE-ZnPF is synthesized in high yield and characterized by single-crystal X-ray *** propeller-shaped TPE groups not only enable exceptional aggregation-induced emission(AIE)in the solid state but also abolish the strongπ-πstacking of porphyrin moieties and thus prohibit aggregation-caused quenching(ACQ).TPE-ZnPF aggregates feature longlived photoexcited states,which subsequently suppress non-radiative decay channels and enhance emission ***,its aggregates show more efficient lightharvesting ability due to the Förster resonance energy transfer from the TPE energy donor to the porphyrin core energy acceptor,well-defined nanosphere morphology,and more efficient photoinduced charge separation than the porphyrin Ph-ZnPF,which possesses ACQ and agglomerated *** a result,an excellent photocatalytic hydrogen evolution rate(ηH_(2))of 56.20 mmol g^(‒1)h^(‒1)is recorded for TPE-ZnPF aggregates,which is 94-fold higher than that of the aggregates of Ph-ZnPF(0.60 mmol g^(‒1)h^(‒1))without the TPE groups.

关键词： aggregation-induced emission AIEgen porphyrin π-π-stacking photocatalytic hydrogen evolution

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The clinical association of programmed cell death protein 4(PDCD4) with solid tumors and its prognostic significance:a meta-analysis

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Chinese Journal of Cancer 2016年第12期35卷 683-698页

作者： John Zeng Hong Li Wei Gao wai-Kuen Ho Wen Bin Lei William Ignace Wei Jimmy Yu-wai Chan Thian-Sze wong Department of Surgery The University of Hong KongQueen Mary Hospital Department of Otolaryngology The First Affiliated Hospital of Sun Yat?sen University

Background: Programmed cell death protein 4(PDCD4) is a novel tumor suppressor protein involved in pro?grammed cell death. Its association with cancer progression has been observed in multiple tumor models, but evidence supporting its association with solid tumors in humans remains controversial. This study aimed to determine the clinical signiicance and prognostic value of PDCD4 in solid ***: A systematic literature review was performed to retrieve publications with available clinical informa?tion and survival data. The eligibility of the selected articles was based on the criteria of the Dutch Cochrane Centre proposed by the Meta?analysis Of Observational Studies in Epidemiology group. Pooled odds ratios(ORs), hazard ratios(HRs), and 95% conidence intervals(CIs) for survival analysis were calculated. Publication bias was examined by Begg's and Egger's ***: Clinical data of 2227 cancer patients with solid tumors from 23 studies were evaluated. PDCD4 expression was signiicantly associated with the diferentiation status of head and neck cancer(OR 4.25, 95% CI 1.87–9.66) and digestive system cancer(OR 2.87, 95% CI 1.84–4.48). Down?regulation of PDCD4 was signiicantly associated with short overall survival of patients with head and neck(HR: 3.44, 95% CI 2.38–4.98), breast(HR: 1.86, 95% CI 1.36–2.54), digestive system(HR: 2.12, 95% CI 1.75–2.56), and urinary system cancers(HR: 3.16, 95% CI 1.06–9.41).Conclusions: The current evidence suggests that PDCD4 down?regulation is involved in the progression of several types of solid tumor and is a potential marker for solid tumor prognoses. Its clinical usefulness should be conirmed by large?scale prospective studies.

关键词： Programmed cell death protein 4(PDCD4) Solid tumor Meta-analysis Prognosis Overall survival Disease-free survival Recurrence-free survival

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Optomechanically-induced-transparency cooling of massive mechanical resonators to the quantum ground state

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Science China(Physics,Mechanics & Astronomy) 2015年第5期58卷 46-51页

作者： LIU Yong-chun XIAO Yun-Feng LUAN Xing-Sheng wong Chee Wei State Key Laboratory for Mesoscopic Physics and School of Physics Peking University Collaborative Innovation Center of Quantum Matter Optical Nanostructures Laboratory Columbia University

Ground state cooling of massive mechanical objects remains a difficult task restricted by the unresolved mechanical sidebands. We propose an optomechanically-induced-transparency cooling scheme to achieve ground state cooling of mechanical motion without the resolved sideband condition in a pure optomechanical system with two mechanical modes coupled to the same optical cavity mode. We show that ground state cooling is achievable for sideband resolution ωm/k as low as - 0.003. This provides a new route for quantum manipulation of massive macroscopic devices and high-precision measurements.

关键词： ground state cooling resolved sideband limit optomechanics

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Influence of screw length and diameter on tibial strain energy density distribution after anterior cruciate ligament reconstruction

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Acta Mechanica Sinica 2014年第2期30卷 241-249页

作者： Jie Yao Guan-Ming Kuang Duo wai-Chi wong Wen-Xin Niu Ming Zhang Yu-Bo Fan Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education School of Biological Science and Medical Engineering/National Key Lab of Virtual Reality TechnologyBeihang University Interdisciplinary Division of Biomedical Engineering Faculty of EngineeringThe Hong Kong Polytechnic University Shenzhen Key Laboratory for Innovative Technology in Orthopaedic Trauma Department of Orthopaedics and TraumatologyThe University of Hong Kong-Shenzhen Hospital The University of Hong Kong Tongji University School of Medicine

Postoperative tunnel enlargement has been frequently reported after anterior cruciate ligament（ACL）*** screw,as a surgical implant in ACL reconstruction,may influence natural loading transmission and contribute to tunnel *** aims of this study are（1）to quantify the alteration of strain energy density（SED）distribution after the anatomic single-bundle ACL reconstruction;and（2）to characterize the influence of screw length and diameter on the degree of the SED alteration.A validated finite element model of human knee joint was *** screw length ranging from 20 to 30 mm with screw diameter ranging from 7 to 9 mm were *** the post-operative knee,the SED increased steeply at the extra-articular tunnel aperture under compressive and complex loadings,whereas the SED decreased beneath the screw shaft and nearby the intra-articular tunnel *** the screw length could lower the SED deprivation in the proximal part of the bone tunnel;whereas increasing either screw length or diameter could aggravate the SED deprivation in the distal part of the bone *** the elastic modulus of the screw could lower the bone SED deprivation around the *** consideration of both graft stability and SED alteration,a biodegradable interference screw with a long length is recommended,which could provide a beneficial mechanical environment at the distal part of the tunnel,and meanwhile decrease the bone-graft motion and synovial fluid propagation at the proximal part of the *** findings together with the clinical and histological factors could help to improve surgical outcome,and serve as a preliminary knowledge for the following study of biodegradable interference screw.

关键词： Anterior crucial ligament reconstruction Strain energy density Screw length Screw diameter

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Multifunctional oxygen-enriching nano-theranostics for cancer-specific magnetic resonance imaging and enhanced photodynamic/photothermal therapy

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Nano Research 2020年第5期13卷 1389-1398页

作者： Li Zhang Zhe Yang Jinghua Ren Li Ba Wenshan He chun-Yuen wong Department of Chemistry City University of Hong KongHong KongChina Department of Breast and Thyroid Surgery Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430022China State Key Laboratory of Terahertz and Millimeter Waves City University of Hong KongHong KongChina Cancer Center Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430022China

The combination of photodynamic therapy(PDT)and photothermal therapy(PTT)has attracted much interest in recent years,but non-specific distribution of photosensitizers and intrinsic tumor hypoxic microenvironment have continued to limit its therapeutic *** herein report a nano-theranostic system,denoted as Ce6-CuS/MSN@PDA@MnO2-FA NPs,which combines PDT,PTT,magnetic resonance(MR)imaging with hypoxia-relieving and tumor-targeting *** to this design is the use of mussel-inspired polydopamine(PDA)coating to encapsulate the chlorin e6(Ce6)and copper sulfide nanoparticles(CuS NPs)loaded mesoporous silica nanoparticle(MSN)*** PDA coating not only acts as pH sensitive gatekeeper to prevent the premature release of Ce6 under non-acidic tumor microenvironment(TME),but also facilitates post-functionalization so that hypoxia-relieving MnO2 nano-sheets and tumor-targeting ligand folic acid-PEG-thiol(FA-PEG-SH)can be decorated on the outer part of the drug *** vitro and in vivo measurements clearly demonstrated that all these functionalities worked synergistically as *** system,having a low dark cytotoxicity,can be effectively internalized by 4T1 cells and decrease the cell viability to 2%upon 660 nm/808 nm laser *** in 4T1 tumor-bearing mice can almost be completely destroyed in 2 weeks via combined PDT/*** with the TME-sensitive MR imaging performance demonstrated,Ce6-CuS/MSN@PDA@MnO2-FA NPs represent a multifunctional prototype which holds great potential to be developed into clinical theranostics.

关键词： hypoxia relief MnO2 nano-sheet photodynamic therapy photothermal therapy magnetic resonance imaging

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