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Analogous comparison unravels heightened antiviral defense and boosted viral infection upon immunosuppression in bat organoids

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Signal Transduction and Targeted Therapy 2023年第1期8卷 276-287页

作者： Xiaojuan Liu Cun Li Zhixin Wan Man Chun Chiu Jingjing Huang Yifei Yu Lin Zhu Jian-Piao Cai Lei Rong You-qiang Song Hin Chu Zongwei Cai Shibo Jiang Kwok-yung Yuen Jie Zhou Department of Microbiology School of Clinical MedicineLi Ka Shing Faculty of MedicineThe University of Hong KongHong KongChina State Key Laboratory of Environmental and Biological Analysis Department of ChemistryHong Kong Baptist UniversityHong KongChina Department of medicine The University of Hong KongShenzhen HospitalShenzhenGuangdongChina School of Biomedical Sciences State Key Laboratory of Brain and Cognitive SciencesThe University of HongkongHong KongChina State Key Laboratory of Emerging Infectious Diseases Carol Yu Centre for InfectionThe University of Hong KongHong KongChina Centre for Virology Vaccinology and TherapeuticsHong Kong Science and Technology ParkHong KongChina Key Laboratory of Medical Molecular Virology(MOE/NHC/CAMS) Institute of Infectious Disease and BiosecuritySchool of Basic Medical SciencesFudan UniversityShanghaiChina

Horseshoe bats host numerous SARS-related coronaviruses without overt disease *** intestinal organoids,a unique model of bat intestinal epithelium,allow direct comparison with human intestinal *** sought to unravel the cellular mechanism(s)underlying bat tolerance of coronaviruses by comparing the innate immunity in bat and human *** optimized the culture medium,which enabled a consecutive passage of bat intestinal organoids for over one *** expression levels of IFNs and IFN-stimulated genes were higher in bat organoids than in their human ***,bat organoids mounted a more rapid,robust and prolonged antiviral defense than human organoids upon Poly(I:C)***3 and RLR might be the conserved pathways mediating antiviral response in bat and human intestinal *** susceptibility of bat organoids to a bat coronavirus CoV-HKU4,but resistance to EV-71,an enterovirus of exclusive human origin,indicated that bat organoids adequately recapitulated the authentic susceptibility of bats to certain ***,TLR3/RLR inhibition in bat organoids significantly boosted viral growth in the early phase after SARS-CoV-2 or CoV-HKU4 ***,the higher basal expression of antiviral genes,especially more rapid and robust induction of innate immune response,empowered bat cells to curtail virus propagation in the early phase of infection.

关键词： boost comparison mounted

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Gradient descent decomposition of force-field motor primitives optogenetically elicited for motor mapping of the murine lumbosacral spinal cord

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Zoological Research 2023年第3期44卷 604-619页

作者： Paola Salmas Vincent C.K Cheung School of Biomedical Sciences and Gerald Choa Neuroscience InstituteThe Chinese University of Hong KongHong Kong SARChina Kunming institute of Zoology-The Chinese University of hong kong(KIZ-CUHK)Joint Laboratory of Bioresources and Molecular Research of Common Diseases Hong Kong SARChina

Generating diverse motor behaviors critical for survival is a challenge that confronts the central nervous system(CNS)of all *** movement execution,the CNS performs complex calculations to control a large number of neuromusculoskeletal *** theory of modular motor control proposes that spinal interneurons are organized in discrete modules that can be linearly combined to generate a variety of behavioral *** modules have been previously represented as stimulus-evoked force fields(FFs)comprising isometric limb-endpoint forces across workspace ***,we ask whether FFs elicited by different stimulations indeed represent the most elementary units of motor control or are themselves the combination of a limited number of even more fundamental motor *** probe for potentially more elementary modules,we optogenetically stimulated the lumbosacral spinal cord of intact and spinalized Thy1-ChR2 transgenic mice(n=21),eliciting FFs from as many single stimulation loci as possible(20-70 loci per mouse)at minimally necessary *** found that the resulting varieties of FFs defied simple categorization with just a few *** used gradient descent to further decompose the FFs into their underlying basic force fields(BFFs),whose linear combination explained FF *** mice,we identified 4-5 BFFs with partially localizable but overlapping representations along the spinal *** BFFs were structured and topographically distributed in such a way that a rostral-to-caudal traveling wave of activity across the lumbosacral spinal cord may generate a swing-to-stance gait *** BFFs may represent more rudimentary submodules that can be flexibly merged to produce a library of motor modules for building different motor behaviors.

关键词： Motor mapping Optogenetics Spinal cord Motor primitives Traveling wave

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Editorial:minor stroke is not minor

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Stroke & Vascular Neurology 2023年第3期8卷 175-177页

作者： Xinyi Leng David Wang medicine&Therapeutics The Chinese University of Hong KongHong KongChina Barrow Neurological institute Petznick Stroke Center PhoenixAZUSA

Defining minor stroke can be complicated.A minor stroke can be called a mini or small *** is often defined by the severity of neurological deficit,size of ischaemic lesion(s)on neuroimaging,and level of *** definition... 详细信息

关键词： minor severity transient

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Ferroptosis and glaucoma: implications in retinal ganglion cell damage and optic nerve survival

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Neural Regeneration Research 2023年第3期18卷 545-546页

作者： Ming Yang Kwok-Fai So Wai-Ching Lam Amy Cheuk Yin Lo Department of Ophthalmology School of Clinical MedicineLi Ka Shing Faculty of MedicineThe University of Hong KongHong Kong Special Administrative RegionChina State Key Laboratory of Brain and Cognitive Sciences The University of Hong KongHong Kong Special Administrative RegionChina GHM institute of CNS Regeneration Jinan UniversityGuangzhouGuangdong ProvinceChina

Glaucoma and visual pathway degeneration:Glaucoma is the leading cause of irreversible blindness worldwide,which leads to a progressive loss of *** can be classified into two types:primary open-angle glaucoma and primary closed-angle *** open-angle glaucoma can be caused by the blockage of the trabecular meshwork,and this results in elevation of the intraocular pressure(IOP),leading to retinal ganglion cell(RGC)***,many glaucoma patients have normal IOP;this is known as normal-tension ***,excitotoxic damage and oxidative stress can also lead to RGC damage in normal-tension glaucoma(Almasieh et al.,2012).Glaucomatous genes such as TIGR,OPTN,and CYP1B1 have been suggested to contribute to the pathogenesis of ***,some glaucomatous patients may remain asymptomatic in the early,moderate,and late *** type of glaucoma is primary closed-angle *** this clinical condition,a relative pupillary block is contributed by the iris obstructing aqueous *** patients may suffer from corneal swelling,headache,nausea,and blurred vision during the acute phase.

关键词： glaucoma damage degeneration

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Exacerbated VEGF up-regulation accompanies diabetes-aggravated hemorrhage in mice after experimental cerebral ischemia and delayed reperfusion

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Neural Regeneration Research 2022年第7期17卷 1566-1575页

作者： Angela Ka Wai Lai Tsz Chung Ng Victor Ka Lok Hung Ka Cheung Tam Chi Wai Cheung Sookja Kim Chung Amy Cheuk Yin Lo Department of Ophthalmology Li Ka Shing Faculty of MedicineThe University of Hong KongHong Kong Special Administration RegionChina Department of Anesthesiology Laboratory and Clinical Research Institute for PainThe University of Hong KongHong Kong Special Administration RegionChina Macao University of Science and Technology TaipaMacao Special Administration RegionChinaSchool of Biomedical SciencesThe State Key Laboratory of Pharmaceutical BiotechnologyThe University of Hong KongHong Kong Special Administration RegionChina

Reperfusion therapy is the preferred treatment for ischemic stroke,but is hindered by its short treatment window,especially in patients with diabetes whose reperfusion after prolonged ischemia is often accompanied by exacerbated *** mechanisms underlying exacerbated hemorrhage are not fully *** study aimed to identify this mechanism by inducing prolonged 2-hour transient intraluminal middle cerebral artery occlusion in diabetic Ins2Akita/+mice to mimic patients with diabetes undergoing delayed mechanical *** results showed that at as early as 2 hours after reperfusion,Ins2Akita/+mice exhibited rapid development of neurological deficits,increased infarct and hemorrhagic transformation,together with exacerbated down-regulation of tight-junction protein ZO-1 and upregulation of blood-brain barrier-disrupting matrix metallopeptidase 2 and matrix metallopeptidase 9 when compared with normoglycemic Ins2+/+*** indicated that diabetes led to the rapid compromise of vessel integrity immediately after reperfusion,and consequently earlier death and further aggravation of hemorrhagic transformation 22 hours after *** observation was associated with earlier and stronger up-regulation of pro-angiogenic vascular endothelial growth factor(VEGF)and its downstream phospho-Erk1/2 at 2 hours after reperfusion,which was suggestive of premature angiogenesis induced by early VEGF up-regulation,resulting in rapid vessel disintegration in diabetic *** reticulum stress-related pro-apoptotic C/EBP homologous protein was overexpressed in challenged Ins2Akita/+mice,which suggests that the exacerbated VEGF up-regulation may be caused by overwhelming endoplasmic reticulum stress under diabetic *** conclusion,the results mimicked complications in patients with diabetes undergoing delayed mechanical thrombectomy,and diabetes-induced accelerated VEGF up-regulation is likely to underlie exacerbated hemorrhagic transformat

关键词： blood-brain barrier brain injury diabetes mellitus hemorrhagic transformation infarct ischemia/reperfusion injury middle cerebral artery occlusion mouse model stroke vascular endothelial growth factor

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Drug discovery of sclerostin inhibitors

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Acta Pharmaceutica Sinica B 2022年第5期12卷 2150-2170页

作者： Sifan Yu Dijie Li Ning Zhang Shuaijian Ni Meiheng Sun Luyao Wang Huan Xiao Dingdong Liu Jin Liu Yuanyuan Yu Zongkang Zhang Samuel Tin Yui Yeung Shu Zhang Aiping Lu Zhenlin Zhang Baoting Zhang Ge Zhang Law Sau Fai institute for Advancing Translational medicine in Bone and Joint Diseases School of Chinese MedicineHong Kong Baptist UniversityKowloon TsaiHong Kong 999077China institute of Integrated Bioinfomedicine and Translational Science School of Chinese MedicineHong Kong Baptist UniversityKowloon TsaiHong Kong 999077China institute of Precision medicine and Innovative Drug Discovery HKBU Institute for Research and Continuing EducationShenzhen 518000China School of Chinese medicine Faculty of Medicinethe Chinese University of Hong KongHong Kong 999077China The Key Laboratory of Aerospace medicine Ministry of EducationAir Force Medical UniversityXi’an 710000China Shanghai Clinical Research Center of Bone Disease Department of Osteoporosis and Bone DiseasesShanghai Jiao Tong University Afﬁliated Sixth People’s HospitalShanghai 200000China

Sclerostin, a protein secreted from osteocytes, negatively regulates the WNT signaling pathway by binding to the LRP5/6 co-receptors and further inhibits bone formation and promotes bone resorption. Sclerostin contributes to musculoskeletal system-related diseases, making it a promising therapeutic target for the treatment of WNT-related bone diseases. Additionally, emerging evidence indicates that sclerostin contributes to the development of cancers, obesity, and diabetes, suggesting that it may be a promising therapeutic target for these diseases. Notably, cardiovascular diseases are related to the protective role of sclerostin. In this review, we summarize three distinct types of inhibitors targeting sclerostin, monoclonal antibodies, aptamers, and small-molecule inhibitors, from which monoclonal antibodies have been developed. As the first-in-class sclerostin inhibitor approved by the U.S. FDA,the monoclonal antibody romosozumab has demonstrated excellent effectiveness in the treatment of postmenopausal osteoporosis;however, it conferred high cardiovascular risk in clinical trials. Furthermore,romosozumab could only be administered by injection, which may cause compliance issues for patients who prefer oral therapy. Considering these above safety and compliance concerns, we therefore present relevant discussion and offer perspectives on the development of next-generation sclerostin inhibitors by following several ways, such as concomitant medication, artificial intelligence-based strategy, druggable modification, and bispecific inhibitors strategy.

关键词： Sclerostin WNT signalling pathway Sclerostin inhibitors Antibody Bone diseases Aptamer Small molecule inhibitors Artificial intelligence

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Atypical electrocardiographic manifestations of ischemia: a case of dynamic Wellens patterns

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Journal of Geriatric Cardiology 2018年第11期15卷 710-712页

作者： Alex Tsz Lai Ngan RN Cynthia Yeung Lorraine Chiang Tong LIU Gary Tse Ka Hou Christien Li Department of medicine and Therapeutics Faculty of Medicine Chinese University of Hong Kong Hong Kong China Li Ka Shing institute of Health Sciences Faculty of Medicine Chinese University of Hong Kong Hong Kong China Department of medicine Queen's University Kingston Ontario Canada Li Ka Shing Faculty of medicine University of Hong Kong Hong Kong China Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease Department of Cardiology Tianjin Institute of Cardiology the Second Hospital of Tianjin Medical University Tianjin China Faculty of medicine Newcastle University NewcastleUK

A 55-year-old male with hypertension, hyperlipidemia, impaired fasting glucose, obesity, gout, and osteoarthritis, statin-induced myopathy, but no known cardiac disease, presented with a one day history of intermittent exertional chest discomfort without radiation. Symptoms included sweating, dyspnea, dizziness, and upper limb numbness.

关键词： Dynamic pattern Ischemia Wellens

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Analgesic Effect of Sinew Acupuncture for Patients with Soft-Tissue Injuries: A Pilot Trial

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Chinese Journal of integrative medicine 2019年第8期25卷 613-616页

作者： CHEN Hai-yong LIU Nong-yu School of Chinese medicine The University of Hong Kong Hong Kong SARChina The Second School of Clinical medicine Nanjing University of Traditional Chinese Medicine Nanjing (210023)China

Objective: To investigate the immediate analgesic effect of sinew acupuncture for patients with soft-tissue injuries (STIs). Methods: Two hundreds eligible adult patients suffering from STIs were recruited and received sinew acupuncture with flexible treatment schedules. The number of treatment sessions was pragmatically decided by each patient on the basis of their pain relief. The outcome measurement was the change of pain rating in the Visual Analogue Scale (VAS) during the first 5 sessions. The adverse effect was also observed. Results: Of the 200 patients recruited, 7 were excluded due to incomplete data. In total, 888 sinew acupuncture treatments were administered to patients at 14 injury sites (including head, neck, shoulder, arm, chest, elbow, wrist, hand, waist and hip, knee, thigh, calf, ankle, and foot) where pain was felt. Compared with the baseline, the VAS rating after the first and last treatments were both significantly reduced at all the injury sites (P<0.01). The VAS rating was also significantly reduced after each session of treatment in the first five sessions (P<0.01). No serious adverse effect was observed. Conclusion: Sinew acupuncture had not only an immediate analgesic effect for STIs, but also an accumulated analgesic effect during the first 5 treatment sessions.

关键词： sinew acupuncture soft-tissue injury analgesic effect pain Visual Analogue Scale

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The combined role of MRI prostate and prostate health index in improving detection of significant prostate cancer in a screening population of Chinese men

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Asian Journal of Andrology 2023年第6期25卷 674-679页

作者： Peter KF Chiu Thomas YT Lam Chi-Fai Ng Jeremy YC Teoh Carmen CM Cho Hiu-Yee Hung Cindy hong Monique J Roobol Winnie CW Chu Samuel YS Wong Joseph JY Sung SH Ho Urology Centre Department of SurgeryThe Chinese University of Hong KongHong Kong SARChina The Jockey Club School of Public Health and Primary Care The Chinese University of Hong KongHong Kong SARChina Department of Imaging and Interventional Radiology The Chinese University of Hong KongHong Kong SARChina Erasmus MC Cancer institute Erasmus Medical UniversityRotterdam 3015The Netherlands Lee kong Chian School of medicine Nanyang Technological UniversitySingapore 308232Singapore

Using prostate-specific antigen(PSA)for prostate cancer(PCa)screening led to overinvestigation and overdiagnosis of indolent *** aimed to investigate the value of prostate health index(PHI)and magnetic resonance imaging(MRI)prostate in an Asian PCa screening *** aged 50–75 years were prospectively recruited from a community-based PSA screening *** with PSA 4.0–10.0 ng ml^(−1) had PHI result *** prostate was offered to men with PSA 4.0–50.0 ng ml−1.A systematic prostate biopsy was offered to men with PSA 4.0–9.9 ng ml^(−1) and PHI≥35,or PSA 10.0–50.0 ng ml^(−1).Additional targeted prostate biopsy was offered if they had PI-RADS score≥*** significant PCa(csPCa)was defined as the International Society of Urological Pathology(ISUP)grade group(GG)≥2 or ISUP GG 1 with involvement of≥30%of total systematic *** total,12.8%(196/1536)men had PSA≥4.0 ng ml^(−1).Among 194 men with PSA 4.0–50.0 ng ml^(−1),187(96.4%)received MRI *** them,28.3%(53/187)had PI-RADS≥3 ***,7.0%(107/1536)men were indicated for biopsy and 94.4%(101/107)men received *** the men received biopsy,PCa,ISUP GG≥2 PCa,and csPCa was diagnosed in 42(41.6%),24(23.8%),and 34(33.7%)men,*** with PSA/PHI pathway in men with PSA 4.0–50.0 ng ml^(−1),additional MRI increased diagnoses of PCa,ISUP GG≥2 PCa,and csPCa by 21.2%(from 33 to 40),22.2%(from 18 to 22),and 18.5%(from 27 to 32),*** benefit of additional MRI was only observed in PSA 4.0–10.0 ng ml^(−1),and the number of MRI needed to diagnose one additional ISUP GG≥2 PCa was 20 in PHI≥35 and 94 in PHI<*** them,45.4%(89/196)men with PSA≥4.0 ng ml^(−1) avoided unnecessary biopsy with the use of PHI and MRI.A screening algorithm with PSA,PHI,and MRI could effectively diagnose csPCa while reducing unnecessary *** benefit of MRI prostate was mainly observed in PSA 4.0–9.9 ng ml^(−1) and PHI≥35 *** was an important risk stratification step for PCa

关键词： magnetic resonance imaging prostate prostate cancer prostate health index prostate-specific antigen screening

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Molecular Characterization of Plant Prevacuolar and Endosomal Compartments

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Journal of integrative Plant Biology 2007年第8期49卷 1119-1128页

作者： Sheung Kwan Lam Yu Chung Tse Yansong Miao hong-Ye Li Junqi Wang Sze Wan Lo Liwen Jiang Department of Biology and Molecular Biotechnology Program The Chinese University of Hong Kong Shatin New Territories Hong Kong China institute of Plant Molecular Biology & Agricultural Biotechnology The Chinese University of Hong Kong Shatin New Territories Hong Kong China

Prevacuolar compartments （PVCs） and endosomal compartments are membrane-bound organelles mediating protein traffic to vacuoles in the secretory and endocytic pathways of plant cells. Over the years, great progress has been made towards our understanding in these two compartments in plant cells. In this review, we will summarize our contributions toward the identification and characterization of plant prevacuolar and endosomal compartments. Our studies will serve as important steps in future molecular characterization of PVC biogenesis and PVC-mediated protein traffickinq in plant cells.

关键词： BY-2 cells endosomal compartment prevacuolar compartment organelle proteomic vacuolar sorting receptor

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