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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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IgA肾病患儿治疗的研究进展

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中华儿科杂志 2007年第4期45卷 244-247页

作者： James C. M. Chan man-chun chiu Satoshi Hisano Ching-Yuang Lin 管娜（翻译）丁洁（审校） The Barbara Bush Children＇s Hospital Maine Medical Center Portland Maine USA The Department of Paediatrics Princess Margaret Hospital Hong Kong China Department of Pathology Fukuoka University Fukuoka Japan Children＇s Hospital Changhua Christian Hospital Institute of Medical Research Chang Jung Christian UniversityTaiwanChina 不详

1968年IgA肾病首次被描述，最初称为Berger病。先证者为法国患儿，表现为急性上呼吸道感染数天后出现无症状肉眼血尿。肾活检显示系膜区显著扩大、IgA沉积，因此被命名为IgA肾病。此后40年临床治疗实践中，对该病自然病程了解逐渐增多... 详细信息

1968年IgA肾病首次被描述，最初称为Berger病。先证者为法国患儿，表现为急性上呼吸道感染数天后出现无症状肉眼血尿。肾活检显示系膜区显著扩大、IgA沉积，因此被命名为IgA肾病。此后40年临床治疗实践中，对该病自然病程了解逐渐增多，但对其发病机制知之甚少。20世纪80年代，D，Amico和其他学者已经认识到IgA肾病是世界上最常见的肾小球肾炎。因此，Julian等指出该病对1％以上的人口有影响。

关键词： IgA肾病临床治疗患儿急性上呼吸道感染 IgA沉积肾小球肾炎肉眼血尿自然病程

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A prospective cohort of men with localized prostate cancer on active surveillance protocol in Hong Kong,China:what did we learn?

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Asian Journal of Andrology 2024年第3期26卷 245-249页

作者： Xiaobo Wu Ivan Ching-Ho Ko Cindy Yeuk-Lam Hong Samuel Chi-Hang Yee Jeremy Yuen-chun Teoh Samson Yun-Sang Chan Ho-man Tam Chi-Kwok Chan Chi-Fai Ng Peter Ka-Fung chiu SH Ho Urology Centre Department of SurgeryFaculty of MedicineThe Chinese University of Hong KongHong KongChina

This study aimed to report the outcomes of active surveillance(AS)in the management of low-risk prostate cancer(PCa).It recruited87 men who were prospectively followed up according to the Prostate Cancer Research International Active Surveillance(PRIAS)protocol with local adaptation at SH Ho Urology Centre,Prince of Wales Hospital,Hong Kong,*** investigated the predictorsof disease progression and found that baseline prostate-specific antigen density(PSAD)and the presence of the highest ProstateImaging-Reporting and Data System(PI-RADS)score 5 lesion on magnetic resonance imaging(MRI)are significantly correlatedwith disease ***,men with PSAD>0.2 ng ml^(−2)or PI-RADS 4 or 5 lesions had significantly worse upgradingfree survival compared to those with PSAD≤0.2 ng ml−2 and PI-RADS 2 or 3 *** study concludes that AS is a safe andeffective management strategy for selected patients to defer radical treatment and that most disease progression can be detectedafter the first repeated *** combination of PSAD>0.2 ng ml^(−2)and PI-RADS 4 or 5 lesions may serve as a useful predictorof early disease progression and provide a guide to optimize follow-up protocols for men in different risk groups.

关键词： active surveillance cohort localized prostate cancer

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Review of Computational Approaches to Optimization Problems in Inhomogeneous Rods and Plates

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Communications on Applied Mathematics and Computation 2024年第1期6卷 236-256页

作者： Weitao Chen chiu-Yen Kao Department of Mathematics University of California at Riverside900 University AveRiversideCA92521USA Department of Mathematical Sciences Claremont McKenna College850 Columbia AveClaremontCA91711USA

In this paper,we review computational approaches to optimization problems of inhomogeneous rods and *** consider both the optimization of eigenvalues and the localization of *** problems are motivated by physical problems including the determination of the extremum of the fundamental vibration frequency and the localization of the vibration *** demonstrate how an iterative rearrangement approach and a gradient descent approach with projection can successfully solve these optimization problems under different boundary conditions with different densities given.

关键词： Inhomogeneous rods and plates Bi-Laplacian Optimization of eigenvalues Localization of eigenfunctions Rearrangement

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Unique anti-angiogenic effects,pharmacological targets and therapeutic mechanisms of Chinese herbal medicines for endometriosis

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Genes & Diseases 2024年第5期11卷 63-65页

作者： Bo Liang Rui Dong Sze Wan Hung Yiran Li Yuezhen Lin Ling Wu Tao Zhang Gene Chi Wai man Hui Xu Jacqueline Pui Wah chung Chi chiu Wang Guangdong Provincial Key Laboratory of Marine Biotechnology Institute of Marine SciencesShantou UniversityShantouGuangdong 515063China Department of Obstetrics and Gynaecology The Chinese University of Hong KongHong Kong SARChina Reproduction and Development Laboratory Li Ka Shing Institute of Health SciencesThe Chinese University of Hong KongHong Kong SARChina School of Biomedical Sciences The Chinese University of Hong KongHong Kong SARChina Chinese University of Hong Kong-Sichuan University Joint Laboratory in Reproductive Medicine The Chinese University of Hong KongHong Kong SARChina

Endometriosis is a common and benign angiogenesisdependent gynecological disorder,which refers to the proliferation and growth of endometrium-like tissues with neovasculature formation outside of the uterus.1 Available medical treatments for endometriosis containing hormonal and non-hormonal treatments had been limited for longterm usage by their side effects.2 Ideal medical treatment for endometriosis with efficacy to relieve symptoms and suppress endometriotic lesion growth and minimal side effects has been longing for decades.3 Angiogenesis is a promising therapeutic target for endometriosis.

关键词： therapeutic endometriosis herbal

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Vonoprazan 10 mg or 20 mg *** 15 mg as maintenance therapy in Asian patients with healed erosive esophagitis:A randomized controlled trial

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Chinese Medical Journal 2024年第8期137卷 962-971页

作者： Yinglian Xiao Jiaming Qian Shutian Zhang Ning Dai Hoon Jai chun Chengtang chiu Chui Fung Chong Nobuo Funao Yuuichi Sakurai Jessica D.Eisner Li Xie Minhu Chen Department of Gastroenterology The First Affiliated HospitalSun Yat-sen UniversityGuangzhouGuangdong 510062China Department of Gastroenterology Peking Union Medical College HospitalPeking Union Medical CollegeChinese Academy of Medical SciencesBeijing 100006China Department of Gastroenterology Beijing Friendship HospitalCapital Medical UniversityBeijing 100050China Department of Gastroenterology Sir Run Run Shaw HospitalSchool of Medicine Zhejiang UniversityHangzhouZhejiang 310020China Department of Internal Medicine Korea University Anam HospitalKorea University College of Medicine73 Goryeodae-roSeongbuk-guSeoul 02841Republic of Korea Department of Gastroenterology&Hepatology Linkou Medical CenterChang Gung Memorial HospitalTaoyuanTaiwan 33353China College of Medicine Chang Gung UniversityTaoyuanTaiwan 33353China Takeda Development Center Asia Singapore 018981Singapore Takeda Pharmaceutical Company Chuo-kuOsaka 540-8645Japan Takeda Pharmaceuticals International Company CambridgeMA02142 USA China Medical Team Takeda ChinaBeijing 100027China Hoffmann-La Roche Basel4070 Switzerland Abbott Laboratories Lake ForestIL 60045USA

Background:Erosive esophagitis(EE)is a gastroesophageal reflux disease characterized by mucosal breaks in the *** pump inhibitors are widely used as maintenance therapy for EE,but many patients still *** this trial,we evaluated the noninferiority of vonoprazan *** as maintenance therapy in patients with healed ***:We performed a double-blind,double-dummy,multicenter,phase 3 clinical trial among non-Japanese Asian adults with endoscopically confirmed healed EE from April 2015 to February *** from China,South Korea,and Malaysia were randomized to vonoprazan 10 mg or 20 mg once daily or lansoprazole 15 mg once daily for 24 *** primary endpoint was endoscopically confirmed EE recurrence rate over 24 weeks with a noninferiority margin of 10%using a two-sided 95%confidence interval(CI).Treatment-emergent adverse events(TEAEs)were ***:Among 703 patients,EE recurrence was observed in 24/181(13.3%)and 21/171(12.3%)patients receiving vonoprazan 10 mg or 20 mg,respectively,and 47/184(25.5%)patients receiving lansoprazole(differences:-12.3%[95%CI,-20.3%to-4.3%]and-13.3%[95%CI,-21.3%to-5.3%],respectively),meeting the primary endpoint of noninferiority to lansoprazole in preventing EE recurrence at 24 *** of superiority(upper bound of 95%CI<0%)was also *** 12 weeks,endoscopically confirmed EE recurrence was observed in 5/18,2/20,and 7/20 of patients receiving vonoprazan 10 mg,vonoprazan 20 mg,and lansoprazole,*** were experienced by 66.8%(157/235),69.0%(156/226),and 65.3%(158/242)of patients receiving vonoprazan 10 mg,vonoprazan 20 mg,and lansoprazole,*** most common TEAE was upper respiratory tract infection in 12.8%(30/235)and 12.8%(29/226)patients in vonoprazan 10 mg and 20 mg groups,respectively and 8.7%(21/242)patients in lansoprazole ***:Vonoprazan maintenance therapy was well-tolerated and noninferior to lansoprazole for preventing EE recurrence i

关键词： Erosive esophagitis Lansoprazole Maintenance therapy Potassium-competitive acid blockers Vonoprazan

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Low-dose immune tolerance induction for severe hemophilia A inhibitor patients:Immunosuppressants are generally not necessary for inhibitor-titer below 200 BU/mL

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Pediatric Investigation 2024年第2期8卷 91-100页

作者： Zhengping Li Jie Sun Zekun Li Zhenping Chen Guoqing Liu Wanru Yao Xiaoling Cheng Gang Li Yingzi Zhen Di Ai Yaohan Zhou Qianqian Mao man-chiu Poon Runhui Wu Hemophilia Comprehensive Care Center Hematology DepartmentHematology CenterBeijing Key Laboratory of Pediatric Hematology-OncologyKey Laboratory of Major Diseases in ChildrenNational Key Discipline of Pediatrics(Capital Medical University)Ministry of EducationBeijing Children’s HospitalCapital Medical UniversityNational Center for Children’s HealthBeijingChina Hematologic Disease Laboratory Hematology DepartmentHematology CenterBeijing Key Laboratory of Pediatric Hematology-OncologyKey Laboratory of Major Diseases in ChildrenNational Key Discipline of Pediatrics(Capital Medical University)Ministry of EducationBeijing Pediatric Research InstituteBeijing Children’s HospitalCapital Medical UniversityNational Center for Children’s HealthBeijingChina Department of Pharmacy Beijing Children’s HospitalCapital Medical UniversityNational Center for Children’s HealthBeijingChina Departments of Medicine Pediatrics and OncologyUniversity of Calgary Cumming School of MedicineCalgaryCanada

Importance:It remained unclear that the efficacy comparison between low-dose immune tolerance induction(LD-ITI)incorporating immunosuppressants(IS)when severe hemophilia A(SHA)patients had inhibitor-titer≥200 Bethesda Units(BU)/mL(LD-ITI-IS^(200) regimen)and LD-ITI combining with IS when SHA patients had inhibitor-titer≥40 BU/mL(LD-ITI-IS^(40) regimen).Objective:To compare the efficacy of the LD-ITI-IS^(200) regimen with that of the LD-ITI-IS^(40) regimen for SHA patients with high-titer ***:A prospective cohort study on patients receiving LD-ITI-IS^(200) compared to those receiving LD-ITI-IS^(40) from January 2021 to December *** received LD-ITI[FVIII 50 IU/kg every other day].IS(rituximab+prednisone)was added when peak inhibitor tier≥200 BU/mL in the LD-ITI-IS^(200) regimen and≥40 BU/mL in the LD-ITI-IS^(40) *** is defined as a negative inhibitor plus FVIII recovery≥66%of the ***:We enrolled 30 patients on LD-ITI-IS^(200) and 64 patients on LD-ITI-IS^(40),with similar baseline clinical characteristics.A lower IS-use rate was discovered in the LD-ITI-IS^(200) regimen compared to the LD-ITI-IS^(40) regimen(30.0%vs.62.5%).The two regimens(LD-ITI-IS^(200) ***-ITI-IS^(40))had similar success rate(70.0%vs.79.7%),median time to success(9.4 vs.10.6 months),and annualized bleeding rate during ITI(3.7 vs.2.8).The cost to success was lower for LD-ITI-IS^(200) than for LD-ITI-IS^(40)(2107 vs.3256 US Dollar/kg).Among patients with peak inhibitor-titer 40-199 BU/mL,10 non-IS-using(on LD-ITI-IS^(200) regimen)and 28 IS-using(on LD-ITI-IS^(40) regimen)had similar success rates(70.0%vs.78.6%)and time to success(9.0 vs.8.8 months).Interpretation:In LD-ITI,IS are not necessary for inhibitor titer<200 BU/mL.

关键词： Hemophilia A High-titer inhibitor Immune tolerance induction Immunosuppressant Low-dose

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Distinct molecular targets of ProEGCG from EGCG and superior inhibition of angiogenesis signaling pathways for treatment of endometriosis

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Journal of Pharmaceutical Analysis 2024年第1期14卷 100-114页

作者： Sze Wan Hung Massimiliano Gaetani Yiran Li Zhouyurong Tan Xu Zheng Ruizhe Zhang Yang Ding Gene Chi Wai man Tao Zhang Yi Song Yao Wang Jacqueline Pui Wah chung Tak Hang Chan Roman A.Zubarev Chi chiu Wang Department of Obstetrics&Gynaecology The Chinese University of Hong KongHong KongChina Division of Physiological Chemistry I Department of Medical Biochemistry and BiophysicsKarolinska InstitutetStockholmSE 17177Sweden Chemical Proteomics Core Facility Department of Medical Biochemistry and BiophysicsKarolinska InstitutetStockholmSE 17177Sweden Unit of Chemical Proteomics Science for Life Laboratory(SciLifeLab)StockholmSE 17177Sweden Center for Reproductive Medicine Henan Key Laboratory of Reproduction and GeneticsThe First Affiliated Hospital of Zhengzhou UniversityZhengzhou450003China Department of Chemistry McGill UniversityMontrealH3A2K6Canada Department of Pharmacological&Technological Chemistry I.M.Sechenov First Moscow State Medical UniversityMoscow119146Russia Reproduction and Development Li Ka Shing Institute of Health SciencesThe Chinese University of Hong KongHong KongChina School of Biomedical Sciences The Chinese University of Hong KongHong KongChina Chinese University of Hong Kong-Sichuan University Joint Laboratory in Reproductive Medicine The Chinese University of Hong KongHong KongChina

Endometriosis is a common chronic gynecological disease with endometrial cell implantation outside the *** is a major pathophysiology in *** previous studies have demonstrated that the prodrug of epigallocatechin gallate(ProEGCG)exhibits superior anti-endometriotic and anti-angiogenic effects compared to epigallocatechin gallate(EGCG).However,their direct binding targets and underlying mechanisms for the differential effects remain *** this study,we demonstrated that oral ProEGCG can be effective in preventing and treating ***,1D and 2D Proteome Integral Solubility Alteration assay-based chemical proteomics identified metadherin(MTDH)and PX domain containing serine/threonine kinase-like(PXK)as novel binding targets of EGCG and ProEGCG,*** simulation and BioLayer interferometry were used to confirm their binding *** results showed that MTDH-EGCG inhibited protein kinase B(Akt)-mediated angiogenesis,while PXK-ProEGCG inhibited epidermal growth factor(EGF)-mediated angiogenesis via the EGF/hypoxia-inducible factor(HIF-1a)/vascular endothelial growth factor(VEGF)*** vitro and in vivo knockdown assays and microvascular network imaging further confirmed the involvement of these signaling ***,our study demonstrated that ProEGCG has superior therapeutic effects than EGCG by targeting distinct signal transduction pathways and may act as a novel antiangiogenic therapy for endometriosis.

关键词： Molecular targets ProEGCG EGCG Angiogenesis Treatment Endometriosis

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Classification of high-ordered topological nodes towards Moiré flat bands in twisted bilayers

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Science China(Physics,Mechanics & Astronomy) 2024年第9期67卷 133-147页

作者： Fan Cui Congcong Le Qiang Zhang Xianxin Wu Jiangping Hu Ching-Kai chiu Beijing National Laboratory for Condensed Matter Physics Institute of PhysicsChinese Academy of SciencesBeijing 100190China School of Physical Sciences University of Chinese Academy of SciencesBeijing 100190China RIKEN Interdisciplinary Theoretical and Mathematical Sciences(iTHEMS) Wako 351-0198Japan CAS Key Laboratory of Theoretical Physics Institute of Theoretical PhysicsChinese Academy of SciencesBeijing 100190China Kavli Institute of Theoretical Sciences University of Chinese Academy of SciencesBeijing 100190China New Cornerstone Science Laboratory Beijing 100190China

At magic twisted angles,Dirac cones in twisted bilayer graphene(TBG)can evolve into flat bands,serving as a critical playground for the study of strongly correlated *** chiral symmetry is introduced,rigorous mathematical proof confirms that the flat bands are locked at zero energy in the entire Moiré Brillouin zone(BZ).Yet,TBG is not the sole platform that exhibits this absolute band *** to this flatness phenomenon are topological nodes and their specific locations in the *** this study,considering twisted bilayer systems that preserve chiral symmetry,we classify various ordered topological nodes in base layers and all possible node locations across different ***,we constrain the node locations to rotational centers,such as Γ and M points,to ensure the interlayer coupling retains equal strength in all *** this classification as a foundation,we systematically identify the conditions under which Moiré flat bands ***,through the extension of holomorphic functions,we provide proof that flat bands are locked at zero energy,shedding light on the origin of the band ***,beyond Dirac cones,numerous twisted bilayer nodal platforms can host flat bands with a degeneracy number of more than two,such as four-fold,six-fold,and *** multiplicity of degeneracy in flat bands might unveil more complex and enriched correlation physics.

关键词： twisted bilayer systems high-ordered topological nodes Moriéflat bands high degeneracy

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“If Somebody Needed Help, I Went Over”: Social Capital and Therapeutic Communities of Older Adult Farmers in British Columbia Floods

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International Journal of Disaster Risk Science 2024年第2期15卷 290-301页

作者： Kyle Breen Siyu Ru Luna Vandeweghe Jenna chiu Lindsay Heyland Haorui Wu School of Social Work Dalhousie UniversityHalifaxNS B3H 1S2Canada

Older adults in disaster contexts are often thought of as a passive, vulnerable population that lacks agency and capacities to cope in the aftermath. However, it can be argued that older adults may have underrecognized strengths that can be utilized pre-, peri-, and post-disaster. One of these strengths is older adults' unique social capital that stems from long-standing connections with other members of their respective communities. Using data from in-depth, semistructured interviews with farmers in British Columbia 3–11 months after the 2021 floods, this research explored the experiences of older adult farmers' recovery. The farmers discussed how they leveraged their social capital to aid in their recovery efforts from the flood event. By using their bonding social capital, older adult farmers transformed their existing, deep-rooted connections into post-disaster assistance. This, in turn, generated the idea of the therapeutic community, helping community members cope in the aftermath. This research indicated the need to further examine how older adults in disaster settings can be viewed as assets with community knowledge and skills as opposed to solely as a vulnerable population.

关键词： British Columbia Flood disaster Older adults Qualitative research Social capital Therapeutic community

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