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Glucagon-like peptide-1 receptor agonists rescued diabetic vascular endothelial damage through suppression of aberrant STING signaling

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Acta Pharmaceutica Sinica B 2024年第6期14卷 2613-2630页

作者： Xuemin He Siying wen Xixiang tang Zheyao wen Rui Zhang Shasha li Rong Gao jin Wang Yanhua Zhu Dong Fang Ting li Ruiping Peng Zhaotian Zhang Shiyi wen li Zhou Heying Ai Yan Lu Shaochong Zhang Guojun Shi Yanming Chen Department of Endocrinology and Metabolic Diseases the Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhou 510630China Guangdong Provincial Key laboratory of Diabetology&guangzhou Municipal Key laboratory of Mechanistic and Translational Obesity Research the Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhou 510630China VIP Medical Service Center the Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhou 510630China Department of Clinical Immunology the Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhou 510630China Department of Ophthalmology the Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhou 510630China State Key laboratory of Ophthalmology Zhongshan Ophthalmic CenterSun Yat-sen UniversityGuangzhou 510060China Department of Fundus Shenzhen Eye Hospital of Jinan UniversityShenzhen 518048China

Glucagon-like peptide-1 receptor agonists(GLP-1 RAs)protect against diabetic cardiovascular diseases and ***,their activity in diabetic retinopathy(DR)remains *** retrospective cohort study involving 1626 T2DM patients revealed superior efficacy of GLP-1 RAs in controlling DR compared to other glucose-lowering medications,suggesting their advantage in DR *** single-cell RNA-sequencing analysis and immunostaining,we observed a high expression of GLP-1R in retinal endothelial cells,which was down-regulated under diabetic *** of GLP-1 RAs significantly restored the receptor expression,resulting in an improvement in retinal degeneration,vascular tortuosity,avascular vessels,and vascular integrity in diabetic *** and GSEA analyses further implicated enhanced mitochondrial gene translation and mitochondrial functions by GLP-1 ***,the treatment attenuated STING signaling activation in retinal endothelial cells,which is typically activated by leaked mitochondrial *** of STING mRNA was positively correlated to the levels of angiogenic and inflammatory factors in the endothelial cells of human fibrovascular *** investigation revealed that the cAMP-responsive element binding protein played a role in the GLP-1R signaling pathway on suppression of STING *** study demonstrates a novel role of GLP-1 RAs in the protection of diabetic retinal vasculature by inhibiting STING-elicited inflammatory signals.

关键词： GLP-1 RAs STING signaling Retinal endothelial cells Mitochondrial leakage Retinal vascular dysfunction Diabetic retinopathy CREB Inflammation

Epidemiological Surveillance: Genetic Diversity of Rotavirus Group A in the Pearl River Delta, Guangdong, china in 2019

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Biomedical and Environmental Sciences 2024年第3期37卷 278-293页

作者： JIANG Jie Ying liANG Dan WANG li xiaO Yun liANG Yu feng KE Bi xia SU Juan xiaO Hong WANG Tao ZOU Min li Hong Jian KE Chang wen School of Public Health Shantou UniversityShantou 515063GuangdongChina Guangdong Provincial Center for Disease Control and Prevention Guangdong Workstation for Emerging Infectious Disease Control and PreventionGuangzhou 511430GuangdongChina Guangdong Provincial Key laboratory of Virology Institute of Medical MicrobiologyJinan UniversityGuangzhou 510632GuangdongChina School of Public Health Sun Yat-sen UniversityGuangzhou 510275GuangdongChina School of Public Health Southern Medical UniversityGuangzhou 510515GuangdongChina Shantou university Medical College Shantou 515041GuangdongChina

Objective This study aimed to understand the epidemic status and phylogenetic relationships of rotavirus group A(RVA)in the Pearl River Delta region of Guangdong Province,*** This study included individuals aged 28 days–85 years.A total of 706 stool samples from patients with acute gastroenteritis collected between January 2019 and January 2020 were analyzed for 17 causative pathogens,including RVA,using a Gastrointestinal Pathogen Panel,followed by genotyping,virus isolation,and complete sequencing to assess the genetic diversity of *** The overall RVA infection rate was 14.59%(103/706),with an irregular epidemiological *** proportion of co-infection with RVA and other pathogens was 39.81%(41/103).Acute gastroenteritis is highly prevalent in young children aged 0–1 year,and RVA is the key pathogen circulating in patients 6–10 months of age with diarrhea.G9P[8](58.25%,60/103)was found to be the predominant genotype in the RVA strains,and the 41 RVA-positive strains that were successfully sequenced belonged to three different RVA genotypes in the phylogenetic *** analysis showed that gene reassortment events,selection pressure,codon usage bias,gene polymorphism,and post-translational modifications(PTMs)occurred in the G9P[8]and G3P[8]*** This study provides molecular evidence of RVA prevalence in the Pearl River Delta region of china,further enriching the existing information on its genetics and evolutionary characteristics and suggesting the emergence of genetic *** the surveillance of genotypic changes and gene reassortment in RVA strains is essential for further research and a better understanding of strain variations for further vaccine development.

关键词： Infectious diarrheal disease Rotavirus Phylogenetic analysis Gene rearrangement Codon usage bias Genetic diversity

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FG020326-loaded nanoparticle with PEG and PDLLA improved pharmacodynamics of reversing multidrug resistance in vitro and in vivo

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Acta Pharmacologica Sinica 2007年第6期28卷 913-920页

作者： wen-jing DENG~2,xiao-qiang YANG~2,Yong-ju liANG~2,li-ming CHEN~2,Yan-yan YAN~2,Xin-tao SHUAI~3,li-wu FU~(2,4)~2 State Key laboratory of Oncology in Southern china Cancer Center,sun yat-sen university,guangzhou 510060,china ~3 School ofChemistry and Chemical Engineering of sun yat-sen university,guangzhou 510275,china State Key laboratory of Oncology in Southern china Cancer Center Sun Yat-Sen University Guangzhou China School of Chemistry and Chemical Engineering of sun yat-sen university Guangzhou China

Aim:FG020326,a novel imidazole derivative,is a potent multidrug-resistance(MDR) modulator in vitro and in ***,FG020326 is ***-FG020326 is a FG020326-1oaded nanoparticle formed with diblock copolymers ofpoly (ethylene glycol)-block-poly (D,L-lactic acid) (PEG:PDLLA,PEDLLA) thatcan solubilize *** work was intended to evaluate the pharmacody-namics of PEDLLA-FG020326 on reversing MDR in vitro and in ***:Cytotoxicity was determined by tetrazolium *** intracellular accumulationand efflux of doxorubicin (Dox) were detected by fluorescence *** function of P-glycoprotein was examined by Rhodamine 123 (Rh123) accumu-lation detected by flow *** KBv200 cell xenograft model was estab-lished to investigate the effect of PEDLLA-FG020326 on reversing MDR in ***:PEDLLA-FG020326 and FG020326 exhibited 56.4-and 35.9-fold activityin reversing KBv200 cells to vincristine (VCR) resistance,respectively and 14.98-and 7.64-fold to Dox resistance,***-FG020326 was much stron-ger than FG020326,resulting in the increase of Dox and Rh 123 accumulation andthe decrease of intracellular Dox extrusion in KBv200 ***,PEDLLA-FG020326 exhibited more powerful activity than FG020326 in enhancing the effectof VCR against KBv200 cell xenografts in nude mice,but did not appear more ***:The pharmacodynamics of FG020326 was improved by incorporatingit into a micellar nanoparticle formed with PEG-block-PDLLA copolymers.

关键词： FG020326 micellar nanoparticle multidrug resistance xenografts

Broadband and fabrication-tolerant 3-dB couplers with topological valley edge modes

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light(Science & Applications) 2024年第8期13卷 1623-1630页

作者： Guo-jing tang xiao-Dong Chen Lu sun Chao-Heng Guo Meng-Yu li Zhong-Tao Tian Hou-Hong Chen Hong-Wei Wang Qi-Yao sun Ying-Di Pan Xin-Tao He Yi-Kai Su Jian-wen Dong School of Physics&State Key laboratory of Optoelectronic Materials and Technologies Sun Yat-sen UniversityGuangzhou 510275China State Key laboratory of Advanced Optical Communication Systems and Networks Department of Electronic EngineeringShanghai Jiao Tong UniversityShanghai 200240China

3-dB couplers,which are commonly used in photonic integrated circuits for on-chip information processing,precision measurement,and quantum computing,face challenges in achieving robust performance due to their limited 3-dB bandwidths and sensitivity to fabrication *** address this,we introduce topological physics to nanophotonics,developing a framework for topological 3-dB *** couplers exhibit broad working wavelength range and robustness against fabrication dimensional *** leveraging valley-Hall topology and mirror symmetry,the photonic-crystal-slab couplers achieve ideal 3-dB splitting characterized by a wavelength-insensitive scattering *** analysis confirms the superiority on broad bandwidth of 48 nm and robust splitting against dimensional errors of 20 *** further propose a topological interferometer for on-chip distance measurement,which also exhibits robustness against dimensional *** extension of topological principles to the fields of interferometers,may open up new possibilities for constructing robust wavelength division multiplexing,temperature-drift-insensitive sensing,and optical coherence tomography applications.

关键词： topological splitting insensitive

Copper transportion of WD protein in hepatocytes from Wilson disease patients in vitro

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World Journal of Gastroenterology 2001年第6期7卷 846-851页

作者： Guo-Qing Hou~1 Xiu-ling liang~2 Rong Chen~2 li-wen tang~3 Ying Wang~2 Ping-Yi Xu~2 Ying-Ru Zhang~2 Cui-Hua Ou~2 1 Department of Neurology.guangzhou first Municipal People’s hospital,guangzhou Medical College,guangzhou 510180,Guangdong Province.china2 Department of Neurology.first affiliated hospital.sun yat-sen university of Medical Sciences.guangzhou 510080.Guangdong Province.china3 Department of Pharmacology,university of Kentucky.Lexington,KY 40506.USA Department of Neurology Guangzhou First Municipal People's Hospital Guangzhou Medical College Guangdong Province China. spring-hua@***

AIM: To study the effect of copper transporting P-type ATPase in copper metabolism of hepatocyte and pathogenesis of Wilson disease (WD). METHODS: WD copper transporting properties in some organelles of the cultured hepatocytes were studied from WD patients and normal *** cultured hepatocytes were incubated in the media of copper 15 mg x L(-1) only, copper 15 mg x L(-1) with vincristine (agonist of P-type ATPase) 0.5mg x L(-1), or copper 15 mg x L(-1) with vanadate (antagonist of P-type ATPase) 18.39 mg x L(-1) separately. Microsome (endoplasmic reticulum and Golgi apparatus), lysosome, mitochondria, and cytosol were isolated by differential centrifugation. Copper contents in these organelles were measured with atomic absorption spectrophotometer, and the influence in copper transportion of these organelles by vanadate and vincristine were comparatively analyzed between WD patients and controls. WD copper transporting P-type ATPase was detected by SDS-PAGE in conjunction with Western blot in liver samples of WD patients and controls. RESULTS: The specific WD proteins (M(r)155,000 lanes) were expressed in human hepatocytes, including the control and WD patients. After incubation with medium containing copper for 2 h or 24 h, the microsome copper concentration in WD patients was obviously lower than that of controls, and the addition of vanadate or vincristine would change the copper transporting of microsomes obviously. When incubated with vincristine, levels of copper in microsome were significantly increased, while incubated with vanadate, the copper concentrations in microsome were obviously decreased. The results indicated that there were WD proteins, the copper transportion P-type ATPase in the microsome of hepatocytes. WD patients possessed abnormal copper transporting function of WD protein in the microsome, and the agonist might correct the defect of copper transportion by promoting the activity of copper transportion P-type ATPase. CONCLUSION: Cop

关键词： Adenosinetriphosphatase Adolescent Adult Cation Transport Proteins Copper Female Hepatocytes Hepatolenticular Degeneration Humans Male Research Support, Non-U.S. Gov't

Hierarchical learning of gastric cancer molecular subtypes by integrating multi-modal DNA-level omics data and clinical stratification

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Quantitative Biology 2024年第2期12卷 182-196页

作者： Binyu Yang Siying liu Jiemin Xie Xi tang Pan Guan Yifan Zhu Xuemei liu Yunhui Xiong Zuli Yang Weiyao li Yonghua Wang wen Chen Qingjiao li li C.xia Department of Statistics and Financial Mathematics School of MathematicsSouth China University of TechnologyGuangzhouChina School of Physics and Optoelectronics South China University of TechnologyGuangzhouChina Department of Pathology The Sixth Affiliated HospitalSun Yat-sen UniversityGuangzhouChina School of Food Science and Engineering South China University of TechnologyGuangzhouChina Department of laboratory Medicine the Eighth Affiliated HospitalSun Yat-sen UniversityShenzhenChina

Molecular subtyping of gastric cancer(GC)aims to comprehend its genetic ***,the efficacy of current subtyping methods is hampered by their mixed use of molecular features,a lack of strategy optimization,and the limited availability of public GC *** is a pressing need for a precise and easily adoptable subtyping approach for early DNA-based screening and *** on TCGA subtypes,we developed a novel DNA-based hierarchical classifier for gastric cancer molecular subtyping(HCG),which employs gene mutations,copy number aberrations,and methylation patterns as *** incorporating the closely related esophageal adenocarcinomas dataset,we expanded the TCGA GC dataset for the training and testing of HCG(n=453).The optimization of HCG was achieved through three hierarchical strategies using Lasso-Logistic regression,evaluated by their overall the area under receiver operating characteristic curve(auROC),accuracy,F1 score,the area under precision-recall curve(auPRC)and their capability for clinical stratification using multivariate survival ***-specific DNA alteration biomarkers were discerned through difference tests based on HCG defined *** HCG classifier demonstrated superior performance in terms of overall auROC(0.95),accuracy(0.88),F1 score(0.87)and auPRC(0.86),significantly improving the clinical stratification of patients(overall p-value=0.032).Difference tests identified 25 subtype-specific DNA alterations,including a high mutation rate in the SYNE1,ITGB4,and COL22A1 genes for the MSI subtype,and hypermethylation of ALS2CL,KIAA0406,and RPRD1B genes for the EBV *** is an accurate and robust classifier for DNA-based GC molecular subtyping with highly predictive clinical stratification *** training and test datasets,along with the analysis programs of HCG,are accessible on the GitHub website(***/LabxSCUT).

关键词： DNA alterations gastric cancer hierarchical classification molecular subtyping multi-omics

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Acceptance and Factors Associated With Participation in Functional Cure–Related Trials Among People living With HIV: A Cross-sectional Study in Southern china

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Infectious Microbes & Diseases 2024年第1期6卷 11-19页

作者： Zhaomin Deng Minjuan Shi yue Yuan GuangjinCao Chunyan wen lijuan Chen Xueying Fan linan Wu Jianhui Yuan Huachun Zou linghua li Caijun sun School of Public Health(Shenzhen) Shenzhen Campus of Sun Yat-sen UniversityShenzhenChina Department of Diseases Control Panyu District Center for Disease Control and PreventionGuangzhouChina Infectious Disease Center Guangzhou Eighth People's HospitalGuangzhou Medical UniversityGuangzhouChina Nanshan District Center for Disease Control and Prevention ShenzhenChina Key laboratory of Tropical Disease Control(sun yat-sen university) Ministry of EducationGuangzhouChina

HIV remains a global health challenge,and research efforts directed towards a functional cure require people living with HIV(PLHIV)in-volvement in clinical *** study assessed willingness to participate in HIV functional cure–related clinical trials and associated factors among PLHIV in guangzhou,china,using a questionnaire survey *** analyzed responses from 718 questionnaires,finding that 71.2%were willing to participate in Phase Ⅲtrials,while 51.7%were willing to participate in Phase I trials and 42.9%expressed acceptability for analytic treatment *** logistic regression demonstrated that male PLHIV,those with awareness of functional cure,and PLHIV,who had been on antiretroviral therapy(ART)for less than 1 year,were more willing to partic-ipate in Phase Ⅲ*** with a body mass index greater than 24,and those without resistance to ART drug were more willing to participate in Phase I *** major motivations for participation in Phase Ⅲtrials were access to cutting-edge treatments(62.6%)and supporting research(55.3%).Safety was the main concern contributing to *** study revealed a high willingness to participate in HIV functional cure–related trials among PLHIV in guangzhou,china,and willingness varied across different trial phases and was influenced by multiple *** study provides valuable references for future clinical trial recruitment strategies and public health policy formulation.

关键词： people living with HIV functional cure clinical trials willingness

Risk factors for renal outcomes in children with antineutrophil cytoplasmic antibody-associated vasculitis:a nationwide retrospective study in china

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World Journal of Pediatrics 2024年第5期20卷 506-516页

作者： li-wen Tan Jun-li Wan Chun-Hua Zhu Hong Xu Zheng-Kun xia li-Zhi Chen xiao-Chuan Wu Fang Wang xiao-Rong liu Cheng-Guang Zhao xiao-Zhong li Jian-Hua Mao xiao-wen Wang wen-Yan Huang Yu-Hong li Jian-Jiang Zhang Shi-Pin feng Jun Yang Jiao-Jiao liu Chun-lin Gao li-Ping Rong Lan-Jun Shuai Ke Xu He-Jia Zhang Qiu li Ai-Hua Zhang Mo Wang Department of Nephrology Children’s Hospital of Chongqing Medical UniversityZhongshan 2nd Rd.136Chongqing400014China Ministry of Education Key laboratory of Child Development and Disorders National Clinical Research Center for Child Health and DisordersChina International Science and Technology Cooperation Base of Child Development and Critical DisordersChildren’s Hospital of Chongqing Medical UniversityChongqingChina Chongqing Key laboratory of Pediatrics Children’s Hospital of Chongqing Medical UniversityChongqingChina Department of Nephrology Children’s Hospital of Nanjing Medical University72 Guangzhou RoadNanjing210008China Department of Nephrology Children’s Hospital of Fudan UniversityNational Paediatric Medical Center of ChinaShanghaiChina Department of Pediatrics Jinling HospitalNanjing Medical UniversityNanjingChina Department of Pediatrics Jinling HospitalThe First School of Clinical MedicineSouthern Medical UniversityNanjingChina Department of Pediatrics Jinling HospitalMedical School of Nanjing UniversityNanjingChina Department of Pediatric Nephrology and Rheumatology The First Affiliated Hospital of Sun Yat-Sen UniversityGuangzhouChina Department of Pediatrics The Second Xiangya Hospital of Central South UniversityChangshaChina Department of Pediatrics Peking University First HospitalBeijingChina Department of Nephrology Beijing Children’s HospitalCapital Medical UniversityBeijing100045China National Center for Children’s Health BeijingChina Department of Pediatrics Shengjing Hospital of China Medical UniversityShenyangChina Department of Nephrology and Immunology Children’s Hospital of Soochow UniversitySuzhouChina Department of Nephrology Children HospitalZhejiang University School of MedicineHangzhouChina Department of Nephrology Wuhan Children’s Hospital(Wuhan Maternal and Child Healthcare Hospital)Tongji Medical CollegeHuazhong University of Science&TechnologyWuhanChina Department of Nephrology and Rheumatology Shanghai Children’s HospitalSchool

Background Pediatric antineutrophil cytoplasmic antibody-associated vasculitis(AAV)is a life-threatening systemic vasculitis featured by liability to renal ***,there are few studies on the risk factors and predictive models for renal outcomes of AAV in *** Data from 179 AAV children in multiple centers between January 2012 and March 2020 were collected *** risk factors and predictive model of end-stage renal disease(ESRD)in AAV were *** Renal involvement was the most typical manifestation(95.5%),and the crescent was the predominant pathological lesion(84.9%).The estimated glomerular filtration rate(eGFR)was evaluated in 114 patients,of whom 59.6%developed ESRD,and the median time to ESRD was 3.20 *** eGFR[P=0.006,odds ratio(OR)=0.955,95%confidence interval(CI)=0.924–0.987]and the percentages of global glomerulosclerosis(pGGS;P=0.018,OR=1.060,95%CI=1.010–1.112)were independent risk factors for ESRD of renal *** on the pGGS and eGFR at renal biopsy,we developed three risk grades of ESRD and one predictive *** Kaplan‒Meier curve indicated that renal outcomes were significantly different in different risk grades(Pline,the predictive model had higher accuracy(0.86 versus 0.58,P2)in external *** Renal involvement is the most common manifestation of pediatric AAV in china,of which more than half deteriorates into *** predictive model based on eGFR at renal biopsy and the pGGS may be stable and accurate in speculating the risk of ESRD in AAV children.

关键词： Antineutrophil cytoplasmic antibody End-stage renal disease Glomerulonephritis Pediatric nephrology Vasculitis

Secure multi-party computation protocol for sequencing problem

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Science china(Information Sciences) 2011年第8期54卷 1654-1662页

作者： tang ChunMing 1,2,SHI GuiHua 1 & YAO ZhengAn 3 1 School of Mathematics and Information Science,guangzhou university,guangzhou 510006, china 2State Key laboratory of Information Security, Institute of Software Science,Chinese Academy of Sciences,Beijing 100080,china 3 School of Mathematics and Computational Science,sun yat-sen university,guangzhou 510275,china School of Mathematics and Information Science Guangzhou University Guangzhou China State Key laboratory of Information Security Institute of Software Science Chinese Academy of Sciences Beijing China School of Mathematics and Computational Science Sun Yat-Sen University Guangzhou China

In the field of multi-party computation,an important problem is how to construct an efficient and secure multi-party computation protocol for certain specific *** the present study,we make use of a secret sharing scheme to construct an efficient and secure multi-party computation protocol for sequencing *** protocols are perfectly secure against both a passive adversary that can corrupt at most t (n-1)/2 participants, and an active adversary that can corrupt at most t 3 *** simplest sequencing problem is the Millionaires' problem.

关键词： secure multi-party computation sequencing problem secret sharing