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Targeting protein modifications in metabolic diseases:molecular mechanisms and targeted therapies

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Signal Transduction and Targeted Therapy 2023年第6期8卷 2968-3012页

作者： Xiumei Wu Mengyun Xu Mengya Geng Shuo Chen Peter JLittle Suowen Xu jianping weng Department of Endocrinology Institute of Endocrine and Metabolic DiseasesThe First Affiliated Hospital of USTCDivision of Life Sciences and MedicineClinical Research Hospital of Chinese Academy of Sciences(Hefei)University of Science and Technology of ChinaHefeiAnhui230001China Department of Endocrinology and Metabolism Guangdong Provincial Key Laboratory of DiabetologyThe Third Affiliated Hospital of Sun Yat-sen University510000GuangzhouChina School of Pharmacy University of QueenslandPharmacy Australia Centre of ExcellenceWoolloongabbaQLD4102Australia Sunshine Coast Health Institute and School of Health and Behavioural Sciences University of the Sunshine CoastBirtinyaQLD4575Australia Bengbu Medical College Bengbu233000China

The ever-increasing prevalence of noncommunicable diseases(NCDs)represents a major public health burden worldwide.The most common form of NCD is metabolic diseases,which affect people of all ages and usually manifest their pathobiology through life-threatening cardiovascular complications.A comprehensive understanding of the pathobiology of metabolic diseases will generate novel targets for improved therapies across the common metabolic spectrum.Protein posttranslational modification(PTM)is an important term that refers to biochemical modification of specific amino acid residues in target proteins,which immensely increases the functional diversity of the proteome.The range of PTMs includes phosphorylation,acetylation,methylation,ubiquitination,SUMOylation,neddylation,glycosylation,palmitoylation,myristoylation,prenylation,cholesterylation,glutathionylation,S-nitrosylation,sulfhydration,citrullination,ADPribosylation,and several novel PTMs.Here,we offer a comprehensive review of PTMs and their roles in common metabolic diseases and pathological consequences,including diabetes,obesity,fatty liver diseases,hyperlipidemia,and atherosclerosis.Building upon this framework,we afford a through description of proteins and pathways involved in metabolic diseases by focusing on PTM-based protein modifications,showcase the pharmaceutical intervention of PTMs in preclinical studies and clinical trials,and offer future perspectives.Fundamental research defining the mechanisms whereby PTMs of proteins regulate metabolic diseases will open new avenues for therapeutic intervention.

关键词： diseases mechanisms consequences

Intrapartum and early postpartum glycemic profiles in women with gestational diabetes mellitus:an observational study

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Chinese Medical Journal 2022年第21期135卷 2547-2553页

作者： Yu Ding Xueying Zheng Yujie Liu Tian Wei Tong Yue Siqi Wang Suyu Chen jianping weng Sihui Luo Department of Endocrinology The First Affiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefeiAnhui 230001China Department of Obstetrics and Gynecology The First Affiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefeiAnhui 230001China Institute of Endocrine and Metabolic Diseases The First Affiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefeiAnhui 230001China

Background: Data on the glycemic profile of pregnant women with gestational diabetes mellitus (GDM) during the perinatal period are sparse. This study described the intrapartum and early postpartum glucose profiles among pregnant women with GDM, and analyzed factors potentially affecting glycemic parameters during the period.Methods: This was a prospective observational study conducted from March 2020 to November 2021. Pregnant women with GDM receiving lifestyle interventions alone during pregnancy and matched women with non-diabetic pregnancies (NDPs) were enrolled from among patients admitted to the obstetrics department for childbirth. Glucose monitoring was performed via a flash glucose monitoring (FGM) system on admission, and glucose readings during labor and early postpartum were analyzed. The clinical characteristics and FGM-based parameters of participants in the two groups were compared.Results: A total of 124 participants (mean age: 29.5 ± 3.5 years, 92 [74.2%] primipara) were included in the final analysis. A total of 17,571 glucose readings were retrieved. There were no significant differences in clinical characteristics between the GDM (n = 60) and NDP (n = 64) groups. The average glucose level was 92.2 mg/dL, and the level was higher in the GDM group (95.5 ± 12.1 mg/dLvs. 89.1 ± 13.4 mg/dL,P = 0.008) during the intrapartum and early postpartum periods. The data were split into the intrapartum period (from the start of labor to delivery of the placenta) and the early postpartum period (within 24 h after placental delivery) for analysis. During intrapartum, women with GDM exhibited glycemic profiles and fluctuations similar to those in the NDP group. However, women with GDM had higher postpartum glucose levels (97.7 ± 13.4 mg/dLvs. 90.8 ± 15.3 mg/dL,P = 0.009), a longer time spent >140 mg/dL (8.7 ± 9.3%vs. 5.9 ± 10.3%,P = 0.011), and greater glycemic fluctuations than those with NDP. Postpartum hyperglycemia in GDM might be associated with high parity and postprandial glucose abnormalities in GDM scr

关键词： Blood glucose Flash glucose monitoring Gestational diabetes mellitus Glycemic profiles

A thorough analysis of diabetes research in China from 1995 to 2015: current scenario and future scope

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Science China(Life Sciences) 2019年第1期62卷 46-62页

作者： Zekai Wu Tianru Jin jianping weng Department of Endocrinology and Metabolism Guangdong Provincial Key Laboratory of Diabetology The Third Affiliated Hospital of Sun Yat-Sen University Department of Physiology University of Toronto

The prevalence of diabetes has increased dramatically over the past three decades, and currently, China has the largest number of diabetics worldwide; this number continues to grow and puts ongoing strains on the medical resources. In this review, we reviewed the diabetes research conducted in China from 1995 to 2015 with the aim of providing new insights regarding the current status and future perspectives for researchers, diabetes health providers, and respective policy-makers. Remarkable progress has been made in diabetes research in China during the past two decades in terms of both the quantity and publication influence. The progress, however, struggles to adequately manage diabetes in China. Here we addressed opportunities to strengthen researches, including new drug development, high quality studies on health economics, and healthcare quality improvement studies. As the expected wave of diabetic complications is upcoming and overwhelming, we therefore recommend that immediate improvements are required to implement the researches regarding their prevention and treatment.

关键词： diabetes publication number publication influence clinical research basic research traditional Chinese medicine

Chemical inhibition of Arabidopsis PIN-FORMED auxin transporters by the anti-inflammatory drug naproxen

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Plant Communications 2023年第6期4卷 234-243页

作者： Jing Xia Mengjuan Kong Zhisen Yang Lianghanxiao Sun Yakun Peng Yanbo Mao Hong Wei Wei Ying Yongxiang Gao Jiri Friml jianping weng Xin Liu Linfeng Sun Shutang Tan MOE Key Laboratory for Cellular Dynamics Hefei National Laboratory for Physical Sciences at the MicroscaleThe First Affiliated Hospital of USTCBiomedical Sciences and Health Laboratory of Anhui ProvinceDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefei 230027China Institute of Science and Technology Austria(ISTA) Am Campus 13400 KlosterneuburgAustria Center for Advanced Interdisciplinary Science and Biomedicine of IHM Division of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefei 230027China

The phytohormone auxin plays central roles in many growth and developmental processes in plants.Development of chemical tools targeting the auxin pathway is useful for both plant biology and agriculture.Here we reveal that naproxen,a synthetic compound with anti-inflammatory activity in humans,acts as an auxin transport inhibitor targeting PIN-FORMED(PIN)transporters in plants.Physiological experiments indicate that exogenous naproxen treatment affects pleiotropic auxin-regulated developmental processes.Additional cellular and biochemical evidence indicates that naproxen suppresses auxin transport,specifically PIN-mediated auxin efflux.Moreover,biochemical and structural analyses confirm that naproxen binds directly to PIN1 protein via the same binding cavity as the indole-3-acetic acid substrate.Thus,by combining cellular,biochemical,and structural approaches,this study clearly establishes that naproxen is a PIN inhibitor and elucidates the underlying mechanisms.Further use of this compound may advance our understanding of the molecular mechanisms of PIN-mediated auxin transport and expand our toolkit in auxin biology and agriculture.

关键词： auxin transport PIN naproxen Arabidopsis NPA

Decreased b-Cell Function is Associated with Cardiovascular Autonomic Neuropathy in Chinese Patients Newly Diagnosed with Type 2 Diabetes

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Neuroscience Bulletin 2019年第1期35卷 25-33页

作者： Xubin Yang Wen Xu Yanhua Zhu Hongrong Deng Ying Tan Longyi Zeng jianping weng Department of Endocrinology and Metabolism Guangdong Provincial Key Laboratory of DiabetologyThird Affiliated Hospital of Sun Yat-sen UniversityGuangzhou 510630China

The influence of b-cell function on cardiovascular autonomic neuropathy(CAN), an important diabetesrelated complication, is still unclear. In this study, we aimed to investigate the association between residual b-cell function and CAN in patients newly diagnosed with type 2 diabetes. We enrolled 90 newly-diagnosed type 2 diabetic patients and 37 participants with normal glucose tolerance as controls. The patients were divided into a CAN? group(diabetic patients with CAN, n = 20) and a CAN-group(diabetic patients without CAN, n = 70) according to the standard Ewing battery of tests. Fasting and postprandial plasma glucose, insulin, and C-peptide were measured.Homeostasis model assessment-beta cells(HOMA-B) and HOMA-insulin resistance(IR) were calculated. The prevalence of CAN in this population was 22.2%. Compared with the CAN-group, the CAN? group had significantly lower fasting plasma insulin(6.60 ± 4.39 vs 10.45 ± 7.82 l/L, P = 0.029), fasting C-peptide(0.51 ± 0.20 vs0.82 ± 0.51 nmol/L, P = 0.004), and HOMA-B(21.44 ± 17.06 vs 44.17 ± 38.49, P = 0.002). Fasting C-peptide was correlated with the Valsalva ratio(r = 0.24, P = 0.043) and the 30:15 test(r = 0.26,P = 0.023). Further analysis showed that fasting C-peptide(OR: 0.041, 95% CI 0.003–0.501, P = 0.012) and HOMAB(OR: 0.965, 95% CI 0.934–0.996, P = 0.028) were independently associated with cardiovascular autonomic nerve function in this population. The patients with fasting C-peptide values \ 0.67 nmol/L were more likely to have CAN than those with C-peptide levels C0.67 nmol/L(OR:6.00, 95% CI 1.815–19.830, P = 0.003). A high prevalence of CAN was found in patients with newly-diagnosed type 2 diabetes. Decreased b-cell function was closely associated with CAN in this population.

关键词： Cardiovascular autonomic neuropathy b-cell function Type 2 diabetes mellitus

Erratum to:A thorough analysis of diabetes research in China from 1995 to 2015:current scenario and future scope

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Science China(Life Sciences) 2023年第12期66卷 2958-2958页

作者： Zekai Wu Tianru Jin jianping weng Department of Endocrinology and Metabolism Guangdong Provincial Key Laboratory of DiabetologyThe Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhou 510630China Department of Physiology University of TorontoToronto ON M5S 1A8Canada

Zekai Wu1, Tianru Jin2&jianping weng1*1Department of Endocrinology and Metabolism, Guangdong Provincial Key Laboratory of Diabetology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China;2Department of Physiology, University of Toronto, Toronto ON M5S 1A8, Canada Received April 24, 2023; accepted April 24, 2023; published online July 17, 2023

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Insulin requirement profiles and related factors of insulin pump therapy in patients with type 2 diabetes

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Science China(Life Sciences) 2019年第11期62卷 1506-1513页

作者： Xubin Yang Hongrong Deng Xiuzhen Zhang Daizhi Yang Jinhua Yan Bin Yao jianping weng Wen Xu Department of Endocrinology and Metabolism Guangdong Provincial Key Laboratory of Diabetologythe Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhou 510630China Department of Endocrinology and Metabolism Shenzhen People s HospitalShenzhen 518020China Department of Endocrinology of the First Affiliated Hospital Division of Life Sciences and Medicine of the University of Science and Technology of China(USTC)Hefei 230026China

Continuous subcutaneous insulin infusion(CSII)is an effective therapy to control hyperglycemia in both patients with type 1 diabetes and type 2 diabetes.However,there is little data investigating the insulin dose setting during CSII therapy in type 2 diabetes to achieve optimal glycemic control and avoid the risk of hypoglycemia.Thus,this study is aimed to assess the dose characteristics of insulin requirement and explore the related clinical factors in patients with type 2 diabetes who were treated with CSII.A total of 327 patients(195 males)aged 52.9±12.5 years old were included in this study.Patients were treated with CSII to achieve the target fasting capillary blood glucose(4.4-7.0 mmol L^(-1))and 2-h postprandial capillary blood glucose(4.4-10.0 mmol L^(-1))by adjusting insulin infusion according to the seven-point capillary blood glucose profiles.Total daily insulin dose(TDD),total daily insulin dose per kilogram(TDD kg-1)and the ratio of total basal insulin dose(TBD)to TDD(%TBa)were calculated after patients achieved the glucose targets for at least 3 days via 1-2 weeks of CSII treatment.And insulin dose,insulin dosing patterns and the relevant clinical factors were analyzed.The mean ratio of basal/bolus insulin distribution of all patients was 40%:60%.Patients with central obesity needed more TDD(51.3±17.1 U versus 43.5±14.0 U,P<0.05)and TDD kg^(-1)(0.8±0.3 U kg^(-1)versus 0.7±0.2 U kg^(-1),P<0.05)than those without central obesity.Pearson's correlation analysis demonstrated that TDD was positively correlated with body mass index(BMI),waist circumference(WC),baseline fasting plasma glucose(FPG),fasting C-peptide level,2 h-postprandial C-peptide level and time to achieve glycemic target(all P<0.05);TDD kg^(-1)was positively correlated with waist-to-hip ratio(WHR),baseline FPG,glycosylated hemoglobin Ale(HbAlc),fasting C-peptide level and time to achieve glycemic target,and negatively correlated with BMI(all P<0.05).Multiple linear regression analyses revealed that BMI(β=1.796,P<0.01),WC(β=0.109,P<0.01),ba

关键词： continuous subcutaneous insulin infusion insulin requirement profiles type 2 diabetes

Association between population migration and epidemic control of coronavirus disease 2019

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Science China(Life Sciences) 2020年第6期63卷 936-939页

作者： Yu Ding Sihui Luo Xueying Zheng Ping Ling Tong Yue Zhirong Liu jianping weng The First Affiliated Hospital of USTC Division of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefei 230001China Institute of Public Health University of Science and Technology of ChinaHefei 230026China Joint Laboratory of Public Health USTC and Anhui NHCHefei 230001China Anhui Provincial Center for Disease Control and Prevention Hefei 230601China Division of Life Sciences and Medicine University of Science and Technology of ChinaHefei 230026China

Dear Editor,In January 2020,a widespread outbreak of coronavirus disease 2019(COVID-19)occurred after the beginning of the largest annual migration in China,which is known as the Spring Festival migration.Starting in January 20,2020,the Chinese government took a series of unprecedented measures to contain the spread of COVID-19.Because of the role of Wuhan as a central transportation hub.

关键词： Association between population migration and epidemic control of coronavirus disease 2019

Asymptomatic patients and asymptomatic phases of Coronavirus Disease 2019(COVID-19): a population-based surveillance study

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National Science Review 2020年第10期7卷 1527-1539页

作者： Xueying Zheng Sihui Luo Yong Sun Mingfeng Han Jian Liu Liangye Sun Liangming Zhang Ping Ling Yu Ding Tengchuan Jin Zhirong Liu jianping weng The First Affiliated Hospital of USTC Division of Life Science and Medicine University of Science and Technology of China Key Laboratory for Medical and Health of the 13th Five-Year Plan Anhui Provincial Center for Disease Control and Prevention Fuyang No.2 People's Hospital Anqing Hospital Affiliated to Anhui Medical University (Anqing Municipal Hospital) Lu'an People's Hospital Department of Infectious Disease the First Affiliated Hospital of USTCDivision of Life Science and Medicine University of Science and Technology of China Division of Life Science and Medicine University of Science and Technology of China

In this population-based study, we identified 307 confirmed COVID-19 cases from massive surveillance,including 129 551 individuals screened at fever clinics or returning from Hubei and 3710 close contacts of confirmed COVID-19 patients. Among them, 17 patients were asymptomatic at initial clinical assessment.These asymptomatic patients on admission accounted for a small proportion of all patients(5.54%) with relatively weak transmissibility, and the detection rate was 0.35 per 100 close contacts. Moreover, the dynamics of symptoms of the 307 patients showed that the interval from symptom remission to the final negativity of viral nucleic acid was 5.0 days(interquartile range 2.0 to 11.0 days), with 14 patients(4.56%)having re-detectable viral RNA after discharge. Overall, our findings suggested asymptomatic carriers and presymptomatic patients only accounted for a small proportion of COVID-19 patients. Also, the asymptomatic phase during recovery from COVID-19 implied that negativity in viral RNA is necessary as a de-isolation criterion and follow-up is recommended.

关键词： epidemiology public health surveillance asymptomatic COVID-19 SARS-CoV-2