Bacterial small laccases(SLAC) are promising industrial biocatalysts due to their ability to oxidize a broad range of substrates with exceptional thermostability and tolerance for alkaline p H. Electron transfer betwe...Bacterial small laccases(SLAC) are promising industrial biocatalysts due to their ability to oxidize a broad range of substrates with exceptional thermostability and tolerance for alkaline p H. Electron transfer between substrate, copper centers, and O2is one of the key steps in the catalytic turnover of SLAC. However, limited research has been conducted on the electron transfer pathway of SLAC and SLAC-catalyzed reactions, hindering further engineering of SLAC to produce tunable biocatalysts for novel applications. Herein, the combinational use of electron paramagnetic resonance(EPR) and ultraviolet-visible(UV-vis) spectroscopic methods coupled with redox titration were employed to monitor the electron transfer processes and obtain further insights into the electron transfer pathway in SLAC. The reduction potentials for type 1 copper(T1Cu), type 2 copper(T2Cu) and type 3copper(T3Cu) were determined to be 367 ± 2 mV, 378 ± 5 m V and 403 ± 2 mV,respectively. Moreover, the reduction potential of a selected substrate of SLAC, hydroquinone(HQ), was determined to be 288 mV using cyclic voltammetry(CV). In this way, an electron transfer pathway was identified based on the reduction potentials. Specifically,electrons are transferred from HQ to T1Cu, then to T2Cu and T3Cu, and finally to O2.Furthermore, superhyperfine splitting observed via EPR during redox titration indicated a modification in the covalency of T2Cu upon electron uptake, suggesting a conformational alteration in the protein environment surrounding the copper sites, which could potentially influence the reduction potential of the copper sites during catalytic processes. The results presented here not only provide a comprehensive method for analyzing the electron transfer pathway in metalloenzymes through reduction potential measurements, but also offer valuable insights for further engineering and directed evolution studies of SLAC in the aim for biotechnological and industrial applications.展开更多
Objective To explore the association between soil selenium levels and the risk of diabetes in Chinese adults aged 35–74 years.Methods Data for this study were derived from the China Chronic Diseases and Behavioral Ri...Objective To explore the association between soil selenium levels and the risk of diabetes in Chinese adults aged 35–74 years.Methods Data for this study were derived from the China Chronic Diseases and Behavioral Risk Factors Surveillance 2010 survey.Selenium concentrations in soil were obtained from the Atlas of Soil Environmental Background Values in China.A two-level binary logistic regression model was used to determine the association between soil selenium concentrations and the risk of diabetes,with participants nested within districts/counties.Results A total of 69,332 participants aged 35–74 years,from 158 districts/counties were included in the analysis.Concentrations of selenium in soil varied greatly across the 158 districts/counties,with a median concentration of 0.219 mg/kg(IQR:0.185–0.248).The results showed that both Quartile 1(0.119–0.185 mg/kg)and Quartile 4(0.249–0.344 mg/kg)groups were positively associated with diabetes compared to a soil selenium concentration of 0.186–0.219 mg/kg(Quartile 2),crude odds ratios(ORs)(95%CI)were 1.227(1.003–1.502)and 1.280(1.048–1.563).The P values were 0.045 and 0.013,for Quartile 1 and Quartile 4 groups,respectively.After adjusting for all confounding factors of interest,the Quartile 1 group became non-significant,and the Quartile 4 group had an adjusted OR(95%CI)of 1.203(1.018–1.421)relative to the reference group(Quartile 2),the P values was 0.030.No significant results were seen for the Quartile 3 group(0.220–0.248 mg/kg)compared to the reference group.Conclusion Excessive selenium concentrations in soil could increase the risk of diabetes among Chinese adults aged 35–74 years.展开更多
Metabolic syndrome(MetS) is a cluster of metabolic disorders including obesity, hypertension, hyperglycemia, elevated triglyceride levels, and low high-density lipoprotein cholesterol(HDL-C) levels. In recent years, t...Metabolic syndrome(MetS) is a cluster of metabolic disorders including obesity, hypertension, hyperglycemia, elevated triglyceride levels, and low high-density lipoprotein cholesterol(HDL-C) levels. In recent years, the prevalence of MetS[1]has increased dramatically worldwide.展开更多
Nonalcoholic fatty liver disease(NAFLD)is known for its insidious onset and chronic nature,which have jeopardized the health and life of 29.2%of adults in China[1].In 2020,metabolic dysfunctionassociated fatty liver d...Nonalcoholic fatty liver disease(NAFLD)is known for its insidious onset and chronic nature,which have jeopardized the health and life of 29.2%of adults in China[1].In 2020,metabolic dysfunctionassociated fatty liver disease(MAFLD),a more accurate nomenclature to replace NAFLD,was put forward in an international consensus of experts involving 22 countries[2].In China,at least 300 million people will suffer from MAFLD by 2030,which will be a heavy burden on national health[3].展开更多
Multiple endocrine neoplasia type 2A ( MEN2A ) is an autosomal dominant cancer syndrome that is characterized by medullary thyroid carcinoma (MTC), pheochromaocytoma (50% - 60% of cases ), and hyperplasia of the...Multiple endocrine neoplasia type 2A ( MEN2A ) is an autosomal dominant cancer syndrome that is characterized by medullary thyroid carcinoma (MTC), pheochromaocytoma (50% - 60% of cases ), and hyperplasia of the parathyroid glands ( 20% - 30% of cases ). MEN-2A comprises a heterogeneous group of neoplastic disorders that most commonly have a single missense substitution of the Ret proto-oncogene (RET) involving exons 10 and 11. Here, we reported a novel case of MEN2A associated with two variations in two distinct genes, Cys634Gly in RET and a rare Ser73Gly substitution in succinate dehydrogenase, subunit D (SDHD). Because the patient presented with medullary thyroid carcinoma and pheochromocytoma but without parathyroid gland involvement, we speculated that this clinical feature could be correlated with the two substitutions. This is the first report of a MEN2A case involving two different changes one in the RET gene and the other in the SDHD gene.展开更多
Objective The association between lipoprotein(a)[Lp(a)] levels and metabolic syndrome(MetS) remains uncertain, especially in the Asian population. The purpose of this study was to demonstrate the association between L...Objective The association between lipoprotein(a)[Lp(a)] levels and metabolic syndrome(MetS) remains uncertain, especially in the Asian population. The purpose of this study was to demonstrate the association between Lp(a) levels and MetS in a middle-aged and elderly Chinese cohort. Methods A cross-sectional study of 10,336 Chinese adults aged 40 years or older was conducted in Jiading District, Shanghai, China. Logistic regression analysis was used to evaluate the association between serum Lp(a) levels and MetS. Results In the overall population, 37.5% of participants had MetS. Compared with individuals in the lowest quartile of serum Lp(a) levels, those in the highest quartile had a lower prevalence of MetS(30.9% vs. 46.9%, P for trend < 0.0001). Multivariate logistic regression analyses showed that compared with participants in the bottom quartile of serum Lp(a) levels, those in the top quartile had decreased odds ratio(OR) for prevalent MetS [multivariate-adjusted OR 0.45(95% confidence interval 0.39-0.51);P < 0.0001]. Additionally, Lp(a) level was conversely associated with the risk of central obesity, high fasting glucose, high triglycerides, and low HDL cholesterol, but not with hypertension. Stratified analyses suggested that increasing levels of Lp(a) was associated with decreased risk of MetS in all the subgroups. Conclusion Serum Lp(a) level was inversely associated with the risk of prevalent MetS in a middle-aged and elderly Chinese cohort.展开更多
Objective Liver fibrosis is an important predictor of mortality in nonalcoholic fatty liver disease(NAFLD).Peripheral artery disease(PAD)and liver fibrosis share many common metabolic dysfunctions.We aimed to explore ...Objective Liver fibrosis is an important predictor of mortality in nonalcoholic fatty liver disease(NAFLD).Peripheral artery disease(PAD)and liver fibrosis share many common metabolic dysfunctions.We aimed to explore the association between PAD and risk of fibrosis deterioration in NAFLD patients.Methods The study recruited 1,610 NAFLD patients aged≥40 years from a well-defined community at baseline in 2010 and followed up between August 2014 and May 2015.Fibrosis deterioration was defined as the NAFLD fibrosis score(NFS)status increased to a higher category at the follow-up visit.PAD was defined as an ankle-brachial index of<0.90 or>1.40.Results During an average of 4.3 years’follow-up,618 patients progressed to a higher NFS category.PAD was associated with 92%increased risk of fibrosis deterioration[multivariable-adjusted odds ratio(OR):1.92,95%confidence interval(CI):1.24,2.98].When stratified by baseline NFS status,the OR for progression from low to intermediate or high NFS was 1.74(95%CI:1.02,3.00),and progression from intermediate to high NFS was 2.24(95%CI:1.05,4.80).There was a significant interaction between PAD and insulin resistance(IR)on fibrosis deterioration(P for interaction=0.03).As compared with non-PAD and non-IR,the coexistence of PAD and IR was associated with a 3.85-fold(95%CI:2.06,7.18)increased risk of fibrosis deterioration.Conclusion PAD is associated with an increased risk of fibrosis deterioration in NAFLD patients,especially in those with IR.The coexistence of PAD and IR may impose an interactive effect on the risk of fibrosis deterioration.展开更多
A total of 1 116 middle-aged and elderly men and 1 442 postmenopausal women were recruited in this study. Whether bisphenol A exposure was associated with circulating sex hormone concentrations was studied. Univariate...A total of 1 116 middle-aged and elderly men and 1 442 postmenopausal women were recruited in this study. Whether bisphenol A exposure was associated with circulating sex hormone concentrations was studied. Univariate analysis revealed that the urinary bisphenol A concentration was negatively correlated with the serum levels of luteinizing hormone (B=-0.061, P〈0.0001) and follicle-stimulating hormone (B=-0.086, P〈0.0001) in men, and with the serum levels of follicle-stimulating hormone (B=-0.037, P=0.018) and sex hormone-binding globulin (B=-0.043, P=0.006) in women. However, no significant association was observed between the serum levels of urinary bisphenol A and circulating sex hormone after adjustment for the potential confounders.展开更多
Objective The relationship between serum uric acid(SUA)levels and glycemic indices,including plasma glucose(FPG),2-hour postload glucose(2 h-PG),and glycated hemoglobin(HbA1 c),remains inconclusive.We aimed to explore...Objective The relationship between serum uric acid(SUA)levels and glycemic indices,including plasma glucose(FPG),2-hour postload glucose(2 h-PG),and glycated hemoglobin(HbA1 c),remains inconclusive.We aimed to explore the associations between glycemic indices and SUA levels in the general Chinese population.Methods The current study was a cross-sectional analysis using the first follow-up survey data from The China Cardiometabolic Disease and Cancer Cohort Study.A total of 105,922 community-dwelling adults aged≥40 years underwent the oral glucose tolerance test and uric acid assessment.The nonlinear relationships between glycemic indices and SUA levels were explored using generalized additive models.Results A total of 30,941 men and 62,361 women were eligible for the current analysis.Generalized additive models verified the inverted U-shaped association between glycemic indices and SUA levels,but with different inflection points in men and women.The thresholds for FPG,2 h-PG,and HbA1 c for men and women were 6.5/8.0 mmol/L,11.0/14.0 mmol/L,and 6.1/6.5,respectively(SUA levels increased with increasing glycemic indices before the inflection points and then eventually decreased with further increases in the glycemic indices).Conclusion An inverted U-shaped association was observed between major glycemic indices and uric acid levels in both sexes,while the inflection points were reached earlier in men than in women.展开更多
Severe acute respiratory syndrome coronavirus 2(SARSCo V-2)infection can result in more severe syndromes and poorer outcomes in patients with diabetes and obesity.However,the precise mechanisms responsible for the com...Severe acute respiratory syndrome coronavirus 2(SARSCo V-2)infection can result in more severe syndromes and poorer outcomes in patients with diabetes and obesity.However,the precise mechanisms responsible for the combined impact of coronavirus disease 2019(COVID-19)and diabetes have not yet been elucidated,and effective treatment options for SARS-Co V-2-infected diabetic patients remain limited.To investigate the disease pathogenesis,K18-h ACE2 transgenic(h ACE2^(Tg))mice with a leptin receptor deficiency(h ACE2-Lepr^(-/-))and high-fat diet(h ACE2-HFD)background were generated.The two mouse models were intranasally infected with a 5×10^(5) median tissue culture infectious dose(TCID_(50))of SARSCo V-2,with serum and lung tissue samples collected at 3days post-infection.The h ACE2-Lepr^(-/-)mice were then administered a combination of low-molecular-weight heparin(LMWH)(1 mg/kg or 5 mg/kg)and insulin via subcutaneous injection prior to intranasal infection with1×10^(4) TCID_(50)of SARS-Co V-2.Daily drug administration continued until the euthanasia of the mice.Analyses of viral RNA loads,histopathological changes in lung tissue,and inflammation factors were conducted.Results demonstrated similar SARS-Co V-2 susceptibility in h ACE2^(Tg)mice under both lean(chow diet)and obese(HFD)conditions.However,compared to the h ACE2-Lepr^(+/+)mice,h ACE2-Lepr^(-/-)mice exhibited more severe lung injury,enhanced expression of inflammatory cytokines and hypoxia-inducible factor-1α(HIF-1α),and increased apoptosis.Moreover,combined LMWH and insulin treatment effectively reduced disease progression and severity,attenuated lung pathological changes,and mitigated inflammatory responses.In conclusion,preexisting diabetes can lead to more severe lung damage upon SARS-Co V-2 infection,and LMWH may be a valuable therapeutic approach for managing COVID-19patients with diabetes.展开更多
Objective The association between neutrophil-to-lymphocyte ratio(NLR)with subclinical macrovascular and microvascular diseases has been less investigated.We sought to examine the association between NLR and new-onset ...Objective The association between neutrophil-to-lymphocyte ratio(NLR)with subclinical macrovascular and microvascular diseases has been less investigated.We sought to examine the association between NLR and new-onset subclinical macrovascular and microvascular abnormalities in the Chinese population.Methods From a community cohort,we included 6,430 adults aged≥40 years without subclinical macrovascular and microvascular diseases at baseline.We measured subclinical macrovascular and microvascular abnormalities separately using the ankle-brachial index(ABI),brachial-ankle pulse wave velocity(baPWV),and albuminuria.Results During a mean follow-up of 4.3 years,110 participants developed incident abnormal ABI,746 participants developed incident elevated baPWV,and 503 participants developed incident albuminuria.Poisson regression analysis indicated that NLR was significantly associated with an increased risk of newonset abnormal ABI,elevated baPWV,and albuminuria.Compared to overweight/obese participants,we found a much stronger association between NLR and subclinical vascular abnormalities in participants with normal weight.Furthermore,we found an interaction between the NLR and body mass index(BMI)on the risk of new-onset abnormal ABI(P for interaction:0.01).Conclusion NLR was associated with subclinical macrovascular and microvascular diseases in the Chinese population.Furthermore,in participants with normal weight,the association between NLR and subclinical vascular abnormalities was much stronger.展开更多
Objective This study aimed to examine the association of visit-to-visit variabilities in metabolic factors with chronic kidney disease(CKD)in Shanghai community residents.Methods We used data from a cohort study of co...Objective This study aimed to examine the association of visit-to-visit variabilities in metabolic factors with chronic kidney disease(CKD)in Shanghai community residents.Methods We used data from a cohort study of community residents who participated in three examinations in 2008,2009,and 2013,respectively.Fasting plasma glucose(FPG)level,blood pressure(BP),and lipid levels were determined in 2,109 participants at all three visits,and CKD was evaluated between the second and the third visits.Visit-to-visit variabilities in metabolic factors were described by coefficients of variation(CV)at three visits.A variability score was calculated by adding the numbers of metabolic factors with a high variability defined as the highest quartile of CV.CKD was defined as the estimated glomerular filtration rate<60 mL/min per 1.73 m2 or urinary albumin-to-creatinine ratio≥30 mg/g.Results A total of 200(9.5%)participants had CKD at the third visit.Compared with the lowest quartile of CV,the highest quartile was associated with a 70%increased risk of CKD for FPG[odds ratio,OR=1.70;95%confidence interval(CI)1.06–2.72],62%for systolic BP(OR=1.62,95%CI 1.04–2.50),and 85%for low-density lipoprotein cholesterol(OR=1.85,95%CI 1.23–2.80).Furthermore,the risk of CKD increased significantly with an increasing variability score.Compared with participants with score 0,participants with scores of 1,2,and 3 were associated with 58%(OR=1.58,95%CI 1.08–2.32),121%(OR=2.21,95%CI 1.40–3.49),and 548%(OR=6.48,95%CI 3.18–13.21)higher risks of CKD,respectively.Conclusion The visit-to-visit variabilities in metabolic factors were significantly associated with the risks of CKD in Shanghai community residents.展开更多
Diabetes has become a serious public health concern worldwide,and China is the epidemic center.In China,the prevalence of type 2 diabetes(T2D)was 11.6%among adults aged≥18 years[1].Cardiovascular disease(CVD)occurs e...Diabetes has become a serious public health concern worldwide,and China is the epidemic center.In China,the prevalence of type 2 diabetes(T2D)was 11.6%among adults aged≥18 years[1].Cardiovascular disease(CVD)occurs earlier and with greater severity in patients with T2D than in individuals without T2D[2].Thus,potential risk factors for screening T2D are needed to prevent such poor clinical outcomes.展开更多
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 ...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.展开更多
Malnutrition in early life increases the risk of osteoporosis,but the association of early-life undernutrition combined with adulthood obesity patterns with low-energy fracture remains unknown.This study included 5323...Malnutrition in early life increases the risk of osteoporosis,but the association of early-life undernutrition combined with adulthood obesity patterns with low-energy fracture remains unknown.This study included 5323 community-dwelling subjects aged⩾40 years from China.Early-life famine exposure was identified based on the participants’birth dates.General obesity was assessed using the body mass index(BMI),and abdominal obesity was evaluated with the waist-to-hip ratio(WHR).Low-energy fracture was defined as fracture occurring after the age of⩾40 typically caused by falls from standing height or lower.Compared to the nonexposed group,the group with fetal,childhood,and adolescence famine exposure was associated with an increased risk of fracture in women with odds ratios(ORs)and 95%confidence intervals(CIs)of 3.55(1.57–8.05),3.90(1.57–9.71),and 3.53(1.05–11.88),respectively,but not in men.Significant interactions were observed between fetal famine exposure and general obesity with fracture among women(P for interaction=0.0008).Furthermore,compared with the groups with normal BMI and WHR,the group of women who underwent fetal famine exposure and had both general and abdominal obesity had the highest risk of fracture(OR,95%CI:3.32,1.17–9.40).These results indicate that early-life famine exposure interacts with adulthood general obesity and significantly increases the risk of low-energy fracture later in life in women.展开更多
Background and Aims:Stress granules(SGs)as membrane-less cytoplasmic foci formed in response to unfavorable external stimuli could promote cancer cells to adapt to hostile environments.Hepatocellular carcinoma(HCC)is ...Background and Aims:Stress granules(SGs)as membrane-less cytoplasmic foci formed in response to unfavorable external stimuli could promote cancer cells to adapt to hostile environments.Hepatocellular carcinoma(HCC)is prone to be highly aggressive once diagnosed,which markedly reduces patient survival time.Therefore,it is crucial to develop valid diagnostic markers to prognosticate HCC patient prognosis,which promotes individualized precision therapeutics in HCC.Considering the pro-tumorigenic activity of SGs,it is of great potential value to construct a prognostic tool for HCC based on the expression profiles of SG-related genes(SGGs).Methods:Bioinformatic analysis was employed to establish an SGG-based prognostic signature.Western blotting and realtime polymerase chain reaction assays were used to assess the expression patterns of the related SGGs.Loss-of-function experiments were performed to analyze the effect of the SGGs on SG formation and cell survival.Results:A four-SGG signature(KPNA2,MEX3A,WDR62,and SFN)targeting HCC was established and validated to exhibit a robust performance in predicting HCC prognosis.Consistently,all four genes were further found to be highly expressed in human HCC tissues.More important,we demonstrated that individually knocking down the four SGGs significantly reduced HCC cell proliferation and metastasis by compromising the SG formation process.Conclusions:We developed an SGG-based predictive signature that can be used as an independent prognostic tool for HCC.The strong predictive power of this signature was further elucidated by the carcinogenic activity of KPNA2,MEX3A,WDR62,and SFN in HCC cells by regulating SG formation.展开更多
BACKGROUND The cognitive impairment in type 2 diabetes mellitus(T2DM)is a multifaceted and advancing state that requires further exploration to fully comprehend.Neu-roinflammation is considered to be one of the main m...BACKGROUND The cognitive impairment in type 2 diabetes mellitus(T2DM)is a multifaceted and advancing state that requires further exploration to fully comprehend.Neu-roinflammation is considered to be one of the main mechanisms and the immune system has played a vital role in the progression of the disease.AIM To identify and validate the immune-related genes in the hippocampus associated with T2DM-related cognitive impairment.METHODS To identify differentially expressed genes(DEGs)between T2DM and controls,we used data from the Gene Expression Omnibus database GSE125387.To identify T2DM module genes,we used Weighted Gene Co-Expression Network Analysis.All the genes were subject to Gene Set Enrichment Analysis.Protein-protein interaction network construction and machine learning were utilized to identify three hub genes.Immune cell infiltration analysis was performed.The three hub genes were validated in GSE152539 via receiver operating characteristic curve analysis.Validation experiments including reverse transcription quantitative real-time PCR,Western blotting and immunohistochemistry were conducted both in vivo and in vitro.To identify potential drugs associated with hub genes,we used the Comparative Toxicogenomics Database(CTD).RESULTS A total of 576 DEGs were identified using GSE125387.By taking the intersection of DEGs,T2DM module genes,and immune-related genes,a total of 59 genes associated with the immune system were identified.Afterward,machine learning was utilized to identify three hub genes(H2-T24,Rac3,and Tfrc).The hub genes were associated with a variety of immune cells.The three hub genes were validated in GSE152539.Validation experiments were conducted at the mRNA and protein levels both in vivo and in vitro,consistent with the bioinformatics analysis.Additionally,11 potential drugs associated with RAC3 and TFRC were identified based on the CTD.CONCLUSION Immune-related genes that differ in expression in the hippocampus are closely linked to microglia.We validated the expression of three hub genes both in vivo and in vitro,consistent with our bioinformatics results.We discovered 11 compounds associated with RAC3 and TFRC.These findings suggest that they are co-regulatory molecules of immunometabolism in diabetic cognitive impairment.展开更多
Studies have found a U-shaped relationship between sleep duration and chronic kidney disease(CKD)risk,but limited research evaluated the association of reallocating excessive sleep to other behavior with CKD.We includ...Studies have found a U-shaped relationship between sleep duration and chronic kidney disease(CKD)risk,but limited research evaluated the association of reallocating excessive sleep to other behavior with CKD.We included 104538 participants from the nationwide cohort of the Risk Evaluation of Cancers in Chinese Diabetic Individuals:A Longitudinal Study,with self-reported time of daily-life behavior.Using isotemporal substitution models,we found that substituting 1 h of sleeping with sitting,walking,or moderate-to-vigorous physical activity was associated with a lower CKD prevalence.Leisure-time physical activity displacement was associated with a greater prevalence reduction than occupational physical activity in working population.In stratified analysis,a lower CKD prevalence related to substitution toward physical activity was found in long sleepers.More pronounced correlations were observed in long sleepers with diabetes than in those with prediabetes,and they benefited from other behavior substitutions toward a more active way.The U-shaped association between sleep duration and CKD prevalence implied the potential effects of insufficient and excessive sleep on the kidneys,in which the pernicious link with oversleep could be reversed by time reallocation to physical activity.The divergence in the predicted effect on CKD following time reallocation to behavior of different domains and intensities and in subpopulations with diverse metabolic statuses underlined the importance of optimizing sleeping patterns and adjusting integral behavioral composition.展开更多
Objective To examine the association between serum uric acid levels and cardiovascular disease risk among individuals without diabetes.Methods We investigated the association between serum uric acid levels and the ris...Objective To examine the association between serum uric acid levels and cardiovascular disease risk among individuals without diabetes.Methods We investigated the association between serum uric acid levels and the risk of prevalent cardiometabolic diseases, 10-year Framingham risk for coronary heart disease, and 10-year risk for atherosclerotic cardiovascular diseases (ASCVD) among 8,252 participants aged 〉 40 years without diabetes from Jiading district, Shanghai, China.Results Body mass index, waist circumference, blood glucose, glycated hemoglobin, blood pressure, and serum lipids increased progressively across the sex-specific quartiles of uric acid (all P trend 〈 0.05). Compared with individuals in the lowest quartile, those in the higher quartiles had a significantly higher prevalence of obesity, hypertension, and dyslipidemia (all P trend 〈 0.05). A fully adjusted logistic regression analysis revealed that individuals in the highest quartile had an increased risk of predicted cardiovascular disease compared with those in the lowest quartile of uric acid. The multivariate adjusted odds ratios (ORs) [95% confidence intervals (C/s)] for the highest quartiles for high Framingham risk were 3.00 (2.00-4.50) in men and 2.95 (1.08-8.43) in women. The multivariate adjusted ORs (95% C/s) for the highest quartile for high ASCVD risk were 1.93 [1.17-3.17) in men and 4.53 (2.57-7.98) in women.Conclusion Serum uric acid level is associated with an increased risk of prevalent obesity, hypertension, dystipidemia, 10-year Framingham risk for coronary heart disease, and lO-year risk for ASCVD among Chinese adults without diabetes.展开更多
This current cross-sectional study investigates the relationship between thyroid hormones and peripheral artery disease (PAD) among euthyroid Chinese population aged 40 years and above. Serum free triiodothyronine ...This current cross-sectional study investigates the relationship between thyroid hormones and peripheral artery disease (PAD) among euthyroid Chinese population aged 40 years and above. Serum free triiodothyronine (FT3), free thyroxin (FT4), thyroid-stimulating hormone (TSH), and thyroid antibodies were measured.展开更多
基金supported by the National Natural Science Foundation of China (21825703, 21927814)the National Key R&D Program of China (2019YFA0405600, 2019YFA0706900, 2021YFA1200104, 2022YFC3400500)+3 种基金the Strategic Priority Research Program of Chinese Academy of Sciences (XDB0540200, XDB37040201)Plans for Major Provincial Science&Technology Projects (202303a07020004)Basic Research Program Based on Major Scientific Infrastructures,CAS (JZHKYPT-2021-05)the Youth Innovation Promotion Association,CAS (2022455)
文摘Bacterial small laccases(SLAC) are promising industrial biocatalysts due to their ability to oxidize a broad range of substrates with exceptional thermostability and tolerance for alkaline p H. Electron transfer between substrate, copper centers, and O2is one of the key steps in the catalytic turnover of SLAC. However, limited research has been conducted on the electron transfer pathway of SLAC and SLAC-catalyzed reactions, hindering further engineering of SLAC to produce tunable biocatalysts for novel applications. Herein, the combinational use of electron paramagnetic resonance(EPR) and ultraviolet-visible(UV-vis) spectroscopic methods coupled with redox titration were employed to monitor the electron transfer processes and obtain further insights into the electron transfer pathway in SLAC. The reduction potentials for type 1 copper(T1Cu), type 2 copper(T2Cu) and type 3copper(T3Cu) were determined to be 367 ± 2 mV, 378 ± 5 m V and 403 ± 2 mV,respectively. Moreover, the reduction potential of a selected substrate of SLAC, hydroquinone(HQ), was determined to be 288 mV using cyclic voltammetry(CV). In this way, an electron transfer pathway was identified based on the reduction potentials. Specifically,electrons are transferred from HQ to T1Cu, then to T2Cu and T3Cu, and finally to O2.Furthermore, superhyperfine splitting observed via EPR during redox titration indicated a modification in the covalency of T2Cu upon electron uptake, suggesting a conformational alteration in the protein environment surrounding the copper sites, which could potentially influence the reduction potential of the copper sites during catalytic processes. The results presented here not only provide a comprehensive method for analyzing the electron transfer pathway in metalloenzymes through reduction potential measurements, but also offer valuable insights for further engineering and directed evolution studies of SLAC in the aim for biotechnological and industrial applications.
基金National Key Research and Development Programme[2018YFC1315305]China CDC’s Scientific Research Project[JY18-2-22]China CDC’s Public Health and Emergency Response Mechanism Programme[131031001000150001]。
文摘Objective To explore the association between soil selenium levels and the risk of diabetes in Chinese adults aged 35–74 years.Methods Data for this study were derived from the China Chronic Diseases and Behavioral Risk Factors Surveillance 2010 survey.Selenium concentrations in soil were obtained from the Atlas of Soil Environmental Background Values in China.A two-level binary logistic regression model was used to determine the association between soil selenium concentrations and the risk of diabetes,with participants nested within districts/counties.Results A total of 69,332 participants aged 35–74 years,from 158 districts/counties were included in the analysis.Concentrations of selenium in soil varied greatly across the 158 districts/counties,with a median concentration of 0.219 mg/kg(IQR:0.185–0.248).The results showed that both Quartile 1(0.119–0.185 mg/kg)and Quartile 4(0.249–0.344 mg/kg)groups were positively associated with diabetes compared to a soil selenium concentration of 0.186–0.219 mg/kg(Quartile 2),crude odds ratios(ORs)(95%CI)were 1.227(1.003–1.502)and 1.280(1.048–1.563).The P values were 0.045 and 0.013,for Quartile 1 and Quartile 4 groups,respectively.After adjusting for all confounding factors of interest,the Quartile 1 group became non-significant,and the Quartile 4 group had an adjusted OR(95%CI)of 1.203(1.018–1.421)relative to the reference group(Quartile 2),the P values was 0.030.No significant results were seen for the Quartile 3 group(0.220–0.248 mg/kg)compared to the reference group.Conclusion Excessive selenium concentrations in soil could increase the risk of diabetes among Chinese adults aged 35–74 years.
基金supported by the Ministry of Science and Technology of the People's Republic of China [Grant Number 2016YFC1305202]the National Natural Science Foundation of China [Grant Numbers 81670795 and 81700764]+2 种基金the Shanghai Municipal Education Commission [Grant Numbers 15SG15 and 20152202]the Shanghai Municipal Health Commission [Grant Number 201740040]the Shanghai Sailing Program [Grant Numbers 18YF1419900 and 17YF1416800]
文摘Metabolic syndrome(MetS) is a cluster of metabolic disorders including obesity, hypertension, hyperglycemia, elevated triglyceride levels, and low high-density lipoprotein cholesterol(HDL-C) levels. In recent years, the prevalence of MetS[1]has increased dramatically worldwide.
基金supported by the Shanghai Science and Technology Commission[19411964200]National Natural Science Foundation of China[81930021,81970728,81970691,82170819,and 21904084]+4 种基金Shanghai Outstanding Academic Leaders Plan[20XD1422800]Chinese Academy of Medical Sciences[2018PT32017 and 2019PT330006]Shanghai Medical and Health Development Foundation[DMRFP_I_01]Clinical Research Plan of SHDC[SHDC2020CR3064B]Science and Technology Committee of Shanghai[20Y11905100]
文摘Nonalcoholic fatty liver disease(NAFLD)is known for its insidious onset and chronic nature,which have jeopardized the health and life of 29.2%of adults in China[1].In 2020,metabolic dysfunctionassociated fatty liver disease(MAFLD),a more accurate nomenclature to replace NAFLD,was put forward in an international consensus of experts involving 22 countries[2].In China,at least 300 million people will suffer from MAFLD by 2030,which will be a heavy burden on national health[3].
基金Supported by National Nature Science Foundation of China(30771018)Shanghai Rising-Star Program,China(08QA14057)
文摘Multiple endocrine neoplasia type 2A ( MEN2A ) is an autosomal dominant cancer syndrome that is characterized by medullary thyroid carcinoma (MTC), pheochromaocytoma (50% - 60% of cases ), and hyperplasia of the parathyroid glands ( 20% - 30% of cases ). MEN-2A comprises a heterogeneous group of neoplastic disorders that most commonly have a single missense substitution of the Ret proto-oncogene (RET) involving exons 10 and 11. Here, we reported a novel case of MEN2A associated with two variations in two distinct genes, Cys634Gly in RET and a rare Ser73Gly substitution in succinate dehydrogenase, subunit D (SDHD). Because the patient presented with medullary thyroid carcinoma and pheochromocytoma but without parathyroid gland involvement, we speculated that this clinical feature could be correlated with the two substitutions. This is the first report of a MEN2A case involving two different changes one in the RET gene and the other in the SDHD gene.
基金supported by grants from the Ministry of Science and Technology of the People’s Republic of China [2016YFC1305202]Shanghai Sailing Program [17YF1416800]+1 种基金supported by the ‘Chenxing Plan’ of Shanghai Jiaotong University,Shuguang Program [15SG15]Gaofeng Clinical Medicine Grant Support [20152202] from Shanghai Municipal Education Commission
文摘Objective The association between lipoprotein(a)[Lp(a)] levels and metabolic syndrome(MetS) remains uncertain, especially in the Asian population. The purpose of this study was to demonstrate the association between Lp(a) levels and MetS in a middle-aged and elderly Chinese cohort. Methods A cross-sectional study of 10,336 Chinese adults aged 40 years or older was conducted in Jiading District, Shanghai, China. Logistic regression analysis was used to evaluate the association between serum Lp(a) levels and MetS. Results In the overall population, 37.5% of participants had MetS. Compared with individuals in the lowest quartile of serum Lp(a) levels, those in the highest quartile had a lower prevalence of MetS(30.9% vs. 46.9%, P for trend < 0.0001). Multivariate logistic regression analyses showed that compared with participants in the bottom quartile of serum Lp(a) levels, those in the top quartile had decreased odds ratio(OR) for prevalent MetS [multivariate-adjusted OR 0.45(95% confidence interval 0.39-0.51);P < 0.0001]. Additionally, Lp(a) level was conversely associated with the risk of central obesity, high fasting glucose, high triglycerides, and low HDL cholesterol, but not with hypertension. Stratified analyses suggested that increasing levels of Lp(a) was associated with decreased risk of MetS in all the subgroups. Conclusion Serum Lp(a) level was inversely associated with the risk of prevalent MetS in a middle-aged and elderly Chinese cohort.
基金Grants from the Ministry of Science and Technology of China[2018YFC1311705,2016YFC1305600,and 2016YFC1304904]the National Natural Science Foundation of China[81770842,81941017,and 81870604]+1 种基金the Shanghai Science and Technology Commission[YDZX20173100004881]the Shanghai Shen-Kang Hospital Development Center[SHDC12016202]。
文摘Objective Liver fibrosis is an important predictor of mortality in nonalcoholic fatty liver disease(NAFLD).Peripheral artery disease(PAD)and liver fibrosis share many common metabolic dysfunctions.We aimed to explore the association between PAD and risk of fibrosis deterioration in NAFLD patients.Methods The study recruited 1,610 NAFLD patients aged≥40 years from a well-defined community at baseline in 2010 and followed up between August 2014 and May 2015.Fibrosis deterioration was defined as the NAFLD fibrosis score(NFS)status increased to a higher category at the follow-up visit.PAD was defined as an ankle-brachial index of<0.90 or>1.40.Results During an average of 4.3 years’follow-up,618 patients progressed to a higher NFS category.PAD was associated with 92%increased risk of fibrosis deterioration[multivariable-adjusted odds ratio(OR):1.92,95%confidence interval(CI):1.24,2.98].When stratified by baseline NFS status,the OR for progression from low to intermediate or high NFS was 1.74(95%CI:1.02,3.00),and progression from intermediate to high NFS was 2.24(95%CI:1.05,4.80).There was a significant interaction between PAD and insulin resistance(IR)on fibrosis deterioration(P for interaction=0.03).As compared with non-PAD and non-IR,the coexistence of PAD and IR was associated with a 3.85-fold(95%CI:2.06,7.18)increased risk of fibrosis deterioration.Conclusion PAD is associated with an increased risk of fibrosis deterioration in NAFLD patients,especially in those with IR.The coexistence of PAD and IR may impose an interactive effect on the risk of fibrosis deterioration.
基金supported by the grants from Key Laboratory for Endocrine and Metabolic Diseases of Ministry of Health(1994DP131044)National Natural Science Foundation of China(No.81170739,81170719,81270877,81222008,81200563)+3 种基金Shanghai New Excellent Youth Program(XYQ2011009)Shanghai Health Bureau(2011293)Shanghai Committee of Science and Technology(12PJ1407700)EFSD-CDS-Lilly Program for Collaborative Research between China and Europe(2011)
文摘A total of 1 116 middle-aged and elderly men and 1 442 postmenopausal women were recruited in this study. Whether bisphenol A exposure was associated with circulating sex hormone concentrations was studied. Univariate analysis revealed that the urinary bisphenol A concentration was negatively correlated with the serum levels of luteinizing hormone (B=-0.061, P〈0.0001) and follicle-stimulating hormone (B=-0.086, P〈0.0001) in men, and with the serum levels of follicle-stimulating hormone (B=-0.037, P=0.018) and sex hormone-binding globulin (B=-0.043, P=0.006) in women. However, no significant association was observed between the serum levels of urinary bisphenol A and circulating sex hormone after adjustment for the potential confounders.
基金supported by grants from the Ministry of Science and Technology of the People’s Republic of China[grant nos.2016YFC1305600,2016YFC1305202,2016YFC1304904,2017YFC1310700,2018YFC1311800]the National Natural Science Foundation of China[grant nos.81970706,81970691,81970728,81800683]。
文摘Objective The relationship between serum uric acid(SUA)levels and glycemic indices,including plasma glucose(FPG),2-hour postload glucose(2 h-PG),and glycated hemoglobin(HbA1 c),remains inconclusive.We aimed to explore the associations between glycemic indices and SUA levels in the general Chinese population.Methods The current study was a cross-sectional analysis using the first follow-up survey data from The China Cardiometabolic Disease and Cancer Cohort Study.A total of 105,922 community-dwelling adults aged≥40 years underwent the oral glucose tolerance test and uric acid assessment.The nonlinear relationships between glycemic indices and SUA levels were explored using generalized additive models.Results A total of 30,941 men and 62,361 women were eligible for the current analysis.Generalized additive models verified the inverted U-shaped association between glycemic indices and SUA levels,but with different inflection points in men and women.The thresholds for FPG,2 h-PG,and HbA1 c for men and women were 6.5/8.0 mmol/L,11.0/14.0 mmol/L,and 6.1/6.5,respectively(SUA levels increased with increasing glycemic indices before the inflection points and then eventually decreased with further increases in the glycemic indices).Conclusion An inverted U-shaped association was observed between major glycemic indices and uric acid levels in both sexes,while the inflection points were reached earlier in men than in women.
基金supported by the Strategic Priority Research Program of the Chinese Academy of Sciences (CAS) (XDB29010102)National Natural Science Foundation of China (NSFC) (91957124,82161148010,32041010)+4 种基金Self-supporting Program of Guangzhou Laboratory (SRPG22-001)National Science and Technology Infrastructure of China (National Pathogen Resource Center-NPRC-32)Management Strategy of the Tertiary Prevention and Treatment of Diabetes Based on DIP system (supported by China Health Promotion Foundation)supported by the Youth Innovation Promotion Association of CAS (Y2021034)Innovation Team and Talents Cultivation Program of the National Administration of Traditional Chinese Medicine (ZYYCXTD-D-202208)。
文摘Severe acute respiratory syndrome coronavirus 2(SARSCo V-2)infection can result in more severe syndromes and poorer outcomes in patients with diabetes and obesity.However,the precise mechanisms responsible for the combined impact of coronavirus disease 2019(COVID-19)and diabetes have not yet been elucidated,and effective treatment options for SARS-Co V-2-infected diabetic patients remain limited.To investigate the disease pathogenesis,K18-h ACE2 transgenic(h ACE2^(Tg))mice with a leptin receptor deficiency(h ACE2-Lepr^(-/-))and high-fat diet(h ACE2-HFD)background were generated.The two mouse models were intranasally infected with a 5×10^(5) median tissue culture infectious dose(TCID_(50))of SARSCo V-2,with serum and lung tissue samples collected at 3days post-infection.The h ACE2-Lepr^(-/-)mice were then administered a combination of low-molecular-weight heparin(LMWH)(1 mg/kg or 5 mg/kg)and insulin via subcutaneous injection prior to intranasal infection with1×10^(4) TCID_(50)of SARS-Co V-2.Daily drug administration continued until the euthanasia of the mice.Analyses of viral RNA loads,histopathological changes in lung tissue,and inflammation factors were conducted.Results demonstrated similar SARS-Co V-2 susceptibility in h ACE2^(Tg)mice under both lean(chow diet)and obese(HFD)conditions.However,compared to the h ACE2-Lepr^(+/+)mice,h ACE2-Lepr^(-/-)mice exhibited more severe lung injury,enhanced expression of inflammatory cytokines and hypoxia-inducible factor-1α(HIF-1α),and increased apoptosis.Moreover,combined LMWH and insulin treatment effectively reduced disease progression and severity,attenuated lung pathological changes,and mitigated inflammatory responses.In conclusion,preexisting diabetes can lead to more severe lung damage upon SARS-Co V-2 infection,and LMWH may be a valuable therapeutic approach for managing COVID-19patients with diabetes.
基金supported by the grants from the National Key R&D Program of China[2017YFC1310700,2016YFC1305600,2016YFC0901200,2016YFC1305202,2016YFC1304904,2018YFC1311800,2018YFC1311705]the National Natural Science Foundation of China[81870560,81561128019,81621061,81700764,81941017,81770842]+9 种基金the Chinese Academy of Medical Sciences[2018PT32017,2019PT330006]the Shanghai Municipal Government[18411951800]the Shanghai Shenkang Hospital Development Center[SHDC12019101]Shanghai Municipal Commission of Health and Family Planning[20174Y0014]National Major Scientific and Technological Special Project for“Significant New Drugs Development”[2017ZX09304007]Shanghai Rising-Star Program[21QA1408100]the Scientific and Technological Committee of Shanghai[19411964200]Innovative research team of high-level local universities in Shanghaithe Shanghai Jiaotong University School of Medicine[DLY201801,20161301,20161307]the Ruijin Hospital[2018CR002]。
文摘Objective The association between neutrophil-to-lymphocyte ratio(NLR)with subclinical macrovascular and microvascular diseases has been less investigated.We sought to examine the association between NLR and new-onset subclinical macrovascular and microvascular abnormalities in the Chinese population.Methods From a community cohort,we included 6,430 adults aged≥40 years without subclinical macrovascular and microvascular diseases at baseline.We measured subclinical macrovascular and microvascular abnormalities separately using the ankle-brachial index(ABI),brachial-ankle pulse wave velocity(baPWV),and albuminuria.Results During a mean follow-up of 4.3 years,110 participants developed incident abnormal ABI,746 participants developed incident elevated baPWV,and 503 participants developed incident albuminuria.Poisson regression analysis indicated that NLR was significantly associated with an increased risk of newonset abnormal ABI,elevated baPWV,and albuminuria.Compared to overweight/obese participants,we found a much stronger association between NLR and subclinical vascular abnormalities in participants with normal weight.Furthermore,we found an interaction between the NLR and body mass index(BMI)on the risk of new-onset abnormal ABI(P for interaction:0.01).Conclusion NLR was associated with subclinical macrovascular and microvascular diseases in the Chinese population.Furthermore,in participants with normal weight,the association between NLR and subclinical vascular abnormalities was much stronger.
基金the grants from the National Key R&D Program of China[2017YFC1310700,2016YFC1305600,2018YFC1311800,2016YFC0901200]the National Natural Science Foundation of China[81870560,81700764,81561128019]+4 种基金the Shanghai Municipal Government[18411951800]the Shanghai Shenkang Hospital Development Center[SHDC12019101]the Shanghai Jiaotong University School of Medicine[DLY201801]the Ruijin Hospital[2018CR002]the Shanghai Municipal Education Commission[HJWR20196619]。
文摘Objective This study aimed to examine the association of visit-to-visit variabilities in metabolic factors with chronic kidney disease(CKD)in Shanghai community residents.Methods We used data from a cohort study of community residents who participated in three examinations in 2008,2009,and 2013,respectively.Fasting plasma glucose(FPG)level,blood pressure(BP),and lipid levels were determined in 2,109 participants at all three visits,and CKD was evaluated between the second and the third visits.Visit-to-visit variabilities in metabolic factors were described by coefficients of variation(CV)at three visits.A variability score was calculated by adding the numbers of metabolic factors with a high variability defined as the highest quartile of CV.CKD was defined as the estimated glomerular filtration rate<60 mL/min per 1.73 m2 or urinary albumin-to-creatinine ratio≥30 mg/g.Results A total of 200(9.5%)participants had CKD at the third visit.Compared with the lowest quartile of CV,the highest quartile was associated with a 70%increased risk of CKD for FPG[odds ratio,OR=1.70;95%confidence interval(CI)1.06–2.72],62%for systolic BP(OR=1.62,95%CI 1.04–2.50),and 85%for low-density lipoprotein cholesterol(OR=1.85,95%CI 1.23–2.80).Furthermore,the risk of CKD increased significantly with an increasing variability score.Compared with participants with score 0,participants with scores of 1,2,and 3 were associated with 58%(OR=1.58,95%CI 1.08–2.32),121%(OR=2.21,95%CI 1.40–3.49),and 548%(OR=6.48,95%CI 3.18–13.21)higher risks of CKD,respectively.Conclusion The visit-to-visit variabilities in metabolic factors were significantly associated with the risks of CKD in Shanghai community residents.
基金the National Natural Science Foundation of China[Grant/Award Number 81870604]Ministry of Science and Technology of the People's Republic of China[Grand/Award Number 2016YFC1304904]Yuhong Chen was supported by the Shanghai Shenkang Hospital Development Center for improving the control of type 2 diabetes in the suburbs of Shanghai[16CR4020A].
文摘Diabetes has become a serious public health concern worldwide,and China is the epidemic center.In China,the prevalence of type 2 diabetes(T2D)was 11.6%among adults aged≥18 years[1].Cardiovascular disease(CVD)occurs earlier and with greater severity in patients with T2D than in individuals without T2D[2].Thus,potential risk factors for screening T2D are needed to prevent such poor clinical outcomes.
基金supported by grants from the National Key R&D Program of China(Grant No.2021YFC2500500)the National Natural Science Foundation of China(Grant Nos.82070464,81941022,81530025)+4 种基金the Strategic Priority Research Program of the Chinese Academy of Sciences(Grant No.XDB38010100)supported by Program for Innovative Research Team of The First Affliated Hospital of USTC(CXGG02)Anhui Provincial Key Research and Development Program(Grant No.202104j07020051)Anhui Provincial Natural Science Foundation(Grant No.2208085J08)Local Innovative and Research Teams Project of Guangdong Pearl River Talents Program(Grant No.2017BT01S131)。
文摘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.
基金supported by the Ministry of Science and Technology of China(No.2022YFC2505202)the National Natural Science Foundation of China(Nos.81970691 and 82170819)+4 种基金Shanghai Outstanding Academic Leaders Plan(No.20XD1422800)Shanghai Medical and Health Development Foundation(No.DMRFP_I_01)Clinical Research Plan of SHDC(No.SHDC2020CR3064B)Science and Technology Committee of Shanghai(No.20Y11905100)Key Medical Subject of Jiading District,Shanghai(No.2020-jdyxzdzk-01).
文摘Malnutrition in early life increases the risk of osteoporosis,but the association of early-life undernutrition combined with adulthood obesity patterns with low-energy fracture remains unknown.This study included 5323 community-dwelling subjects aged⩾40 years from China.Early-life famine exposure was identified based on the participants’birth dates.General obesity was assessed using the body mass index(BMI),and abdominal obesity was evaluated with the waist-to-hip ratio(WHR).Low-energy fracture was defined as fracture occurring after the age of⩾40 typically caused by falls from standing height or lower.Compared to the nonexposed group,the group with fetal,childhood,and adolescence famine exposure was associated with an increased risk of fracture in women with odds ratios(ORs)and 95%confidence intervals(CIs)of 3.55(1.57–8.05),3.90(1.57–9.71),and 3.53(1.05–11.88),respectively,but not in men.Significant interactions were observed between fetal famine exposure and general obesity with fracture among women(P for interaction=0.0008).Furthermore,compared with the groups with normal BMI and WHR,the group of women who underwent fetal famine exposure and had both general and abdominal obesity had the highest risk of fracture(OR,95%CI:3.32,1.17–9.40).These results indicate that early-life famine exposure interacts with adulthood general obesity and significantly increases the risk of low-energy fracture later in life in women.
基金funded by the National Natural Science Foundation of China(32200557 to DW)the“Outstanding University Driven by Talents”Program and Academic Promotion Program of Shandong First Medical University(2019LJ007 to JZ)+1 种基金the Natural Science Foundation of Shandong Province(ZR2022QH271 to DW)the Postdoctoral Innovative Projects of Shandong Province(SDCX-ZG-202203047 to DW).
文摘Background and Aims:Stress granules(SGs)as membrane-less cytoplasmic foci formed in response to unfavorable external stimuli could promote cancer cells to adapt to hostile environments.Hepatocellular carcinoma(HCC)is prone to be highly aggressive once diagnosed,which markedly reduces patient survival time.Therefore,it is crucial to develop valid diagnostic markers to prognosticate HCC patient prognosis,which promotes individualized precision therapeutics in HCC.Considering the pro-tumorigenic activity of SGs,it is of great potential value to construct a prognostic tool for HCC based on the expression profiles of SG-related genes(SGGs).Methods:Bioinformatic analysis was employed to establish an SGG-based prognostic signature.Western blotting and realtime polymerase chain reaction assays were used to assess the expression patterns of the related SGGs.Loss-of-function experiments were performed to analyze the effect of the SGGs on SG formation and cell survival.Results:A four-SGG signature(KPNA2,MEX3A,WDR62,and SFN)targeting HCC was established and validated to exhibit a robust performance in predicting HCC prognosis.Consistently,all four genes were further found to be highly expressed in human HCC tissues.More important,we demonstrated that individually knocking down the four SGGs significantly reduced HCC cell proliferation and metastasis by compromising the SG formation process.Conclusions:We developed an SGG-based predictive signature that can be used as an independent prognostic tool for HCC.The strong predictive power of this signature was further elucidated by the carcinogenic activity of KPNA2,MEX3A,WDR62,and SFN in HCC cells by regulating SG formation.
基金Supported by National Natural Science Foundation of China,No.82270845。
文摘BACKGROUND The cognitive impairment in type 2 diabetes mellitus(T2DM)is a multifaceted and advancing state that requires further exploration to fully comprehend.Neu-roinflammation is considered to be one of the main mechanisms and the immune system has played a vital role in the progression of the disease.AIM To identify and validate the immune-related genes in the hippocampus associated with T2DM-related cognitive impairment.METHODS To identify differentially expressed genes(DEGs)between T2DM and controls,we used data from the Gene Expression Omnibus database GSE125387.To identify T2DM module genes,we used Weighted Gene Co-Expression Network Analysis.All the genes were subject to Gene Set Enrichment Analysis.Protein-protein interaction network construction and machine learning were utilized to identify three hub genes.Immune cell infiltration analysis was performed.The three hub genes were validated in GSE152539 via receiver operating characteristic curve analysis.Validation experiments including reverse transcription quantitative real-time PCR,Western blotting and immunohistochemistry were conducted both in vivo and in vitro.To identify potential drugs associated with hub genes,we used the Comparative Toxicogenomics Database(CTD).RESULTS A total of 576 DEGs were identified using GSE125387.By taking the intersection of DEGs,T2DM module genes,and immune-related genes,a total of 59 genes associated with the immune system were identified.Afterward,machine learning was utilized to identify three hub genes(H2-T24,Rac3,and Tfrc).The hub genes were associated with a variety of immune cells.The three hub genes were validated in GSE152539.Validation experiments were conducted at the mRNA and protein levels both in vivo and in vitro,consistent with the bioinformatics analysis.Additionally,11 potential drugs associated with RAC3 and TFRC were identified based on the CTD.CONCLUSION Immune-related genes that differ in expression in the hippocampus are closely linked to microglia.We validated the expression of three hub genes both in vivo and in vitro,consistent with our bioinformatics results.We discovered 11 compounds associated with RAC3 and TFRC.These findings suggest that they are co-regulatory molecules of immunometabolism in diabetic cognitive impairment.
基金supported by the grants from the National Natural Science Foundation of China(Nos.82088102,91857205,82022011,81970728,and 81930021)the Shanghai Rising-Star Program(No.21QA1408100)+2 种基金Shanghai Outstanding Academic Leaders Plan(No.20XD1422800)the National Top Young Scholar Program(Yu Xu),the Innovative Research Team of High-Level Local Universities in Shanghai,the Shanghai Clinical Research Center for Metabolic Diseases(No.19MC1910100)the Shanghai Shen Kang Hospital Development Center(Nos.SHDC2020CR1001A and SHDC2020CR3064B).
文摘Studies have found a U-shaped relationship between sleep duration and chronic kidney disease(CKD)risk,but limited research evaluated the association of reallocating excessive sleep to other behavior with CKD.We included 104538 participants from the nationwide cohort of the Risk Evaluation of Cancers in Chinese Diabetic Individuals:A Longitudinal Study,with self-reported time of daily-life behavior.Using isotemporal substitution models,we found that substituting 1 h of sleeping with sitting,walking,or moderate-to-vigorous physical activity was associated with a lower CKD prevalence.Leisure-time physical activity displacement was associated with a greater prevalence reduction than occupational physical activity in working population.In stratified analysis,a lower CKD prevalence related to substitution toward physical activity was found in long sleepers.More pronounced correlations were observed in long sleepers with diabetes than in those with prediabetes,and they benefited from other behavior substitutions toward a more active way.The U-shaped association between sleep duration and CKD prevalence implied the potential effects of insufficient and excessive sleep on the kidneys,in which the pernicious link with oversleep could be reversed by time reallocation to physical activity.The divergence in the predicted effect on CKD following time reallocation to behavior of different domains and intensities and in subpopulations with diverse metabolic statuses underlined the importance of optimizing sleeping patterns and adjusting integral behavioral composition.
基金supported by Grants from the Ministry of Science and Technology of the People’s Republic of China[2016YFC1305202,2016YFC1305601,2016YFC0901201,2016YFC1304904]the National Natural Science Foundation of China[81670795]
文摘Objective To examine the association between serum uric acid levels and cardiovascular disease risk among individuals without diabetes.Methods We investigated the association between serum uric acid levels and the risk of prevalent cardiometabolic diseases, 10-year Framingham risk for coronary heart disease, and 10-year risk for atherosclerotic cardiovascular diseases (ASCVD) among 8,252 participants aged 〉 40 years without diabetes from Jiading district, Shanghai, China.Results Body mass index, waist circumference, blood glucose, glycated hemoglobin, blood pressure, and serum lipids increased progressively across the sex-specific quartiles of uric acid (all P trend 〈 0.05). Compared with individuals in the lowest quartile, those in the higher quartiles had a significantly higher prevalence of obesity, hypertension, and dyslipidemia (all P trend 〈 0.05). A fully adjusted logistic regression analysis revealed that individuals in the highest quartile had an increased risk of predicted cardiovascular disease compared with those in the lowest quartile of uric acid. The multivariate adjusted odds ratios (ORs) [95% confidence intervals (C/s)] for the highest quartiles for high Framingham risk were 3.00 (2.00-4.50) in men and 2.95 (1.08-8.43) in women. The multivariate adjusted ORs (95% C/s) for the highest quartile for high ASCVD risk were 1.93 [1.17-3.17) in men and 4.53 (2.57-7.98) in women.Conclusion Serum uric acid level is associated with an increased risk of prevalent obesity, hypertension, dystipidemia, 10-year Framingham risk for coronary heart disease, and lO-year risk for ASCVD among Chinese adults without diabetes.
基金supported by the National Natural Science Foundation of China(No.81370960 and 81670795)the Ministry of Science and Technology(No.2015BAI12B14,2015BAI12B02,2016YFC0901200,and 2016YFC1305202)
文摘This current cross-sectional study investigates the relationship between thyroid hormones and peripheral artery disease (PAD) among euthyroid Chinese population aged 40 years and above. Serum free triiodothyronine (FT3), free thyroxin (FT4), thyroid-stimulating hormone (TSH), and thyroid antibodies were measured.