Background:Although light-intensity physical activity(LPA)has been suggested to be associated with a lower risk of mortality,the minimal and optimal volumes of LPA remain unclear.We aimed to examine the minimal and op...Background:Although light-intensity physical activity(LPA)has been suggested to be associated with a lower risk of mortality,the minimal and optimal volumes of LPA remain unclear.We aimed to examine the minimal and optimal volumes of LPA associated with the risks of mortality and disease incidence(i.e.,cardiovascular diseases and cancer).Methods:Data were derived from the population-based UK Biobank cohort study,including 69,492 adults aged 43-78 years.Accelerometermeasured LPA was defined using a validated,published machine learning-based Random Forest activity method,which was categorized into 4 quartile groups.All-cause and cause-specific mortality(cardiovascular disease-and cancer-specific)were determined according to the International Classification of Diseases,10th version codes.Disease incidence was defined based on primary care,hospitalization,or death records.Results:During a median follow-up period of 8.04 years,2024 adults died from all causes,539 from cardiovascular disease,and 1175 from cancer.For all-cause mortality,compared with participants in the lowest quartile of LPA(<3.9 h/day),the hazard ratios(HRs)and 95%confidence intervals(95%CIs)were 0.82(95%CI:0.73-0.93)for those with 3.9 to<5.0 h/day,0.75(95%CI:0.66-0.85)for those with 5.0 to<6.1 h/day,and 0.77(95%CI:0.68-0.88)for those with≥6.1 h/day,respectively.There was an inverse non-linear dose-response association between LPA and all-cause mortality,with an optimal dose of 5.72 h/day(95%CI:5.45-6.41;HR=0.63,95%CI:0.56-0.71)and a minimal dose of 3.59 h/day(95%CI:3.53-8.56;HR=0.81,95%CI:0.78-0.86),with the 5th percentile as the reference.Similar patterns were observed for cause-specific mortality and disease incidence(cardiovascular disease and cancer).Conclusion:Engaging in LPA for~3.5 h/day was conservatively associated with lower risk of mortality and disease incidence,with further risk reductions observed up to an optimal dose of~6.0 h/day.These findings suggest that sufficient LPA offers important health benefits,which can inform the development of future PA guidelines.展开更多
Objective To explore the metabolic syndrome and its association with arterial compliance in Chinese children and adolescents. Methods 337 participants aged 6 to 18 years with males accounted for 55.8% were grouped acc...Objective To explore the metabolic syndrome and its association with arterial compliance in Chinese children and adolescents. Methods 337 participants aged 6 to 18 years with males accounted for 55.8% were grouped according to their traits of metablic syndrome. Anthropometry, blood pressure, fasting plasma glucose, insulin and serum lipid profile were measured. Homeostasis model was assessed and insulin resistance （HOMA-IR） index was measured and calculated for estimating individual insulin resistance. Arterial compliance was also measured using digital pulse wave analyzing method （Micro medical, London）, and stiffness index was calculated. Results The stiffness index in participants with metablic syndrome was significant higher than that in participants with no riskof metablic syndrome [（7.69±1.63） vs （6.25±0.86） m/s, P〈0.01] and stiffness index and HOMA-IR were progressively increased with the increase of traits of metablic syndrom （P for linear trend 〈0.001）. After gender, age, and pubertal development were adjusted, both traits of metablic syndrome and HOMA-IR were correlated positively with stiffness index （both P〈0.05）. Conclusion The clustering of metablic syndrome was closely associated with risk at increased arterial stiffness in Chinese children and adolescents. It was suggested that arterial compliance assessment of children and adolescents might be an important measure for prevention of cardiovascular diseases.展开更多
Objective： MnSOD plays a vital role in carcinogenesis, partly in that it converts superoxide radical to oxygen and hydrogen peroxide. The conflicting results of studies on the role of MnSOD polymorphism （Val-9Ala） ...Objective： MnSOD plays a vital role in carcinogenesis, partly in that it converts superoxide radical to oxygen and hydrogen peroxide. The conflicting results of studies on the role of MnSOD polymorphism （Val-9Ala） with the risk of prostate cancer encouraged us to perform a meta-analysis to examine the association. Methods： A comprehensive search was conducted to examine all the eligible studies of MnSOD polymorphism and prostate cancer risk. We used odds ratios （ORs） with 95% confidence intervals （CIs） to assess the strength of the association. The pooled estimates of ORs were computed using the fixed-effects model or randomeffects model. Results： Ten eligible studies, including 4 608 cases and 5 861 controls, were included in this meta-analysis. Overall, individuals with Ala/Ala and Ala/Val genotypes have an increased risk of prostate cancer, compared with those carrying the Val/Val genotype （Ala/Ala vs. Val/Val： OR=1.13; 95% CI=1.02～1.25; P = 0.020, Pheterogescily=0.370; Ala/Val vs. Val/Val： OR=1.14; 95% CI=1.04～1.25; P = 0.004, Phctrogrnety=0.940）. This significant association was also found in a dominant model with -9Ala allele （Ala/ Ala＋Ala/Val vs. Val/Val： OR=1.12; 95% CI： 1.03～1.22; P = 0.009, Pheterogeneity=0.64）. In the subgroup by ethnicity, it Was observed that significantly elevated prostate cancer risk was associated with -9Ala allele in Caucasians （Ala/Ala vs. Val/Val： OR=l.14; 95% CI=1.03～1.27; P = 0.01, Pheterogeselity=0.31; Ala/Val vs. Val/Val： OR=1.14; 95% CI=1.04～1.24; P = 0.006, Pheterogeneity=0.87） but not in African-Americans. Furthermore, this meta-analysis showed that the -9Ala allele was associated with both nonaggressive and aggressive prostate cancer risks. Conclusion： Our meta-analysis suggests that MnSOD Val-9Ala polymorphism is associated with prostate cancer risk, especially in Caucasians.展开更多
Objective To clarify the contradictory findings in patients with obesity and type 2 diabetes by meta-analysis. Methods PubMed and Embase were searched for articles published up to March 2009. All studies on the associ...Objective To clarify the contradictory findings in patients with obesity and type 2 diabetes by meta-analysis. Methods PubMed and Embase were searched for articles published up to March 2009. All studies on the association of FTO polymorphisms with obesity and type 2 diabetes were included. Pooled odds ratio was calculated using the model of fixed or random effects. Sensitivity analysis was performed to evaluate the stability of meta-analytic results. Results Meta-analysis suggested that rs9939609 A allele was more significantly associated with obesity risk than T allele （3 studies / 2 004 cases and 4 544 control subjects）： random effect odds ratio （OR）-1.28, 95%CI=1.05 and 1.55, P heterogeneity =0.05, I^2=66.6%. Similar results were observed in rs8050136 polymorphism （3 studies/2 404 cases and 5 713 control subjects）： fixed effect OR =1.25, 95%CI-1.13, 1.37, Pheterogeneity =0.12, 12=51.9%. However, no significant association was found between genetics and risk of type 2 diabetes after control of potential confounders （at least for BMI） either for rs9939609 （fixed effect OR=1.05, 95% CI 0.97,1.13） or for rs8050136 polymorphism （fixed effect OR -1.07, 95%CI： 0.99, 1.16）. Furthermore, the sensitivity analysis strengthened our confidence in validity of the association. Conclusion FTO polymorphisms are associated with obesity but not with type 2 diabetes in East Asian populations. Further large-scale studies are required to conclusively establish the association.展开更多
Brooding is a major breeding investment of parental birds during the early nestling stage, and has important effects on the development and survival of nestlings. Investigating brooding behavior can help to understand...Brooding is a major breeding investment of parental birds during the early nestling stage, and has important effects on the development and survival of nestlings. Investigating brooding behavior can help to understand avian breeding investment strategies. From January to June in 2013 and 2014, we studied the brooding behaviors of long-tailed tits （Aegithalos caudatus glaucogularis） in Dongzhai National Nature Reserve, Henan Province, China. We analyzed the relationships between parental diurnal brooding duration and nestling age, brood size, temperature, relative breeding season, time of day and nestling frequencies during brooding duration. Results showed that female and male long-tailed tit parents had different breeding investment strategies during the early nestling stage. Female parents bore most of the brooding investment, while male parents performed most of the nestling feedings. In addition, helpers were not found to brood nestlings at the two cooperative breeding nests. Parental brooding duration was significantly associated with the food delivered to nestlings （F=86.10, dr=l, 193.94, P〈0.001）, and was longer when the nestlings received more food. We found that parental brooding duration declined significantly as nestlings aged （F=5.99, dr=-1, 50.13, P=0.018）. When nestlings were six days old, daytime parental brooding almost ceased, implying that long- tailed tit nestlings might be able to maintain their own body temperature by this age. In addition, brooding duration was affected by both brood size （F=12.74, dr=-1,32.08, P=0.001） and temperature （F=5.83, df=-l, 39.59, P=-0.021）, with it being shorter in larger broods and when ambient temperature was higher.展开更多
Theconstruction of an integrative shuttle expression vector and potential utility was reported inEscherichiacoliandAnabaena(Nostoc) sp. strain PCC 7120. The vector comprised of the following elements: (a) an intergeni...Theconstruction of an integrative shuttle expression vector and potential utility was reported inEscherichiacoliandAnabaena(Nostoc) sp. strain PCC 7120. The vector comprised of the following elements: (a) an intergenic non-coding region fromAnabaenato facilitate its genomic integration (b) a strong functional PpsbAIpromoter fromAnabaenafor desired gene expression and (c) neomycin phosphotransferase gene with its own promoter for the selection of transfor-mants. The constructed vectorpAnFP was evaluated by cloning, transfer and expression of thegfpgene encoding green fluorescent protein. When theE.coliandAnabaenasp. strain PCC 7120 were transformed, intensive green fluorescence produced by the products of GFP protein was observed. This result indicated that the integrative shuttle vector pAnFP can be promisingly used in genome transformation for expression of heterologous genes inE.coliand microalgae such asAnabaenaandNostocstrains.展开更多
Objective：The cytochrome P450 17α-hydroxylase（CYP17）plays a vital role in androgen biosynthesis.A T-to-C polymorphism in the 5＇promoter region of CYP17 has been implicated as a risk factor for prostate cancer,but...Objective：The cytochrome P450 17α-hydroxylase（CYP17）plays a vital role in androgen biosynthesis.A T-to-C polymorphism in the 5＇promoter region of CYP17 has been implicated as a risk factor for prostate cancer,but the results of individual studies are inconclusive or controversial.To derive a more precise estimation of the relationship,we performed an updated meta-analysis from 31 studies based on 27 publications.Methods：A comprehensive search was conducted to examine all the eligible studies of CYP17 polymorphism and prostate cancer risk.We used odds ratios（ORs）with 95%confidence intervals（CIs）to assess the strength of the association.Results：Overall,individuals with CC/CT genotype were not associated with prostate cancer risk （CC vs.TT：OR=1.03,95%CI=0.86-1.24,P=0.72,P heterogeneity 〈0.0001;CT vs.TT：OR=0.99,95%CI=0.87- 1.12,P=0.88,P heterogeneity =0.0006）.In the stratified analysis by ethnicity,there was a significantly increased risk of prostate cancer among individuals of African descent under the recessive model（OR=1.56,95%CI=1.01- 2.39,P=0.04,P heterogeneity =0.65）.Conclusion：This meta-analysis suggested that CYP17 polymorphism might be associated with prostate cancer risk among individuals of African descent.展开更多
Previous studies suggested a beneficial effect of natriuretic peptides in animal models of cardiovascular disease,but the role of natriuretic peptide receptor C(NPRC)in the pathogenesis of atherosclerosis(AS)remains u...Previous studies suggested a beneficial effect of natriuretic peptides in animal models of cardiovascular disease,but the role of natriuretic peptide receptor C(NPRC)in the pathogenesis of atherosclerosis(AS)remains unknown.This study was designed to test the hypothesis that NPRC may promote AS lesion formation and instability by enhancing oxidative stress,inflammation,and apoptosis via protein kinase A(PKA)signaling.ApoE^(−/−)mice were fed chow or Western diet for 12 weeks and NPRC expression was significantly increased in the aortic tissues of Western diet-fed mice.Systemic NPRC knockout mice were crossed with ApoE^(−/−)mice to generate ApoE^(−/−)NPRC^(−/−)mice,and NPRC deletion resulted in a significant decrease in the size and instability of aortic atherosclerotic lesions in ApoE^(−/−)NPRC^(−/−)versus ApoE^(−/−)mice.In addition,endothelial cell-specific NPRC knockout attenuated atherosclerotic lesions in mice.In contrast,endothelial cell overexpression of NPRC aggravated the size and instability of atherosclerotic aortic lesions in mice.Experiments in vitro showed that NPRC knockdown in human aortic endothelial cells(HAECs)inhibited ROS production,pro-inflammatory cytokine expression and endothelial cell apoptosis,and increased eNOS expression.Furthermore,NPRC knockdown in HAECs suppressed macrophage migration,cytokine expression,and phagocytosis via its effects on endothelial cells.On the contrary,NPRC overexpression in endothelial cells resulted in opposite effects.Mechanistically,the anti-inflammation and anti-atherosclerosis effects of NPRC deletion involved activation of cAMP/PKA pathway,leading to downstream upregulated AKT1 pathway and downregulated NF-κB pathway.In conclusion,NPRC deletion reduced the size and instability of atherosclerotic lesions in ApoE^(−/−)mice via attenuating inflammation and endothelial cell apoptosis and increasing eNOS expression by modulating cAMP/PKA-AKT1 and NF-κB pathways.Thus,targeting NPRC may provide a promising approach to the prevention and treatment of atherosclerosis.展开更多
The pathogenesis of doxorubicin-induced cardiomyopathy remains unclear.This study was carried out to test our hypothesis that ADAM17 aggravates cardiomyocyte apoptosis induced by doxorubicin and inhibition of ADAM17 m...The pathogenesis of doxorubicin-induced cardiomyopathy remains unclear.This study was carried out to test our hypothesis that ADAM17 aggravates cardiomyocyte apoptosis induced by doxorubicin and inhibition of ADAM17 may ameliorate doxorubicininduced cardiomyopathy.C57BL/6J mice were intraperitoneally injected with a cumulative dose of doxorubicin to induce cardiomyopathy.Cardiomyocyte-specific ADAM17-knockout(A17^(α-MHCKO))and ADAM17-overexpressing(AAV9-oeA17)mice were generated.In addition,RNA sequencing of the heart tissues in different mouse groups and in vitro experiments in neonatal rat cardiomyocytes(NRCMs)receiving different treatment were performed.Mouse tumor models were constructed in A17^(fl/fl )and A17α-MHCKO mice.In addition,cardiomyocyte-specific TRAF3-knockdown and TRAF3-overexpressing mice were generated.ADAM17 expression and activity were markedly upregulated in doxorubicin-treated mouse hearts and NRCMs.A17^(α-MHCKO) mice showed less cardiomyocyte apoptosis induced by doxorubicin than A17^(fl/fl) mice,and cardiomyocyte ADAM17 deficiency did not affect the anti-tumor effect of doxorubicin.In contrast,AAV9-oeA17 mice exhibited markedly aggravated cardiomyocyte apoptosis relative to AAV9-oeNC mice after doxorubicin treatment.Mechanistically,doxorubicin enhanced the expression of transcription factor C/EBPβ,leading to increased expression and activity of ADAM17 in cardiomyocyte,which enhanced TNF-αshedding and upregulated the expression of TRAF3.Increased TRAF3 promoted TAK1 autophosphorylation,resulting in activated MAPKs pathway and cardiomyocyte apoptosis.ADAM17 acted as a positive regulator of cardiomyocyte apoptosis and cardiac remodeling and dysfunction induced by doxorubicin by upregulating TRAF3/TAK1/MAPKs signaling.Thus,targeting ADAM17/TRAF3/TAK1/MAPKs signaling holds a promising potential for treating doxorubicin-induced cardiotoxicity.展开更多
After online publication of the article,the authors noticed one inadvertent mistake in Fig.2b.The image of Sirus Red Dark in ApoE^(-/-)NPRC^(-/-)group Was mistakenly inserted as the image of Sirus Red Bright in ApoE^(...After online publication of the article,the authors noticed one inadvertent mistake in Fig.2b.The image of Sirus Red Dark in ApoE^(-/-)NPRC^(-/-)group Was mistakenly inserted as the image of Sirus Red Bright in ApoE^(-/-)group,during the final revision process.The correct figure was provided as follows.展开更多
Background and Objectives:Obesity and related target organ damage such as high carotid intima-media thickness(cIMT)in children is associated with cardiovascular disease(CVD)later in life.However,the association betwee...Background and Objectives:Obesity and related target organ damage such as high carotid intima-media thickness(cIMT)in children is associated with cardiovascular disease(CVD)later in life.However,the association between gut microbiota and obesity combined with high cIMT among children remains unclear.Therefore,we compared differences in composition,community diversity,and richness of gut microbiota among normal children and obesity combined with or without high cIMT to identify differential microbiota biomarkers.Methods and Study Design:A total of 24 children with obesity combined with high cIMT(OB+high-cIMT),24 with obesity but normal cIMT(OB+non-high cIMT),and 24 with normal weight and normal cIMT aged 10-11 years matched by age and sex from the“Huantai Childhood Cardiovascular Health Cohort Study”were included.All included fecal samples were tested using 16S rRNA gene sequencing.Results:The community richness and diversity of gut microbiota in OB+high-cIMT children were decreased compared with OB+non-high cIMT children and normal children.At the genus level,the relative abundances of Christensenellaceae_R-7_group,UBA1819,Family_XIII_AD3011_group,and unclassified_o_Bacteroidales were associated with reduced odds of OB+highcIMT among children.Receiver operating characteristic(ROC)analysis showed that combined Christensenellaceae_R-7_group,UBA1819,Family_XIII_AD3011_group,and unclassified_o_Bacteroidales performed a high ability in identifying OB+high-cIMT.Phylogenetic Investigation of Communities by Reconstruction of Unobserved States(PICRUSt)showed that several pathways such as biosynthesis of amino acids and aminoacyl-tRNA pathways were lower in the OB+high-cIMT group compared with the normal group.Conclusions:We found that the alteration of gut microbiota was associated with OB+high-cIMT among children,which indicates that the gut microbiota may be a marker for obesity and related cardiovascular damage among children.展开更多
基金supported by the National Key Research and Development Plan:Real-Time Intelligent Active Intervention on Integration of Ten Important Chronic Diseases(2020YFC2003504-2,to BX)。
文摘Background:Although light-intensity physical activity(LPA)has been suggested to be associated with a lower risk of mortality,the minimal and optimal volumes of LPA remain unclear.We aimed to examine the minimal and optimal volumes of LPA associated with the risks of mortality and disease incidence(i.e.,cardiovascular diseases and cancer).Methods:Data were derived from the population-based UK Biobank cohort study,including 69,492 adults aged 43-78 years.Accelerometermeasured LPA was defined using a validated,published machine learning-based Random Forest activity method,which was categorized into 4 quartile groups.All-cause and cause-specific mortality(cardiovascular disease-and cancer-specific)were determined according to the International Classification of Diseases,10th version codes.Disease incidence was defined based on primary care,hospitalization,or death records.Results:During a median follow-up period of 8.04 years,2024 adults died from all causes,539 from cardiovascular disease,and 1175 from cancer.For all-cause mortality,compared with participants in the lowest quartile of LPA(<3.9 h/day),the hazard ratios(HRs)and 95%confidence intervals(95%CIs)were 0.82(95%CI:0.73-0.93)for those with 3.9 to<5.0 h/day,0.75(95%CI:0.66-0.85)for those with 5.0 to<6.1 h/day,and 0.77(95%CI:0.68-0.88)for those with≥6.1 h/day,respectively.There was an inverse non-linear dose-response association between LPA and all-cause mortality,with an optimal dose of 5.72 h/day(95%CI:5.45-6.41;HR=0.63,95%CI:0.56-0.71)and a minimal dose of 3.59 h/day(95%CI:3.53-8.56;HR=0.81,95%CI:0.78-0.86),with the 5th percentile as the reference.Similar patterns were observed for cause-specific mortality and disease incidence(cardiovascular disease and cancer).Conclusion:Engaging in LPA for~3.5 h/day was conservatively associated with lower risk of mortality and disease incidence,with further risk reductions observed up to an optimal dose of~6.0 h/day.These findings suggest that sufficient LPA offers important health benefits,which can inform the development of future PA guidelines.
基金supported by the National Nature Science Foundation in China (30872165)the Beijing Municipal Nature Science Foundation (7072011)Beijing Municipal Science & Technology Commission (D08050700320801, H030930030031)
文摘Objective To explore the metabolic syndrome and its association with arterial compliance in Chinese children and adolescents. Methods 337 participants aged 6 to 18 years with males accounted for 55.8% were grouped according to their traits of metablic syndrome. Anthropometry, blood pressure, fasting plasma glucose, insulin and serum lipid profile were measured. Homeostasis model was assessed and insulin resistance （HOMA-IR） index was measured and calculated for estimating individual insulin resistance. Arterial compliance was also measured using digital pulse wave analyzing method （Micro medical, London）, and stiffness index was calculated. Results The stiffness index in participants with metablic syndrome was significant higher than that in participants with no riskof metablic syndrome [（7.69±1.63） vs （6.25±0.86） m/s, P〈0.01] and stiffness index and HOMA-IR were progressively increased with the increase of traits of metablic syndrom （P for linear trend 〈0.001）. After gender, age, and pubertal development were adjusted, both traits of metablic syndrome and HOMA-IR were correlated positively with stiffness index （both P〈0.05）. Conclusion The clustering of metablic syndrome was closely associated with risk at increased arterial stiffness in Chinese children and adolescents. It was suggested that arterial compliance assessment of children and adolescents might be an important measure for prevention of cardiovascular diseases.
文摘Objective： MnSOD plays a vital role in carcinogenesis, partly in that it converts superoxide radical to oxygen and hydrogen peroxide. The conflicting results of studies on the role of MnSOD polymorphism （Val-9Ala） with the risk of prostate cancer encouraged us to perform a meta-analysis to examine the association. Methods： A comprehensive search was conducted to examine all the eligible studies of MnSOD polymorphism and prostate cancer risk. We used odds ratios （ORs） with 95% confidence intervals （CIs） to assess the strength of the association. The pooled estimates of ORs were computed using the fixed-effects model or randomeffects model. Results： Ten eligible studies, including 4 608 cases and 5 861 controls, were included in this meta-analysis. Overall, individuals with Ala/Ala and Ala/Val genotypes have an increased risk of prostate cancer, compared with those carrying the Val/Val genotype （Ala/Ala vs. Val/Val： OR=1.13; 95% CI=1.02～1.25; P = 0.020, Pheterogescily=0.370; Ala/Val vs. Val/Val： OR=1.14; 95% CI=1.04～1.25; P = 0.004, Phctrogrnety=0.940）. This significant association was also found in a dominant model with -9Ala allele （Ala/ Ala＋Ala/Val vs. Val/Val： OR=1.12; 95% CI： 1.03～1.22; P = 0.009, Pheterogeneity=0.64）. In the subgroup by ethnicity, it Was observed that significantly elevated prostate cancer risk was associated with -9Ala allele in Caucasians （Ala/Ala vs. Val/Val： OR=l.14; 95% CI=1.03～1.27; P = 0.01, Pheterogeselity=0.31; Ala/Val vs. Val/Val： OR=1.14; 95% CI=1.04～1.24; P = 0.006, Pheterogeneity=0.87） but not in African-Americans. Furthermore, this meta-analysis showed that the -9Ala allele was associated with both nonaggressive and aggressive prostate cancer risks. Conclusion： Our meta-analysis suggests that MnSOD Val-9Ala polymorphism is associated with prostate cancer risk, especially in Caucasians.
基金supported by Beijing Health Bureau(Grant No.2009-1-08)
文摘Objective To clarify the contradictory findings in patients with obesity and type 2 diabetes by meta-analysis. Methods PubMed and Embase were searched for articles published up to March 2009. All studies on the association of FTO polymorphisms with obesity and type 2 diabetes were included. Pooled odds ratio was calculated using the model of fixed or random effects. Sensitivity analysis was performed to evaluate the stability of meta-analytic results. Results Meta-analysis suggested that rs9939609 A allele was more significantly associated with obesity risk than T allele （3 studies / 2 004 cases and 4 544 control subjects）： random effect odds ratio （OR）-1.28, 95%CI=1.05 and 1.55, P heterogeneity =0.05, I^2=66.6%. Similar results were observed in rs8050136 polymorphism （3 studies/2 404 cases and 5 713 control subjects）： fixed effect OR =1.25, 95%CI-1.13, 1.37, Pheterogeneity =0.12, 12=51.9%. However, no significant association was found between genetics and risk of type 2 diabetes after control of potential confounders （at least for BMI） either for rs9939609 （fixed effect OR=1.05, 95% CI 0.97,1.13） or for rs8050136 polymorphism （fixed effect OR -1.07, 95%CI： 0.99, 1.16）. Furthermore, the sensitivity analysis strengthened our confidence in validity of the association. Conclusion FTO polymorphisms are associated with obesity but not with type 2 diabetes in East Asian populations. Further large-scale studies are required to conclusively establish the association.
基金Foundation item： This study was supported by the National Natural Science Foundation of China （31472011）ACKNOWLEDGEMENTS We are grateful to Peng ZHANG, Zheng CHEN, Jia-Hui WANG, and Hui-Jia YUAN of Beijing Normal University for field assistance, and staff from Henan Dongzhai National Nature Reserve for help during field work. We also thank editor for revising the English, and the two reviewers for their constructive comments, which have helped to improve the manuscript.
文摘Brooding is a major breeding investment of parental birds during the early nestling stage, and has important effects on the development and survival of nestlings. Investigating brooding behavior can help to understand avian breeding investment strategies. From January to June in 2013 and 2014, we studied the brooding behaviors of long-tailed tits （Aegithalos caudatus glaucogularis） in Dongzhai National Nature Reserve, Henan Province, China. We analyzed the relationships between parental diurnal brooding duration and nestling age, brood size, temperature, relative breeding season, time of day and nestling frequencies during brooding duration. Results showed that female and male long-tailed tit parents had different breeding investment strategies during the early nestling stage. Female parents bore most of the brooding investment, while male parents performed most of the nestling feedings. In addition, helpers were not found to brood nestlings at the two cooperative breeding nests. Parental brooding duration was significantly associated with the food delivered to nestlings （F=86.10, dr=l, 193.94, P〈0.001）, and was longer when the nestlings received more food. We found that parental brooding duration declined significantly as nestlings aged （F=5.99, dr=-1, 50.13, P=0.018）. When nestlings were six days old, daytime parental brooding almost ceased, implying that long- tailed tit nestlings might be able to maintain their own body temperature by this age. In addition, brooding duration was affected by both brood size （F=12.74, dr=-1,32.08, P=0.001） and temperature （F=5.83, df=-l, 39.59, P=-0.021）, with it being shorter in larger broods and when ambient temperature was higher.
文摘Theconstruction of an integrative shuttle expression vector and potential utility was reported inEscherichiacoliandAnabaena(Nostoc) sp. strain PCC 7120. The vector comprised of the following elements: (a) an intergenic non-coding region fromAnabaenato facilitate its genomic integration (b) a strong functional PpsbAIpromoter fromAnabaenafor desired gene expression and (c) neomycin phosphotransferase gene with its own promoter for the selection of transfor-mants. The constructed vectorpAnFP was evaluated by cloning, transfer and expression of thegfpgene encoding green fluorescent protein. When theE.coliandAnabaenasp. strain PCC 7120 were transformed, intensive green fluorescence produced by the products of GFP protein was observed. This result indicated that the integrative shuttle vector pAnFP can be promisingly used in genome transformation for expression of heterologous genes inE.coliand microalgae such asAnabaenaandNostocstrains.
文摘Objective：The cytochrome P450 17α-hydroxylase（CYP17）plays a vital role in androgen biosynthesis.A T-to-C polymorphism in the 5＇promoter region of CYP17 has been implicated as a risk factor for prostate cancer,but the results of individual studies are inconclusive or controversial.To derive a more precise estimation of the relationship,we performed an updated meta-analysis from 31 studies based on 27 publications.Methods：A comprehensive search was conducted to examine all the eligible studies of CYP17 polymorphism and prostate cancer risk.We used odds ratios（ORs）with 95%confidence intervals（CIs）to assess the strength of the association.Results：Overall,individuals with CC/CT genotype were not associated with prostate cancer risk （CC vs.TT：OR=1.03,95%CI=0.86-1.24,P=0.72,P heterogeneity 〈0.0001;CT vs.TT：OR=0.99,95%CI=0.87- 1.12,P=0.88,P heterogeneity =0.0006）.In the stratified analysis by ethnicity,there was a significantly increased risk of prostate cancer among individuals of African descent under the recessive model（OR=1.56,95%CI=1.01- 2.39,P=0.04,P heterogeneity =0.65）.Conclusion：This meta-analysis suggested that CYP17 polymorphism might be associated with prostate cancer risk among individuals of African descent.
基金This work was supported by grants of the National Natural Science Foundation of China(No.82241203,81920108003,82030051,81970366,82000411,82200498,and 82200502)State Key R&D Program of China(2021YFF0501403)+2 种基金Key R&D Program of Shandong Province(2021SFGC0503,2021ZLGX02,2021ZDSYS05,and 2020ZLYS05)Shandong Provincial Natural Science Foundation(ZR2020QH023,ZR2022QH026,and ZR2022QH089)the Taishan Scholars Program of Shandong Province(Zhang C,Zhang M).
文摘Previous studies suggested a beneficial effect of natriuretic peptides in animal models of cardiovascular disease,but the role of natriuretic peptide receptor C(NPRC)in the pathogenesis of atherosclerosis(AS)remains unknown.This study was designed to test the hypothesis that NPRC may promote AS lesion formation and instability by enhancing oxidative stress,inflammation,and apoptosis via protein kinase A(PKA)signaling.ApoE^(−/−)mice were fed chow or Western diet for 12 weeks and NPRC expression was significantly increased in the aortic tissues of Western diet-fed mice.Systemic NPRC knockout mice were crossed with ApoE^(−/−)mice to generate ApoE^(−/−)NPRC^(−/−)mice,and NPRC deletion resulted in a significant decrease in the size and instability of aortic atherosclerotic lesions in ApoE^(−/−)NPRC^(−/−)versus ApoE^(−/−)mice.In addition,endothelial cell-specific NPRC knockout attenuated atherosclerotic lesions in mice.In contrast,endothelial cell overexpression of NPRC aggravated the size and instability of atherosclerotic aortic lesions in mice.Experiments in vitro showed that NPRC knockdown in human aortic endothelial cells(HAECs)inhibited ROS production,pro-inflammatory cytokine expression and endothelial cell apoptosis,and increased eNOS expression.Furthermore,NPRC knockdown in HAECs suppressed macrophage migration,cytokine expression,and phagocytosis via its effects on endothelial cells.On the contrary,NPRC overexpression in endothelial cells resulted in opposite effects.Mechanistically,the anti-inflammation and anti-atherosclerosis effects of NPRC deletion involved activation of cAMP/PKA pathway,leading to downstream upregulated AKT1 pathway and downregulated NF-κB pathway.In conclusion,NPRC deletion reduced the size and instability of atherosclerotic lesions in ApoE^(−/−)mice via attenuating inflammation and endothelial cell apoptosis and increasing eNOS expression by modulating cAMP/PKA-AKT1 and NF-κB pathways.Thus,targeting NPRC may provide a promising approach to the prevention and treatment of atherosclerosis.
基金supported by grants of the National Natural Science Foundation of China(Nos.82000411,82030051,82241203,81920108003 and 81970366)State Key R&D Program of China(2021YFF0501403)+4 种基金Key R&D Program of Shandong Province(2021SFGC0503,2021ZLGX02,2021ZDSYS05,2020ZLYS05)Shandong Provincial Natural Science Foundation(ZR2020QH023)the Taishan Scholars Program of Shandong Province(C.Z.)China Postdoctoral Science Foundation(2023M742124)Postdoctoral Innovation Talents Support Program(BX20230210).
文摘The pathogenesis of doxorubicin-induced cardiomyopathy remains unclear.This study was carried out to test our hypothesis that ADAM17 aggravates cardiomyocyte apoptosis induced by doxorubicin and inhibition of ADAM17 may ameliorate doxorubicininduced cardiomyopathy.C57BL/6J mice were intraperitoneally injected with a cumulative dose of doxorubicin to induce cardiomyopathy.Cardiomyocyte-specific ADAM17-knockout(A17^(α-MHCKO))and ADAM17-overexpressing(AAV9-oeA17)mice were generated.In addition,RNA sequencing of the heart tissues in different mouse groups and in vitro experiments in neonatal rat cardiomyocytes(NRCMs)receiving different treatment were performed.Mouse tumor models were constructed in A17^(fl/fl )and A17α-MHCKO mice.In addition,cardiomyocyte-specific TRAF3-knockdown and TRAF3-overexpressing mice were generated.ADAM17 expression and activity were markedly upregulated in doxorubicin-treated mouse hearts and NRCMs.A17^(α-MHCKO) mice showed less cardiomyocyte apoptosis induced by doxorubicin than A17^(fl/fl) mice,and cardiomyocyte ADAM17 deficiency did not affect the anti-tumor effect of doxorubicin.In contrast,AAV9-oeA17 mice exhibited markedly aggravated cardiomyocyte apoptosis relative to AAV9-oeNC mice after doxorubicin treatment.Mechanistically,doxorubicin enhanced the expression of transcription factor C/EBPβ,leading to increased expression and activity of ADAM17 in cardiomyocyte,which enhanced TNF-αshedding and upregulated the expression of TRAF3.Increased TRAF3 promoted TAK1 autophosphorylation,resulting in activated MAPKs pathway and cardiomyocyte apoptosis.ADAM17 acted as a positive regulator of cardiomyocyte apoptosis and cardiac remodeling and dysfunction induced by doxorubicin by upregulating TRAF3/TAK1/MAPKs signaling.Thus,targeting ADAM17/TRAF3/TAK1/MAPKs signaling holds a promising potential for treating doxorubicin-induced cardiotoxicity.
文摘After online publication of the article,the authors noticed one inadvertent mistake in Fig.2b.The image of Sirus Red Dark in ApoE^(-/-)NPRC^(-/-)group Was mistakenly inserted as the image of Sirus Red Bright in ApoE^(-/-)group,during the final revision process.The correct figure was provided as follows.
基金supported by the National Natural Science Foundation of China(Grant ID:81722039,81673195,82204066)China Postdoctoral Science Foundation(Grant ID:2021M701978)Natural Science Foundation of Shandong Province(Grant ID:ZR2021QH272).
文摘Background and Objectives:Obesity and related target organ damage such as high carotid intima-media thickness(cIMT)in children is associated with cardiovascular disease(CVD)later in life.However,the association between gut microbiota and obesity combined with high cIMT among children remains unclear.Therefore,we compared differences in composition,community diversity,and richness of gut microbiota among normal children and obesity combined with or without high cIMT to identify differential microbiota biomarkers.Methods and Study Design:A total of 24 children with obesity combined with high cIMT(OB+high-cIMT),24 with obesity but normal cIMT(OB+non-high cIMT),and 24 with normal weight and normal cIMT aged 10-11 years matched by age and sex from the“Huantai Childhood Cardiovascular Health Cohort Study”were included.All included fecal samples were tested using 16S rRNA gene sequencing.Results:The community richness and diversity of gut microbiota in OB+high-cIMT children were decreased compared with OB+non-high cIMT children and normal children.At the genus level,the relative abundances of Christensenellaceae_R-7_group,UBA1819,Family_XIII_AD3011_group,and unclassified_o_Bacteroidales were associated with reduced odds of OB+highcIMT among children.Receiver operating characteristic(ROC)analysis showed that combined Christensenellaceae_R-7_group,UBA1819,Family_XIII_AD3011_group,and unclassified_o_Bacteroidales performed a high ability in identifying OB+high-cIMT.Phylogenetic Investigation of Communities by Reconstruction of Unobserved States(PICRUSt)showed that several pathways such as biosynthesis of amino acids and aminoacyl-tRNA pathways were lower in the OB+high-cIMT group compared with the normal group.Conclusions:We found that the alteration of gut microbiota was associated with OB+high-cIMT among children,which indicates that the gut microbiota may be a marker for obesity and related cardiovascular damage among children.
