Objective Cardiac fibroblasts(CFs)proliferation and extracellular matrix deposition are important features of cardiac fibrosis.Various studies have indicated that vitamin D displays an anti-fibrotic property in chroni...Objective Cardiac fibroblasts(CFs)proliferation and extracellular matrix deposition are important features of cardiac fibrosis.Various studies have indicated that vitamin D displays an anti-fibrotic property in chronic heart diseases.This study explored the role of vitamin D in the growth of CFs via an integrin signaling pathway.Methods MTT and 5-ethynyl-2′-deoxyuridine assays were performed to determine cell viability.Western blotting was performed to detect the expression of proliferating cell nuclear antigen(PCNA)and integrin signaling pathway.The fibronectin was observed by ELISA.Immunohistochemical staining was employed to evaluate the expression of integrinβ3.Results The PCNA expression in the CFs was enhanced after isoproterenol(ISO)stimulation accompanied by an elevated expression of integrin beta-3(β3).The blockade of the integrinβ3 with a specific integrinβ3 antibody reduced the PCNA expression induced by the ISO.Decreasing the integrinβ3 by siRNA reduced the ISO-triggered phosphorylation of FAK and Akt.Both the FAK inhibitor and Akt inhibitor suppressed the PCNA expression induced by the ISO in the CFs.Calcitriol(CAL),an active form of vitamin D,attenuated the ISO-induced CFs proliferation by downregulating the integrinβ3 expression,and phosphorylation of FAK and Akt.Moreover,CAL reduced the increased levels of fibronectin and hydroxyproline in the CFs culture medium triggered by the ISO.The administration of calcitriol decreased the integrinβ3 expression in the ISO-induced myocardial injury model.Conclusion These findings revealed a novel role for CAL in suppressing the CFs growth by the downregulation of the integrinβ3/FAK/Akt pathway.展开更多
Few effective treatments for chronic Keshan disease have been available till now.The efficacy of long-term selenium supplementation in the treatment of chronic Keshan disease with congestive heart failure is inconclus...Few effective treatments for chronic Keshan disease have been available till now.The efficacy of long-term selenium supplementation in the treatment of chronic Keshan disease with congestive heart failure is inconclusive.This study aimed to determine whether selenium supplementation is associated with a decreased risk of cardiac death in chronic Keshan disease with congestive heart failure by ten years of follow-up.A retrospective long-term follow-up analysis was performed on a monitored cohort consisting of 302 chronic Keshan disease patients with a mean age of 40.8±11.4 years.Of the 302 chronic Keshan disease patients,170(56.3%)were given selenium supplementation until the end point of follow-up.Cox proportional hazards regression models were used to identify the independent predictors of cardiac events.Our results showed that during the follow-up,there were 101 deaths of patients with chronic Keshan disease in the selenium supplementation group(101/170,59.4%)and 98 in non-selenium supplementation group(98/132,74.2%).Multivariate analyses suggested that selenium supplementation was associated with a decreased risk of cardiac death(HR 0.39,95%CI 0.28-0.53)after adjustment for baseline age,sex,cigarette smoking,family history of Keshan disease,body mass index(BMI),heart rate,electrocardiogram(ECG)abnonnalities,blood pressure,initial cardiothoracic ratio,left ventricular可ection fractions(LVEF)and whole-blood selenium concentration.Our ten-year follow-up analysis indicated that selenium supplementation,specifically combined with the use of angiotensinconverting cnzyme inhibitor and beta blocker therapy,improved the survival of patients with chronic Keshan disease with congestive heart failure.BMI,selenium deficiency,male,combined ECG abnonnalities,LVEF,and fast heart rate increased the risk of cardiac events.展开更多
Common wheat(Triticum aestivum,BBAADD)is a major staple food crop worldwide.The diploid progenitors of the A and D subgenomes have been unequivocally identified;that of B,however,remains ambiguous and controversial bu...Common wheat(Triticum aestivum,BBAADD)is a major staple food crop worldwide.The diploid progenitors of the A and D subgenomes have been unequivocally identified;that of B,however,remains ambiguous and controversial but is suspected to be related to species of Aegilops,section Sitopsis.Here,we report the assembly of chromosome-level genome sequences of all five Sitopsis species,namely Aegilops bicornis,Ae.longissima,Ae.searsii,Ae.sharonensis,and Ae.speltoides,as well as the partial assembly of the Amblyopyrum muticum(synonym Aegilops mutica)genome for phylogenetic analysis.Our results reveal that the donor of the common wheat B subgenome is a distinct,and most probably extinct,diploid species that diverged from an ancestral progenitor of the B lineage to which the still extant Ae.speltoides and Am.muticum belong.In addition,we identified interspecific genetic introgressions throughout the evolution of the Triticum/Aegilops species complex.The five Sitopsis species have various assembled genome sizes(4.11-5.89 Gb)with high proportions of repetitive sequences(85.99%-89.81%);nonetheless,they retain high collinearity with other genomes or subgenomes of species in the Triticum/Aegilops complex.Differences in genome size were primarily due to independent post-speciation amplification of transposons.We also identified a set of Sitopsis genes pertinent to important agronomic traits that can be harnessed for wheat breeding.These newly assembled genome resources provide a new roadmap for evolutionary and genetic studies of the Triticum/Aegilops complex,as well as for wheat improvement.展开更多
DNA methylation is one important epigenetic type to play a vital role in many diseases including cancers.With the development of the high-throughput sequencing technology,there is much progress to disclose the relatio...DNA methylation is one important epigenetic type to play a vital role in many diseases including cancers.With the development of the high-throughput sequencing technology,there is much progress to disclose the relations of DNA methylation with diseases.However,the analyses of DNA methylation data are challenging due to the missing values caused by the limitations of current techniques.While many methods have been developed to impute the missing values,these methods are mostly based on the correlations between individual samples,and thus are limited for the abnormal samples in cancers.In this study,we present a novel transfer learning based neural network to impute missing DNA methylation data,namely the TDimpute-DNAmeth method.The method learns common relations between DNA methylation from pan-cancer samples,and then fine-tunes the learned relations over each specific cancer type for imputing the missing data.Tested on 16 cancer datasets,our method was shown to outperform other commonly-used methods.Further analyses indicated that DNA methylation is related to cancer survival and thus can be used as a biomarker of cancer prognosis.展开更多
基金supported by grants from the National Natural Science Foundation of China(No.81441016)and Key R&D Plan in Shaanxi Province of China(No.2020SF-262 and No.2019SF-200).
文摘Objective Cardiac fibroblasts(CFs)proliferation and extracellular matrix deposition are important features of cardiac fibrosis.Various studies have indicated that vitamin D displays an anti-fibrotic property in chronic heart diseases.This study explored the role of vitamin D in the growth of CFs via an integrin signaling pathway.Methods MTT and 5-ethynyl-2′-deoxyuridine assays were performed to determine cell viability.Western blotting was performed to detect the expression of proliferating cell nuclear antigen(PCNA)and integrin signaling pathway.The fibronectin was observed by ELISA.Immunohistochemical staining was employed to evaluate the expression of integrinβ3.Results The PCNA expression in the CFs was enhanced after isoproterenol(ISO)stimulation accompanied by an elevated expression of integrin beta-3(β3).The blockade of the integrinβ3 with a specific integrinβ3 antibody reduced the PCNA expression induced by the ISO.Decreasing the integrinβ3 by siRNA reduced the ISO-triggered phosphorylation of FAK and Akt.Both the FAK inhibitor and Akt inhibitor suppressed the PCNA expression induced by the ISO in the CFs.Calcitriol(CAL),an active form of vitamin D,attenuated the ISO-induced CFs proliferation by downregulating the integrinβ3 expression,and phosphorylation of FAK and Akt.Moreover,CAL reduced the increased levels of fibronectin and hydroxyproline in the CFs culture medium triggered by the ISO.The administration of calcitriol decreased the integrinβ3 expression in the ISO-induced myocardial injury model.Conclusion These findings revealed a novel role for CAL in suppressing the CFs growth by the downregulation of the integrinβ3/FAK/Akt pathway.
基金the National Natural Science Foundation of China(Nos.81441016,81273008).
文摘Few effective treatments for chronic Keshan disease have been available till now.The efficacy of long-term selenium supplementation in the treatment of chronic Keshan disease with congestive heart failure is inconclusive.This study aimed to determine whether selenium supplementation is associated with a decreased risk of cardiac death in chronic Keshan disease with congestive heart failure by ten years of follow-up.A retrospective long-term follow-up analysis was performed on a monitored cohort consisting of 302 chronic Keshan disease patients with a mean age of 40.8±11.4 years.Of the 302 chronic Keshan disease patients,170(56.3%)were given selenium supplementation until the end point of follow-up.Cox proportional hazards regression models were used to identify the independent predictors of cardiac events.Our results showed that during the follow-up,there were 101 deaths of patients with chronic Keshan disease in the selenium supplementation group(101/170,59.4%)and 98 in non-selenium supplementation group(98/132,74.2%).Multivariate analyses suggested that selenium supplementation was associated with a decreased risk of cardiac death(HR 0.39,95%CI 0.28-0.53)after adjustment for baseline age,sex,cigarette smoking,family history of Keshan disease,body mass index(BMI),heart rate,electrocardiogram(ECG)abnonnalities,blood pressure,initial cardiothoracic ratio,left ventricular可ection fractions(LVEF)and whole-blood selenium concentration.Our ten-year follow-up analysis indicated that selenium supplementation,specifically combined with the use of angiotensinconverting cnzyme inhibitor and beta blocker therapy,improved the survival of patients with chronic Keshan disease with congestive heart failure.BMI,selenium deficiency,male,combined ECG abnonnalities,LVEF,and fast heart rate increased the risk of cardiac events.
基金This work was financially supported by the National Natural Science Foundation of China （31470010 to L.F.L.） and the Program for Introducing Talents to Universities （B07017 to B.L.）.We thank James Schnable and two anonymous reviewers for their valuable comments and suggestions, which have greatly improved the manuscript, We also thank Richard Abbott for his pre-reviewing of the manuscript, Joao Sollari Lopes for his help with the popABC analyses, Mingzhou Sun, Yuezhi Pan, Zhenhui Wang, and Peng Peng for their assistance with material collection and data analyses. No conflict of interest declared.
基金This study was supported by the Natural Science Foundation of China(31991211 to B.L.and 31970235 to L.F.L.)the Shanghai Pujiang Program(19PJ1401500 to L.F.L.),Israel Science Foundation(ISF)-China National Natural Science Foundation(NSFC)collaborative grants to B.L.(32061143001)and A.A.L.(3394/20)a China Postdoctoral Science Foundation grant(2021M690683).
文摘Common wheat(Triticum aestivum,BBAADD)is a major staple food crop worldwide.The diploid progenitors of the A and D subgenomes have been unequivocally identified;that of B,however,remains ambiguous and controversial but is suspected to be related to species of Aegilops,section Sitopsis.Here,we report the assembly of chromosome-level genome sequences of all five Sitopsis species,namely Aegilops bicornis,Ae.longissima,Ae.searsii,Ae.sharonensis,and Ae.speltoides,as well as the partial assembly of the Amblyopyrum muticum(synonym Aegilops mutica)genome for phylogenetic analysis.Our results reveal that the donor of the common wheat B subgenome is a distinct,and most probably extinct,diploid species that diverged from an ancestral progenitor of the B lineage to which the still extant Ae.speltoides and Am.muticum belong.In addition,we identified interspecific genetic introgressions throughout the evolution of the Triticum/Aegilops species complex.The five Sitopsis species have various assembled genome sizes(4.11-5.89 Gb)with high proportions of repetitive sequences(85.99%-89.81%);nonetheless,they retain high collinearity with other genomes or subgenomes of species in the Triticum/Aegilops complex.Differences in genome size were primarily due to independent post-speciation amplification of transposons.We also identified a set of Sitopsis genes pertinent to important agronomic traits that can be harnessed for wheat breeding.These newly assembled genome resources provide a new roadmap for evolutionary and genetic studies of the Triticum/Aegilops complex,as well as for wheat improvement.
基金supported by the National Key Research and Development Program of China under Grant No.2020YFB0204803the National Natural Science Foundation of China under Grant No.61772566+2 种基金the Guangdong Key Field Research and Development Plan under Grant Nos.2019B020228001 and 2018B010109006the Introducing Innovative and Entrepreneurial Teams of Guangdong under Grant No.2016ZT06D211the Guangzhou Science and Technology Research Plan under Grant No.202007030010.
文摘DNA methylation is one important epigenetic type to play a vital role in many diseases including cancers.With the development of the high-throughput sequencing technology,there is much progress to disclose the relations of DNA methylation with diseases.However,the analyses of DNA methylation data are challenging due to the missing values caused by the limitations of current techniques.While many methods have been developed to impute the missing values,these methods are mostly based on the correlations between individual samples,and thus are limited for the abnormal samples in cancers.In this study,we present a novel transfer learning based neural network to impute missing DNA methylation data,namely the TDimpute-DNAmeth method.The method learns common relations between DNA methylation from pan-cancer samples,and then fine-tunes the learned relations over each specific cancer type for imputing the missing data.Tested on 16 cancer datasets,our method was shown to outperform other commonly-used methods.Further analyses indicated that DNA methylation is related to cancer survival and thus can be used as a biomarker of cancer prognosis.
