Bucky ball(Buc)is involved in germ plasm(GP)assembly during early zebrafish development by regulating GP mRNA expression via an unknown mechanism.The present study demonstrates that an m^(6)A reader Igf2bp3 interacts ...Bucky ball(Buc)is involved in germ plasm(GP)assembly during early zebrafish development by regulating GP mRNA expression via an unknown mechanism.The present study demonstrates that an m^(6)A reader Igf2bp3 interacts and colocalizes with Buc in the GP.Similar to the loss of Buc,the genetic deletion of maternal igf2bp3 in zebrafish leads to abnormal GP assembly and insufficient germ cell specification,which can be partially restored by the injection of igf2 bp3 mRNA.Igf2bp3 binds to m^(6)A-modified GPorganizer and GP mRNAs in an m^(6)A-dependent manner and prevents their degradation.These findings indicate that the functions of Igf2bp3,a direct effector protein of Buc,in GP mRNA expression and GP assembly involve m^(6)A-dependent regulation;these results emphasize a critical role of m^(6)A modification in the process of GP assembly.展开更多
Background： Inoperable chronic thromboembolic pulmonary hypertension （CTEPH） is a severe clinical syndrome characterized by right cardiac failure and possibly subsequent liver dysfunction. However, whether serum ma...Background： Inoperable chronic thromboembolic pulmonary hypertension （CTEPH） is a severe clinical syndrome characterized by right cardiac failure and possibly subsequent liver dysfunction. However, whether serum markers of liver dysfunction can predict prognosis in inoperable CTEPH patients has not been determined. Our study aimed to evaluate the potential role of liver function markers （such as serum levels of transaminase, bilirubin, and gamma-glutamyl transpeptidase [GGT]） combined with 6-min walk test in the prediction of prognosis in patients with inoperable CTEPH. Methods： From June 2005 to May 2013, 77 consecutive patients with inoperable CTEPH without confounding co-morbidities were recruited for this prospective cohort study. Baseline clinical characteristics and 6-min walk distance （6MWD） results were collected. Serum biomarkers of liver function, including levels of aspartate aminotransferase, alanine aminotransferase, GGT, uric acid, and serum bilirubin, were also determined at enrollment. All-cause mortality was recorded during the follow-up period. Results： During the follow-up, 22 patients （29%） died. Cox regression analyses demonstrated that increased serum concentration of total bilirubin （hazard ratio [HR] = 7.755, P 〈 0.001）, elevated N-terminal of the prohormone brain natriuretic peptide （HR = 1.001, P = 0.001）, decreased 6MWD （HR = 0.990, P 〈 0.001）, increased central venous pressure （HR = 1.074, P = 0.040）, and higher pulmonary vascular resistance （HR = 1.001, P = 0.018） were associated with an increased risk of mortality. Serum concentrations of total bilirubin （HR = 4.755, P = 0.007） and 6MWD （HR = 0.994, P = 0.017） were independent prognostic predictors for CTEPH patients. Patients with hyperbilirubinemia （≥23.7 μmol/L） had markedly worse survival than those with normobilirubinemia. Conclusion： Elevated serum bilirubin and decreased 6MWD are potential predictors for poor prognosis in inoperable CTEPH.展开更多
基金supported by the National Key R&D Program of China(2018YFD0901201 and 2019YFA0802801)China Agricultural Research System(CARS-46)+3 种基金the National Natural Science Foundation of China(31870820)the Innovative Research Group Program of Hubei Province(2020CFA017)the Medical Science Advancement Program of Wuhan University(TFJC2018004)the Fundamental Research Funds for the Central Universities(2042019kf0207)。
文摘Bucky ball(Buc)is involved in germ plasm(GP)assembly during early zebrafish development by regulating GP mRNA expression via an unknown mechanism.The present study demonstrates that an m^(6)A reader Igf2bp3 interacts and colocalizes with Buc in the GP.Similar to the loss of Buc,the genetic deletion of maternal igf2bp3 in zebrafish leads to abnormal GP assembly and insufficient germ cell specification,which can be partially restored by the injection of igf2 bp3 mRNA.Igf2bp3 binds to m^(6)A-modified GPorganizer and GP mRNAs in an m^(6)A-dependent manner and prevents their degradation.These findings indicate that the functions of Igf2bp3,a direct effector protein of Buc,in GP mRNA expression and GP assembly involve m^(6)A-dependent regulation;these results emphasize a critical role of m^(6)A modification in the process of GP assembly.
基金Acknowledgments The authors thank Dr. Lan Zhao and Christopher J Rhodes for their valuable assistance in the statistical analyses, grammar correction, and efforts in the preparation of this manuscript.Financial support and sponsorship This study was supported by National Natural Science Foundation of China （ No. 81570049 and No. 81300044） the Fund of China Key Research Projects of the 12th National Five-year Development Plan （No. 2011BAI11B17）+2 种基金 the Beijing Youth Star of Science and Technology Program （No. 2007B037） the National Department of Public Benefit Research Foundation by the Ministry of Health P. R. China （No. 201302008） and the Beijing Natural Science Foundation （No. 7152062）.
文摘Background： Inoperable chronic thromboembolic pulmonary hypertension （CTEPH） is a severe clinical syndrome characterized by right cardiac failure and possibly subsequent liver dysfunction. However, whether serum markers of liver dysfunction can predict prognosis in inoperable CTEPH patients has not been determined. Our study aimed to evaluate the potential role of liver function markers （such as serum levels of transaminase, bilirubin, and gamma-glutamyl transpeptidase [GGT]） combined with 6-min walk test in the prediction of prognosis in patients with inoperable CTEPH. Methods： From June 2005 to May 2013, 77 consecutive patients with inoperable CTEPH without confounding co-morbidities were recruited for this prospective cohort study. Baseline clinical characteristics and 6-min walk distance （6MWD） results were collected. Serum biomarkers of liver function, including levels of aspartate aminotransferase, alanine aminotransferase, GGT, uric acid, and serum bilirubin, were also determined at enrollment. All-cause mortality was recorded during the follow-up period. Results： During the follow-up, 22 patients （29%） died. Cox regression analyses demonstrated that increased serum concentration of total bilirubin （hazard ratio [HR] = 7.755, P 〈 0.001）, elevated N-terminal of the prohormone brain natriuretic peptide （HR = 1.001, P = 0.001）, decreased 6MWD （HR = 0.990, P 〈 0.001）, increased central venous pressure （HR = 1.074, P = 0.040）, and higher pulmonary vascular resistance （HR = 1.001, P = 0.018） were associated with an increased risk of mortality. Serum concentrations of total bilirubin （HR = 4.755, P = 0.007） and 6MWD （HR = 0.994, P = 0.017） were independent prognostic predictors for CTEPH patients. Patients with hyperbilirubinemia （≥23.7 μmol/L） had markedly worse survival than those with normobilirubinemia. Conclusion： Elevated serum bilirubin and decreased 6MWD are potential predictors for poor prognosis in inoperable CTEPH.
