Genetic variants in super-enhancers(SEs)are increasingly implicated as a disease risk-driving mechanism.Previous studies have reported an associations between benzo[a]pyrene(BaP)exposure and some malignant tumor risk....Genetic variants in super-enhancers(SEs)are increasingly implicated as a disease risk-driving mechanism.Previous studies have reported an associations between benzo[a]pyrene(BaP)exposure and some malignant tumor risk.Currently,it is unclear whether BaP is involved in the effect of genetic variants in SEs on prostate cancer risk,nor the associated intrinsic molecular mechanisms.In the current study,by using logistic regression analysis,we found that rs5750581T>C in 22q-SE was significantly associated with prostate cancer risk(odds ratio=1.26,P=7.61×10^(-5)).We also have found that the rs6001092T>G,in a high linkage disequilibrium with rs5750581T>C(r^(2)=0.98),is located in a regulatory aryl hydrocarbon receptor(AhR)motif and may interact with the FAM227A promoter in further bioinformatics analysis.We then performed a series of functional and BaP acute exposure experiments to assess biological function of the genetic variant and the target gene.Biologically,the rs6001092-G allele strengthened the transcription factor binding affinity to AhR,thereby upregulating FAM227A,especially upon exposure to BaP,which induced the malignant phenotypes of prostate cancer.The current study highlights that AhR acts as an environmental sensor of BaP and is involved in the SE-mediated prostate cancer risk,which may provide new insights into the etiology of prostate cancer associated with the inherited SE variants under environmental carcinogen stressors.展开更多
Objective:Red blood cell distribution width(RDW)has been utilized as a prognostic indicator for mortality risk assessment in cardiovascular and cerebrovascular patients.Nevertheless,the prognostic significance of RDW ...Objective:Red blood cell distribution width(RDW)has been utilized as a prognostic indicator for mortality risk assessment in cardiovascular and cerebrovascular patients.Nevertheless,the prognostic significance of RDW in critically ill patients with cerebral infarction is yet to be investigated.The objective of this study is to examine the association between RDW and the risk of all-cause mortality in cerebral infarction patients admitted to the intensive care unit(ICU).Method:A retrospective cohort study was conducted using the Medical Information Mart for Intensive Care IV 2.2(MIMIC-IV)intensive care dataset for data analysis.The main results were the all-cause mortality rates at 3 and 12 months of follow-up.Cumulative curves were plotted using the Kaplan-Meier method,and Cox proportional hazards analysis was used to examine the relationship between RDW and mortality rates in critically ill cerebral infarction patients.Results:The findings indicate that RDW serves as a significant prognostic factor for mortality risk in critically ill stroke patients,specifically at the 3 and 12-month follow-up periods.The observed correlation between increasing RDW levels and higher mortality rates among cerebral infarction patients further supports the potential utility of RDW as a predictive indicator.Conclusion:RDW emerges as an independent predictor of mortality risk during the 3 and 12-month follow-up periods for critically ill patients with cerebral infarction.展开更多
The effects of Cu on stacking fault energy,dislocation slip,mechanical twinning,and strain hardening in Fe–20Mn–1.3C twinning-induced plasticity(TWIP) steels were systematically investigated.The stacking fault energ...The effects of Cu on stacking fault energy,dislocation slip,mechanical twinning,and strain hardening in Fe–20Mn–1.3C twinning-induced plasticity(TWIP) steels were systematically investigated.The stacking fault energy was raised with an average slope of 2 mJ/m2 per 1 wt% Cu.The Fe–20Mn–1.3C–3Cu steel exhibited superior tensile properties,with the ultimate tensile strength reached at 2.27 GPa and elongation up to 96.9% owing to the high strain hardening that occurred.To examine the mechanism of this high strain hardening,dislocation density determination by XRD was calculated.The dislocation density increased with the increasing strain,and the addition of Cu resulted in a decrease in the dislocation density.A comparison of the strain-hardening behavior of Fe–20Mn–1.3C and Fe–20Mn–1.3C–3Cu TWIP steels was made in terms of modified Crussard–Jaoul(C–J) analysis and microstructural observations.Especially at low strains,the contributions of all the relevant deformation mechanisms—slip,twinning,and dynamic strain aging—were quantitatively evaluated.The analysis revealed that the dislocation storage was the leading factor to the increase of the strain hardening,while dynamic strain aging was a minor contributor to strain hardening.Twinning,which interacted with the matrix,acted as an effective barrier to dislocation motion.展开更多
文摘Genetic variants in super-enhancers(SEs)are increasingly implicated as a disease risk-driving mechanism.Previous studies have reported an associations between benzo[a]pyrene(BaP)exposure and some malignant tumor risk.Currently,it is unclear whether BaP is involved in the effect of genetic variants in SEs on prostate cancer risk,nor the associated intrinsic molecular mechanisms.In the current study,by using logistic regression analysis,we found that rs5750581T>C in 22q-SE was significantly associated with prostate cancer risk(odds ratio=1.26,P=7.61×10^(-5)).We also have found that the rs6001092T>G,in a high linkage disequilibrium with rs5750581T>C(r^(2)=0.98),is located in a regulatory aryl hydrocarbon receptor(AhR)motif and may interact with the FAM227A promoter in further bioinformatics analysis.We then performed a series of functional and BaP acute exposure experiments to assess biological function of the genetic variant and the target gene.Biologically,the rs6001092-G allele strengthened the transcription factor binding affinity to AhR,thereby upregulating FAM227A,especially upon exposure to BaP,which induced the malignant phenotypes of prostate cancer.The current study highlights that AhR acts as an environmental sensor of BaP and is involved in the SE-mediated prostate cancer risk,which may provide new insights into the etiology of prostate cancer associated with the inherited SE variants under environmental carcinogen stressors.
基金Project of Science and Technology Plan of Tianjin City(Grant number 20ZYJDSY00020)。
文摘Objective:Red blood cell distribution width(RDW)has been utilized as a prognostic indicator for mortality risk assessment in cardiovascular and cerebrovascular patients.Nevertheless,the prognostic significance of RDW in critically ill patients with cerebral infarction is yet to be investigated.The objective of this study is to examine the association between RDW and the risk of all-cause mortality in cerebral infarction patients admitted to the intensive care unit(ICU).Method:A retrospective cohort study was conducted using the Medical Information Mart for Intensive Care IV 2.2(MIMIC-IV)intensive care dataset for data analysis.The main results were the all-cause mortality rates at 3 and 12 months of follow-up.Cumulative curves were plotted using the Kaplan-Meier method,and Cox proportional hazards analysis was used to examine the relationship between RDW and mortality rates in critically ill cerebral infarction patients.Results:The findings indicate that RDW serves as a significant prognostic factor for mortality risk in critically ill stroke patients,specifically at the 3 and 12-month follow-up periods.The observed correlation between increasing RDW levels and higher mortality rates among cerebral infarction patients further supports the potential utility of RDW as a predictive indicator.Conclusion:RDW emerges as an independent predictor of mortality risk during the 3 and 12-month follow-up periods for critically ill patients with cerebral infarction.
基金financially supported by the Major Project for Industry-University-Research of Fujian Province,China (No.2011H6012)the Natural Science Foundation of Fujian Province,China (No.2011J01292)the Key Project of Fujian Provincial Department of Science and Technology (No.2011H0001)
文摘The effects of Cu on stacking fault energy,dislocation slip,mechanical twinning,and strain hardening in Fe–20Mn–1.3C twinning-induced plasticity(TWIP) steels were systematically investigated.The stacking fault energy was raised with an average slope of 2 mJ/m2 per 1 wt% Cu.The Fe–20Mn–1.3C–3Cu steel exhibited superior tensile properties,with the ultimate tensile strength reached at 2.27 GPa and elongation up to 96.9% owing to the high strain hardening that occurred.To examine the mechanism of this high strain hardening,dislocation density determination by XRD was calculated.The dislocation density increased with the increasing strain,and the addition of Cu resulted in a decrease in the dislocation density.A comparison of the strain-hardening behavior of Fe–20Mn–1.3C and Fe–20Mn–1.3C–3Cu TWIP steels was made in terms of modified Crussard–Jaoul(C–J) analysis and microstructural observations.Especially at low strains,the contributions of all the relevant deformation mechanisms—slip,twinning,and dynamic strain aging—were quantitatively evaluated.The analysis revealed that the dislocation storage was the leading factor to the increase of the strain hardening,while dynamic strain aging was a minor contributor to strain hardening.Twinning,which interacted with the matrix,acted as an effective barrier to dislocation motion.
