Pancreatic ductal adenocarcinoma stands out as an exceptionally fatal cancer owing to the complexities associated with its treatment and diagnosis,leading to a notably low five-year survival rate.This study offers a d...Pancreatic ductal adenocarcinoma stands out as an exceptionally fatal cancer owing to the complexities associated with its treatment and diagnosis,leading to a notably low five-year survival rate.This study offers a detailed exploration of epidemiological trends in pancreatic cancer and key molecular drivers,such as mutations in CDKN2A,KRAS,SMAD4,and TP53,along with the influence of cancer-associated fibroblasts(CAFs)on disease progression.In particular,we focused on the pivotal roles of signaling pathways such as the transforming growth factor-βand Wnt/β-catenin pathways in the development of pancreatic cancer and investigated their application in emerging therapeutic strategies.This study provides new scientific perspectives on pancreatic cancer treatment,especially in the development of precision medicine and targeted therapeutic strategies,and demonstrates the importance of signaling pathway research in the development of effective therapeutic regimens.Future studies should explore the subtypes of CAFs and their specific roles in the tumor microenvironment to devise more effective therapeutic methods.展开更多
Background:A quality diet and an active lifestyle are both important cornerstones of cardiovascular disease(CVD)prevention.However,despite their interlinked effects on metabolic health,the 2 behaviors are rarely consi...Background:A quality diet and an active lifestyle are both important cornerstones of cardiovascular disease(CVD)prevention.However,despite their interlinked effects on metabolic health,the 2 behaviors are rarely considered jointly,particularly within the context of CVD prevention.We examined the independent,interactive,and joint associations of diet and physical activity with CVD hospitalization,CVD mortality,and all-cause mortality.Methods:CVD-free Australian participants aged 4574 years(n=85,545)reported physical activity,diet,sociodemographic,and lifestyle characteristics at baseline(20062009)and follow-up(20122015),and data were linked to hospitalization and death registries(03/31/2019 for CVD hospitalization and all-cause mortality and 12/08/2017 for CVD mortality).Diet quality was categorized as low,medium,and high based on meeting dietary recommendations.Physical activity was operationalized as(a)total moderate-to-vigorous physical activity(MVPA)as per guidelines,and(b)the composition of MVPA as the ratio of vigorous-intensity physical activity(VPA)to total MVPA.We used a left-truncated cause-specific Cox proportional hazards model using time-varying covariates.Results:During a median of 10.7 years of follow-up,6576 participants were admitted to the hospital for CVD and 6581 died from all causes(876 from CVD during 9.3 years).A high-quality diet was associated with a 17%lower risk of all-cause mortality than a low-quality diet,and the highest MVPA category(compared with the lowest)was associated with a 44%and 48%lower risk of CVD and all-cause mortality,respectively.Multiplicative interactions between diet and physical activity were non-significant.For all outcomes,the lowest risk combinations involved a high-quality diet and the highest MVPA categories.Accounting for total MVPA,some VPA was associated with further risk reduction of CVD hospitalization and all-cause mortality.Conclusion:For CVD prevention and longevity,one should adhere to both a healthy diet and an active lifestyle and incorporate some VPA when possible.展开更多
Purpose:This study aimed to quantify the dose-response association and the minimal effective dose of leisure-time physical activity(PA)to prevent mortality and cardiovascular disease in adults with type 2 diabetes.Met...Purpose:This study aimed to quantify the dose-response association and the minimal effective dose of leisure-time physical activity(PA)to prevent mortality and cardiovascular disease in adults with type 2 diabetes.Methods:Cross-country comparison of 2 prospective cohort studies including 14,913 and 17,457 population-based adults with type 2 diabetes from the UK and China.Baseline leisure-time PA was self-reported and categorized by metabolic equivalent hours per week(MET-h/week)according to World Health Organization recommendations:none,below recommendation(>0-7.49 MET-h/week);at recommended level(7.5-14.9 MET-h/week);above recommendation(>15 MET-h/week).Mortality and cardiovascular disease data were obtained from national registries.Results:During a median follow-up of 12.4 and 9.7 years,in the UK and China cohorts,repectively,higher levels of leisure-time PA were inversely associated with all-cause(1571 and 2351 events)and cardiovascular mortality(392 and 1060 events),mostly consistent with a linear dose-response relationship.PA below,at,and above recommendations,compared with no activity,yielded all-cause mortality hazard ratios of0.94(95%confidence interval(95%CI):0.79-1.12),0.90(95%CI:0.74-1.10),and 0.85(95%CI:0.70-1.02)in British adults and 0.87(95%CI:0.68-1.10),0.88(95%CI:0.74-1.03),and 0.77(95%CI:0.70-0.85)in Chinese adults.Associations with cardiovascular mortality were more pronounced in British adults(0.80(95%CI:0.58-1.11),0.75(95%CI:0.52-1.09),and 0.69(95%CI:0.48-0.97))but less pronounced in Chinese adults(1.06(95%CI:0.76-1.47),1.01(95%CI:0.80-1.28),and 0.79(95%CI:0.69-0.92)).PA at recommended levels was not associated with lower rates of major adverse cardiovascular events(2345 and 4458 events).Conclusion:Leisure-time PA at the recommended levels was not convincingly associated with lower mortality and had no association with risk of major adverse cardiovascular events in British or Chinese adults with type 2 diabetes.Leisure-time PA above current recommendations may be needed to prevent cardiovascular disease and premature mortality in adults with type 2 diabetes.展开更多
Background:Optimal patterns of accrual of recommended levels of physical activity(PA)for prevention of hypertension and obesity are not known.The overall aim of this study was to investigate whether different patterns...Background:Optimal patterns of accrual of recommended levels of physical activity(PA)for prevention of hypertension and obesity are not known.The overall aim of this study was to investigate whether different patterns of accumulation of PA are differentially associated with hypertension and obesity in Australian women over 21 years.Specifically,we investigated whether,for the same weekly volume of PA,the number of sessions(frequency)and vigorousness of PA(intensity)were associated with a reduction in the occurrence of hypertension and obesity in women.Methods:Data from the 1973-1978 and 1946-1951 cohorts of the Australian Longitudinal Study on Women's Health were analyzed(n=20,588;12%-16%with a Bachelor's or higher degree).Self-reported PA,hypertension,height,and weight were collected using mail surveys every 3 years from 1998/2000 to 2019/2021.Generalized Estimating Equation models with a 3-year lag model were used to investigate the association of PA volume(metabolic equivalent min/week)(none;33-499;500-999;≥1000,weekly frequency(none;1-2 times;3-4times;5-7 times;≥8 times),and the proportion of vigorous PA to total volume of PA(none;0%;1%-33%;34%-66%;67%-100%)with odds of hypertension and obesity from 2000 to 2021.Results:The cumulative incidence of hypertension was 6%in the 1973-1978 and 23%in the 1946-1951 cohort;27%of women in the 1973-1978;and 15%in the 1946-1951 cohort developed obesity over the period.Overall,a higher volume of PA was associated with reduced odds of hypertension and obesity.When the volume of PA was considered,the odds of hypertension did not vary according to the frequency or intensity of PA.However,increased proportion of vigorous PA to the total volume of PA was associated with a small additional reduction in the risk of obe sity.Conclusion:PA volume appears to be more important than the pattern of accumulation for the prevention of hypertension and obesity.Incorporating more sessions,particularly of vigorous-intensity PA,may provide extra benefits for the prevention of obesity.展开更多
Drought events have become more severe under climate change,and this can pose a major threat to the survival of various organisms.The molecular mechanisms involved in dehydration resistance are not well known.Here,adu...Drought events have become more severe under climate change,and this can pose a major threat to the survival of various organisms.The molecular mechanisms involved in dehydration resistance are not well known.Here,adults of the migratory locust,Locusta migratoria,were subjected to food-mediated dehydration,and adipokinetic hormone(AKH)signaling was found to play a key role in regulating dehydration resistance.Specifically,dehydration shortened the lifespan,increased the body weight loss,and reduced the water loss rate in adult locusts.Global transcriptome profiles revealed variations in tissue-specific gene expression between dehydration-resistant locusts and normal locusts.Importantly,dehydration selection and exposure induced prominent expression of AKH genes in the retrocerebral complex of adult locusts.Furthermore,individual knockdown of AKH1,AKH2,or AKH receptor(AKHR)accelerated water loss and shortened the lifespan of adult locusts under dehydration conditions,and trehalose supplementation ameliorated the negative effects caused by interference with AKH or AKHR.These findings demonstrated that AKH/AKHR signaling-dependent trehalose metabolism plays a crucial role in regulating locust dehydration resistance and thus provide novel insights into the regulatory mechanism underlying drought resistance.展开更多
基金Supported by National Key Research and Development Program Project,No.2017YFC1700601Shaanxi Provincial Key Research and Development Program Project,No.2018SF-350Leading Talents in Scientific and Technological Innovation of the Shaanxi Province Special Support Plan,No.00518。
文摘Pancreatic ductal adenocarcinoma stands out as an exceptionally fatal cancer owing to the complexities associated with its treatment and diagnosis,leading to a notably low five-year survival rate.This study offers a detailed exploration of epidemiological trends in pancreatic cancer and key molecular drivers,such as mutations in CDKN2A,KRAS,SMAD4,and TP53,along with the influence of cancer-associated fibroblasts(CAFs)on disease progression.In particular,we focused on the pivotal roles of signaling pathways such as the transforming growth factor-βand Wnt/β-catenin pathways in the development of pancreatic cancer and investigated their application in emerging therapeutic strategies.This study provides new scientific perspectives on pancreatic cancer treatment,especially in the development of precision medicine and targeted therapeutic strategies,and demonstrates the importance of signaling pathway research in the development of effective therapeutic regimens.Future studies should explore the subtypes of CAFs and their specific roles in the tumor microenvironment to devise more effective therapeutic methods.
基金the Heart Foundation Australia(#101234,#101583)an Emerging Leader Fellowship from the National Health and Medical Research Council(2009254)an Early-Mid Career Researcher Grant under the New South Wales Cardiovascular Research Capacity Program.
文摘Background:A quality diet and an active lifestyle are both important cornerstones of cardiovascular disease(CVD)prevention.However,despite their interlinked effects on metabolic health,the 2 behaviors are rarely considered jointly,particularly within the context of CVD prevention.We examined the independent,interactive,and joint associations of diet and physical activity with CVD hospitalization,CVD mortality,and all-cause mortality.Methods:CVD-free Australian participants aged 4574 years(n=85,545)reported physical activity,diet,sociodemographic,and lifestyle characteristics at baseline(20062009)and follow-up(20122015),and data were linked to hospitalization and death registries(03/31/2019 for CVD hospitalization and all-cause mortality and 12/08/2017 for CVD mortality).Diet quality was categorized as low,medium,and high based on meeting dietary recommendations.Physical activity was operationalized as(a)total moderate-to-vigorous physical activity(MVPA)as per guidelines,and(b)the composition of MVPA as the ratio of vigorous-intensity physical activity(VPA)to total MVPA.We used a left-truncated cause-specific Cox proportional hazards model using time-varying covariates.Results:During a median of 10.7 years of follow-up,6576 participants were admitted to the hospital for CVD and 6581 died from all causes(876 from CVD during 9.3 years).A high-quality diet was associated with a 17%lower risk of all-cause mortality than a low-quality diet,and the highest MVPA category(compared with the lowest)was associated with a 44%and 48%lower risk of CVD and all-cause mortality,respectively.Multiplicative interactions between diet and physical activity were non-significant.For all outcomes,the lowest risk combinations involved a high-quality diet and the highest MVPA categories.Accounting for total MVPA,some VPA was associated with further risk reduction of CVD hospitalization and all-cause mortality.Conclusion:For CVD prevention and longevity,one should adhere to both a healthy diet and an active lifestyle and incorporate some VPA when possible.
文摘Purpose:This study aimed to quantify the dose-response association and the minimal effective dose of leisure-time physical activity(PA)to prevent mortality and cardiovascular disease in adults with type 2 diabetes.Methods:Cross-country comparison of 2 prospective cohort studies including 14,913 and 17,457 population-based adults with type 2 diabetes from the UK and China.Baseline leisure-time PA was self-reported and categorized by metabolic equivalent hours per week(MET-h/week)according to World Health Organization recommendations:none,below recommendation(>0-7.49 MET-h/week);at recommended level(7.5-14.9 MET-h/week);above recommendation(>15 MET-h/week).Mortality and cardiovascular disease data were obtained from national registries.Results:During a median follow-up of 12.4 and 9.7 years,in the UK and China cohorts,repectively,higher levels of leisure-time PA were inversely associated with all-cause(1571 and 2351 events)and cardiovascular mortality(392 and 1060 events),mostly consistent with a linear dose-response relationship.PA below,at,and above recommendations,compared with no activity,yielded all-cause mortality hazard ratios of0.94(95%confidence interval(95%CI):0.79-1.12),0.90(95%CI:0.74-1.10),and 0.85(95%CI:0.70-1.02)in British adults and 0.87(95%CI:0.68-1.10),0.88(95%CI:0.74-1.03),and 0.77(95%CI:0.70-0.85)in Chinese adults.Associations with cardiovascular mortality were more pronounced in British adults(0.80(95%CI:0.58-1.11),0.75(95%CI:0.52-1.09),and 0.69(95%CI:0.48-0.97))but less pronounced in Chinese adults(1.06(95%CI:0.76-1.47),1.01(95%CI:0.80-1.28),and 0.79(95%CI:0.69-0.92)).PA at recommended levels was not associated with lower rates of major adverse cardiovascular events(2345 and 4458 events).Conclusion:Leisure-time PA at the recommended levels was not convincingly associated with lower mortality and had no association with risk of major adverse cardiovascular events in British or Chinese adults with type 2 diabetes.Leisure-time PA above current recommendations may be needed to prevent cardiovascular disease and premature mortality in adults with type 2 diabetes.
基金supported by a National Health and Medical Research Council(NHMRC)Investigator Grant(APP2008702)supported by the National Council for Scientific and Technological Developments-CNPq(process number 308772/2022-9)。
文摘Background:Optimal patterns of accrual of recommended levels of physical activity(PA)for prevention of hypertension and obesity are not known.The overall aim of this study was to investigate whether different patterns of accumulation of PA are differentially associated with hypertension and obesity in Australian women over 21 years.Specifically,we investigated whether,for the same weekly volume of PA,the number of sessions(frequency)and vigorousness of PA(intensity)were associated with a reduction in the occurrence of hypertension and obesity in women.Methods:Data from the 1973-1978 and 1946-1951 cohorts of the Australian Longitudinal Study on Women's Health were analyzed(n=20,588;12%-16%with a Bachelor's or higher degree).Self-reported PA,hypertension,height,and weight were collected using mail surveys every 3 years from 1998/2000 to 2019/2021.Generalized Estimating Equation models with a 3-year lag model were used to investigate the association of PA volume(metabolic equivalent min/week)(none;33-499;500-999;≥1000,weekly frequency(none;1-2 times;3-4times;5-7 times;≥8 times),and the proportion of vigorous PA to total volume of PA(none;0%;1%-33%;34%-66%;67%-100%)with odds of hypertension and obesity from 2000 to 2021.Results:The cumulative incidence of hypertension was 6%in the 1973-1978 and 23%in the 1946-1951 cohort;27%of women in the 1973-1978;and 15%in the 1946-1951 cohort developed obesity over the period.Overall,a higher volume of PA was associated with reduced odds of hypertension and obesity.When the volume of PA was considered,the odds of hypertension did not vary according to the frequency or intensity of PA.However,increased proportion of vigorous PA to the total volume of PA was associated with a small additional reduction in the risk of obe sity.Conclusion:PA volume appears to be more important than the pattern of accumulation for the prevention of hypertension and obesity.Incorporating more sessions,particularly of vigorous-intensity PA,may provide extra benefits for the prevention of obesity.
基金supported by the National Key Research and Development Program of China(2022YFD1400503)the National Natural Science Foundation of China(32102208)the Hebei Natural Science Foundation,China(C2022201042,C2021201052 and C2023201075).
文摘Drought events have become more severe under climate change,and this can pose a major threat to the survival of various organisms.The molecular mechanisms involved in dehydration resistance are not well known.Here,adults of the migratory locust,Locusta migratoria,were subjected to food-mediated dehydration,and adipokinetic hormone(AKH)signaling was found to play a key role in regulating dehydration resistance.Specifically,dehydration shortened the lifespan,increased the body weight loss,and reduced the water loss rate in adult locusts.Global transcriptome profiles revealed variations in tissue-specific gene expression between dehydration-resistant locusts and normal locusts.Importantly,dehydration selection and exposure induced prominent expression of AKH genes in the retrocerebral complex of adult locusts.Furthermore,individual knockdown of AKH1,AKH2,or AKH receptor(AKHR)accelerated water loss and shortened the lifespan of adult locusts under dehydration conditions,and trehalose supplementation ameliorated the negative effects caused by interference with AKH or AKHR.These findings demonstrated that AKH/AKHR signaling-dependent trehalose metabolism plays a crucial role in regulating locust dehydration resistance and thus provide novel insights into the regulatory mechanism underlying drought resistance.
