Background Both medication and non-medication therapies are effective approaches to control blood pressure (BP) in hypertension patients.However,the association of joint changes in antihypertensive medication use and ...Background Both medication and non-medication therapies are effective approaches to control blood pressure (BP) in hypertension patients.However,the association of joint changes in antihypertensive medication use and healthy lifestyle index (HLI)with BP control among hypertension patients is seldom reported,which needs to provide more evidence by prospective intervention studies.We examined the association of antihypertensive medication use and HLI with BP control among employees with hypertension in China based on a workplace-based multicomponent intervention program.Methods Between January 2013 and December 2014,a cluster randomized clinical trial of a workplace-based multicomponent intervention program was conducted in 60 workplaces across 20 urban areas in China.Workplaces were randomly divided into intervention (n=40) and control (n=20) groups.Basic information on employees at each workplace was collected by trained professionals,including sociodemographic characteristics,medical history,family history,lifestyle behaviors,medication status and physical measurements.After baseline,the intervention group received a 2-year intervention to achieve BP control,which included:(1) a workplace wellness program for all employees;(2) a guidelines-oriented hypertension management protocol.HLI including nonsmoking,nondrinking,adequate physical activity,weight within reference range and balanced diet,were coded on a 5-point scale (range:0-5,with higher score indicating a healthier lifestyle).Antihypertensive medication use was defined as taking drug within the last 2 weeks.Changes in HLI,antihypertensive medication use and BP control from baseline to 24 months were measured after the intervention.Results Overall,4655 employees were included (age:46.3±7.6 years,men:3547 (82.3%)).After 24 months of the intervention,there was a significant improvement in lifestyle[smoking (OR=0.65,95%CI:0.43-0.99;P=0.045),drinking (OR=0.52,95%CI:0.40-0.68;P<0.001),regular exercise (OR=3.10,95%CI:2.53-3.78;P<0.001),excessive intake of fatty food (OR=0.17,95%CI:0.06-0.52;P=0.002),restrictive use of salt (OR=0.26,95%CI:0.12-0.56;P=0.001)].Compare to employees with a deteriorating lifestyle after the intervention,those with an improved lifestyle had a higher BP control.In the intervention group,compared with employees not using antihypertensive medication,those who consistent used (OR=2.34;95%CI:1.16-4.72;P=0.017) or changed from not using to using antihypertensive medication (OR=2.24;95%CI:1.08-4.62;P=0.030) had higher BP control.Compared with those having lower HLI,participants with a same (OR=1.38;95%CI:0.99-1.93;P=0.056) or high (OR=1.79;95%CI:1.27~2.53;P<0.001) HLI had higher BP control.Those who used antihypertensive medication and had a high HLI had the highest BP control (OR=1.88;95%CI:1.32-2.67,P<0.001).Subgroup analysis also showed the consistent effect as the above.Conclusion These findings suggest that adherence to antihypertensive medication treatment and healthy lifestyle were associated with a significant improvement in BP control among employees with hypertension.展开更多
Clear cell renal cell carcinoma(ccRCC)is characterized by profound lipid metabolic dysregulation,yet the mechanisms linking peritumoral adipose tissue(PAT)-derived lipid metabolites to tumor aggressiveness remain poor...Clear cell renal cell carcinoma(ccRCC)is characterized by profound lipid metabolic dysregulation,yet the mechanisms linking peritumoral adipose tissue(PAT)-derived lipid metabolites to tumor aggressiveness remain poorly defined.Here,we identified lysophosphatidylethanolamine 18:1(LPE18:1),a lipid metabolite enriched in PAT and the arterial blood of ccRCC patients,as a critical driver of tumor growth and lipid deposition.Through multiomics analyses and functional studies,we demonstrated that LPE18:1 upregulates F-actin-capping protein subunit alpha-1(CAPZA1),which recruits ubiquitin-specific peptidase 48(USP48)to stabilize the NAD-dependent protein deacetylase sirtuin-6(SIRT6)by inhibiting its proteasomal degradation.Increased SIRT6 epigenetically promotes acetyl-CoA acetyltransferase 2(ACAT2)expression,redirecting lipid metabolism toward free cholesterol accumulation—a hallmark of ccRCC aggressiveness.Clinically,CAPZA1 and SIRT6 levels correlate with advanced tumor stage and poor prognosis in ccRCC cohorts.Genetic or pharmacological inhibition of the CAPZA1/SIRT6 axis can reverse LPE18:1-induced lipid deposition and tumor progression in xenograft models.Notably,targeting this axis with the SIRT6 inhibitor OSS-128167 combined with CAPZA1 depletion significantly suppresses ccRCC cell growth.Our study reveals a PAT-derived lipid metabolite-fuelled signaling cascade that reprograms lipid metabolism in ccRCC,identifying CAPZA1/USP48/SIRT6 as actionable therapeutic targets for metabolic malignancies.展开更多
The quest for efficient and robust deep learning models for molecular systems representation is increasingly critical in scientific exploration.The advent of message passing neural networks has marked a transformative...The quest for efficient and robust deep learning models for molecular systems representation is increasingly critical in scientific exploration.The advent of message passing neural networks has marked a transformative era in graph-based learning,particularly in the realm of predicting chemical properties and expediting molecular dynamics studies.We present the Moment Graph Neural Network(MGNN),a rotation-invariantmessage passing neural network architecture that capitalizes on the moment representation learning of 3D molecular graphs,is adept at capturing the nuanced spatial relationships inherent in three-dimensional molecular structures.From benchmark tests on public datasets,MGNN delivers multiple state-of-the-art results on QM9,revised MD17 and MD17-ethanol.Its generalizability and efficiency are also tested in additional systems including 3BPA and 25-element high-entropy alloys.The prowess of MGNN also extends to dynamic simulations,accurately predicting the structural and kinetic properties of complex systems such as amorphous electrolytes,with results that closely align with those from ab-initio simulations.The application of MGNN to the simulation of molecular spectra exemplifies its potential to offer a promising alternative to traditional electronic structure methods.展开更多
基金supported by grant 2011BAI11B01 from the Projects in the Chinese National Science and Technology Pillar Program during the 12th Five-year Plan Periodby grant 2017-I2M-1-004 from the Chinese Academy of Medical Science Innovation Fund for Medical Sciencesby the Major science and technology special plan project of Yunnan Province (202302AA310045)。
文摘Background Both medication and non-medication therapies are effective approaches to control blood pressure (BP) in hypertension patients.However,the association of joint changes in antihypertensive medication use and healthy lifestyle index (HLI)with BP control among hypertension patients is seldom reported,which needs to provide more evidence by prospective intervention studies.We examined the association of antihypertensive medication use and HLI with BP control among employees with hypertension in China based on a workplace-based multicomponent intervention program.Methods Between January 2013 and December 2014,a cluster randomized clinical trial of a workplace-based multicomponent intervention program was conducted in 60 workplaces across 20 urban areas in China.Workplaces were randomly divided into intervention (n=40) and control (n=20) groups.Basic information on employees at each workplace was collected by trained professionals,including sociodemographic characteristics,medical history,family history,lifestyle behaviors,medication status and physical measurements.After baseline,the intervention group received a 2-year intervention to achieve BP control,which included:(1) a workplace wellness program for all employees;(2) a guidelines-oriented hypertension management protocol.HLI including nonsmoking,nondrinking,adequate physical activity,weight within reference range and balanced diet,were coded on a 5-point scale (range:0-5,with higher score indicating a healthier lifestyle).Antihypertensive medication use was defined as taking drug within the last 2 weeks.Changes in HLI,antihypertensive medication use and BP control from baseline to 24 months were measured after the intervention.Results Overall,4655 employees were included (age:46.3±7.6 years,men:3547 (82.3%)).After 24 months of the intervention,there was a significant improvement in lifestyle[smoking (OR=0.65,95%CI:0.43-0.99;P=0.045),drinking (OR=0.52,95%CI:0.40-0.68;P<0.001),regular exercise (OR=3.10,95%CI:2.53-3.78;P<0.001),excessive intake of fatty food (OR=0.17,95%CI:0.06-0.52;P=0.002),restrictive use of salt (OR=0.26,95%CI:0.12-0.56;P=0.001)].Compare to employees with a deteriorating lifestyle after the intervention,those with an improved lifestyle had a higher BP control.In the intervention group,compared with employees not using antihypertensive medication,those who consistent used (OR=2.34;95%CI:1.16-4.72;P=0.017) or changed from not using to using antihypertensive medication (OR=2.24;95%CI:1.08-4.62;P=0.030) had higher BP control.Compared with those having lower HLI,participants with a same (OR=1.38;95%CI:0.99-1.93;P=0.056) or high (OR=1.79;95%CI:1.27~2.53;P<0.001) HLI had higher BP control.Those who used antihypertensive medication and had a high HLI had the highest BP control (OR=1.88;95%CI:1.32-2.67,P<0.001).Subgroup analysis also showed the consistent effect as the above.Conclusion These findings suggest that adherence to antihypertensive medication treatment and healthy lifestyle were associated with a significant improvement in BP control among employees with hypertension.
基金supported by the National Natural Science Foundation of China(No.82472667,Z.Y.,82473101,X.C.,and 82573927,Y.Z.)the Taishan Scholars Young Experts Project(No.tsqn202312380,Z.Y.)+2 种基金the China Higher Education Innovation Fund Project(No.2024GR041,Z.Y.)the Natural Science Foundation of Shandong Province(ZR2025MS1491,Z.Y.)the Liaoning Province Science and Technology Plan Project(2023 China Medical University High-quality Development Plan)(Grant No.2023JH2/20200122,X.C.).
文摘Clear cell renal cell carcinoma(ccRCC)is characterized by profound lipid metabolic dysregulation,yet the mechanisms linking peritumoral adipose tissue(PAT)-derived lipid metabolites to tumor aggressiveness remain poorly defined.Here,we identified lysophosphatidylethanolamine 18:1(LPE18:1),a lipid metabolite enriched in PAT and the arterial blood of ccRCC patients,as a critical driver of tumor growth and lipid deposition.Through multiomics analyses and functional studies,we demonstrated that LPE18:1 upregulates F-actin-capping protein subunit alpha-1(CAPZA1),which recruits ubiquitin-specific peptidase 48(USP48)to stabilize the NAD-dependent protein deacetylase sirtuin-6(SIRT6)by inhibiting its proteasomal degradation.Increased SIRT6 epigenetically promotes acetyl-CoA acetyltransferase 2(ACAT2)expression,redirecting lipid metabolism toward free cholesterol accumulation—a hallmark of ccRCC aggressiveness.Clinically,CAPZA1 and SIRT6 levels correlate with advanced tumor stage and poor prognosis in ccRCC cohorts.Genetic or pharmacological inhibition of the CAPZA1/SIRT6 axis can reverse LPE18:1-induced lipid deposition and tumor progression in xenograft models.Notably,targeting this axis with the SIRT6 inhibitor OSS-128167 combined with CAPZA1 depletion significantly suppresses ccRCC cell growth.Our study reveals a PAT-derived lipid metabolite-fuelled signaling cascade that reprograms lipid metabolism in ccRCC,identifying CAPZA1/USP48/SIRT6 as actionable therapeutic targets for metabolic malignancies.
基金supported by National Key R&D Program of China(Grant Nos.2022YFC3203900 and 2023YFC 2812700)the National Natural Science Foundation of China(no.12002304,no.12272337)+1 种基金the Distinguished Young Scientists Fund from the Natural Science Foundation of Zhejiang Province(no.LR23A020001)the“Pioneer”R&D Program of Zhejiang(Grant no.2023C03007).
文摘The quest for efficient and robust deep learning models for molecular systems representation is increasingly critical in scientific exploration.The advent of message passing neural networks has marked a transformative era in graph-based learning,particularly in the realm of predicting chemical properties and expediting molecular dynamics studies.We present the Moment Graph Neural Network(MGNN),a rotation-invariantmessage passing neural network architecture that capitalizes on the moment representation learning of 3D molecular graphs,is adept at capturing the nuanced spatial relationships inherent in three-dimensional molecular structures.From benchmark tests on public datasets,MGNN delivers multiple state-of-the-art results on QM9,revised MD17 and MD17-ethanol.Its generalizability and efficiency are also tested in additional systems including 3BPA and 25-element high-entropy alloys.The prowess of MGNN also extends to dynamic simulations,accurately predicting the structural and kinetic properties of complex systems such as amorphous electrolytes,with results that closely align with those from ab-initio simulations.The application of MGNN to the simulation of molecular spectra exemplifies its potential to offer a promising alternative to traditional electronic structure methods.
