Forecasting uncertainties among meteorological fields have long been recognized as the main limitation on the accuracy and predictability of air quality forecasts.However,the particular impact of meteorological foreca...Forecasting uncertainties among meteorological fields have long been recognized as the main limitation on the accuracy and predictability of air quality forecasts.However,the particular impact of meteorological forecasting uncertainties on air quality forecasts specific to different seasons is still not well known.In this study,a series of forecasts with different forecast lead times for January,April,July,and October of 2018 are conducted over the Beijing-Tianjin-Hebei(BTH)region and the impacts of meteorological forecasting uncertainties on surface PM_(2.5)concentration forecasts with each lead time are investigated.With increased lead time,the forecasted PM_(2.5)concentrations significantly change and demonstrate obvious seasonal variations.In general,the forecasting uncertainties in monthly mean surface PM_(2.5)concentrations in the BTH region due to lead time are the largest(80%)in spring,followed by autumn(~50%),summer(~40%),and winter(20%).In winter,the forecasting uncertainties in total surface PM_(2.5)mass due to lead time are mainly due to the uncertainties in PBL heights and hence the PBL mixing of anthropogenic primary particles.In spring,the forecasting uncertainties are mainly from the impacts of lead time on lower-tropospheric northwesterly winds,thereby further enhancing the condensation production of anthropogenic secondary particles by the long-range transport of natural dust.In summer,the forecasting uncertainties result mainly from the decrease in dry and wet deposition rates,which are associated with the reduction of near-surface wind speed and precipitation rate.In autumn,the forecasting uncertainties arise mainly from the change in the transport of remote natural dust and anthropogenic particles,which is associated with changes in the large-scale circulation.展开更多
Hypoxia affects the advancement,metastasis,and metabolism of breast cancer(BC).The circular RNA ribonuclease P RNA component H1(circRPPH1)(has_circ_0000515)is implicated in tumor progression.Nevertheless,the regulator...Hypoxia affects the advancement,metastasis,and metabolism of breast cancer(BC).The circular RNA ribonuclease P RNA component H1(circRPPH1)(has_circ_0000515)is implicated in tumor progression.Nevertheless,the regulatory mechanism related to circRPPH1 in hypoxia-mediated triple-negative breast cancer(TNBC)progression is indistinct.The expression levels of circRPPH1,miR-1296-5p,tripartite motif-containing 14(TRIM14)mRNA in tissue samples and cells were examined through quantitative real-time polymerase chain reaction(qRT-PCR).Cell viability,migration,and invasion were determined with Cell Counting Kit-8(CCK-8)or transwell assays.The levels of glucose consumption and lactate production were assessed via the Glucose Assay Kit or Lactate Assay Kit.The protein levels of TRIM14,Glucose Transporter GLUT1(GLUT1),and lactic dehydrogenase A(LDHA)were detected by western blot analysis.The targeting relationship between circRPPH1 or TRIM14 and miR-1296-5p was verified with dual-luciferase reporter assay.The role of circRPPH1 was confirmed via xenograft assay.We verified that circRPPH1 and TRIM14 expression were increased while miR-1296-5p expression was decreased in BC tissues and hypoxia-cultured TNBC cells.Functionally,circRPPH1 silencing reversed the promoting effect of hypoxia on viability,migration,invasion,and glycolysis of TNBC cells.CircRPPH1 knockdown repressed decreased TNBC cell growth in vivo.Mechanistically,circRPPH1 sponged miR-1296-5p to modulate TRIM14 expression.Also,miR-1296-5p silencing restored circRPPH1 inhibition-mediated influence on the viability,migration,invasion,and glycolysis of hypoxia-treated TNBC cells.TRIM14 elevation overturned the inhibitory impact of miR-1296-5p mimic on viability,migration,invasion,and glycolysis of hypoxia-cultured TNBC cells.In conclusion,hypoxia-induced circRPPH1 fostered TNBC progression through regulation of the miR-1296-5p/TRIM14 axis,indicating that circRPPH1 was a promising target for TNBC treatment.展开更多
Cardiac biological pacing(BP)is one of the future directions for bradyarrhythmias intervention.Currently,cardiac pacemaker cells(PCs)used for cardiac BP are mainly derived from pluripotent stem cells(PSCs).However,the...Cardiac biological pacing(BP)is one of the future directions for bradyarrhythmias intervention.Currently,cardiac pacemaker cells(PCs)used for cardiac BP are mainly derived from pluripotent stem cells(PSCs).However,the production of high-quality cardiac PCs from PSCs remains a challenge.Here,we developed a cardiac PC differentiation strategy by adopting dual PC markers and simulating the developmental route of PCs.First,two PC markers,Shox2 and Hcn4,were selected to establish Shox2:EGFP;Hcn4:mCherry mouse PSC reporter line.Then,by stepwise guiding naïve PSCs to cardiac PCs following naïve to formative pluripotency transition and manipulating signaling pathways during cardiac PCs differentiation,we designed the FSK method that increased the yield of SHOX2^(+);HCN4^(+)cells with typical PC characteristics,which was 12 and 42 folds higher than that of the embryoid body(EB)and the monolayer M10 methods respectively.In addition,the in vitro cardiac PCs differentiation trajectory was mapped by single-cell RNA sequencing(scRNA-seq),which resembled in vivo PCs development,and ZFP503 was verified as a key regulator of cardiac PCs differentiation.These PSC-derived cardiac PCs have the potential to drive advances in cardiac BP technology,help with the understanding of PCs(patho)physiology,and benefit drug discovery for PC-related diseases as well.展开更多
基金supported by the National Key Research and Development Program of China(No.2022YFC3700701)National Natural Science Foundation of China(Grant Nos.41775146,42061134009)+1 种基金USTC Research Funds of the Double First-Class Initiative(YD2080002007)Strategic Priority Research Program of Chinese Academy of Sciences(XDB41000000).
文摘Forecasting uncertainties among meteorological fields have long been recognized as the main limitation on the accuracy and predictability of air quality forecasts.However,the particular impact of meteorological forecasting uncertainties on air quality forecasts specific to different seasons is still not well known.In this study,a series of forecasts with different forecast lead times for January,April,July,and October of 2018 are conducted over the Beijing-Tianjin-Hebei(BTH)region and the impacts of meteorological forecasting uncertainties on surface PM_(2.5)concentration forecasts with each lead time are investigated.With increased lead time,the forecasted PM_(2.5)concentrations significantly change and demonstrate obvious seasonal variations.In general,the forecasting uncertainties in monthly mean surface PM_(2.5)concentrations in the BTH region due to lead time are the largest(80%)in spring,followed by autumn(~50%),summer(~40%),and winter(20%).In winter,the forecasting uncertainties in total surface PM_(2.5)mass due to lead time are mainly due to the uncertainties in PBL heights and hence the PBL mixing of anthropogenic primary particles.In spring,the forecasting uncertainties are mainly from the impacts of lead time on lower-tropospheric northwesterly winds,thereby further enhancing the condensation production of anthropogenic secondary particles by the long-range transport of natural dust.In summer,the forecasting uncertainties result mainly from the decrease in dry and wet deposition rates,which are associated with the reduction of near-surface wind speed and precipitation rate.In autumn,the forecasting uncertainties arise mainly from the change in the transport of remote natural dust and anthropogenic particles,which is associated with changes in the large-scale circulation.
基金was funded by the Xinjiang Uygur Autonomous Region Natural Science Foundation(No.2017D01C379).
文摘Hypoxia affects the advancement,metastasis,and metabolism of breast cancer(BC).The circular RNA ribonuclease P RNA component H1(circRPPH1)(has_circ_0000515)is implicated in tumor progression.Nevertheless,the regulatory mechanism related to circRPPH1 in hypoxia-mediated triple-negative breast cancer(TNBC)progression is indistinct.The expression levels of circRPPH1,miR-1296-5p,tripartite motif-containing 14(TRIM14)mRNA in tissue samples and cells were examined through quantitative real-time polymerase chain reaction(qRT-PCR).Cell viability,migration,and invasion were determined with Cell Counting Kit-8(CCK-8)or transwell assays.The levels of glucose consumption and lactate production were assessed via the Glucose Assay Kit or Lactate Assay Kit.The protein levels of TRIM14,Glucose Transporter GLUT1(GLUT1),and lactic dehydrogenase A(LDHA)were detected by western blot analysis.The targeting relationship between circRPPH1 or TRIM14 and miR-1296-5p was verified with dual-luciferase reporter assay.The role of circRPPH1 was confirmed via xenograft assay.We verified that circRPPH1 and TRIM14 expression were increased while miR-1296-5p expression was decreased in BC tissues and hypoxia-cultured TNBC cells.Functionally,circRPPH1 silencing reversed the promoting effect of hypoxia on viability,migration,invasion,and glycolysis of TNBC cells.CircRPPH1 knockdown repressed decreased TNBC cell growth in vivo.Mechanistically,circRPPH1 sponged miR-1296-5p to modulate TRIM14 expression.Also,miR-1296-5p silencing restored circRPPH1 inhibition-mediated influence on the viability,migration,invasion,and glycolysis of hypoxia-treated TNBC cells.TRIM14 elevation overturned the inhibitory impact of miR-1296-5p mimic on viability,migration,invasion,and glycolysis of hypoxia-cultured TNBC cells.In conclusion,hypoxia-induced circRPPH1 fostered TNBC progression through regulation of the miR-1296-5p/TRIM14 axis,indicating that circRPPH1 was a promising target for TNBC treatment.
基金National Natural Science Foundation of China(grant number 82088101 and 81930013 to Y.-H.C.,31871491 to J.Y.,82070338 and 82222008 to D.X.,82370396 to D.S.,82122007 to D.L.)National Key Research and Development Plan(grant number 2019YFA0801501 to Y.-H.C.)+4 种基金Program for the Research Unit of Origin and Regulation of Heart Rhythm,Chinese Academy of Medical Sciences(grant number 2019RU045 to Y.-H.C.)Top-Level Clinical Discipline Project of Shanghai Pudong(grant number PWYgf2021-01 to Y.-H.C.)Key Research Center Construction Project of Shanghai(grant number 2022ZZ01008 to Y.-H.C.)Shanghai Key Clinical Specialty Project(shslczdzk06202 to Y.-H.C.)National Key Clinical Specialty and Fundamental Research Funds for the Central Universities to Y.-H.C.
文摘Cardiac biological pacing(BP)is one of the future directions for bradyarrhythmias intervention.Currently,cardiac pacemaker cells(PCs)used for cardiac BP are mainly derived from pluripotent stem cells(PSCs).However,the production of high-quality cardiac PCs from PSCs remains a challenge.Here,we developed a cardiac PC differentiation strategy by adopting dual PC markers and simulating the developmental route of PCs.First,two PC markers,Shox2 and Hcn4,were selected to establish Shox2:EGFP;Hcn4:mCherry mouse PSC reporter line.Then,by stepwise guiding naïve PSCs to cardiac PCs following naïve to formative pluripotency transition and manipulating signaling pathways during cardiac PCs differentiation,we designed the FSK method that increased the yield of SHOX2^(+);HCN4^(+)cells with typical PC characteristics,which was 12 and 42 folds higher than that of the embryoid body(EB)and the monolayer M10 methods respectively.In addition,the in vitro cardiac PCs differentiation trajectory was mapped by single-cell RNA sequencing(scRNA-seq),which resembled in vivo PCs development,and ZFP503 was verified as a key regulator of cardiac PCs differentiation.These PSC-derived cardiac PCs have the potential to drive advances in cardiac BP technology,help with the understanding of PCs(patho)physiology,and benefit drug discovery for PC-related diseases as well.
