Sediments are one of the main carbon sinks in subduction zones,with CaCO_(3)and SiO_(2)being the main components in sediments.Their chemical stability plays a significant role in the form of carbon in the Earth’s man...Sediments are one of the main carbon sinks in subduction zones,with CaCO_(3)and SiO_(2)being the main components in sediments.Their chemical stability plays a significant role in the form of carbon in the Earth’s mantle.Here we report the reactions of CaCO_(3)with SiO_(2)in hydrated sediments at 0.8-2.0 GPa,400-500℃and redox-buffered conditions relevant to shallow subduction zones.Our results show that the reaction CaCO_(3)+SiO_(2)=CaSiO_(3)+C+O_(2)(fluid)occurs under CoCoO and IW buffered conditions to generate wollastonite(CaSiO_(3))and carbonaceous material(CM).Moreover,wollastonite is formed by the dissolution-crystallization process,which may be significantly affected by oxygen fugacity,leading to distinct crystallization habits(Yui,1966,Schott et al.,2012).Anhydrous experiments indicate that the reaction proceeds only in the presence of H2O within the pressure and temperature(P-T)range of this study.The reaction occurs more rapidly with aragonite-structured than calcite-structured CaCO_(3).Further,the experiment buffered with natural olivine at 1.0 GPa and 400℃proves that the above reaction can occur during serpentinization processes in shallow subduction zones.More importantly,nanoscale CM may be generated under relatively reducing conditions,exhibiting Raman characteristics of kerogen.These results provide new insights into how deep carbon is distributed in the Earth’s interior.展开更多
Background:Metastasis is the leading cause of cancer-related mortality,with circulating tumor cell(CTC)clusters serving as highly efficient precursors of distant metastasis.Survival of CTC clusters in the bloodstream ...Background:Metastasis is the leading cause of cancer-related mortality,with circulating tumor cell(CTC)clusters serving as highly efficient precursors of distant metastasis.Survival of CTC clusters in the bloodstream is the primary contributor to tumor metastasis.However,the underlying mechanisms of how CTC clusters respond to the blood environment and drive metastasis remain elusive.This study aimed to elucidate the potential mechanisms that enable CTC clusters to adapt and survive in the bloodstream.Methods:CTC clusters were detected using a microfluidic system in cancer patients,as well as in patient-derived xenograft(PDX),cell line-derived xenograft,and syngeneic models.The key molecules responsible for the adaptive survival of CTC clusters were characterized using RNA-sequencing(RNAseq),gene interference,and flow cytometry.To investigate the underlying mechanisms of adaptive survival,RNA-seq,targeted metabolomics,isotope tracing experiments,chromatin immunoprecipitation(ChIP)sequencing,and immunofluorescence(IF)staining were employed.The therapeutic potential of survival pathway inhibitor combined with chemotherapy drug was evaluated in patient-derived CTCs and the PDX model.Results:CTC clusters exhibited superior survival and metastatic capacity compared to single CTCs and were associated with adverse clinical outcomes.The unfolded protein response mediator protein kinase R-like endoplasmic reticulum kinase(PERK)was activated in CTC clusters and maintained Sadenosylmethionine(SAM)availability,facilitating their adaptive survival in the bloodstream.Mechanistically,PERK mediated the upregulation of activating transcription factor 4(ATF4),which enhanced methionine adenosyltransferase 2A(MAT2A)expression,contributing to SAM synthesis.Increased SAM enhanced H3K4me3 modification of the platelet-derived growth factor B(PDGFB)promoter,leading to elevated PDGFB secretion and its accumulation in the intercellular region within CTC clusters.PDGFB functioned as a shared survival signal,triggering the phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT)pathway via platelet-derived growth factor receptor beta(PDGFRβ),supporting CTC cluster survival in the bloodstream.Inhibition of PERK and PDGFRβprofoundly impaired the survival signaling and suppressed the metastatic dissemination of CTC clusters.Conclusions:Our findings revealed a PERK/MAT2A/PDGFB axis that confers adaptive survival capabilities to CTC clusters in the bloodstream.Targeting this survival signaling pathway represents a promising therapeutic strategy for metastatic cancer.展开更多
Background Gestational diabetes mellitus （GDM） is a common complication during pregnancy,and gestational weight gain is one of the major and modifiable risk factors.This study aims to estimate the relationship betwe...Background Gestational diabetes mellitus （GDM） is a common complication during pregnancy,and gestational weight gain is one of the major and modifiable risk factors.This study aims to estimate the relationship between the rate of gestational weight gain before diagnosis of GDM and the subsequent risk of GDM.Methods A case-control study was conducted with 90 GDM cases and 165 women in the control group from May 2012 to August 2012 at Peking University First Affiliated Hospital.GDM was diagnosed according to the standards issued by the Ministry of Health of China in 2011.The plasma glucose levels,weights,and covariate data of the women were obtained based on medical records.Univariate analysis and unconditional Logistic regression model were used to estimate the associations.Results After adjusting for age at delivery,parity,and pre-pregnancy body mass index,the risk of GDM increased with increasing rates of gestational weight gain.Compared with the lower rate of gestational weight gain （less than 0.28 kg per week）,a rate of weight gain of 0.28 kg per week or more was associated with increased risk of GDM （odds ratio：2.03; 95％ confidence interval：1.15 to 3.59）.The association between the rate of gestational weight gain and GDM was primarily attributed to the increased weight gain in the first trimester.Conclusion High rates of gestational weight gain,particular during early pregnancy,may increase a woman＇s risk of GDM.展开更多
基金supported by the National Key Research and Development Program of China(Grant No.2023YFF0804100)the United Laboratory of High-Pressure Physics and Earthquake Science(Grant No.2022HPPES01)Some experiments are supported by the Synergic Extreme Condition User Facility(SECUF).
文摘Sediments are one of the main carbon sinks in subduction zones,with CaCO_(3)and SiO_(2)being the main components in sediments.Their chemical stability plays a significant role in the form of carbon in the Earth’s mantle.Here we report the reactions of CaCO_(3)with SiO_(2)in hydrated sediments at 0.8-2.0 GPa,400-500℃and redox-buffered conditions relevant to shallow subduction zones.Our results show that the reaction CaCO_(3)+SiO_(2)=CaSiO_(3)+C+O_(2)(fluid)occurs under CoCoO and IW buffered conditions to generate wollastonite(CaSiO_(3))and carbonaceous material(CM).Moreover,wollastonite is formed by the dissolution-crystallization process,which may be significantly affected by oxygen fugacity,leading to distinct crystallization habits(Yui,1966,Schott et al.,2012).Anhydrous experiments indicate that the reaction proceeds only in the presence of H2O within the pressure and temperature(P-T)range of this study.The reaction occurs more rapidly with aragonite-structured than calcite-structured CaCO_(3).Further,the experiment buffered with natural olivine at 1.0 GPa and 400℃proves that the above reaction can occur during serpentinization processes in shallow subduction zones.More importantly,nanoscale CM may be generated under relatively reducing conditions,exhibiting Raman characteristics of kerogen.These results provide new insights into how deep carbon is distributed in the Earth’s interior.
基金National Natural Science Foundation of China,Grant/Award Numbers:NSFC 82072938,NSFC82173155,NSFC82372823the Senior Medical Talents Program of Chongqing Medical University for Young and Middle-aged Scientist,Grant/Award Number:2021-W0068+1 种基金the Outstanding Professorship Program of Chongqing Medical University,Grant/Award Number:R10005the Outstanding Postgraduate Fund of Chongqing Medical University,Grant/Award Number:BJRC202313。
文摘Background:Metastasis is the leading cause of cancer-related mortality,with circulating tumor cell(CTC)clusters serving as highly efficient precursors of distant metastasis.Survival of CTC clusters in the bloodstream is the primary contributor to tumor metastasis.However,the underlying mechanisms of how CTC clusters respond to the blood environment and drive metastasis remain elusive.This study aimed to elucidate the potential mechanisms that enable CTC clusters to adapt and survive in the bloodstream.Methods:CTC clusters were detected using a microfluidic system in cancer patients,as well as in patient-derived xenograft(PDX),cell line-derived xenograft,and syngeneic models.The key molecules responsible for the adaptive survival of CTC clusters were characterized using RNA-sequencing(RNAseq),gene interference,and flow cytometry.To investigate the underlying mechanisms of adaptive survival,RNA-seq,targeted metabolomics,isotope tracing experiments,chromatin immunoprecipitation(ChIP)sequencing,and immunofluorescence(IF)staining were employed.The therapeutic potential of survival pathway inhibitor combined with chemotherapy drug was evaluated in patient-derived CTCs and the PDX model.Results:CTC clusters exhibited superior survival and metastatic capacity compared to single CTCs and were associated with adverse clinical outcomes.The unfolded protein response mediator protein kinase R-like endoplasmic reticulum kinase(PERK)was activated in CTC clusters and maintained Sadenosylmethionine(SAM)availability,facilitating their adaptive survival in the bloodstream.Mechanistically,PERK mediated the upregulation of activating transcription factor 4(ATF4),which enhanced methionine adenosyltransferase 2A(MAT2A)expression,contributing to SAM synthesis.Increased SAM enhanced H3K4me3 modification of the platelet-derived growth factor B(PDGFB)promoter,leading to elevated PDGFB secretion and its accumulation in the intercellular region within CTC clusters.PDGFB functioned as a shared survival signal,triggering the phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT)pathway via platelet-derived growth factor receptor beta(PDGFRβ),supporting CTC cluster survival in the bloodstream.Inhibition of PERK and PDGFRβprofoundly impaired the survival signaling and suppressed the metastatic dissemination of CTC clusters.Conclusions:Our findings revealed a PERK/MAT2A/PDGFB axis that confers adaptive survival capabilities to CTC clusters in the bloodstream.Targeting this survival signaling pathway represents a promising therapeutic strategy for metastatic cancer.
文摘Background Gestational diabetes mellitus （GDM） is a common complication during pregnancy,and gestational weight gain is one of the major and modifiable risk factors.This study aims to estimate the relationship between the rate of gestational weight gain before diagnosis of GDM and the subsequent risk of GDM.Methods A case-control study was conducted with 90 GDM cases and 165 women in the control group from May 2012 to August 2012 at Peking University First Affiliated Hospital.GDM was diagnosed according to the standards issued by the Ministry of Health of China in 2011.The plasma glucose levels,weights,and covariate data of the women were obtained based on medical records.Univariate analysis and unconditional Logistic regression model were used to estimate the associations.Results After adjusting for age at delivery,parity,and pre-pregnancy body mass index,the risk of GDM increased with increasing rates of gestational weight gain.Compared with the lower rate of gestational weight gain （less than 0.28 kg per week）,a rate of weight gain of 0.28 kg per week or more was associated with increased risk of GDM （odds ratio：2.03; 95％ confidence interval：1.15 to 3.59）.The association between the rate of gestational weight gain and GDM was primarily attributed to the increased weight gain in the first trimester.Conclusion High rates of gestational weight gain,particular during early pregnancy,may increase a woman＇s risk of GDM.
