Background:Glutamine synthetase(GS)and arginase 1(Arg1)are widely used pathological markers that discriminate hepatocellular carcinoma(HCC)from intrahepatic cholangiocarcinoma;however,their clinical significance in HC...Background:Glutamine synthetase(GS)and arginase 1(Arg1)are widely used pathological markers that discriminate hepatocellular carcinoma(HCC)from intrahepatic cholangiocarcinoma;however,their clinical significance in HCC remains unclear.Methods:We retrospectively analyzed 431 HCC patients:251 received hepatectomy alone,and the other 180 received sorafenib as adjuvant treatment after hepatectomy.Expression of GS and Arg1 in tumor specimens was evaluated using immunostaining.mRNA sequencing and immunostaining to detect progenitor markers(cytokeratin 19[CK19]and epithelial cell adhesion molecule[EpCAM])and mutant TP53 were also conducted.Results:Up to 72.4%(312/431)of HCC tumors were GS positive(GS+).Of the patients receiving hepatectomy alone,GS negative(GS-)patients had significantly better overall survival(OS)and recurrence-free survival(RFS)than GS+patients;negative expression of Arg1,which is exclusively expressed in GS-hepatocytes in the healthy liver,had a negative effect on prognosis.Of the patients with a high risk of recurrence who received additional sorafenib treatment,GS-patients tended to have better RFS than GS+patients,regardless of the expression status of Arg1.GS+HCC tumors exhibit many features of the established proliferation molecular stratification subtype,including poor differentiation,high alpha-fetoprotein levels,increased progenitor tumor cells,TP53 mutation,and upregulation of multiple tumor-related signaling pathways.Conclusions:GS-HCC patients have a better prognosis and are more likely to benefit from sorafenib treatment after hepatectomy.Immunostaining of GS may provide a simple and applicable approach for HCC molecular stratification to predict prognosis and guide targeted therapy.展开更多
Background:Florida’s Everglades is a vast freshwater peatland that has been impacted by the alterations of hydrological pattern and water quality which led to changes in plant species composition and biodiversity.In ...Background:Florida’s Everglades is a vast freshwater peatland that has been impacted by the alterations of hydrological pattern and water quality which led to changes in plant species composition and biodiversity.In this study,carbon and nitrogen stable isotopes(δ13C andδ15N)in cattail(Typha domingensis)are evaluated as indicators of environmental changes in the Everglades wetlands along nutrient and hydrological gradients represented by reference sites with total phosphorus(TP)<10μg L−1,transition sites with TP≥10μg L−1<20μg L−1 and impacted sites with TP≥20μg L−1 which differed in hydrology or habitats(marsh and canal).Results:Cattailδ13C values decreased significantly from reference(–24.1‰),transition(–26.8‰)to the impacted sites(–28.2‰).In contrast,δ15N values increased significantly from reference(–5.2‰),transition(2.4‰)to the impacted site(5.9‰).In response to a poor hydrological condition,cattail in marsh area displayed 13C enrichment(–26.0‰)and 15N depletion(0.2‰).By contrast,cattail grown in the canal sites with favorable hydropattern displayed 13C depletion(–27.6‰)and 15N enrichment(5.9‰)from the canal sites with more favorable hydrological condition.Conclusions:The different patterns for the changes inδ13C andδ15N in cattail suggested that increased nutrients led to increased stomatal conductance and 13C fractionation during carbon uptake and decreased 15N fractionation with increasing nitrogen demand while poor hydrological condition coupled with low nutrients led to reduced plant growth indicated by higherδ13C and lowerδ15N values.Findings from this study suggested thatδ13C in emerged macrophytes such as cattail can be used as an indicator for environmental stress whileδ15N is a robust indicator for wetland eutrophication.展开更多
基金Natural Science Foundation of China(No.82072689)1.3.5 Project for Disciplines of Excellence,West China Hospital,Sichuan University(No.2020HXFH010)+1 种基金China Postdoctoral Science Foundation Grant(No.2021M692304)PostDoctor Research Project,West China Hospital,Sichuan University(Nos.2020HXBH069,2021HXBH031)
文摘Background:Glutamine synthetase(GS)and arginase 1(Arg1)are widely used pathological markers that discriminate hepatocellular carcinoma(HCC)from intrahepatic cholangiocarcinoma;however,their clinical significance in HCC remains unclear.Methods:We retrospectively analyzed 431 HCC patients:251 received hepatectomy alone,and the other 180 received sorafenib as adjuvant treatment after hepatectomy.Expression of GS and Arg1 in tumor specimens was evaluated using immunostaining.mRNA sequencing and immunostaining to detect progenitor markers(cytokeratin 19[CK19]and epithelial cell adhesion molecule[EpCAM])and mutant TP53 were also conducted.Results:Up to 72.4%(312/431)of HCC tumors were GS positive(GS+).Of the patients receiving hepatectomy alone,GS negative(GS-)patients had significantly better overall survival(OS)and recurrence-free survival(RFS)than GS+patients;negative expression of Arg1,which is exclusively expressed in GS-hepatocytes in the healthy liver,had a negative effect on prognosis.Of the patients with a high risk of recurrence who received additional sorafenib treatment,GS-patients tended to have better RFS than GS+patients,regardless of the expression status of Arg1.GS+HCC tumors exhibit many features of the established proliferation molecular stratification subtype,including poor differentiation,high alpha-fetoprotein levels,increased progenitor tumor cells,TP53 mutation,and upregulation of multiple tumor-related signaling pathways.Conclusions:GS-HCC patients have a better prognosis and are more likely to benefit from sorafenib treatment after hepatectomy.Immunostaining of GS may provide a simple and applicable approach for HCC molecular stratification to predict prognosis and guide targeted therapy.
基金from an Overseas Research collaboration grant(2018AHB020)funded by Hubei Province,China.
文摘Background:Florida’s Everglades is a vast freshwater peatland that has been impacted by the alterations of hydrological pattern and water quality which led to changes in plant species composition and biodiversity.In this study,carbon and nitrogen stable isotopes(δ13C andδ15N)in cattail(Typha domingensis)are evaluated as indicators of environmental changes in the Everglades wetlands along nutrient and hydrological gradients represented by reference sites with total phosphorus(TP)<10μg L−1,transition sites with TP≥10μg L−1<20μg L−1 and impacted sites with TP≥20μg L−1 which differed in hydrology or habitats(marsh and canal).Results:Cattailδ13C values decreased significantly from reference(–24.1‰),transition(–26.8‰)to the impacted sites(–28.2‰).In contrast,δ15N values increased significantly from reference(–5.2‰),transition(2.4‰)to the impacted site(5.9‰).In response to a poor hydrological condition,cattail in marsh area displayed 13C enrichment(–26.0‰)and 15N depletion(0.2‰).By contrast,cattail grown in the canal sites with favorable hydropattern displayed 13C depletion(–27.6‰)and 15N enrichment(5.9‰)from the canal sites with more favorable hydrological condition.Conclusions:The different patterns for the changes inδ13C andδ15N in cattail suggested that increased nutrients led to increased stomatal conductance and 13C fractionation during carbon uptake and decreased 15N fractionation with increasing nitrogen demand while poor hydrological condition coupled with low nutrients led to reduced plant growth indicated by higherδ13C and lowerδ15N values.Findings from this study suggested thatδ13C in emerged macrophytes such as cattail can be used as an indicator for environmental stress whileδ15N is a robust indicator for wetland eutrophication.
