Background:Peripheral helper T(T_(PH))cells are uniquely positioned within pathologically inflamed non-lymphoid tissues to stimulate B-cell responses and antibody production.However,the phenotype,function,and clinical...Background:Peripheral helper T(T_(PH))cells are uniquely positioned within pathologically inflamed non-lymphoid tissues to stimulate B-cell responses and antibody production.However,the phenotype,function,and clinical relevance of T_(PH) cells in hepatocellular carcinoma(HCC)are currently unknown.Methods:Blood,tumor,and peritumoral liver tissue samples from 39 HCC patients(Sep 2016-Aug 2017)and 101 HCC patients(Sep 2011-Dec 2012)at the Third Affiliated Hospital of Sun Yat-sen University were used.Flow cytometry was used to quantify the expression,phenotype,and function of T_(PH) cells.Log-rank tests were performed to evaluate disease-free survival and overall survival in samples from 39 patients and 101 patients with HCC.T_(PH) cells,CD19^(+)B cells,and T follicular helper(T_(FH))cells were cultured separately in vitro or isolated from C57/B6L mice in vivo for functional assays.Results:T_(PH) cells highly infiltrated tumor tissues,which was correlated with tumor size,early recurrence,and shorter survival time.The tumor-infiltrated T_(PH) cells showed a unique ICOS^(hi)CXCL13^(+)IL-21-MAF^(+)BCL-6^(-) phenotype and triggered naïve B-cell differentiation into regulatory B cells.Triggering programmed cell death protein 1(PD-1)induced the production of C-X-C motif chemokine ligand 13(CXCL13)by T_(PH) cells,which then suppressed tumor-specific immunity and promoted disease progression.Conclusion:Our study reveals a novel regulatory mechanism of T_(PH) cell-regulatory B-cell-mediated immunosuppression and provides an important perspective for determining the balance between the differentiation of protumorigenic T_(PH) cells and that of antitumorigenic T_(FH) cells in the HCC microenvironment.展开更多
The pollution of antibiotics in aquatic environments has received extensive attention.Yet,research on antibiotic contamination in river-lake systems,a significant form of modern aquatic environments,still needs to be ...The pollution of antibiotics in aquatic environments has received extensive attention.Yet,research on antibiotic contamination in river-lake systems,a significant form of modern aquatic environments,still needs to be explored.This study focuses on the Chaohu Basin(China)investigating the occurrence characteristics,influencing factors,and risk assessments of antibiotics in the river-lake system.The total antibiotic concentrations in the water phase and sediment phase were 3.14–1887.49 ng/L and 0.92–1553.75 ng/g,respectively.Clindamycin was the predominant antibiotic in the water phase,whereas tetracycline prevailed in the sediment phase.Notable differences in concentration and structural composition of antibiotics between the tributaries(river system)and Chaohu Lake were observed,indicating the involvement of various geochemical processes in the attenuation of antibiotics during transport to the receiving lake.Spatial analysis suggested that the western river is the primary source of antibiotics in Chaohu Lake.Controlling nutrient influx in heavily polluted areas is crucial to addressing the escalating issue of antibiotic pollution in the river-lake system.The widespread occurrence of clindamycin in the waters is likely due to wastewater treatment plant discharges,and high-intensity human activities continue to exacerbate antibiotic contamination.Risk assessment indicated that sulfamethoxazole,tetracycline,lincomycin,and clindamycin ranked in the top four with the highest risks to the most sensitive aquatic organisms.Nonetheless,the antibiotics presented no risk to consumer health.This study provides valuable insights for controlling antibiotic pollution in riverlake systems.展开更多
基金supported by the National Natural Science Foundation of China(Nos.82103448 and 81972286)the Guangdong Natural Science Foun dation(No.2023A1515010322)+2 种基金Guangdong Basic and Applied Basic Research foundation(No.2024A1515010553)the Science and Technology Program of Guangdong Province(No.2019B020236003)the Guangdong Key Laboratory of Liver Disease Research(No.2020B1212060019).
文摘Background:Peripheral helper T(T_(PH))cells are uniquely positioned within pathologically inflamed non-lymphoid tissues to stimulate B-cell responses and antibody production.However,the phenotype,function,and clinical relevance of T_(PH) cells in hepatocellular carcinoma(HCC)are currently unknown.Methods:Blood,tumor,and peritumoral liver tissue samples from 39 HCC patients(Sep 2016-Aug 2017)and 101 HCC patients(Sep 2011-Dec 2012)at the Third Affiliated Hospital of Sun Yat-sen University were used.Flow cytometry was used to quantify the expression,phenotype,and function of T_(PH) cells.Log-rank tests were performed to evaluate disease-free survival and overall survival in samples from 39 patients and 101 patients with HCC.T_(PH) cells,CD19^(+)B cells,and T follicular helper(T_(FH))cells were cultured separately in vitro or isolated from C57/B6L mice in vivo for functional assays.Results:T_(PH) cells highly infiltrated tumor tissues,which was correlated with tumor size,early recurrence,and shorter survival time.The tumor-infiltrated T_(PH) cells showed a unique ICOS^(hi)CXCL13^(+)IL-21-MAF^(+)BCL-6^(-) phenotype and triggered naïve B-cell differentiation into regulatory B cells.Triggering programmed cell death protein 1(PD-1)induced the production of C-X-C motif chemokine ligand 13(CXCL13)by T_(PH) cells,which then suppressed tumor-specific immunity and promoted disease progression.Conclusion:Our study reveals a novel regulatory mechanism of T_(PH) cell-regulatory B-cell-mediated immunosuppression and provides an important perspective for determining the balance between the differentiation of protumorigenic T_(PH) cells and that of antitumorigenic T_(FH) cells in the HCC microenvironment.
基金supported by the National Natural Science Youth Science Foundation of China(No.42007330)the Open Project of State Key Laboratory of Urban Water Resources and Environment(China)(No.ES202124)the Academic New Talent Enhancement Program B of Hefei University of Technology(China)(No.JZ2021HGTB0112)。
文摘The pollution of antibiotics in aquatic environments has received extensive attention.Yet,research on antibiotic contamination in river-lake systems,a significant form of modern aquatic environments,still needs to be explored.This study focuses on the Chaohu Basin(China)investigating the occurrence characteristics,influencing factors,and risk assessments of antibiotics in the river-lake system.The total antibiotic concentrations in the water phase and sediment phase were 3.14–1887.49 ng/L and 0.92–1553.75 ng/g,respectively.Clindamycin was the predominant antibiotic in the water phase,whereas tetracycline prevailed in the sediment phase.Notable differences in concentration and structural composition of antibiotics between the tributaries(river system)and Chaohu Lake were observed,indicating the involvement of various geochemical processes in the attenuation of antibiotics during transport to the receiving lake.Spatial analysis suggested that the western river is the primary source of antibiotics in Chaohu Lake.Controlling nutrient influx in heavily polluted areas is crucial to addressing the escalating issue of antibiotic pollution in the river-lake system.The widespread occurrence of clindamycin in the waters is likely due to wastewater treatment plant discharges,and high-intensity human activities continue to exacerbate antibiotic contamination.Risk assessment indicated that sulfamethoxazole,tetracycline,lincomycin,and clindamycin ranked in the top four with the highest risks to the most sensitive aquatic organisms.Nonetheless,the antibiotics presented no risk to consumer health.This study provides valuable insights for controlling antibiotic pollution in riverlake systems.
