Objective: DNA damage response(DDR) deficiency has emerged as a prominent determinant of tumor immunogenicity. This study aimed to construct a DDR-related immune activation(DRIA) signature and evaluate the predictive ...Objective: DNA damage response(DDR) deficiency has emerged as a prominent determinant of tumor immunogenicity. This study aimed to construct a DDR-related immune activation(DRIA) signature and evaluate the predictive accuracy of the DRIA signature for response to immune checkpoint inhibitor(ICI) therapy in gastrointestinal(GI) cancer.Methods: A DRIA signature was established based on two previously reported DNA damage immune response assays. Clinical and gene expression data from two published GI cancer cohorts were used to assess and validate the association between the DRIA score and response to ICI therapy. The predictive accuracy of the DRIA score was validated based on one ICI-treated melanoma and three pan-cancer published cohorts.Results: The DRIA signature includes three genes(CXCL10, IDO1, and IFI44L). In the discovery cancer cohort, DRIA-high patients with gastric cancer achieved a higher response rate to ICI therapy than DRIA-low patients(81.8% vs. 8.8%;P < 0.001), and the predictive accuracy of the DRIA score [area under the receiver operating characteristic curve(AUC) = 0.845] was superior to the predictive accuracy of PD-L1 expression, tumor mutational burden, microsatellite instability, and Epstein–Barr virus status. The validation cohort demonstrated that the DRIA score identified responders with microsatellite-stable colorectal and pancreatic adenocarcinoma who received dual PD-1 and CTLA-4 blockade with radiation therapy. Furthermore, the predictive performance of the DRIA score was shown to be robust through an extended validation in melanoma, urothelial cancer, and pan-cancer.Conclusions: The DRIA signature has superior and robust predictive accuracy for the efficacy of ICI therapy in GI cancer and pancancer, indicating that the DRIA signature may serve as a powerful biomarker for guiding ICI therapy decisions.展开更多
Livestock and poultry breeding environments suffer from serious microbial aerosol pollution,posing a significant challenge to maintaining healthy animal rearing.This study reviewed the sources,pollution status,hazards...Livestock and poultry breeding environments suffer from serious microbial aerosol pollution,posing a significant challenge to maintaining healthy animal rearing.This study reviewed the sources,pollution status,hazards,pathogenic mechanisms,and mitigation measures of microbial aerosols in livestock and poultry breeding settings,based on research conducted over the past two decades.Notably,the study analyzed the distribution characteristics of aerosol components in various animal houses,with a focus on identifying the main factors affecting these characteristics and the molecular mechanisms by which they damage the animal immune system.Quantitative analysis revealed varying concentrations of bacterial and fungal aerosols in different animal houses,with poultry houses often exhibiting higher concentrations.The dominant bacterial and fungal species varied across different animal houses,emphasizing the complex composition of microbial aerosols.Furthermore,antibiotic-resistant bacteria and genes,particularly those resistant to tetracycline,are prevalent in these environments,challenging disease prevention and control efforts.Thus,the infection source must be controlled through isolation measures and proper waste management.Proper disinfectant use,responsible antibiotic stewardship,biosecurity measures,and alternative disease prevention strategies should be implemented.Future research should focus on developing monitoring technologies for pathogenic microorganisms,implementing purification technologies,and investigating the immune-damaging mechanisms of microbial aerosols.By addressing these areas,we can further understand microbial aerosols in livestock and poultry environments and develop effective strategies to mitigate their harmful effects.This review contributes to the sustainable development of animal farming to ensure the health and welfare of animals.展开更多
基金supported by the National Natural Science Foundation of China (Grant Nos. 81972761 and 82202837)the National Key R&D Program of China (Grant Nos. 2016YFC1303200 and 2022YFC2505100)。
文摘Objective: DNA damage response(DDR) deficiency has emerged as a prominent determinant of tumor immunogenicity. This study aimed to construct a DDR-related immune activation(DRIA) signature and evaluate the predictive accuracy of the DRIA signature for response to immune checkpoint inhibitor(ICI) therapy in gastrointestinal(GI) cancer.Methods: A DRIA signature was established based on two previously reported DNA damage immune response assays. Clinical and gene expression data from two published GI cancer cohorts were used to assess and validate the association between the DRIA score and response to ICI therapy. The predictive accuracy of the DRIA score was validated based on one ICI-treated melanoma and three pan-cancer published cohorts.Results: The DRIA signature includes three genes(CXCL10, IDO1, and IFI44L). In the discovery cancer cohort, DRIA-high patients with gastric cancer achieved a higher response rate to ICI therapy than DRIA-low patients(81.8% vs. 8.8%;P < 0.001), and the predictive accuracy of the DRIA score [area under the receiver operating characteristic curve(AUC) = 0.845] was superior to the predictive accuracy of PD-L1 expression, tumor mutational burden, microsatellite instability, and Epstein–Barr virus status. The validation cohort demonstrated that the DRIA score identified responders with microsatellite-stable colorectal and pancreatic adenocarcinoma who received dual PD-1 and CTLA-4 blockade with radiation therapy. Furthermore, the predictive performance of the DRIA score was shown to be robust through an extended validation in melanoma, urothelial cancer, and pan-cancer.Conclusions: The DRIA signature has superior and robust predictive accuracy for the efficacy of ICI therapy in GI cancer and pancancer, indicating that the DRIA signature may serve as a powerful biomarker for guiding ICI therapy decisions.
基金supported by the National Natural Science Foundation of China(Grant No.32300087)the Poultry Innovation Team Environmental Control Post Expert(China)(SDAIT-11-09).
文摘Livestock and poultry breeding environments suffer from serious microbial aerosol pollution,posing a significant challenge to maintaining healthy animal rearing.This study reviewed the sources,pollution status,hazards,pathogenic mechanisms,and mitigation measures of microbial aerosols in livestock and poultry breeding settings,based on research conducted over the past two decades.Notably,the study analyzed the distribution characteristics of aerosol components in various animal houses,with a focus on identifying the main factors affecting these characteristics and the molecular mechanisms by which they damage the animal immune system.Quantitative analysis revealed varying concentrations of bacterial and fungal aerosols in different animal houses,with poultry houses often exhibiting higher concentrations.The dominant bacterial and fungal species varied across different animal houses,emphasizing the complex composition of microbial aerosols.Furthermore,antibiotic-resistant bacteria and genes,particularly those resistant to tetracycline,are prevalent in these environments,challenging disease prevention and control efforts.Thus,the infection source must be controlled through isolation measures and proper waste management.Proper disinfectant use,responsible antibiotic stewardship,biosecurity measures,and alternative disease prevention strategies should be implemented.Future research should focus on developing monitoring technologies for pathogenic microorganisms,implementing purification technologies,and investigating the immune-damaging mechanisms of microbial aerosols.By addressing these areas,we can further understand microbial aerosols in livestock and poultry environments and develop effective strategies to mitigate their harmful effects.This review contributes to the sustainable development of animal farming to ensure the health and welfare of animals.
