The tumor microenvironment （TME） plays a prominent role in the growth of tumor cells. As the major inflammatory component of the TME, M2d macrophages are educated by the TME such that they adopt an immunosnppressive...The tumor microenvironment （TME） plays a prominent role in the growth of tumor cells. As the major inflammatory component of the TME, M2d macrophages are educated by the TME such that they adopt an immunosnppressive role that promotes tumor metastasis and progression. Fra-1 forms activator protein-1 heterodimers with Jun partners and drives gene transcription. Fra-1 is thought to drastically induce tumorigenesis and progression. However, the functional role of Fra-1 in the generation of M2d macrophages is poorly understood to date. Here, we demonstrate that 4T1 mammary carcinoma cells, when co-cultured with RAW264.7 macrophage cells, skew the RAW264.7 macrophage cell differentiation into M2d macrophages. The 4T1 cells stimulate de novo overexpression of Fra-1 in RAW264.7 cells, and then Fra-1 binds to the interleukin 6 （IL-6） promoter to increase the production of the cytokine IL-6 in RAW264.7 cells. IL-6 acts in an autocrine fashion to skew RAW264.7 macrophage cell differentiation into M2d macrophages. These findings open new insights into how to reverse M2d macrophage-induced immune tolerance to improve the efficacy of immunotherapeutic approaches.展开更多
Hard coatings are used to improve the wear resistance of metals which largely depends on adhesion between substrate and coating.The wear and friction behavior of uncoated and TiCN-coated D2,M2 and M4 steels were evalu...Hard coatings are used to improve the wear resistance of metals which largely depends on adhesion between substrate and coating.The wear and friction behavior of uncoated and TiCN-coated D2,M2 and M4 steels were evaluated by apin-on-disk test under lubricated conditions.In order to evaluate the influence of lubricant on wear performance,dry friction tests were also performed.The results showed that friction coefficients were very similar for both uncoated and TiCN-coated steels.Under lubricated conditions,the uncoated D2 tool steel exhibited the lowest friction coefficient,but the TiCN-coated D2 steel presented the smallest wear rate.Abrasion was the main wear mechanism in all the tribocouples.Additionally,microhardness measurements were carried out,finding an influence of the steel substrate on the hardness of the coatings.Besides,adhesion test was conducted,suggesting agood adhesion of class 1 between substrates and TiCN coatings.展开更多
文摘The tumor microenvironment （TME） plays a prominent role in the growth of tumor cells. As the major inflammatory component of the TME, M2d macrophages are educated by the TME such that they adopt an immunosnppressive role that promotes tumor metastasis and progression. Fra-1 forms activator protein-1 heterodimers with Jun partners and drives gene transcription. Fra-1 is thought to drastically induce tumorigenesis and progression. However, the functional role of Fra-1 in the generation of M2d macrophages is poorly understood to date. Here, we demonstrate that 4T1 mammary carcinoma cells, when co-cultured with RAW264.7 macrophage cells, skew the RAW264.7 macrophage cell differentiation into M2d macrophages. The 4T1 cells stimulate de novo overexpression of Fra-1 in RAW264.7 cells, and then Fra-1 binds to the interleukin 6 （IL-6） promoter to increase the production of the cytokine IL-6 in RAW264.7 cells. IL-6 acts in an autocrine fashion to skew RAW264.7 macrophage cell differentiation into M2d macrophages. These findings open new insights into how to reverse M2d macrophage-induced immune tolerance to improve the efficacy of immunotherapeutic approaches.
基金support of Tecnológico Nacional de México(TNM)(Grant No.5724.16P)
文摘Hard coatings are used to improve the wear resistance of metals which largely depends on adhesion between substrate and coating.The wear and friction behavior of uncoated and TiCN-coated D2,M2 and M4 steels were evaluated by apin-on-disk test under lubricated conditions.In order to evaluate the influence of lubricant on wear performance,dry friction tests were also performed.The results showed that friction coefficients were very similar for both uncoated and TiCN-coated steels.Under lubricated conditions,the uncoated D2 tool steel exhibited the lowest friction coefficient,but the TiCN-coated D2 steel presented the smallest wear rate.Abrasion was the main wear mechanism in all the tribocouples.Additionally,microhardness measurements were carried out,finding an influence of the steel substrate on the hardness of the coatings.Besides,adhesion test was conducted,suggesting agood adhesion of class 1 between substrates and TiCN coatings.
