The Ti-36Nb-2Ta-3Zr-0.350 （mass fraction, %） （TNTZO） alloy was produced by cold isostatic pressing and sintering from elemental powders, followed by hot and cold deformation. The effects of deformation process on ...The Ti-36Nb-2Ta-3Zr-0.350 （mass fraction, %） （TNTZO） alloy was produced by cold isostatic pressing and sintering from elemental powders, followed by hot and cold deformation. The effects of deformation process on microstructures and mechanical properties were investigated using the SEM, TEM, OM and the universal material testing machine. Results show that the alloy can be easily hot forged and cold swaged due to the fine-grained microstructure. Only after cold swaging by 85%, the alloy shows the typical ＂marble-like＂ structure. And thecold deformation is accompanied by stress-induced a＂ phase transformations. Moreover, both the strength and the ductility of the alloy are significantly improved by hot and cold working.展开更多
DNA mismatch repair （MMR） processes the chemically induced mispairs following treatment with clinically important nucleoside analogs such as 6-thioguanine （6-TG） and 5-fluorouracil （5-FU）. MMR processing of thes...DNA mismatch repair （MMR） processes the chemically induced mispairs following treatment with clinically important nucleoside analogs such as 6-thioguanine （6-TG） and 5-fluorouracil （5-FU）. MMR processing of these drugs has been implicated in activation of a prolonged G2/M cell cycle arrest for repair and later induction of apoptosis and/or autophagy for irreparable DNA damage. In this study, we investigated the role of Bcl2 and adenovirus EIB Nineteen-kilodalton Interacting Protein （BNIP3） in the activation of autophagy, and the temporal relationship between a G2/M cell cycle arrest and the activation of BNIP3-mediated autophagy following MMR processing of 6-TG and 5-FU. We found that BNIP3 protein levels are upregulated in a MLHI （MMR＋）-dependent manner following 6-TG and 5-FU treatment. Subsequent small-interfering RNA （siRNA）-mediated BNIP3 knockdown abrogates 6-TG- induced autophagy. We also found that p53 knockdown or inhibition of mTOR activity by rapamycin cotreatment impairs 6-TG- and 5-FU-induced upregulation of BNIP3 protein levels and autophagy. Furthermore, suppression of Checkpoint kinase 1 （Chkl） expression with a subsequent reduction in 6-TG-induced G2/M cell cycle arrest by Chkl siRNA promotes the extent of 6-TG-induced autophagy. These findings suggest that BNIP3 mediates 6-TG- and 5-FU-induced autophagy in a p53- and mTOR-dependent manner. Additionally, the duration of Chkl-activated G2/ M cell cycle arrest determines the level of autophagy following MMR processing of these nucleoside analogs.展开更多
基金Project(2014CB644002)supported by the National Key Fundamental Research and Development Project of ChinaProject(51301203)supported by the National Natural Science Foundation of China+1 种基金Project(2015CX004)supported by the Innovation-driven Plan in Central South University,Chinasupported by the Outstanding Graduate Project of Advanced Non-ferrous Metal Structural Materials and Manufacturing Collaborative Innovation Center,China
文摘The Ti-36Nb-2Ta-3Zr-0.350 （mass fraction, %） （TNTZO） alloy was produced by cold isostatic pressing and sintering from elemental powders, followed by hot and cold deformation. The effects of deformation process on microstructures and mechanical properties were investigated using the SEM, TEM, OM and the universal material testing machine. Results show that the alloy can be easily hot forged and cold swaged due to the fine-grained microstructure. Only after cold swaging by 85%, the alloy shows the typical ＂marble-like＂ structure. And thecold deformation is accompanied by stress-induced a＂ phase transformations. Moreover, both the strength and the ductility of the alloy are significantly improved by hot and cold working.
文摘DNA mismatch repair （MMR） processes the chemically induced mispairs following treatment with clinically important nucleoside analogs such as 6-thioguanine （6-TG） and 5-fluorouracil （5-FU）. MMR processing of these drugs has been implicated in activation of a prolonged G2/M cell cycle arrest for repair and later induction of apoptosis and/or autophagy for irreparable DNA damage. In this study, we investigated the role of Bcl2 and adenovirus EIB Nineteen-kilodalton Interacting Protein （BNIP3） in the activation of autophagy, and the temporal relationship between a G2/M cell cycle arrest and the activation of BNIP3-mediated autophagy following MMR processing of 6-TG and 5-FU. We found that BNIP3 protein levels are upregulated in a MLHI （MMR＋）-dependent manner following 6-TG and 5-FU treatment. Subsequent small-interfering RNA （siRNA）-mediated BNIP3 knockdown abrogates 6-TG- induced autophagy. We also found that p53 knockdown or inhibition of mTOR activity by rapamycin cotreatment impairs 6-TG- and 5-FU-induced upregulation of BNIP3 protein levels and autophagy. Furthermore, suppression of Checkpoint kinase 1 （Chkl） expression with a subsequent reduction in 6-TG-induced G2/M cell cycle arrest by Chkl siRNA promotes the extent of 6-TG-induced autophagy. These findings suggest that BNIP3 mediates 6-TG- and 5-FU-induced autophagy in a p53- and mTOR-dependent manner. Additionally, the duration of Chkl-activated G2/ M cell cycle arrest determines the level of autophagy following MMR processing of these nucleoside analogs.
