Combination therapy has shown its promise in the clinic for enhancing the efficacy of tumor treatment.However,the dose control of multiple drugs and their non-overlapping toxicity from different drugs are still great ...Combination therapy has shown its promise in the clinic for enhancing the efficacy of tumor treatment.However,the dose control of multiple drugs and their non-overlapping toxicity from different drugs are still great challenge.In this work,a single model drug,paclitaxel(PTX),is used to realize combination therapy and solve the problems mentioned above.Either PTX or its triphenylphosphine derivative(TPTX)is encapsulated in galactose-modified liposomes(GLips)to obtain GLips-P or GLips-TP,which are simply mixed in different ratios to finely control the proportion of PTX and TPTX.These mixed liposomes,GLips-P/TP,feature a cascade target delivery of PTX,from tissue to cell,and then to organelle.PTX plays a primary role to cause the cytotoxicity by microtubule bindings in cytoplasm,while TPTX is proved to increase the intracellular levels of caspase-3 and caspase-9 that cause apoptosis via a mitochondria-mediated pathway.Notably,GLips-P/TP 3:1 exhibited the significant drug synergy in both cytotoxicity assay of HepG2 cells and the treatment efficacy in Heps xenograft ICR mouse models.This work not only demonstrates the great promise of a cascade targeting delivery for precise tumor treatment,but also offers a novel platform to design combinatory therapy systems using a single drug.展开更多
[Objective] This study aimed to analyze the yield potential of newly developed Yinshui-type japonica hybrid rice parents and provide the theoretical basis for breeding of Yinshui-type japonica hybrid rice. [Method] An...[Objective] This study aimed to analyze the yield potential of newly developed Yinshui-type japonica hybrid rice parents and provide the theoretical basis for breeding of Yinshui-type japonica hybrid rice. [Method] An incomplete diallel cross of four cytoplasmic male sterile （CMS） lines and four restorer lines was designed to investigate the combining ability for yield and yield components of Yinshui-type japonica hybrid rice. [Result] The variances of general combining ability （GCA） for yield traits were extremely significantly different. GCA variances of male parents were higher than that of female parents except for seed-setting rate. The variances of specific combining ability （SCA） for grain yield per plant, number of effective spikes and seed-setting rate were significantly or extremely significantly different. 139A and Wanlun 422 exhibited higher GCA effects. Most yield traits of these two parents be- longed to type II. Combinations 139AxWanlun 422 and Liaojingl0AxWanlun 422 had relatively high grain yield per plant and SCA effects. GCA effects of restorer lines and SCA effects of combinations greatly affected yield traits, while GCA ef- fects of CMS lines slightly affected yield traits. [Conclusion] In this study, restorer lines exhibited greater genetic differences and impact on yield traits than CMS lines; 139A and Wanlun 422 possessed higher application potential.展开更多
基金supported by grants from the National Natural Science Foundation of China(31870946,31470916 and 51672010)the Funding of Double First-rate discipline construction(CPU2018GF07,China)+1 种基金the Priority Academic Program Development of Jiangsu Higher Education Institutionsthe Open Project Program of MOE Key Laboratory of Drug Quality Control and Pharmacovigilance(DQCP2015MS01,China).
文摘Combination therapy has shown its promise in the clinic for enhancing the efficacy of tumor treatment.However,the dose control of multiple drugs and their non-overlapping toxicity from different drugs are still great challenge.In this work,a single model drug,paclitaxel(PTX),is used to realize combination therapy and solve the problems mentioned above.Either PTX or its triphenylphosphine derivative(TPTX)is encapsulated in galactose-modified liposomes(GLips)to obtain GLips-P or GLips-TP,which are simply mixed in different ratios to finely control the proportion of PTX and TPTX.These mixed liposomes,GLips-P/TP,feature a cascade target delivery of PTX,from tissue to cell,and then to organelle.PTX plays a primary role to cause the cytotoxicity by microtubule bindings in cytoplasm,while TPTX is proved to increase the intracellular levels of caspase-3 and caspase-9 that cause apoptosis via a mitochondria-mediated pathway.Notably,GLips-P/TP 3:1 exhibited the significant drug synergy in both cytotoxicity assay of HepG2 cells and the treatment efficacy in Heps xenograft ICR mouse models.This work not only demonstrates the great promise of a cascade targeting delivery for precise tumor treatment,but also offers a novel platform to design combinatory therapy systems using a single drug.
文摘[Objective] This study aimed to analyze the yield potential of newly developed Yinshui-type japonica hybrid rice parents and provide the theoretical basis for breeding of Yinshui-type japonica hybrid rice. [Method] An incomplete diallel cross of four cytoplasmic male sterile （CMS） lines and four restorer lines was designed to investigate the combining ability for yield and yield components of Yinshui-type japonica hybrid rice. [Result] The variances of general combining ability （GCA） for yield traits were extremely significantly different. GCA variances of male parents were higher than that of female parents except for seed-setting rate. The variances of specific combining ability （SCA） for grain yield per plant, number of effective spikes and seed-setting rate were significantly or extremely significantly different. 139A and Wanlun 422 exhibited higher GCA effects. Most yield traits of these two parents be- longed to type II. Combinations 139AxWanlun 422 and Liaojingl0AxWanlun 422 had relatively high grain yield per plant and SCA effects. GCA effects of restorer lines and SCA effects of combinations greatly affected yield traits, while GCA ef- fects of CMS lines slightly affected yield traits. [Conclusion] In this study, restorer lines exhibited greater genetic differences and impact on yield traits than CMS lines; 139A and Wanlun 422 possessed higher application potential.
