No abstract

To increase the efficacy of small molecule chemotherapeutic drug (SMCD) and reduce its toxic and side effects, we selected two model drugs doxorubicin (DOX) and chloroquine (CQ). DOX is a SMCD and CQis a chemosensitizer with autophagy inhibition. Poly(lactic-co-glycolic acid) (PLGA) and alpha-tocopherol polyethylene glycol 1000 succinate were chosen as delivery carriers to design and prepare a novel type of drug co-delivery single-nanoparticles by emulsification-solvent volatilisation, named NP DOX+CQ . The physicochemical properties of NP DOX+CQ were characterised. Then A549 cells and A549/Taxol cells were used for the in vitro anti-cancer effect study. At the same time, cellular uptake, intracellular migration and anti-cancer mechanism of nanoparticles were studied. The NPs showed a uniform spherical shape with good dispersibility, and both drugs had good encapsulation efficiency and loading capacity. In all formulations, NP DOX+CQ showed the highest in vitro cytotoxicity. The results showed that NPs could protect drugs from being recognised and excluded by P-glycoprotein (P-gp). Moreover, the results of the mechanistic study demonstrated that NPs were transported by autophagy process after being taken up by the cells. Therefore, during the migration of NP DOX+CQ , CQ could exert its efficacy and block autophagy so that DOX would not be hit by autophagy. Western Blot results showed that NP DOX+CQ had the best inhibition effect of autophagy. It can be concluded that the system can prevent the drug from being recognised and excluded by P-gp, and CQ blocks the process of autophagy so that the DOX is protected and more distributed to the nucleus of multidrug resistance (MDR) cell. The NP DOX+CQ constructed in this study provides a feasible strategy for reversing MDR in tumour cells.

Most waterlily flowers open at dawn and close after noon usually for three to four days, and thereafter wilt. The short lifespan of flowers restricts the development of the flower postharvest industry. The termination of flower movements is a key event during flower aging process. However, it is still unclear when the senescence process initiates and how it terminates the movement rhythm. In this study, we observed that the opening diameter of flowers was the smallest on the fourth (last) flowering day. Subsequent transcriptome profiles generated from petals at different flowering stages showed that the multiple signaling pathways were activated at the last closure stage (Time 3, T3) of the flowers, including Ca2+, reactive oxygen species and far red light signaling pathways, as well as auxin, ethylene and jasmonic acid signaling pathways. Moreover, In terms of cell metabolism regulation, the genes related to hydrolase (protease, phospholipase, nuclease) were upregulated at T3 stage, indicating that petals entered the senescence stage at that time; and the genes related to water transport and cell wall modification were also differentially regulated at T3 stage, which would affect the ability of cell expand and contract, and eventually lead to petal not open after the fourth day. Collectively, our data provided a new insight into the termination of flower opening in the waterlilies, and a global understanding of the senescence process of those opening-closure rhythm flowers.

Abstract Background: Dacrydiumpectinatum de Laubenfels is a perennial gymnosperm dominant in tropical montane rain forests. Due to severe damages by excessive deforestation, typhoons, and other external forces, the population of the species has been significantly reduced. Furthermore, natural regeneration is poor. In order to better understand the reproductive process in D. pectinatum, we examined the morphological and anatomical changes during the development of male cone and analyzed the endogenous hormone dynamics.Results: Our study indicates that D. pectinatum male buds become distinguishable in April in tropical montane rain forests, while microspore sac forms in September and pollen mother cell forms and divides in December. Pollen grains mature and disperse in the following February. A mature male cone averages 8.5 mm in length. Level of GA, IAA, ABA and JA and their ratios fluctuated during late August to late November when sporogenous tissues were actively differentiated.Conclusions: The differentiation of sporogenous tissues is accompanied by variations in levels of endogenous hormones (GA, ABA, IAA, and JA) and their balances. The new insights about the cone development in D. pectinatum lay the foundation for future cone induction with hormones and study of factors contributing to the species’ low rate of seed germination.

Dacrydium pectinatum de Laubenfels is a perennial gymnosperm species dominant in tropical montane rain forests. Due to severe damages by excessive deforestation, typhoons, and other external forces, the population of the species has been significantly reduced. Furthermore, its natural regeneration is poor. To better understand the male cone development in D. pectinatum, we examined the morphological and anatomical changes, analyzed the endogenous hormone dynamics, and profiled gene expression. The morpho-histological observations suggest that the development of D. pectinatum male cone can be largely divided into four stages: microspore primordium formation (April to May), microspore sac and pollen mother cell formation (July to November), pollen mother cell division (January), and pollen grain formation (February). The levels of gibberellins (GA), auxin (IAA), abscisic Acid (ABA), cytokinin (CTK), and jasmonic acid (JA) fluctuated during the process of male cone development. The first transcriptome database for a Dacrydium species was generated, revealing >70,000 unigene sequences. Differential expression analyses revealed several floral and hormone biosynthesis and signal transduction genes that could be critical for male cone development. Our study provides new insights on the cone development in D. pectinatum and the foundation for male cone induction with hormones and studies of factors contributing to the species’ low rate of seed germination.