To circumvent the rapid clearance in vivo and consequent low tumor targeting of 5-fluorouracil (5-Fu), hyaluronan-5-fluorouracil conjugate (HA-5-Fu) was firstly synthesized and characterized. The stability of HA-5-Fu in vitro was evaluated by incubation with phosphate buffered saline, hyaluronidase solution, and mice plasma, respectively. The tumor targeting was tested by in vitro cytotoxicity evaluation and in vivo pharmacokinetics study in plasma and tumor. HA-5-Fu with drug loading of 87.674 mg/g was successfully obtained and confirmed. HA-5-Fu showed high stability in acidic environment and moderate stability under enzymatic cleavage. The enhanced cytotoxicity of HA-5-Fu over 5-Fu depended on drug concentration, incubation time, and cell lines type. The t 1/2 of HA-5-Fu in plasma after injection of prodrug was extended up to 10 times compared with that of 5-Fu. Notably, AUC 0-t in tumors of HA-5-Fu was 3.6 times higher than 5-Fu, demonstrating its excellent tumor targeting and quite promising prospect in anti-cancer therapy.
In the rolling process of heavy cylinders, the deformation section is subjected to the effects of compression and shear. In order to analyze the influences of the shear effect on the microstructure evolution characteristics, a mathematical model was established and the rolling process was simulated. Firstly, shear-compression specimen (SCS) and ordinary cylinder specimens were designed, high-temperature compression experiments were carried out and the mathematical model of microstructure evolution considering shear effect was established; then, a program based on finite element software was developed to simulate the microstructure evolution process, and the feasibility of the development program was verified by compression experiments. Finally, a macro–micro coupling model based on the development program was established to simulate the microstructure evolution of the heavy cylinder during the rolling process. Then, the influence of the shear effect on the microstructure evolution was analyzed. The results showed that the shear effect had a great influence on the heavy cylinder. Dynamic recrystallization was more likely to occur in the heavy cylinder during the rolling process and the grain refinement was more obvious; compared with the case without considering the shear effect, the volume fraction of dynamic recrystallization was increased by 0.25%, and the grain size was refined by 30 μm.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.