Background The high postoperative recurrence rate and refractoriness of relapsed tumors are still a conundrum for the clinical management of osteosarcoma (OS). New therapeutic options are urgently needed. Depriving the nourishment of myeloid-derived suppressor cells is a novel strategy to improve the immunosuppressive tumor microenvironment for enhanced OS therapy. Methods We synthesized a hyaluronic acid (HA)-modified metal–organic framework for combinational chemotherapy and immunotherapy of OS. Zeolitic Imidazolate Framework-8 (ZIF-8) was prepared by a one-pot synthetic method, Gemcitabine (Gem) and D-1-Methyltryptophan (D-1-MT) were loaded into the ZIF-8 during the synthesis process to make ZIF-8@Gem/D-1-MT nanoparticles (NPs). The end product (HA/ZIF-8@Gem/D-1-MT NPs) was obtained by HA modification on the surface of ZIF-8@Gem/D-1-MT NPs. The obtained HA/ZIF-8@Gem/D-1-MT NPs have excellent potential as a drug delivery vector for chemotherapy and immunotherapy in vitro and vivo. Results The results indicate that HA/ZIF-8@Gem/D-1-MT NPs were readily taken up by OS cells, and that the Gem and D-1-MT were effectively released into the acidic environment. The HA/ZIF-8@Gem/D-1-MT NPs could efficiently decrease OS cell viability (proliferation, apoptosis, cell cycle, migration and invasion). And HA/ZIF-8@Gem/D-1-MT NPs could reactivate antitumor immunity by inhibiting indoleamine 2,3 dioxygenase and myeloid-derived suppressor cells. Furthermore, animal experiments confirmed that HA/ZIF-8@Gem/D-1-MT NPs could induce intratumoral immune responses and inhibit tumor growth. Additionally, HA/ZIF-8@Gem/D-1-MT NPs have a good safety profile. Conclusions Our findings demonstrate that the combination of Gem with D-1-MT brings new hope for the improved treatment of OS, while the generation of the nanosystem has increased the application potential and flexibility of this strategy.

No abstract

Reactive oxygen species (ROS) play a major role in plant defense against pathogens, but the evidence for their role in defense against insects is still limited. In this study, HN16 and its mutated line (asm1) were used as research objects, and the potential role of H 2 O 2 in sorghum against aphid was examined. Constitutive H 2 O 2 was considered the main factor associated with increased aphid tolerance, although aphid feeding also induced an increase in the H 2 O 2 concentration. By studying ROS scavenging enzymes, it was found that APX and GPX were closely related, but SOD, POX and CAT were not involved in RMES1-mediated resistance. DEGs involved in the detoxification of ROS in HN16 worked through different means. Analysis of three DEGs encoding APX and GPX revealed that although the expression changes of SbAPx1 were consistent and those of SbGPx1 and SbGPx2 were inconsistent with enzyme activity, they all played an important role in RMES1-mediated resistance to aphids.

No abstract