A generalizable reactive blending strategy to construct flame-retardant, mechanically-strong and toughened poly(L-lactic acid) bioplastics.

Poly(L-lactic acid) (PLA) is an environmentally-friendly bioplastic with high mechanical strength, but suffers from inherent flammability and poor toughness. Many tougheners have been reported for PLA, but their synthesis usually involves organic solvents, and they tend to dramatically reduce the mechanical strength and cannot settle the flammability matter. Herein, we develop strong, tough, and flame-retardant PLA composites by reactive blending PLA, 6-((double (2-hydroxyethyl) amino) methyl) dibenzo [c, e] [1,2] oxyphosphate acid 6-oxide (DHDP) and diphenylmethane diisocyanate (MDI) and define it PLA/xGH, where x indicates that the molar ratio of -NCO group in MDI to -OH group in PLA and DHDP is 1.0x: 1. This fabrication requires no solvents. PLA/2GH with a -NCO/-OH molar ratio of 1.02: 1 maintains high tensile strength of 63.0 MPa and achieves a 23.4 % increase in impact strength compared to PLA due to the incorporation of rigid polyurethane chain segment. The vertical combustion (UL-94) classification and limiting oxygen index (LOI) of PLA/2GH reaches V-0 and 29.8 %, respectively, because DHDP and MDI function in gas and condensed phases. This study displays a generalizable strategy to create flame-retardant bioplastics with great mechanical performances by the in-situ formation of P/N-containing polyurethane segment within PLA.

Eurycomanone inhibits osteosarcoma growth and metastasis by suppressing GRP78 expression.

ETHNOPHARMACOLOGICAL RELEVANCE: Osteosarcoma (OS) is characterized by rapid growth and frequent pulmonary metastasis. Eurycoma longifolia Jack, a flowering plant primarily found in Southeast Asian countries, is commonly used in traditional herbal medicine. Its root extract is mainly used for against cancer, malaria, parasites and other conditions. The active compound in its root extract, eurycomanone (EUR), has been proven to inhibit lung and liver cancer proliferation. AIM OF THE STUDY: Our research aimed to investigate the inhibitory effect and underlying molecular mechanism of EUR on OS growth and metastasis. MATERIALS AND METHODS: In vitro experiments: western blotting (WB) screened 41 compounds that inhibited GRP78 expression and evaluated the protein levels of GRP78, PARP, cleaved-PARP, MMP2, and MMP9. Cell proliferation was evaluated using CCK-8, EdU, colony formation assay, and cell apoptosis was assessed by flow cytometry. Transwell, wound healing, and tube formation assays were performed to determine the effect of EUR on tumor invasion, migration, and angiogenesis, respectively. Quantitative real-time polymerase chain (qRT-PCR) and dual-luciferase activity assays detected GRP78 mRNA stability and transcription levels post-EUR and thapsigargin treatment. RNA-Seq identified signaling pathways inhibited by EUR. In vivo experiments: effects of EUR in mice were evaluated by H&E staining to detect lung metastasis and potential toxic effects in tissues. Immunohistochemical (IHC) staining detected the expression of Ki-67, CD31, and cleaved caspase-3 in tumors. RESULTS: GRP78 is highly expressed in OS and correlated with poor prognosis. In vitro, eurycomanone (EUR) significantly downregulated GRP78 expression, inhibited cell proliferation, migration, invasion, tube formation, and induced apoptosis. Moreover, it enhanced trichostatin A (TSA) sensitivity and exhibited inhibitory effects on other cancer types. Mechanistically, EUR decreased GRP78 mRNA stability and transcription. In vivo, EUR inhibited proliferation and invasion in tibial and PDX models. CONCLUSIONS: Our study demonstrated that EUR inhibits the growth and metastasis of OS by reducing GRP78 mRNA stability and inhibiting its transcription, which offers a novel approach for clinical treatment of OS.