Rhodium(III)-catalyzed oxidative cross-coupling of benzoxazinones with styrenes via C-H activation.

Vinylarenes represent an important class of core skeleton embedded in natural products, organic materials, and pharmaceutical molecules. Therefore, numerous efforts have been devoted to developing efficient methods for their preparation. Among them, transition-metal-catalyzed oxidative coupling of arenes and alkenes has proved to be a powerful method due to its high atom and step economy. Although a wide range of oxidative alkenylations of arenes have been developed, the alkenes employed in most cases are still limited to electron-deficient alkenes. Reported herein is a Rh(III)-catalyzed C-H cross-coupling of benzoxazinones and simple unactivated styrenes to furnish a variety of vinylarene scaffolds. This established protocol is characterized by wide functional group compatibility, high yields, and excellent regio- and chemo-selectivity. Mechanistic studies and gram-scale experiments on this high-value conversion are disclosed. Moreover, the potential utility of this method was highlighted by a series of further transformations.

HMGA2 alleviates ferroptosis by promoting GPX4 expression in pancreatic cancer cells.

Pancreatic cancer is one of the most malignant tumor types and is characterized by high metastasis ability and a low survival rate. As a chromatin-binding protein, HMGA2 is widely overexpressed and considered an oncogene with various undefined regulatory mechanisms. Herein, we demonstrated that HMGA2 is highly expressed in pancreatic cancer tissues, mainly distributed in epithelial cells, and represents a subtype of high epithelial-mesenchymal transition. Deletion of HMGA2 inhibits tumor malignancy through cell proliferation, metastasis, and xenograft tumor growth in vivo. Moreover, HMGA2 enhanced the cellular redox status by inhibiting reactive oxygen species and promoting glutathione production. Importantly, ferroptotic cell death was significantly ameliorated in cells overexpressing HMGA2. Conversely, HMGA2 deletion exacerbated ferroptosis. Mechanistically, HMGA2 activated GPX4 expression through transcriptional and translational regulation. HMGA2 binds and promotes cis-element modification in the promoter region of the GPX4 gene by enhancing enhancer activity through increased H3K4 methylation and H3K27 acetylation. Furthermore, HMGA2 stimulated GPX4 protein synthesis via the mTORC1-4EBP1 and -S6K signaling axes. The overexpression of HMGA2 alleviated the decrease in GPX4 protein levels resulting from the pharmacologic inhibition of mTORC1. Conversely, compared with the control, HMGA2 deletion more strongly reduced the phosphorylation of 4EBP1 and S6K. A strong positive correlation between HMGA2 and GPX4 expression was confirmed using immunohistochemical staining. We also demonstrated that HMGA2 mitigated the sensitivity of cancer cells to combination treatment with a ferroptosis inducer and mTORC1 inhibition or gemcitabine. In summary, our results revealed a regulatory mechanism by which HMGA2 coordinates GPX4 expression and underscores the potential value of targeting HMGA2 in cancer treatment.

HMGA1 and FOXM1 Cooperate to Promote G2/M Cell Cycle Progression in Cancer Cells.

HMGA1 is a chromatin-binding protein and performs its biological function by remodeling chromatin structure or recruiting other transcription factors. However, the role of abnormally high level of HMGA1 in cancer cells and its regulatory mechanism still require further investigation. In this study, we performed a prognostic analysis and showed that high level of either HMGA1 or FOXM1 was associated with poor prognosis in various cancers based on the TCGA database. Furthermore, the expression pattern of HMGA1 and FOXM1 showed a significant strong positive correlation in most type of cancers, especially lung adenocarcinoma, pancreatic cancer and liver cancer. Further analysis of the biological effects of their high correlation in cancers suggested that cell cycle was the most significant related pathway commonly regulated by HMGA1 and FOXM1. After knockdown of HMGA1 and FOXM1 by specific siRNAs, an obvious increased G2/M phase was observed in the siHMGA1 and siFOXM1 groups compared to the siNC group. The expression levels of key G2/M phase regulatory genes PLK1 and CCNB1 were significantly downregulated. Importantly, HMGA1 and FOXM1 were identified to form a protein complex and co-located in the nucleus based on co-immunoprecipitation and immunofluorescence staining, respectively. Thus, our results provide the basic evidence that HMGA1 and FOXM1 cooperatively accelerate cell cycle progression by up-regulating PLK1 and CCNB1 to promote cancer cell proliferation.

Effect of Emulsion Particle Size on the Encapsulation Behavior and Oxidative Stability of Spray Microencapsulated Sweet Orange Oil (Citrus aurantium var. dulcis).

Three different feed emulsions of different particle sizes were mixed with a modified starch and maltodextrin and spray dried to make a large (LP), small (SP), and nano-size encapsulated powder (NP), respectively. Emulsion size, oil content, loading capacity (LC), encapsulation efficiency (EE), water content, aw, scanning electron microscopy (SEM), glass transition temperature (Tg), as well as d-limonene release characteristic and limonene oxide formation rate during 37 °C and various aw storage were determined. With the increase of the feed emulsion size, the reconstituted emulsion size of the LP tended to increase and change to a bimodal distribution. The surface oil content increased with the increasing size of the reconstituted emulsion, and the opposite was true for EE. The smaller the reconstituted emulsion size, the higher Tg during a low aw condition. The Tg of the LP, SP and NP were 62, 88, and 100 °C, respectively, and NP > SP > LP. The release and the oxidative rate of d-limonene was the lowest for the NP and then increased for the SP and LP. The release and oxidative rates increased with the elevation of aw and peaked at 0.33. The powder surface morphological structure was intact, the spray-dried powder was more stable, and microstructure changed from a glass state to a rubbery state during storage.

Benzoate anions-intercalated cobalt-nickel layered hydroxide nanobelts as high-performance electrode materials for aqueous hybrid supercapacitors.

Layered metal hydroxide salts (LHSs) have recently gained extensive interests as an efficient electrode material for supercapacitors (SCs). Herein, we report, for the first time ever, the synthesis of a cobalt-nickel layered hybrid organic-inorganic LHS that was intercalated with benzoate anions (B-CoNi-LHSs) and observe a high performance as electrode materials for hybrid supercapacitors (HSCs). B-CoNi-LHSs were synthesized by using a co-precipitation method, where sodium benzoate was added dropwise to cobalt and nickel salt solution, without the addition of any organic solvent or surfactant. Due to the intercalation of anions and synergistic interactions of the multi-metallic components, the B-CoNi-LHSs electrode showed a high specific capacity of 570 C g-1 (specific capacitance of 1267 F·g-1) at 1 A g-1, excellent rate performance (65% from 1 to 10 A g-1) and outstanding cycling performance (81.09% over 8000 cycles), in comparison to the mono-metallic counterparts. An HSC device, assembled by using B-CoNi-LHSs as the positive electrode and activated carbon (AC) as the negative one, exhibited a power density of 780 W kg-1 at the energy density of 31.7 Wh kg-1, and 8543 W kg-1 at 18.1 Wh kg-1. Results from this study show that the organic-inorganic hybrids of layered dual-metal hydroxides intercalated with benzoate anions may be a viable candidate as electrode materials for high-performance SCs.