Purpose: To investigate the efficacy of the combination of the FLT3 inhibitors midostaurin or gilteritinib with the Bcl-2 inhibitor venetoclax in FLT3-ITD acute myeloid leukemia (AML) and the underlying molecular mechanism. Experimental Design: Using both FLT3-ITD cell lines and primary patient samples, annexin V-FITC/propidium iodide staining and flow cytometry analysis were used to quantify cell death induced by midostaurin or gilteritinib, alone or in combination with venetoclax. Western blot analysis was performed to assess changes in protein expression levels of members of the JAK/ STAT, MAPK/ERK, and PI3K/AKT pathways, and members of the Bcl-2 family of proteins. The MV4-11-derived xenograft mouse model was used to assess in vivo efficacy of the combination of gilteritinib and venetoclax. Lentiviral overexpression of Mcl-1 was used to confirm its role in cell
Based on the unique multilayered structure of ginkgo leaves, interconnected carbon nanosheets with rich micro/meso pores have been fabricated, showing excellent electrochemical performance in multiple energy storage devices.
Accurate information on the distribution of permafrost and its thermal and hydrological properties is critical for environmental management and engineering development. This study modeled the current state of permafrost on the Qinghai‐Tibet Plateau (QTP), including the spatial distribution of permafrost, active‐layer thickness (ALT), mean annual ground temperature (MAGT), depth of zero annual amplitude (DZAA) and ground‐ice content using an improved Noah land surface model (LSM). The improved model was examined at a typical permafrost site and then applied to the entire QTP using existing gridded meteorological data and newly developed soil data. The simulated permafrost distribution and properties were validated against existing permafrost maps in three representative survey areas and with measurements from 54 boreholes. The results indicate that the Noah LSM with augmented physics and proper soil data support can model permafrost over the QTP. Permafrost was simulated to underlie an area of 1.113 × 106 km2 in 2010, accounting for 43.8% of the entire area of the QTP. The modeled regional average ALT and MAGT were 3.23 m and −1.56°C, respectively. Spatially, MAGT increases and DZAA becomes shallower from north to south. Thermally unstable permafrost (MAGT above −0.5°C) is predominant, accounting for 38.75% of the whole permafrost area on the QTP. Ice‐rich permafrost was mainly simulated around lakes across the north‐central QTP.
Ginseng is an economically important medicinal plant. The major bioactive ingredients of ginseng are ginsenosides, which are triterpene saponins. Because of difficulties in ginseng cultivation and the low productivity of ginseng cell and tissue culture, it has become important to improve ginsenoside levels by using metabolic engineering based on the biosynthetic pathway of ginsenosides. During the last decade, substantial advances have been made in biosynthesis of ginsenosides. This review is concerned with recent developments in our understanding of the biosynthesis of ginsenosides.
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