YTH Domain Containing 1 (YTHDC1) is one of the m6A readers that is essential for oocyte development and tumor progression. The role of YTHDC1 in neuronal survival and ischemic stroke is unknown. Here, we found that YTHDC1 was unregulated in the early phase of ischemic stroke. Knockdown of YTHDC1 exacerbated ischemic brain injury and overexpression of YTHDC1 protected rats against brain injury. Mechanistically, YTHDC1 promoted PTEN mRNA degradation to increase Akt phosphorylation, thus facilitating neuronal survival in particular after ischemia. These data identify YTHDC1 as a novel regulator of neuronal survival and modulating m6A reader YTHDC1 may provide a potential therapeutic target for ischemic stroke.
Sphingolipid metabolic dysregulation has increasingly been considered to be a drug-resistance mechanism for a variety of tumors. In this study, through an LC–MS assay, LIM and SH3 protein 1 (LASP1) was identified as a sphingolipid-metabolism-involved protein, and short-chain enoyl-CoA hydratase (ECHS1) was identified as a new LASP1-interacting protein through a protein assay in colorectal cancer (CRC). Gain- and loss-of-function analyses demonstrated the stimulatory role played by ECHS1 in CRC cell proliferation, migration, and invasion in vitro and in vivo. Mechanistic studies of the underlying tumor-supportive oncometabolism indicate that ECHS1 enables altering ceramide (Cer) metabolism that increases glycosphingolipid synthesis (HexCer) by promoting UDP-glucose ceramide glycosyltransferase (UGCG). Further analysis showed that ECHS1 promotes CRC progression and drug resistance by releasing reactive oxygen species (ROS) and interfering mitochondrial membrane potential via the PI3K/Akt/mTOR-dependent signaling pathway. Meanwhile, the phenomenon of promoting the survival and drug resistance of CRC cells caused by ECHS1 could be reversed by Eliglustat, a specific inhibitor of UCCG, in vitro and in vivo. IHC assay showed that ECHS1 was overexpressed in CRC tissues, which was related to the differentiation and poor prognosis of CRC patients. This study provides new insight into the mechanism by which phospholipids promote drug resistance in CRC and identifies potential targets for future therapies.
An extracellular biosynthesis method has been developed to prepare cadmium selenide (CdSe) quantum dots (QDs) with strong fluorescence emission by incubating cheap Cd and Se inorganic salts with Escherichia coli (E.coli) bacteria. Ultraviolet-visible absorption spectra, photoluminescence (PL) spectra, and high-resolution transmission electron microscopy analysis showed that the biosynthesised CdSe QDs have an average size of 3.1 nm, the excellent optical properties with fluorescence emission around 494 nm, and the good crystallinity. It was found that addition of 80 mg of mercaptosuccinic acid resulted in the formation of CdSe QDs with highest PL intensity. Furthermore, Fourier-transform infrared spectra of assynthesised CdSe QDs confirmed the presence of a surface protein capping layer. The biosynthesised CdSe QDs were incorporated into the yeast cells as illustrated by laser confocal scanning microscopy images, showing a great potential in bioimaging and bio-labelling application. (a) Recorded under excitation by an Ar/Kr laser giving green emission, (b) Bright field image, (c) Overlaid image
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