Cancer cells are exposed to diverse metabolites in the tumor microenvironment that are used to support the synthesis of nucleotides, amino acids, and lipids needed for rapid cell proliferation. Recent work has shown that ketone bodies such as β-hydroxybutyrate (β-OHB), which are elevated in circulation under fasting conditions or low glycemic diets, can serve as an alternative fuel that is metabolized in the mitochondria to provide acetyl-CoA for the tricarboxylic acid (TCA) cycle in some tumors. Here, we discover a non-canonical route for β-OHB metabolism, in which β-OHB can bypass the TCA cycle to generate cytosolic acetyl-CoA for fatty acid synthesis in cancer cells.
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Background: Power outages have been increasing in frequency in the past few years, therefore becoming an increased threat to healthcare delivery.1 While most studies related to the effects of power outages are focused on outpatient care, such as acute exacerbations of chronic lung conditions and the lack of chargeable equipment, with the increasing number of power outages, hospitals must be prepared for this situation as well.
We describe the single-step formation of complex tetracyclic fused scaffolds enabled by (3 + 2) cycloaddition of azomethine ylides. Various indoles, N-protecting groups, and amino acids are well tolerated. The products are obtained in a catalyst-free manner with moderate to excellent yield and high diastereoselectivity.
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