Summary
Altered lipid metabolism is increasingly recognized as a signature of cancer cells. Enabled by label-free Raman spectromicroscopy, we performed quantitative analysis of lipogenesis at single cell level in human patient cancerous tissues. Our imaging data revealed an unexpected, aberrant accumulation of esterified cholesterol in lipid droplets of high-grade prostate cancer and metastases. Biochemical study showed that such cholesteryl ester accumulation was a consequence of loss of tumor suppressor PTEN and subsequent activation of PI3K/AKT pathway in prostate cancer cells. Furthermore, we found that such accumulation arose from significantly enhanced uptake of exogenous lipoproteins and required cholesterol esterification. Depletion of cholesteryl ester storage significantly reduced cancer proliferation, impaired cancer invasion capability, and suppressed tumor growth in mouse xenograft models with negligible toxicity. These findings open opportunities for diagnosing and treating prostate cancer by targeting the altered cholesterol metabolism.
The application of transition metal fluorides as energy dense cathode materials for lithium ion batteries has been hindered by inadequate understanding of their electrochemical capabilities/limitations. Here, we present an ideal system for mechanistic study through the colloidal synthesis of single crystalline, monodisperse iron(II) fluoride nanorods. Near theoretical capacity (570 mA h g −1 ) and extraordinary cycling stability (>90% capacity retention after 50 cycles at C/20) is achieved solely through the use of an ionic liquid electrolyte (1 m LiFSI/Pyr 1,3 FSI), which forms a stable solid electrolyte interphase and prevents the fusing of particles. This stability extends over 200 cycles at much higher rates (C/2) and temperatures (50 • C). High-resolution analytical transmission electron microscopy reveals intricate morphological features, lattice orientation relationships, and oxidation state changes that comprehensively describe the conversion mechanism. Phase evolution, diffusion kinetics and cell failure are critically influenced by surface specific reactions. The reversibility of the conversion reaction is governed by topotactic cation diffusion through an invariant lattice of fluoride anions and the nucleation of metallic particles on semi-coherent interfaces. This new understanding is used to showcase the inherently high discharge rate capability of FeF 2 .
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