A facile synthetic strategy to engineer improved fluorescent quantum yield, colloidally stable, and low toxic Cu nanoclusters is introduced. These nanoclusters have the potential to be used as excellent bioimaging probes.

Summary Infiltration of arterial intima by foamy macrophages is a hallmark of early atherosclerotic lesions. Here, we investigated the potential role of Ser/Thr phosphatase PHLPP1 in foam cell development. PHLPP1 levels were elevated in OxLDL-exposed macrophages and high-fat diet (HFD)-fed zebrafish larvae. Using overexpression and knockdown approaches, we show that PHLPP1 promotes the accumulation of neutral lipids, and augments cellular total cholesterol and free fatty acid (FFA) levels. RNA-Seq analysis uncovered PHLPP1 role in lipid metabolism pathways. PHLPP1 interacted with and modestly increased ChREBP recruitment to Fasn promoter. PHLPP1-mediated lipid accumulation was attenuated by AMPK activation. Pharmacological inhibition or CRISPR/Cas9-mediated disruption of PHLPP1 resulted in lower lipid accumulation in the intersegmental vessels of HFD-fed zebrafish larvae along with a reduction in total cholesterol and triglyceride levels. Deficiency of phlp-2, C. elegans PHLPP1/2 ortholog, abolished lipid accumulation in high cholesterol-fed worms. We conclude that PHLPP1 exerts a significant effect on lipid buildup.

Metal Nanoclusters (NCs) composed of the least number of atoms (few to tens) became very attractive for their emerging properties owing to their ultrasmall size. Preparing copper nanoclusters (Cu NCs) in an aqueous medium with high emission properties, strong colloidal stability, and low toxicity has been a long-standing challenge. Although they are earth-abundant and inexpensive, they are comparatively less explored due to their limitations such as ease of surface oxidation, poor colloidal stability, and high toxicity. To overcome these constraints, we established a facile synthetic route by optimizing the reaction parameters, especially altering the effective concentration of the reducing agent to influence their optical characteristics. The improvement of photoluminescence intensity and superior colloidal stability was modeled from a theoretical standpoint. Moreover, the as-synthesized Cu NCs showed a significant reduction of toxicity in both in vitro and in vivo models. The possibilities of using such Cu NCs as a diagnostic probe towards C. elegans were explored. Also, the extension of our approach towards improving the photoluminescence intensity of the Cu NCs on other ligand systems was demonstrated.