Triple-negative breast cancers (TNBCs) are characterized by poor survival, prognosis, and gradual resistance to cytotoxic chemotherapeutics, like doxorubicin (DOX). The clinical utility of DOX is limited by its cardiotoxic and chemoresistant effects that manifest over time. To induce chemoresistance, TNBC rewires oncogenic gene expression and cell signaling pathways. Recent studies have demonstrated that reprogramming of branched-chain amino acids (BCAAs) metabolism facilitates tumor growth and survival. Branched-chain ketoacid dehydrogenase kinase (BCKDK), a regulatory kinase of the rate-limiting enzyme of the BCAA catabolic pathway, is reported to activate RAS/RAF/MEK/ERK signaling to promote tumor cell proliferation. However, it remains unexplored if BCKDK action remodels TNBC proliferation and survival per se and influences susceptibility to DOX-induced genotoxic stress. TNBC cells treated with DOX exhibited reduced BCKDK expression and intracellular BCKAs. Genetic and pharmacological inhibition of BCKDK in TNBC cell lines also showed a similar reduction in intracellular and secreted BCKAs. BCKDK silencing in TNBC cells downregulated mitochondrial metabolism genes, reduced electron complex protein expression, oxygen consumption, and ATP production. Transcriptome analysis of BCKDK silenced cells confirmed dysregulation of mitochondrial metabolic networks and upregulation of the apoptotic signaling pathway. Furthermore, BCKDK inhibition with concurrent DOX treatment exacerbated apoptosis, caspase activity, and loss of TNBC proliferation. Inhibition of BCKDK in TNBC also upregulated sestrin 2 and concurrently decreased mTORC1 signaling and protein synthesis. Overall, loss of BCKDK action in TNBC remodels BCAA flux, reduces protein translation triggering cell death, ATP insufficiency, and susceptibility to genotoxic stress.

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The necessity for sustainable energy production has driven the rapid development of technologies to harness solar energy effectively. The microphotosynthetic power cells (μPSC) aim to harness solar energy from living photosynthetic cells. Currently, the power density of the μPSC is low, due to several factors. One of the major impediments and challenges of the μPSC is its lower charge transfer efficiency between the photosynthetic microorganisms and the electrodes. Herein, the proposed strategy explores the interaction of gold nanoparticles (Au NPs) with photosynthetic microorganisms for enhanced power generation from the μPSC. Herein, the intracellular biocompatible, efficient light absorbers in the form of Au NPs are introduced. Translocation of gold colloidal solution of 25 μL of 50 μg mL−1 (253.8 μmol mL−1) concentration into 2 mL whole liquid culture of algal cells (Chlamydomonas reinhardtii: ≈1 million cells mL−1) enhances operational quantum yield (ϕ0) of the algal cells by 30.2% and power generation capability by 15.2% in μPSCs. Internalized Au NPs in the algal cells quench chlorophyll fluorescence, thereby contributing to increased photosynthetic efficiency. With multiple advantages such as light absorption capability, biocompatibility, and ability to transfer the electrons, Au NPs can efficiently harvest sunlight for enhanced power generation from the μPSC.

Glycosylation is one of the key components influencing several signaling pathways implicated in cell survival and growth. The Notch signaling pathway plays a pivotal role in numerous cell fate specifications during metazoan development. Both Notch and its ligands are repeatedly glycosylated by the addition of sugar moieties, such as O-fucose, O-glucose, or O-xylose, to bring about structural and functional changes. Disruption to glycosylation processes of Notch proteins result in developmental disorders and disease, including cancer. This review summarizes the importance and recent updates on the role of glycosylated Notch proteins in tumorigenesis and tumor metastasis.

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