Lipid nanoparticles (LNPs) are the most extensively validated clinical delivery vehicles for mRNA therapeutics, exemplified by their widespread use in the mRNA COVID-19 vaccines. The pace of lipid nanoparticle (LNP) development for mRNA therapeutics is restricted by the limitations of existing methods for large-scale LNP screening. To address this challenge, we developed Quantitative Analysis of Reverse Transcribed Barcodes (QuART), a novel nucleic-acid-based system for measuring LNP functional delivery in vivo.
View Article and Find Full Text PDFPrevious studies highlight the potential for sodium-glucose cotransporter type 2 (SGLT2) inhibitors (SGLT2i) to exert cardioprotective effects in heart failure by increasing plasma ketones and shifting myocardial fuel utilization toward ketone oxidation. However, SGLT2i have multiple in vivo effects and the differential impact of SGLT2i treatment and ketone supplementation on cardiac metabolism remains unclear. Here, using gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) methodology combined with infusions of [13C6]glucose or [13C4]βOHB, we demonstrate that acute SGLT2 inhibition with dapagliflozin shifts relative rates of myocardial mitochondrial metabolism toward ketone oxidation, decreasing pyruvate oxidation with little effect on fatty acid oxidation in awake rats.
View Article and Find Full Text PDFBackground: Private wells use groundwater as their source and their drinking water quality is unregulated in the United States at the federal level. Due to the lack of water quality regulations, those reliant on private wells have the responsibility of ensuring that the water is safe to drink. Where extreme weather is projected to increase with climate change, contamination due to climate-related hazards adds further layers of complexity for those relying on private wells.
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