Vitamin B2 Operates by Dual Thermodynamic and Kinetic Mechanisms to Selectively Tailor Urate Crystallization.

Here we demonstrate how a biologically relevant molecule, riboflavin (vitamin B2), operates by a dual mode of action to effectively control crystallization of ammonium urate (NHHU), which is associated with cetacean kidney stones. In situ microfluidics and atomic force microscopy experiments confirm a strong interaction between riboflavin and NHHU crystal surfaces that substantially inhibits layer nucleation and spreading by kinetic mechanisms of step pinning and kink blocking. Riboflavin does not alter the distribution of tautomeric urate isomers, but its adsorption on NHHU crystal surfaces does interfere with the effects of minor urate tautomer by limiting its ability to induce NHHU crystal defects while also suppressing NHHU nucleation and inhibiting crystal growth by 80% at an uncharacteristically low modifier concentration.

IL-1β-driven NF-κB transcription of ACE2 as a Mechanism of Macrophage Infection by SARS-CoV-2.

Coronavirus disease 2019 (COVID-19), caused by infection with the enveloped RNA betacoronavirus, SARS-CoV-2, led to a global pandemic involving over 7 million deaths. Macrophage inflammatory responses impact COVID-19 severity; however, it is unclear whether macrophages are infected by SARS-CoV-2. We sought to identify mechanisms regulating macrophage expression of ACE2, the primary receptor for SARS-CoV-2, and to determine if macrophages are susceptible to productive infection.

Metabolic response of Klebsiella oxytoca to ciprofloxacin exposure: a metabolomics approach.

Introduction: Rapid detection and identification of pathogens and antimicrobial susceptibility is essential for guiding appropriate antimicrobial therapy and reducing morbidity and mortality associated with sepsis.

Objectives: The metabolic response of clinical isolates of Klebsiella oxytoca exposed to different concentrations of ciprofloxacin (the second generation of quinolones antibiotics) were studied in order to investigate underlying mechanisms associated with antimicrobial resistance (AMR).

Methods: Metabolomics investigations were performed using Fourier-transform infrared (FT-IR) spectroscopy as a metabolic fingerprinting approach combined with gas chromatography-mass spectrometry (GC-MS) for metabolic profiling.

Improved Automated Radiosynthesis of [F]Dolutegravir: Toward Clinical Applications.

Positron emission tomography imaging using radiolabeled dolutegravir (DTG) is an interesting approach to understand the biodistribution of this antiretroviral drug at HIV-1 sanctuary sites. In the course of clinical translation, we depict herein an improved and pharmaceutically compliant radiosynthesis of [F]DTG from an original tin precursor. The radiosynthesis was achieved in two steps by copper-mediated radiofluorination, followed by enol ether deprotection using a kit-based AllInOne module.