Advances in the Search for SARS-CoV-2 M and PL Inhibitors.

SARS-CoV-2 is a spherical, positive-sense, single-stranded RNA virus with a large genome, responsible for encoding both structural proteins, vital for the viral particle's architecture, and non-structural proteins, critical for the virus's replication cycle. Among the non-structural proteins, two cysteine proteases emerge as promising molecular targets for the design of new antiviral compounds. The main protease (M) is a homodimeric enzyme that plays a pivotal role in the formation of the viral replication-transcription complex, associated with the papain-like protease (PL), a cysteine protease that modulates host immune signaling by reversing post-translational modifications of ubiquitin and interferon-stimulated gene 15 (ISG15) in host cells.

Involvement of extracellular vesicle microRNA clusters in developing healthy and Rett syndrome brain organoids.

Rett syndrome (RTT) is a neurodevelopmental disorder caused by de novo mutations in the MECP2 gene. Although miRNAs in extracellular vesicles (EVs) have been suggested to play an essential role in several neurological conditions, no prior study has utilized brain organoids to profile EV-derived miRNAs during normal and RTT-affected neuronal development. Here we report the spatiotemporal expression pattern of EV-derived miRNAs in region-specific forebrain organoids generated from female hiPSCs with a MeCP2:R255X mutation and the corresponding isogenic control.

The Influence of Recombinant Bovine Somatotropin (rbST) on the Metabolic Profile and Milk Composition of Lactating Murrah Buffalo.

The use of recombinant bovine somatotropin (rbST) leads to an increase in variable amounts of milk production in buffalo, but there is a lack of information on the influence of rbST on their metabolism. This study looked at the effects of a single 500 mg dose of rbST on the lipid profile, liver and kidney function, and physical, chemical, and cellular constitution of milk in 14 buffalo over 14 days, from the 100th day of lactation, compared with 14 animals in a control group. From the first day after rbST, there was a rise in beta-hydroxybutyrate (β-HBO), possibly due to higher dry matter intake or the biotransformation of NEFA into β-HBO.

Unsupervised analysis of whole transcriptome data from human pluripotent stem cells cardiac differentiation.

The main objective of the present work was to highlight differences and similarities in gene expression patterns between different pluripotent stem cell cardiac differentiation protocols, using a workflow based on unsupervised machine learning algorithms to analyse the transcriptome of cells cultured as a 2D monolayer or as 3D aggregates. This unsupervised approach effectively allowed to portray the transcriptomic changes that occurred throughout the differentiation processes, with a visual representation of the entire transcriptome. The results allowed to corroborate previously reported data and also to unveil new gene expression patterns.

Tubular phosphate transport: a comparison between different methods of urine sample collection in FGF23-dependent hypophosphatemic syndromes.

Objectives: Tubular maximum phosphate reabsorption per glomerular filtration rate (TmP/GFR) is used to evaluate renal phosphate reabsorption and it is a useful tool for the differential diagnosis of hypophosphatemic syndromes. TmP/GFR is typically calculated from fasting plasma and second morning void urine samples, obtained 2 h after the first void (TmP/GFR 2 h). The purpose of this study was to evaluate if TmP/GFR calculated from 24 h urine collection (TmP/GFR 24 h) can be used as an alternative for TmP/GFR 2 h in patients with urine phosphate wasting.