Correlation between the structures of natural polysaccharides and their properties in regulating gut microbiota: Current understanding and beyond.

Natural polysaccharides have complex structural properties and a wide range of health-promoting effects. Accumulating evidence suggests that the effects are significantly mediated through fermentation by gut microbiota. In recent years, the relationship between the structures of natural polysaccharides and their properties in regulating gut microbiota has garnered significant research attention as researchers attempt to precisely understand the role of gut microbiota in the bioactivities of natural polysaccharides.

Differential impacts of healthy cognitive aging on directed and random exploration.

Deciding whether to explore unknown opportunities or exploit well-known options is a ubiquitous part of our everyday lives. Extensive work in college students suggests that young people make explore-exploit decisions using a mixture of information seeking and random behavioral variability. Whether, and to what extent, older adults use the same strategies is unknown.

Optimization of mTOR Inhibitors Using Property-Based Drug Design and Free-Wilson Analysis for Improved In Vivo Efficacy.

The mTOR kinase regulates a variety of critical cellular processes and has become a target for the treatment of various cancers. Using a combination of property-based drug design and Free-Wilson analysis, we further optimized a series of selective mTOR inhibitors based on the ()-6a-methyl-6a,7,9,10-tetrahydro[1,4]oxazino[3,4-]pteridin-6(5)-one scaffold. Our efforts resulted in , which showed similar in vivo efficacy compared to previous lead at 1/15 the dose, a result of its improved drug-like properties.

Evaluation of antiviral activity of SARS-CoV-2 M inhibitor pomotrelvir and cross-resistance to nirmatrelvir resistance substitutions.

The unprecedented scale of the COVID-19 pandemic and the rapid evolution of SARS-CoV-2 variants underscore the need for broadly active inhibitors with a high barrier to resistance. The coronavirus main protease (M) is an essential cysteine protease required for viral polyprotein processing and is highly conserved across human coronaviruses. Pomotrelvir is a novel M inhibitor that has recently completed a phase 2 clinical trial.

Abnormal developmental trajectory and vulnerability to cardiac arrhythmias in tetralogy of Fallot with DiGeorge syndrome.

Tetralogy of Fallot (TOF) is the most common cyanotic congenital heart disease. Ventricular dysfunction and cardiac arrhythmias are well-documented complications in patients with repaired TOF. Whether intrinsic abnormalities exist in TOF cardiomyocytes is unknown.