A single inactivating amino acid change in the SARS-CoV-2 NSP3 Mac1 domain attenuates viral replication in vivo.

Despite unprecedented efforts, our therapeutic arsenal against SARS-CoV-2 remains limited. The conserved macrodomain 1 (Mac1) in NSP3 is an enzyme exhibiting ADP-ribosylhydrolase activity and a possible drug target. To determine the role of Mac1 catalytic activity in viral replication, we generated recombinant viruses and replicons encoding a catalytically inactive NSP3 Mac1 domain by mutating a critical asparagine in the active site.

The Effect of Antioxidants on Dentin Bond Strength after Application of Common Endodontic Irrigants: A Systematic Review.

The purpose of this systematic review was to evaluate how an antioxidant treatment would influence the immediate bond strength of dental adhesives to endodontically treated dentine. Scientific evidence was researched in five databases using selected descriptors. Two independent reviewers conducted the investigation and assessed the data and methodological quality of the studies.

Limited cross-variant immunity from SARS-CoV-2 Omicron without vaccination.

SARS-CoV-2 Delta and Omicron are globally relevant variants of concern. Although individuals infected with Delta are at risk of developing severe lung disease, infection with Omicron often causes milder symptoms, especially in vaccinated individuals. The question arises of whether widespread Omicron infections could lead to future cross-variant protection, accelerating the end of the pandemic.

Circulating endotoxin and systemic immune activation in sporadic amyotrophic lateral sclerosis (sALS).

The present study reports elevated levels of endotoxin/lipopolysaccharide (LPS) concentrations in plasma from patients with sporadic amyotrophic lateral sclerosis (sALS) and Alzheimer's (AD) as compared to healthy controls. Levels of plasma LPS showed a significant positive correlation with degree of blood monocyte/macrophage activation in disease groups and was most elevated in patients with advanced sALS disease. There was a significant negative relationship between plasma LPS and levels of monocyte/macrophage IL-10 expression in sALS blood.

MCP-1 chemokine receptor CCR2 is decreased on circulating monocytes in sporadic amyotrophic lateral sclerosis (sALS).

Recent studies suggest that monocyte activation may play a role in ALS pathogenesis. Therefore, monocyte CCR2, the receptor for monocyte chemoattractant protein-1 (MCP-1), and plasma levels of MCP-1 were measured in 42 sALS patients, 38 healthy and 34 age-related macular degeneration (ARMD) controls. MCP-1 was elevated in both sALS and ARMD patients, but CCR2 levels were significantly decreased on sALS but not on ARMD monocytes.