Structural insights into the biochemical mechanism of the E2/E3 hybrid enzyme UBE2O.

The E2/E3 hybrid enzyme UBE2O plays important roles in key biological events, but its autoubiquitination mechanism remains largely unclear. In this study, we determined the crystal structures of full-length (FL) UBE2O from Trametes pubescens (tp) and its ubiquitin-conjugating (UBC) domain. The dimeric FL-tpUBE2O structure revealed interdomain interactions between the conserved regions (CR1-CR2) and UBC.

The S1'-S3' Pocket of the SARS-CoV-2 Main Protease Is Critical for Substrate Selectivity and Can Be Targeted with Covalent Inhibitors.

The main protease (M ) of SARS-CoV-2 is a well-characterized target for antiviral drug discovery. To date, most antiviral drug discovery efforts have focused on the S4-S1' pocket of M ; however, it is still unclear whether the S1'-S3' pocket per se can serve as a new site for drug discovery. In this study, the S1'-S3' pocket of M was found to differentially recognize viral peptidyl substrates.

Effectiveness of home-based exercise interventions on pain, physical function and quality of life in individuals with knee osteoarthritis: a systematic review and meta-analysis.

Objective: The objective of the study was to evaluate the effectiveness of home-based exercise interventions on pain, physical function and quality of life in individuals with knee osteoarthritis (KOA).

Methods: Five databases (PubMed, Embase, Cochrane Library, CINAHL, Web of Science Core Collection) were searched for relevant randomized controlled trials (RCTs) published from database inception to 2 August 2022. The Cochrane Collaboration's standards were followed for study selection, eligibility criteria, data extraction and statistics, using the Cochrane Collaboration Risk of Bias Tool and PEDro for quality assessment.

The complex structure of GRL0617 and SARS-CoV-2 PLpro reveals a hot spot for antiviral drug discovery.

SARS-CoV-2 is the pathogen responsible for the COVID-19 pandemic. The SARS-CoV-2 papain-like cysteine protease (PLpro) has been implicated in playing important roles in virus maturation, dysregulation of host inflammation, and antiviral immune responses. The multiple functions of PLpro render it a promising drug target.

Effects of simazine and food deprivation chronic stress on energy allocation among the costly physiological processes of male lizards (Eremias argus).

The residue of simazine herbicide in the environment is known as one of pollutant stress for lizards by crippling its fitness on direct toxic effects and indirect food shortage via the food chain effects. Both stressors were considered in our experiment in the simazine exposure and food availability to lizards (Eremias argus). The results revealed that starvation significantly reduced the lizard's energy reserve and native immune function, while the accumulation of simazine in the liver was significantly increased.