Dual Inhibitors of SARS-CoV-2 3CL Protease and Human Cathepsin L Containing Glutamine Isosteres Are Anti-CoV-2 Agents.

SARS-CoV-2 3CL protease (Main protease) and human cathepsin L are proteases that play unique roles in the infection of human cells by SARS-CoV-2, the causative agent of COVID-19. Both proteases recognize leucine and other hydrophobic amino acids at the P position of a peptidomimetic inhibitor. At the P position, cathepsin L accepts many amino acid side chains, with a partial preference for phenylalanine, while 3CL-PR protease has a stringent specificity for glutamine or glutamine analogues.

A Ralstonia solanacearum type III effector alters the actin and microtubule cytoskeleton to promote bacterial virulence in plants.

Cellular responses to biotic stress frequently involve signaling pathways that are conserved across eukaryotes. These pathways include the cytoskeleton, a proteinaceous network that senses external cues at the cell surface and signals to interior cellular components. During biotic stress, dynamic cytoskeletal rearrangements serve as a platform from which early immune-associated processes are organized and activated.

Perspectives of Canadian Plastic Surgeons on the Surgical Management of Pressure Injuries.

Pressure injuries, particularly among patients with spinal cord injuries and the elderly, significantly contribute to morbidity, mortality, and financial sequelae. Surgical interventions, including debridement and flaps, may improve outcomes, especially for stage 3 and 4 pressure injuries. This survey assesses Canadian plastic surgeons' perspectives and practices regarding the surgical management of these injuries.

The cost of recovering Australia's threatened species.

Accounting for the cost of repairing the degradation of Earth's biosphere is critical to guide conservation and sustainable development decisions. Yet the costs of repairing nature through the recovery of a continental suite of threatened species across their range have never been calculated. We estimated the cost of in situ recovery of nationally listed terrestrial and freshwater threatened species (n = 1,657) across the megadiverse continent of Australia by combining the spatially explicit costs of all strategies required to address species-specific threats.

Sex hormone deficiency in male and female mice expressing the Alzheimer's disease-associated risk-factor TREM2 R47H variant impacts the musculoskeletal system in a sex- and genotype-dependent manner.

The R47H variant of the triggering receptor expressed on myeloid cells 2 (TREM2) is a risk factor for Alzheimer's disease in humans and leads to lower bone mass accrual in female but not male 12-mo-old mice. To determine whether, as with aging, gonadectomy results in sex-specific musculoskeletal effects, gonad removal or SHAM surgery was performed in 4-mo-old TREM2 mice and WT male and female littermates ( = 10-12/group), with sexes analyzed separately. Body weight was lower in males, but higher in females after gonadectomy, independently of their genotype.