Safety and efficacy of selective RIPK1 inhibitor SIR1-365 in hospitalized patients with severe COVID-19: A multicenter, randomized, double-blind, phase 1b trial.

Background: Receptor-interacting protein kinase 1 (RIPK1), a serine/threonine protein kinase, is mainly activated by pro-inflammatory cytokines and pathogens, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and its activation could result in apoptosis, necroptosis, or inflammation. This study was conducted to evaluate the safety and efficacy of a potent and selective inhibitor of RIPK1, SIR1-365, in hospitalized patients with severe coronavirus disease 2019 (COVID-19).

Methods: This multicenter, randomized, double-blind, phase 1b study screened patients from December 18, 2020 until November 27, 2021.

Cascade reservoirs affect mercury concentrations in fish from Teles Pires river, Brazilian Amazon.

Hydroelectric reservoirs favor mercury contamination in biota, but the contamination in cascade reservoirs is not yet clear. We investigated total mercury (THg) contamination in fish in four cascade reservoirs in the Brazilian Amazon between August 2022 and April 2023. Overall, downstream predatory fish showed higher mercury concentrations than those upstream.

Targeting RGMb interactions: Discovery and preclinical characterization of potent anti-RGMb antibodies blocking multiple ligand bindings.

Therapeutic efficacy with durable responses has been demonstrated with several antibody drugs that block key immune checkpoint receptors, including PD-1, PD-L1, and CTLA-4. Despite the success of these drugs, a substantial proportion of patients do not benefit. Targeting multiple inhibitory pathways simultaneously to augment anti-tumor immunity has proven to be a promising approach.

The microbiome diversifies -acyl lipid pools - including short-chain fatty acid-derived compounds.

-acyl lipids are important mediators of several biological processes including immune function and stress response. To enhance the detection of -acyl lipids with untargeted mass spectrometry-based metabolomics, we created a reference spectral library retrieving -acyl lipid patterns from 2,700 public datasets, identifying 851 -acyl lipids that were detected 356,542 times. 777 are not documented in lipid structural databases, with 18% of these derived from short-chain fatty acids and found in the digestive tract and other organs.

Temporal variation of mercury levels in fish, soil, and sediments in an Amazon reservoir: insights from 35 years of river impoundment in Pará State, Brazil.

The increase of mercury (Hg) concentrations in abiotic and biotic compartments of aquatic ecosystems following the river impoundment for building a hydroelectric reservoir is one of many environmental and social impacts that the construction of hydroelectric plants can trigger. Yet, long-term studies in Amazon reservoirs are still scarce. The present study aimed to understand the effects of dam impoundment in THg concentrations in an Amazon reservoir up to 35 years of its creation.