Hepatotoxicity of antipsychotics: an exploratory pharmacoepidemiologic and pharmacodynamic study integrating FAERS data and receptor-binding affinities.

Introduction: Antipsychotic psychopharmacotherapy is associated with the risk of drug-induced liver injury (DILI). However, understanding specific risk factors remains challenging due to limited data. This study investigates the relationship between receptor binding affinities and occupancies of antipsychotics and their associated hepatotoxic risks.

Exploiting WEE1 Kinase Activity as FUS::DDIT3-Dependent Therapeutic Vulnerability in Myxoid Liposarcoma.

Purpose: The pathognomonic FUS::DDIT3 fusion protein drives myxoid liposarcoma (MLS) tumorigenesis via aberrant transcriptional activation of oncogenic signaling. As FUS::DDIT3 has so far not been pharmacologically tractable to selectively target MLS cells, this study investigated the functional role of the cell cycle regulator WEE1 as novel FUS::DDIT3-dependent therapeutic vulnerability in MLS.

Experimental Design: Immunohistochemical evaluation of the cell cycle regulator WEE1 was performed in a large cohort of MLS specimens.

Pig manure degradation and carbon emission: Measuring and modeling combined aerobic-anaerobic transformations.

Greenhouse gas emissions from liquid livestock manure storage significantly contribute to global warming. Accurate farm-scale models are essential for predicting these emissions and evaluating manure management strategies, but they rely on multiple parameters describing carbon loss dynamics. Surface respiration may significantly influence carbon loss and methane emission, yet it is not explicitly included in current models.

Multicolor, Cell-Impermeable, and High Affinity BACE1 Inhibitor Probes Enable Superior Endogenous Staining and Imaging of Single Molecules.

The prevailing but not undisputed amyloid cascade hypothesis places the β-site of APP cleaving enzyme 1 (BACE1) center stage in Alzheimer's Disease pathogenesis. Here, we investigated functional properties of BACE1 with novel tag- and antibody-free labeling tools, which are conjugates of the BACE1-inhibitor IV (also referred to as C3) linked to different impermeable Alexa Fluor dyes. We show that these fluorescent small molecules bind specifically to BACE1, with a 1:1 labeling stoichiometry at their orthosteric site.