Laboratory evolution in enables rapid catabolism of a model lignin-derived aromatic dimer.

Lignin contains a variety of interunit linkages, leading to a range of potential decomposition products that can be used as carbon and energy sources by microbes. β-O-4 linkages are the most common in native lignin, and associated catabolic pathways have been well characterized. However, the fate of the mono-aromatic intermediates that result from β-O-4 dimer cleavage has not been fully elucidated.

In situ RAS:RAF binding correlates with response to KRASG12C inhibitors in KRASG12C--mutant non-small cell lung cancer.

Purpose: Therapeutic efficacy of KRASG12C(OFF) inhibitors (KRASG12Ci) in KRASG12C-mutant non-small cell lung cancer (NSCLC) varies widely. The activation status of RAS signaling in tumors with KRASG12C mutation remains unclear, as its ability to cycle between the active GTP-bound and inactive GDP-bound states may influence downstream pathway activation and therapeutic responses. We hypothesized that the interaction between RAS and its downstream effector RAF in tumors may serve as indicators of RAS activity, rendering NSCLC tumors with a high degree of RAS engagement and downstream effects more responsive to KRASG12Ci compared to tumors with lower RAS---RAF interaction.

Persisting challenges in the development of predictive biomarkers for immuno-oncology therapies for renal cell carcinoma.

Introduction: Immuno-oncology (IO) therapies have become integral to renal cell carcinoma (RCC) management, RCC remains a complex malignancy with diverse clinical behaviors and a heterogeneous tumor microenvironment, highlighting the need for predictive biomarkers to optimize therapy.

Areas Covered: This review synthesizes recent findings from clinical trials, translational studies, and molecular analyses to provide an updated perspective on biomarker research for IO therapies in RCC. A literature search was conducted using PubMed, Embase, and Web of Science for articles published between January 2010 and November 2024.

Reactive Metabolites Cause Idiosyncratic Drug-Induced Liver Injury via Inflammasome Activation in Antigen-Presenting Cells.

Although the pathophysiology of idiosyncratic drug-induced liver injury (IDILI) is unclear, it is presumed to be immune-mediated, involving complex interactions between drug metabolism and activation of the immune system. The following four reactive metabolite production patterns are considered: (1) parent compounds into reactive metabolites within neutrophils or antigen-presenting cells (APCs), (2) reactive metabolites produced by cytochrome P450 (CYP), (3) nonreactive metabolites produced by CYP into reactive metabolites within APCs, and (4) reactive metabolites produced by non-CYPs. Reactive metabolites indirectly activate inflammasomes in APCs, leading to IDILIs.