E3 ubiquitin ligase CHIP facilitates cAMP and cGMP signalling cross-talk by polyubiquitinating PDE9A.

The carboxyl terminus of Hsc70-interacting protein (CHIP) is pivotal for managing misfolded and aggregated proteins via chaperone networks and degradation pathways. In a preclinical rodent model of CHIP-related ataxia, we observed that CHIP mutations lead to increased levels of phosphodiesterase 9A (PDE9A), whose role in this context remains poorly understood. Here, we investigated the molecular mechanisms underlying the role of PDE9A in CHIP-related ataxia and demonstrated that CHIP binds to PDE9A, facilitating its polyubiquitination and autophagic degradation.

Protein Fusion of Biosynthetic Enzymes and a Thermo-Responsive Polypeptide Expedites Facile Access to Biocatalysts for Nucleotide Sugars.

Nucleotide sugars (NSs) are essential building blocks for the enzymatic assembly of glycans. In this study, we established a preparation and recycling avenue to the biocatalysts for the enzymatic synthesis of NSs. This approach involves fusing two enzymes into a bifunctional chimera and using elastin-like polypeptides (ET64) as a purification tag, which allows for easy recovery of these biocatalysts without the need for chromatography.

A multicenter, randomized, double-blind, placebo-controlled phase 3 study of Socazolimab or placebo combined with carboplatin and etoposide in the first-line treatment of extensive-stage small cell lung cancer.

This is a randomized, double-blind, placebo-controlled phase 3 clinical trial (ClinicalTrials.gov, NCT04878016) conducted in 54 hospitals in China. Adults who were histologically diagnosed and never treated for extensive-stage small cell lung cancer (ES-SCLC) were enrolled.

Enhanced priming effect in agricultural soils driven by high-quality exogenous organic carbon additions: A meta-analysis.

The addition of exogenous organic carbon (C) to soil can either accelerate or retard the soil organic carbon (SOC) mineralization, i.e., the priming effect (PE), which plays a crucial role in SOC sequestration and thus is significant in the context of global warming.

Inhibited peroxidase activity of peroxiredoxin 1 by palmitic acid exacerbates nonalcoholic steatohepatitis in male mice.

Reactive oxygen species exacerbate nonalcoholic steatohepatitis (NASH) by oxidizing macromolecules; yet how they promote NASH remains poorly understood. Here, we show that peroxidase activity of global hepatic peroxiredoxin (PRDX) is significantly decreased in NASH, and palmitic acid (PA) binds to PRDX1 and inhibits its peroxidase activity. Using three genetic models, we demonstrate that hepatic PRDX1 protects against NASH in male mice.