Dynamics of the mammalian pyruvate dehydrogenase complex revealed by in-situ structural analysis.

The multi-enzyme pyruvate dehydrogenase complex (PDHc) links glycolysis to the citric acid cycle and plays vital roles in metabolism, energy production, and cellular signaling. Although all components have been individually characterized, the intact PDHc structure remains unclear, hampering our understanding of its composition and dynamical catalytic mechanisms. Here, we report the in-situ architecture of intact mammalian PDHc by cryo-electron tomography.

L-cysteine modulates the Maillard reaction: Impacts on PhIP and pyrazine formation.

L-Cysteine (L-Cys) serves as both an inhibitor of the carcinogen 1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and an enhancer of food flavor, supporting efforts to improve food safety and quality. Using a glucose/phenylalanine/creatinine model system, this study assessed the effects of varying L-Cys concentrations on PhIP inhibition and pyrazine flavor enhancement through UPLC-MS/MS and GC-MS analyses. The optimal PhIP reduction (82.

De novo biosynthesis of quercetin in Yarrowia Lipolytica through systematic metabolic engineering for enhanced yield.

Kaempferol and quercetin possess various biological activities, making them valuable in food and medicine. However, their production via traditional methods is often inefficient. This study aims to address this gap by engineering the yeast Yarrowia lipolytica to achieve high yields of these flavonoids.

Predicting Survival Rates in Brain Metastases Patients from Non-Small Cell Lung Cancer Using Radiomic Signatures Associated with Tumor Immune Heterogeneity.

Non-small cell lung cancer (NSCLC) frequently metastasizes to the brain, significantly worsened prognoses. This study aimed to develop an interpretable model for predicting survival in NSCLC patients with brain metastases (BM) integrating radiomic features and RNA sequencing data. 292 samples are collected and analyzed utilizing T1/T2 MRIs.

HACD2 Promotes Pancreatic Cancer Progression by Enhancing PKM2 Dissociation From PRKN in a Dehydratase-Independent Manner.

3-Hydroxyacyl-CoA dehydratase 2 (HACD2), an obesity-related gene involved in the elongation of long-chain fatty acids, is highly expressed in pancreatic cancer (PC) and is associated with patient prognosis. Interestingly, the study reveals that HACD2 mediated the proliferation of PC cells in a dehydratase-independent manner, affecting the downstream glycolytic pathway. Mechanistically, HACD2 promotes PC cells proliferation by binding to E3 ubiquitin-protein ligase parkin (PRKN) and enhancing pyruvate kinase PKM (PKM2) dissociation from PRKN, resulting in reduced ubiquitination of PKM2 and increased dimerization of PKM2, which subsequently promote c-Myc expression and tumor growth.