Hydrogen sulfide coordinates glucose metabolism switch through destabilizing tetrameric pyruvate kinase M2.

Most cancer cells reprogram their glucose metabolic pathway from oxidative phosphorylation to aerobic glycolysis for energy production. By reducing enzyme activity of pyruvate kinase M2 (PKM2), cancer cells attain a greater fraction of glycolytic metabolites for macromolecule synthesis needed for rapid proliferation. Here we demonstrate that hydrogen sulfide (H2S) destabilizes the PKM2 tetramer into monomer/dimer through sulfhydration at cysteines, notably at C326, leading to reduced PKM2 enzyme activity and increased PKM2-mediated transcriptional activation. Blocking PKM2 sulfhydration at C326 through amino acid mutation stabilizes the PKM2 tetramer and crystal structure further revealing the tetramer organization of PKM2-C326S. The PKM2-C326S mutant in cancer cells rewires glucose metabolism to mitochondrial respiration, significantly inhibiting tumor growth. In this work, we demonstrate that PKM2 sulfhydration by H2S inactivates PKM2 activity to promote tumorigenesis and inhibiting this process could be a potential therapeutic approach for targeting cancer metabolism.

Unraveling RNA contribution to the molecular origins of bacterial surface-enhanced Raman spectroscopy (SERS) signals.

Surface-enhanced Raman spectroscopy (SERS) is widely utilized in bacterial analyses, with the dominant SERS peaks attributed to purine metabolites released during sample preparation. Although adenosine triphosphate (ATP) and nucleic acids are potential molecular origins of these metabolites, research on their exact contributions remains limited. This study explored purine metabolite release from E. coli and RNA integrity following various sample preparation methods. Standard water washing generated dominant SERS signals within 10 s, a duration shorter than the anticipated RNA half-lives under starvation. Evaluating RNA integrity indicated that the most abundant ribosomal RNA species remained intact for hours post-washing, whereas messenger RNA and transfer RNA species degraded gradually. This suggests that bacterial SERS signatures observed after the typical washing step could originate from only a small fraction of endogenous purine-containing molecules. In contrast, acid depurination led to degradation of most RNA species, releasing about 40 times more purine derivatives than water washing. Mild heating also instigated the RNA degradation and released more purine derivatives than water washing. Notably, differences were also evident in the dominant SERS signals following these treatments. This work provides insights into SERS-based studies of purine metabolites released by bacteria and future development of methodologies.

Photo-Fries rearrangement in flow under aqueous micellar conditions.

A flow edition of photo-Fries rearrangement for the synthesis of 2-acylphenols in an aqueous micellar medium has been described. We take advantage of a narrow channel reactor and micelle-induced confinement effect to refine both the efficiency and selectivity of the parent photoreaction.

Electromechanical delay of the vastus medialis obliquus and vastus lateralis in individuals with patellofemoral pain syndrome.

STUDY DESIGN: Case-control study. OBJECTIVE: To examine electromechanical delay (EMD) of the vastus medialis obliquus (VMO) and the vastus lateralis (VL) in individuals with patellofemoral pain syndrome (PFPS). BACKGROUND: EMD is a mechanical property of muscles related to protective reflex and sports performance. The time duration of the EMD can be shortened with strength training and, conversely, can be lengthened secondary to immobilization. However, it is unclear if EMD between various components of the quadriceps is affected in individuals with PFPS. METHODS: Twenty-six individuals with PFPS and 26 healthy volunteers were studied. The VMO and VL were electrically stimulated to evoke muscle twitches. Ultrasound was used to assess patellar movement elicited by the muscle twitch. The time from the onset of electrical stimulation to the onset of patellar movement was measured as the EMD. The EMDs of the VMO and VL were compared between groups using a mixed-model analysis of variance. RESULTS: Subsequent to a significant interaction (P<.001), post hoc analysis indicated that the EMD of the VMO was longer (PFPS, 37.3 ± 0.7 milliseconds; control, 25.9 ± 0.7 milliseconds; P<.001) and the EMD of the VL was shorter (PFPS, 18.4 ± 0.5 milliseconds; control, 25.1 ± 0.5 milliseconds; P<.001) in the PFPS group. Therefore, in the individuals with PFPS, the EMD of the VMO was significantly longer than that of the VL (P<.001), which was not the case for those in the control group (P = .20). CONCLUSION: The mechanical properties of the VMO and VL may be altered in patients with PFPS.J Orthop Sports Phys Ther 2012;42(9):791-796, Epub 2 August 2012. doi:10.2519/jospt.2012.3973.