Streptococcus mutans (S. mutans) is a cariogenic bacterium in the oral cavity that plays a significant role in plaque formation and dental caries. In previous research by our group, we showed that the endocannabinoid anandamide (AEA) has anti-bacterial and anti-biofilm activities against S. mutans. Here, we aimed to investigate its effects on S. mutans through metabolomics analyses. S. mutans was cultivated in the absence or presence of AEA at a sub-minimum inhibitory concentration (MIC), and changes in metabolites and metabolic pathways were assessed through liquid chromatography–mass spectrometry (LC-MS). Treatment of S. mutans using AEA at 10 µg/mL significantly disturbed the glycolytic flux in the bacteria, which was indicated by a reduced glucose uptake into the cell, suppression of key glycolytic intermediates, reduced acid production into the media, imbalance of NAD⁺/NADH, and decreased adenosine triphosphate (ATP) production. The disruption of carbohydrate metabolism impacts critical cellular processes, including energy production, redox balance, and biosynthetic pathways, leading to metabolic stress and impaired cellular function. These results highlight the mode of action of AEA as an antimicrobial agent. Altogether, these findings suggest that AEA has potential as a novel antimicrobial agent in the development of therapeutics against S. mutans.

Metabolomic studies in COPD reveal systemic metabolic perturbations, yet sex is often treated as a covariate rather than a biological driver. We aimed to identify plasma metabolites differentiating COPD from controls and to define sex-specific metabolic signatures in both groups. Methods: In this controlled observational study (BIOMEPOC cohort), untargeted plasma metabolomics was performed by LC-MS/MS. Differential abundance was tested across four contrasts (COPD vs. controls; men vs. women within controls; men vs. women within COPD; sex-by-disease interaction) with a false discovery rate (FDR) correction. Because smoking history differed between COPD and controls, a post hoc ever-smokers analysis was conducted. Results: COPD differed from controls in nine metabolites (all decreased): DL-stachydrine, 3-methyl-L-histidine, fructose, pipecolinic and nipecotic acids, 5-nitro-o-toluidine, conjugated linoleic acid, aminoadipate, and creatinine. This pattern is compatible with metabolic depletion, remodeling, and/or altered flux across multiple compartments rather than simple substrate deficiency, spanning muscle-related pools, amino acid handling, carbohydrate-associated metabolism, and exposome-linked inputs. In ever-smokers, results were directionally consistent, with five metabolites remaining nominally significant. Among controls, five metabolites were higher in men after FDR correction (PABA, cis-4-hydroxy-D-proline, N-acetylasparagine, deoxycarnitine, and creatinine), consistent with physiological sex dimorphism in energy pathways, connective-tissue remodeling, and diet/microbiome-related metabolism. Within COPD, six metabolites differed by sex after FDR correction, defining three axes: creatine energy buffering (men: higher GAA/creatinine, lower creatine), purine/urate handling (men: higher urate), and conjugated bile acids (men: higher GCDCA), implicating muscle bioenergetics, redox/inflammatory tone, and gut–liver crosstalk. Conclusions: Plasma metabolomics identifies a pattern compatible with systemic remodeling in COPD and sex-associated divergences in creatine, purine/urate, and bile-acid pathways, supporting a sex-influenced view of systemic COPD heterogeneity and highlighting targets for mechanistic validation.

The magnitude of helicity in nonplanar polyaromatic materials affects their electronic, optical, and chiroptical properties. However, controlling helicity in different systems typically requires different multistep synthetic approaches for each target compound, often with significant complexity, thereby limiting its applicability. Here, we introduce a helical synthon, isobenzofuranophane, with either a short or long tether, which enables late-stage helicity induction and control in aromatic frameworks. We demonstrate the applicability of this synthon by reacting it with a [5]helicene aryne precursor, where both the handedness and helicene pitch are remotely-controlled by the tether length, directly affecting the (chiro)optical properties of the helicene. The X-ray structures support these findings with up to 35° torsion for a single benzene ring, demonstrating the potential of isobenzofuranophane to induce significant curvature to polyaromatic molecules.