Mendelian randomization analysis identifies causal associations between serum lipidomic profile, amino acid biomarkers and sepsis.

Background: Sepsis is a life-threatening condition marked by a severe systemic response to infection, leading to widespread inflammation, cellular signaling disruption, and metabolic dysregulation. The role of lipid and amino acid metabolism in sepsis is not fully understood, but aberrations in this pathway could contribute to the disease's pathophysiology. Methods: To explore the potential of lipid and amino acid compounds as biomarkers for the diagnosis and prognosis of sepsis, a two-sample Mendelian Randomization (MR) study was conducted, examining the relationship between sepsis and 249 serum lipid and amino acid-related markers. Key enzymes involved in synthesis of phosphatidylcholine, including choline/ethanolamine phosphotransferase 1 (CEPT1), choline phosphotransferase 1 (CPT1), and ethanolamine phosphotransferase 1 (EPT1), were also targeted for drug-target Mendelian randomization. Results: The study found that phosphatidylcholines (OR IVW: 0.88, 95%CI: 0.80-0.96, p = 0.005) and phospholipids in medium HDL (OR IVW: 0.86, 95%CI: 0.77-0.96, p = 0.007) potentially exhibit a protective effect against sepsis nominally. However, the potential drug target of CEPT1, CPT1, and EPT1 was found to be unrelated to septic outcomes. Conclusion: Our findings suggest that increasing levels of phosphatidylcholines and medium HDL phospholipids may reduce the incidence of sepsis. This highlights the potential of lipid-based biomarkers in the diagnosis and management of sepsis, opening avenues for new therapeutic strategies.

Base-promoted cascade ß-F-elimination/electrocyclization/Diels-Alder/retro-Diels-Alder reaction: efficient access to δ-carboline derivatives.

A serendipitous and highly efficient approach for the construction of a variety of δ-carboline derivatives was developed through base-promoted cascade ß-F-elimination/electrocyclization/Diels-Alder/retro-Diels-Alder reaction of N-2,2,2-trifluoroethylisatin ketoimine esters with alkynes in good to high yields with excellent regio-/chemoselectivity control. Moreover, a reasonable reaction pathway was proposed, which was in accordance with the prepared reaction intermediate and control experiment results. The δ-carboline product could be easily converted into a new chiral Py-box-type ligand through simple synthetic transformations. This salient strategy featured the advantages of metal-free conditions, excellent regio-/chemoselectivity, good to high yields, and outstanding substrate tolerance. Importantly, the potential application of these fascinating δ-carboline derivative products is well demonstrated in the recognition of ferric ions.