The study of trimethylamine oxide (TMAO), a metabolite of gut microbiota, and heart failure and chronic kidney disease has made preliminary achievements and been summarized by many researchers, but its research in the field of cardiorenal syndrome is just beginning. TMAO is derived from the trimethylamine (TMA) that is produced by the gut microbiota after consumption of carnitine and choline and is then transformed by flavin-containing monooxygenase (FMO) in the liver. Numerous research results have shown that TMAO not only participates in the pathophysiological progression of heart and renal diseases but also significantly affects outcomes in chronic heart failure (CHF) and chronic kidney disease (CKD), besides influencing the general health of populations. Elevated circulating TMAO levels are associated with adverse cardiovascular events such as HF, myocardial infarction, and stroke, patients with CKD have a poor prognosis as well. However, no study has confirmed an association between TMAO and cardiorenal syndrome (CRS). As a syndrome in which heart and kidney diseases intersect, CRS is often overlooked by clinicians. Here, we summarize the research on TMAO in HF and kidney disease and review the existing biomarkers of CRS. At the same time, we introduced the relationship between exercise and gut microbiota, and appropriately explored the possible mechanisms by which exercise affects gut microbiota. Finally, we discuss whether TMAO can serve as a biomarker of CRS, with the aim of providing new strategies for the detection, prognostic, and treatment evaluation of CRS.

Imidazolium salts containing , , , , or ionic liquids were blended with an epoxy prepolymer, dyglycidylether of bisphenol A (DGEBA) to obtain a series of compositions. To characterize the resulting mixtures and determine the influence of the imidazolium anion on the reactivity and properties of epoxy systems, we performed the following analyses and tests: (i) differential scanning calorimetry (DSC), to determine the curing reaction characteristics, (ii) in situ fourier-transform infrared spectroscopy (FTIR), to assess chemical structure changes, (iii) mechanical property testing of the hardened epoxy material, and (iv) thermogravimetric analysis (TGA). The DSC and FTIR analyses indicate that [Hmim]BF₄, and [Hmim]PF₆ cannot induce the epoxy ring opening reaction and thus these materials are unable to function as epoxy curing agents. In contrast, the imidazolium ionic liquids [Hmim]FeCl₄, [Hmim]N(CN)₂, and [Hmim]Zn₂Cl₅ independently promote the epoxy ring opening reaction. TGA analyses show that the cured DGEBA/[Hmim]Zn₂Cl₅ system exhibits thermal stability similar to the cured DGEBA/[Hmim]FeCl₄. These results can provide an essential reference not only for studying the synergistic effect of [C₆mim]FeCl₄/mixed-amines on the curing process of epoxy systems and the mechanism of the ring opening of epoxides with [C₆mim]FeCl₄/mixed-amines, but also for designing new epoxy curing systems.

Background. Cuproptosis, a copper-dependent form of regulated cell death, has been repeatedly reported to be transcriptionally activated in atherosclerotic plaque, and cuproptosis- and copper-transport genes have been nominated as candidate biomarkers and therapeutic targets on the basis of descriptive expression studies. Whether genetically determined expression of these genes is causally related to atherosclerotic cardiovascular disease has not been tested. Methods. We first confirmed, across two independent carotid plaque transcriptomic cohorts (GSE43292 and GSE28829), that a panel of copper-metabolism and cuproptosis genes is concordantly dysregulated in plaque and that the copper importers track the degree of inflammatory-cell infiltration. We then performed two-sample cis-Mendelian randomization (MR) and Bayesian colocalization to test the causal effect of the genetically predicted expression of 11 cuproptosis/copper genes on coronary artery disease (CAD). Instruments were cis-eQTLs from whole-blood (eQTLGen, n = 31,684) and tibial artery (GTEx v8, n = 584); the outcome was CAD (CARDIoGRAMplusC4D/Aragam 2022; 181,522 cases, 1,165,690 participants, European ancestry). Large-artery atherosclerotic stroke (GIGASTROKE) was examined as a secondary outcome. LPL served as a positive control. The positive control was intended to validate the direction and harmonization of the MR pipeline, not to demonstrate that single-causal-variant colocalization must succeed at a known multi-signal locus such as LPL. Results. In plaque, copper-import genes (SLC31A2, SLC31A1) were upregulated and correlated strongly with myeloid/inflammatory infiltration (SLC31A2 vs. M1-macrophage r = +0.87), whereas the exporter ATP7B correlated inversely (r = −0.73). The positive control LPL showed the expected robust protective effect on CAD (IVW OR 0.90 per SD higher expression, 95% CI 0.87-0.93, P = 4.1 × 10 ⁻¹² ), validating the pipeline. None of the 11 cuproptosis/copper genes showed colocalization-supported causal evidence for CAD. Two genes reached nominal MR significance in single-instrument analyses (MTF1 OR 1.16, P = 2.7 × 10 ⁻³ , DLAT OR 1.41, P = 2.2 × 10 ⁻³ ,) but were not supported by colocalization (MTF1 PP.H4 = 4 × 10 ⁻⁶ with PP.H3 = 0.9998; DLAT PP.H4 = 0.29), indicating linkage-disequilibrium confounding rather than causality. For well-instrumented genes (e.g. ATP7B, SLC31A2, FDX1), estimates were null and precise enough to exclude odds ratios larger than ≈1.05 per SD. Conclusions. Common cis-regulatory variation determining the baseline expression of cuproptosis/copper-transport genes in available eQTL tissues did not support a detectable causal effect on CAD risk. This does not exclude locally acquired plaque cuproptosis; rather, the reported upregulation of these genes in plaque is most consistent with a consequence or marker of established disease rather than a germline-encoded causal driver, and cautions against target nomination based on descriptive transcriptomics alone. Keywords: cuproptosis; atherosclerosis; coronary artery disease; Mendelian randomization; colocalization