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Emerging evidence suggests that gut bacteria‐derived trimethylamine N‐oxide (TMAO) elevates the risk of cardiovascular disease, and dietary fiber holds the potential to attenuate TMAO formation. However, the effectiveness of dietary fiber, such as inulin, in inhibiting TMAO formation remains controversial. Therefore, this study investigated the effect of inulin supplementation on TMAO formation in mice with high TMAO levels induced by a high‐fat diet (HFD) combined with choline and L‐carnitine. Results showed that HFD treatment significantly elevated blood TMAO concentrations and increased the abundances of TMAO formation‐associated gut bacteria, as well as the abundances of functional genes responsible for TMA formation. While the supplementation of choline and L‐carnitine greatly enhanced blood trimethylamine (TMA) and TMAO levels, inulin supplementation did not significantly affect TMAO levels and had limited impact on TMA‐associated gut bacteria, except for Desulfitobacterium hafniense. [ABSTRACT FROM AUTHOR]

Trimethylamine (TMA), a byproduct of gut microbiota metabolism from dietary precursors, is not only the precursor of trimethylamine-N-oxide (TMAO) but may also affect gut health. An in vitro model of intestinal epithelium of Caco-2 cells was used to evaluate the impact of TMA on inflammation, paracellular permeability, epigenetics and mitochondrial functions. The expression levels of pro-inflammatory cytokines (IL-6, IL-1β) increased significantly after 24 h exposure to TMA 1 mM. TMA exposure was associated with an upregulation of SIRT1 (TMA 1 mM, 400 μM, 10 μM) and DNMT1 (TMA 1 mM, 400 µM) genes, while DNMT3A expression decreased (TMA 1 mM). In a cell-free model, TMA (from 0.1 µM to 1 mM) induced a dose-dependent reduction in Sirtuin enzyme activity. In Caco-2 cells, TMA reduced total ATP levels and significantly downregulated ND6 expression (TMA 1 mM). TMA excess (1 mM) reduced intracellular mitochondrial DNA copy numbers and increased the methylation of the light-strand promoter in the D-loop area of mtDNA. Also, TMA (1 mM, 400 µM, 10 µM) increased the permeability of Caco-2 epithelium, as evidenced by the reduced transepithelial electrical resistance values. Based on our preliminary results, TMA excess might promote inflammation in intestinal cells and disturb epigenetic and mitochondrial homeostasis. [ABSTRACT FROM AUTHOR]

Acinetobacter baumannii is an opportunistic human pathogen which can use host-derived L-carnitine as sole carbon and energy source. Recently, an L-carnitine transporter (Aci1347) and a specific monooxygense (CntA/CntB) for the intracellular cleavage of L-carnitine have been characterized. Subsequent conversion of the resulting malic semialdehyde into the central metabolite L-malate was hypothesized. Alternatively, L-carnitine degradation via D-malate with subsequent oxidation into pyruvate was proposed. Here we describe the in vitro and in vivo reconstitution of the entire pathway, starting from the as yet uncharacterized gene products of the carnitine degradation gene operon. Using recombinantly purified enzymes, enantiomer-specific formation of D-malate by the NAD(P)+-dependent malic semialdehyde dehydrogenase (MSA-DH) is demonstrated. The solved X-ray crystal structure of tetrameric MSA-DH reveals the key catalytic residues Cys290 and Glu256, accessible through opposing substrate and cofactor funnels. Specific substrate binding is enabled by Arg166, Arg284 and Ser447 while dual cofactor specificity for NAD+ and NADP+ is mediated by Asn184. The subsequent conversion of the unusual D-malate reaction product by an uncharacterized NAD+-dependent malate dehydrogenase (MDH) is shown. Tetrameric MDH is a ß-decarboxylating dehydrogenase that synthesizes pyruvate. MDH experiments with alternative substrates showed a high degree of substrate specificity. Finally, the entire A. baumannni pathway was heterologously reconstituted, allowing E. coli to grow on L-carnitine as a carbon and energy source. Overall, the metabolic conversion of L-carnitine via malic semialdehyde and D-malate into pyruvate, CO2 and trimethylamine was demonstrated. Trimethylamine is also an important gut microbiota-dependent metabolite that is associated with an increased risk of cardiovascular disease. The pathway reconstitution experiments allowed us to assess the TMA forming capacity of gut microbes which is related to human cardiovascular health. [ABSTRACT FROM AUTHOR]

Background: Tissue fibrosis is a common pathway to failure in many organ systems and is the cellular and molecular driver of myriad chronic diseases that are incompletely understood and lack effective treatment. Recent studies suggest that gut microbe-dependent metabolites might be involved in the initiation and progression of fibrosis in multiple organ systems. Main body of the manuscript: In a meta-organismal pathway that begins in the gut, gut microbiota convert dietary precursors such as choline, phosphatidylcholine, and L-carnitine into trimethylamine (TMA), which is absorbed and subsequently converted to trimethylamine N-oxide (TMAO) via the host enzyme flavin-containing monooxygenase 3 (FMO3) in the liver. Chronic exposure to elevated TMAO appears to be associated with vascular injury and enhanced fibrosis propensity in diverse conditions, including chronic kidney disease, heart failure, metabolic dysfunction-associated steatotic liver disease, and systemic sclerosis. Conclusion: Despite the high prevalence of fibrosis, little is known to date about the role of gut dysbiosis and of microbe-dependent metabolites in its pathogenesis. This review summarizes recent important advances in the understanding of the complex metabolism and functional role of TMAO in pathologic fibrosis and highlights unanswered questions. [ABSTRACT FROM AUTHOR]

Introduction: Understanding why subjects with overweight and with obesity vary in their response to dietary interventions is of major interest for developing personalized strategies for body mass regulation. Objectives: The aim of this study was to investigate the relationship between changes in the urine metabolome and body mass during a breakfast meal intervention. Furthermore, we aimed to elucidate if the baseline urine metabolome could predict the response to the two types of breakfast meals (high versus low protein) during the intervention. Methods: A total of 75 young, women with overweight were randomly allocated to one of two intervention groups: (1) High-protein (HP) or (2) low-protein (LP) breakfast as part of their habitual diet during a 12-week intervention. Beside the breakfast meal, participants were instructed to eat their habitual diet and maintain their habitual physical activity level. Nuclear magnetic resonance-based metabolomics was conducted on urine samples collected at baseline (wk 0), mid-intervention (wk 6), and at endpoint (wk 12). At baseline and endpoint, body mass was measured and DXA was used to measure lean body mass and fat mass. Results: The baseline urine metabolite profile showed a slightly higher correlation (R2 = 0.56) to body mass in comparison with lean body mass (R2 = 0.51) and fat mass (R2 = 0.53). Baseline 24-h urinary excretion of trigonelline (p = 0.04), N, N-dimethylglycine (p = 0.02), and trimethylamine (p = 0.03) were significantly higher in individuals who responded with a reduction in body mass to the HP breakfast. Conclusions: Differences in the urine metabolome were seen for women that obtained a body weight loss in the response to the HP breakfast intervention and women who did not obtain a body weight loss, indicating that the urine metabolome contains information about the metabolic phenotype that influences the responsiveness to dietary interventions. [ABSTRACT FROM AUTHOR]

ZnO/Ag nanocomposite was prepared via in situ method by using silver nitrate and ZnSO4 as the raw material. ZnO and ZnO/Ag were characterized by utilizing SEM, UV-vis, XRD, FTIR, and so on. The photocataytic degradation behaviors of ZnO and ZnO/Ag for trimethylamine (TEA) in air and solution were studied. The results indicated that ZnO/Ag had better photocatalytic degradation properties on trimethylamine under the condition of 0.06 g catalyst, 2 h photocatalytic time, and 15 A light intensity, and the degradation rates of TEA were up to 44 and 67% in air and solution, respectively. Furtherly, ZnO and ZnO/Ag also indicated perfect photocatalytic degradation properties toward to organic compounds in wastewater. Especially, the harmless treatment of triethylamine was achieved by using photocatalytic degradation method that provided a novel method for treating triethylamine. In all the above results leaded to a good application prospect of ZnO/Ag in the degradation of organic compounds in air and solution. [ABSTRACT FROM AUTHOR]

Context Type 2 diabetes (T2D) is the major contributor to chronic kidney disease and end-stage kidney disease (ESKD). The influence of trimethylamine N-oxide (TMAO) on kidney outcomes in T2D remains unclear. Objective To examine the association between fasting serum TMAO levels and adverse kidney outcomes in patients with T2D. Methods Between October 2016 and June 2020, patients with T2D were recruited and monitored every 3 months until December 2021. Serum TMAO levels were assessed using liquid chromatography-mass spectrometry. The primary kidney outcomes were doubling of serum creatinine levels or progression to ESKD necessitating dialysis; the secondary kidney outcome was a rapid 30% decline in estimated glomerular filtration rate within 2 years. All-cause mortality was also evaluated. Results Among the 440 enrolled patients with T2D, those in the highest serum TMAO tertile (≥0.88 μM) were older, had a longer diabetes duration, elevated blood urea nitrogen, and lower estimated glomerular filtration rate. Over a median follow-up period of 4 years, 26 patients (5.9%) had a doubling of serum creatinine level or progression to ESKD. After propensity score weighting, the patients in the highest serum TMAO tertile had a 6.45-fold increase in the risk of doubling of serum creatinine levels or progression to ESKD and 5.86-fold elevated risk of rapid decline in kidney function compared with those in the lowest tertile. Additionally, the stepwise increase in serum TMAO was associated with all-cause mortality. Conclusion Patients with T2D with elevated circulating TMAO levels are at higher risk of doubling serum creatinine, progressing to ESKD, and mortality. TMAO is a potential biomarker for kidney function progression and mortality in patients with T2D. [ABSTRACT FROM AUTHOR]

Abstract Background Tissue fibrosis is a common pathway to failure in many organ systems and is the cellular and molecular driver of myriad chronic diseases that are incompletely understood and lack effective treatment. Recent studies suggest that gut microbe-dependent metabolites might be involved in the initiation and progression of fibrosis in multiple organ systems. Main body of the manuscript In a meta-organismal pathway that begins in the gut, gut microbiota convert dietary precursors such as choline, phosphatidylcholine, and L-carnitine into trimethylamine (TMA), which is absorbed and subsequently converted to trimethylamine N-oxide (TMAO) via the host enzyme flavin-containing monooxygenase 3 (FMO3) in the liver. Chronic exposure to elevated TMAO appears to be associated with vascular injury and enhanced fibrosis propensity in diverse conditions, including chronic kidney disease, heart failure, metabolic dysfunction-associated steatotic liver disease, and systemic sclerosis. Conclusion Despite the high prevalence of fibrosis, little is known to date about the role of gut dysbiosis and of microbe-dependent metabolites in its pathogenesis. This review summarizes recent important advances in the understanding of the complex metabolism and functional role of TMAO in pathologic fibrosis and highlights unanswered questions.

The objective of this study was to investigate influences of polyvinyl alcohol/ hydroxypropyl methyl cellulose/roselle anthocyanin–based (PHR) film on shrimp biochemical and flavor profiles. PHR films led to better preservation behaviors, and the film contained the highest anthocyanin contents exhibited the best biochemical properties with total volatile basic nitrogen (TVB-N) content of 47.87 ± 3.57 mg/100 g, thiobarbituric acid (TBA) value of 0.55 ± 0.05 mg MDA/kg, and total viable counts (TVC) value of 6.63 ± 0.11 log CFU/g. The PHR film had obvious effects on the metabolism pathway of flavor compounds. It could modify flavor profiles by increasing pleasant components such as glutamate, glycine, decanal, and 3-methylbutanal, while decreasing the off-related components like histidine, indole, and trimethylamine. Furthermore, the characteristic flavor markers which were highly correlated with chemical spoilage indexes were identified, and their concentration variations suggested that PHR film could affect their formation and release behavior. Meanwhile, the possible mechanism of PHR film in shelf-life prolongation and flavor profile enhancement was proposed. In conclusion, the PHR film had promising potentials in extension of shelf-life and modification of flavor profiles of refrigerated shrimp. [ABSTRACT FROM AUTHOR]

Diet for many years has been considered a general health determinant. Recent research shows a connection between gut microbiota composition that is shaped by our diet and lifestyle diseases. Plasma trimethylamine N-oxide (TMAO) originates from gut bacteria metabolism of dietary l-carnitine, betaine, and choline. A number of studies suggest a positive correlation between elevated plasma trimethylamine N-oxide levels and a risk for cardiovascular diseases, diabetes, and cancer. Recent experimental and clinical evidence shows that TMAO may serve as a diagnostic and prognostic marker of many pathologic conditions. Therefore, rapid determination of serum TMAO concentration is of clinical interest. [ABSTRACT FROM AUTHOR]

The development of sensors with excellent and low detection limits is critical for detecting trimethylamine (TMA) in seafood safety monitoring and healthcare. Herein, WO3 flower-like structures functionalized with NiWO4 were fabricated using a combination of solvothermal and hydrothermal methods and subsequently utilized in gas sensors for TMA detection. The gas-sensing results demonstrated that the incorporation of NiWO4 nanoparticles onto the WO3 surface reduced the optimal operating temperature and further enhanced the selectivity and response to TMA. Representatively, the 10-NiWO4/WO3 sensor exhibited a sensing response of 12.05 to 10 ppm TMA, along with rapid response/recovery times (14/17 s), a low theoretical detection limit of 14.26 ppb, a wide detection range, and excellent long-term stability at 150 °C. These improved capabilities are primarily ascribed to the modulation of surface carrier concentration within the n–n heterojunction at the NiWO4/WO3 interface, coupled with the catalytic promotion effect of NiWO4 on gas-sensing reactions, and the unique hierarchical flower-like structures. This study highlights the considerable potential of 3D flower-like NiWO4/WO3 heterostructures as a highly promising sensing material for TMA gas sensors. [ABSTRACT FROM AUTHOR]

Drying process was used in this study as a preserving method of octopus quality during storage. Octopus vulgaris quality attributes in terms of pH, water activity, color properties, total volatile basic nitrogen (TVB-N), trimethylamine (TMA), total viable count, and yeast and molds (YM) were evaluated. Samples were dried under sun drying and convective air drying and stored at ambient temperature. During storage, TVBN and TMA obtained were within the recommended level for good quality of dried samples. Accelerating shelf-life test was evaluated based on TVB-N, TMA, and YM, with shelf lives of 388 and 603 days for convective air drying and sun drying, respectively. [ABSTRACT FROM AUTHOR]

This article explores the catalytic C–H functionalization of trimethylamine, an important intermediate in the chemical industry. Trimethylamine is often obtained as an undesired by-product, and separating it from other methylamines is challenging and expensive. The authors discuss the development of new chemical reactions that use trimethylamine as a starting material for the synthesis of valuable products, particularly those with a dimethylaminomethyl substructure commonly found in pharmaceuticals. The article reports successful reactions of trimethylamine with various compounds, offering flexible and direct methods for its functionalization. The authors highlight the efficient activation of the α-C–H bond of trimethylamine using titanium catalysts, which allows for the synthesis of various dimethylaminomethyl-substituted products. The article also mentions the successful synthesis of the antidepressant butriptyline as an example of the potential of these new reactions. The assistance of Jessica Reimer and the supply of ampoules by Kirstin Glaser, Karin Grittner, and Frank Fleischer are acknowledged. [Extracted from the article]

Trimethylamine N‐oxide (TMAO) is a circulating microbiome‐derived metabolite implicated in the development of atherosclerosis and cardiovascular disease (CVD). We investigated whether plasma levels of TMAO, its precursors (betaine, carnitine, deoxycarnitine, choline), and TMAO‐to‐precursor ratios are associated with clinical outcomes, including CVD and mortality. This was followed by an in‐depth analysis of their genetic, gut microbial, and dietary determinants. The analyses were conducted in five Dutch prospective cohort studies including 7834 individuals. To further investigate association results, Mendelian Randomization (MR) was also explored. We found only plasma choline levels (hazard ratio [HR] 1.17, [95% CI 1.07; 1.28]) and not TMAO to be associated with CVD risk. Our association analyses uncovered 10 genome‐wide significant loci, including novel genomic regions for betaine (6p21.1, 6q25.3), choline (2q34, 5q31.1), and deoxycarnitine (10q21.2, 11p14.2) comprising several metabolic gene associations, for example, CPS1 or PEMT. Furthermore, our analyses uncovered 68 gut microbiota associations, mainly related to TMAO‐to‐precursors ratios and the Ruminococcaceae family, and 16 associations of food groups and metabolites including fish‐TMAO, meat‐carnitine, and plant‐based food‐betaine associations. No significant association was identified by the MR approach. Our analyses provide novel insights into the TMAO pathway, its determinants, and pathophysiological impact on the general population. Highlights: Exploration of microbiome‐related metabolites (trimethylamine N‐oxide [TMAO], choline, betaine, l‐carnitine, and deoxycarnitine) in 7834 participants from five population cohorts.Cardiovascular risk was associated with elevated choline concentrations, but not with TMAO concentrations.Characterization of the genetic architecture behind metabolite concentration variability.Identification of gut microbial taxonomic abundance associated with metabolite's plasma concentration levels.Fish intake is the major dietary driver of TMAO concentrations, and betaine is related to grains and vegetable intake. [ABSTRACT FROM AUTHOR]

A series of mononuclear ruthenium(II) tetra-tert-butyl-phthalocyaninates bearing axial N-donor ligands [tBu4PcRu]L2 (L = trimethylamine, pyrazine, 4,4′-bipyridine and N-methyl-4,4′-bipyridinium iodide) as well as the binuclear complex [tBu4PcRu]2(BiPy)3 were synthesized starting from the complex with axially coordinated carbonyl group [tBu4PcRu](CO). All compounds have been characterized by NMR, UV-Vis and cyclic voltammetry. The latter allowed the determination of oxidation and reduction potentials, HOMO-LUMO gaps and revealed the possibility of electropolymerization of BiPy-containing complexes in clear contrast to complexes containing another bidentate ligand – pyrazine. Comparative electrochemical studies of the mono- and binuclear complexes [tBu4PcRu](BiPy)2 and [tBu4PcRu]2(BiPy)3 revealed that the phthalocyanine rings are not conjugated in the binuclear species. The remarkable dependence of singlet oxygen generation from axial ligands in ruthenium phthalocyaninates was observed: the complexes with carbonyl group [tBu4PcRu](CO) and with pyrazine molecules [tBu4PcRu](Pyz)2 show higher 1O2 quantum yields, whereas the complex with axially coordinated molecules of trimethylamine [tBu4PcRu](NMe3)2 and quaternized BiPy ligands [tBu4PcRu](BiPy-Me+)2 have the lowest ability to generate singlet oxygen. The revealed influence of axial ligands on key physicochemical properties paves the way for the design of new ruthenium phthalocyaninates with potential optoelectronic and biomedical applications. [ABSTRACT FROM AUTHOR]

[Display omitted] • The self-standing COFM PDI-THSTZ is synthesized via liquid–liquid interfacial method. • The semiconductor characteristics of PDI and multi-channel structure of COF endow the sensor with real-time sensing properties. • The mechanism for the enhanced TMA sensing response of COFM PDI-THSTZ is investigated. • The TMA sensor can be used for the quality monitoring in IoT. The unprecedented demand for highly selective, real-time monitoring and low-power gas sensors used in food quality control has been driven by the increasing popularity of the Internet of Things (IoT). Herein, the self-standing perylene diimide based covalent organic framework membranes (COFM PDI-THSTZ) were prepared via liquid–liquid interfacial synthesis method. By incorporating the perylene diimide monomer into the COFM through molecular engineering, COFM PDI-THSTZ based sensor demonstrated an outstanding trimethylamine (TMA)-sensing performance at room temperature. Benefited from the TMA-accessible self-standing membrane morphology, π-electron delocalization effect, and extensive surface area with continuous nanochannels, the specific and highly sensitive TMA measurement has been achieved within the range of 0.03–400 ppm, with an exceptional theoretical detection limit as low as 10 ppb. Moreover, the primary internal mechanism of COFM PDI-THSTZ for this efficient TMA detection was investigated through in-situ FT-IR spectra, thereby directly elucidating that the chemisorption interaction of oxygen modulated the depletion layers on sensing material surface, resulting in alterations in sensor resistance upon exposure to the target gas. For practical usage, COFM PDI-THSTZ based sensor exhibited exceptional real-time in-situ sensing capabilities, further confirmed their potential for application in dynamic prediction evaluation of marine fish products and quality monitoring in IoT. [ABSTRACT FROM AUTHOR]

Existence of Trimethylamine N-oxide (TMAO) and trimethylamine (TMA) are well recognized through our multiple human activities. Most of them are derived from quaternary ammoniums widely distributed in natural products, which have N-trimethyl moiety. There could also be some inhibitors to reduce their yield. TMAO is known as a representative component in seafood and is recently gaining large attention. TMAO is formed mostly from choline and carnitine in animal products by mediating gut microbes and host monooxygenase in the human body. Teleost tilapia also has a similar mechanism well mediating choline. In marine habitants, TMAO is utilized as an osmolyte. In human, however, the endogenous TMAO is reported to be associated with a risk of cardiovascular events. During the organic evolution, marine creatures could develop utilizing TMAO while avoiding risks. This article, therefore, reviews and characterize the TMAO/TMA having different profiles, and consider the possible inhibitors preventing undesired metabolisms, to try to find clues of the TMAO subjects and consider possibilities and prospects. [ABSTRACT FROM AUTHOR]

There are conflicting animal experiments on the effect of trimethylamine N-oxide (TMAO), the dietary metabolite, on non-alcoholic fatty liver disease (NAFLD). This study aims to determine the effect of TMAO on NAFLD. A diet containing 0.3% TMAO was fed to farnesoid X receptor (Fxr)-null mice, a model of NAFLD, for 13 weeks. Fxr-null mice fed TMAO showed significant reductions in liver damage markers but not wild-type mice. Hepatic bile acid and cholesterol levels were significantly decreased, and triacylglycerol levels tended to decrease in TMAO-fed Fxr-null mice. Changes in mRNA levels of hepatic bile acid and cholesterol transporters and synthetic enzymes were observed, which could explain the decreased hepatic bile acid and cholesterol levels in Fxr-null mice given the TMAO diet but not in the wild-type mice. These results suggest that TMAO intake ameliorates liver damage in Fxr-null mice, further altering bile acid/cholesterol metabolism in an FXR-independent manner. [ABSTRACT FROM AUTHOR]

Four different concentrations of an aqueous extract of cuttlefish (Sepia spp.) ink (CI) were introduced, respectively, into the packing medium employed during golden seabream (Sparus aurata) canning. The quality parameters of the resulting canned fish were determined and compared to the initial fish and the control canned muscle. An important effect of the CI concentration introduced in the packing medium was proved. The presence in the packing medium of a relatively low CI concentration (CI-2 batch) led to a lower (p < 0.05) lipid oxidation development (fluorescent compound formation), lower (p < 0.05) changes of colour parameters (L* and a* values), and lower (p < 0.05) trimethylamine values in canned fish when compared to control canned samples. Additionally, the two lowest CI concentrations tested led to higher average values of C22:6ω3, ω3/ω6 ratios, and polyene index. On the contrary, the use of the most concentrated CI extract (CI-4 condition) led to a prooxidant effect (higher fluorescence ratio value). In agreement with environmental sustainability and circular economy requirements, the study can be considered the first approach to a novel and valuable use of the current marine byproduct for the quality enhancement of canned fish. On-coming research focused on the optimisation of the CI-extract concentration is envisaged. [ABSTRACT FROM AUTHOR]

Background: The gut-derived metabolite Trimethylamine N-oxide (TMAO) and its precursors - betaine, carnitine, choline, and deoxycarnitine – have been associated with an increased risk of cardiovascular disease, but their relation to cognition, neuroimaging markers, and dementia remains uncertain. Methods: In the population-based Rotterdam Study, we used multivariable regression models to study the associations between plasma TMAO, its precursors, and cognition in 3,143 participants. Subsequently, we examined their link to structural brain MRI markers in 2,047 participants, with a partial validation in the Leiden Longevity Study (n = 318). Among 2,517 participants, we assessed the risk of incident dementia using multivariable Cox proportional hazard models. Following this, we stratified the longitudinal associations by medication use and sex, after which we conducted a sensitivity analysis for individuals with impaired renal function. Results: Overall, plasma TMAO was not associated with cognition, neuroimaging markers or incident dementia. Instead, higher plasma choline was significantly associated with poor cognition (adjusted mean difference: -0.170 [95% confidence interval (CI) -0.297;-0.043]), brain atrophy and more markers of cerebral small vessel disease, such as white matter hyperintensity volume (0.237 [95% CI: 0.076;0.397]). By contrast, higher carnitine concurred with lower white matter hyperintensity volume (-0.177 [95% CI: -0.343;-0.010]). Only among individuals with impaired renal function, TMAO appeared to increase risk of dementia (hazard ratio (HR): 1.73 [95% CI: 1.16;2.60]). No notable differences were observed in stratified analyses. Conclusions: Plasma choline, as opposed to TMAO, was found to be associated with cognitive decline, brain atrophy, and markers of cerebral small vessel disease. These findings illustrate the complexity of relationships between TMAO and its precursors, and emphasize the need for concurrent study to elucidate gut-brain mechanisms. [ABSTRACT FROM AUTHOR]

Background: Trimethylamine N-oxide (TMAO) is synthesized by the intestinal microbiota and is an independent predictor of cardiovascular disease (CVD). However, its underlying mechanisms remain unclear. We investigated TMAO levels across different CVD-risk patient groups, and evaluated associations between TMAO and vascular alterations (e.g., arterial stiffness, intima-media thickness [IMT], and the presence and grade of carotid artery plaques [CAPs]). Methods: We examined 95 patients (58.5 +- 7.3 years): 40 with clinical atherosclerotic cardiovascular disease (ASCVD), 40 with atherosclerosis risk factors (RF), and 15 controls. Arterial stiffness was measured by Carotid-Femoral Pulse Wave Velocity (C-F PWV). B-mode ultrasound was used to evaluate the presence and grade of CAPs and carotid IMT (CIMT). TMAO was measured by high performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) and results were presented as the median (interquartile range). Results: TMAO levels were higher in patients with ASCVD (251.5 [164.5] µg/l) when compared with patients with RFs (194.0 [174] µg/l, P=0.04) and controls (122.0 (77) µg/l, P<0.001). A significant correlation was observed between TMAO and PWV (r = 0.31, P=0.003), which was not confirmed after adjustment for RFs. TMAO levels were significantly correlated with plaque score (r = 0.46, P<0.001) and plaque height (r=0.41, P=0.003), and were independent predictors for grade III plaques (odds ratio [OR] = 1.002, confidence interval (CI) 95%: 1.000047-1.003, P=0.044). Conclusions: TMAO levels are increased with expanded CVD risk. Across different types of vascular damage, TMAO is associated with atherosclerotic changes. [ABSTRACT FROM AUTHOR]

Background and Aims: Emerging evidence suggests a detrimental impact of high red meat intake on hepatic steatosis. We investigated the potential interplay between red meat intake and gut microbiome on circulating levels of trimethylamine N‐oxide (TMAO) and hepatic steatosis risk. Methods: This cross‐sectional study was conducted in a representative sample of 754 community‐dwelling adults in Huoshan, China. Diet was collected using 4 quarterly 3 consecutive 24‐h dietary (12‐day) recalls. We profiled faecal microbiome using 16S ribosomal RNA sequencing and quantified serum TMAO and its precursors using LC‐tandem MS (n = 333). We detected hepatic steatosis by FibroScan. The adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were calculated using logistic regression. Results: TMAO levels but not its precursors were positively associated with the likelihood of hepatic steatosis (aOR per 1‐SD increment 1.86, 95% CI 1.04–3.32). We identified 14 bacterial genera whose abundance was associated with TMAO concentration (pFDR <.05) belonging to the phyla Firmicutes, Bacteroidetes, Actinobacteria and Proteobacteria families. Per 10 g/day increase in red meat intake was positively associated with TMAO levels among participants who had higher red meat intake (>70 g/day) and higher TMAO‐predicting microbial scores (TMS, β =.045, p =.034), but not among others (pinteraction =.030). TMS significantly modified the positive association between red meat and steatosis (pinteraction =.032), with a stronger association being observed among participants with higher TMS (aOR 1.30, 95% CI 1.07–1.57). Conclusions: The bacterial genera that predicted TMAO levels may jointly modify the association between red meat intake and TMAO levels and the subsequent risk of hepatic steatosis. [ABSTRACT FROM AUTHOR]

ABSTRACT Microorganisms can produce a vast diversity of volatile organic compounds of different chemical classes that are capable of mediating intra- and inter-kingdom interactions. In this study, we showed that the soil-dwelling bacterium Streptomyces venezuelae can produce alkaline volatiles under multiple growth conditions, which we discovered through investigation of the S. venezuelae mutant strain MU-1. Strain MU-1 has a defective morphology and exhibits a bald phenotype due to the lack of aerial mycelia and spores, as confirmed by scanning electron microscopy. Using physical barriers to separate the strains on culture plates, we determined that volatile compounds produced by wild-type S. venezuelae could rescue the phenotype of strain MU-1, and pH analysis of the growth medium indicated that these volatile compounds were alkaline. Ultra-high-performance liquid chromatography, combined with mass spectrometry analysis, showed that wild-type S. venezuelae produced abundant levels of the alkaline volatile trimethylamine (TMA) and the oxide form TMAO; however, the levels of these compounds were much lower in strain MU-1. Notably, exposure to TMA alone could rescue the phenotype of this mutant strain, restoring the production of aerial mycelia and spores. We also showed that the rescue effect by alkaline volatiles is mostly species-specific, suggesting that the volatiles may aid particular mutants or other less-fit variants of closely related species to resume normal physiological status and to compete more effectively in complex communities such as soil. Our study reveals a new and intriguing role for bacterial volatiles, including volatiles that may have toxic effects on other species.IMPORTANCEBacterial volatiles have a wide range of biological roles at intra- or inter-kingdom levels. The impact of volatiles has mainly been observed between producing bacteria and recipient bacteria, mostly of different species. In this study, we report that the wild-type, soil-dwelling bacterium Streptomyces venezuelae, which forms aerial hypha and spores as part of its normal developmental cycle, also produces the alkaline volatile compound trimethylamine (TMA) under multiple growth conditions. We showed that the environmental dispersion of TMA produced by S. venezuelae promotes the growth and differentiation of growth-deficient mutants of the same species or other slowly growing Streptomyces bacteria, and thus aids in their survival and their ability to compete in complex environmental communities such as soil. Our novel findings suggest a potentially profound biological role for volatile compounds in the growth and survival of communities of volatile-producing Streptomyces species.

Acinetobacter baumannii is an opportunistic human pathogen which can use host-derived L-carnitine as sole carbon and energy source. Recently, an L-carnitine transporter (Aci1347) and a specific monooxygense (CntA/CntB) for the intracellular cleavage of L-carnitine have been characterized. Subsequent conversion of the resulting malic semialdehyde into the central metabolite L-malate was hypothesized. Alternatively, L-carnitine degradation via D-malate with subsequent oxidation into pyruvate was proposed. Here we describe the in vitro and in vivo reconstitution of the entire pathway, starting from the as yet uncharacterized gene products of the carnitine degradation gene operon. Using recombinantly purified enzymes, enantiomer-specific formation of D-malate by the NAD(P)+-dependent malic semialdehyde dehydrogenase (MSA-DH) is demonstrated. The solved X-ray crystal structure of tetrameric MSA-DH reveals the key catalytic residues Cys290 and Glu256, accessible through opposing substrate and cofactor funnels. Specific substrate binding is enabled by Arg166, Arg284 and Ser447 while dual cofactor specificity for NAD+ and NADP+ is mediated by Asn184. The subsequent conversion of the unusual D-malate reaction product by an uncharacterized NAD+-dependent malate dehydrogenase (MDH) is shown. Tetrameric MDH is a β-decarboxylating dehydrogenase that synthesizes pyruvate. MDH experiments with alternative substrates showed a high degree of substrate specificity. Finally, the entire A. baumannni pathway was heterologously reconstituted, allowing E. coli to grow on L-carnitine as a carbon and energy source. Overall, the metabolic conversion of L-carnitine via malic semialdehyde and D-malate into pyruvate, CO2 and trimethylamine was demonstrated. Trimethylamine is also an important gut microbiota-dependent metabolite that is associated with an increased risk of cardiovascular disease. The pathway reconstitution experiments allowed us to assess the TMA forming capacity of gut microbes which is related to human cardiovascular health.

We report a computer simulation study of the effect of trimethylamine N-oxide (TMAO) on the pressure stability of the hydrophobic contact interaction of two nonpolar α-helices. We found that TMAO counterbalanced the disruptive effect of pressure destabilization on account of an earlier reported electronic polarization effect that led to an increased TMAO dipole moment under compression of the solvent. This direct stabilization mechanism became ineffective when the dipole polarization of TMAO was not considered and was linked to nonspecific van der Waals interactions of TMAO with the nonpolar surfaces of the two helices, which became weaker as TMAO became stronger polarized at high pressure. The corresponding thermodynamic driving forces are discussed and should be generic for hydrophobic interactions under high pressure. The proposed mechanism suggests that TMAO stands out as a piezolyte among stabilizing osmolytes, potentially protecting biological assemblies formed by hydrophobic interactions under extreme pressure conditions. [ABSTRACT FROM AUTHOR]

Compounds containing one carbon atom or no carbon-carbon bond (C1 compounds), such as trimethylamine and methanol, are important climate relevant gases in the atmosphere and play key roles in global warming. The ocean is a significant source or sink of such compounds, while the concentrations of trimethylamine and methanol in seawater remain largely unconstrained due to the analytical challenges involved. Therefore, it is necessary to establish a continuous, rapid and sensitive method for the determination of these compounds with high polarity, volatility or solubility at low seawater concentrations. Here we developed a purge and trap system, coupled to a gas chromatography equipped with dual nitrogen phosphorus detector (NPD) and flame ionization detector (FID) for the simultaneous online analysis of trimethylamine and methanol at nanomolar range using a small sample volume (~ 10 mL). The dual detection of trimethylamine and methanol with NPD or FID was achieved by installing a capillary flow splitter between the capillary column and detectors. After modification and optimization of the setup and conditions, excellent linearity (R² > 0.99) and repeatability (< 6%) were obtained for both compounds; the detection limits for trimethylamine andmethanol were 0.3 nM and 17.6 nM, respectively. Using this method, water samples collected from coastal and open ocean were analyzed; trimethylamine and methanol concentrations ranged from 0.6 to 18.8 nM and 26.0 to 256.2 nM, respectively. Collectively, this method allowed for online, rapid, sensitive and simultaneous quantification of trace trimethylamine and methanol concentrations with low-cost instrumentation and small sample volume, which makes it promising for further application in volatile compounds analysis in marine environments. [ABSTRACT FROM AUTHOR]

Aortic dissection (AD) is the most catastrophic vascular disease with a high mortality rate. Trimethylamine N-oxide (TMAO), a gut microbial metabolite, has been implicated in the pathogenesis of cardiovascular diseases. However, the role of TMAO in AD and the underlying mechanisms remain unclear. This study aimed to explore the effects of TMAO on AD. Plasma and fecal samples from patients with AD and healthy individuals were collected to analyze TMAO levels and gut microbial species, respectively. The plasma levels of TMAO were significantly higher in 253 AD patients compared with those in 98 healthy subjects (3.47, interquartile range (IQR): 2.33 to 5.18 μM vs. 1.85, IQR: 1.40 to 3.35 μM; p < 0.001). High plasma TMAO levels were positively associated with AD severity. An increase in the relative abundance of TMA-producing genera in patients with AD was revealed using 16S rRNA sequencing. In the angiotensin II or β-aminopropionitrile-induced rodent model of AD, mice fed a TMAO-supplemented diet were more likely to develop AD compared to mice fed a normal diet. Conversely, TMAO depletion mitigated AD formation in the BAPN model. RNA sequencing of aortic endothelial cells isolated from mice administered TMAO revealed significant upregulation of genes involved in inflammatory pathways. The in vitro experiments verified that TMAO promotes endothelial dysfunction and activates nuclear factor (NF)-κB signaling. The in vivo BAPN-induced AD model confirmed that TMAO increased aortic inflammation. Our study demonstrates that the gut microbial metabolite TMAO aggravates the development of AD at least in part by inducing endothelial dysfunction and inflammation. This study provides new insights into the etiology of AD and ideas for its management. [Display omitted] • Plasma levels of TMAO were significantly higher in AD patients compared with those in healthy subjects. • TMAO aggravates the development of AD. • TMAO induces EC dysfunction and activates the NF-κB signaling pathway. • Gut microbiota may be a new therapeutic target in AD. [ABSTRACT FROM AUTHOR]

Graphene materials have shown a great promise for gas sensors, however, the effect of different modification strategies on gas sensing mechanisms has not been studied. In this research, the adsorption and sensitivity properties of trimethylamine (TMA) on pristine (PG), Zn-decorated (Zn-G1), Zn-doped (Zn-G2), ZnN 4 -embedded (ZnN 4 -G), Zn-defect combined (ZnC 4 -G) graphene are carefully discussed by density functional theory (DFT) calculations. Among five substrates, Zn-G2, ZnN 4 -G, and ZnC 4 -G exhibit high sensitivity and selectivity toward TMA due to the shorter adsorption distances, large amount of charge transfer and stronger adsorption strengths. Especially for Zn-G2, energy gap and work function are obviously altered after interaction with the TMA molecule. The recovery time of ZnN 4 -G and ZnC 4 -G are 269 and 6 s at 398 K, respectively. When the conditional temperature reaches 498 K, the recovery time of Zn-G2 only takes 91 s by applying negative electric field of 8 × 106 a.u. Such short recovery time makes Zn-G2, ZnN 4 -G, and ZnC 4 -G as a reversible gas sensor. Moreover, the applied positive electric fields can further enhance the selectivity and sensitivity of Zn-G2, ZnN 4 -G, and ZnC 4 -G. In light of these findings may provide theoretical guidance for developing high selectivity and sensitivity graphene-based gas sensor. • Adsorption of TMA gas on the five graphene substrates is explored. • The energy gap of Zn-G2 is obviously altered after interaction with TMA. • Zn-G2, ZnN 4 -G, and ZnC 4 -G exhibit high sensitivity and selectivity to TMA. • The adsorption behavior can be controlled by applying electric field. [ABSTRACT FROM AUTHOR]

Copyright of Electronic Components & Materials is the property of Electronic Components & Materials and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Cervical cancer (CC) is a danger to women's health, especially in many developing countries. Metabolomics can make the connection between genotypes and phenotypes. It provides a wide spectrum profile of biological processes under pathological or physiological conditions. Method: In this study, we conducted plasma metabolomics of healthy volunteers and CC patients and integratively analyzed them with public CC tissue transcriptomics from Gene Expression Omnibus (GEO). Result: Here, we screened out a panel of 5 metabolites to precisely distinguish CC patients from healthy volunteers. Furthermore, we utilized multi-omics approaches to explore patients with stage I-IIA1 and IIA2-IV4 CC and comprehensively analyzed the dysregulation of genes and metabolites in CC progression. We identified that plasma levels of trimethylamine N-oxide (TMAO) were associated with tumor size and regarded as a risk factor for CC. Moreover, we demonstrated that TMAO could promote HeLa cell proliferation in vitro. In this study, we delineated metabolic profiling in healthy volunteers and CC patients and revealed that TMAO was a potential biomarker to discriminate between I-IIA1 and IIA2-IV patients to indicate CC deterioration. Conclusion: Our study identified a diagnostic model consisting of five metabolites in plasma that can effectively distinguish CC from healthy volunteers. Furthermore, we proposed that TMAO was associated with CC progression and might serve as a potential non-invasive biomarker to predict CC substage. Impact: These findings provided evidence of the important role of metabolic molecules in the progression of cervical cancer disease, as well as their ability as potential biomarkers. [ABSTRACT FROM AUTHOR]

Supplementing fish oil is one of the strategies to reduce the risk of cardiovascular disease, the leading cause of death around the world. Contradictorily, fish oil may also contain trimethylamine-N-oxide, a recently emerged risk factor for cardiovascular disease, as well as one of its precursors, trimethylamine. A method suitable for routine quantification of trimethylamine-N-oxide and trimethylamine in fish oil with a quick and easy liquid extraction without derivatization has been developed. Liquid chromatography with tandem mass spectrometry detection was employed along with a zwitterionic hydrophilic interaction liquid chromatography column and a gradient elution with eluents containing 50 mmol/L of ammonium formate. An internal standard (triethylamine) was used for quantification by mass spectrometry with an external calibration. The assay proved high linearity in the ranges of 10 to 100 ng/mL and 100 to 1000 ng/mL for trimethylamine-N-oxide and trimethylamine, respectively. The lowest limit of quantification was determined to be 100 µg/kg for trimethylamine and 10 µg/kg for trimethylamine-N-oxide, with the limit of detection at 5 µg/kg and 0.25 µg/kg, respectively. Accuracy ranged from 106–119%. Precision was below 7% the relative standard deviation for both analytes. The method was successfully applied for the determination of trimethylamine-N-oxide and trimethylamine contents in nine commercially available liquid fish oils and three commercially available fish oil capsules, showing that trimethylamine and trimethylamine-N-oxide are not present in highly refined fish oils. [ABSTRACT FROM AUTHOR]

The combination of two-dimensional material MXene and one-dimensional metal oxide semiconductor can improve the carrier transmission rate, which can effectively improve sensing performance. We prepared a trimethylamine gas sensor based on MoO3 nanofibers and layered Ti3C2Tx MXene. Using electrospinning and chemical etching methods, one-dimensional MoO3 nanofibers and two-dimensional Ti3C2Tx MXene nanosheets were prepared, respectively, and the composites were characterized via XPS, SEM, and TEM. The Ti3C2Tx MXene–MoO3 composite material exhibits excellent room-temperature response characteristics to trimethylamine gas, showing high response (up to four for 2 ppm trimethylamine gas) and rapid response–recovery time (10 s/7 s). Further, we have studied the possible sensitivity mechanism of the sensor. The Ti3C2Tx MXene–MoO3 composite material has a larger specific surface area and more abundant active sites, combined with p–n heterojunction, which effectively improves the sensitivity of the sensor. Because of its low detection limit and high stability, it has the potential to be applied in the detection system of trimethylamine as a biomarker in exhaled air. [ABSTRACT FROM AUTHOR]

Gut microbes play a pivotal role in host physiology by producing beneficial or detrimental metabolites. Gut bacteria metabolize dietary choline and L‐carnitine to trimethylamine (TMA) which is then converted to trimethylamine‐N‐oxide (TMAO). An elevated circulating TMAO is associated with diabetes, obesity, cardiovascular disease, and cancer in humans. In the present study, we investigated the effect of dietary blueberries and strawberries at a nutritional dosage on TMA/TMAO production and the possible role of gut microbes. Blueberry cohort mice received a control (C) or freeze‐dried blueberry supplemented (CB) diet for 12 weeks and subgroups received an antibiotics cocktail (CA and CBA). Strawberry cohort mice received a control (N) or strawberry‐supplemented (NS) diet and subgroups received antibiotics (NA and NSA). Metabolic parameters, choline, TMA, and TMAO were assessed in addition to microbial profiling and characterization of berry powders. Blueberry supplementation (equivalent to 1.5 human servings) reduced circulating TMAO in CB versus C mice (~48%) without changing choline or TMA. This effect was not mediated through alterations in metabolic parameters. Dietary strawberries did not reduce choline, TMA, or TMAO. Depleting gut microbes with antibiotics in these cohorts drastically reduced TMA and TMAO to not‐quantified levels. Further, dietary blueberries increased the abundance of bacterial taxa that are negatively associated with circulating TMA/TMAO suggesting the role of gut microbes. Our phenolic profiling indicates that this effect could be due to chlorogenic acid and increased phenolic contents in blueberries. Our study provides evidence for considering dietary blueberries to reduce TMAO and prevent TMAO‐induced complications. [ABSTRACT FROM AUTHOR]

Trimethylamine N-oxide, Me3N(+)O(−), is an important molecule in biology and medicine. Herein, a survey of the interactions involving the oxide-O atom in crystals containing derivatives of Me3N(+)O(−), namely RR′R″N(+)O(−), is presented; R,R′, R″ = alkyl and/or aryl. A total of 119 RR′R″N(+)O(−) molecules were analysed for the supramolecular interactions involving the oxide-O atom. Hydrates form the largest class of crystals, comprising over 40 % of the 91 crystals investigated, a value slightly higher than expectation. Over 80 % of molecules had at least one O–H⋯O(−)(oxide) hydrogen bond: 3, 45 and 33 % of all molecules had three, two or one O–H⋯O(−)(oxide) hydrogen bonds, respectively. Further, nearly 15 % of molecules formed at least one N–H⋯O(−)(oxide) hydrogen bond, sometimes operating in concert with O–H⋯O(−)(oxide) hydrogen bonds. The overwhelming majority of molecules featured inter- and/or intra-molecular supporting C–H⋯O(−)(oxide) contacts so that a diverse range of supramolecular interaction patterns is apparent, a situation made more complicated by the appearance of different supramolecular association patterns often observed for independent molecules in crystals with more than one molecule in the crystallographic asymmetric-unit. Of the 6 % of molecules devoid of conventional A–H⋯O(−)(oxide) hydrogen bonds, all formed three or four inter-/intra-molecular C–H⋯O(−)(oxide) contacts usually characterised by at least one short H⋯O(−)(oxide) distance. [ABSTRACT FROM AUTHOR]

Copyright of Arquivos Brasileiros de Oftalmologia is the property of Arquivos Brasileiros de Oftalmologia and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Overall diet, lifestyle choices, genetic predisposition, and other underlying health conditions may contribute to higher trimethylamine N‐oxide (TMAO) levels and increased cardiovascular risk. This review explores the potential therapeutic ability of RSV to protect against cardiovascular diseases (CVD) and affect TMAO levels. This review considers recent studies on the association of TMAO with CVD. It also examines the sources, mechanisms, and metabolism of TMAO along with TMAO‐induced cardiovascular events. Plant polyphenolic compounds, including resveratrol (RSV), and their cardioprotective mechanism of regulating TMAO levels and modifying gut microbiota are also discussed here. RSV's salient features and bioactive properties in reducing CVD have been evaluated. The close relationship between TMAO and CVD is clearly understood from currently available data, making it a potent biomarker for CVD. Precise investigation, including clinical trials, must be performed to understand RSV's mechanism, dose, effects, and derivatives as a cardioprotectant agent. [ABSTRACT FROM AUTHOR]

Trimethylamine N-oxide, Me3N(+)O(−), is an important molecule in biology and medicine. Herein, a survey of the interactions involving the oxide-O atom in crystals containing derivatives of Me3N(+)O(−), namely RR′R″N(+)O(−), is presented; R,R′, R″ = alkyl and/or aryl. A total of 119 RR′R″N(+)O(−) molecules were analysed for the supramolecular interactions involving the oxide-O atom. Hydrates form the largest class of crystals, comprising over 40 % of the 91 crystals investigated, a value slightly higher than expectation. Over 80 % of molecules had at least one O–H⋯O(−)(oxide) hydrogen bond: 3, 45 and 33 % of all molecules had three, two or one O–H⋯O(−)(oxide) hydrogen bonds, respectively. Further, nearly 15 % of molecules formed at least one N–H⋯O(−)(oxide) hydrogen bond, sometimes operating in concert with O–H⋯O(−)(oxide) hydrogen bonds. The overwhelming majority of molecules featured inter- and/or intra-molecular supporting C–H⋯O(−)(oxide) contacts so that a diverse range of supramolecular interaction patterns is apparent, a situation made more complicated by the appearance of different supramolecular association patterns often observed for independent molecules in crystals with more than one molecule in the crystallographic asymmetric-unit. Of the 6 % of molecules devoid of conventional A–H⋯O(−)(oxide) hydrogen bonds, all formed three or four inter-/intra-molecular C–H⋯O(−)(oxide) contacts usually characterised by at least one short H⋯O(−)(oxide) distance. [ABSTRACT FROM AUTHOR]

Background and Aim: An elevated triglyceride-glucose (TyG) level is associated with increased risk of mortality in patients with CAD. Trimethylamine N-oxide (TMAO) has mechanistic links to atherosclerotic coronary artery disease (CAD) pathogenesis and is correlated with adverse outcomes. However, the incremental prognostic value of TMAO and TyG in the cohort of optical coherence tomography (OCT)-defined high-risk ST-segment elevation myocardial infarction (STEMI) patients is unknown. Methods: We studied 274 consecutive aged ≥ 18 years patients with evidence of STEMI and detected on pre-intervention OCT imaging of culprit lesions between March 2017 and March 2019. Outcomes: There were 22 (22.68%), 27 (27.84%), 26 (26.80%), and 22 (22.68%) patients in groups A-D, respectively. The baseline characteristics according to the level of TMAO and TyG showed that patients with higher level in both indicators were more likely to have higher triglycerides (p < 0.001), fasting glucose (p < 0.001) and higher incidence of diabetes (p = 0.008). The group with TMAO > median and TyG ≤ median was associated with higher rates of MACEs significantly (p = 0.009) in fully adjusted analyses. During a median follow-up of 2.027 years, 20 (20.6%) patients experienced MACEs. To evaluate the diagnostic value of the TyG index combined with TMAO, the area under the receiver operating characteristic curve for predicting MACEs after full adjustment was 0.815 (95% confidence interval, 0.723– 0.887; sensitivity, 85.00%; specificity, 72.73%; cut-off level, 0.577). Among the group of patients with TMAO > median and TyG ≤ median, there was a significantly higher incidence of MACEs (p= 0.033). A similar tendency was found in the cohort with hyperlipidemia (p= 0.016) and diabetes mellitus (p= 0.036). Conclusion: This study demonstrated the usefulness of combined measures of the TyG index and TMAO in enhancing risk stratification in STEMI patients with OCT-defined high-risk plaque characteristics. Trial Registration: This study was registered at ClinicalTrials.gov as NCT03593928. [ABSTRACT FROM AUTHOR]

The phase distribution and organic spacer cations play pivotal roles in determining the emission performance and stability of perovskite quantum wells (QWs). Here, we propose a universal molecular regulation strategy to tailor phase distribution and enhance the stability of CsPbBr3 QWs. The capability of sterically hindered ligands with formidable surface binding groups is underscored in directing CsPbBr3 growth and refining phase distribution. With trimethylamine modified boron dipyrromethene (BDP‐TMA) ligand as a representative, the BDP‐TMA driven can precisely control phase distribution and passivate defects of CsPbBr3. Notably, BDP‐TMA acts as a co‐spacer organic entity in obtained BDP‐TMA‐CsPbBr3, facilitating efficient singlet energy transfer and tailoring the luminescence to produce a distinctive bluish‐white emission. The BDP‐TMA‐CsPbBr3 demonstrates significant phase stability under water exposure, light irradiation, and moderate temperature. Interestingly, BDP‐TMA‐CsPbBr3 exhibits the thermally‐induced dynamic fluorescence control at elevated temperatures, which can be achieved feasible for advanced information encryption. This discovery paves the way for the exploration of perovskite QWs in applications like temperature sensing, anti‐counterfeiting, and other advanced optical smart technologies. [ABSTRACT FROM AUTHOR]

Many attempts have been proposed to evaluate the linkage between the oral–gut–liver axis and the mechanisms related to the diseases' establishment. One of them is the oral microbiota translocation into the bloodstream, liver, and gut, promoting a host dysbiosis and triggering the presence of some metabolites such as trimethylamine N-oxide (TMAO), known as a risk marker for cardiovascular disease, and especially the myocardial infarction (MI). In the present pilot study, the involvement of oral dysbiosis related to the presence of TMAO has been considered an independent component of the standard risk factors (SRs) in the development of MI, which has not been previously described in human cohorts. A positive and significant correlation of TMAO levels with Porphyromonas was identified; likewise, the increase of the genus Peptidiphaga in patients without SRs was observed. We determined that the presence of SRs does not influence the TMAO concentration in these patients. This report is the first study where the relationship between oral dysbiosis and TMAO is specified in the Mexican population. Our findings provide information on the possible contribution of the oral pathogens associated with gut dysbiosis in the development of MI, although further analysis should be performed. [ABSTRACT FROM AUTHOR]

Trimethylamine N-oxide (TMAO) has attracted interest because of its association with cardiovascular disease and diabetes, and evidence for the beneficial effects of TMAO is accumulating. This study investigates the role of TMAO in improving exercise performance and elucidates the underlying molecular mechanisms. Using C2C12 cells, we established an oxidative stress model and administered TMAO treatment. Our results indicate that TMAO significantly protects myoblasts from oxidative stress-induced damage by increasing the expression of Nrf2, heme oxygenase-1 (HO-1), NAD(P)H dehydrogenase (NQO1), and catalase (CAT). In particular, suppression of Nrf2 resulted in a loss of the protective effects of TMAO and a significant decrease in the expression levels of Nrf2, HO-1, and NQO1. In addition, we evaluated the effects of TMAO in an exhaustive swimming test in mice. TMAO treatment significantly prolonged swimming endurance, increased glutathione and taurine levels, enhanced glutathione peroxidase activity, and increased the expression of Nrf2 and its downstream antioxidant genes, including HO-1, NQO1, and CAT, in skeletal muscle. These findings underscore the potential of TMAO to counteract exercise-induced oxidative stress. This research provides new insights into the ability of TMAO to alleviate exercise-induced oxidative stress via the Nrf2 signaling pathway, providing a valuable framework for the development of sports nutrition supplements aimed at mitigating oxidative stress. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the changes in the quality of fish (Argyrosomus regius) and shrimp (Penaeus japonicus) cooked with sous-vide. Vacuum-packed fish fillets and shrimps were cooked with the sous-vide method under different temperature-time conditions and stored at 3 °C. Lower volatile bases and trimethylamine were found with cooking sous-vide than in control samples (cooked in an oven). Microbiological analysis results showed that the sous-vide cooking method provides bacterial inhibition in fish and shrimp. The sensory properties of samples cooked with sous-vide were found to be better than those of the traditional method. Sous-vide cooking did not affect the L* value of fish but affected that of shrimp. Sous-vide cooking resulted in higher a* values and lower hardness, gumminess, and chewiness values. As a result, sous-vide cooking increased the shelf life of fish and shrimp, reduced cooking loss, preserved color and texture, and provided microbial safety. [ABSTRACT FROM AUTHOR]

We aimed to analyze the mechanisms underlying spleen-and-stomach-tonifying, yin-fire-purging, and yang-raising decoction derived from the trimethylamine N-oxide (TMAO) metabolic pathway of intestinal microbiota in the treatment of macrovascular lesions caused by type 2 diabetes mellitus (T2DM). Methods: Hartley-guinea pigs were randomly divided into 3 groups—the blank, model, and intervention groups. The T2DM combined with atherosclerosis guinea pig models were established in the model and intervention groups. After successful modeling, spleen-and-stomach-tonifying, yin-fire-purging, and yang-raising decoction were administered intragastrically to the intervention group, while the same volume of normal saline was administered via gavage to the blank and model groups. After 6 weeks of continuous gavage, guinea pigs were sacrificed in all groups, the colon contents were obtained, and the diversity and structural differences of intestinal microbiota were analyzed via bioinformatics. Serum was collected to detect differences in lipids, TMAO, oxidative stress, and inflammation markers between groups. Results: Compared to the blank group, the species diversity of the intestinal microbiota in the model and intervention groups was significantly reduced. Based on the results of Analysis of Similarities and Multiple Response Permutation Procedure, the microbiota structure of the intervention group was closer to that of the blank group. After modeling, the blood lipid levels of guinea pigs increased significantly, and drug intervention significantly reduced the levels of TC, TG, and LDL-C (P < 0.05). TMAO expression was significantly increased after modeling (P < 0.05), while drug intervention reduced TMAO expression (P < 0.05). Compared to the model group, drug intervention significantly increased the concentrations of SOD while decreasing the concentrations of MDA, ICAM-1, VCAM-1, IL-6, and hs-CRP. Conclusion: Spleen-and-stomach-tonifying, yin-fire-purging, and yang-raising decoction can reduce the risk of macrovascular lesions in T2DM, and its mechanism may be associated with its ability to regulate the TMAO metabolic pathway of intestinal microbiota. [ABSTRACT FROM AUTHOR]

Trimethylamine (TMA), a byproduct of gut microbiota metabolism from dietary precursors, is not only the precursor of trimethylamine-N-oxide (TMAO) but may also affect gut health. An in vitro model of intestinal epithelium of Caco-2 cells was used to evaluate the impact of TMA on inflammation, paracellular permeability, epigenetics and mitochondrial functions. The expression levels of pro-inflammatory cytokines (IL-6, IL-1β) increased significantly after 24 h exposure to TMA 1 mM. TMA exposure was associated with an upregulation of SIRT1 (TMA 1 mM, 400 μM, 10 μM) and DNMT1 (TMA 1 mM, 400 µM) genes, while DNMT3A expression decreased (TMA 1 mM). In a cell-free model, TMA (from 0.1 µM to 1 mM) induced a dose-dependent reduction in Sirtuin enzyme activity. In Caco-2 cells, TMA reduced total ATP levels and significantly downregulated ND6 expression (TMA 1 mM). TMA excess (1 mM) reduced intracellular mitochondrial DNA copy numbers and increased the methylation of the light-strand promoter in the D-loop area of mtDNA. Also, TMA (1 mM, 400 µM, 10 µM) increased the permeability of Caco-2 epithelium, as evidenced by the reduced transepithelial electrical resistance values. Based on our preliminary results, TMA excess might promote inflammation in intestinal cells and disturb epigenetic and mitochondrial homeostasis.

Resveratrol (RSV), obtained from dietary sources, has been shown to reduce trimethylamine oxide (TMAO) levels in humans, and much research indicates that TMAO is recognized as a risk factor for cardiovascular disease. Therefore, this study investigated the effects of RSV and RSV-butyrate esters (RBE) on the proliferation of co-cultured bacteria and HepG2 cell lines, respectively, and also investigated the changes in trimethylamine (TMA) and TMOA content in the medium and flavin-containing monooxygenase-3 (FMO3) gene expression. This study revealed that 50 µg/mL of RBE could increase the population percentage of Bifidobacterium longum at a rate of 53%, while the rate was 48% for Clostridium asparagiforme. In contrast, co-cultivation of the two bacterial strains effectively reduced TMA levels from 561 ppm to 449 ppm. In addition, regarding TMA-induced HepG2 cell lines, treatment with 50 μM each of RBE, 3,4′-di-O-butanoylresveratrol (ED2), and 3-O-butanoylresveratrol (ED4) significantly reduced FMO3 gene expression from 2.13 to 0.40–1.40, which would also contribute to the reduction of TMAO content. This study demonstrated the potential of RBE, ED2, and ED4 for regulating TMA metabolism in microbial co-cultures and cell line cultures, which also suggests that the resveratrol derivative might be a daily dietary supplement that will be beneficial for health promotion in the future. [ABSTRACT FROM AUTHOR]

Without early detection and treatment, chronic and excessive alcohol consumption can lead to the development of alcoholic liver disease (ALD). With this in mind, we exploit the recent concept of the liver–gut axis and analyze the serum profile of ALD patients for identification of microbiome-derived metabolites that can be used as diagnostic biomarkers for onset of ALD. 1H-NMR was used to analyze serum metabolites of 38 ALD patients that were grouped according to their Child–Turcotte–Pugh scores (CTP): class A (CTP-A; 19), class B(CTP-B; 10), and class C (CTP-C; 9). A partial least squares-discriminant analysis (PLS-DA) and a variable importance of projection (VIP) score were used to identify significant metabolites. A receiver operating characteristic (ROC) curve and correlation heatmap were used to evaluate the predictability of identified metabolites as ALD biomarkers. Among 42 identified metabolites, 6 were significantly correlated to exacerbation of ALD. As ALD progressed in CTP-C, the levels of trimethylamine N-oxide (TMAO), malate, tyrosine, and 2-hydroxyisovalerate increased, while isobutyrate and isocitrate decreased. Out of six metabolites, elevated levels of TMAO and its precursors (carnitine, betaine, choline) were associated with severity of ALD. This indicates that TMAO can be used as an effective biomarker for the diagnosis of ALD progression. [ABSTRACT FROM AUTHOR]

In this study, the plausible role of trimethylamine N-oxide (TMAO), a microbiota metabolite, was investigated as a link between peripheral inflammation and the inflammation of the central nervous system using different cell lines. TMAO treatment favored the differentiation of adipocytes from preadipocytes (3T3-L1 cell line). In macrophages (RAW 264.7 cell line), which infiltrate adipose tissue in obesity, TMAO increased the expression of pro-inflammatory cytokines. The treatment with 200 μM of TMAO seemed to disrupt the blood–brain barrier as it induced a significant decrease in the expression of occludin in hCMECs. TMAO also increased the expression of pro-inflammatory cytokines in primary neuronal cultures, induced a pro-inflammatory state in primary microglial cultures, and promoted phagocytosis. Data obtained from this project suggest that microbial dysbiosis and increased TMAO secretion could be a key link between peripheral and central inflammation. Thus, TMAO-decreasing compounds may be a promising therapeutic strategy for neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]