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L-Proline (l-Pro) is a non-essential amino acid which, in high concentrations, can cause neurological problems including seizures, although the causative mechanism for this is unclear. Here, we studied the impact of physiological levels of proline on brain energy metabolism and investigated the metabolism of l-Pro itself, using the cortical brain tissue slice and stable isotope labelling from [1-13 C]glucose and [1,2-13 C]acetate detected by NMR spectroscopy and LCMS. l-Pro was actively taken up by the slices and significantly reduced the total metabolic pools of all measured metabolites with glutamine the least affected, while reducing net flux of 13C into glycolytic byproducts (lactate and alanine). Conversely, net flux into Krebs cycle intermediates was increased, suggesting that L-Pro at lower concentrations was driving increased mitochondrial activity in both neurons and glia at the expense of glycolysis and metabolic pool sizes. As there was no evidence of metabolism of [1-13 C] l-Pro in slices under normo-glycemic conditions, the effect of proline on metabolism was not due to displacement of metabolites by added l-Pro. Comparison of the metabolic fingerprint generated by l-Pro in slices metabolizing [3-13 C]pyruvate with that generated by ligands active in the GABAergic system suggested that l-Pro may engender effects similar to that of the inhibitory neurotransmitter and metabolite γ-aminobutyric acid (GABA), in line with previous suggestions that l-Pro may be a GABA mimetic in addition to its role as a modulator of mitochondrial metabolism. [ABSTRACT FROM AUTHOR]

Background Preeclampsia (PE) is a pregnancy-associated hypertension disorder with high morbidity and mortality. Short-chain fatty acids (SCFAs)—molecules produced by gut microbes—have been associated with hypertension, yet their relation to PE remains uncertain. Objectives The aim was to review existing human studies that examined associations of the major SCFAs (acetate, propionate, butyrate) in pregnancy with PE development. Methods Two reviewers independently searched online databases (EMBASE, PubMed, Web of Science, and Cochrane Database of Systematic Reviews) in January 2024 using the following terms: "short-chain fatty acids," "acetic acid," "butyric acid," "propionic acid," and "preeclampsia." The final set of included studies had to report associations of SCFAs with PE, be peer-reviewed, be written in English, and be conducted in humans. Results The abstracts of 907 studies were screened; 43 underwent full-text screening and 11 (1318 total participants, 352 with PE) were included in the final review. All studies used a case-control design. SCFAs were measured in a range of biospecimens (eg, serum, plasma, feces, placentas, and amniotic fluid) that were collected at distinct time points in pregnancy. All 7 studies that investigated butyrate found that it was lower in PE cases than in controls, with 6 of these showing statistical significance (P < .05). Five studies showed that acetate was significantly lower in individuals with PE compared with healthy individuals, while 1 study found that acetate was significantly higher in PE cases. One study reported significantly higher propionate among PE cases vs controls, while 2 studies reported significantly lower propionate levels in PE cases. The nuance in results for acetate and propionate may owe to reasons such as differences in distributions of population characteristics associated with SCFA level and PE or type of PE (early vs late). Conclusion Current epidemiologic evidence, which derives only from case-control studies, suggests that SCFAs, particularly butyrate (protective), in pregnancy are related to the development of PE. Large-cohort studies are warranted to investigate the temporality and potential causality of these associations. [ABSTRACT FROM AUTHOR]

Bone is a dynamic tissue that is constantly remodeled throughout adult life. Recently, it has been shown that bone turnover decreases shortly after food consumption. This process has been linked to the fermentation of non-digestible food ingredients such as inulin by gut microbes, which results in the production of the short-chain fatty acids (SCFAs) acetate, propionate and butyrate. SCFAs exert various metabolic functions, which in part can be explained by activation of G protein-coupled receptors (Gpr) 41 and 43. However, the potential relevance of a SCFA-Gpr41/43 signaling axis for bone metabolism has not been established. The aim of our study is to investigate the role of Gpr41/43 in bone metabolism and osteogenic differentiation of mesenchymal stem cells. For this purpose, we analyzed the skeletal phenotype of wild type controls (WT) and Gpr41/43 double knockout (Gpr41/43 dKO) mice fed either a chow or an inulin-enriched diet. In addition, we isolated bone marrow derived mesenchymal stem cells from WT and Gpr41/43 dKO mice and differentiated them into osteoblasts in the absence or presence of acetate. MicroCT scanning of femoral bones of Gpr41/43 dKO mice revealed a significant increase of trabecular bone volume and trabecular compared to WT controls. Treatment of WT bone marrow-derived osteoblasts with acetate resulted in decreased mineralization and substantial downregulation of bone formation markers such as Phex , Ptgs2 and Col1a1. Notably, this effect was strongly attenuated in differentiated osteoblasts lacking Gpr41/43. Inversely, acetate supplementation resulted in higher levels of adipocyte marker genes including Pparg , Lpl and Adipoq in bone marrow-derived cells from WT mice, an effect blunted in differentiated cells isolated from Gpr41/43 dKO mice. Overall, these data indicate that acetate regulates bone architecture via SCFA-Gpr41/43 signaling by modulating the osteogenic versus adipogenic differentiation of mesenchymal stem cells. [ABSTRACT FROM AUTHOR]

Background: Clinical practice guidelines recommend use of buffered crystalloid solutions in critically ill patients but do not distinguish between solutions based on different buffering anions, that is, acetate‐ versus lactate‐buffered solutions. We therefore surveyed relevant physicians about their preferences and attitudes toward each solution. Methods: We conducted an international online survey of anesthesiologists (within perioperative care) and intensive care unit (ICU) physicians. The survey comprised 13 questions on respondents' attitudes and preferences regarding the use of acetate‐ and/or lactate‐buffered crystalloid solutions, including their opinions on a potential clinical trial comparing these solutions and the clinical importance of such a trial. Results: A total of 1321 respondents participated, with a response rate of 34%, ranging from 14% to 96% across 18 countries. Most surveyed physicians reported using buffered crystalloid solutions "very often" (76%) or "often" (16%). Availability of acetate‐ and lactate‐buffered solutions varied, as 35% of respondents reported having both types available, 35% reported having only acetate‐, and 24% reported having only lactate‐buffered solutions available. Most respondents (87%) would support a randomized trial in adult emergency surgical patients and ICU patients comparing an acetate‐ versus lactate‐buffered crystalloid solution. The median rating of the clinical importance of this question was 5 (interquartile range 4–6) on a scale from 1 to 9. Conclusions: In this international survey, the reported use of buffered crystalloid solutions was high. Availability of the different solutions varied widely. The support for a potential randomized trial was high, with the clinical importance rated important but not critical by most respondents. [ABSTRACT FROM AUTHOR]

Alterations in tricarboxylic acid (TCA) cycle metabolism are associated with hepatic metabolic disorders. Elevated hepatic acetate concentrations, often attributed to high caloric intake, are recognized as a pivotal factor in the etiology of obesity and metabolic syndrome. Therefore, the assessment of acetate breakdown and TCA cycle activity plays a central role in understanding the impact of diet‐induced alterations on liver metabolism. Magnetic resonance‐based deuterium metabolic imaging (DMI) could help to unravel the underlying mechanisms involved in disease development and progression, however, the application of conventional deuterated glucose does not lead to substantial enrichment in hepatic glutamine and glutamate. This study aimed to demonstrate the feasibility of DMI for tracking deuterated acetate breakdown via the TCA cycle in lean and diet‐induced fatty liver (FL) rats using 3D DMI after an intraperitoneal infusion of sodium acetate‐d3 at 9.4T. Localized and nonlocalized liver spectra acquired at 10 time points post‐injection over a 130‐min study revealed similar intrahepatic acetate uptake in both animal groups (AUCFL = 717.9 ± 131.1 mM▯min−1, AUClean = 605.1 ± 119.9 mM▯min−1, p = 0.62). Metabolic breakdown could be observed in both groups with an emerging glutamine/glutamate (Glx) peak as a downstream metabolic product (AUCFL = 113.6 ± 23.8 mM▯min−1, AUClean = 136.7 ± 41.7 mM▯min−1, p = 0.68). This study showed the viability of DMI for tracking substrate flux through the TCA cycle, underscoring its methodological potential for imaging metabolic processes in the body. [ABSTRACT FROM AUTHOR]

Cytokine storm is a hallmark for acute systemic inflammatory disease like sepsis. Intrinsic microbiome-derived short-chain fatty acid (SCFAs) like acetate modulates immune cell function and metabolism has been well studied. However, it remains poorly investigated about the effects and the underlying mechanism of exogenous acetate in acute inflammation like sepsis. Here, we observed that serum acetate accumulates in patients undergoing abdominal gastrointestinal surgery and in septic mice. Short exposure to high-dose exogenous acetate protects mice from sepsis by inhibiting glycolysis in macrophages, both in vivo and in vitro. Hypoxia-inducible factor 1 subunit alpha (HIF-1α) stabilization or overexpression reverses the decreased glycolysis and pro-inflammatory cytokine production in macrophages and abrogates acetate's protective effect in septic mice. Meanwhile, we also found acetyl-CoA synthetase-2, but not GPR41 or GPR43, plays a key role in acetate's immunosuppressive effect. Acetate transiently increases acetyl-coenzyme A production, promoting histone acetylation and decreasing acetyl-transfer to NF-κB p65. These findings suggest that short exposure to mM-level acetate inhibits macrophage immune response linked to HIF-1α-dependent glycolysis. Taken together, we demonstrate short-term exposure of exogenous acetate could regulate inflammatory responses through attenuating HIF-1α-dependent glycolysis. [ABSTRACT FROM AUTHOR]

Interest in citrate-based dialysate (Cit-D) is growing due to its benefits, including anticoagulation and dialysis efficacy. However, research on safety and efficiency of Cit-D in high-volume hemodiafiltration (HDF) via central concentrate delivery system (CCDS) is scarce. This study aimed to investigate the safety and efficacy of Cit-D when switching from acetate-based dialysate (Acet-D) in high-volume HDF via CCDS. This is a retrospective analysis of 28 patients who underwent post-dilution online HDF via CCDS, who switched from Acet-D to Cit-D. The study period was divided into 3 periods for analysis: 12 weeks using Acet-D (AD period), the first 12 weeks using Cit-D (CD-1 period), and the second 12 weeks using Cit-D (CD-2 period). We collected the laboratory, dialysis, and safety parameters in each period from electrical medical records. After switching from Acet-D to Cit-D, heparin dosage decreased by 17%, whereas the incidence of complications did not increase. Kt/VBUN and urea reduction ratio increased by 4.6% and 2.1%, respectively. Pre-dialysis beta2-microglobulin concentration decreased after using Cit-D. The corrected calcium levels decreased in the CD-1 period compared to the AD period, but in CD-2, they subsequently increased to levels similar to those observed during the AD period. Symptomatic hypocalcemia did not occur, and there was no significant difference in the incidence of hyperparathyroidism. Endotoxin levels and the bacterial culture of ultrapure dialysate were unremarkable throughout all periods. These results might suggest that Cit-D could potentially offer advantages over Acet-D, such as reducing the heparin dose and increasing dialysis efficiency, in patients undergoing high-volume HDF using CCDS. [ABSTRACT FROM AUTHOR]

Mixotrophic cultivation of Haematococcus lacustris is one of the most promising strategies to produce natural astaxanthin. During mixotrophic growth, microalgae assimilate and metabolize organic carbon in addition to photosynthetic growth, resulting in increased biomass productivity. Several studies have evaluated the effect of different organic carbon sources on mixotrophic growth in various microalgae species. However, knowledge of detailed growth kinetics as a function of substrate concentration and light intensity is lacking. In this study, the growth kinetics of H. lacustris using four different carbon sources and the effect of light under mixotrophic and photoautotrophic conditions are described. Mixotrophic cultivation showed significant differences in respect to applied substrate and achieved maximum specific growth rates of 0.91 ± 0.13, 0.19 ± 0.05, 0.36 ± 0.05, and 0.23 ± 0.05 day−1, for acetate, methanol, glucose, and glycerol, respectively. Optimal growth at mixotrophic conditions using acetate was 1.8 times higher than the sum of hetero- and photoautotrophic growth. Furthermore, the optimum light intensity was 1.3 times higher for mixotrophic than for autotrophic growth. Thus, mixotrophy increases light intensity tolerance. These results indicate a strong interconnection between carbon metabolism and photosynthetic activity and lay the foundation for more detailed mathematical models describing the mixotrophic growth of H. lacustris. [ABSTRACT FROM AUTHOR]

Background: Emerging literature indicates that the microbiome and its byproducts, such as short-chain fatty acids (SCFAs), play an important role in childhood diseases such as allergies and asthma. Specifically, there is evidence suggesting that SCFAs play a critical role in fetal immunoprogramming during the late saccular phase of fetal lung development. An increase in acetate during the late saccular phase is known to play a critical role in inhibiting histone deacetylases (HDACs), resulting in a cascade of events, including Treg immune regulation, involved in fetal immunoprogramming, and reduction in the asthma phenotype. However, it is not known whether changes in SCFA levels, especially acetate, occurred during the canalicular or early saccular phase among pregnant women whose children did not develop asthma. Methods: In this research, we investigated this question using plasma samples obtained from mothers during the 20th and 28th weeks of pregnancy. Mothers whose children developed asthma were categorized as cases, while those whose children did not were categorized as controls. The specimens were assayed for a panel of SCFAs consisting of acetate, propionate, butyrate, valerate, isobutyrate, and isovalerate. Results: The resulting data indicated no significant differences between the cases and controls, either at week 20 or week 28, in any of the SCFAs measured, despite the vascularization during these phases. Conclusions: We did not find differences in measured SCFAs at week 20 or at week 28. A larger prospective study covering multiple time points is necessary to confirm the findings of this preliminary study. Such a study, together with the published literature regarding later time points, may help discover critical windows during pregnancy when simple manipulation of diet will result in healthier outcomes for infants. [ABSTRACT FROM AUTHOR]

Complete assignments of the 1H NMR chemical shifts for monoterpenes, borneol, and isoborneol, and their derivatives in which the secondary hydroxy group is protected with an acetyl group or a benzoyl group, have been made in CDCl3 and C6D6. Upon the protection of the hydroxy group with the carbonyl functional groups, or acetyl or benzoyl groups, many protons constituting the bicyclic ring exhibited downfield and upfield shifts in the chemical shift values, aiding in the unambiguous assignments of protons and carbons. [ABSTRACT FROM AUTHOR]

The list of standard abbreviations for JDS is available at adsa.org/jds-abbreviations-24. Nonstandard abbreviations are available in the Notes. The objective of our study was to evaluate the effect of altering the dietary supply of acetate, palmitic acid (PA), and cottonseed on the yields of milk components and milk fatty acids (FA) in lactating dairy cows. Thirty-two multiparous Holstein cows (133 ± 57 DIM, 50.5 ± 7.2 kg/d of milk) were used in a 4 × 4 Latin square split plot design with a 2 × 2 factorial arrangement of subplot treatments. Cows were blocked by ECM yield and allocated to a main plot receiving a basal diet (n = 16) with no supplemental PA (low PA) or a basal diet (n = 16) with 1.5% inclusion of a FA supplement containing ∼85% PA (high PA). In each main plot, the following subplots of treatment diets were fed in a Latin square arrangement consisting of 14-d periods: (1) a control diet (CON), (2) the control diet supplemented with 3% sodium acetate (AC), (3) the control diet supplemented with 12% whole cottonseed (CS), and (4) the control diet supplemented with 3% sodium acetate and 12% whole cottonseed (CS+AC). The PA supplement and sodium acetate replaced soyhulls, and whole cottonseed replaced cottonseed hulls and meal. All diets were balanced for 30% NDF, 23% forage NDF, 28% starch, and 17% CP. Sources of FA were classified as de novo (<16 carbons), mixed (16-carbon), and preformed (>16 carbons). The statistical model included the random effect of cow nested within basal diet and fixed effect of period, basal diet, acetate, cottonseed, and their interactions. Three-way interactions among basal diet, acetate, and cottonseed were observed for the yields of milk fat, 3.5% FCM, and the molar yields of de novo FA, mixed FA, and preformed FA. In the low PA diets, AC and CS+AC increased the yields of milk fat and FCM compared with CON and CS, whereas, in the high PA diets, CS+AC increased the yields of milk fat and FCM compared with the other treatments and AC increased milk fat yield compared with CON and CS. Compared with low PA, high PA increased milk fat content, mixed FA yield, and tended to increase C4:0 yield. Diets containing acetate increased DMI and the yields of milk fat, ECM, FCM, de novo FA, mixed FA, and preformed FA compared with diets without acetate. Diets containing cottonseed increased the yields of milk and preformed FA, tended to increase the yields of FCM and protein, and decreased DMI and the yields of de novo FA and mixed FA compared with diets without cottonseed. In summary, in high PA diets, the inclusion of acetate plus cottonseed increased milk fat yield compared with the other treatments. The CON diet in high PA increased milk fat yield to the same extent as AC and CS+AC in low PA suggesting PA is important for initiating milk TG synthesis. Balancing the supply of de novo FA substrates and preformed FA is important for increasing the synthesis of milk fat triglycerides and milk fat production. [ABSTRACT FROM AUTHOR]

Background/Objectives: Allergic contact dermatitis (ACD), an inflammatory skin condition, is commonly treated with topical corticosteroids; however, long-term use of these drugs is associated with various risks, such as skin atrophy and steroid resistance. Triacetin (TA), a triglyceride metabolized to acetate, exerts anti-inflammatory affects by activating AMP-activated protein kinase (AMPK) and suppressing mast cell degranulation. Here, we aimed to assess the immediate and long-term effects of TA on ACD suppression, focusing on AMPK activation, using a 2,4-dinitrofluorobenzene-induced rodent model. Methods: Various concentrations of TA were topically applied to rats with 2,4-dinitrofluorobenzene-induced dermatitis. Ear thickness was measured, and histological analysis was performed to assess the inflammation, mast cell infiltration, and degranulation in the established models. AMPK activation was analyzed via Western blotting, and TA degradation was assessed via gas chromatography-mass spectrometry. Dorsomorphin (an AMPK inhibitor) was used to evaluate the effects of AMPK on ACD. Results: TA significantly inhibited inflammation and mast cell degranulation in a dose-dependent manner, with 0.25 mmol/L showing the most potent effects. It also activated AMPK activation. Notably, AMPK inhibition reversed the effects of TA. Conclusions: Overall, TA exerted immediate and long-term anti-inflammatory effects via AMPK activation and inhibition of mast cell degranulation, showing potential as a non-steroidal therapeutic for ACD.

Although we have learned much about how the brain fuels its functions over the last decades, there remains much still to discover in an organ that is so complex. This article lays out major gaps in our knowledge of interrelationships between brain metabolism and brain function, including biochemical, cellular, and subcellular aspects of functional metabolism and its imaging in adult brain, as well as during development, aging, and disease. The focus is on unknowns in metabolism of major brain substrates and associated transporters, the roles of insulin and of lipid droplets, the emerging role of metabolism in microglia, mysteries about the major brain cofactor and signaling molecule NAD+ , as well as unsolved problems underlying brain metabolism in pathologies such as traumatic brain injury, epilepsy, and metabolic downregulation during hibernation. It describes our current level of understanding of these facets of brain energy metabolism as well as a roadmap for future research.

BACKGROUND: Microcystins (MCs), potent hepatotoxins pose a significant health risk to humans, particularly children, who are more vulnerable due to higher water intake and increased exposure during recreational activities. METHODS: Here, we investigated the role of host microbiome-linked acetate in modulating inflammation caused by early-life exposure to the cyanotoxin Microcystin-LR (MC-LR) in a juvenile mice model. RESULTS: Our study revealed that early-life MC-LR exposure disrupted the gut microbiome, leading to a depletion of key acetate-producing bacteria and decreased luminal acetate concentration. Consequently, the dysbiosis hindered the establishment of a gut homeostatic microenvironment and disrupted gut barrier function. The NOD-like receptor family pyrin domain - containing 3 (NLRP3) inflammasome, a key player in MC-induced hepatoxicity emerged as a central player in this process, with acetate supplementation effectively preventing NLRP3 inflammasome activation, attenuating hepatic inflammation, and decreasing pro-inflammatory cytokine production. To elucidate the mechanism underlying the association between early-life MC-LR exposure and the progression of metabolic dysfunction associated steatotic liver disease (MASLD), we investigated the role of acetate binding to its receptor -G-protein coupled receptor 43 (GPR43) on NLRP3 inflammasome activation. Our results demonstrated that acetate-GPR43 signaling was crucial for decreasing NLRP3 protein levels and inhibiting NLRP3 inflammasome assembly. Further, acetate-induced decrease in NLRP3 protein levels was likely mediated through proteasomal degradation rather than autophagy. Overall, our findings underscore the significance of a healthy gut microbiome and its metabolites, particularly acetate, in the progression of hepatotoxicity induced by early life toxin exposure, crucial for MASLD progression. CONCLUSIONS: This study highlights potential therapeutic targets in gut dysbiosis and NLRP3 inflammasome activation for mitigating toxin-associated inflammatory liver diseases.

Abstract Background Acetate is an important chemical feedstock widely applied in the food, chemical and textile industries. It is now mainly produced from petrochemical materials through chemical processes. Conversion of lignocellulose biomass to acetate by biotechnological pathways is both environmentally beneficial and cost-effective. However, acetate production from carbohydrate in lignocellulose hydrolysate via glycolytic pathways involving pyruvate decarboxylation often suffers from the carbon loss and results in low acetate yield. Results Escherichia coli BL21 (DE3) was confirmed to have high tolerance to acetate in this work. Thus, it was selected from seven laboratory E. coli strains for acetate production from lignocellulose hydrolysate. The byproduct-producing genes frdA, ldhA, and adhE in E. coli BL21 (DE3) were firstly knocked out to decrease the generation of succinate, lactate, and ethanol. Then, the genes pfkA and edd were also deleted and bifunctional phosphoketolase and fructose-1,6-bisphosphatase were overexpressed to construct an EP-bifido pathway in E. coli BL21 (DE3) to increase the generation of acetate from glucose. The obtained strain E. coli 5K/pFF can produce 22.89 g/L acetate from 37.5 g/L glucose with a yield of 0.61 g/g glucose. Finally, the ptsG gene in E. coli 5K/pFF was also deleted to make the engineered strain E. coli 6K/pFF to simultaneously utilize glucose and xylose in lignocellulosic hydrolysates. E. coli 6K/pFF can produce 20.09 g/L acetate from corn stover hydrolysate with a yield of 0.52 g/g sugar. Conclusion The results presented here provide a promising alternative for acetate production with low cost substrate. Besides acetate production, other biotechnological processes might also be developed for other acetyl-CoA derivatives production with lignocellulose hydrolysate through further metabolic engineering of E. coli 6K/pFF.

Abstract This study hypothesized that SCFA, acetate impacts positively on hypothalamic pyroptosis and its related abnormalities in experimentally induced PCOS rat model, possibly through NrF2/HIF1-α modulation. Eight-week-old female Wister rats were divided into groups (n = 5), namely control, PCOS, acetate and PCOS + acetate groups. Induction of PCOS was performed by administering 1 mg/kg body weight of letrozole for 21 days. After PCOS confirmation, the animals were treated with 200 mg/kg of acetate for 6 weeks. Rats with PCOS were characterized with insulin resistance, leptin resistance, increased plasma testosterone as well as degenerated ovarian follicles. There was also a significant increase in hypothalamic triglyceride level, triglyceride-glucose index, inflammatory biomarkers (SDF-1 and NF-kB) and caspase-6 as well as plasma LH and triglyceride. A decrease was observed in plasma adiponectin, GnRH, FSH, and hypothalamic GABA with severe inflammasome expression in PCOS rats. These were accompanied by decreased level of NrF2/HIF1-α, and the alterations were reversed when treated with acetate. Collectively, the present results suggest the therapeutic impact of acetate on hypothalamic pyroptosis and its related comorbidity in PCOS, a beneficial effect that is accompanied by modulation of NrF2/HIF1-α.

Electrocatalytic carbon monoxide reduction (CORR) is effective in achieving renewable synthesis of valuable C2+ species from CO. However, the production of C2+ species is challenged by low activity and selectivity. Here, the surface of the atomically dispersed Cu–Au alloy is functionalized with aromatic heterocycle, thiadiazole derivate (N2SN), to enhance the conversion of CO into C2+ species with acetate as the main product. The N2SN functional groups with electron withdrawing property can alternate the oxidization state of copper, as confirmed by XPS and XAS, thus orienting the CORR pathway to the formation of C2+/acetate. In situ Raman reveals that the N2SN treated sample exhibits stronger signal of *CO intermediate for further dimerization and the C–C–O intermediate relates to acetate formation. Theoretical calculation demonstrates the N2SN molecule doping contributes to lowered energy barrier for C–C coupling, improved activity and selectivity to CORR, and suppressed hydrogen evolution reaction. High Faradaic efficiency (FEC2+, 89%), partial current density (jC2+, 397 mA cm−2), and energy efficiency for C2+ species (EEC2+, 24%) and total current density (jtotal, up to 1000 mA cm−2) are achieved in membrane electrode assembly (MEA), surpassing most of the reported catalysts for total C2+ products. [ABSTRACT FROM AUTHOR]

Background: Acetate is an important chemical feedstock widely applied in the food, chemical and textile industries. It is now mainly produced from petrochemical materials through chemical processes. Conversion of lignocellulose biomass to acetate by biotechnological pathways is both environmentally beneficial and cost-effective. However, acetate production from carbohydrate in lignocellulose hydrolysate via glycolytic pathways involving pyruvate decarboxylation often suffers from the carbon loss and results in low acetate yield. Results: Escherichia coli BL21 (DE3) was confirmed to have high tolerance to acetate in this work. Thus, it was selected from seven laboratory E. coli strains for acetate production from lignocellulose hydrolysate. The byproduct-producing genes frdA, ldhA, and adhE in E. coli BL21 (DE3) were firstly knocked out to decrease the generation of succinate, lactate, and ethanol. Then, the genes pfkA and edd were also deleted and bifunctional phosphoketolase and fructose-1,6-bisphosphatase were overexpressed to construct an EP-bifido pathway in E. coli BL21 (DE3) to increase the generation of acetate from glucose. The obtained strain E. coli 5K/pFF can produce 22.89 g/L acetate from 37.5 g/L glucose with a yield of 0.61 g/g glucose. Finally, the ptsG gene in E. coli 5K/pFF was also deleted to make the engineered strain E. coli 6K/pFF to simultaneously utilize glucose and xylose in lignocellulosic hydrolysates. E. coli 6K/pFF can produce 20.09 g/L acetate from corn stover hydrolysate with a yield of 0.52 g/g sugar. Conclusion: The results presented here provide a promising alternative for acetate production with low cost substrate. Besides acetate production, other biotechnological processes might also be developed for other acetyl-CoA derivatives production with lignocellulose hydrolysate through further metabolic engineering of E. coli 6K/pFF. [ABSTRACT FROM AUTHOR]

The efficient acetate conversion from CO electroreduction is challenging due to the poor selectivity at high reaction rate, which requires the competition with H2 and other C2+ (i. e., ethylene, ethanol, n‐propanol) reduction products. Electrolyte engineering is one of the efficient strategies to regulate the reaction microenvironment. In this work, the adding of sulfite (SO32−) with high nucleophilicity in KOH electrolytes was demonstrated to enable improving the CO‐to‐acetate conversion via generating a S−O chemical bond between SO32− and oxygenated *C2 intermediates (i. e., *CO−CO, *CO−COH) compared with that in pure KOH system on both synthesized Cu(200)‐ and normal commercial Cu(111)‐facets‐exposed metallic Cu catalysts. As a result, the prepared Cu(200)‐facets‐exposed metallic Cu catalyst with surface ions modification showed an superior Faradaic efficiency of 63.6 % at −0.6 A ⋅ cm−2, and extraordinary absolute value of peak partial current density as high as 1.52 A ⋅ cm−2 with adding SO32− in KOH electrolytes, compared to the best reported values in both CO and CO2 electroreduction. Our work suggests an attractive strategy to introduce the oxyanion with high nucleophilicity in electrolytes to regulate the microenvironment for industrial‐current‐density electrosynthesis of acetate from CO electroreduction. [ABSTRACT FROM AUTHOR]

Background: Acetate, a short-chain fatty acid, has gained attention for its contrasting roles, with evidence suggesting it may offer cardiovascular protection but also promote cancer, particularly those involving sex hormones. However, these influences have been scarcely assessed in epidemiological research. Objective: To investigate the relationship between acetate and ischemic heart disease (IHD), diabetes, and cancers related to sex hormones. Methods: Mendelian randomization (MR) was used to assess potential causal effects, selecting genetic variants without linkage disequilibrium (r2 < 0.001) and with genome-wide significance for acetate (p < 5 × 10−8). These variants were applied to large genome-wide association studies (GWAS) for ischemic heart disease (IHD; up to 154,373 cases), diabetes (109,731 cases), and five sex-hormone-related cancers (breast, colorectal, prostate, ovarian, and endometrial cancers, ranging from 8679 to 122,977 cases). We employed various methods for analysis, including penalized inverse variance weighting (pIVW), inverse variance weighting, weighted mode, and weighted median. Results: This study indicates that acetate may be associated with a lower risk of ischemic heart disease (IHD), with an odds ratio (OR) of 0.62 per standard deviation (SD) increase in acetate and a 95% confidence interval (CI) of 0.39 to 0.98. Additionally, acetate was linked to a higher breast cancer risk, with an OR of 1.26 and a 95% CI ranging from 1.08 to 1.46. This association remained robust across multiple sensitivity analyses. Conclusions: Acetate, along with factors that influence its activity, may serve as possible targets for breast cancer treatment and possibly IHD, offering opportunities for new drug development. [ABSTRACT FROM AUTHOR]

Background; Turmeric starch (TS) has gained significant attention due to its potential health benefits. Rich in resistant starch (RS) and higher in phosphorus, TS is anticipated to possess properties of high-phosphorus-type RS. Objectives; To understand the host physiology of TS, this study investigated the dose-dependent effects of TS on colonic fermentation in rats. Methods; Four experimental diets containing different levels of TS (5%, 10%, and 20% w/w) were formulated and fed to male Fischer 344 rats for two weeks and compared with rats fed a 0% TS diet (TS0). Results; Results showed that increasing the dose of TS resulted in reduced body weight gain, lower visceral tissue weight, and increased cecal mucin and IgA levels compared with the TS0 group. Further, fecal dry weight increased dose-dependently parallel to the starch excretion rate. Higher doses of TS resulted in increased short chain fatty acid (SCFA) production, specifically cecal acetate content, as well as in a dose-dependent decrease in the cecal pH level. However, this study did not observe a positive effect of TS on colonic alkaline phosphatase (ALP) activity, and the impact on small intestinal ALP activity remains unclear. Notably, beneficial bacteria such as the family Oscillospiraceae, genus Lachnospiraceae NK4A136 group, and Ruminococcus spp. were found to have been enriched in the TS-fed groups, further supporting the beneficial effects of TS on gut microbiota and SCFA production. Additionally, the genus Mucispirillum, which is known to possess beneficial and opportunistic pathogenic traits under immunocompromised states, was found in the TS-fed groups. Conclusions; According to these results, it is clear that TS served as a prebiotic substrate in rats, with a notable modulation of the microbial composition. [ABSTRACT FROM AUTHOR]

This study investigated the effects of Enterococcus hirae (Eh) derived from Ningxiang pigs on growth performance, diarrhea incidence, and immune responses in ETEC-challenged piglets. The results showed that compared to the CON group, ETEC infection significantly reduced the average daily gain (ADG) and average daily feed intake (ADFI), increased rectal temperature, and resulted in a diarrhea rate of up to 24%. Additionally, ETEC infection significantly increased the spleen index and the expression of inflammatory cytokines in the spleen, serum and intestine, with decreasing serum sIgA and colonic SCFAs of piglets. Compared to the ETEC group, orally Eh significantly increased ADFI in ETEC-infected piglets, reduced the diarrhea rate to 11.53%, reduced the spleen index and the expression of inflammatory cytokines in the spleen, serum and intestine, with decreasing serum sIgA and colonic SCFAs of ETEC-infected piglets. Furthermore, correlation analysis revealed that the levels of SCFAs (particularly acetate) were significantly negatively correlated with the expression levels of inflammatory cytokines in colonic and splenic tissues, suggesting that acetate may be a key metabolite in the anti-inflammatory effects of Eh. These results indicate that Eh can enhance the protection of piglets against ETEC K88 via intestine-acetate-spleen axis, thereby alleviating diarrhea and improving growth performance in piglets. [ABSTRACT FROM AUTHOR]

Carbon capture and utilization (CCU) are technologies sought to reduce the level of CO2 in the atmosphere. Industrial carbon capture is associated with energetic penalty, thus there is an opportunity to research alternatives. In this work, spectroelectrochemistry was used to analyze the electrochemical CO2 reduction (eCO2R) in CO2 saturated monoethanolamine (MEA)‐based capture solutions, in a novel CCU process. The in situ Fourier transform infrared (FTIR) spectroscopy experiments show that at the Bi catalyst, the active species involved in the eCO2R is the dissolved CO2 in solution, and not carbamate. In addition, the products of eCO2R were evaluated under flow, using commercial Bi2O3 NP as catalyst. Formate and acetate were detected, with normalized FE for acetate up to 14.5 %, a remarkable result, considering the catalyst used. Acetate is formed either in the presence of cetrimonium bromide (CTAB) as surfactant or at higher current density (>−100 mA cm−2) and the results enabled the proposition of a pathway for its production. This work sheds light on the complex reaction environment of a capture medium electrolyte and is thus relevant for an improved understanding of the conversion of CO2 into value‐added products and to evaluate the feasibility of a combined CCU approach. [ABSTRACT FROM AUTHOR]

Introduction: Ischemic stroke is a leading cause of morbidity and mortality in older adults. Therefore, in this study, we sought to understand the interplay between the microbiota, gut, and brain in the context of stroke in older adults. Objective: To determine whether gut microbiota from younger individuals promotes recovery through angiogenesis in both elderly stroke patients and aged stroke mice, we explored the changes in gut microbiota and the correlation between short-chain fatty acids (SCFAs) and angiogenesis in the aged stroke population. Then, we altered the gut microbiome in aged mice by transplanting microbiota from younger donors before inducing experimental stroke to explore the mechanism by which gut microbiota-derived SCFAs promote angiogenesis. Methods: Part I: We conducted a single-center, double-blind trial to compare gut microbiota diversity and SCFA levels in fecal samples from older stroke patients with those from younger stroke patients. Additionally, we measured levels of vascular endothelial growth factor (VEGF) and VEGFC levels in plasma to assess their correlation with SCFA levels. Part II: We performed fecal microbiota transplantation (FMT) 3 days before inducing ischemic stroke in aged male mice (16-18) via distal middle cerebral artery occlusion (dMCAO). The FMT was conducted using gut microbiomes from either young donors (2-3 months) or aged donors (16-18 months). Results: In older stroke patients, gut microbiota diversity was significantly reduced compared to that in younger stroke patients. Furthermore, levels of acetate, a bacterially derived SCFA, were lower and positively correlated with angiogenesis markers (VEGF and VEGF-C). In aged stroke mice, transplantation of young microbiota improved stroke outcomes by promoting angiogenesis, which was facilitated by lymphatic ingrowth into the cortex. This protective effect was linked to gut microbiota-derived acetate, which enhanced lymphangiogenesis by replenishing acetyl coenzyme A. Conclusions: (a) Gut microbiota-derived acetate promotes angiogenesis post-stroke and (b) lymphatic ingrowth into the cerebral cortex was observed in post-dMCAO mice. These findings suggest that selectively promoting SCFA-producing bacteria, particularly acetate-producers, could be a promising therapeutic strategy to reduce functional impairments in older stroke subjects. [ABSTRACT FROM AUTHOR]

Bone is a dynamic tissue that is constantly remodeled throughout adult life. Recently, it has been shown that bone turnover decreases shortly after food consumption. This process has been linked to the fermentation of non-digestible food ingredients such as inulin by gut microbes, which results in the production of the short-chain fatty acids (SCFAs) acetate, propionate and butyrate. SCFAs exert various metabolic functions, which in part can be explained by activation of G protein-coupled receptors (Gpr) 41 and 43. However, the potential relevance of a SCFA-Gpr41/43 signaling axis for bone metabolism has not been established. The aim of our study is to investigate the role of Gpr41/43 in bone metabolism and osteogenic differentiation of mesenchymal stem cells. For this purpose, we analyzed the skeletal phenotype of wild type controls (WT) and Gpr41/43 double knockout (Gpr41/43 dKO) mice fed either a chow or an inulin-enriched diet. In addition, we isolated bone marrow derived mesenchymal stem cells from WT and Gpr41/43 dKO mice and differentiated them into osteoblasts in the absence or presence of acetate. MicroCT scanning of femoral bones of Gpr41/43 dKO mice revealed a significant increase of trabecular bone volume and trabecular compared to WT controls. Treatment of WT bone marrow-derived osteoblasts with acetate resulted in decreased mineralization and substantial downregulation of bone formation markers such as Phex, Ptgs2 and Col1a1. Notably, this effect was strongly attenuated in differentiated osteoblasts lacking Gpr41/43. Inversely, acetate supplementation resulted in higher levels of adipocyte marker genes including Pparg, Lpl and Adipoq in bone marrow-derived cells from WT mice, an effect blunted in differentiated cells isolated from Gpr41/43 dKO mice. Overall, these data indicate that acetate regulates bone architecture via SCFA-Gpr41/43 signaling by modulating the osteogenic versus adipogenic differentiation of mesenchymal stem cells. [ABSTRACT FROM AUTHOR]

The bioconversion of agricultural and industrial wastes is considered a green and sustainable alternative method for producing high-value biochemicals. As a major catalytic product of greenhouse gases and a by-product in the fermentation and lignocellulose processing industries, acetate is a promising bioconversion raw material. In this work, endogenous and heterologous enzymes were manipulated in Yarrowia lipolytica to achieve the conversion of acetate to high-value citric acid and itaconic acid, respectively. After the combinational expression of the key enzymes in the acetate metabolic pathway, the citric acid synthesis pathway, and the mitochondrial transport system, acetate could be efficiently converted to citric acid. Coupled with the down-regulation of fatty acid synthase expression in the competitive pathway, more acetyl-CoA flowed into the synthesis of citric acid, and the titer reached 15.11 g/L with a productivity of 0.51 g/g acetate by the engineered Y. lipolytica, which is comparable to the results using glucose as the substrate. On this basis, the heterologous cis-aconitate decarboxylase from Aspergillus terreus was introduced into the engineered Y. lipolytica to achieve the catalytic synthesis of itaconic acid from acetate. Combined with investigating the effects of multiple enzymes in the synthesis pathway, the titer of itaconic acid reached 1.87 g/L with a yield of 0.43 g/g DCW by the final engineered strain, which is the highest reported titer of itaconic acid derived from acetate by engineered microbes in shake flasks. It is demonstrated that acetate has the potential to replace traditional starch-based raw materials for the synthesis of high-value organic acids and our work lays a foundation for the rational utilization of industrial wastes and the catalytic products of greenhouse gases. [ABSTRACT FROM AUTHOR]