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Cipaglucosidase alfa plus miglustat (cipa + mig) is a novel, two-component therapy for Pompe disease. We report data from the Phase I/II ATB200-02 study for up to 48 months of treatment. Four adult cohorts, including one non-ambulatory ERT-experienced (n = 6) and three ambulatory cohorts, (two enzyme replacement therapy [ERT]-experienced cohorts [2-6 years (n = 11) and ≥ 7 years (n = 6)]), one ERT-naïve cohort (n = 6), received 20 mg/kg intravenous-infused cipa plus 260 mg oral mig biweekly. Change from baseline (CFBL) for multiple efficacy endpoints at 12, 24, 36, and 48 months, pharmacodynamics, pharmacokinetics, safety, and immunogenicity data were assessed. Six-minute walking distance (% predicted) improved at 12, 24, 36, and 48 months: pooled ambulatory ERT-experienced cohorts, mean(± standard deviation [SD]) CFBL: 6.1(± 7.84), n = 16; 5.4(± 10.56), n = 13; 3.4(± 14.66), n = 12; 5.9(± 17.36), n = 9, respectively; ERT-naïve cohort: 10.7(± 3.93), n = 6; 11.0(± 5.06), n = 6; 9.0(± 7.98), n = 5; 11.7(± 7.69), n = 4, respectively. Percent predicted forced vital capacity was generally stable in ERT-experienced cohorts, mean(± SD) CFBL - 1.2(± 5.95), n = 16; 1.0(± 7.96), n = 13; - 0.3(± 6.68), n = 10; 1.0(± 6.42), n = 6, respectively, and improved in the ERT-naïve cohort: 3.2(± 8.42), n = 6; 4.7(± 5.09), n = 6; 6.2(± 3.35), n = 5; 8.3(± 4.50), n = 4, respectively. Over 48 months, CK and Hex4 biomarkers improved in ambulatory cohorts. Overall, cipa + mig was well tolerated with a safety profile like alglucosidase alfa. ATB200-02 results show the potential benefits of cipa + mig as a long-term treatment option for Pompe disease. Trial registration number: NCT02675465 January 26, 2016.

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]

In the context of the FEEDAP opinion on the safety and efficacy of a feed additive consisting of chromium propionate (KemTRACE™ Chromium) of 18 March 2021, the EU Reference Laboratory for feed additives (EURL) was not in a position to recommend the method proposed by the applicant for the official control of added organic chromium content in premixtures and feedingstuffs. The applicant subsequently proposed a new method of analyses, incorporating a tracer in the composition of a premix, which has been evaluated by EURL and recommended as an official method for the quantification of the organic chromium content in premixtures and feeding-stuffs. In view of the above, the Commission asked EFSA to issue a new opinion on the safety and efficacy of chromium proprionate (KemTRACE™ Chromium) as feed additive for all growing poultry species including the newly submitted information by the applicant that involves the use of the microtracer. The present opinion is limited to the assessment of the new information submitted by the applicant in support of safety of the proposed use of the microtracer in the composition of the premix. The FEEDAP Panel concluded that the use of the microtracer in the premixture, at the proposed level of use, does not present a risk for the target species and the consumer. The microtracer should be considered a dermal and respiratory sensitiser. Therefore, any exposure of users to the microtracer via skin or the respiratory tract is considered a risk. The use of the microtracer at proposed conditions of use is safe for the terrestrial environmental compartment, but no conclusion can be made for the groundwater. The addition of the microtracer in the premix/feedingstuffs is not expected to have any impact on the efficacy of the additive, and therefore, the previous conclusion on the efficacy is still valid. [ABSTRACT FROM AUTHOR]

Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the safety and efficacy of chromium propionate as zootechnical feed additive for all growing poultry species. The safety and efficacy of chromium propionate has been assessed previously in 2021 by the Panel and it was concluded that the additive is considered safe for chickens for fattening and chickens reared for laying/breeding at the proposed use level 0.2--0.4 mg Cr/kg complete feed, but the conclusion was not extrapolated to other growing species. During that assessment, the EU Reference Laboratory for feed additives (EURL) was not in a position to recommend the method for official control for the quantification of the organic chromium content in premixtures and feedingstuffs. The applicant subsequently proposed a new method of analyses, incorporating a tracer in the composition of a premixture, which has been evaluated by EURL and recommended as official method for the quantification of the organic chromium content in premixtures and feedingstuffs. The safety of the use of the microtracer has been assessed in 2024. The Panel considered that the use of the microtracer as proposed in the conditions of use would not introduce safety concerns for the target animals, the consumers and terrestrial environmental compartment, but no conclusion could be made for the groundwater. The microtracer should be considered a dermal and respiratory sensitiser. In the current assessment, the FEEDAP Panel concluded that the additive is safe for turkeys for fattening at the maximum proposed supplementation level of 0.4 mg Cr/kg feed, but a margin of safety cannot be established. This conclusion can be extended to turkeys reared for reproduction, but cannot be extrapolated to other growing poultry species. The use of the additive according to the proposed conditions of use causes no concern for consumer safety. The conclusions made previously for user safety remain the same: the additive does not present a risk by inhalation, the additive is irritant to the eyes, not irritant to the skin and is not a skin sensitiser. The use of the additive is considered safe for the environment. The previous conclusion on efficacy remains valid. [ABSTRACT FROM AUTHOR]

BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) is a common but poorly understood form of heart failure, characterized by impaired diastolic function. It is highly heterogeneous with multiple comorbidities, including obesity and diabetes, making human studies difficult. METHODS: Metabolomic analyses in a mouse model of HFpEF showed that levels of indole-3-propionic acid (IPA), a metabolite produced by gut bacteria from tryptophan, were reduced in the plasma and heart tissue of HFpEF mice as compared with controls. We then examined the role of IPA in mouse models of HFpEF as well as 2 human HFpEF cohorts. RESULTS: The protective role and therapeutic effects of IPA were confirmed in mouse models of HFpEF using IPA dietary supplementation. IPA attenuated diastolic dysfunction, metabolic remodeling, oxidative stress, inflammation, gut microbiota dysbiosis, and intestinal epithelial barrier damage. In the heart, IPA suppressed the expression of NNMT (nicotinamide N-methyl transferase), restored nicotinamide, NAD+/NADH, and SIRT3 (sirtuin 3) levels. IPA mediates the protective effects on diastolic dysfunction, at least in part, by promoting the expression of SIRT3. SIRT3 regulation was mediated by IPA binding to the aryl hydrocarbon receptor, as Sirt3 knockdown diminished the effects of IPA on diastolic dysfunction in vivo. The role of the nicotinamide adenine dinucleotide circuit in HFpEF was further confirmed by nicotinamide supplementation, Nnmt knockdown, and Nnmt overexpression in vivo. IPA levels were significantly reduced in patients with HFpEF in 2 independent human cohorts, consistent with a protective function in humans, as well as mice. CONCLUSIONS: Our findings reveal that IPA protects against diastolic dysfunction in HFpEF by enhancing the nicotinamide adenine dinucleotide salvage pathway, suggesting the possibility of therapeutic management by either altering the gut microbiome composition or supplementing the diet with IPA.

Background: Accumulating evidence suggested that Alzheimer's disease (AD) was associated with altered gut microbiota. However, the relationships between gut microbiota and specific cognitive domains of AD patients have yet been fully elucidated. The aim of this study was to explore microbial signatures associated with global cognition and specific cognitive domains in AD patients and to determine their predictive value as biomarkers. Methods: A total of 64 subjects (18 mild AD, 23 severe AD and 23 healthy control) were recruited in the study. 16 s rDNA sequencing was performed for the gut bacteria composition, followed by liquid chromatography electrospray ionization tandem mass spectrometry (LC/MS/MS) analysis of short-chain fatty acids (SCFAs). The global cognition, specific cognitive domains (abstraction, orientation, attention, language, etc.) and severity of cognitive impairment, were evaluated by Montreal Cognitive Assessment (MoCA) scores. We further identified characteristic bacteria and SCFAs, and receiver operating characteristic (ROC) curve was used to determine the predictive value. Results: Our results showed that the microbiota dysbiosis index was significantly higher in the severe and mild AD patients compared to the healthy control (HC). Linear discriminant analysis (LDA) showed that 12 families and 17 genera were identified as key microbiota among three groups. The abundance of Butyricicoccus was positively associated with abstraction, and the abundance of Lachnospiraceae_UCG-004 was positively associated with attention, language, orientation in AD patients. Moreover, the levels of isobutyric acid and isovaleric acid were both significantly negatively correlated with abstraction, and level of propanoic acid was significantly positively associated with the attention. In addition, ROC models based on the characteristic bacteria Lactobacillus , Butyricicoccus and Lachnospiraceae_UCG-004 could effectively distinguished between low and high orientation in AD patients (area under curve is 0.891), and Butyricicoccus and Agathobacter or the combination of SCFAs could distinguish abstraction in AD patients (area under curve is 0.797 and 0.839 respectively). Conclusion: These findings revealed the signatures gut bacteria and metabolite SCFAs of AD patients and demonstrated the correlations between theses characteristic bacteria and SCFAs and specific cognitive domains, highlighting their potential value in early detection, monitoring, and intervention strategies for AD patients. [ABSTRACT FROM AUTHOR]

Ethyl propionate can be produced from CO, C2H4, and CH3CH2OH as raw materials by ethylene hydroesterification in one step. In this paper, a solvent‐free composite catalytic system (Ru/CeO2‐NaI‐NaOH) is developed to catalyze the hydroesterification of C2H4, CO, and C2H5OH. The formation and inhibition mechanisms of 3‐pentanone and acetal are studied, and the pathway for the generation of ethyl propionate has also been analyzed. The factors that influence the performance of catalytic system were researched, such as catalyst reduction temperature, the addition of Ru/CeO2, reaction temperature, reaction time, the partial pressure of CO, and so forth. In Ru/CeO2‐NaOH‐NaI heterogeneous catalytic system, at the experiment conditions of 3 MPa and 180 °C, the C2H4 conversion and the ethyl propionate selectivity are 66.7% and 92.0%, respectively after 4 h reaction. This work presents a strategy for the production of propionate by ethylene hydroesterification, catalyzed by a heterogeneous catalytic system. [ABSTRACT FROM AUTHOR]

Highlights: What are the main findings? For the first time, this study demonstrates a shift in DIET-related genes (pilA and hgtR) alongside the established mcrA/16SrRNA ratio as a key indicator of OLR stress. Methane production halted after OLR shock, correlating with significant reduction in the mcrA/16SrRNA ratio, and pilA (1.43-log) and hgtR (1.34-log) gene abundances. mcrA and pilA are robust indicators of reactor performance under both stable and disturbed states. Partial recovery of pilA and hgtR gene abundance to the near-steady-state level was observed in the control reactor. Propionate, a critical intermediate in anaerobic digestion, and its syntrophic removal, is sensitive to stress. To our knowledge, this study investigates for the first time the response of a metabolic gene panel to organic loading rate (OLR) stress in propionate-degrading methanogenic consortia in lab-scale upflow anaerobic sludge blanket (UASB) reactors. The experimental phases included stabilisation (1.4–2.8 g COD/L/day), electroactive enrichment, OLR shock (6 g COD/L/day), and early recovery. Quantitative PCR was used to assess the abundance of key functional genes (16SrRNA, mcrA, pilA, and hgtR). During stabilisation, ~200 mLCH₄/h was produced, the mcrA/16SrRNA ratio was 0.78–2.64, and pilA and hgtR abundances were 1.29–2.27 × 105 and 2.12–4.37 × 104 copies/gVS. Following the OLR shock, methane production ceased entirely, accompanied by a sharp decline in the mcrA/16S ratio (0.08–0.24) and significant reductions in pilA (1.43-log) and hgtR (1.34-log) abundance. Partial recovery of pilA and hgtR abundance (1.19 × 105 and 8.57 × 104) was observed in the control reactor after the early recovery phase. The results highlight the utility of mcrA, 16SrRNA, pilA, and associated ratios, as reliable indicators of OLR stress in lab-scale UASB reactors. This study advances the understanding of molecular stress responses in propionate-degrading methanogenic consortia, focusing on direct interspecies electron transfer in process stability and recovery. [ABSTRACT FROM AUTHOR]

We have developed a highly efficient, ligand‐free Suzuki–Miyaura cross‐coupling protocol employing our lab‐prepared air and moisture‐stable Pd‐PEPPSI catalysts. The reaction of ethyl 2‐{4‐[(6‐chloroquinoxalin‐2‐yl)oxy]phenoxy}propionate (Assure) with various boronic acids afforded both traditional and decarbonylative coupling products in high yields. The catalyst's steric influence was assessed computationally using %Vbur calculations. The decarbonylative coupling pathway proved more efficient than the traditional Suzuki–Miyaura coupling under these conditions. Additionally, regioselectivity studies have been conducted on a variety of Assure analogues. This method excels in efficiency, requiring minimal catalyst, moderate temperatures, and rapid reaction completion. [ABSTRACT FROM AUTHOR]

(1) Background: Odd-chain fatty acids (OCFAs) have garnered attention for their potential health benefits and unique roles in various biochemical pathways. Yarrowia lipolytica, a versatile yeast species, is increasingly studied for its capability to produce OCFAs under controlled genetic and environmental conditions. However, optimizing the synthesis of specific OCFAs, such as cis-9-heptadecenoic acid (C17:1), remains a challenge. (2) Methods: The gene coding for the Δ9 fatty acid desaturase, YlOLE1, and the gene coding the diacylglycerol O-acyltransferase 2, YlDGA2, were overexpressed in Y. lipolytica. With the engineered strain, the main goal was to fine-tune the production of OCFA-enriched lipids by optimizing the concentrations of sodium propionate and sodium acetate used as precursors for synthesizing odd- and even-chain fatty acids, respectively. (3) Results: In the strain overexpressing only YlDGA2, no significant changes in fatty acid composition or lipid content were observed compared to the control strain. However, in the strain overexpressing both genes, while no significant changes in lipid content were noted, a significant increase was observed in OCFA content. The optimal conditions for maximizing the cell density and the C17:1 content in lipids were found to be 2.23 g/L of sodium propionate and 17.48 g/L of sodium acetate. These conditions resulted in a cell density (optical density at 600 nm) of 19.5 ± 0.46 and a C17:1 content of 45.56% ± 1.29 in the culture medium after 168 h of fermentation. (4) Conclusions: By overexpressing the YlOLE1 gene and optimizing the concentrations of fatty acid precursors, it was possible to increase the content of OCFAs, mainly C17:1, in lipids synthesized by Y. lipolytica. [ABSTRACT FROM AUTHOR]

Propionate is one of the main short chain fatty acids in the gut. Previously, we found that propionate significantly down‐regulated the expression of NleH. NleH is a virulence effector secreted by Citrobacter rodentium (C. rodentium, C.r.) and is essential for its intestinal colonisation and infection. Therefore, this study intends to explore the effect and mechanism of propionate on C.r. infection by regulating the expression of NleH. Wild‐type C.r. and its NleH mutant (C.r.△NleH), E.coli and its NleH1 mutant (E.coli△NleH1) were co‐cultured with propionate separately, changes in strain growth and invasion adhesion were detected. Meanwhile, C57BL/6J mice were infected with C.r. and C.r.△NleH to establish animal model, and propionate intervention was given. Through detecting the invasive and infectious ability of strains in mice and the changes related to colon inflammation, to analyse the effect of propionate on C.r. infection by regulating NleH expression. The results showed that propionate can reduce the adhesion of C.r. and intestinal damage by down‐regulating NleH expression, meanwhile changes of microbial functional metabolism enhance the resistance to C.r. infection in mice. [ABSTRACT FROM AUTHOR]

Ammonium propionate is authorised as a liquid preparation of ≥ 19% ammonium propionate, ≤ 80% propionic acid and ≤ 30% water. The applicant requested for the renewal of the authorisation of ammonium propionate when used as a feed additive for all terrestrial animal species. The applicant has provided evidence that the additive in the market complies with the conditions of the authorisation. The Panel on Additives and Products or Substances used in Animal Feed (FEEDAP Panel) confirms that the use of ammonium propionate under the current authorised conditions of use is safe for the target species, the consumers and the environment. Concerning the user safety, the additive is corrosive to skin and eyes. Any exposure is considered a risk. There is no need for assessing the efficacy of the additive in the context of the renewal of the authorisation. [ABSTRACT FROM AUTHOR]

Objectives Xylopia aethiopica (XAE), commonly known as African pepper or Ethiopian pepper, is a plant native to West Africa and known for its aromatic and medicinal properties. It was used to investigate the antioxidative, antihepatotoxic, and antinephrotoxic potentials of XAE in benign prostatic hyperplasia (BPH) in Wister albino rats. Methods The proximate, and vitamin composition, oxidative stress indicators, and indices of kidney and hepatic functions were performed by standard methods. Results The proximate composition of the XAE leaf showed varied concentrations of Mg, Ca, Na, Zn, Se, and Cl, as well as vitamins A, E, B3, D, C, K, B2, and Bi. The activities of catalase glutathione, superoxide dismutase, malondialdehyde levels, K, Na, Cl − , urea, uric acid, and creatinine in the kidney were increased in testosterone propionate (Tp)-induced BPH compared with the control groups. Total protein levels significantly decreased in Tp-induced BPH compared with XAE-treated groups increased on XAE treatment. The aspartate transaminase, alanine aminotransferase, and alkaline phosphatase activities were not significantly different in Tp-induced BPH, XAE, and normal controls. Conclusion The study revealed that XAE can be used in the management of oxidative stress and hepatorenal damage in BPH condition. [ABSTRACT FROM AUTHOR]

BACKGROUND: Adipocytes are crucial regulators of cardiovascular health. However, not much is known about gene expression profiles of adipocytes residing in nonfat cardiovascular tissues, their genetic regulation, and contribution to coronary artery disease. Here, we investigated whether and how the gene expression profiles of adipocytes in the subcutaneous adipose tissue differ from adipocytes residing in the heart. METHODS: We used single-nucleus RNA-sequencing data sets of subcutaneous adipose tissue and heart and performed in-depth analysis of tissue-resident adipocytes and their cell-cell interactions. RESULTS: We first discovered tissue-specific features of tissue-resident adipocytes, identified functional pathways involved in their tissue specificity, and found genes with cell type-specific expression enrichment in tissue-resident adipocytes. By following up these results, we discovered the propanoate metabolism pathway as a novel distinct characteristic of the heart-resident adipocytes and found a significant enrichment of coronary artery disease genome-wide association study risk variants among the right atrium-specific adipocyte marker genes. Our cell-cell communication analysis identified 22 specific heart adipocyte-associated ligand-receptor pairs and signaling pathways, including THBS (thrombospondin) and EPHA (ephrin type-A), further supporting the distinct tissue-resident role of heart adipocytes. Our results also suggest chamber-level coordination of heart adipocyte expression profiles as we observed a consistently larger number of adipocyte-associated ligand-receptor interactions and functional pathways in the atriums than ventricles. CONCLUSIONS: Overall, we introduce a new function and genetic link to coronary artery disease for the previously unexplored heart-resident adipocytes.

Propionate is a microbial metabolite formed in the gastrointestinal tract, and it affects host physiology as a source of energy and signaling molecule. Despite the importance of propionate, the biochemical pathways responsible for its formation are not clear in all microbes. For the succinate pathway used during fermentation, a key enzyme appears to be missing-one that oxidizes ferredoxin and reduces NAD. Here we show that Rnf [ferredoxin-NAD+ oxidoreductase (Na+-transporting)] is this key enzyme in two abundant bacteria of the rumen (Prevotella brevis and Prevotella ruminicola). We found these bacteria form propionate, succinate, and acetate with the classic succinate pathway. Without ferredoxin:NAD+ oxidoreductase, redox cofactors would be unbalanced; it would produce almost equal excess amounts of reduced ferredoxin and oxidized NAD. By combining growth experiments, genomics, proteomics, and enzyme assays, we point to the possibility that these bacteria solve this problem by oxidizing ferredoxin and reducing NAD with Rnf [ferredoxin-NAD+ oxidoreductase (Na+-transporting)]. Genomic and phenotypic data suggest many bacteria may use Rnf similarly. This work shows the ferredoxin:NAD+ oxidoreductase activity of Rnf is important to propionate formation in Prevotella species and other bacteria from the environment, and it provides fundamental knowledge for manipulating fermentative propionate production.

ObjectivesNonalcoholic fatty liver disease is the most common chronic liver disease in children. Elafibranor, a dual peroxisome proliferator-activated receptor α/δ agonist, has been proposed as a treatment for nonalcoholic steatohepatitis (NASH). The aims were to (1) describe pharmacokinetics (PK), safety, and tolerability of oral elafibranor at 2 doses (80 and 120 mg) in children 8-17 years and (2) assess changes in aminotransferases.MethodsChildren with NASH were randomized to open-label elafibranor 80 mg or 120 mg daily for 12 weeks. The intent-to-treat analysis included all participants who received at least 1 dose. Standard descriptive statistics and PK analyses were performed.ResultsTen males [mean 15.1 years, standard deviation (SD) 2.2] with NASH were randomized to 80 mg (n = 5) or 120 mg (n = 5). Baseline mean alanine aminotransferase (ALT) was 82 U/L (SD 13) and 87 U/L (SD 20) for 80 mg and 120 mg groups, respectively. Elafibranor was rapidly absorbed and well tolerated. Elafibranor plasma exposure increased between the 80 mg and 120 mg dose with a 1.9- and 1.3-fold increase in median Cmax and AUC 0-24 , respectively. End of treatment mean ALT was 52 U/L (SD 20) for the 120 mg group, with a relative mean ALT change from baseline of -37.4% (SD 23.8%) at 12 weeks.ConclusionsOnce daily dosing of elafibranor was well tolerated in children with NASH. There was a 37.4% relative reduction from mean baseline ALT in the 120 mg group. Decreasing ALT may be associated with improvement in liver histology, thus could be considered a surrogate for histology in early phase trials. These results may support further exploration of elafibranor in children with NASH.

Corynebacterium glutamicum is a promising host for production of valuable polyketides. Propionate addition, a strategy known to increase polyketide production by increasing intracellular methylmalonyl-CoA availability, causes growth inhibition in C. glutamicum. The mechanism of this inhibition was unclear before our work. Here we provide evidence that accumulation of propionyl-CoA and methylmalonyl-CoA induces growth inhibition in C. glutamicum. We then show that growth inhibition can be relieved by introducing methylmalonyl-CoA-dependent polyketide synthases. With germicidin as an example, we used adaptive laboratory evolution to leverage the fitness advantage of polyketide production in the presence of propionate to evolve improved germicidin production. Whole-genome sequencing revealed mutations in germicidin synthase, which improved germicidin titer, as well as mutations in citrate synthase, which effectively evolved the native glyoxylate pathway to a new methylcitrate pathway. Together, our results show that C. glutamicum is a capable host for polyketide production and we can take advantage of propionate growth inhibition to drive titers higher using laboratory evolution or to screen for production of polyketides.

Non‐directed regioselective activation of bis(boronic esters), followed by functionalization, is reported. A bulky activator is shown to selectively activate the less hindered boronic ester enabling it to undergo stereospecific cross‐coupling to a variety of electrophiles. This steric‐based regioselectivity provides a simple and efficient method to prepare highly functionalized, enantiomerically enriched products starting from simple alkenes. [ABSTRACT FROM AUTHOR]

Alkoxycarbonylation reactions are common in the chemical industry, yet process sustainability is limited by the inefficient utilization of CO. In this study, we address this issue and demonstrate that significant improvements can be achieved by adopting a heterogeneously catalyzed process, using a Ru/NbOx catalyst. The Ru/NbOx catalyst enables the direct synthesis of methyl propionate, a key industrial commodity, with over 98% selectivity from CO, ethylene and methanol, without any ligands or acid/base promoters. Under ambient CO pressure, a high CO utilization efficiency (336 mmolestermolCO−1h−1) is achieved. Mechanistic investigations reveal that CO undergoes a methoxycarbonyl (COOCH3) intermediate pathway, attacking the terminal carbon atom of alkene and yielding linear esters. The origins of prevailing linear regioselectivity in esters are revealed. The infrared spectroscopic feature of the key COOCH3 species is observed at 1750 cm−1 (C=O vibration) both experimentally and computationally. The broad substrate applicability of Ru/NbOx catalyst for ester production is demonstrated. This process offers a sustainable and efficient approach with high CO utilization and atom economy for the synthesis of esters. Alkoxycarbonylation reactions are widely used in the chemical industry, but their sustainability is often hindered by inefficient CO utilization. Here, the authors tackle the challenge by developing a sustainable and efficient carbonylation process for producing methyl propionate, achieving high CO utilization and regioselectivity. [ABSTRACT FROM AUTHOR]

Coccomyxa sp. KJ is a unicellular green microalga that accumulates abundant lipids when cultured under nitrogen-deficient conditions (KJ1) and high nitrogen levels when cultured under nitrogen-sufficient conditions (KJ2). Considering the different characteristics between KJ1 and KJ2, they are expected to have different effects on rumen fermentation. This study aimed to determine the effects of KJ1 and KJ2 on in vitro ruminal fermentation, digestibility, CH4 production, and the ruminal microbiome as corn silage substrate condition. Five treatments were evaluated: substrate only (CON) and CON + 0.5% dry matter (DM) KJ1 (KJ1_L), 1.0% DM KJ1 (KJ1_H), 0.5% DM KJ2 (KJ2_L), and 1.0% DM KJ2 (KJ2_H). DM degradability-adjusted CH4 production was inhibited by 48.4 and 40.8% in KJ2_L and KJ2_H, respectively, compared with CON. The proportion of propionate was higher in the KJ1 treatments than the CON treatment and showed further increases in the KJ2 treatments. The abundances of Megasphaera, Succiniclasticum, Selenomonas, and Ruminobacter, which are related to propionate production, were higher in KJ2_H than in CON. The results suggested that the rumen microbiome was modified by the addition of 0.5–1.0% DM KJ1 and KJ2, resulting in increased propionate and reduced CH4 production. In particular, the KJ2 treatments inhibited ruminal CH4 production more than the KJ1 treatments. These findings provide important information for inhibiting ruminal CH4 emissions, which is essential for increasing animal productivity and sustaining livestock production under future population growth. [ABSTRACT FROM AUTHOR]

Sodium propionate is authorised containing at least 98.5% of sodium propionate. The applicants requested for the renewal of the authorisation of sodium propionate when used as a feed additive for all terrestrial animal species. The applicant has provided evidence that the additive in the market complies with the conditions of the authorisation. The Panel on Additives and Products or Substances used in Animal Feed (FEEDAP Panel) confirms that the use of sodium propionate under the current authorised conditions of use is safe for the target species, the consumers and the environment. Considering the user safety, the additive is corrosive to skin, eyes and respiratory tract, but is not a skin sensitiser. There is no need for assessing the efficacy of the additive in the context of the renewal of the authorisation. [ABSTRACT FROM AUTHOR]

Waste glycerol is produced in excess by several industries, such as during biodiesel production. In this work, the metabolic versatility of anaerobic sludge was explored towards waste glycerol valorization. By applying different environmental (methanogenic and sulfate-reducing) conditions, three distinct microbial cultures were obtained from the same inoculum (anaerobic granular sludge), with high microbial specialization, within three different phyla (Thermodesulfobacteriota, Euryarchaeota and Pseudomonadota). The cultures are capable of glycerol conversion through different pathways: (i) glycerol conversion to methane by a bacterium closely related to Solidesulfovibrio alcoholivorans (99.8% 16S rRNA gene identity), in syntrophic relationship with Methanofollis liminatans (98.8% identity), (ii) fermentation to propionate by Propionivibrio pelophilus strain asp66 (98.6% identity), with a propionate yield of 0.88 mmol mmol−1 (0.71 mg mg−1) and a propionate purity of 80–97% and (iii) acetate production coupled to sulfate reduction by Desulfolutivibrio sulfoxidireducens (98.3% identity). In conclusion, starting from the same inoculum, we could drive the metabolic and functional potential of the microbiota towards the formation of several valuable products that can be used in industrial applications or as energy carriers. Key points: Versatility of anaerobic cultures was explored for waste glycerol valorization Different environmental conditions lead to metabolic specialization Biocommodities such as propionate, acetate and methane were produced [ABSTRACT FROM AUTHOR]

Introduction: An expert panel of Canadian dermatologists was assembled to develop consensus statements regarding the current landscape of topical therapies for plaque psoriasis and the place in therapy of the recently approved fixed-dose combination halobetasol propionate (HP)/tazarotene (TAZ) lotion (HP/TAZ) in the treatment algorithm for plaque psoriasis. Method: A modified nominal group technique, which combined both independent and group input from the expert panel, was used to develop the consensus statements. The expert panel completed surveys to elicit their independent views on the current landscape of topical therapies for plaque psoriasis in Canada. The first expert panel session was held to discuss the existing body of literature and develop draft consensus statements about topical therapies and the place in therapy of HP/TAZ. Independent feedback on the draft consensus statements was solicited from expert panel members prior to another expert panel session where the amended consensus statements were further discussed, edited and, finally, voted on. Results: The expert panel reached consensus on 20 statements. Conclusion: Expert panel members agreed, based on the existing body of literature, that there is a place in therapy for HP/TAZ to address several current unmet treatment needs of patients with plaque psoriasis. Studies have shown that HP/TAZ is an effective and safe first-line treatment for moderate-to-severe plaque psoriasis. Due to its cosmetically pleasing vehicle and once-daily administration, HP/TAZ may improve patient acceptance and treatment adherence. [ABSTRACT FROM AUTHOR]

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BACKGROUND: Spotted wing drosophila, Drosophila suzukii (Matsumura) (Diptera: Drosophilidae), is an economically important pest of soft and stone fruit crops. The aim of this study was to identify repellents, formulated in dispensers, which could protect crops from D. suzukii. Fourteen potential repellents were screened against summer‐ and winter‐morph D. suzukii through electroantennography and behavioural bioassays. Repellents effective in the laboratory were tested in polytunnels to determine their efficacy in reducing catches in fruit‐baited traps. Further trials of three potential repellents were conducted to determine the distances over which repellent dispensers could reduce D. suzukii emergence in a strawberry crop. RESULTS: All 14 chemicals screened were detected by the antennae of both D. suzukii morphs. Hexyl acetate and geosmin both elicited a significantly greater corrected EAG response in summer morphs than winter morphs. Summer‐morph D. suzukii were repelled by butyl acetate, ethyl propionate, methyl N,N‐dimethyl anthranilate, geosmin, methyl salicylate, DEET and benzaldehyde at one or more doses test in laboratory bioassays. Winter morphs were repelled by ethyl propionate, methyl anthranilate, methyl N,N‐dimethyl anthranilate, DEET, benzaldehyde and butyl anthranilate at one or more of the doses tested in the laboratory. Ethyl propionate, methyl N,N‐dimethylanthranilate and benzaldehyde repelled both morphs from fruit‐baited traps in polytunnel trapping trials. Ethyl propionate and methyl N,N‐dimethylanthranilate reduced emergence of D. suzukii in a strawberry crop over 3–5 m. CONCLUSIONS: Ethyl propionate and methyl N,N‐dimethylanthranilate may protect strawberry crops against D. suzukii. Future work should test these repellents in combination with attractants in a 'push‐pull' strategy. © 2024 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Our sense of smell enables us to navigate a vast space of chemically diverse odour molecules. This task is accomplished by the combinatorial activation of approximately 400 odorant G protein-coupled receptors encoded in the human genome1-3. How odorants are recognized by odorant receptors remains unclear. Here we provide mechanistic insight into how an odorant binds to a human odorant receptor. Using cryo-electron microscopy, we determined the structure of the active human odorant receptor OR51E2 bound to the fatty acid propionate. Propionate is bound within an occluded pocket in OR51E2 and makes specific contacts critical to receptor activation. Mutation of the odorant-binding pocket in OR51E2 alters the recognition spectrum for fatty acids of varying chain length, suggesting that odorant selectivity is controlled by tight packing interactions between an odorant and an odorant receptor. Molecular dynamics simulations demonstrate that propionate-induced conformational changes in extracellular loop 3 activate OR51E2. Together, our studies provide a high-resolution view of chemical recognition of an odorant by a vertebrate odorant receptor, providing insight into how this large family of G protein-coupled receptors enables our olfactory sense.

Background: Mediterranean diet rich in polyphenolic compounds holds great promise to prevent and alleviate multiple sclerosis (MS), a central nervous system autoimmune disease associated with gut microbiome dysbiosis. Health-promoting effects of natural polyphenols with low bioavailability could be attributed to gut microbiota reconstruction. However, its underlying mechanism of action remains elusive, resulting in rare therapies have proposed for polyphenol-targeted modulation of gut microbiota for the treatment of MS. Results: We found that oral ellagic acid (EA), a natural polyphenol rich in the Mediterranean diet, effectively halted the progression of experimental autoimmune encephalomyelitis (EAE), the animal model of MS, via regulating a microbiota-metabolites-immunity axis. EA remodeled the gut microbiome composition and particularly increased the relative abundances of short-chain fatty acids -producing bacteria like Alloprevotella. Propionate (C3) was most significantly up-regulated by EA, and integrative modeling revealed a strong negative correlation between Alloprevotella or C3 and the pathological symptoms of EAE. Gut microbiota depletion negated the alleviating effects of EA on EAE, whereas oral administration of Alloprevotella rava mimicked the beneficial effects of EA on EAE. Moreover, EA directly promoted Alloprevotella rava (DSM 22548) growth and C3 production in vitro. The cell-free supernatants of Alloprevotella rava co-culture with EA suppressed Th17 differentiation by modulating acetylation in cell models. C3 can alleviate EAE development, and the mechanism may be through inhibiting HDAC activity and up-regulating acetylation thereby reducing inflammatory cytokines secreted by pathogenic Th17 cells. Conclusions: Our study identifies EA as a novel and potentially effective prebiotic for improving MS and other autoimmune diseases via the microbiota-metabolites-immunity axis. 7AEBLBqRMMqqUZLLsSi8h5 Video Abstract [ABSTRACT FROM AUTHOR]

Aligned with the UN's Sustainable Development Goals (SDGs), self‐healing elastomers stand out as a cutting‐edge field in Rubber Science and Technology. These materials have the potential to reduce resource consumption, prolong the lifespan of infrastructure and products, and contribute to the Circular Economy. This study presents the development of bio‐based self‐healing elastomeric composites prepared from blends of epoxidized natural rubber (ENR) and cellulose propionate (CP) reinforced with cellulose fibers (CFs). The ENR/CP ratio was optimized, with a 70/30 ratio enhancing the tensile strength (TS) of the base rubber and slightly reducing the elongation at break. This blend demonstrated a TS healing efficiency of 75% after a temperature‐driven healing protocol (200 bar at 150°C during 12 h). Then, the CF content was varied to enhance both mechanical performance and self‐healing capabilities. Remarkably, from medium‐high (5 phr to 15 phr) CF content, healing efficiencies higher than 85% were observed with important improvements in the mechanical performance. The self‐healing process was attributed to the synergistic interplay between the polymeric chain mobility and the formation of hydrogen bonds. This innovative approach promises materials with extended lifespans, mechanical robustness, and repairability, underscoring the commitment to SDGs 9, 11, 12, 13, 14, and 15. Highlights: Matrix of epoxidized natural rubber (ENR) and cellulose propionate (CP) blends.Cellulose fibers (CFs) reinforced the ENR/CP 70/30 optimized blend.CF addition increases tensile strength (TS) by up to 60%.Healing efficiency over 85% achieved with 5 phr to 15 phr CFs content.Self‐healing attributed to polymeric chain mobility and hydrogen bonds. [ABSTRACT FROM AUTHOR]

Ruminalmethane production is themain sink formetabolic hydrogen generated during rumen fermentation, and is a major contributor to greenhouse gas (GHG) emission. Individual ruminants exhibit varying methane production efficiency; therefore, understanding the microbial characteristics of low-methane-emitting animals could offer opportunities for mitigating enteric methane. Here, we investigated the association between rumen fermentation and rumen microbiota, focusing on methane production, and elucidated the physiological characteristics of bacteria found in low methane-producing cows. Thirteen Holstein cows in the late lactation stage were fed a corn silage-based totalmixed ration (TMR), and feed digestion, milk production, rumen fermentation products, methane production, and rumen microbial composition were examined. Cows were classified into two ruminal fermentation groups using Principal component analysis: low and high methane-producing cows (36.9 vs. 43.2 L/DMI digested) with different ruminal short chain fatty acid ratio [(C2+C4)/C3] (3.54 vs. 5.03) and dry matter (DM) digestibility (67.7% vs. 65.3%). However, there were no significant differences in dry matter intake (DMI) and milk production between both groups. Additionally, there were differences in the abundance of OTUs assigned to uncultured Prevotella sp., Succinivibrio, and other 12 bacterial phylotypes between both groups. Specifically, a previously uncultured novel Prevotella sp. with lactate-producing phenotype was detected, with higher abundance in low methane-producing cows. These findings provide evidence that Prevotella may be associated with low methane and high propionate production. However, further research is required to improve the understanding of microbial relationships and metabolic processes involved in the mitigation of enteric methane. [ABSTRACT FROM AUTHOR]

Caffeic acid is a valuable product due to its wide-ranging utilities. Currently, caffeic acid can be produced via fermentation process using native or engineered microorganisms. The reactive extraction is a prominent technique that is used for the recovery of carboxylic acids. In this work, caffeic acid was recovered by an organophosphate (trioctylphosphine oxide) from its aqueous solution in the presence of different kinds of solvents namely 1-butanol, ethyl propionate, and ethyl methyl ketone. The values of reactive extraction parameters were optimised by Box–Behnken design. 98.19% The maximum extraction efficiency was obtained as 98.19% at the optimum conditions of 0.003 mol kg−1 caffeic acid concentration, 50% (v/v) trioctylphosphine oxide quantity, and 306.2 K in the presence of 1-butanol as the solvent. Our study is the first ever to examine the reactive extraction of caffeic acid, and therefore very important in modern scientific disciplines. [ABSTRACT FROM AUTHOR]

(1) The study aims to utilize a reported approach for culturing mesophilic bacteria from a plastic waste environment; (2) The work revived mesophilic microbial population from an aged PET recycling site using a culture-based approach, and determined the purified isolates in genus level in 16S identification; (3) A total of 59 bacterial isolates were obtained, in which microbial species, including Pseudomonas spp, Rhodococcus spp, and Burkholderia spp were identified as abundance. It was observed that the surviving microbes favoured sodium propionate as a short-chain carbon source for growth, rather than the intended plastic substrate, PET. The preference of sodium propionate utilization by several bacterial isolates, including 5601W (detected as Rhodococcus spp.), 5601Y, 7801, and 7802 (detected as Burkholderia spp.), was confirmed through growth curve analysis and cell enumeration conducted in a medium where sodium propionate served as the sole carbon source.; (4) The microbial demonstration revealed the metabolic complex of microbial communities in the environment and indicated the challenges associated with bacterial isolation from environments with accumulated plastic waste. [ABSTRACT FROM AUTHOR]

Background: Itch is the most common symptom of atopic dermatitis (AD) and significantly decreases the quality of life. Skin microbiome is involved in AD pathogenesis, whereas its role in the regulation of itch remains elusive. In this study, we aimed to investigate the effects of skin microbial metabolite propionate on acute and chronic pruritus and to explore the mechanism. Methods: Using various mouse models of itch, the roles of propionate were explored by behavioral tests and histopathology/immunofluorescent analysis. Primary‐cultured dorsal root ganglion neurons and HEK293 cells expressing recombinant human TRP channels were utilized for in vitro calcium imaging/in vivo miniature two‐photon imaging in combination with electrophysiology and molecular docking approaches for investigation of the mechanism. Results: Propionate significantly alleviated itch and alloknesis in various mouse models of pruritus and AD and decreased the density of intraepidermal nerve fibers. Propionate reduced the responsiveness of dorsal root ganglion neurons to pruritogens in vitro, attenuated the hyper‐excitability in sensory neurons in MC903‐induced AD model, and inhibited capsaicin‐evoked hTRPV1 currents (IC50 = 20.08 ± 1.11 μM) via interacting with the vanilloid binding site. Propionate also decreased the secretion of calcitonin gene‐related peptide by nerves in MC903‐induced AD mouse model, which further attenuated itch and skin inflammation. Conclusion: Our study revealed a protective effect of propionate against persistent itch through direct modulation of sensory TRP channels and neuropeptide production in neurons. Regulation of itch via the skin microbiome might be a novel strategy for the treatment of AD. [ABSTRACT FROM AUTHOR]

Rasmalai is a very popular, delicious, and nutritious indigenous sweet dish in Indo‐Pakistani civilization. It has a very short shelf life, i.e., up to 3 days. The study was designed to assess the effect of preservatives (potassium sorbate and calcium propionate) on the shelf stability of Rasmalai. Moreover, proximate composition and sensory evaluation of prepared Rasmalai were also carried out in the present study. In general, potassium sorbate and calcium propionate significantly increased the shelf life of Rasmalai. But treatment (R5) containing a combination of both potassium sorbate and calcium propionate (500 ppm each) improved its shelf life by up to 12 days by keeping good sensorial characteristics. The maximum total plate counts as well as yeast and molds were observed in control Rasmalai (without any preservatives) whereas minimum counts were found in R5 treatment containing a combination of both potassium sorbate and calcium propionate (500 ppm each). In conclusion, all the preservatives used in the present study were effective in enhancing the shelf life of Rasmalai but R5 treatment containing a combination of both potassium sorbate and calcium propionate (500 ppm each) was the most effective in enhancing shelf life without deleterious effect on sensorial characteristics. [ABSTRACT FROM AUTHOR]

This work presents the use of natural rubber (NR) grafted with poly(vinyl propionate) (NR-g-PVP) as an alternative compatibilizer in silica-filled NR compounds. The effects of NR-g-PVP with 10, 20 and 30% grafting on the properties of NR compounds were studied and compared with a commercial coupling agent (bis[3-(triethoxysilyl)propyl] tetrasulfide, TESPT). NR-g-PVP was compatible with silica and NR. The NR-g-PVP reduced filler-filler interactions and increased fillerrubber interactions. The crosslink density decreased with the percentage of grafting due to the steric hindrance. The compatibilization affected the physical and mechanical properties. The interactions of NR-g-PVP with silica via hydrogen bonding and subsequent vulcanization prevented undesirable filler-filler interactions and reduced the absorption of accelerators or basic materials. It caused a good dispersion of silica in the NR matrix and improved physical and mechanical properties. A 10% grafting (G10) was suitable for the compatibilizer in a silica-filled NR compound, showing the largest improvements in tensile properties, tear strength, and hardness. However, TESPT provided better properties than G10. [ABSTRACT FROM AUTHOR]

Although postruminal glucose infusion into dairy cows has increased milk protein yield in some past experiments, the same trend has not been observed in others. A meta-regression of 64 sets of observations from 29 previously published glucose and propionate infusion studies in dairy cattle, treating study and experiment (study) as random effects, was performed to establish the general effects of glucose equivalent (GlcE) infusion rate on milk true protein (MTP) yield and content, if any, and to identify independent, fixed-effect variables that accounted for the changes in MTP yield and content that were observed. Candidate explanatory variables included rate and site of infusion, diet composition and intake, body weight and lactation stage of the cows, and the change in nutrient intake between GlcE and control treatments. Across all studies, according to a model containing only the random effects of study and experiment, GlcE infusion at an average of 954 g/d increased MTP yield by 26 g/d, on average, whereas mean MTP content was not affected. Backward stepwise elimination of potential explanatory variables from a full mixed model produced a final, reduced model for MTP yield that retained a positive, second-order quadratic effect of infusion rate of GlcE and a positive, linear effect of the change in crude protein intake (CPI) between GlcE treatment and control. This change in CPI due to GlcE infusion ranged from −0.546 to 0.173 kg/d in the dataset. The model fit indicated that when CPI was allowed to drop during GlcE infusion, the effect of GlcE on MTP yield was smaller than when CPI was maintained or increased, in a manifestation of the classic protein:energy interaction. The final reduced model for MTP content contained the same explanatory variables as for MTP yield, plus a negative effect of intravenous compared with gastrointestinal infusion. Overall, the meta-analysis revealed that both MTP yield, and content were positively related to GlcE infusion rate and to the change in CPI between glucose treatment and control. [ABSTRACT FROM AUTHOR]

The six dimethylsulfonium propionate (DMSP) lyases DddQ, DddW, DddP, DddY, DddK and DddL catalyze the elimination of dimethyl sulfide from DMSP and can also cleave the marine metabolite dimethylsulfoxonium propionate (DMSOP) to DMSO and acrylate. In this study the potency of all six enzymes for the conversion of four DMSOP analogs with longer alkyl chains that were synthesized in three steps from 3‐mercaptopropionic acid was investigated. For this purpose, the pH dependency of the enzyme reactions was determined, showing optimal conditions at pH 8 for all enzymes but DddP, for which an optimum of pH 6 was found. Efficient transformations were observed for DddQ, DddW, DddY and DddK, for which the Michaelis‐Menten kinetics were determined for all four substrate analogs. HPLC analysis of the dialkylsulfoxides obtained with the most efficient enzyme DddW revealed that these compounds were obtained with a low to moderate enantiomeric excess (up to 25 % ee), demonstrating that this enzyme has a preference for one of the enantiomers of the DMSOP analogs. [ABSTRACT FROM AUTHOR]

Background: Intestinal barrier is a dynamic interface between the body and the ingested food components, however, dietary components or xenobiotics could compromise intestinal integrity, causing health risks to the host. Gossypol, a toxic component in cottonseed meal (CSM), caused intestinal injury in fish or other monogastric animals. It has been demonstrated that probiotics administration benefits the intestinal barrier integrity, but the efficacy of probiotics in maintaining intestinal health when the host is exposed to gossypol remains unclear. Here, a strain (YC) affiliated to Pediococcus pentosaceus was isolated from the gut of Nile tilapia (Oreochromis niloticus) and its potential to repair gossypol-induced intestinal damage was evaluated. Results: A total of 270 Nile tilapia (2.20 ± 0.02 g) were allotted in 3 groups with 3 tanks each and fed with 3 diets including CON (control diet), GOS (control diet containing 300 mg/kg gossypol) and GP (control diet containing 300 mg/kg gossypol and 108 colony-forming unit (CFU)/g P. pentosaceus YC), respectively. After 10 weeks, addition of P. pentosaceus YC restored growth retardation and intestinal injury induced by gossypol in Nile tilapia. Transcriptome analysis and siRNA interference experiments demonstrated that NOD-like receptors (NLR) family caspase recruitment domain (CARD) domain containing 3 (Nlrc3) inhibition might promote intestinal stem cell (ISC) proliferation, as well as maintaining gut barrier integrity. 16S rRNA sequencing and gas chromatography-mass spectrometry (GC-MS) revealed that addition of P. pentosaceus YC altered the composition of gut microbiota and increased the content of propionate in fish gut. In vitro studies on propionate's function demonstrated that it suppressed nlrc3 expression and promoted wound healing in Caco-2 cell model. Conclusions: The present study reveals that P. pentosaceus YC has the capacity to ameliorate intestinal barrier injury by modulating gut microbiota composition and elevating propionate level. This finding offers a promising strategy for the feed industry to incorporate cottonseed meal into fish feed formulations. [ABSTRACT FROM AUTHOR]

The title compound, C12H15N3O2S, adopts an E configuration with respect to the C=N bond. The propionate group adopts an antiperiplanar (ap) conformation. There are short intramolecular N--H...N and C--H...O contacts, forming S(5) and S(6) ring motifs, respectively. In the crystal, molecules are connected into ribbons extending parallel to [010] by pairs of N--H...S interactions, forming rings with R2²(8) graph-set motifs, and by pairs of C--H...S interactions, where rings with the graph-set motif R2¹(7) are observed. The O atom of the carbonyl group is disordered over two positions, with a refined occupancy ratio of 0.27 (2):0.73 (2). The studied crystal consisted of two domains. [ABSTRACT FROM AUTHOR]

Purpose: Probiotics have been reported to effectively alleviate hyperuricemia and regulate the gut microbiota. The aim of this work was to study the in vivo anti-hyperuricemic properties and the mechanism of a novel strain, Lactiplantibacillus plantarum X7022. Methods: Purine content and mRNA expression of purine assimilation related enzymes were determined by HPLC and qPCR, respectively. Hyperuricemic mice were induced by potassium oxonate and hypoxanthine. Uric acid (UA), blood urea nitrogen, creatinine and renal inflammation were examined by kits. The expression of renal UA transporters was subjected to western blotting. Kidney tissues were sectioned for histological analysis. The fecal short-chain fatty acids (SCFAs) were determined by HPLC, and gut microbiota was investigated using the 16S rDNA metagenomic sequencing. Results: L. plantarum X7022 possesses a complete purine assimilation pathway and can exhaust xanthine, guanine, and adenine by 82.1%, 33.1%, and 12.6%, respectively. The strain exhibited gastrointestinal viability as 44% at the dose of 109 CFU/mL in mice. After four-week administration of the strain, a significant decrease of 35.5% in the serum UA level in hyperuricemic mice was achieved. The diminished contents of fecal propionate and butyrate were dramatically boosted. The treatment also alleviated renal inflammation and restored renal damage. The above physiological changes may due to the inhibited xanthine oxidase (XO) activity, as well as the expressional regulation of UA transporters (GLUT9, URAT1 and OAT1) to the normal level. Notably, gut microbiota dysbiosis in hyperuricemic mice was improved with the inflammation and hyperuricemia related flora depressed, and SCFAs production related flora promoted. Conclusion: The strain is a promising probiotic strain for ameliorating hyperuricemia. [ABSTRACT FROM AUTHOR]

Background: Growing evidence has demonstrated the important roles of gut microbiota and short chain fatty acids, especially acetate, propionate and butyrate, in the development of obesity and metabolic diseases. To date, the effects of acetate, propionate and butyrate on human adiposity and glucose metabolism remain controversial. This study aimed to explore the associations of systemically acetate, propionate and butyrate with obesity and glucose homeostasis in patients with type 2 diabetes (T2D) and obesity. Methods: A total of 12 patients with T2D and obesity and 8 age- and sex-matched healthy individuals with BMI < 24 kg/m2 were enrolled in this study. Height, weight, body composition, blood pressure, biochemical indices, a 75-g oral glucose tolerance test, and plasma acetate, propionate and butyrate were measured at baseline. Then, participants in T2D group were given a weight control therapy, in addition to conventional medication, and all the measurements were repeated 12 months from baseline. The direct segmental multi-frequency bioelectrical impedance analysis was used to assess body composition. Acetate, propionate and butyrate levels were determined by liquid chromatography coupled to tandem mass spectrometry. Results: Butyrate concentration significantly increased from baseline after obvious weight loss (P< 0.05). Correlation analysis showed that propionate was negatively correlated with percent of body fat (PBF) and 2-h plasma glucose (2-h PG) (P< 0.05), and butyrate was negatively associated with body mass index, visceral fat area, PBF and 2-h PG (P< 0.05). No association was found between acetate and obesity. Conclusion: Butyrate and propionate are negatively correlated with obesity and glucose levels in patients with T2D and obesity. [ABSTRACT FROM AUTHOR]

Generally, fasting and refeeding confer anti- and proinflammatory effects, respectively. In humans, these caloric-load interventions function, in part, via regulation of CD4+ T cell biology. However, mechanisms orchestrating this regulation remain incomplete. We employed integrative bioinformatics of RNA sequencing and high-performance liquid chromatography–mass spectrometry data to measure serum metabolites and gene expression of peripheral blood mononuclear cells isolated from fasting and refeeding in volunteers to identify nutrient-load metabolite-driven immunoregulation. Propionate, a short chain fatty acid (SCFA), and the SCFA-sensing G protein–coupled receptor 43 (ffar2) were coordinately and inversely regulated by fasting and refeeding. Propionate and free fatty acid receptor agonists decreased interferon-γ and interleukin-17 and significantly blunted histone deacetylase activity in CD4+ T cells. Furthermore, propionate blunted nuclear factor κB activity and diminished interleukin-6 release. In parallel, propionate reduced phosphorylation of canonical T helper 1 (TH1) and TH17 regulators, STAT1 and STAT3, respectively. Conversely, knockdown of free fatty acid receptors significantly attenuated the anti-inflammatory role of propionate. Interestingly, propionate recapitulated the blunting of CD4+ TH cell activation in primary cells from obese individuals, extending the role of this metabolite to a disease associated with low-grade inflammation. Together, these data identify a nutrient-load responsive SCFA–G protein–coupled receptor linked pathway to regulate CD4+ TH cell immune responsiveness. Propionate blunts T helper cell responsiveness. [ABSTRACT FROM AUTHOR]

This study examined the impact of sodium propionate concentration (0–40 g/L) on the methanogenic archaea in an inoculum which was cultured in basal nutrient medium, exploring its mechanisms and nonlinear stress intensity. The results indicated that at low concentrations, propionate-maintained homeostasis of the anaerobic digestion (AD) system and enriched Methanosaeta. However, when the concentration exceeded 16 g/L, the stability of the AD system was disrupted. The methanogenic pathway shifted towards a predominantly hydrogenotrophic pathway, resulting in a significant increase in methane yield. Below concentrations of 28 g/L, the AD system gradually enhanced its ability to utilize propionate in an orderly manner. At concentrations of 24–28 g/L, genera (e.g., Advenella and Methanosarcina) were enriched to adapt to the high-VFA environment. This was accompanied by a significant upregulation of genes related to the methylotrophic and hydrogenotrophic pathways, effectively mitigating propionate inhibition and enhancing methanogenesis. Conversely, excess concentrations (>30 g/L) suppressed methanogenesis-related genes and led to methane production arrest despite activating specialized propionate-metabolizing bacteria such as genus Pelotomaculum schinkii. As such, an increase in the stress intensity of propionate promotes a change in the metabolic pathways of methanogens and increases methane production; however, excessive sodium propionate was not conducive to maintaining the steady state of the system. [ABSTRACT FROM AUTHOR]

Anabolic metabolism of carbon in mammals is mediated via the one- and two-carbon carriers S-adenosyl methionine and acetyl-coenzyme A. In contrast, anabolic metabolism of three-carbon units via propionate has not been shown to extensively occur. Mammals are primarily thought to oxidize the three-carbon short chain fatty acid propionate by shunting propionyl-CoA to succinyl-CoA for entry into the TCA cycle. Here, we found that this may not be absolute as, in mammals, one nonoxidative fate of propionyl-CoA is to condense to two three-carbon units into a six-carbon trans-2-methyl-2-pentenoyl-CoA (2M2PE-CoA). We confirmed this reaction pathway using purified protein extracts provided limited substrates and verified the product via LC-MS using a synthetic standard. In whole-body in vivo stable isotope tracing following infusion of 13C-labeled valine at steady state, 2M2PE-CoA was found to form via propionyl-CoA in multiple murine tissues, including heart, kidney, and to a lesser degree, in brown adipose tissue, liver, and tibialis anterior muscle. Using ex vivo isotope tracing, we found that 2M2PE-CoA also formed in human myocardial tissue incubated with propionate to a limited extent. While the complete enzymology of this pathway remains to be elucidated, these results confirm the in vivo existence of at least one anabolic three- to six-carbon reaction conserved in humans and mice that utilizes propionate.

Intestinal pathogens must combat host and microbiota-associated resistance to establish an infection. A new study (Shelton et al.) highlights how Salmonella manipulates the mammalian host to produce anaerobic respiratory electron acceptors, allowing catabolism of propionate and providing a competitive edge to Salmonella residing in the gut.

Calcium propionate, as an approved food additive, is widely used as a mold inhibitor in food and feed. It is recognized as safe, but when metabolized in the gastrointestinal tract, it can affect the body’s metabolism both directly and indirectly through the intestinal microbiota. The effect of various doses of calcium propionate on the body of model animals, with the study of the quantitative and qualitative composition of their intestinal microbiome, was investigated in this experiment. Four groups of male laboratory rats were formed, which for 20 days consumed: a high-fat diet with the addition of 0.0%, 0.5%, 1.0%, 2.0% calcium propionoate. We determined changes in body weight, the condition and mass indices of the internal organs, biochemical blood parameters, the functional state of the nervous system using the “open field” method, as well as changes in the intestinal microbiota. Adding calcium propionate to a high-fat diet does not affect the rate of animals’ weight gain, nor the amount of feed and water consumed. High dose consumption of calcium propionate caused a decrease in the relative weight of the spleen and an increase in the relative weight of the kidneys, without affecting the functional state of the nervous system. With the addition of calcium propionate to a high-fat diet, only minor changes in some biochemical blood parameters were observed (increased De Ritis ratio and Ca/P ratio, moderate dyslipidemia). Calcium propionate had the most significant changes in the quantitative and qualitative composition of the intestinal microbiota in laboratory rats. Among the representatives of the microflora, the most sensitive to this substance against the background of a high-fat diet were obligate microorganisms from the genera Bifidobacterium and Lactobacillus. The antimicrobial action of calcium propionate was also demonstrated by the pathogenic Staphylococcus aureus. Amid a deficiency of obligate microflora, proliferation of transient microflora was found – facultative anaerobic and aerobic microorganisms (bacteria of the genera Klebsiella, Enterococcus, Clostridium, fungi of the genus Candida). Further research will be aimed at studying the effect of calcium propionate in various doses on the biological systems of different age group laboratory animals in a long-term experiment.

Background: Imidazole propionate (IMP) is a histidine metabolite produced by some gut microorganisms in the human colon. Increased levels of IMP are associated with intestinal inflammation and the development and progression of cardiovascular disease and diabetes. However, the anti-inflammatory activity of IMP has not been investigated. This study aimed to elucidate the role of IMP in treating atopic dermatitis (AD). Methods: To understand how IMP mediates immunosuppression in AD, IMP was intraperitoneally injected into a Dermatophagoides farinae extract (DFE)/1-chloro-2,4 dinitrochlorobenzene (DNCB)-induced AD-like skin lesions mouse model. We also characterized the anti-inflammatory mechanism of IMP by inducing an AD response in keratinocytes through TNF-α/IFN-γ or IL-4 stimulation. Results: Contrary to the prevailing view that IMP is an unhealthy microbial metabolite, we found that IMP-treated AD-like skin lesions mice showed significant improvement in their clinical symptoms, including ear thickness, epidermal and dermal thickness, and IgE levels. Furthermore, IMP antagonized the expansion of myeloid (neutrophils, macrophages, eosinophils, and mast cells) and Th cells (Th1, Th2, and Th17) in mouse skin and prevented mitochondrial reactive oxygen species production by inhibiting mitochondrial energy production. Interestingly, we found that IMP inhibited AD by reducing glucose uptake in cells to suppress proinflammatory cytokines and chemokines in an AD-like in vitro model, sequentially downregulating the PI3K and mTORC2 signaling pathways centered on Akt, and upregulating DDIT4 and AMPK. Discussion: Our results suggest that IMP exerts anti-inflammatory effects through the metabolic reprogramming of skin inflammation, making it a promising therapeutic candidate for AD and related skin diseases. [ABSTRACT FROM AUTHOR]

Short-chain fatty acids (SCFAs), particularly propionate and butyrate, have been reported in many cancers. However, the relationship between propionate and acute myeloid leukemia (AML) remains unclear. Additionally, Acyl-CoA synthetase long chain family member 4 (ACSL4) has been reported to regulate immunity in solid tumors, but there are still many gaps to be filled in AML. Here, we discovered the underlying mechanism of propionate and ACSL4-mediated ferroptosis for immunotherapy. Our results showed that the level of propionate in the AML patients' feces was decreased, which was correlated to gut microbiota dysbiosis. Moreover, we demonstrated that propionate suppressed AML progression both in vivo and in vitro. In mechanism, propionate induced AML cells apoptosis and ferroptosis. The imbalance of reactive oxygen species (ROS) and redox homeostasis induced by propionate caused mitochondrial fission and mitophagy, which enhanced ferroptosis and apoptosis. Furthermore, ACSL4-mediated ferroptosis caused by propionate increased the immunogenicity of AML cells, induced the release of damage-associated molecular patterns (DAMPs), and promoted the maturation of dendritic cells (DCs). The increased level of immunogenicity due to ferroptosis enable propionate-based whole-cell vaccines to activate immunity, thus further facilitating effective killing of AML cells. Collectively, our study uncovers a crucial role for propionate suppresses AML progression by inducing ferroptosis and the potential mechanisms of ACSL4-mediated ferroptosis in the regulation of AML immunity. [ABSTRACT FROM AUTHOR]

Considering the importance of reducing the use of chemical preservatives in food and the increasing attention of consumers to consume food products with minimal additives, the main goal of this research was to study the effect of use of chemical (calcium propionate) and biological (Lactobacillus plantarum) preservatives on increasing shelf life of yufka paste considering its physicochemical and microbial characteristics. For this purpose, three samples of yufka paste were prepared by adding concentrations of 103, 105, and 107 cfu/mL of L. plantarum individually and three samples of paste were prepared by adding the same amount of bacteria in combination with 0.3% calcium propionate and these samples were compared with the control sample (without preservative) and the sample only containing 0.3% calcium propionate. The obtained results showed that different treatments and time had a significant effect on physicochemical properties including pH, moisture, and protein of yufka paste (p <.05). The results of the survival of L. plantarum showed that with increasing time, the survival rate of bacteria increased (p <.05). The pH of the samples showed that the L. plantarum has a significant effect on controlling the chemical quality of yufka during storage. The count of mold and yeast in the combined use of L. plantarum and 0.3% propionate was lower than the single use of propionate chemical preservative, which indicated the very good effect of the green preservative in controlling the moldy spoilage of yufka. Low concentrations of bacteria showed better antimold results than treatments containing bacteria and propionate in a combined form, propionate or control treatment. [ABSTRACT FROM AUTHOR]

Present study was carried out on twenty-four lactating dairy cows (HF x Jersey, Jersey x Sahiwal) to assess the effect of feeding different levels of calcium propionate for 40 days on nutrient digestibility, milk yield and milk composition. The cows were divided into four groups having six animals in each group and randomly allotted to four dietary treatments, i.e. T1 (control diet) (ad libitum APBN-1 green fodder, concentrate pellet feed and paddy straw) with no calcium propionate supplementation. Group T2, T3 and T4 were fed control diet with 60 g, 70 g, and 80 g calcium propionate/cow/day, respectively. After 30 days feeding, a digestion trial of 7 days was conducted. The digestibility (%) of DM, OM, CP, EE, CF and NFE were found to vary significantly (p<0.05) among treatments, and increased with increasing level of calcium propionate compared to control group. The digestibility (%) of cell wall fractions, ADF and NDF, though improved, did not vary significantly. Average dry matter intake (kg/day) was 9.98, 10.34, 10.27 and 10.45 and the feed conversion ratio in terms of milk yield was 2.31, 2.27, 2.29 and 2.16 for T1, T2, T3 and T4, respectively, indicating an increasing trend in DMI, eventual increasing milk yield, though there was no significant variation in the milk composition. It was concluded that supplementation of higher dose of calcium propionate improved the nutrient digestibility and milk yield than middle and lower levels. [ABSTRACT FROM AUTHOR]

This study was aimed to explore the effects of supplementation of different rates of calcium propionate on nutrient utilization, rumen fermentation pattern and blood biochemical profile of mid lactating dairy cattle. The dairy cows were fed with a common diet of ad libitum APBN-1 green fodder, concentrate pellet feed and paddy straw. Twenty-four lactating dairy cows (4th to 6th month of lactation) were randomly divided in to four treatment groups each of six cows. The groups were designated as T1 (control) common diet without calcium propionate supplementation, whereas the treatment groups T2, T3 and T4 were supplemented with calcium propionate at the rate of 60 g, 70 g and 80 g/animal/day in addition to the common diet. Feeding trial was carried out for a period of 40 days. The supplementation of calcium propionate to the dairy cattle had no major changes in the rumen pH within the treatment. In the present study, there was no significant difference in mean pH values among the dietary treatments, time/hours after feeding and diet x hour interaction. The mean TVFA (mEq/L) was lowest at 0 h and highest (p<0.05) at 3 h of SRL collection, and then showed a decreasing trend (p<0.05) from 6 h to 12-h post-feeding in all groups. The mean NH3-N (mg/100 mL SRL) was higher (p<0.05) at 3 h and thereafter showed a reducing trend from 6 to 12 h intervals. The serum glucose and calcium values were found to be significantly (p<0.05) higher among treatment groups when compared with control group, whereas the BUN levels did not vary much. It was concluded that supplementation of calcium propionate to dairy cows showed a significant increase in the ruminal TVFA, NH3-N, and total nitrogen as well as serum glucose and calcium concentrations by 3rd hour of feeding and then either persists at almost same level till 6th hour or gradually declined till 12 h of sampling. [ABSTRACT FROM AUTHOR]