Fumarate Research Articles

Combining the Elicitor Up-Regulated Production of Unusual Linear Diterpene-Derived Variants for an In-Depth Assessment of the Application Value and Risk of the Medicinal and Edible Basidiomycete Schizophyllum commune.

To better assess the practical value and avoid potential risks of the traditionally medicinal and edible basidiomycete Schizophyllum commune, which may arise from undescribed metabolites, a combination of elicitors was introduced for the first time to discover products from cryptic and low-expressed gene clusters under laboratory cultivation. Treating S. commune NJFU21 with the combination of five elicitors led to the upregulated production of a class of unusual linear diterpene-derived variants, including eleven new ones (1-11), along with three known ones (12-14). The structures and stereochemistry were determined by 1D and 2D NMR, HRESIMS, ECD, OR and VCD calculations. Notably, the elongation terminus of all the diterpenes was decorated by an unusual butenedioic acid moiety. Compound 1 was a rare monocyclic diterpene, while 2-6 possessed a tetrahydrofuran moiety. The truncated metabolites 4, 5 and 13 belong to the trinorditerpenes. All the diterpenes displayed approximately 70% scavenging of hydroxyl radicals at 50 μM and null cytotoxic activity at 10 μM. In addition, compound 1 exhibited potent antifungal activity against the plant pathogenic fungi Colletotrichum camelliae, with MIC values of 8 μg/mL. Our findings indicated that this class of diterpenes could provide valuable protectants for cosmetic ingredients and the lead compounds for agricultural fungicide development.

Effects of Different Essential Oil Blends and Fumaric Acid on In Vitro Fermentation, Greenhouse Gases, Nutrient Degradability, and Total and Molar Proportions of Volatile Fatty Acid Production in a Total Mixed Ration for Dairy Cattle

The present study evaluated the inclusion of fumaric acid and essential oil blends (EOBs) containing anise, cedarwood, clove, cumin, eucalyptus, garlic, ginger, lavender, lemongrass, nutmeg, oregano, and peppermint at different proportions on in vitro dry matter (DM) disappearance (DMD), fiber fraction disappearance, the efficiency of microbial production, and the total volatile fatty acids (VFAs). Ten treatments without (control treatment) or with different EOB/fumaric combinations were used in the study with eight replicates. The EOB inclusion level was 200 μL/g of feed (total mixed ration, (TMR)) while fumaric acid was administered at 3% of the TMR (DM basis). The highest DMD, in vitro true degradable DM, partitioning factor (PF24), and in vitro apparent degradable DM were recorded for the fumaric only treatment and the control. Neutral detergent fiber disappearance was reduced with the inclusion of EOB/fumaric combinations. The production of microbial mass and undegraded DM were higher (p < 0.001) for all EOBs and EOB and fumaric treatments. The inclusion of EOB and fumaric combinations reduced (p < 0.001) the total gas production, methane, and ammonia, with a higher PF24 value noted for EOB3 treatment. The inclusion of individual EOB1 containing garlic, lemongrass, cumin, lavender, and nutmeg in a ratio of 4:2:2:1:1 or combined with fumaric acid yielded the highest propionate concentration across all treatments. We concluded that EOBs decreased methane production and nutrient degradability with better results with the individual EOB1 or EOB1/fumaric combination, which showed a potential enhancement in energy production.

Knowledge mapping of disease-modifying therapy (DMT) in multiple sclerosis (MS): A bibliometrics analysis

BackgroundMultiple sclerosis (MS) is a heterogeneous autoimmune disease, with a rapidly evolving body of literature on disease-modifying therapy (DMT) that urgently needs to be synthesized and regularized. MethodsThe original material used for the analysis was obtained from the Web of Science Core Collection (WoSCC) in the Science Citation Index Expanded Edition (SCI-E). The data material was accessed through VOSviewer, Citespace, R package “Bibliometrix”, and Scimago Graphica for data analysis and visualization. Among them, the clustering algorithm based on the Largest Likelihood Ratio (LLR) and the burst citation algorithm is the key. ResultsAs of November 6th, 2022, 4142 publications related to emerging disease-modifying therapies (e-DMT) for MS, 6521 publications related to traditional disease-modifying therapies (t-DMT) for MS, and 1793 publications in cross-cutting disease-modifying therapies (I-DMT) for MS were included in the analysis, respectively. Publications related to DMT in MS were analyzed descriptively (for three subjects: country, institution, and author) and predictively (for two subjects: keywords and references) separately according to three sections: e-DMT, t-DMT, and I-DMT. Topics that still have relevant reference output as of 2022 include the safety of Coronavirus disease 2019 (COVID-19) mRNA vaccination, therapeutic inertia (TI), cladribine tablets, autologous hematopoietic stem cell transplantation (aHSCT), progressive multiple sclerosis, and pediatric multiple sclerosis. ConclusionThe future research focus for MS DMT is the combination trial or cross-trial of various treatment methods to improve the development of individualized treatment plans for MS patients. The exact contents of the research frontiers are included but not limited to ocrelizumab, fingolimod and other monoclonal antibodies, fumaric acid ester, cladribine tablet, aHSCT, and other interventions of randomized controlled trials (RCTs); the impact of mRNA COVID-19 vaccination on MS patients; TI, patient adherence, and other medical management issues; and continued exploration of biomarkers for more accurate disease classification based on the existing clinical indication classification.

«Lace Miracle», lichens as an indicator of the ecological situation using the example of Turkey Creek, Florida

In this article, we took a walk-exploration of a piece of paradise called Turkey Creek in the center of Florida. Enjoying the spring period of the awakening of nature, accompanied by a multitude of birds and other unique sounds of the inhabitants of Turkey Creek, we paid special attention to the diversity of lichens, which, as bioindicators, react and reflect the state and quality of the environment. Lichens are very sensitive to air pollution and die when there is a high content of carbon monoxide, sulfur compounds, nitrogen and fluorine. The degree of sensitivity varies among species, so they can be used as living indicators of environmental cleanliness. Based on the composition of lichens, the concentration of various pollutants in the air can be quantified using developed scales and formulas. Lichens are a unique group of lower plants. Lichens combine two organisms with opposite properties: an alga (usually green), which creates organic matter through the process of photosynthesis, and a fungus that consumes this substance. Lichens are characterized by fairly high tolerance to climatic factors and sensitivity to environmental pollutants and are widely used as environmental indicators. Lichens contain many macro- and microelements, organic acids, hormones and enzymes. Vitamins are produced by lichens in very small quantities. Lichens produce specific substances that are not found in other organisms (lichen starch, lichen acids, etc.). Lichens have the ability to extract various elements from the environment and accumulate in their thallus. The number of currently known lichen substances exceeds 250, of which 75 are found only in lichens. Lichens are indicators of the environmental situation. Our goal is to find out whether recreational load affects the state of the environment in people’s recreation areas. We carried out our study of the state of the environment in the state of Florida in the Turkey Creek natural park. This territory was chosen because the natural complexes of the area are characterized by high environment-forming, environmental, and recreational significance. In the last decade, the anthropogenic load on ecosystems associated with the recreational use of the territory has been increasing. It is worth familiarizing yourself with the types of lichens that were seen in the study area.

Synthesis of a novel cost-effective double-ligand Zr-based MOF via an inverted modulator strategy towards enhanced adsorption and photodegradation of tetracycline

Developing visible-light response photocatalysts with high activity and adsorption alongside sustainability is vitally important to environmental restoration. Here, we fabricated a novel metal organic framework (MOF) with cost-effective double-ligands (fumaric acid and 2-aminoterephthalic acid as ligand precursors, denoted as MA-MOF) via a facile solvothermal method. Specifically, crystalline [Zr6O4(OH)4(fumarate)6] (MOF-801) can be only formed with monocarboxylic acids as modulators. Therefore, in the construction of crystalline double-ligand MA-MOF, the absence of monocarboxylic acid modulators successfully prevents the formation of crystalline MOF-801. Instead, the crystalline double-ligand MA-MOF is formed. Properties of MA-MOFs including the surface area, porosity, charge transfer resistance, and energy level position can be adjusted via altering the ratio of ligands. The optimal sample, MA-MOF2 (prepared with a molar ratio of fumaric acid and 2-aminoterephthalic acid being 2:1), shows a total 94.6% removal of tetracycline via adsorption and photodegradation, far exceeding the corresponding single-ligand counterparts. This work proposes an innovative inverted modulator strategy for constructing double-ligand MOFs.

Ensitrelvir Fumaric Acid: First Approval.

Ensitrelvir fumaric acid (Xocova®) is an oral SARS-CoV-2 main protease inhibitor developed by Shionogi for the treatment of SARS-CoV-2 infection. It is the first single-entity, nonpeptidic, noncovalent, small molecule antiviral of its kind. Following emergency regulatory approval in Japan in November 2022, ensitrelvir received standard approval in Japan on 5 March 2024 for the treatment of SARS-CoV-2 infection. This article summarizes the milestones in the development of ensitrelvir leading to this first standard approval for SARS-CoV-2 infection.

Selective activation of cellular stress response pathways by fumaric acid esters.

The cellular response to oxidants or xenobiotics comprises two key pathways, resulting in modulation of NRF2 and FOXO transcription factors, respectively. Both mount a cytoprotective response, and their activation relies on crucial protein thiol moieties. Using fumaric acid esters (FAEs), known thiol-reactive compounds, we tested for activation of NRF2 and FOXO pathways in cultured human hepatoma cells by dimethyl/diethyl as well as monomethyl/monoethyl fumarate. Whereas only the diesters caused acute glutathione depletion and activation of the stress kinase p38MAPK, all four FAEs stimulated NRF2 stabilization and upregulation of NRF2 target genes. However, no significant FAE-induced activation of FOXO-dependent target gene expression was observed. Therefore, while both NRF2 and FOXO pathways are responsive to oxidants and xenobiotics, FAEs selectively activate NRF2 signaling.

Sustainable process intensification: Ultrasonic preparation of MIL-88A for benzoxazole synthesis

This study provides a biodegradable fumaric acid-based MIL-88A metal-organic framework, a cost-effective and non-toxic catalyst, for biologically active benzoxazoles synthesis. Initially, the ultrasonic approach is used for MIL-88A preparation at room temperature, significantly reducing the synthesis time compared to conventional heating protocols. The ultrasonic approach is once again used for the three-component production of benzoxazoles in the presence of MIL-88A catalyst. Subsequently, the benzoxazole reaction is accelerated and yields are also improved. Impressive yields ranging between 84 % and 96 % were obtained within one hour at room temperature for the three-component synthesis of benzoxazoles. Characterization techniques, including FT-IR, TEM, XRD, and SEM-EDS mapping, confirm the successful synthesis of MIL-88A. Moreover, a large-scale reaction for benzoxazole synthesis can be performed with minimal yield loss, indicating its practical application. Notably, fumaric acid, found in many fruits and vegetables, serves as the precursor for catalyst synthesis. Catechol, sourced from various plant sources, is employed for three-component production of benzoxazoles. By integrating sustainable techniques, including ultrasound-assisted synthesis and naturally available substrates, an innovative strategy was developed utilizing a renewable catalyst for an eco-friendly reaction.

A europium(III) metal-organic framework as effective fluorescence sensor for detection of ofloxacin antibiotic

Antibiotic overuse, a critical global concern, poses significant threats to both the eco-environment and human health. Thus, selective and sensitive detection of antibiotics is an extremely important issue. Herein, a europium(III) metal-organic framework Eu2(FA)3(H2O)4·2DMAC (1) (FA = fumaric acid, DMAC = dimethylacetamide) was synthesized by solvothermal strategy. Single-crystal structural analyses indicate that Eu3+ ions are double-bridged by carboxylate groups of fumarate ligands to create one-dimensional (1D) infinite chains, which further form a 3D pillared-layer framework. 1 exhibits superior fluorescence detection performance toward ofloxacin (OFLX) with a high quenching efficiency Ksv of 4.1 × 104 M−1 and low detection limit of 2.4 × 10−6 M, and demonstrates excellent anti-interference properties and durability. Furthermore, the mechanism of fluorescence quenching was mainly attributed to static quenching process and internal filtration effect.

Green Extraction of Depsidones and Depsides from Hypogymnia physodes (L.) Nyl. Using Natural Deep Eutectic Solvents.

Various studies have shown that Hypogymnia physodes are a source of many biologically active compounds, including lichen acids. These lichen-specific compounds are characterized by antioxidant, antiproliferative, and antimicrobial properties, and they can be used in the cosmetic and pharmaceutical industries. The main aim of this study was to optimize the composition of natural deep eutectic solvents based on proline or betaine and lactic acid for the extraction of metabolites from H. physodes. The design of the experimental method and the response surface approach allowed the optimization of the extraction process of specific lichen metabolites. Based on preliminary research, a multivariate model of the experiment was developed. For optimization, the following parameters were employed in the experiment to confirm the model: a proline/lactic acid/water molar ratio of 1:2:2. Such a mixture allowed the efficient extraction of three depsidones (i.e., physodic acid, physodalic acid, 3-hydroyphysodic acid) and one depside (i.e., atranorin). The developed composition of the solvent mixtures ensured good efficiency when extracting the metabolites from the thallus of H. physodes with high antioxidant properties.

Cocrystal Phase Diagrams for Systems Formed by Succinic Acid, Fumaric Acid, and Benzoic Acid in Ethanol with Tebuconazole

Cocrystal Phase Diagrams for Systems Formed by Succinic Acid, Fumaric Acid, and Benzoic Acid in Ethanol with Tebuconazole

Multi‐response optimization of characteristics for graphite reinforced biodegradable PVA‐fumaric acid cross‐linked composite: A gray‐fuzzy logic‐based hybrid approach

AbstractIn the current investigation, enhancement in the mechanical properties, thermal stability, and decrement in the moisture absorption capabilities of polyvinyl alcohol was observed by cross‐linking it with different weight percentages (wt. %) of fumaric acid and reinforcing them along with sulfuric acid‐modified graphite particles. The effects of altering the cross‐linking duration and fumaric acid wt. % were investigated in the resulting composite using the Taguchi L16 experimental design method. As in this contemporary era of rapid industrial expansion and fierce competition, the primary goals of manufacturers revolve around the production of high‐quality goods at optimal costs within a specified timeframe. Therefore, to save both cost and time, the authors have utilized a technique known as “gray‐fuzzy optimization” to balance competing goals between mechanical (toughness, elongation and strength) and physical (water intake capacity) attributes. The present approach aimed to reduce the experimentation expenses and increase the effectiveness of composite manufacturing by considerably reducing the intricacy of practical multi‐response optimization issues. Response graphs and analysis of variance tests were also utilized to calculate the percentage contribution of the input variables and provide model significance.Highlights Polyvinyl alcohol is cross‐linked with different weight percentages (wt. %) of fumaric acid, and reinforced them with sulfuric acid‐modified graphite particles. Enhancement in mechanical properties, thermal stability, and decrease in moisture absorption capabilities were perceived for the fabricated composite. Effects of altering the cross‐linking duration and fumaric acid wt. % were investigated in the resulting composite using the Taguchi L16 experimental design. Gray‐fuzzy optimization technique was utilized to balance competing goals between water intake and mechanical attributes like toughness, elongation and strength. Response graphs and analysis of variance (ANOVA) tests were also utilized to evaluate the percentage contribution of input variables and provide model significance.

Fine-tuning porosity of In-MOFs with ncb topology based on reticular chemistry for one-step purification C2H4 from ternary C2H6/C2H4/C2H2 mixtures

One-step purification of C2H4 from ternary C2H6/C2H4/C2H2 mixtures by single adsorbent is of great industrial significance, but few adsorbents can achieve this purpose. Herein, four isoreticular In-MOFs, In-BDC-AINA, In-ATC-INA, In-Fum-INA, and In-Fum-AINA (H2BDC, H2ATC, H2Fum, HINA, and HAINA are 1,4-benzenedicarboxylic acid, 2-amino-terephthalic acid, fumaric acid, isonicotinic acid and 3-amino-isonicotinic acid, respectively), were designed and synthesized by the guidance of reticular chemistry, using the known In-BDC-INA as the platform, through amino modification and ligand shortening approaches. In-ATC-INA and In-BDC-AINA were aminations of H2BDC and HINA, respectively. In-Fum-INA is replacing H2BDC to shorter H2Fum. In-Fum-AINA is obtained by further amination of In-Fum-INA. Due to the molar ratio of isoniacic and dicarboxylic ligands in this series structure is 2/1, they exhibit different site numbers, site distributions, pore sizes and pore volumes after regulation. These frameworks without open metal sites provided the ability of C2H6/C2H4 inversion adsorption. The amino modification and ligand shortening approaches successfully improved the selectivity of C2H2/C2H4, and the equimolar C2H2/C2H4 selectivities of In-ATC-INA (1.82) and In-Fum-INA (2.81) were higher than that of In-BDC-INA (1.73) calculated by IAST method. The breakthrough results show that In-BDC-INA, In-ATC-INA and In-Fum-INA can achieve one-step separation of the ternary C2 mixtures and the C2H4 yields are 0.08, 0.13 and 0.09 mmol/g, respectively, demonstrating that the two approaches have successfully improved the gas separation performance. In addition, these materials possess exceptional thermal and chemical stability, the low-cost ligand used in In-Fum-INA synthesis further enhances its potential application for industrial gas separation.

135 Effects of altering diet acid-binding capacity-4 (ABC-4) with specialty soy protein sources or acidifiers on nursery pig performance and fecal dry matter

Abstract A total of 300 pigs (initial body weight = 6.0 kg) were used to evaluate the effects of altering diet acid-binding capacity-4 (ABC-4) with specialty soy protein sources or acidifiers on nursery pig performance and fecal dry matter (DM). At weaning, pigs were allotted to 1 of 5 dietary treatments. There were 5 pigs/pen and 12 replications/treatment. Pigs were fed experimental diets in two phases with phase 1 fed from d 0 to 10 post-weaning followed by phase 2 from d 10 to 24. A low ABC-4 diet was formulated to 200 and 250 meq/kg in phase 1 and 2, respectively. The low ABC-4 diet utilized 0.38% fumaric acid, 0.36% formic acid, and specialty soy protein concentrate (AX3 Digest; Protekta; Newport Beach, CA) at 9.38 and 7.50% of the diet in phase 1 and 2, respectively. For the first medium ABC-4 diet, specialty soy protein concentrate was replaced with enzymatically treated soybean meal (HP 300; Hamlet Protein; Findlay, OH) on an SID Lys-basis and resulted in an ABC-4 of 290 and 322 meq/kg for phase 1 and 2, respectively. For the second medium ABC-4 diet, acidifiers were removed resulting in an ABC-4 of 271 and 321 meq/kg for phase 1 and 2, respectively. In the high ABC-4 diet, both soy protein replacement and acidifier removal strategies were utilized resulting in ABC-4 values of 362 and 394 meq/kg for phase 1 and 2, respectively. In addition, a control diet was utilized with the same formulation as the high ABC-4 diet but with 3,000 and 2,000 mg/kg of Zn from ZnO in phase 1 and 2, respectively. Following phase 2, all pigs were fed a common diet until d 38 of the study. Increasing ABC-4 decreased (linear, P ≤ 0.043) gain to feed ratio (G:F) during the experimental period and overall (Table). Increasing ABC-4 decreased (linear, P ≤ 0.005) fecal DM on d 10 and 24, with no differences on d 17. Pigs fed the medium ABC-4 diet based on specialty soy protein replacement had increased (P = 0.003) fecal DM on d 10 compared with the medium ABC-4 diet where acidifiers were removed. Pigs fed diets containing pharmacological levels of Zn from ZnO had increased (P ≤ 0.047) body weight (BW), average daily gain (ADG), average daily feed intake (ADFI), and G:F during the experimental period but decreased (P = 0.005) ADG and G:F during the common period, with no differences overall compared with pigs fed diets not containing ZnO. In conclusion, as dietary ABC-4 increased from 200 to 362 meq/kg in phase 1 and 250 to 294 meq/kg in phase 2, growth performance and fecal DM decreased. This study suggests a dietary ABC-4 of 200 and 250 meq/kg in phase 1 and 2, respectively, can be utilized to improve growth performance and fecal dry matter of weanling pigs.

PSIV-16 Evaluation of specialty soybean products and organic acids to alter nursery diet acid-binding capacity-4 on pig performance and fecal dry matter

Abstract A total of 300 weanling pigs (241 × 600, DNA, initial body weight = 5.6 ± 0.2 kg) were used to evaluate the effects of altering the acid-binding capacity-4 (ABC-4) of nursery diets with different specialty soybean products and organic acids on performance and fecal dry matter (DM). At weaning, pigs were allotted to 1 of 6 dietary treatments. There were 5 pigs/pen and 10 replications/treatment. Diet 1 was formulated with 12.0% specialty soy protein concentrate (AX3 Digest; Protekta; Newport Beach, CA), 1.06% citric acid, and 0.5% fumaric acid to achieve an ABC-4 of 223 meq/kg. Diets 2 and 3 were the same as diet 1 except citric and fumaric acid were reduced by 50 and 100% to achieve an ABC-4 of 280 or 338 meq/kg, respectively. Diets 4 and 5 were the same as diet 1 except 50 and 100% of the specialty soy protein concentrate was replaced with enzymatically treated soybean meal (HP 300; Hamlet Protein; Findlay, OH) on an SID Lys basis to achieve ABC-4 of 280 and 338 meq/kg, respectively. Diet 6 was a positive control with the same formulation as diet 5 except for the addition of 2,500 mg/kg of Zn from ZnO and a diet ABC-4 of 410 meq/kg. Dietary treatment structure allowed for the comparison of increasing ABC-4 (223 to 338 meq/kg) and formulation method (decreasing acidifier vs. specialty soy protein concentrate replacement) as well as their interactions. Pigs were fed the experimental diet for 24 d postweaning (d 0 to 24) followed by a common diet for an additional 18 d. There were no significant (P > 0.05) ABC-4 method × level interactions throughout the study (Table). From d 0 to 10, increasing ABC-4 decreased (linear, P = 0.042) gain to feed ratio (G:F) with no other differences in performance due to ABC-4. Formulation method influenced fecal DM with replacement of specialty soy protein concentrate (diets 4 and 5) reducing (P = 0.038) fecal DM compared with decreasing acidifier level (diets 2 and 3) on d 17. During the experimental period (d 0 to 24), pigs fed the diet with pharmacological Zn from ZnO had increased (P < 0.05) body weight (BW), average daily gain (ADG), average daily feed intake (ADFI), and G:F compared with pigs fed diets without ZnO. In summary, pharmacological Zn from ZnO improved nursery pig performance when experimental diets were fed. Increasing ABC-4 and the formulation method had minimal effects on nursery pig performance; however, fecal DM was influenced by formulation method. Increasing ABC-4 from 223 to 338 meq/kg may not have been a large enough difference to observe a response to changing ABC-4 of the diet. Further research is warranted to determine the influence of lower ABC-4 levels or other ingredient changes to achieve target ABC-4.

75 Diet acid-binding capacity-4 influences nursery pig performance and fecal dry matter

Abstract A total of 360 pigs (initial body weight = 5.9 kg) were used to evaluate the effects of increasing acid-binding capacity-4 (ABC-4) of the diet on nursery pig performance and fecal dry matter (DM). At weaning, pigs were allotted to 1 of 6 dietary treatments. There were 5 pigs/pen and 12 replications/treatment. Pigs were fed experimental diets in two phases with phase 1 from d 0 to 10 post-weaning followed by phase 2 from d 10 to 23. Diets were formulated with increasing ABC-4 levels ranging from 150 meq/kg (diet 1, low ABC-4) to 312 meq/kg (diet 5, high ABC-4) in phase 1 and 200 meq/kg (diet 1, low ABC-4) to 343 meq/kg (diet 5, high ABC-4) in phase 2. For diet 1, low ABC-4 diets were formulated using specialty soy protein concentrate (AX3 Digest; Protekta; Newport Beach, CA) at 12.5 and 10.0% of the diet in phase 1 and 2, respectively. The low ABC-4 diet also utilized fumaric and formic acid at 0.50 and 0.48% of the diet, respectively, for both phase 1 and 2. For diets 2 (medium low), 3 (medium), 4 (medium high), and 5 (high), increasing dietary ABC-4 was achieved by progressively decreasing the level of acidifiers and replacing specialty soy protein concentrate with enzymatically treated soybean meal (HP 300; Hamlet Protein; Findlay, OH) on an SID Lys basis. Diets 1 through 5 were formulated without the addition of pharmacological levels of Zn from ZnO. For diet 6, a positive control diet was used which had the same formulation as the highest ABC-4 diet but with the addition of 3,000 and 2,000 mg/kg of Zn from ZnO in phase 1 and 2, respectively. Following phase 2, all pigs were fed a common diet until d 38 of the study. In the experimental period and overall, there was a quadratic response observed (P ≤ 0.030) where body weight (BW) and average daily gain (ADG) were greatest for pigs fed the medium low and medium ABC-4 diets (Table). During the experimental period, increasing ABC-4 decreased (linear, P = 0.002) gain to feed ratio (G:F). For overall G:F, a quadratic response was observed (P = 0.023) where G:F was most improved for pigs fed the medium low and medium ABC-4 levels. For fecal DM, increasing ABC-4 decreased (linear, P ≤ 0.036) fecal DM on d 10 and 17, with no differences on d 23. Pigs fed the diet with pharmacological levels of Zn from ZnO had increased (P ≤ 0.038) ADG compared with pigs fed diets without ZnO during the experimental period and overall. In summary, a dietary ABC-4 level of 203 and 247 meq/kg for phase 1 and 2, respectively, was most beneficial to improve both growth performance and fecal DM in weanling pigs.

Development of a rapid quantitative method of analysis of carbohydrate fatty acid ester reaction mixtures using 1H qNMR

Two new analytical methods, applying absolute 1H qNMR, were developed to monitor product yield and quantify unreacted carbohydrate and fatty acid reactants, in the synthesis of carbohydrate fatty acid esters (CFAE). These methods provide a mass balance of the crude reaction mixtures and diversify the analytical screening and quantitation approaches available within the synthesis of these molecules. Both methods were validated for the model reaction of methyl α-d-glucopyranoside (MAG) and lauric acid (LA) to form the mono ester product, methyl 6-O-dodecanoyl-α-d-glucopyranoside. Analysis in CD3OD by 1H qNMR, with fumaric acid (FA) as an internal standard (IS), allowed monitoring of all reaction components. Alternatively, using CDCl3 and (E)-stilbene as IS enabled the analysis of CFAE and fatty acid. Parameters calculated for method validation included specificity and selectivity, linearity, accuracy, intermediate precision, limit of detection (LOD), limit of quantification (LOQ) and robustness. Both methods provided excellent linearity with R2 > 0.997. The accuracy, precision, and robustness of the method in CD3OD was <2 % uncertainty making it suitable for complete reaction analysis. The method completed in CDCl3 resulted in accuracy, intermediate precision, and robustness of <5 %, except for accuracy in the lowest levels of concentration (>5 %). For all related analytes in the CD3OD and CDCl3 methods, the LOD and LOQ were determined to ensure applicability for the intended use in the assessment of reaction crude composition. Finally, the system suitability was assessed in a scaled lipase catalysed CFAE synthetic reaction. The determined qNMR product yields were verified against isolated purified product yields with <5 % uncertainty.

Punicalagin prevents obesity-related cardiac dysfunction through promoting DNA demethylation in mice

The aim of this study was to investigate whether punicalagin (PU) could prevent obesity-related cardiac dysfunction by promoting DNA demethylation, and to explore its possible mechanism. C57BL/6J mice were fed with standard diet, high-fat diet (HFD), HFD supplemented with resveratrol, low-dose PU (LPU) and high-dose PU (HPU) for 8 weeks. Compared with HFD group, body weight was significantly lower in PU treatment groups, number of cardiomyocytes and the protein level of myosin heavy chain 7B were significantly higher in PU treatment groups. Levels of 5-hydroxymethylcytosine and 5-formylcytosine were significantly lower in HFD group than in other groups. Compared with the HFD group, the protein level of ten-eleven translocation enzyme (TET) 2 was significantly higher in PU treatment groups, p-AMP-activated protein kinase (AMPK) was significantly higher in LPU group. Levels of total antioxidant capacity and the protein levels of complexes II/III/V, oxoglutarate dehydrogenase, succinate dehydrogenase B and fumarate hydrolase were significantly lower in HFD group than PU treatment group. The ratio of (succinic acid + fumaric acid)/α-ketoglutarate was significantly higher in HFD group than other groups. In conclusion, PU up-regulated TETs enzyme activities and TET2 protein stability through alleviating mitochondrial dysfunction and activating AMPK, so as to promote DNA demethylation, thus preventing obesity-related cardiac dysfunction.

Extraction of bioactive compounds from Vitex megapotamica: A study and selection of variables

AbstractFruits are widely used to obtain and study bioactive compounds. Among them, the tarumã (Vitex megapotamica) is still understudied. The extraction of bioactive compounds from the powdered pulp of the ripe fruit of the tarumã was studied from the selection of several variables of the extraction process through the experimental design Plackett–Burman: the pH, the solid:liquid ratio, agitation, and temperature in an extraction time of 3 h. The extracts obtained were evaluated for antioxidant activity by 2,2′‐azino‐bis‐(3‐ethylbenzothiazoline‐6‐sulfonic acid) (ABTS), 2,2‐diphenyl‐1‐picrylhydrazyl (DPPH), and for total phenolic compounds, as well as the presence of flavonoids, anthocyanins, carotenoids, and identification of bioactive compounds was assessed by high‐performance liquid chromatography (HPLC). Using the experimental design, the best extraction condition was defined with a pH of 5, solid:liquid ratio of 1:30, stirring at 100 rpm, with a temperature of 80°C, obtaining 104.21 mg Gallic Acid Equivalent (GAE) 100 g−1 for phenolic compounds total, 742.71 μmol Trolox g−1 for ABTS, and EC50 of 2884.98 mg L−1 for DPPH. From HPLC, the presence of fumaric acid, gallic acid, p‐coumaric acid, and caffeic acid in the extracts was detected. Regarding flavonoids, anthocyanins, and carotenoids, the values obtained were 6.38 mg ECG g−1, 1.67 mg ECG g−1, and 2.89 mg 100 g−1, respectively. The selection of extraction conditions allowed obtaining better levels of bioactive compounds in the powdered pulp of tarumã extract, even with the use of water as a solvent, to avoid the presence of chemical residues in the extract, with antioxidant potential and viability for application in food products.Practical applicationsRecent research suggests a change in perspective regarding the consumption of healthier foods from plants and fruits that have important health properties. In this regard, tarumã (Vitex megapotamica) fruit has been standing out as a potential source of bioactive compounds with significant medicinal properties. The extracts obtained have a significant amount of phenolic compounds, as well as the presence of flavonoids, anthocyanins, and carotenoids, in which all of these have great potential bioactive activities. Thus, a good methodology of extraction and characterization of tarumã extract becomes a crucial part of any food, chemical, or pharmaceutical industry sector. In this regard, the present study with experimental design Plackett–Burman extraction is the way ahead due to high bioactive retention and the cost implications of the process.

Pathophysiology of Carnitine Palmitoyltransferase 2 (CPT2) Deficiency in the Dahl Salt-sensitive R at

Carnitine palmitoyltransferase 2 (CPT2) is an essential enzyme of the carnitine shuttle, which facilitates fatty acid -oxidation in mitochondria. This study aims to characterize the various effects of CPT2 deficiency on the Dahl salt-sensitive (SS) rat metabolome and its concomitant influence on renal homeostasis. CRISPR/Cas9 was used to insert a single base pair into the SS Cpt2 gene, causing a frameshift mutation found to be lethal in homozygotes (SSCpt2−/−). Western blotting and qPCR analysis of renal cortex tissue confirmed a reduced expression of CPT2 in heterozygous (SSCpt2+/-) rats compared to wild-type (WT) littermates; therefore, male and female heterozygotes were used for all experiments. Lipid metabolomics of renal cortex samples collected from SSCpt2+/- animals at 8 weeks old on a baseline 0.4% NaCl diet revealed a significant upregulation in inflammatory lipids such as 11-HETE (p&lt;0.01) and 12-HHT (p&lt;0.05) when compared to WT littermates. Urine analysis from the SSCpt2+/- group demonstrated a severe reduction in acetoacetic acid production (p&lt;0.001), indicating ketogenesis is likely impacted by the loss of CPT2 in -oxidation. Additionally, TCA cycle metabolites fumaric acid (p&lt;0.05) and oxaloacetic acid (p&lt;0.01) are significantly downregulated in urine from SSCpt2+/- animals. Radio telemeters were implanted into the rats at 8 weeks of age to continuously record mean arterial pressure (MAP) and monitor the development of SS hypertension over the course of several dietary treatment protocols. Three weeks of either a 4% NaCl high-salt (HS) diet or a HS + ketogenic (HSK) diet with equivalent caloric content (4:1 caloric ratio, fat: carbohydrate) were administered to the animals. No difference in MAP elevation occurred between groups after the HS challenge alone, but SSCpt2+/- animals on the HSK diet had a significantly attenuated development of hypertension (p=0.03). Further metabolic analysis after the HSK diet illustrated that both groups had similar increases in long-chain fatty acids, liver enzymes, and cholesterol levels with a decrease in short-chain fatty acids. These experiments show that the partial loss of CPT2 in the Dahl SS rat leads to dysregulation across multiple metabolic pathways. Moreover, a ketogenic diet appears to protect heterozygous animals from the development of salt-sensitive hypertension. Funding: NIH R35 HL135749 and VA I01 BX004024. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.