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Introduction: Alfalfa (Medicago sativa L.) is a globally important legume crop with high nutritional and ecological value. Drought poses a serious threat to alfalfa acreage and yields. Spermine (Spm) has been shown to protect plants from drought damage. The aim of this study was to clarify the mechanism of exogenous Spm to improve drought resistance of alfalfa. Methods: In this study, we root applied 0.1, 0.5, and 1mM Spm to Gannong No. 3 (G3) alfalfa under drought stress, and then determined their physiological and metabolic changes. Results: The results showed that exogenous Spm increased chlorophyll content, chlorophyll fluorescence parameters and gas exchange parameters, enhanced antioxidant enzymes activity, improved ascorbic acid-glutathione (AsA-GSH) cycle, increased osmoregulatory substances content, reduced hydrogen peroxide and superoxide anion levels, and inhibited malondialdehyde accumulation in alfalfa under drought stress, thereby increasing plant height and leaf relative water content and enhancing drought tolerance of alfalfa. The redundancy analysis of the above physiological indicators showed that the addition of the optimal Spm to improve drought tolerance of alfalfa under drought stress was mainly achieved by increasing catalase activity and improving the ASA-GSH cycle. In addition, metabolomics analysis revealed that exogenous Spm increased the content of oxobutanedioic acid, citric acid, fumaric acid and malic acid to enhance the tricarboxylic acid cycle. Meanwhile, exogenous Spm increased endogenous Spm and proline (Pro) content to resist drought stress by enhancing Spm and Pro metabolism. Moreover, exogenous Spm increased the accumulation of the signaling substance abscisic acid. Discussion: In conclusion, exogenous Spm enhanced drought resistance of alfalfa leaves under drought stress. [ABSTRACT FROM AUTHOR]

Many soils face dual challenges of cadmium (Cd) contamination and salinization. However, the response of crops, especially wheat, to combined Cd and salinity stress is not understood. Here, wheat was grown in a hydroponic model for 14 days under single and combined Cd and NaCl stresses. Growth parameters, tissue Cd2+ and Na+ contents, and leaf chlorophyll (Chl), O2•-, and MDA levels were determined. Comparative transcriptomic and metabolomic analyses of the leaves were performed. The results showed that combined stress had a greater inhibitory effect on Chl contents and generated more O2•- and MDA, resulting in more severe wheat growth retardation than those under Cd or NaCl stress. Stress-induced decrease in Chl levels may be attributed to the inhibition of Chl biosynthesis, activation of Chl degradation, or a decline in glutamate content. Cd addition weakened the promotional effect of NaCl on SOS1 gene expression, thereby increasing the Na+ content. Contrastingly, NaCl supplementation downregulated the Nramp and ZIP gene expressions related to Cd uptake and transport, thereby impeding Cd2+ accumulation. All stresses enhanced tryptophan content via promoting tryptophan biosynthesis. Meanwhile, Cd and NaCl stresses activated phenylpropanoid biosynthesis and purine metabolism, respectively, thereby increasing the levels of caffeic acid, fumaric acid, and uric acid. Activating the TCA cycle was important in the wheat's response to combined stress. Additionally, NaCl and combined stresses affected starch and sucrose metabolism, resulting in sucrose and trehalose accumulation. Our findings provide a comprehensive understanding of the response of wheat to the combined Cd and salinity stress. [ABSTRACT FROM AUTHOR]

Mouth cancer is the most frequent cancer of the head and neck in both older and younger people. Achyranthes aspera L. has been used in ethnotraditional and pharmacological applications since ancient times for a variety of disorders. This study was formulated to examine bioactive phenolic and flavonoid compounds from the ethanolic extract of Achyranthes aspera and their binding efficacy targeting growth factor receptors (GFRs) against mouth cancer through in silico molecular docking and simulation studies. Phytochemicals were investigated through the UHPLC technique. A molecular docking study was accomplished using docking software AutoDock 4.2, and MD simulation was executed through GROMACS software. Drug‐likeness, pharmacokinetics, and toxicity profiles of phytocompounds were evaluated using Molinspiration, Swiss ADME, OSIRIS Data Warrior tools, respectively. UHPLC analysis detected phenolics and flavonoids, viz., fisetin, rutin, and fumaric acid, which satisfied Lipinski's rule of five and pharmacokinetic properties. In molecular docking assessment, fisetin exhibited promising interactions with core targeted proteins VEGFR‐2 (B.E. = −8.30 kcal mol−1) and FGFR‐2 (B.E. = −7.64 kcal mol−1) of mouth cancer. Moreover, molecular dynamics simulation data demonstrated stable interactions with both VEGFR‐2 and FGFR‐2 proteins. This binding interaction and stability of A. aspera phytocompounds with therapeutic proteins might contribute to their therapeutic potential in mouth cancer management. [ABSTRACT FROM AUTHOR]

Three nickel, copper, and zinc complexes with dicarboxylic acids (3,3′-dithiodipropionic acid (H2dtdp) and fumaric acid (H2fu)) and N-donor ligands (1,10-phenanthroline (phen), N′–methyldipropylenetriamine (mdpta), and N,N,N′,N″,N″-pentamethyldiethylenetriamine (pmdien)) were synthesized. These complexes were characterized using elemental analysis, IR spectroscopy, and single-crystal X-ray diffraction. Interestingly, [Ni(dtdp)(phen)(H2O)3]∙0.5H2O (1) is a mononuclear complex, where the dtdp dianion employs only one carboxylate group for coordination to the central nickel atom. [(ClO4)(mdpta)Cu(μ-dtdp)Cu(mdpta)(H2O)](ClO4) (2) is a dinuclear copper complex with a dtdp bridge and different coordination on the copper center. [{Zn(pmdien)(H2O)}2(μ-fu)](ClO4)2 (3) is a symmetric dimer with a bridging fumarate ligand. These coordination compounds were tested for their antibacterial activities on Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Enterococcus faecalis bacteria strains. All the complexes show moderate activities on the mentioned strains. [ABSTRACT FROM AUTHOR]

AbstractObjective: Fumaric acid is a dicarboxylic acid that belongs to the phenolic class enriched in fruits and vegetables that are traditionally used for the treatment of various ailments. The research was planned to find out the anti-inflammatory and anti-arthritic activities of fumaric acid using in-vitro and in-vivo assays. Moreover, safety study was also done.Materials and methods: The 0.1 ml complete Freund’s adjuvant was injected in left hind paw in all Wistar rats except normal rats at day 1 to induced arthritis. The treatment with fumaric acid at 10, 20, 40, and fumaric acid 40 mg/kg together with methotrexate (MTX) was administered to immunized rats at 8th day via oral gavage and continued till 28th day though, MTX was administered as standard control.Results: The fumaric acid notably (p < 0.0001) lessened the paw edema and arthritic scoring, reinstated body and immune organ weight, and oxidation status in treated rats. Fumaric acid notably restored altered C-reactive protein, rheumatoid factor, liver function tests, ESR, WBCs, RBCs and Hb levels in treated rats. The fumaric acid in combination noticeably (p < 0.01–0.0001) suppressed the expression of TNF- α, IL-6, IL-1β, NF-kβ, and COX-2, and over expressed IL-4, and IL-10 in contrast to other treated groups. Fumaric acid had presented a dose-dependent antioxidant, anti-inflammatory and anti-arthritic activities while notable activity exhibited by fumaric acid in combination with MTX. The fumaric acid exhibited non-significant clinical signs of toxicity and mortality in acute toxicity study. The LD50 was more than 2000 mg/kg.Conclusion: Fumaric acid in combination can be used as disease-modifying anti-rheumatic drug but it will need extensive pre-clinical and clinical studies. [ABSTRACT FROM AUTHOR]

[Display omitted] • Inverted modulator synthesis of a novel cheap double-ligand Zr-based MOF (MA-MOF). • MA-MOF shows enhanced adsorption and photocatalytic degradation toward tetracycline. • MA-MOF yields holes, ·OH and ·O2− under visible-light for degrading 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 [Zr 6 O 4 (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. [ABSTRACT FROM AUTHOR]

Fumaric acid, a naturally occurring preservative with antimicrobial properties, has been widely used in the baking industry. However, its direct addition interferes with yeast activity and negatively impacts the gluten structure. This study investigates the potential of spray-congealing as a method for encapsulating fumaric acid within solid lipid microparticles. The selection of lipid carriers and surfactants is critical, so hydrogenated palm stearin, hydrogenated rapeseed oil, and Compritol ATO 888 (glyceryl behenate) were chosen as lipid carriers, and propylene glycol monostearate and glyceryl monolaurate were utilised as surfactants with varying concentrations. Rheological properties, encapsulation efficiency, particle size, moisture content, and thermal behaviour were assessed, along with the release profiles under different temperature conditions simulating the baking process. The findings indicate that the addition of surfactants significantly impacts the viscosity and stability of the molten mixtures, which in turn affects the spray-congealing process and the release of fumaric acid. The temperature-dependent and time-dependent release profiles demonstrate the potential for customising release kinetics to suit specific applications, such as the baking industry. This study may contribute to the development of a controlled-release system that synchronises with the baking process, thereby optimising fumaric acid's functionality while preserving the quality of baked goods. [ABSTRACT FROM AUTHOR]

Organic saline wastewater has become a concern in recent decades due to its resistance to biological treatment and potential harm to municipal wastewater treatment plants. While photocatalytic methods have been used for treatment, they often lead to catalyst deterioration. The use of salt-tolerant catalysts presents a viable solution for treating organic saline wastewater. In this study, a Zn-rich g-C3N4 was synthesized, demonstrating excellent performance in removing 2,4-DCP and its derivatives from saline wastewater. More than 75.6% of 2,4-DCP was effectively removed with the addition of Zn-rich g-C3N4, nearly doubling the removal rate compared to pure g-C3N4 and those doped with Co, Ag, Mo, and Bi. Notably, the removal efficiency of 2,4-DCP slightly increased as salinity rose from 0.1 to 2.3 wt.%. Adding 0.1 g L−1 of Zn-rich g-C3N4 resulted in the removal of 2,4-DCP, 2-chlorohydroquinone, chloroacetophenone, and 2-chloropropionic acid by 99.3%, 99.8%, 98.2%, and 99.9%, respectively, from a real saline wastewater sample with 2.2 wt.% salinity, corresponding to a 67.7% removal of TOC. The EPR results indicated that Zn-rich g-C3N4 generated more free radicals compared to pure g-C3N4, such as·OH and Cl, to degrade organic contaminants. The degradation pathway revealed that 2,4-DCP was first dechlorinated into p-phenol and catechol, which were subsequently degraded into maleic acid/fumaric acid, trihydroxyethylene, acetic acid, oxalic acid, and other products. Furthermore, Zn-rich g-C3N4 demonstrated excellent stability and holds promising potential for applications in saline wastewater treatment. [ABSTRACT FROM AUTHOR]

Materials that show significant negative linear compressibility (NLC) reported so far suffer from a number of shortcomings that affect their applicability. The cocrystal of 1,2-bis(4-pyridyl)ethane and fumaric acid, which exhibits exceptional NLC behaviour, overcomes these problems and sets the foundation for the development of environmentally friendly metal-free NLC materials. [ABSTRACT FROM AUTHOR]

This study investigated the effects of dietary resveratrol (RES) and β-Hydroxy-β-methyl butyric acid (HMB) on immune, oxidative, and morphological changes in the livers of Tibetan sheep using transcriptomics and metabolomics. One hundred and twenty male Tibetan lambs of a similar initial weight (15.5 ± 0.14 kg) were randomly divided into four groups with thirty lambs per treatment: (1) H group (basal diet without RES or HMB); (2) H-RES group (1.5 g/day of RES); (3) H-HMB group (1250 mg/day of HMB); (4) H-RES-HMB group (1.5 g/day of RES and 1250 mg/day of HMB). The experiment was conducted for 100 days, including a pre-test period of 10 days and a formal period of 90 days. The results showed significantly increased concentrations of glutathione peroxidase, superoxide dismutase, and IgM in the H-RES-HMB group (p < 0.05), while the malondialdehyde levels were significantly decreased (p < 0.05). The glycolytic indices including creatinine kinase (CK), malate dehydrogenase (MDH), and succinate dehydrogenase (SDH) were significantly increased in the H-RES-HMB group compared with the others (p < 0.05). A histological analysis showed that the hepatic plate tissue in the H-RES-HMB group appeared normal with multiple cells. The transcriptomic analysis showed that the expression of genes associated with the calcium signaling pathway (MYLK2, CYSLTR2, ADCY1, HRH1, ATP2B2, NOS2, HRC, ITPR1, and CAMK2B) and the NF-κB signaling pathway (BCL2 and CARD14) in the H-RES-HMB group were upregulated. The key differential metabolites (d-pyroglutamic acid, DL-serine, DL-threonine, fumarate, and glyceric acid) were enriched in the pathways associated with D-amino acid metabolism, the citrate cycle (TCA cycle), and carbon metabolism. The combined transcriptomic and non-targeted metabolomic analyses showed the co-enrichment of differential genes (NOS2 and GLUD1) and metabolites (fumarate) in arginine biosynthesis-regulated glycolytic activity, whereas the differential genes (ME1, SCD5, FABP2, RXRG, and CPT1B) and metabolites (Leukotriene b4) co-enriched in the PPAR signaling pathway affected the immune response by regulating the PI3K/AKT and cGMP/PKG signaling. In conclusion, the dietary RES and HMB affected the hepatic antioxidant capacity, immune response, and glycolytic activity through modulating the transcriptome (BCL2, CAMK2B, ITPR1, and IL1R1) and metabolome (DL-serine, DL-threonine, fumaric acid, and glycolic acid). [ABSTRACT FROM AUTHOR]

Soil salinity pollution is increasing worldwide, seriously affecting plant growth and crop production. Existing reports on how potassium indole-3-butyric acid (IBAK) regulates rice salt stress adaptation by affecting rice carbon metabolism, transcription factor (TF) genes expression, and biosynthesis of secondary metabolites still have limitations. In this study, an IBAK solution at 40 mg L-1 was sprayed on rice leaves at the seedling stage. The results showed that the IBAK application could promote shoot and root growth, decrease sucrose and fructose content, increase starch content, and enhance acid invertase (AI) and neutral invertase (NI) activity under salt stress, indicating altered carbon allocation. Furthermore, the expression of TF genes belonging to the ethylene responsive factor (ERF), WRKY, and basic helix-loop-helix (bHLH) families was influenced by IBAK. Many key genes (OsSSIIc, OsSHM1, and OsPPDKB) and metabolites (2-oxoglutaric acid, fumaric acid, and succinic acid) were upregulated in the carbon metabolism pathway. In addition, this study highlighted the role of IBAK in regulating the biosynthesis of secondary metabolites pathway, potentially contributing to rice stress adaptability. The results of this study can provide new sustainable development solutions for agricultural production. [ABSTRACT FROM AUTHOR]

In this study, the appropriate polymer solutions were prepared to create chitosan/PVA blends. By altering the ratio of the ingredients, several chitosan/PVA mixtures were produced, as follows: 12% chitosan and 88% PVA, 40% chitosan and 60% PVA, and 15% chitosan and 85% PVA. To generate physically crosslinked hydrogels for the drug delivery of atenolol, several acid cross-linkers, such as fumaric acid and phthalic acid, were applied to the chitosan/PVA blends. The formulations included 15% chitosan and 85% PVA with 0.02% (0.0024, 0.0041, 0.02) mol of fumaric acid, as well as 15% chitosan and 85% PVA with 0.002, 0.003, and 0.0064 mol of phthalic acid. Using an ultraviolet-visible spectrophotometer, the chemical structures of the modified and unmodified chitosan (Chitosan/PVA) hydrogels were examined. Results regarding the formation of ionic cross-links between the protonated hydroxyl groups of the chitosan and the anionic functional groups of the cross-linking agent were established. The swelling ratio was determined for each hydrogel structure as a function of time in three distinct fluids with pH values of 2, 4, and 7.5, and at three distinct temperatures of 42°C and 44°C. The samples with the greatest swelling ratios were identified as PVA.PA0.002 (chitosan) and PVA.FA0.0024. [ABSTRACT FROM AUTHOR]

Two copper(II) mixed ligand complexes with dicarboxylate bridges were prepared and studied, namely [Cu2(μ-fu)(pmdien)2(H2O)2](ClO4)2 (complex No. 5) and [Cu2(μ-dtdp)(pmdien)2(H2O)2](ClO4)2 (complex No. 6), where H2fu = fumaric acid, pmdien = N,N,N′,N″,N″ pentamethyldiethylenetriamine, and H2dtdp = 3,3′-dithiodipropionic acid. The copper atoms are coordinated in the same mode by the tridentate pmdien ligand and oxygen of water molecules, and they only differ in the dicarboxylate bridge. This work is focused on the study of the inhibitory effect of these potential antimicrobial drugs on the activity of the most important human liver drug-metabolizing enzymes, cytochromes P450 (CYP), especially their forms CYP2C8, CYP2C19, and CYP3A4. The obtained results allow us to estimate the probability of potential drug interactions with simultaneously administrated drugs that are metabolized by these CYP enzymes. In conclusion, the presence of adverse effects due to drug–drug interactions with concomitantly used drugs cannot be excluded, and hence, topical application may be recommended as a relatively safe approach. [ABSTRACT FROM AUTHOR]

Maintainance of extracellular volume and water balance is important in cellular metabolism and these properties confer to sodium profile, but overconsumption of sodium causes risk to health. The present study aimed to develop and evaluate fastdissolving effervescent tablets using a novel two-step wet granulation method, incorporating Olive (Olea europaea), halophyte marsh plant (Salicornia herbacea L.) and bamboo silica salts natural ingredients and edible organic acids viz. citric acid, malic acid, tartaric acid, apple cider vinegar powder, fumaric acid and alkalizing agents like sodium bicarbonate, anhydrous potassium carbonate, anhydrous sodium carbonate, potassium sulphate dodecahydrate as active ingredients to enhance bioavailability and dissolution. During the process, all active ingredients were milled separately and sifted through a number 40 mesh sieve, followed by blending for 10 min to create uniform wet mass and further, sieved through number 20 mesh to produce granules. Finally, the dried granules of the composition according to formulations were compressed into tablets with 12 mm diameter using a single punch tablet punching machine. The formulations adhered to pharmacopoeial quality standards, displaying favorable mechanical and physical properties. The results revealed that the effervescent granules in all the formulations exhibited excellent flow properties with Angle of Repose, Hausner's ratio and compressibility index in the ranges of 26.10°-29.52°, 1.07-1.12 and 6.12%-10.51% respectively. Formulations F1 and F3 emerged as the most effective, with friability <0.5%, water content <0.05%, effervescence time <2.5 min and excellent solubility on the Likert scale. The findings open avenues for further research into effervescent technology and its application in drug delivery systems. [ABSTRACT FROM AUTHOR]

Lymphopenia is a known adverse effect in patients with relapsing multiple sclerosis (RMS) treated with fumaric acids. We present a case series of four patients diagnosed with RMS with prolonged lymphocyte stability on dimethyl fumarate for over 1 year who developed significant lymphopenia after transitioning to diroximel fumarate. This case series highlights the need for further research to elucidate the risk of lymphopenia in patients switching between fumaric acids. [ABSTRACT FROM AUTHOR]

Background: In the treatment of oncological diseases in children, the search for opportunities for the earlier detection of complications to improve treatment results is very important. Metabolomic studies are actively conducted to stratify different groups of patients in order to identify the most promising markers. Methods: Three groups of patients participated in this study: healthy children as a control group (n = 18), children with various malignant oncological diseases (leukemia, lymphoma, nephroblastoma, ependymoma, etc.) as patients (n = 40) without complications, and patients (n = 31) with complications (inflammatory and infectious). The mitochondrial metabolites (succinic and fumaric acids); biomarkers related to inflammation such as C-reactive protein (CRP), procalcitonin (PCT), and presepsin (PSP); and sepsis-associated aromatic metabolites, such as phenyllactic (PhLA), hydroxyphenyllactic (p-HPhLA), and hydroxyphenylacetic acids (p-HPhAA), were identified. Results: It was found that children with malignant oncological diseases had profound metabolic dysfunction compared to healthy children, regardless of the presence of systemic inflammatory response syndrome (SIRS) or sepsis. The prognostic ability of procalcitonin and presepsin for detecting sepsis was high: AUROC = 0.875, cut-off value (Youden index) = 0.913 ng/mL, and AUROC = 0.774, with cut-off value (Youden index) of 526 pg/mL, respectively. Conclusions: A significant increase in aromatic microbial metabolites and biomarkers in non-survivor patients that is registered already in the first days of the development of complications indicates the appropriateness of assessing metabolic dysfunction for its timely targeted correction. [ABSTRACT FROM AUTHOR]

We present the synthesis and characterisation of three Ce-based metal–organic frameworks (Ce–MOFs) using fumaric acid (Fu), terephthalic acid (BDC), and trimesic acid (H3BTC) as linkers. The use of different linkers influenced the size of the MOF particles, surface area, crystallinity, and microporous structure. The successful implementation of Ce–Fu, Ce–BDC, and Ce–H3BTC MOFs for fluoride ion removal from wastewater was carried out, in which Ce–Fu MOFs exhibited a maximum adsorption capacity (AC) of 64.2 mg g−1. The study also reveals that the use of ultrasound as a mediator for adsorption study over conventional method gives rapid adsorption rate, in which 85% of the fluoride uptake took place just in 10 min and achieved maximum AC in 30 min. The kinetics data were most accurately explained by the pseudo-second-order model (PSO). The existence of co-ions such as NO3−, Cl−, HCO3−, SO42−, Br−, CO32−, and PO43− has a substantial effect on fluoride removal. The mechanism between the fluoride ions and the MOF surface took place via the electrostatic force and the ion exchange process, confirmed using X-ray photoelectron spectroscopy (XPS) and delsa nano. The material is sustained its relatively higher F− ions removal efficiency up to the five cycles. This research might help in the development of novel microporous Ce-based MOFs since it possesses a highly stable crystalline structure in water, suggesting a promising role in aqueous applications. [ABSTRACT FROM AUTHOR]

Simple Summary: Benzoic acid has been supplemented in feeds to improve intestinal health and the growth rate of nursery pigs. Benzoic acid, a colorless crystalline organic compound, consists of a benzene ring with a carboxyl substituent, representing the simplest form of aromatic carboxylic acid. In pig feeds, benzoic acid primarily influences the small intestine rather than the large intestine of pigs, as benzoic acid does not require degradation in the stomach or beyond the small intestine. Benzoic acid possesses acidic properties, making it an effective feed additive in pig production through its antimicrobial action by reducing pH in feed and digesta in the gastrointestinal tract, positively modulating intestinal microbiota and enhancing nutrient utilization and intestinal health in pigs. Benzoic acid supplementation also decreases urinary pH through the production of hippuric acid and reduces ammonia emissions, which can positively affect the conditions of barns considering the intense pig production systems. However, depending on the levels of benzoic acid, its impact on growth is not always consistent. Thus, this review investigated the functional roles of benzoic acid on the intestinal health, nutrient utilization, and growth performance of nursery pigs, determined the optimal dose level of benzoic acid on the growth rate in nursery pigs, and compared the efficacy of benzoic acid and other acids, aiming to clarify the potential benefits of benzoic acid in pig feeds. The objectives of this review are to investigate how benzoic acid can mitigate the negative effects of weaning stress, improve the intestinal microbiota, intestinal health, and growth of nursery pigs, determine the optimal dose level of benzoic acid for the growth rate in nursery pigs, and compare the efficacy of benzoic acid and other acids in pig feeds. After weaning, pigs are exposed to less lactose and solid feed with high acid-binding capacity at infrequent intervals, causing an increase in digesta pH, reducing protein digestion, and increasing ammonia-producing bacteria in the stomach. Benzoic acid supplementation has improved the intestinal health and growth of nursery pigs through its antimicrobial properties and pH reduction in the digesta. The positive modulation of luminal microbiota in the small intestine of pigs by benzoic acid improves intestinal morphology and enhances nutrient utilization, especially nitrogen, of nursery pigs. Benzoic acid supplementation of up to 1% in feeds also increases hippuric acid contents in the urine of nursery pigs, decreasing urinary pH, which is related to ammonia emission and barn conditions in intensive pig production. Supported by the beneficial impacts of benzoic acid, the growth performance of nursery pigs was also improved. However, excessive benzoic acid (over 2.5% up to 5%) in feeds reduces the growth performance of nursery pigs. Thus, this review conducted a meta-analysis of the results from 16 papers to determine the optimal dose level of benzoic acid for body weight gain of nursery pigs, which was found to be 0.60%. The efficacy of benzoic acid was similar to that of other organic acids, including citric acid, fumaric acid, formic acid, and formate salts. Collectively, benzoic acid supplementation can positively modulate the luminal and mucosal microbiota in the small intestine, increase nutrient utilization and intestinal health, decrease urinary pH, and improve the growth performance of nursery pigs. [ABSTRACT FROM AUTHOR]

Semen cryopreservation results in the differential remodeling of the molecules presented in sperm, and these alterations related to reductions in sperm quality and its physiological function have not been fully understood. Given this, this study aimed to investigate the cryoinjury mechanism of goat sperm by analyzing changes of the metabolic characteristics in sperm during the cryopreservation process. The ultra-high-performance liquid chromatography–quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS) technique was performed to explore metabolite profiles of fresh sperm (C group), equilibrated sperm (E group), and frozen–thawed sperm (F group). In total, 2570 metabolites in positive mode and 2306 metabolites in negative mode were identified, respectively. After comparative analyses among these three groups, 374 differentially abundant metabolites (DAMs) in C vs. E, 291 DAMs in C vs. F, and 189 DAMs in E vs. F were obtained in the positive mode; concurrently, 530 DAMs in C vs. E, 405 DAMs in C vs. F, and 193 DAMs in E vs. F were obtained in the negative mode, respectively. The DAMs were significantly enriched in various metabolic pathways, including 31 pathways in C vs. E, 25 pathways in C vs. F, and 28 pathways in E vs. F, respectively. Among them, 65 DAMs and 25 significantly enriched pathways across the three comparisons were discovered, which may be tightly associated with sperm characteristics and function. Particularly, the functional terms such as TCA cycle, biosynthesis of unsaturated fatty acids, sphingolipid metabolism, glycine, serine and threonine metabolism, alpha-linolenic acid metabolism, and pyruvate metabolism, as well as associated pivotal metabolites like ceramide, betaine, choline, fumaric acid, L-malic acid and L-lactic acid, were focused on. In conclusion, our research characterizes the composition of metabolites in goat sperm and their alterations induced by the cryopreservation process, offering a critical foundation for further exploring the molecular mechanisms of metabolism influencing the quality and freezing tolerance of goat sperm. Additionally, the impacts of equilibration at low temperature on sperm quality may need more attentions as compared to the freezing and thawing process. [ABSTRACT FROM AUTHOR]

The list of standard abbreviations for JDS is available at adsa.org/jds-abbreviations-24. Nonstandard abbreviations are available in the Notes. Dietary methane (CH 4) mitigation is in some cases associated with an increased hydrogen (H 2) emission. The objective of the present study was to investigate the acute and short-term effects of acceptors for H 2 (fumaric acid, acrylic acid, or phloroglucinol) supplemented via pulse-dosing to dairy cows fed CH 4 mitigating diets (using nitrate or 3-nitrooxypropanol), on gas exchange, rumen gas, and VFA composition. For this purpose, 2 individual 4 × 4 Latin square experiments were conducted with 4 periods of 3 d (nitrate supplementation) and 7 d (3-nitrooxypropanol supplementation), respectively. In each study, 4 rumen-cannulated Danish Holstein cows were used. Each additive for CH 4 mitigation was included in the ad libitum–fed diet within the 2 experiments (exp. 1 and exp. 2), to which the cows were adapted for at least 14 d. Acceptors for H 2 were administered twice daily in equal portions through the rumen fistula immediately after feeding of the individual cow. In exp. 1 (nitrate), the treatments were CON-1 (no H 2 -acceptor), FUM-1 (fumaric acid), ACR-1 (acrylic acid), and FUM+ACR-1 (50% FUM-1 + 50% ACR-1). In exp. 2 (3-nitrooxypropanol), the 3 treatments, CON-2, FUM-2, and ACR-2, were similar to CON-1, FUM-1 and ACR-1 treatments, however the fourth treatment was PHL-2 (phloroglucinol). Gas exchanges were measured in respiration chambers, and samples of rumen liquid and headspace gas were taken in time series relative to feeding and dosing on specific days. Headspace gas was analyzed for gas composition, and rumen liquid was analyzed for VFA composition and dissolved gas concentrations. Headspace gas composition and dissolved gas concentration were only measured in exp. 2. Dry matter intake was reduced upon acrylic acid supplementation. There were no significant effects of any treatments in any experiments on H 2 emission, except for a decrease in hourly H 2 emission rate (g/h) at 1 h after feeding in both experiments. In exp. 2, H 2 headspace proportions increased with ACR-2 supplementation, whereas dissolved concentrations were unaffected. In exp. 1, cows on ACR-1 increased propionate proportion at 1 h after feeding. In exp. 2, both FUM-2 and ACR-2 increased rumen propionate proportion in the hours after feeding and dosing. There was no effect on rumen acetate for cows on PHL-2. There was a strong positive correlation between rumen dissolved CH 4 and headspace CH 4 (r = 0.84), whereas the equivalent correlation was weaker for H 2 (r = 0.41). For the relationship between dissolved concentrations and emissions of CH 4 and H 2 , there was a moderate positive correlation for CH 4 (r = 0.54), whereas it was weak for H 2 (r = 0.28) with zero slope. In conclusion, the results suggested that fumaric acid and acrylic acid to some extent was reduced to propionate without associative effects on measures for H 2 redirection. Furthermore, phloroglucinol seemed not to be metabolized in the rumen in the present study, because no effects on rumen acetate or measures of H 2 were observed. Changes in H 2 headspace and emission may be a poor proxy for actual changes in the rumen fluid concentration of H 2. [ABSTRACT FROM AUTHOR]

Albendazole (ABZ) is a highly effective yet poorly water-soluble antiparasitic drug known to form salts (ABZ-FMA, ABZ-DTA, and ABZ-HCl) with fumaric acid (FMA), D-tartaric acid (DTA), and hydrochloric acid (HCl). This research utilized a range of analytical techniques, including Fourier transform infrared spectroscopy (FT-IR), nuclear magnetic resonance hydrogen spectroscopy (1H NMR), powder X-ray diffraction (PXRD), dynamic vapor sorption (DVS), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), and scanning electron microscopy (SEM), to validate and characterize the solid-state properties of these drug salts. This study also assessed the solubility and intrinsic dissolution rate (IDR) of these salts under different pH conditions compared to the active pharmaceutical ingredient (API) and conducted stability studies. Moreover, the in vivo pharmacokinetic performance of ABZ salt was evaluated. The results of this study reveal that the new solid form of ABZ is primarily associated with amino acid esters and benzimidazole groups, forming intermolecular interactions. All three ABZ salts significantly improved the solubility and dissolution rate of ABZ, with ABZ-HCl demonstrating the optimal performance. Importantly, the drug salt exhibited robust physical stability when exposed to adverse conditions, including strong light irradiation (4500 ± 500 lux), high humidity (92.5 ± 5% relative humidity), elevated temperatures (50 ± 2 °C), and accelerated test conditions (40 °C/75 ± 5% relative humidity). Lastly, the in vivo pharmacokinetic analysis demonstrated that ABZ salt led to a substantial increase in AUC(0–24) and Cmax compared to ABZ. This elevation in solubility in aqueous solvents signifies that ABZ salt exhibits characteristics that can enhance oral bioavailability and pharmacokinetics. These findings provide potential solutions for the development of more effective and innovative drug formulations. [ABSTRACT FROM AUTHOR]

Lanthanides and actinides are emerging contaminants, but little is known about their uptake and distribution by plants and their interactions in the rhizosphere. To better understand the fate of these metals in plants, the bioassociation of 2, 20 and 200 µM Eu(III) by five hydroponically grown crops endemic to Europe was assessed. The metal's concentration and its speciation were monitored by inductively coupled plasma mass spectrometry and laser spectroscopy, whereas root exudation was investigated by chromatographic methods. It has been shown, that Eu(III) bioassociation is a two-stage process, involving rapid biosorption followed by accumulation in root tissue and distribution to the stem and leaves. Within 96 h of exposure time, the plant induces a change of Eu(III) speciation in the liquid medium, from a predominant Eu(III)aquo species, as calculated by thermodynamic modelling, to a species with longer luminescence lifetime. Root exudates such as citric, malic, and fumaric acid were identified in the cultivation medium and affect Eu(III) speciation in solution, as was shown by a change in the thermodynamic model. These results contribute to a comprehensive understanding of the fate of lanthanides in the biosphere and provide a basis for further investigations with the chemical analogues Cm(III) and Am(III). [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Biocatalytic hydroamination of alkenes is an efficient and selective method to synthesize natural and unnatural amino acids. Phenylalanine ammonia‐lyases (PALs) have been previously engineered to access a range of substituted phenylalanines and heteroarylalanines, but their substrate scope remains limited, typically including only arylacrylic acids. Moreover, the enantioselectivity in the hydroamination of electron‐deficient substrates is often poor. Here, we report the structure‐based engineering of PAL from Planctomyces brasiliensis (PbPAL), enabling preparative‐scale enantioselective hydroaminations of previously inaccessible yet synthetically useful substrates, such as amide‐ and ester‐containing fumaric acid derivatives. Through the elucidation of cryo‐electron microscopy (cryo‐EM) PbPAL structure and screening of the structure‐based mutagenesis library, we identified the key active site residue L205 as pivotal for dramatically enhancing the enantioselectivity of hydroamination reactions involving electron‐deficient substrates. Our engineered PALs demonstrated exclusive α‐regioselectivity, high enantioselectivity, and broad substrate scope. The potential utility of the developed biocatalysts was further demonstrated by a preparative‐scale hydroamination yielding tert‐butyl protected l‐aspartic acid, widely used as intermediate in peptide solid‐phase synthesis. [ABSTRACT FROM AUTHOR]

Zn anodes in aqueous zinc‐ion batteries chronically suffer from pernicious side reactions and ineluctable dendrite growth, resulting in inadequate reversibility and suboptimal Coulombic efficiency (CE) and impeding commercialization. Herein, a multifunctional metal–organic coordination polymer layer (FAZ) is constructed on the zinc anode surface (FAZ@Zn) utilizing a simple self‐assembly strategy. The zincophilic FAZ interfacial layer with a high Zn2+ transfer number and low nucleation barrier effectively facilitates the de‐solvation process, supports the rapid transport of zinc ions, and contributes to the preferential growth of Zn (002) crystal planes, enabling dendrite‐free Zn deposition. Furthermore, the FAZ layer, as an interfacial pH regulating layer, effectively inhibits the direct contact between Zn and active water molecules, lowering the severity of side reactions. Consequently, the FAZ@Zn anode furnishes an eminent cycle stability over 6900 h, with a low polarization voltage at 1 mA cm−2 and 1 mA h cm−2 and a boosted CE of 99.88% over 4100 cycles. More encouragingly, when coupled with Na2V6O16·3H2O, the FAZ@Zn anode enables the full cell to deliver satisfactory rate performance and a 97% capacity retention over 1600 cycles. This work provides a simple strategy for the effective preparation of highly reversible zinc anodes for high‐performance aqueous zinc‐ion batteries. [ABSTRACT FROM AUTHOR]

In this study, we tried to explore the influence of various tricarboxylic acid (TCA) cycle intermediates on carotenoid production and with a focus on enhancing pigment biosynthesis, we conducted two statistical analysis. In case of TCA intermediates influence on pigment production by Paracoccus marcusii RSPO1; fumaric acid, and malic acid were observed as potent enhancers of pigment biosynthesis. Further, to optimize key media components for enhanced carotenoid production, the Plackett–Burman design was employed encompassing carbon, nitrogen sources, TCA cycle intermediates, and metal salts. The selected factors after Plackett Burman were fine-tuned through Response Surface Methodology and the optimal concentrations that have remarkably elevated carotenoid production were starch-2.24 g/l, MgSO4-0.416 g/l, ZnSO4-0.0157 g/l, and fumaric Acid-16 mM. Further, evaluation of pigment cytotoxicity against normal (Vero) and Non-Small Cell Carcinoma (A549) cells was performed. The resultant IC50 values were quantified as 161.3 µg/ml and 7.623 µg/ml for Vero and A549 cells, respectively. Moreover, a reactive oxygen species (ROS) determination study in A549 cells was done which have shown a noteworthy threefold ROS production in A549 cells through fluorescence spectroscopic observation. This implies that the bacterial carotenoids can act as potent pro-oxidants against cancerous cells while being nontoxic toward normal cells. [ABSTRACT FROM AUTHOR]

This study involves the preparation of sodium alginate poly grafted (fumaric acid-polyacrylic acid)/graphene oxide, SA-g-p(FA-AA)/GO hydrogel to explore its potential as a promising adsorbent for water treatment mainly chromium (VI) and lead (II) removal. Prepared adsorbent was characterized by FTIR, TGA, XRD, FESEM, and TEM techniques for exploring the chemical structure, thermal stability, crystallography, surface area and morphology, as well as pore size and distribution of SA-g-p(FA-AA)/GO, respectively. The average size of the prepared nanoparticles was observed to be 78.48 nm. The TEM images exhibit a predominantly spherical shape and heterogeneous. Effect of different physiochemical parameters such as pH, temperature, adsorbent dosage, and contact time was explored for maximum metal adsorption. The results of the study revealed that the maximum adsorption capacity of SA-g-p(FA-AA)/GO (0.045 mg g−1 for Cr (VI) and 22.371 mg g−1 for Pb (II)) was achieved under optimized conditions, i.e., adsorbent dose of 0.05 g at 25 °C for pH of 2, 4.5 when contact time of 5 and 100 min was used for Cr(VI) and Pb(II), respectively. Data fits best to the pseudo-second-order kinetic equation revealing the multilayer adsorption of Cr (VI) and Pb (II) ions on the heterogeneous adsorbent surface. Thermodynamically, the process of Cr (VI) and Pb (II) adsorption was non-spontaneous, exothermic and feasible revealing the potential of the prepared adsorbent to be used as an efficient adsorbent for metal removal. [ABSTRACT FROM AUTHOR]

The salts bis(2‐amino‐3‐methylpyridinium) fumarate dihydrate, 2C6H9N2+·C4H2O22−·2H2O (I), and 2‐amino‐3‐methylpyridinium 5‐chlorosalicylate, C6H9N2+·C7H4ClO3− (II), were synthesized from 2‐amino‐3‐methylpyridine with fumaric acid and 5‐chlorosalicylic acid, respectively. The crystal structures of these salts were characterized by single‐crystal X‐ray diffraction, revealing protonation in I and II by the transfer of a H atom from the acid to the pyridine base. In the crystals of both I and II, N—H...O interactions form an R22(8) ring motif. Hirshfeld surface analysis distinguishes the interactions present in the crystal structures of I and II, and the two‐dimensional (2D) fingerprint plot analysis shows the percentage contribution of each type of interaction in the crystal packing. The volumes of the crystal voids of I (39.65 Å3) and II (118.10 Å3) have been calculated and reveal that the crystal of I is more mechanically stable than II. Frontier molecular orbital (FMO) analysis predicts that the band gap energy of II (2.6577 eV) is lower compared to I (4.0035 eV). The Quantum Theory of Atoms In Molecules (QTAIM) analysis shows that the pyridinium–carboxylate N—H...O interaction present in I is stronger than the other interactions, whereas in II, the hydroxy–carboxylate O—H...O interaction is stronger than the pyridinium–carboxylate N—H...O interaction; the bond dissociation energies also confirm these results. The positive Laplacian [∇2ρ(r) > 0] of these interactions shows that the interactions are of the closed shell type. An in‐silico ADME (Absorption, Distribution, Metabolism and Excretion) study predicts that both salts will exhibit good pharmacokinetic properties and druglikeness. [ABSTRACT FROM AUTHOR]

Background The anti-interleukin-23 antibody guselkumab (GUS) demonstrated favourable week 24 efficacy and safety over fumaric acid esters (FAE) in systemic treatment-naïve patients with moderate-to-severe plaque psoriasis (study part I). Objectives To compare, in study part II, the sustainability of treatment responses (weeks 24–32) in GUS- and FAE-treated patients and treatment responses (weeks 32–56) in patients treated with GUS and FAE and in FAE nonresponders switching to GUS; and, in part III, to investigate the maintenance of response through week 100 in patients withdrawn from GUS at week 56. Methods At week 0, systemic treatment-naïve patients were randomized 1 : 1 to GUS or FAE as per label. At week 32, patients with a Psoriasis Area and Severity Index (PASI) 75 (≥ 75% improvement in PASI score) response (r) continued assigned treatment (GUSr-GUS; FAEr-FAE), whereas nonresponders (nr) received GUS (FAEnr-GUS; GUSnr-GUS). GUS-treated patients with a week 56 PASI 90 response (≥ 90% improvement in PASI score) were withdrawn (w) and followed until loss of response or week 100. Results At week 32, 98% (n = 54/55) of GUS- and 41% (n = 14/34) of FAE-treated patients were PASI 75 responders. At week 56, 91%, 50% and 80% of GUSr-GUS, FAEr-FAE and FAEnr-GUS patients, respectively, achieved a PASI 90 response; 72%, 29% and 45%, respectively, achieved a Dermatology Life Quality Index score of 0/1. At week 100, 44 weeks postwithdrawal, 47% (n = 17/36) and 25% (n = 3/12) of GUS-GUSw and FAE-GUSw patients, respectively, maintained a PASI score ≤ 5. Overall, the adverse event and discontinuation rates were lower for GUS than FAE. Conclusions In these exploratory analyses, GUS, as a first-line systemic treatment or second-line systemic treatment in FAE nonresponders, was associated with long-term clinical efficacy up to week 100, including a withdrawal period. [ABSTRACT FROM AUTHOR]

The presence of organics in Bayer liquors has a notable adverse effect on alumina production. Among these organics, dicarboxylic acids are a class of low molecular weight compounds that have yet to be studied for their decomposition in Bayer liquors using advanced oxidation techniques. This study aims to investigate the oxidation behavior of four dicarboxylic acids, including malonic acid (C3), succinic acid (C4), glutaric acid (C5), and adipic acid (C6), in Bayer liquors. The influences of different variables, such as sodium persulfate (SPS) dosage, initial organic concentration, caustic soda concentration, reaction temperature, and reaction time, on the advanced oxidation process of dicarboxylic acids were also studied. The results of the experiment indicate that an increase in SPS dosage, initial organic concentration, reaction temperature, and reaction time promoted the removal of total organic carbon (TOC). However, the concentration of caustic soda had an inhibitory effect on TOC removal, and it also affected the type of decomposition products of dicarboxylic acids. The EPR results revealed that the reactive groups responsible for organic decomposition were SO 4 - · and HO · . Dicarboxylic acids were found to produce several decomposition products, including carbon dioxide (in the form of carbonate), formic acid, and oxalic acid. Additionally, malonic and fumaric acids were observed as the main oxidation intermediates for dicarboxylic acids with C-atom numbers > 3. A reaction mechanism for succinic acid was also proposed. Advanced oxidation techniques have shown promise as a means of removing organics from Bayer liquors. [ABSTRACT FROM AUTHOR]

Plant protein ingredients are gaining attention for human nutrition, yet they differ significantly from animal proteins in functionality and nutrition. Fungal solid-state fermentation (SSF) can modulate the composition and functionality, increasing their applicability in foods. Quinoa flour (QF) served as a substrate for Aspergillus oryzae and Rhizopus oligosporus, resulting in two fermented ingredients (QFA and QFR) with different nutritional, functional, and aroma characteristics. A higher increase in protein (+35%) and nitrogen (+24%) was observed in the QFA, while fat was predominantly increased in the QFR (+78%). Fermentable oligo-, di-, monosaccharides and polyols (FODMAPs) decreased in the QFR but increased in the QFA due to polyol production. Metabolomic analysis revealed higher lactic acid concentrations in the QFA, and higher citric, malic, and fumaric acid contents in the QFR. The SSF reduced most antinutrients, while R. oligosporus produced saponins. Olfactometry showed the development of fruity ester compounds and a decrease in metallic and cardboard aromas. Both ingredients showed an enhanced water-holding capacity, with the QFA also demonstrating an increased oil-holding capacity. Complex formation increased the particle size, reduced the solubility, and decreased the foaming properties. Mycelium production darkened the ingredients, with the QFR having a higher differential colour index. This study highlights the potential of SSF to produce ingredients with improved nutritional, sensory, and functional properties. [ABSTRACT FROM AUTHOR]

Ion-imprinting methodology was used to fabricate a new cobalt ion-imprinted polymer as a cross-linked copolymer consisting of fumaric acid and 4-vinylpyridine as monomers. Different techniques were used to investigate all of the chemical and morphological changes that occurred during the cobalt ion imprinting process. Furthermore, extraction experiments for cobalt ions using controlled and imprinted polymers were carried out to obtain the essential isotherm, kinetic and thermodynamic parameters. The controlled and imprinted resins had the best agreement with the pseudo-second-order and Langmuir models, with maximum retention capacities of 14.7 ± 2 and 42.0 ± 0.5 mg/g, respectively. In comparison to non-imprinted polymer, the imprinted polymer showed greater affinity for cobalt ions in the presence of other metal ions like Cd2+, Cu2+, Ni2+, La3+, and Y3+. In addition, after the fifth adsorption-desorption cycle, resin regenerates with about 96% of its initial activity, demonstrating its high economic value. [ABSTRACT FROM AUTHOR]

Lactobacillus delbrueckii ssp. bulgaricus and Streptococcus thermophilus are symbiotic starters widely used in yogurt fermentation. They exchange metabolites to meet their nutritional demands during fermentation, promoting mutual growth. Although S. thermophilus produces fumaric acid, and the addition of fumaric acid has been shown to promote the growth of L. bulgaricus monoculture, whether fumaric acid produced by S. thermophilus is used by L. bulgaricus during coculture remains unclear. Furthermore, the importance of fumaric acid metabolism in the growth of L. bulgaricus is yet to be elucidated. Therefore, in this study, we investigated the importance of fumaric acid metabolism in L. bulgaricus monocultures and coculture with S. thermophilus. We deleted the fumarate reductase gene (frd), which is responsible for the metabolism of fumaric acid to succinic acid, in L. bulgaricus strains 2038 and NCIMB 701373. Both Δ frd strains exhibited longer fermentation times than their parent strains, and fumaric acid was metabolized to malic acid rather than succinic acid. Coculture of Δ frd strains with S. thermophilus 1131 also resulted in a longer fermentation time, and the accumulation of malic acid was observed. These results indicated that fumaric acid produced by S. thermophilus is used by L. bulgaricus as a symbiotic substance during yogurt fermentation and that the metabolism of fumaric acid to succinic acid by fumarate reductase is a key factor determining the fermentation ability of L. bulgaricus. [ABSTRACT FROM AUTHOR]

Kombucha is a Far East-originated fermented beverage that is valued by people for its health benefits worldwide. Fruit and fruit juice of the gilaburu plant is used in traditional medicine. In this study, fruit juice of gilaburu is used in a 21-day kombucha fermentation. Sensory properties, microbiological profile, total phenolic and flavonoid content, and antioxidant and antibacterial activity of the prepared beverages for days 0, 7, 14, and 21st were investigated. In addition, chemical compound profiles were determined using LC-MS/MS on the 7th and 14th days. When evaluated in general, gilaburu-flavoured kombucha yielded better results than traditional kombucha in terms of microbiological analysis, antibacterial activity, total phenolic content, and sensory properties. In addition, the LC-MS/MS analysis of the beverages revealed fourteen active compounds. Notably, on the 7th day, gilaburu-flavoured kombucha exhibited elevated levels of fumaric acid, quinic acid, chlorogenic acid, catechin, 4-OH-benzoic acid, epicatechin, vitexin and hesperidin compared to traditional kombucha. [ABSTRACT FROM AUTHOR]

This study investigated the potential of decolourised Moringa oleifera leaf powder (D-MOLP) in cookies to meet consumer demand for healthier food options, addressing the issue of low acceptability due to its green colour. D-MOLP and its non-decolourised counterpart (ND-MOLP) were incorporated into wheat flour to produce cookies. The results showed that neither decolourisation nor addition level (2.5 or 7.5%) significantly affected water activity or flour functionality, though slight differences in cookie colour were observed. The Moringa-enriched cookies exhibited an improved spread ratio as well as higher protein, phenolic content, antioxidant activity, and in vitro protein digestibility compared to control cookies. The detected phenolic acids included chlorogenic, ferulic, and fumaric acids, with the D-MOLP cookies showing superior nutritional properties, likely due to nutrient concentration and reduced antinutrients. Notably, glutamic acid was the major amino acid in all the cookies, but only lysine significantly increased across the cookie types. This suggests D-MOLP could be a promising alternative for food enrichment. Future research should address the consumer acceptability, volatile components, and shelf-life of D-MOLP-enriched cookies. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Helichrysum armenium subsp. armenium plant was extracted with the Soxhlet apparatus. The obtained extract was fractionated and, respectively, AHB (petroleum ether-60% ethanol-chloroform), AHC (ethanol-toluene), AHD (ethanol-chloroform), and AHE (ethanol-ethylacetate) extracts were obtained. Then, antimicrobial, antioxidant, and acetylcholinesterase activity studies were performed on these extracts. In this study, with the using the LC-HRMS method from the aerial parts of Helichrysum armenium subsp. armenium, the flavonoids: apigenin, apigenin 7-glucoside, apigenin 7-methylate, luteolin 7-glucoside, kaempferol, quercetin, quercitrin, (+)-trans taxifolin, (-)-epicatechin gallate, sinensetin, rutin, 3'-o-methyl quercetin, hispidulin, chrysin, acacetin, genkwanin, chrysoeriol; the phenolic acids: chlorogenic acid, ascorbic acid, fumaric acid, caffeic acid, salicylic acid, caffeic acid phenethyl ester, emodin, vanilic acid; the alkaloid: caffeine and the saponoside; glycyrrhizic acid were obtained. [ABSTRACT FROM AUTHOR]

An anthracene thiazole based Schiff base L was synthesized and employed for fluorescence switch-on detection of maleic acid in aqueous DMSO. The non-fluorescent L (10–5 M) showed an instantaneous and selective fluorescence enhancement at 506 nm upon interaction with maleic acid (10–5 M). Other potential carboxylic acids (10–5 M), such as malic acid, citric acid, acetic acid, cinnamic acid, tartaric acid, succinic acid, fumaric acid, oxalic acid and malonic acid failed to alter the chromo-fluorogenic properties of L. Probe L can be employed to detect maleic acid down to 2.74 × 10–6 M. The probe L showed good linearity from 2.97 to 6.87 µM. Analytical utility of L was examined by detecting maleic acid in various food additives and drosophila larvae. [ABSTRACT FROM AUTHOR]

Allium species are consumed extensively as folkloric medicine and dietary elements, but limited studies have been conducted on them. In this study, the effects of an ethanol–water extract obtained from the underground bulb of Allium tuncelianum (Kollmann) Özhatay, B. Mathew & Şiraneci (AT) on the behavioral, antioxidant, and metabolite parameters in rats were evaluated. AT was administered orally once a day at doses of 100 and 400 mg/kg to male Wistar albino rats for 10 consecutive days. The elevated plus maze, rotarod, and hotplate tests were used to examine anxiety‐like behaviors, locomotor activities, and pain perception in the rats, respectively. Additionally, untargeted metabolomic analyses were performed on plasma samples and AT extracts using two orthogonal analytical platforms. The phenolic components, mainly fumaric acid, malic acid, vanillic acid, quercetin‐3‐arabinoside, hydrocinnamic acid, and gallocatechin, were determined in the extract. In addition, arbutin, salicylic acid, trehalose, and nicotinic acid were analyzed in the extract for the first time. The AT extract did not decrease the catalase, glutathione peroxidase, or superoxide dismutase levels; however, diazepam decreased some of those parameters significantly in the brain, liver, and kidney. Although both the AT and diazepam treatments resulted in an increase in anxiolytic‐like effects compared to the control group, no significant differences were observed (p >.05). In the metabolomic analysis, significant changes were observed in the rats treated with AT and diazepam, and they caused significant changes in some metabolic pathways, including amino acid and fatty acid metabolism, compared to the control. [ABSTRACT FROM AUTHOR]

Fruits 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 applications: Recent 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. [ABSTRACT FROM AUTHOR]

Background: Dimethyl fumarate (DMF) is a fumaric acid ester that exhibits immunoregulatory and anti-inflammatory properties. However, the function of DMF in autoimmune uveitis (AU) is incompletely understood, and studies comprehensively exploring the impact of DMF on immune cells are still lacking. Methods: To explore the function of DMF in uveitis and its underlying mechanisms, we conducted single-cell RNA sequencing (scRNA-seq) on the cervical draining lymph node (CDLN) cells of normal, experimental autoimmune uveitis (EAU), and DMF-treated EAU mice. Additionally, we integrated scRNA-seq data of the retina and CDLNs to identify the potential impact of DMF on ocular immune cell infiltration. Flow cytometry was conducted to verify the potential target molecules of DMF. Results: Our study showed that DMF treatment effectively ameliorated EAU symptoms. The proportional and transcriptional alterations in each immune cell type during EAU were reversed by DMF treatment. Bioinformatics analysis in our study indicated that the enhanced expression of Pim1 and Cxcr4 in EAU was reversed by DMF treatment. Further experiments demonstrated that DMF restored the balance between effector T (Teff) /regulatory T (Treg) cells through inhibiting the pathway of PIM1-protein kinase B (AKT)-Forkhead box O1 (FOXO1). By incorporating the scRNA-seq data of the retina from EAU mice into analysis, our study identified that T cells highly expressing Pim1 and Cxcr4 were enriched in the retina. DMF repressed the ocular infiltration of Teff cells, and this effect might depend on its inhibition of PIM1 and CXCR4 expression. Additionally, our study indicated that DMF might reduce the proportion of plasma cells by inhibiting PIM1 expression in B cells. Conclusions: DMF effectively attenuated EAU symptoms. During EAU, DMF reversed the Teff/Treg cell imbalance and suppressed the ocular infiltration of Teff cells by inhibiting PIM1 and CXCR4 expression. Thus, DMF may act as a new drug option for the treatment of AU. [ABSTRACT FROM AUTHOR]

The pore structure of metal-organic frameworks (MOFs) is crucial to their adsorption performance, and it is still a challenge to precisely control the pore size to realize superior removal of uranium. The pore size of MOF-A, MOF-B and MOF-C was fine-tuned by using three organic chains with different lengths (fumaric acid, terephthalic acid and naphthalene dicarboxylic acid, respectively). The synthesized MOF-A, MOF-B and MOF-C had ordered increase in pore sizes with 3.8 Å, 5.7 Å and 7.6 Å, respectively. Pore size of 7.6 Å in MOF-C was a little larger than the geometric dimension of the UO22+ ion (maximum length 6.04-6.84 Å), which facilitated diffusion of UO22+ ions and achieved highly efficient adsorption. The maximum adsorption capacity (584 mg g-1) and removal rate (99.75%) of uranium for MOF-C were higher than those for MOF-A and MOF-B. The excellent adsorption performance of MOF-C was attributed to the specific pore structure of MOF-C and effective complexation of oxygen-containing groups with U(VI). Our work proposes a new strategy for the outstanding removal of uranium by using different organic chains to precisely regulate the pore size of MOF. [ABSTRACT FROM AUTHOR]

BACKGROUND: Crataegus orientalis Pall. ex M. Bieb fruit (COPMB) is extensively used as a source of various products in the medicinal‐aromatic field and holds the potential for erosion control, ornamental purposes, food source, and economic benefits for forest villagers from its fruits. This study aims to determine the chemical components and biological activities of extracts prepared from COPMB using different solvents. RESULTS: The present work was designed to define the antioxidant activity [phosphomolybdenum (total antioxidant capacity), 2,2′‐azino‐bis(3‐ethylbenzothiazoline‐6‐sulfonic acid) (ABTS), ferric reducing antioxidant power (FRAP), cupric ion‐reducing antioxidant capacity (CUPRAC) and metal chelating activity (MCA)], phytochemical screening analysis, enzyme inhibitor (α‐amylase, α‐glucosidase and tyrosinase) potential, and liquid chromatography‐high resolution mass spectrometry (LC‐HRMS) secondary metabolite profiling in different extracts of COPMB. The results of LC‐HRMS revealed that fumaric acid was the main phenolic compound in all extracts. Among the extracts, ethyl acetate extract has the highest phytochemical and antioxidant properties [total phenolic content (TPC): 32.5 mg GAE/g, total flavonoid content (TFC): 12.2 mg QE/g, ABTS: 213.0 mg TE/g; CUPRAC: 126.0 mg TE/g, MCA: 145.0 mg EDTA/g; FRAP: 122.8 mg TE/g; TAC: 2.8 mmol TE/g]. Ethyl acetate and methanol extracts are more effective in α‐amylase (0.27 ± 0.01 mg/mL; 0.12 ± 0.00 mg/mL), α‐glucosidase (0.63 ± 0.02 mg/mL; 0.77 ± 0.02 mg/mL) and tyrosinase (0.03 ± 0.00 mg/mL; 0.03 ± 0.00 mg/mL) enzyme inhibition potentials compared to standard acarbose (0.75 ± 0.02 mg/mL for α‐amylase; 1.11 ± 0.03 mg/mL for α‐glucosidase) and kojic acid (0.04 ± 0.00 mg/mL). CONCLUSION: The findings from this study suggest that COPMB could serve as a valuable source of natural agents for the food and pharmaceutical industry. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Biomaterials utilized for various medical applications are expected to be hemocompatible, i.e., they don't cause any adverse effect on red blood cells in contact with them. Presently, hydrogels prepared from biopolymers with three-dimensional porous networks are considered as prime candidates for biomedical applications. The present study conducted preliminary in vitro assessment of hemocompatibility of different biopolymers, various chemical reagents including cross-linkers, grafting monomers and free radical initiator required for the synthesis of hydrogels of biomedical importance and finally of the synthesized hydrogels. The synthesized hydrogels were characterized using swelling studies, FTIR and mechanical strength. Herein, in vitro hemolytic analysis was utilized as a preliminary indicator to assess the hemocompatibility of a biomaterial. Out of the biopolymers studied (starch, carboxymethyl cellulose, sodium alginate, karaya gum, chitosan, xanthan gum, β-cyclodextrin, gelatin and dextrin), the degree of hemolysis was found to be minimum for chitosan (0.08%) and maximum for β-cyclodextrin (44.57%). The presence of higher charge density seems to be negative for hemocompatibility. Further, the cross-linkers including N,N′-methylenebisacrylamide, glutaraldehyde, maleic acid, fumaric acid, DL-malic acid and citric acid were studied for their hemocompatibility. The maleic acid and fumaric acid were found to possess better compatibilities in the range of 3.25% and 4.43%, respectively. The natural or synthetic origin of a cross-linker does not seem to be a consideration for hemocompatibility. Further, most of the synthesized biopolymer based hydrogels displayed better hemocompatibility in comparison to the starting precursor materials owing to their unique surface chemistry and distribution of the hydrophilic groups. The acrylamide grafted hydrogels displayed hemolytic activity (2.23%) in safer range in comparison to the acrylic acid grafted hydrogels (68.15%). The presence of certain functional groups containing oxygen and nitrogen and moderate negative charge improved hemocompatibility in comparison to carbon containing functional groups and high negative charge density. The hemolytic activity of hydrogels was observed to be increased manifold in the presence of nanoparticles incorporated into hydrogels to improve their physical characteristics. The results indicate that the careful selection of biopolymers, cross-linkers, grafting monomers and further tuning of surface chemistry by controlling functional groups and their charge density over a biomaterial is prerequisite to prevent protein adsorption, inflammatory response and lysis of RBCs in the living host. Undoubtedly, in vitro hemocompatibility analysis is not a satisfactory indicator for measuring hemolytic activity of biomaterials, but can definitely help in preliminary assessment as indicated by the results of the present study. These bio-based hydrogels within safer limits of hemocompatibility can be prime materials for many biomedical applications including scaffolds in tissue engineering, implants, prosthetic devices, antibacterial and dental materials, drug delivery carriers, biosensors and bio adhesives. [ABSTRACT FROM AUTHOR]

The white koji fungus Aspergillus luchuensis mut. kawachii secretes substantial amounts of citric acid through the expression of the citric acid exporter CexA, a member of the DHA1 family. In this study, we aimed to characterize 11 CexA homologs (Chl proteins) encoded in the genome of A. luchuensis mut. kawachii to identify novel transporters useful for organic acid production. We constructed overexpression strains of chl genes using a cexA disruptant of the A. luchuensis mut. kawachii as the host strain, which prevented excessive secretion of citric acid into the culture supernatant. Subsequently, we evaluated the effects of overexpression of chl on producing organic acids by analyzing the culture supernatant. All overexpression strains did not exhibit significant citric acid accumulation in the culture supernatant, indicating that Chl proteins are not responsible for citric acid export. Furthermore, the ChlH overexpression strain displayed an accumulation of 2-oxoglutaric and fumaric acids in the culture supernatant, while the ChlK overexpression strain exhibited the accumulation of 2-oxoglutaric, malic and succinic acids. Notably, the ChlH and ChlK overexpression led to a substantial increase in the production of 2-oxoglutaric acid, reaching approximately 25 mM and 50 mM, respectively. Furthermore, ChlH and ChlK overexpression also significantly increased the secretory production of dicarboxylic acids, including 2-oxoglutaric acid, in the yellow koji fungus, Aspergillus oryzae. Our study demonstrates that overexpression of DHA1 family gene results in enhanced secretion of organic acids in koji fungi of the genus Aspergillus. [ABSTRACT FROM AUTHOR]

Currently, the L-malic acid titer achieved through Aspergillus niger fermentation reaches 201 g/L, meeting industrial demands satisfactorily. However, the co-presence of structurally similar fumaric acid and succinic acid in fermentation products suggests a theoretical potential for further improvement in L-malic acid production. In the tricarboxylic acid cycle, fumarate reductase mediates the conversion of succinic acid to fumaric acid. Subsequently, fumarase catalyzes the conversion of fumaric acid to L-malic acid. Notably, both enzymatic reactions are reversible. Our investigation revealed that A. niger contains only one mitochondria-located fumarase FumA. Employing CRISPR-Cas9 technology, we performed a replacement of the fumA promoter with a doxycycline-induced promoter Tet. Under non-inducing condition, the conditional strain exhibited increased levels of fumaric acid and succinic acid. It strongly suggests that FumA mainly promotes the flow of fumaric acid to L-malic acid. Furthermore, a promoter PmfsA that is exclusively activated in a fermentation medium by calcium carbonate was identified through RNA-sequencing screening. Utilizing PmfsA to regulate fumA expression led to a 9.0% increase in L-malic acid titer, an 8.75% increase in yield (glucose to L-malic acid), and an 8.86% enhancement in productivity. This research serves as a significant step toward expediting the industrialization of L-malic acid synthesis via biological fermentation. Additionally, it offers valuable insights for the biosynthesis of other organic acids. IMPORTANCE This study focuses on enhancing L-malic acid synthesis by modifying the tricarboxylic acid cycle within the mitochondria of Aspergillus niger. We emphasize the significant role of fumarase in converting fumaric acid into L-malic acid, enhancing our understanding of metabolic pathways in A. niger. The precise regulation of fumA is highlighted as a key factor in enhancing L-malic acid production. Furthermore, this research introduces a stringent conditional promoter (PmfsA), exclusively activated by CaCO3. The utilization of PmfsA for fumA expression resulted in heightened L-malic acid titers. The progress in metabolic engineering and bioprocess optimization holds promise for expediting industrial L-malic acid synthesis via biological fermentation. Moreover, it carries implications for the biosynthesis of various other organic acids. [ABSTRACT FROM AUTHOR]

Polyvinyl alcohol (PVA) is a widely used polymer that is biocompatible, nontoxic, and water‐soluble due to the presence of hydroxyl groups in its domain. This study aims to investigate the effects of fumaric acid (FA) cross‐linking and thermal cross‐linking (TC) on the PVA's mechanical and thermal properties. When the FA is mixed with PVA, it was found in the chemical reaction that the OH groups of PVA are condensing with the carboxylic acid units of FA to yield new ester linkages and water as a by‐product, which further results in the reduction of the water absorption capacity. Quantitatively, the addition of 8 (wt. /wt. %) FA resulted in a minimum of 65% water absorption rate, as compared with 117% for pure PVA. The mechanical and thermal properties of PVA also enhanced with the addition of 2% to 8% FA by weight. For the TC case, the % increase in ultimate tensile strength was 30.9% and 42.5% with and without TC, respectively. As the wt. % of FA increased from 2 to 10%, the % elongation value decreased for both with and without TC films relative to pure PVA. The thermogravimetric analysis revealed the change in degradation temperature of FA‐PVA blended film in comparison with pure PVA. Dynamic mechanical analysis was utilized to analyze the viscoelastic nature and temperature variation at the glass transition temperature. The current fabricated film is a potential candidate for the food packaging films application; moreover, the results reported in this investigation will accelerate the industrial applications of biodegradable PVA. Highlights: Increasing the weight percentage of fumaric acid leads to an enhancement in mechanical and thermal properties of the film.Esterification is the usual reaction between fumaric acid and polyvinyl alcohol (PVA), in which ester linkages are formed when the carboxyl groups (‐COOH) of fumaric acid and the hydroxyl groups (‐OH) of PVA combine.Water absorption characteristics of the film reduces as the wt. % of fumaric acid increases.Thermal cross‐linking of the film leads to further improvements in mechanical and thermal properties.The overall effect of increasing the wt. % of fumaric acid is negative on the glass transition temperature of the film.The developed film is a potential candidate for the food packaging films application. [ABSTRACT FROM AUTHOR]

This study investigated the potential of using steam-exploded oil palm empty fruit bunches (EFB) as a renewable feedstock for producing fumaric acid (FA), a food additive widely used for flavor and preservation, through a separate hydrolysis and fermentation process using the fungal isolate K20. The efficiency of FA production by free and immobilized cells was compared. The maximum FA concentration (3.25 g/L), with 0.034 g/L/h productivity, was observed after incubation with the free cells for 96 h. Furthermore, the production was scaled up in a 3-L air-lift fermenter using oil palm EFB-derived glucose as the substrate. The FA concentration, yield, and productivity from 100 g/L initial oil palm EFB-derived glucose were 44 g/L, 0.39 g/g, and 0.41 g/L/h, respectively. The potential for scaling up the fermentation process indicates favorable results, which could have significant implications for industrial applications. [ABSTRACT FROM AUTHOR]

Necrobiosis lipoidica (NL) is a rare granulomatous disease of a not fully understood etiopathogenesis. Classically, NL is associated with insulin-dependent diabetes mellitus. The disease often fails to respond to conventional treatments and adversely affects patients' quality of life. First-line medications are usually topical corticosteroids, but patients respond to them with varying degrees of success. Other options include tacrolimus, phototherapy, cyclosporine, fumaric acid esters, and biologics (adalimumab, etanercept, and infliximab). Our review aims to present new therapeutic approaches potentially effective in patients with refractory lesions, describe the presumed etiopathogenesis, and provide diagnostic guidance for clinicians. The review concludes that Janus kinase inhibitors and biologics such as ustekinumab and secukinumab can be used effectively in patients with recalcitrant NL. Another promising treatment option is tapinarof (an aryl hydrocarbon receptor agonist). However, studies on larger groups of patients are still needed to evaluate the effectiveness of different therapeutic options and to define consistent treatment regimens for NL. It is advisable to improve the awareness of physicians of various specialties regarding necrobiosis lipoidica as lesions diagnosed earlier usually have a better response to treatment. [ABSTRACT FROM AUTHOR]