Fumarate Research Articles

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.

Engineered Phenylalanine Ammonia‐Lyases for the Enantioselective Synthesis of Aspartic Acid Derivatives

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 Planctomycesbrasiliensis (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 a‐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.

Engineered Phenylalanine Ammonia-Lyases for the Enantioselective Synthesis of Aspartic Acid Derivatives.

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 Planctomycesbrasiliensis (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 a-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.

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.

Synthesis, structural characterization, molecular docking analysis and Carbonic Anhydrase IX inhibitory evaluations of novel Cerium(III)-based MOF constructed from 1,10-phenanthroline and fumaric acid.

In this study, a novel Cerium-based MOFs with 1,10-phenanthroline (phen) and fumaric acid (H2fum) has been hydrothermally synthesized as single crystal structurally characterized by X-ray diffraction, IR spectroscopy and ATG measurements. This compound corresponds to the formula: [Ce2(phen)2(fum)3(H2O)2]n(I), it crystallizes in the triclinic system with space group P1¯, with the following parameters: a = 9.062(1) Å, b = 10.0608(5) Å, c = 10.603(1) Å, α = 72.545(6) °, β = 77.57(1) °, γ = 69.959(6) °, V = 859.49(14) Å3, Z = 2.The structure revealed 2D bridged polymeric chains where the adjacent Ce(III) atoms are bridged by fumarate linkers with a mean intermetallic distance of about 9.36 Å. H···O bonds link the 2D sheets leading to a pseudo 3D network, while the stability of the structure is assured by a weak π-π stacking between parallel and opposed phen ligands.The Ce3+ cation is nona-coordinated and it is in a distorted tricapped trigonal prism geometry.Hirshfeld surface analysis was used to investigate the non-covalent intermolecular interactions and the dominant H···O, H···C and H···H contacts were quantified. The thermal properties of the considered coordination polymer (I) are also discussed and disclose that (I) is stable up to 300°C. Besides, this study explores the potential of (I) as an inhibitor of the carbonic anhydrase IX enzyme (CA IX), a critical player in tumor microenvironment regulation. Through molecular docking simulations, we elucidate the binding interactions between (I) and CA IX, the results suggest the efficiency of (I) as a CA IX inhibitor. Moreover, we assessed the drug-likeness properties and ADMET characteristics of (I), providing valuable insights for its potential as a therapeutic agent.

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.

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 (CFAEs). 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.

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.

Beneficial mechanisms of dimethyl fumarate in autoimmune uveitis: insights from single-cell RNA sequencing

BackgroundDimethyl 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.MethodsTo 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.ResultsOur 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.ConclusionsDMF 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.

Bacillus tequilensis influences metabolite production in tomato and restores soil microbial diversity during Fusarium oxysporum infection.

This study evaluates cellular damage, metabolite profiling, and defence-related gene expression in tomato plants and soil microflora during Fusarium wilt disease after treatment with B. tequilensis PBE-1. Histochemical analysis showed that PBE-1 was the primary line of defence through lignin deposition and reduced cell damage. GC-MS revealed that PBE-1 treatment ameliorated stress caused by F. oxysporum infection. PBE-1 also improved transpiration, photosynthesis, and stomatal conductance in tomato. qRT-PCR suggested that the defence-related genes FLS2, SERK, NOS, WRKYT, NHO, SAUR, and MYC2, which spread infection, were highly upregulated during F. oxysporum infection, but either downregulated or expressed normally in PBE-1 + P treated plants. This indicates that the plant not only perceives the bio-control agent as a non-pathogen entity but its presence in normal metabolism and gene expression within the host plant is maintained. The study further corroborated findings that application of PBE-1 does not cause ecological disturbances in the rhizosphere. Activity of soil microflora across four treatments, measured by Average Well Colour Development (AWCD), showed continuous increases from weeks 1 to 4 post-pathogen infection, with distinct substrate usage patterns like tannic and fumaric acids impacting microbial energy source utilization and diversity. Principal Component Analysis (PCA) and diversity indices like McIntosh, Shannon, and Simpson further illustrated significant microbial community shifts over the study period. In conclusion, our findings demonstrate that B. tequilensis PBE-1 is an ideal bio-agent for field application during Fusarium wilt disease management in tomato.

Fumaric acid production by Rhizopus species from acid hydrolysate of oil palm empty fruit bunches.

The hemicellulosic fraction of lignocellulosic biomass is a very important material, due to the significant concentration of pentoses present in its composition and that can be used sustainably in biotechnological processes such as the production of fumaric acid. Research efforts are currently being promoted for the proper disposal and valorization of empty fruit bunches (EFB) from oil palm. In this work, seventeen Rhizopus species were evaluated in a fermentation medium with EFB hydrolyzate, without detoxification, as a carbon source for fumaric acid production. Rhizopus circicans 1475 and Rhizopus 3271 achieved productions of 5.65g.L-1 and 5.25g.L-1 of fumaric acid at 30°C, 120rpm for 96h, respectively. The percentage of consumed sugars, mainly pentoses, was 24.88% and 34.02% for R. circicans 1475 and R 3271, respectively. Soy peptone and ammonium sulfate were evaluated as nitrogen sources, where soy peptone stimulated the formation of biomass pellets while ammonium sulfate produced mycelia and clamps.

Integrative Salt Selection and Formulation Optimization: Perspectives of Disproportionation and Microenvironmental pH Modulation.

We report a novel utilization of a pH modifier as a disproportionation retardant in a tablet formulation. The drug molecule of interest has significant bioavailability challenges that require solubility enhancement. In addition to limited salt/cocrystal options, disproportionation of the potential salt(s) was identified as a substantial risk. Using a combination of Raman spectroscopy with chemometrics and quantitative X-ray diffraction in specially designed stress testing, we investigated the disproportionation phenomena. The learnings and insight drawn from crystallography drove the selection of the maleate form as the target API. Inspired by the fumarate form's unique stability and solubility characteristics, we used fumaric acid as the microenvironmental pH modulator. Proof-of-concept experiments with high-risk (HCl) and moderate-risk (maleate) scenarios confirmed the synergistic advantage of fumaric acid, which interacts with the freebase released by disproportionation to form a more soluble species. The resultant hemifumarate helps maintain the solubility at an elevated level. This work demonstrates an innovative technique to mediate the solubility drop during the "parachute" phase of drug absorption using compendial excipients, and this approach can potentially serve as an effective risk-mitigating strategy for salt disproportionation.

Fumaric acid production from fermented oil palm empty fruit bunches using fungal isolate K20: a comparison between free and immobilized cells.

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.

Classification of buckwheat honey produced in Kazakhstan according to their biochemical ingredients and bioactivities by chemometric approach

Herein, nineteen buckwheat honey samples collected from 19 stations of different ecological zones of Kazakhstan were analysed for their pollen density, physicochemical properties, chemical composition, antioxidant, anticholinesterase, tyrosinase inhibitory, and urease inhibitory activities with chemometric approaches. Twelve phenolic compounds and fumaric acid were identified using HPLC-DAD, and mainly fumaric, p-hydroxybenzoic, p-coumaric, trans-2-hydroxy cinnamic acids, and chrysin were detected in all samples. The honey samples collected from the Northern zone exhibited best antioxidant activity in lipid peroxidation inhibitory (IC50:8.65 ± 0.50 mg/mL), DPPH• (IC50:17.07 ± 1.49 mg/mL), ABTS•+ (IC50:8.90 ± 0.65 mg/mL), CUPRAC (A0.50:7.51 ± 0.30 mg/mL) and metal chelating assay (IC50:10.39 ± 0.71 mg/mL). In contrast, South-eastern zone samples indicated better acetylcholinesterase (55.57 ± 0.83%), butyrylcholinesterase (49.59 ± 1.09%), tyrosinase (44.40 ± 1.21%), and moderate urease (24.57 ± 0.33%) inhibitory activities at 20 mg/mL. The chemometric classification of nineteen buckwheat honey was performed using PCA and HCA techniques. Both were supported by correlation analysis. Thirteen compounds contributed significantly to the clustering of buckwheat honey based on geographical origin.

Exploring the formation and diversity of secnidazole cocrystals

This study investigates the cocrystallization of secnidazole (SNZ), a potent antimicrobial drug, with several coformers, overcoming the inherent stability challenges posed by its hemihydrate form to produce novel solid states. We successfully synthesized and characterized three novel cocrystals with carvacrol (CAR), fumaric acid (FMA), and 3,5-dinitrobenzoic acid (DNZ), employing synchrotron single crystal analysis to elucidate their structures. The application of Hirshfeld surface and 2D fingerprint plots further enriched our understanding of the unique packing arrangements within these cocrystals. Moreover, preliminary powder X-ray diffraction (PXRD) patterns hinted at the emergence of additional novel solid forms with salicylic acid (SLC), oxalic acid (OXA), succinic acid (SUC), citric acid (CTR), and thymol (THY). Supported by literature and a thorough analysis of molecular interactions, we propose the existence of pharmaceutical cocrystals among these newly identified solid forms. Our findings not only augment the repertoire of SNZ based pharmaceuticals but also accentuates the strategic utilization of supramolecular synthons, offering significant advancements in the understanding of novel solid form formation, and the critical role of hydrogen bonding in these processes.

Potato glycoside alkaloids exhibit antifungal activity by regulating the tricarboxylic acid cycle pathway of Fusarium solani.

Fusarium solani is a pathogenic fungus that causes significant harm, leading to crop yield reduction, fruit quality reduction, postharvest decay, and other diseases. This study used potato glycoside alkaloids (PGA) as inhibitors to investigate their effects on the mitochondrial structure and tricarboxylic acid (TCA) cycle pathway of F. solani. The results showed that PGA could inhibit the colony growth of F. solani (54.49%), resulting in the disappearance of the mitochondrial membrane and the loss of contents. PGA significantly decreased the activities of aconitase (ACO), isocitrate dehydrogenase (IDH), α-ketoglutarate dehydrogenase (α-KGDH), succinate dehydrogenase (SDH), fumarase (FH), malate dehydrogenase (MDH), succinyl-CoA synthetase (SCS), and increased the activity of citrate synthase (CS) in F. solani. After PGA treatment, the contents of acetyl coenzyme A (CoA), citric acid (CA), malic acid (L-MA), and α-ketoglutaric acid (α-KG) in F. solani were significantly decreased. The contents of isocitric acid (ICA), succinyl coenzyme A (S-CoA), succinic acid (SA), fumaric acid (FA), and oxaloacetic acid (OA) were significantly increased. Transcriptomic analysis showed that PGA could significantly affect the expression levels of 19 genes related to TCA cycle in F. solani. RT-qPCR results showed that the expression levels of ACO, IDH, α-KGDH, and MDH-related genes were significantly down-regulated, and the expression levels of SDH and FH-related genes were significantly up-regulated, which was consistent with the results of transcriptomics. In summary, PGA can achieve antifungal effects by reducing the tricarboxylic acid cycle's flow and regulating key genes' expression levels. This study reveals the antifungal mechanism of PGA from the perspective of TCA cycle, and provides a theoretical basis for the development and application of PGA as a biopesticide.