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

The purpose of this study is to investigate the previously unknown connection that succinate has with neutrophils in the setting of adjuvant-mediated immunological enhancement. It has been discovered that succinates stimulate the recruitment of neutrophils in immunization sites, which in turn induces the expression of what is known as neutrophil-derived B cell-activating factor (BAFF). Further amplification of vaccine-induced antibody responses is provided via the succinate receptor 1-interferon regulatory factor 5 (SUCNR1-IRF5)-BAFF signaling pathway, which provides insights into a unique mechanism for immunological enhancement. NEW & NOTEWORTHY: This study explores the role of succinate as a vaccine adjuvant, revealing its capacity to enhance neutrophil recruitment at immunization sites, which boosts B cell activation through the succinate receptor 1-interferon regulatory factor 5-B cell-activating factor (SUCNR1-IRF5-BAFF) signaling pathway. Results demonstrate succinate's potential to amplify vaccine-induced antibody responses, highlighting its significance in immunological enhancement and offering new insights into the adjuvant mechanisms of action, particularly in neutrophil-mediated immune responses. [ABSTRACT FROM AUTHOR]

Loss-of-function mutations in genes encoding the Krebs cycle enzymes Fumarate Hydratase (FH) and Succinate Dehydrogenase (SDH) induce accumulation of fumarate and succinate, respectively and predispose patients to hereditary cancer syndromes including the development of aggressive renal cell carcinoma (RCC). Fumarate and succinate competitively inhibit αKG-dependent dioxygenases, including Lysine-specific demethylase 4A/B (KDM4A/B), leading to suppression of the homologous recombination (HR) DNA repair pathway. In this study, we have developed new syngeneic Fh1- and Sdhb-deficient murine models of RCC, which demonstrate the expected accumulation of fumarate and succinate, alterations in the transcriptomic and methylation profile, and an increase in unresolved DNA double-strand breaks (DSBs). The efficacy of poly ADP-ribose polymerase inhibitors (PARPis) and temozolomide (TMZ), alone and in combination, was evaluated both in vitro and in vivo. Combination treatment with PARPi and TMZ results in marked in vitro cytotoxicity in Fh1- and Sdhb-deficient cells. In vivo, treatment with standard dosing of the PARP inhibitor BGB-290 and low-dose TMZ significantly inhibits tumor growth without a significant increase in toxicity. These findings provide the basis for a novel therapeutic strategy exploiting HR deficiency in FH and SDH-deficient RCC with combined PARP inhibition and low-dose alkylating chemotherapy.

Liberal oxygen therapy for COVID-19 causes hyperoxemia in most patients and reduces their survival rate. Even moderate hyperoxemia reduces oxygen delivery, and high levels of oxygen in central venous blood increase mortality in COVID-19 patients. These facts occur due to the manifestation of toxic effects of oxygen (vasoconstriction, bronchoconstriction) requiring the use of medications that reduce toxic effects. The aim of the study was to assess the ability of succinate preparations to eliminate the toxic effects of oxygen affecting central hemodynamics and blood oxygenation in patients with COVID-19. Material and methods. The effect of medicines containing succinates (Cytoflavin and Reamberin) in stopping the manifestations of hyperoxia in 51 surviving patients with the novel coronavirus infection who received high-flow oxygen therapy (HFOT) was analyzed in a retrospective study. Results. Monitoring of heart rate, respiratory rate, SpO₂, PaO₂ and PaO₂/FiO₂ during HFOT within 12 hours from the start of oxygen therapy showed an indirect, but statistically significant effect of stopping the toxic effects of oxygen. This was expressed in a decrease in tachycardia and tachypnea [to 86.7–115.0 (at P

The adverse outcomes in patients with COVID-19 in the initial phase of the disease are often due to the development of cytokine storm, endothelial dysfunction, shifts in the hemostasis system, microangiopathy, angiocentric inflammation, and pathological angiogenesis, which require targeted therapy. Unfortunately, to date, there is still no drug with proven high efficacy. This review is to analyse the literature data on the pathogenesis of vascular homeostasis lesions and possible ways to correct the existing shifts in patients with COVID-19. When the oxygen content in the tissue decreases, one of the most important mechanisms of adaptation is the activation of the succinate oxidase pathway, but under conditions of prolonged hypoxia and intoxication, the succinate reserve is rapidly depleted. That is why exogenous of succinic acid can enhance the adaptive capabilities of the organism and improve the prognosis in patients with COVID-19. Succinic acid preparations contribute to normalization of energy exchange and reduction of oxidative stress, especially in combination with inosine, nicotinamide and riboflavin and are widely used in clinical practice in various nosological forms. Taking into account the analysis of data on the mechanisms of clinical effects of succinate-containing preparations, this group of drugs can be considered as promising with regard to the correction of vascular disorders in COVID-19.

The chemical transformation of waste polymers into value-added chemicals is of significance for circular economy and sustainable development. Herein, we report upcycling poly(succinates) (PSS) with amines into N-substituted succinimides over succinimide anion-based ionic liquids (ILs, e.g, 1,8-diazabicyclo[5.4.0]undec-7-ene succinimide, [HDBU][Suc]). Assisted with H2O, [HDBU][Suc]) showed the best performance, which could achieve complete transformation of a series of PSS into succinimide derivatives and corresponding diols under mild and metal-free conditions. Mechanism investigation indicates that the cation-anion confined hydrogen-bonding interactions among IL, H2O, ester group, and amino/amide groups, strengthens nucleophilicity of the N atoms in amino/amide groups, and improves electrophilicity of carbonyl C atom in ester group. The attack of the amino/amide N atom on carbonyl C of ester group results in cleavage of carbonyl C-O bond in polyester and formation of amide group. This strategy is also effective for aminolysis of poly(trimethylene glutarate) to glutarimides, and poly(1,4-butylene adipate) to caprolactone diimides. Ionic liquids have been employed in dissolution and chemical degradation of waste polymers. Here the authors report a cation-anion confined hydrogen-bonding catalysis strategy to deconstruct poly(succinates) into N-substituted succinimides over ionic liquids. [ABSTRACT FROM AUTHOR]

As one of the most induced genes in activated macrophages, immune-responsive gene 1 (IRG1) encodes a mitochondrial metabolic enzyme catalysing the production of itaconic acid (ITA). Although ITA has an anti-inflammatory property, the underlying mechanisms are not fully understood. Here we show that ITA is a potent inhibitor of the TET-family DNA dioxygenases. ITA binds to the same site on TET2 as the co-substrate α-ketoglutarate, inhibiting TET2 catalytic activity. Lipopolysaccharide treatment, which induces Irg1 expression and ITA accumulation, inhibits Tet activity in macrophages. Transcriptome analysis reveals that TET2 is a major target of ITA in suppressing lipopolysaccharide-induced genes, including those regulated by the NF-κB and STAT signalling pathways. In vivo, ITA decreases the levels of 5-hydroxymethylcytosine, reduces lipopolysaccharide-induced acute pulmonary oedema as well as lung and liver injury, and protects mice against lethal endotoxaemia, depending on the catalytic activity of Tet2. Our study thus identifies ITA as an immune modulatory metabolite that selectively inhibits TET enzymes to dampen the inflammatory responses.

The paper reports the results of the study on the synthesis of new heterometallic complexes of Co(II) and Nd(III) with succinic acid in the presence of 1,10-phenanthroline or pyridine. The following hetero- and monocomplexes were synthesized: [Co(C4H4O4)-2Py]-2H2O and [Co(C4H4O4)- Phen].2H2О; [Nd,(C4H4O4)3]5H2О and [Nd(C4H4O4)3 2Phen]2H2O; [Co2Nd2(C4H4O4)54Py]4H2O and [Co2Nd2(C4H4O4)52Phen]4H2O (Phen - phenanthroline, and Py - pyridine). The study of their composition, structure, thermal properties and determination of the ability of he-terocomplexcs to form complex oxides was carried out. The complexes were characterized by a number of physicochemical methods: elemental analysis, IR- and diffuse reflection spectroscopies, X-ray powder diffraction and differential thermal analysis. Based on the analysis of diffuse reflection spectra and IR spectra ofhcterocomplexcs, it was shown that succinic add and 1,10-phenanthroline are bidentatcly bound to metal atoms. The metals arc connected by succinic acid, forming a chain. Oxide powders were obtained during thermolysis of hc-tcrocomplcxcs up to 00°C. The-composition of the synthesized hcteromctallic compounds was controlled by X-ray powder diffraction. It was shown that a complex oxide of NdCoO3 (cubic crystal system), without impurities, was formed, when the heterocomplex of phenanthroline [Co2Nd2(C4H4O4)3-2 Phen]-411,0 was heated to 800°C. When heating the heterocomplex of pyridine [Co2Nd2(C4H4O4)5-4Py]-4H2O, in addition to the complex oxide-NdCoO3, oxides Nd2O3 (hexagonal crystal system), Nd2O3 (cubic crystal system) and Co3O4 oxide-(cubic crystal system) were forme-d. The he-terocomplex [Co2Nd2(C4H4O4)5-2Phcn]-4H2O can be used as a precursor for the synthesis of cobaltate of neodymium with lower energy costs than in solid-phase synthesis. [ABSTRACT FROM AUTHOR]

Metoprolol has been widely used for controlling high blood pressure, preventing myocardial reinfarction, setting rate changes, setting heart rhythm, treatment of chronic angina, and preventing excessive bleeding during surgery. The purpose of this research is the formulation and manufacture of extended-release tablets of metoprolol succinate that conform to all the in vitro physicochemical US Pharmacopoeia national formulary (USP32). For preparing the tablets, the hydrophilic HPMC(K100M) polymer was used in the direct compression method. The release of metoprolol in phosphate buffer having pH=6.8 (USP32) was measured by HPLC. Also, using experimental correlation of diffusivity in a buffer medium and Gurney-Lurie charts during tablet enlargement with time, diffusion coefficients of drug and partition coefficients were obtained at different time steps. The rate of drug release depends on the type, viscosity, and polymer concentration. Drug release results over 20 hours for polymers of HPMC(K100M), HPMC(K4M), HPMC(K15M), polyethylene oxide, ethyl cellulose, and Eudragit (RL100) were investigated and compared. The results demonstrated that HPMC(K100M) met the standards of USP32 very well and was superior over the other polymers tested. [ABSTRACT FROM AUTHOR]

[Display omitted] • The first regioselective palladium(II)-catalyzed alkoxy-aryloxycarbonylation of olefins is described. • Various olefins, alcohols and phenols have been converted into the corresponding mixed alkyl-aryl succinates in one-step, with yields up to 90%, under mild reaction conditions (4 bar of CO and 20 °C). • The selectivity of the process has been explained by means of DFT calculations. • The unexpected role of the oxidant benzoquinone, in promoting the final elimination step leading to the succinic product, has been identified. The direct alkoxy-aryloxycarbonylation reaction of olefins has been realized for the first time. Under palladium(II) catalysis and with p -benzoquinone as oxidant, various olefins (aromatic, aliphatic and 1,2-disubstituted), alcohols (primary, secondary and tertiary) and phenols (with different para , meta and ortho substituents) have been converted in one-step into mixed alkyl aryl succinates in moderate to excellent yields (up to 90%). The reaction is completely regioselective, as the aryl ester moiety was consistently observed on the more substituted carbon of the starting alkene double bond. Based on experimental results and detailed DFT calculations, a plausible catalytic cycle has been proposed, accounting for the observed regioselectivity. Interestingly, from our computation studies, benzoquinone was found to be crucial not only to regenerate the catalytic active species, but also for promoting the final elimination step, leading to the desired succinate. Finally, some reactions were performed to prove the different chemical behavior of the two installed ester groups. [ABSTRACT FROM AUTHOR]

ObjectivesCerebral ischemia/reperfusion (IR) drives oxidative stress and injurious metabolic processes that lead to redox imbalance, inflammation, and tissue damage. However, the key mediators of reperfusion injury remain unclear, and therefore, there is considerable interest in therapeutically targeting metabolism and the cellular response to oxidative stress.MethodsThe objective of this study was to investigate the molecular, metabolic, and physiological impact of itaconate treatment to mitigate reperfusion injuries in in vitro and in vivo model systems. We conducted metabolic flux and bioenergetic studies in response to exogenous itaconate treatment in cultures of primary rat cortical neurons and astrocytes. In addition, we administered itaconate to mouse models of cerebral reperfusion injury with ischemia or traumatic brain injury followed by hemorrhagic shock resuscitation. We quantitatively characterized the metabolite levels, neurological behavior, markers of redox stress, leukocyte adhesion, arterial blood flow, and arteriolar diameter in the brains of the treated/untreated mice.ResultsWe demonstrate that the "immunometabolite" itaconate slowed tricarboxylic acid (TCA) cycle metabolism and buffered redox imbalance via succinate dehydrogenase (SDH) inhibition and induction of anti-oxidative stress response in primary cultures of astrocytes and neurons. The addition of itaconate to reperfusion fluids after mouse cerebral IR injury increased glutathione levels and reduced reactive oxygen/nitrogen species (ROS/RNS) to improve neurological function. Plasma organic acids increased post-reperfusion injury, while administration of itaconate normalized these metabolites. In mouse cranial window models, itaconate significantly improved hemodynamics while reducing leukocyte adhesion. Further, itaconate supplementation increased survival in mice experiencing traumatic brain injury (TBI) and hemorrhagic shock.ConclusionsWe hypothesize that itaconate transiently inhibits SDH to gradually "awaken" mitochondrial function upon reperfusion that minimizes ROS and tissue damage. Collectively, our data indicate that itaconate acts as a mitochondrial regulator that controls redox metabolism to improve physiological outcomes associated with IR injury.

Background Dipeptidyl peptidase-4 inhibitors (DPP-4Is) are used clinically as oral antidiabetic agents. Although DPP-4Is are known to ameliorate liver fibrosis, the protective mechanism of DPP-4Is in liver fibrosis remains obscure. In this study, gemigliptin was used to investigate the potential of DPP-4Is to alleviate the progression of liver fibrosis. Methods To clarify the effects and mechanisms of gemigliptin, we conducted various experiments in LX-2 cells (immortalized human hepatic stellate cells [HSCs], the principal effectors of hepatic fibrogenesis), which were activated by succinate and exhibited elevated expression of α-smooth muscle actin, collagen type 1, and pro-inflammatory cytokines and increased cell proliferation. In vivo, we examined the effects and mechanisms of gemigliptin on a high-fat, high-cholesterol–induced mouse model of nonalcoholic steatohepatitis (NASH). Results Gemigliptin decreased the expression of fibrogenesis markers and reduced the abnormal proliferation of HSCs. In addition, gemigliptin reduced the succinate-induced production of mitochondrial reactive oxygen species (ROS), intracellular ROS, and mitochondrial fission in HSCs. Furthermore, in the mouse model of NASH-induced liver fibrosis, gemigliptin alleviated both liver fibrosis and mitochondrial dysfunction. Conclusion Gemigliptin protected against HSC activation and liver fibrosis by alleviating mitochondrial dysfunction and ROS production, indicating its potential as a strategy for preventing the development of liver disease.

The synthesis of dibenzyl-(1S*,2S*)-2,3-dihydro-1H-indene-1,2-dicarboxylate has been realized through a diastereospecific bis-alkoxycarbonylation reaction, which starts from the cheap and easily available 1H-indene, benzyl alcohol, and carbon monoxide. The catalyst is formed in situ by mixing Pd(TFA)2, the ligand N2,N3-bis(2,6-dimethylphenyl)butane-2,3-diimine, p-benzoquinone is used as an oxidant, and benzyl alcohol acts both as a nucleophile and as the main solvent. [ABSTRACT FROM AUTHOR]

A new family of succinate‐based plasticizers, consisting of molecules with a linear alkyl chain capped with n‐alkyl succinates on both ends, was evaluated as potential bio‐based plasticizers for stiff polymers. The influence of the central and side alkyl chain lengths on the mechanical and thermal properties as well as the migration behavior of poly(vinyl chloride) (PVC)/plasticizer blends was evaluated. The central chain length had the greatest influence on plasticizer performance, with shorter chains leading to blends with higher stress at break and surface hardness, whereas long chains produced softer blends. An optimum chain central length of five carbon atoms was observed, with longer chains leading to reduced compatibility and exudation of the plasticizer at higher plasticizer concentrations. The entire family of plasticizers performed comparably or better than the commercial plasticizer di(2‐ethylhexyl) phthalate (DEHP) when incorporated into the blend at concentrations of 20–60 parts per hundred resin (phr). Overall, the succinate‐based plasticizers/PVC blends all exhibited equal or improved tensile properties (by up to 77%), surface hardness (reduced by up to 43%), glass transition temperature (reduced by up to 11°C), and migration into organic media (reduced by up to 38%) when compared with blends with DEHP at 40 phr. [ABSTRACT FROM AUTHOR]

Tet methylcytosine dioxygenase 2 (Tet2) is an epigenetic regulator that removes methyl groups from deoxycytosine residues in DNA. Tet2-deficient murine macrophages show increased lipopolysaccharide (LPS)-induced and spontaneous inflammation at least partially because Tet2 acts to restrain interleukin (IL)-1β and IL-6 expression in induced cells. MicroRNAs have emerged as critical regulatory noncoding RNAs that tune immune cell responses to physiological perturbations and play roles in pathological conditions in macrophages. To determine if a microRNA played any role in Tet2 activity, we examined the interrelationship of Tet2 action and the let-7 microRNA family, utilizing several let-7 microRNA engineered murine models. We first showed that Tet2, but not Tet3, is a direct target of the let-7a-1/let-7d/let-7f-1 (let-7adf) microRNAs in macrophages. We found that overexpression or deletion of the let-7adf gene cluster causes altered IL-6 induction both in tissue culture cells induced by LPS treatment in vitro as well as in a Salmonella infection mouse model in vivo. Mechanistically, let-7adf promotes IL-6 by directly repressing Tet2 levels and indirectly by enhancing a Tet2 suppressor, the key TCA cycle metabolite, succinate. We found that Let-7adf promotes succinate accumulation by regulating the Lin28a/Sdha axis. We thereby identify two pathways of let-7 control of Tet2 and, in turn, of the key inflammatory cytokine, IL-6, thus characterizing a regulatory pathway in which a microRNA acts as a feedback inhibitor of inflammatory processes.

Evidence suggests that novel enzyme functions evolved from low-level promiscuous activities in ancestral enzymes. Yet, the evolutionary dynamics and physiological mechanisms of how such side activities contribute to systems-level adaptations are not well characterized. Furthermore, it remains untested whether knowledge of an organism's promiscuous reaction set, or underground metabolism, can aid in forecasting the genetic basis of metabolic adaptations. Here, we employ a computational model of underground metabolism and laboratory evolution experiments to examine the role of enzyme promiscuity in the acquisition and optimization of growth on predicted non-native substrates in Escherichia coli K-12 MG1655. After as few as approximately 20 generations, evolved populations repeatedly acquired the capacity to grow on five predicted non-native substrates-D-lyxose, D-2-deoxyribose, D-arabinose, m-tartrate, and monomethyl succinate. Altered promiscuous activities were shown to be directly involved in establishing high-efficiency pathways. Structural mutations shifted enzyme substrate turnover rates toward the new substrate while retaining a preference for the primary substrate. Finally, genes underlying the phenotypic innovations were accurately predicted by genome-scale model simulations of metabolism with enzyme promiscuity.

HIV-1 protease (PR) cleavage of the Gag polyprotein triggers the assembly of mature, infectious particles. Final cleavage of Gag occurs at the junction helix between the capsid protein CA and the SP1 spacer peptide. Here we used MicroED to delineate the binding interactions of the maturation inhibitor bevirimat (BVM) using very thin frozen-hydrated, 3D microcrystals of a CTD-SP1 Gag construct with and without bound BVM. The 2.9-Å MicroED structure revealed that a single BVM molecule stabilizes the six-helix bundle via both electrostatic interactions with the dimethylsuccinyl moiety and hydrophobic interactions with the pentacyclic triterpenoid ring. These results provide insight into the mechanism of action of BVM and related maturation inhibitors that will inform further drug discovery efforts. This study also demonstrates the capabilities of MicroED for structure-based drug design.

Succinic acid esters are important compounds that find many applications in various industrial fields. One of the most promising and easy ways of producing these molecules is represented by the bis-alkoxycarbonylation reaction of olefins. In particular, a recently developed catalytic system, consisting of an aryl α-diimine/palladium(II) catalyst and p-benzoquinone as an oxidant, has allowed succinates to be obtained in high yields. A similar methodology was applied here for the unprecedented synthesis of the bis(2-hydroxyethyl) 2-phenylsuccinate in 78% isolated yield, starting from the cheap and commercially available compounds styrene and ethylene glycol. To our knowledge, no other examples of bis-alkoxycarbonylations of olefins involving diols have been reported thus far. The obtained product was fully characterized by NMR and ESI-MS analyses. [ABSTRACT FROM AUTHOR]

Carotenoid succinates were synthesized from hydroxy carotenoids and were coupled to a commercially available derivative of melatonin via amide bond for producing more powerful anti-oxidants and yet new hybrid lipophilic bifunctional molecules with additional therapeutic effects. The coupling reactions produced conjugates in acceptable to good yields. Succinylation increased the water solubility of the carotenoids, while the conjugation with melatonin resulted in more lipophilic derivatives. The conjugates showed self-assembly in aqueous medium and yielded relatively stable colloidal solutions in phosphate-buffered saline. Antioxidant behavior was measured with ABTS and the FRAP methods for the carotenoids, the carotenoid succinates, and the conjugates with melatonin. A strong dependence on the quality of the solvent was observed. TEAC values of the new derivatives in phosphate-buffered saline were found to be comparable to or higher than those of parent carotenoids, however, synergism was observed only in FRAP assays. [ABSTRACT FROM AUTHOR]

In this research, aluminum metal-organic framework encapsulated with poly (itaconic acid) grafted crosslinked chitosan composite sponge (Al-MOF@PIC) was prepared. SEM, FTIR, XPS, XRD, and BET techniques were employed to thoroughly characterize the synthesized material and establish its structure and characteristics. The study discovered that the Al-MOF@PIC is an efficient way to remove dyes, which constitute a significant number of contaminants in industrial wastewater. Subsequently the adsorption of methyl violet 2B (MV-2B) dye, the surface area, pore size, and pore volume of the adsorbent decreased from 1860.68 m 2 /g, 1.62 nm, and 1.52 cc/g to 1426.45 m 2 /g, 1.11 nm, and 0.92 cc/g, individually. This modification suggested that a portion of the MV-2B dye had been removed by adsorption over the adsorbent's pores. The excellent adsorption capacity of the material was further confirmed by batch adsorption tests, which displayed a maximum adsorption capability of 646.76 mg/g for the elimination of MV-2B dye. The high adsorption energy of 26.8 kJ/mol designates that chemisorption is primarily responsible for MV-2B dye adsorption against the sponge adsorbent. The Al-MOF@PIC composite sponge demonstrated exceptional reusability over six cycles, demonstrating its strength and durability. The Al-MOF@PIC composite sponge successfully removes MV-2B from water by pore filling, π-π stacking, hydrogen bonding, and electrostatic interactions, which are the key mechanisms behind the adsorption of the dye pollutant. Its potential for practical applications is further demonstrated using Box Behnken-design (BBD) to optimize the adsorption consequences., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Dicaffeoyltartaric acid (diCT) and 3,5-dicaffeoylquinic acid (3,5-diCQ) are described for their aphicidal properties on several aphid species. Intending to valorize diCT and 3,5-diCQ as biocontrol products and because of the high adaptive capacities of aphids to xenobiotics, we sought to determine the existence of adaptation first in Myzus persicae (Sulzer) (Hemiptera: Aphididae) and then other aphids. Resistance of aphids to these biopesticides could be promoted by (i) the existence of resistance to synthetic insecticides that may confer cross-resistance and (ii) the presence of these compounds in wild plants likely which may have led to pre-existing adaptation in aphids. We assessed the resistance levels to diCT and 3,5-diCQ in 7 lab strains (including some resistant to synthetic aphicides) and 7 wild populations of M. persicae using biotests. The activities of detoxification enzymes contributing to insecticide resistance were also measured. Additionally, we followed the same method to characterize susceptibility to these caffeic derivatives in wild populations of Nasonovia ribisnigri (Mosley) (Hemiptera: Aphididae), Brevicoryne brassicae(Linnaeus) (Hemiptera: Aphididae) and, Aphis craccivora(Koch) (Hemiptera: Aphididae). Our results show variability in susceptibility to diCT between populations of M. persicae, but resistance ratios (RR) were low (RR = 3.59). We found no cross-resistance between synthetic insecticides and diCT. Carboxylesterase and glutathione-S-transferase did not seem to be involved in its detoxification. A clone of A. craccivora collected from peanut, a species rich in diCT, was not susceptible to either diCT or 3,5-diCQ, suggesting a common molecular target for these 2 molecules and the existence of a high-effect resistance mechanism. These active botanical substances remain good candidates for M. persicae biocontrol in agriculture., (© The Author(s) 2024. Published by Oxford University Press on behalf of Entomological Society of America.)

The aim of the work was the search for materials from experimental and clinical studies reflecting the pathogenetic role of the possible use of succinates for the correction of hypoxia in COVID-19. Materials and methods. 79 foreign and domestic literature sources were analyzed concerning the pathogenesis of COVID-19 and the pathogenetic role of succinates in hypoxia under conditions of COVID-19, oxidative stress, and diaphragmatic dysfunction were analyzed. The literature search was carried out using Pubmed and ELIBRARY.ru databases. Results. As the analysis of the literature has shown, tissue hypoxia is the basis of COVID-19 pathogenesis, triggering the entire cascade of pathomorphological events leading to the development of multiple organ failure. A number of experimental and clinical studies (on a fairly large number of patients) reflect the positive effect of tissue hypoxia correction using succinates, both in adult patients and in children with a different spectrum of pathology associated with acute respiratory failure syndrome. Conclusion. Analysis of literature data allows to substantiate the prospect of using preparations containing succinate (reamberin, cytoflavin) in the complex therapy of severe cases of COVID-19.

The aim of the study. To evaluate the effect of succinic acid derivatives on changes of mitochondrial function in rats under cerebral ischemia conditions.

[Display omitted] • The earth-abundant and cost-efficient CoCl 2 was employed to afford 1,4-dicarboxylic acid diesters under mild conditions. • The novel ligand (BiPyPhos) is the key to success. • This methodology features 100% atomic efficiency, time-saving, and acid-free. • The reaction affords the desired product directly, and an associative mechanism is proposed. Herein, we report a straightforward approach to access 1,4-dicarboxylic acid diesters via BiPyPhos-enabled cobalt-catalyzed bis-alkoxycarbonylation of alkynes. This strategy utilizes an earth-abundant and cost-efficient cobalt catalyst, free from acid additives or noble metal catalysts. The bifunctional ligand BiPyPhos plays a crucial character in both the rate-determining step and the stability of the cobalt catalytic system. The reaction delivers the product directly with an associative abstraction process. Mechanism studies coupled with NMR, FI-IR, HRMS, and single-crystal X-ray analysis indicate that the carbonyl cobalt hydride complex might be the catalytically active species. Utilizing CoCl 2 for bis-alkoxycarbonylation of alkynes has hardly any precedent. [ABSTRACT FROM AUTHOR]

Microbial cells utilizing electricity to produce high-value fuels and chemicals are the foundation of the biocathodic bioelectrochemical system. However, molecular mechanisms of electron transfer and utilization have not been elucidated. In this work, Escherichia coli engineered by introducing the Mtr pathway from Shewanella oneidensis exhibited stronger electrochemical activity than control and could utilize exogenous electrons to stimulate metabolite profiles and boost succinate production in the bioelectrochemical system. Proteomic analysis and real-time PCR were performed to investigate the effect of exogenous electrons on electroactive E. coli. Bioinformatics analysis suggested that the proteins of molecular function associated with oxidoreductase activity, 4 iron, 4 sulfur([4Fe-4S]) cluster binding, iron-sulfur cluster binding, and metal cluster binding were positively affected by exogenous electrons. Moreover, mapping to the Kyoto Encyclopedia of Genes and Genomes pathway database showed that the up-regulated proteins were mainly involved in metabolic pathways of tricarboxylic acid cycle, pyruvate metabolism, and nitrogen metabolism pathway, providing support for the metabolic balance of microbial cells shifting toward reduced end-products due to electron utilization. Using a biochemical method, the ompF -overexpressed strain was employed to investigate the function of the channel protein. These findings provided a theoretical basis for further improving electron transfer and utilization efficiency, and contributed to the potential applications of the bioelectrochemical system. [ABSTRACT FROM AUTHOR]

A chemoselective method for the carbonylation of allylic substrates CH2=CHCH2X (X=OAc, OC(O)CH2CN, OPh, OEt, OC(O)OPh, OC(O)OiBu, N(H)C(O)Ph, N(Ph)C(O)Ph, N(H)Boc, N(Ph)Boc, Ph, CO2Bn, CN), leading to alkyl succinates with preservation of the X group, under Pd(II)‐catalyzed oxidative carbonylation conditions, has been developed. Our method shows a completely different inverse chemoselectivity with respect to the "classical" substitutive carbonylation of the allyl compounds, which is known to provide β,γ‐unsaturated carbonyl derivatives through the formation of a π‐allylpalladium intermediate. An accurate study, carried out using allyl acetate as model substrate, allowed to maximize the selectivity in the envisioned 2‐CH2X substituted succinates. The best catalyst is generated in situ by mixing Pd(TFA)2 (TFA=trifluoroacetate) and the N,N′‐di(anthracen‐9‐yl)butane‐2,3‐diimine ligand. p‐Benzoquinone was used as oxidant in presence of benzyl alcohol, which acts as a nucleophile and as a solvent, under 4 bar of CO at 20 °C. A combined effect of the ligand and the nucleophile, rationalized through DFT calculations, has been observed both in promoting the bis‐alkoxycarbonylation process and in preventing π‐allylpalladium‐mediated side reactions, allowing the attainment of succinate derivatives with moderate to good yields. [ABSTRACT FROM AUTHOR]

An efficient and convenient three-component reaction of dialkyl acetylene dicarboxylates with trialkyl(aryl) phosphites in the presence of maleimide or phthalimide provides a straightforward approach to the synthesis of stable dialkyl(aryl) phosphoryl succinates in excellent yields. While the reactions were carried out in the presence of triphenylphosphine, stabilized phosphoranes, obtained from three component reaction, undergo a smooth intramolecular Wittig reaction in boiling toluene to produce functionalized 2H-pyrrol-2-ones in good yields. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to examine the impact of CA on DN and elucidate its underlying molecular mechanisms of inflammation., Methods: We fed C57BL/6 mice injected with streptozotocin to induce diabetes. In addition, we stimulated NRK-52E cells with 20 mmol/L d-glucose to mimic the diabetic condition., Results: Our findings demonstrated that CA effectively reduced blood glucose levels, and improved DN in mice models. Additionally, CA reduced kidney injury and inflammation in both mice models and in vitro models. CA decreased high glucose-induced ferroptosis of NRK-52E cells by inducing GSH/GPX4 axis. Conversely, the ferroptosis activator or the PI3K inhibitor reversed positive effects of CA on DN in both mice and in vitro models. CA suppressed PAQR3 expression in DN models to promote PI3K/AKT activity. The PAQR3 activator reduced the positive effects of CA on DN in vitro models. Moreover, CA directly targeted the PAQR3 protein to enhance the ubiquitination of the PAQR3 protein., Conclusion: Overall, our study has uncovered that CA promotes the ubiquitination of PAQR3, leading to the attenuation of ferroptosis in DN. This effect is achieved through the activation of the PI3K/AKT signaling pathways by disrupting the interaction between PAQR3 and the P110α pathway. These findings highlight the potential of CA as a viable therapeutic option for the prevention of DN and other forms of diabetes.

The application of camellia oil is limited by its susceptibility to oxidation and insolubility in water, particularly under high humidity and temperature conditions. In order to effectively reduce the oxidation rate of camellia oil, prolong the shelf life in order to improve the stability in storage under different conditions, this study encapsulates camellia oil in Pickering emulsions stabilized by Octenyl succinic acid (OSA) starch, achieving a 100-fold reduction in release rate and enhanced lipid oxidation stability. The smooth surface and complete particles of the emulsion were observed and no new chemical bonds were formed. The minimum particle sizes were 1.72 μm and 2.73 μm, when the Pickering emulsion was set at pH 6 and 0.1 M NaCl. In the digestion process, the microstructures observed that Pickering emulsion possessed super stability against oral and gastric digestions, prolonged the release time and improved the bioavailability compared with camellia oil, and the digestibility of the emulsion was 56.16 % within 120 min. All these results indicate that OSA-starch stabilized camellia oil can effectively increase solubility, improve stability and expand the application range., Competing Interests: Declaration of competing interest The authors declare that they have no known competing interests in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Metabolic reprogramming is emerging as a hallmark of the innate immune response, and the dynamic control of metabolites such as succinate serves to facilitate the execution of inflammatory responses in macrophages and other immune cells. Immunoresponsive gene 1 (Irg1) expression is induced by inflammatory stimuli, and its enzyme product cis-aconitate decarboxylase catalyzes the production of itaconate from the tricarboxylic acid cycle. Here we identify an immunometabolic regulatory pathway that links Irg1 and itaconate production to the succinate accumulation that occurs in the context of innate immune responses. Itaconate levels and Irg1 expression correlate strongly with succinate during LPS exposure in macrophages and non-immune cells. We demonstrate that itaconate acts as an endogenous succinate dehydrogenase inhibitor to cause succinate accumulation. Loss of itaconate production in activated macrophages from Irg1(-/-) mice decreases the accumulation of succinate in response to LPS exposure. This metabolic network links the innate immune response and tricarboxylic acid metabolism to function of the electron transport chain.