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This study examines the intermolecular interactions between small molecules and solvents, with a particular focus on pyruvic acid (PA). PA plays a significant role in biochemistry, astrochemistry, and atmospheric chemistry, particularly in aerosol particle formation. Previous studies on PA have been expanded upon by exploring its hydration and complexation with 2,2,2-trifluoroethanol (TFE). The clusters were generated using a supersonic expansion and characterized by broadband Fourier transform microwave spectroscopy. The structures of the clusters were identified by comparing the experimental results with high-level quantum-chemical computations. Among the possible isomers for the hydrated complex, the Tc-(H2O)2 kinetic complex, where PA exhibits an internal hydrogen bond, was favored over the Tt-(H2O)2 form, predicted to be the most stable conformer. Transitions from both the A and E internal rotation substates were observed exclusively in the dihydrate. The complex with TFE did not exhibit splitting due to the internal rotation of the methyl top. This is attributed to the presence of electronegative fluorine groups in TFE, stabilizing the complex through additional CH⋯F interactions, thereby hindering the internal rotation motion of the methyl top. [ABSTRACT FROM AUTHOR]

[Display omitted] • MoO 2 nanoparticles of around 10 nm was synthesized by a simple solvothermal method. • CdS-MoO 2 heterojunction was prepared by a two-phase assembling process. • MoO 2 with oxygen vacancies boosts light absorption and the creation of extra catalytic centers. • Hydrogen and pyruvate production rates of 4.73 and 3.73 mmol•g-1•h-1, respectively, with 95.68% selectivity. • S-scheme heterojunction promotes separation of charges while retaining strong oxidizing and reducing capabilities. The persistent hurdles of charge rapid recombination, inefficient use of light and utilization of sacrificial reagents have plagued the field of photocatalytic hydrogen evolution (PHE). In this research, tiny MoO 2 nanoparticles of 10 nm in diameter were prepared through a straightforward solvothermal approach with a specific ratio of oleylamine and oleic acid as stabilizers. The critical factor in the synthesis process was found to be the ratio of oleylamine to oleic acid. Moreover, a two-phase interface assembly method facilitated the uniform deposition of MoO 2 onto CdS nanorods. Due to the localized plasmonic-thermoelectric effect on the surface of MoO 2 along with its abundant oxygen vacancies, the composite catalyst exhibited outstanding photo-utilization efficiency and an abundance of active sites. The CdS-MoO 2 composite displayed a unique photochemical property in transforming lactic acid into pyruvic acid and generating hydrogen simultaneously. After exposure to artificial sunlight for 4 h, significant values of 4.7 and 3.7 mmol⋅g−1⋅h−1 were achieved for hydrogen production and pyruvic acid formation, respectively, exceeding CdS alone by 3.29 and 4.02-fold, while the selectivity of pyruvic acid was 95.68 %. Furthermore, the S-Scheme electron transport mechanism in the composites was elucidated using Electron Paramagnetic Resonance (EPR) spectroscopy, radical trapping experiments, energy band structure analysis, and the identification of critical intermediates in the process of selective oxidation. This work sheds light on the design and preparation of high-performance photocatalysts for biorefining coupled with efficient hydrogen evolution. [ABSTRACT FROM AUTHOR]

Diabetes mellitus (DM) is a significant public health problem and it is known that the identification of molecular markers involved in glycemic control can impact disease control. Although the rs266729 polymorphism located in the promoter of the adiponectin gene (ADP) has been shown to be a candidate for involvement in glycemic control, the genotypic groups have never been characterized in terms of metabolomic aspects. Objective: Analyze the metabolites present in the rs266729 genotype groups. 127 diabetic individuals were compared according to the rs266729 genotype groups CC and GC + GG (RFLP-PCR). Blood plasma metabolites were classified by nuclear magnetic resonance (NMR), and the metabolic pathways of each group using the MetaboAnalyst tool. Insulin therapy (p = 0.049) was more frequent in the GC + GG rs266729 group. Lactate, alanine, glutamine, aspartate, lipid, lysine, isoleucine, citrulline, cholesterol, and fucose impacted the CC group and aspartate, beta-glucose, glutamate, pyruvate, proline, and 2-oxoglutarate impacted the CG + GG group. The glucose-alanine pathway, malate-aspartate transport, and urea cycle impacted the CC group (D-glucose, glutamic acid, L-alanine, oxoglutaric acid, and pyruvic acid). The glutamine/glutamate ratio is likely to be related to the causes of rs266729 influencing the risk of diabetes. [ABSTRACT FROM AUTHOR]

Bacteriocin is a kind of natural substance that can effectively inhibit bacteria, but its production usually limited by environment. Co-culture is a strategy to stimulate bacteriocin production. Bifidocin A produced by Bifidobacterium animalis BB04, is a novel bacteriocin with a broad-spectrum antimicrobial active of foodborne bacteria. In order to enhance bifidocin A production, bacteriocin-inducing strains were screened firstly in co-cultivation. Then, the molecular mechanism of co-cultural induction was investigated by transcriptomic and proteomic analysis. Finally, the key inducing metabolites were identified by using targeted metabolomic technology. The results showed that Wickerhamomyces anomalus Y-5 in co-cultivation could significantly enhance bifidocin A production, with a 3.00-fold increase compared to mono-culture. The induction may not depend on direct contact with cells and may instead be attributed to be continuous exposure to inducing substances at specific concentration. In co-cultivation, W. anomalus Y-5 up-regulated Hxk2 and Tap42 to activate Glucose-cAMP and Tor and HOG-MAPK pathway, stimulated the expression of the retrograde gene, produced glutamine and glycerol to maintain activity. During this process, glutamine, inosine, guanosine, adenine, uracil, fumaric acid and pyruvic acid produced by W. anomalus Y-5 could induce the synthesis of bifidocin A. In conclusion, W. anomalus Y-5 in co-cultivation induced the synthesis of bifidocin A by regulating various signaling pathways to produce inducing substances. These findings establish a foundation for high-efficient synthesis of bifidocin A and provide a new perspective into the industrial production of bacteriocin. [ABSTRACT FROM AUTHOR]

Biopolymers are molecules widely used in many industries because they are biodegradable and have a natural origin. Therefore, they can be obtained from renewable resources and organisms such as animals, plants, or microorganisms. Among the best‐known biopolymers, xanthan gum is an anionic biopolymer composed of glucose, mannose, glucuronic acid, pyruvic acid, and acetyl groups. It can be obtained by fermentation with bacteria of the genus Xanthomonas, has good physicochemical properties, and it is biocompatible with human cells. However, it has disadvantages as it is very susceptible to microbial contamination. Therefore, various physical, chemical, or enzymatic modification methods have been developed to improve its physicochemical and biological properties. Modifications in the backbone of the xanthan gum chains have made it possible to create xanthan gum derivatives with new uses, such as drug delivery systems and improving absorption methods in the pharmaceutical industry to enhance the efficacy of several treatments or therapeutic processes, to promote cell proliferation for tissue engineering as biomedical applications when used in systems such as hydrogels or films. They are also used in food products, in cosmetics, to recover oil from water or ground, to treat wastewater, or granting soil with good conditions to promote plant and vegetables growth. Hence, it is important to know and develop new modification methods to improve and impart new properties to obtain novel applications of xanthan gum. [ABSTRACT FROM AUTHOR]

BACKGROUND: A material of natural origin, clinoptilolite, was modified with selected metals in order to obtain a catalyst for the conversion of xylose – the main component of the hemicellulose fraction present in lignocellulosic biomass – to selected carboxylic acids. RESULTS: The starting material without modification (0‐parent), the hydrogen form (0‐hydrogen) of zeolite and zeolite after hierarchization with hydrochloric acid (0‐dealuminated) were used. Iron, copper and cobalt ions were introduced as active centers using the sonication technique. The catalytic process was carried out in a pressure autoclave for 2 h at a temperature of 220 °C. Compounds such as formic acid with a yield of 91% (0‐parent) and lactic acid with a yield of 66.1% (Fe‐hydrogen) were obtained. Conclusion: The catalytic processes carried out using xylose lead to the obtaining of a mixture of carboxylic acids: lactic acid, pyruvic acid and formic acid. An important role here is played by the presence of iron as an active site, which leads to the transformation of xylose into lactic acid by dehydration, and the presence of Lewis and Brønsted active sites. In the case of formic acid, which has never been reported in publications on a similar topic, the starting zeolite without modification contributed to its preparation. It is possible that the content of alkali metals contributed to its preparation along with the coupling of the oxidation reaction of the intermediate product, because of the presence of small amounts of iron, which are present in the natural material. © 2024 Society of Chemical Industry (SCI). [ABSTRACT FROM AUTHOR]

We have employed the ab initio nanoreactor (AINR) and DFT calculations to explore how the soft impact of comets entering early earth's dense atmosphere could induce chemical reactions in trapped interstellar ice components, leading to the origin of glyoxylic and pyruvic acids the simplest α-ketoacids essential for prebiotic metabolic cycles. [ABSTRACT FROM AUTHOR]

Background: Exanthematous drug eruption and infectious mononucleosis (IM) are both exanthematous diseases. Current research on exanthematous drug eruption and IM mainly targets identifying these disorders, the resulting differences at the metabolism level have not yet been systematically analyzed. Materials and methods: A total of 30 cases of exanthematous drug eruption and IM, 10 patients without exanthema and 10 healthy volunteers were enrolled, 3 mL of fasting venous blood was collected, the serum metabolite content was detected by gas chromatography‐mass spectrometry metabolomics. Results: A total of 165 metabolites were identified, exhibiting significant differences in plasma metabolic trends between exanthematous drug eruption and IM, and pinpointed 28 potential biomarkers. Notable changes were seen in the metabolic activities of the pentose phosphate pathway (PPP), tricarboxylic acid cycle (TCA‐cycle), and galactose metabolism, characterized by increased levels of gluconate, gluconolactone, glucose, galactaric acid, and mannose, along with decreased amounts of pyruvic acid, succinic acid, malic acid, and glycerol, indicating an impairment in the exanthematous drug eruption group's capacity to endure oxidative stress and regulate energy metabolism. In contrast to its medication without rash counterpart, the exanthematous drug eruption group's plasma displayed distinct metabolic routes, predominantly in the processing of arginine and proline, along with the TCA. This resulted in a marked reduction in urea levels and a rise in pyruvate, citrate, and ornithine, indicating hypoxic stress as the primary cause of these rashes. In contrast to the healthy control group, the IM group showed 26 potential biomarkers, marked by increased levels of ketoglutaric acid, malic acid, pyruvic acid, and oxoglutaric acid, and reduced amounts of glutamine, galacturonic acid, arachidonic acid, trimethylphosphonic acid ester, gluconolactone, and indole acetic acid. Mainly, the metabolic pathways included the TCA, breaking down alanine, aspartate and glutamate metabolism, and the processing of D‐glutamine and D‐glutamate metabolism, underscoring the body's crucial role in generating energy and inflammatory agents through the citric acid cycle. Conclusions: The comparison of serum metabolomic features of exanthematous drug eruptions and IM outlines a unique pattern closely related to the differences in the pathogenesis of these two exanthematous diseases. [ABSTRACT FROM AUTHOR]

A novel bimetallic Fe/Co-metal–organic framework (MOF) hydrogel-based wearable sweat sensor was developed. Morphological and structural analysis of the hydrogel shows uniformly sized spines and spindle-shaped particles of the Fe/Co-MOF, and it has a high surface area (132.306 m2 g−1) and porosity (0.059 cm3 g−1) as confirmed by Brunauer–Emmett–Teller (BET) studies. The integration of the bimetallic MOF into a polyvinyl alcohol/chitosan (PVA/CS)-mixed matrix resulted in a multiple network hydrogel. The optimisation study investigated the effects of different pH of the PBS electrolyte, scan rates, and accumulation time in voltammetry. The electrochemical methods such as cyclic voltammetry (CV), square wave voltammetry (SWV), and electrochemical impedance spectroscopy (EIS) provided information on the redox behaviour, electrochemical stability, and catalytic activity of the hydrogel. The sensor demonstrates a wide linear detection range from 0.05 µM to 100 mM, a superior sensitivity of 0.02 mA mM−1 cm−2, and a lower limit of detection of 0.01 µM. Active sites distributed over the hydrogel surface, specifically Fe2+ and Co2+ within the MOF structure, catalyse the oxidation of l-lactic acid, resulting in electron transfer and the formation of pyruvic acid. Notably, the fabricated sensor exhibits high selectivity, effectively discriminating against interfering species such as uric acid, ascorbic acid, glucose, urea, dopamine, NaCl, and CaCl2. Real-time analysis conducted in a simulated sweat sample via the standard addition method resulted in good recovery percentages of a minimum of 98%. The work presented here is a versatile and simple platform for point-of-care testing, especially for athletes and military personnel. [ABSTRACT FROM AUTHOR]

In the present work, the phytotoxic effects of secondary metabolites extracted from lichen Ramalina celastri (usnic acid) and lichen Stereocaulon ramulosum (a naturally occurring mixture of atranorin and perlatolic acid, approx. 3:1) on cultures of the aposymbiotically grown lichen photobiont Asterochloris erici were evaluated. Algae were cultivated on the surface of glass microfiber disks with applied crystals of lichen extracts for 14 days. The toxicity of each extract was tested at the two selected doses in quantities of 0.01 mg/disk and 0.1 mg/disk. Cytotoxicity of lichen extracts was assessed using selected physiological parameters, such as growth (biomass production) of photobiont cultures, content of soluble proteins, chlorophyll a fluorescence, chlorophyll a integrity, contents of chlorophylls and total carotenoids, hydrogen peroxide, superoxide anion, TBARS, ascorbic acid (AsA), reduced (GSH) and oxidized (GSSG) glutathione, and composition of selected organic acids of the Krebs cycle. The application of both tested metabolic extracts decreased the growth of photobiont cells in a dose-dependent manner; however, a mixture of atranorin and perlatolic acid was more effective when compared to usnic acid at the same dose tested. A higher degree of cytotoxicity of extracts from lichen S. ramulosum when compared to identical doses of extracts from lichen R. celastri was also confirmed by a more pronounced decrease in chlorophyll a fluorescence and chlorophyll a integrity, decreased content of chlorophylls and total carotenoids, increased production of hydrogen peroxide and superoxide anion, peroxidation of membrane lipids (assessed as TBARS), and a strong decrease in non-enzymatic antioxidants such as AsA, GSH, and GSSG. The cytotoxicity of lichen compounds was confirmed by a strong alteration in the composition of selected organic acids included in the Krebs cycle. The increased ratio between pyruvic acid and citric acid was a very sensitive parameter of phytotoxicity of lichen secondary metabolites to the algal partner of symbiosis. Secondary metabolites of lichens are potent allelochemicals and play significant roles in maintaining the balance between mycobionts and photobionts, forming lichen thallus. [ABSTRACT FROM AUTHOR]

Background/Objectives: Metabolomics provides insights into the biological underpinnings of disease development and treatment. This systematic review investigated the impact of acupuncture on metabolite levels and associated metabolic pathways using a metabolomic approach. Methods: Five databases (i.e., PubMed, Embase, Scopus, CINAHL, and Cochrane Central) were searched using terms such as "acupuncture" and "metabolites" to retrieve relevant journal articles published through January 2024. Studies utilizing mass spectrometry or nuclear magnetic resonance were included. Risk of bias was evaluated using the Cochrane Risk of Bias tool and the Newcastle–Ottawa scale. Metabolic pathway analysis was conducted using MetaboAnalyst 6.0 to identify common significant pathways affected by acupuncture. Additionally, subgroup pathway enrichment analysis identified metabolites significantly altered in more than two studies. Results: Among 4019 articles, 22 studies met inclusion criteria, examining changes in metabolomic biomarkers before and after acupuncture for various diseases and symptoms. A total of 226 metabolites showed significant changes, with 14 common metabolites altered in more than two studies (glutamine, androsterone glucuronide, choline, citric acid, decanoylcarnitine, estrone, glutathione, glycine, hypoxanthine, lactic acid, pyruvic acid, serine, proline, and sn-glycero-3-phosphocholine). Common pathways affected by acupuncture were glycine, serine, and threonine metabolism, glutathione metabolism, arginine biosynthesis, and glyoxylate and dicarboxylate metabolism. Conclusions: This review provides insights of the metabolomic mechanisms underlying acupuncture, highlighting its impact on specific metabolic pathways. Recognizing these changes can enhance acupuncture's effectiveness and support the development of personalized treatments. The findings underscore metabolomics as a valuable tool for understanding and optimizing acupuncture for various diseases and symptoms. [ABSTRACT FROM AUTHOR]

Background: Pentosidine is an advanced glycation end product that is commonly found in heat-processed foods. Pentosidine has been involved in the occurrence and development of some chronic diseases. It was reported that pentosidine exposure can impair the function of the liver and kidneys. Adipose tissue, as an active endocrine organ, plays an important role in maintaining the normal physiological function of cells. However, the metabolic mechanism that causes pentosidine to induce toxicity in adipose tissue remains unclear. Methods: In the study, thirty male Sprague-Dawley rats were divided into a normal diet group, low dose group, and high dose group. A non-targeted metabolomics approach was used to compare the metabolic profiles of adipose tissue between the pentosidine and normal diet groups. Furthermore, histopathological observation and body weight change analysis were performed to test the results of the metabolomics analysis. Results: A total of forty-two differential metabolites were identified. Pentosidine mainly disturbed twelve metabolic pathways, such as ascorbate and aldarate metabolism, glycine, serine, and threonine metabolism, sulfur metabolism, pyruvate metabolism, etc. Additionally, pyruvic acid was identified as a possible key upregulated metabolite involved in thirty-four metabolic pathways. α-Ketoglutaric acid was named as a probable key downregulated metabolite involved in nineteen metabolic pathways based on enrichment network analysis. In addition, histopathological analysis and body weight changes confirmed the results of the metabolomics analysis. Conclusions: These results provided a new perspective for the molecular mechanisms of adipose tissue toxicity induced by pentosidine. [ABSTRACT FROM AUTHOR]

Fresh onions are dehydrated to increase their shelf-life. Primarily, open dehydration techniques like solar dehydration come with the problem of contamination through natural air convection. A solar conduction dryer that uses conduction, convection, and radiation for dehydration of food samples is exploited in this study. The food samples are often contaminated by Bacillus and Aspergillus species spores. As a remedy, pulsed light treatment as a non-thermal technology and infrared treatment as a thermal technology are studied and compared. Bacillus cereus and Aspergillus niger spores are chosen as a representative of bacterial and fungal contamination in onions. Dehydrated onion shreds with varying water activities (0.4, 0.5, 0.6) were treated. The spore inactivation was best described by Weibull model as compared with first-order model. Scanning electron microscopy images of the microbial cells showed surface distortions on the bacterial and fungal spores. The effect of the treatment technologies on the colour, flavour (thiosulphinate and pyruvic acid concentration), total phenolic and flavonoid content, and ascorbic acid concentration are compared. Overall, pulsed light treatment showed promising inactivation with a maximum log reduction of 4.5 log B. cereus spores·g−1 and 3.1 log A. niger spores·g−1 at 2.131 J·cm−2 in samples with water activity 0.6. The inactivation rate increased with an increase in water activity. The colour was better retained in pulsed light treated samples. The thiosulphinate content (9.24 μmol·g−1), total phenolics (0.268 mg GAE·g−1), and flavonoid content (0.344 mg QE·g−1) in the sample were improved upon pulsed light exposure. [ABSTRACT FROM AUTHOR]

Abstract Fresh onions are dehydrated to increase their shelf-life. Primarily, open dehydration techniques like solar dehydration come with the problem of contamination through natural air convection. A solar conduction dryer that uses conduction, convection, and radiation for dehydration of food samples is exploited in this study. The food samples are often contaminated by Bacillus and Aspergillus species spores. As a remedy, pulsed light treatment as a non-thermal technology and infrared treatment as a thermal technology are studied and compared. Bacillus cereus and Aspergillus niger spores are chosen as a representative of bacterial and fungal contamination in onions. Dehydrated onion shreds with varying water activities (0.4, 0.5, 0.6) were treated. The spore inactivation was best described by Weibull model as compared with first-order model. Scanning electron microscopy images of the microbial cells showed surface distortions on the bacterial and fungal spores. The effect of the treatment technologies on the colour, flavour (thiosulphinate and pyruvic acid concentration), total phenolic and flavonoid content, and ascorbic acid concentration are compared. Overall, pulsed light treatment showed promising inactivation with a maximum log reduction of 4.5 log B. cereus spores·g−1 and 3.1 log A. niger spores·g−1 at 2.131 J·cm−2 in samples with water activity 0.6. The inactivation rate increased with an increase in water activity. The colour was better retained in pulsed light treated samples. The thiosulphinate content (9.24 μmol·g−1), total phenolics (0.268 mg GAE·g−1), and flavonoid content (0.344 mg QE·g−1) in the sample were improved upon pulsed light exposure. Graphical Abstract

PurposeTo investigate high-resolution hyperpolarized (HP) 13 C pyruvate MRI for measuring cerebral perfusion in the human brain.MethodsHP [1-13 C]pyruvate MRI was acquired in five healthy volunteers with a multi-resolution EPI sequence with 7.5 × 7.5 mm2 resolution for pyruvate. Perfusion parameters were calculated from pyruvate MRI using block-circulant singular value decomposition and compared to relative cerebral blood flow calculated from arterial spin labeling (ASL). To examine regional perfusion patterns, correlations between pyruvate and ASL perfusion were performed for whole brain, gray matter, and white matter voxels.ResultsHigh resolution 7.5 × 7.5 mm2 pyruvate images were used to obtain relative cerebral blood flow (rCBF) values that were significantly positively correlated with ASL rCBF values (r = 0.48, 0.20, 0.28 for whole brain, gray matter, and white matter voxels respectively). Whole brain voxels exhibited the highest correlation between pyruvate and ASL perfusion, and there were distinct regional patterns of relatively high ASL and low pyruvate normalized rCBF found across subjects.ConclusionAcquiring HP 13 C pyruvate metabolic images at higher resolution allows for finer spatial delineation of brain structures and can be used to obtain cerebral perfusion parameters. Pyruvate perfusion parameters were positively correlated to proton ASL perfusion values, indicating a relationship between the two perfusion measures. This HP 13 C study demonstrated that hyperpolarized pyruvate MRI can assess cerebral metabolism and perfusion within the same study.

Hyperpolarized (HP) 13C Magnetic Resonance Imaging (MRI) was applied for the first time to image and quantify the uptake and metabolism of [2-13C]pyruvate in the human brain to provide new metabolic information on cerebral energy metabolism. HP [2-13C]pyruvate was injected intravenously and imaged in 5 healthy human volunteer exams with whole brain coverage in a 1-minute acquisition using a specialized spectral-spatial multi-slice echoplanar imaging (EPI) pulse sequence to acquire 13C-labeled volumetric and dynamic images of [2-13C]pyruvate and downstream metabolites [5-13C]glutamate and [2-13C]lactate. Metabolic ratios and apparent conversion rates of pyruvate-to-lactate (kPL) and pyruvate-to-glutamate (kPG) were quantified to investigate simultaneously glycolytic and oxidative metabolism in a single injection.

Background. Benfotiamine, a synthetic analog of thiamine, offers greater bioavailability compared to other thiamine salts and increases thiamine stores upon oral intake. Thiamine is essential for energy metabolism. This study aimed to evaluate the effects of oral benfotiamine supplementation on energy metabolism, particularly the Krebs cycle function, in the muscle of endurance‐trained mice, and to assess its impact on endurance performance. Methods. Twenty‐five mice were randomly assigned to four groups: a standard diet with sedentary behavior (Sta‐Sed), a benfotiamine‐supplemented diet with sedentary behavior (Ben‐Sed), a standard diet with swimming training (Sta‐Tr), and a benfotiamine‐supplemented diet with swimming training (Ben‐Tr). The trained groups underwent five weekly swimming sessions for six weeks, followed by an exhaustive test. Thiamine and its esters were measured in erythrocytes and gastrocnemius muscle. Gene expression of pyruvate dehydrogenase (PDHa) and alpha‐ketoglutarate dehydrogenase (OGDH), along with levels of pyruvic, lactic, and hydroxybutyric acids in muscle, was analyzed. Results. The benfotiamine‐supplemented groups had higher thiamine levels in erythrocytes and muscles compared to the standard‐diet groups. No differences were observed in PDHa and OGDH gene expression. The Ben‐Tr group exhibited increased muscle lactic acid levels and a higher lactic acid to pyruvic acid ratio compared to the sedentary groups. Hydroxybutyric acid levels were also elevated in the Ben‐Tr group. No significant differences in exhaustive test duration were found between the groups. Conclusion. Benfotiamine supplementation increases thiamine levels in erythrocytes and muscle but does not affect the gene expression of thiamine‐dependent enzymes. Although it alters energy metabolism in trained muscle, it does not enhance endurance performance in mice. [ABSTRACT FROM AUTHOR]

During the deamination and amination processes of meso -diaminopimelate dehydrogenase (meso -DAPDH) from Symbiobacterium thermophilum (StDAPDH), residue R71 was observed to display distinct functions. H154 has been proposed as a basic residue that facilitates water molecules to attack the D-chiral carbon of meso -DAP during deamination. Inspired by the phenomenon of R71, the effects of H154 during deamination and amination were investigated in this study with the goal of enhancing the amination activities of StDAPDH. Single site saturation mutagenesis indicated that almost all of the H154 mutants completely lost their deamination activity towards meso -DAP. However, some H154 variants showed enhanced k cat / K m values towards pyruvic acid and other bulky 2-keto acids, such as 2-oxovaleric acid, 4-methyl-2-oxopentanoic acid, 2-ketobutyric acid, and 3-methyl-2-oxobutanoic acid. When combined with the previously reported W121L/H227I mutant, triple mutants with significantly improved k cat / K m values (2.4-, 2.5-, 2.5-, and 4.0-fold) towards these 2-keto acids were obtained. Despite previous attempts, mutations at the H154 site did not yield the desired results. Moreover, this study not only recognizes the distinctive impact of H154 on both the deamination and amination reactions, but also provides guidance for further high-throughput screening in protein engineering and understanding the catalytic mechanism of StDAPDH. • H154 was first experimentally identified to be the fatal residue for deamination. • H154 mutation boosted the amination towards pyruvic acid and bulky 2-keto acids. • Coupling H154 variants with W121L/H227I resulted in enhanced amination activities. • The first report on the contrary effects of H154 during deamination and amination. • A reminder to update the high-throughput screening for DAPDH amination activity. [ABSTRACT FROM AUTHOR]

Deep vein thrombosis (DVT) is a leading cause of morbidity and mortality after trauma. Here, we integrate plasma metabolomics and proteomics to evaluate the metabolic alterations and their function in up to 680 individuals with and without DVT after trauma (pt-DVT). We identify 28 metabolites and 2 clinical parameter clusters associated with pt-DVT. Then, we develop a panel of 9 metabolites (hexadecanedioic acid, pyruvic acid, L-Carnitine, serotonin, PE(P-18:1(11Z)/18:2(9Z,12Z)), 3-Hydroxycapric acid, 5,6-DHET, 3-Methoxybenzenepropanoic acid and pentanenitrile) that can predict pt-DVT with high performance, which can be verified in an independent cohort. Furthermore, the integration analysis of metabolomics and proteomics data indicates that the upregulation of glycolysis/gluconeogenesis-TCA cycle may promote thrombosis by regulating ROS levels in red blood cells, suggesting that interfering with this process might be potential therapeutic strategies for pt-DVT. Together, our study comprehensively delineates the metabolic and hematological dysregulations for pt-DVT, and provides potential biomarkers for early detection. Deep vein thrombosis after trauma (pt-DVT) patients undergo metabolic changes but a comprehensive characterization in humans is lacking. Here the authors integrate metabolome and proteome to reveal pt-DVT-related metabolic alterations and their function, and reveal potential biomarkers. [ABSTRACT FROM AUTHOR]

Background and aims: Elucidating the relationship between extraneous nano-scale carbon properties and the metabolomic response of early Zea mays L. seedling establishment roots is crucial to reveal nano-carbon regulation and nutrient transport mechanisms. Methods: Herein, humic acid and graphite nanoplatelets represented typical organic and inorganic morphologies of nano-scale carbon. We used equimolar exogenous carbon inputs (0.4, 2, 4 mol C kg−1) to investigate the regulation of nitrogen metabolism using LC-MS, phenotype and physiology of root, nitrogen metabolism-related enzyme activities and endogenous hormones. Results: Our findings demonstrate that humic acid and graphite nanoplatelets promote root thickening and branching. The most prominent effects on root vitality, injury intensity, and total active absorption area were observed with 2 mol C kg−1 graphite nanoplatelets and 4 mol C kg−1 humic acid. The trend of nitrogen metabolism activity remained consistent, involving the assimilation of NR and NiR and the primary synergistic regulation of GO and GOGAT. Notably, 2 mol C kg−1 graphite nanoplatelets induced the dynamic and selective up-regulation of pyruvic acid and down-regulation of tyramine and methyl phosphate, resulting in changes in energy metabolism and a small subset of amino acid metabolism. 4 mol C kg−1 humic acid resulted in the down-regulation of the organic acids (L-asparagine, pyruvic acid, L-aspartic acid, L-glutamine, and fumaric acid), which are involved in nitrogen metabolism-related processes. Conclusion: Overall, these findings highlight additional graphite nanoplatelets regulated nitrogen assimilation and protein synthesis pathways to improve nitrogen availability. Nano-carbon demonstrated the potential to reprogram agricultural traits. [ABSTRACT FROM AUTHOR]

The quinoline ring is found in many biologically active natural alkaloids and is still being highly exploited by researchers due to its numerous potential applications in fields ranging from pharmacology to material science. During our synthetic attempts for new quinoline-4-carboxylic acids, using an extended version of the Doebner reaction, a new puzzling compound emerged when para-iodine aniline was reacted with salicylaldehyde and pyruvic acid in acetic acid as a reaction medium. The chemical structure of this new compound was established based on the information obtained from 1D and 2D NMR experiments (1H-, 13C-, and 15N-NMR), corroborated with MS spectrometry and IR spectroscopy. The photophysical properties (UV–vis and fluorescence) were also investigated. The proposed structure contains as the main elements a 1,4-dioxane-2,5-dione core symmetrically substituted with a propylidene chain that has attached to it a salicylaldehyde fragment and a pyrrole-2-one ring containing two 4-iodophenyl fragments. The isolation of this compound, reported here for the first time, is direct evidence that unexpected compounds can emerge from "classical" synthetic pathways when the right components are combined. [ABSTRACT FROM AUTHOR]

Bacteria indigenous to oil-contaminated water exhibited diverse metabolic capabilities in degrading various aromatic and monoaromatic hydrocarbons. Out of the 28 bacterial strains isolated from the wastewater, each was cultivated with at least one hydrocarbon, including kerosene, naphthalene, toluene, diesel, or aniline. Among these strains, Pseudomonas putida AD-128 emerged as one of the most effective polyaromatic hydrocarbon (PAH) degraders. Following a 6-day treatment period, strain P. putida AD-128 demonstrated proficiency in degrading various PAHs, including naphthalene, phenanthrene, and fluorine. After 6 days of incubation at 20 °C, the degradation of Naphthalene (NAP) notably increased. Gas Chromatography Mass Spectrometry analysis identified the degraded compounds, including pyruvic acid, salicylaldehyde, D-gluconic acid, and catechol. Optimal NAP degradation was observed at 20 °C and pH 6.0, with increased agitation speed correlating with enhanced bacterial growth and heightened degradation, particularly evident after 6 days at 20 °C. Peptone emerged as the most effective among the four nitrogen supplements (ammonium sulfate, potassium nitrate, beef extract, and peptone), significantly reducing residual naphthalene in the medium. The isolated indigenous bacterium, P. putida AD-128, exhibits robust capabilities in degrading PAHs under optimized conditions, making it a valuable asset for environmental management initiatives. [ABSTRACT FROM AUTHOR]

Bovine digital dermatitis (BDD) is a cattle infection causing hoof lesions and lameness, with treponemes as key pathogens. We analyzed the metabolic activity of Treponema phagedenis and Treponema pedis using gas chromatography–mass spectrometry for organic acids (OAs), amino acids (AAs), and fatty acids (FAs), and high-performance liquid chromatography for short-chain fatty acids (SCFAs). Key findings include a 61.5% reduction in pyruvic acid in T. pedis and 81.0% in T. phagedenis. 2-hydroxybutyric acid increased by 493.8% in T. pedis, while succinic acid increased by 31.3%, potentially supporting T. phagedenis. Among AAs, glycine was reduced by 97.4% in T. pedis but increased by 64.1% in T. phagedenis. Proline increased by 76.6% in T. pedis but decreased by 13.6% in T. phagedenis. Methionine and glutamic acid were competitively utilized, with methionine reduced by 41.8% in T. pedis and 11.9% in T. phagedenis. Both species showed significant utilization of palmitic acid (reduced by 82.8% in T. pedis and 87.2% in T. phagedenis). Butyric acid production increased by 620.2% in T. phagedenis, and propionic acid increased by 932.8% in T. pedis and 395.6% in T. phagedenis. These reveal metabolic interactions between the pathogens, contributing to disease progression and offering insights to BDD pathogenesis. [ABSTRACT FROM AUTHOR]

Maximizing the utilization of photogenerated electrons and holes to drive the coupling reaction of hydrogen evolution with selective value‐added organic synthesis holds great potential for more efficient exploitation of solar energy. Herein, the interstitial boron‐doped CdS is synthesized by taking SiO2 as a template as well as the adsorption sites of boric acid, which contributes to the boron doping and induces the reinforced Cd─Se bonding for enhancing the interfacial interaction with co‐catalyst MoSe2. Thus, the interfacial Cd─Se bond with more electron localization provides rapid channels at the atomic level for accelerating the charge transfer with a lower energy barrier, achieving the efficient hydrogen evolution and high selectivity pyruvic acid synthesis concurrently. This work provides a new perspective in avoiding the use of sacrificial agents uneconomically and producing green hydrogen with high‐value‐added chemicals simultaneously. [ABSTRACT FROM AUTHOR]

Introduction: Allium is important vegetables and seasonings in China, Tibet is rich in unique resources of the genus Allium, but lacks development and utilization. Methods: We compared the biological features and comprehensively evaluating the quality of twelve germplasm resources of the genus Allium collected from Tibet. Results: The results revealed that nine germplasm resources were bolting and bloom normally except for SC015, SC019, and SC048, all twelve germplasm resources were able to vegetative growth. The individual differences in moisture, soluble sugar, and protein content among the twelve germplasm resources were relatively small, with pyruvic acid content ranging from 0.11 to 1.12 mg/g and a large variation coefficient. A total of 8 categories and 97 volatile compounds were detected in twelve germplasm resources, the majority possessed the highest proportions of aldehydes and organosulfur compounds, but there were certain differences between the different Allium species. Additionally, 11 to 16 types of free amino acids were present in all germplasm resources, proline exhibited the highest content. The total content of essential and non-essential amino acids in SC009 was the highest. Carbon (C) accounted for the largest proportion of all elements, and the contents of other mineral elements varied greatly among the different plants. Conclusion: In conclusion, combined with biological performance and comprehensive evaluation of quality, SC009 is the excellent germplasm resource suitable for growth and capable of reproduction with good quality. These results improved the exploitation and utilization of the genus Allium in Tibet, as well as provided germplasm resources for high-quality breeding of the genus Allium. [ABSTRACT FROM AUTHOR]

Cold stress affects the seed germination and early growth of winter rapeseed, leading to yield losses. We employed transmission electron microscopy, physiological analyses, metabolome profiling, and transcriptome sequencing to understand the effect of cold stress (0 °C, LW) on the cotyledons of cold-tolerant (GX74) and -sensitive (XY15) rapeseeds. The mesophyll cells in cold-treated XY15 were severely damaged compared to slightly damaged cells in GX74. The fructose, glucose, malondialdehyde, and proline contents increased after cold stress in both genotypes; however, GX74 had significantly higher content than XY15. The pyruvic acid content increased after cold stress in GX74, but decreased in XY15. Metabolome analysis detected 590 compounds, of which 32 and 74 were differentially accumulated in GX74 (CK vs. cold stress) and XY15 (CK vs. cold stressed). Arachidonic acid and magnoflorine were the most up-accumulated metabolites in GX74 subjected to cold stress compared to CK. There were 461 and 1481 differentially expressed genes (DEGs) specific to XY15 and GX74 rapeseeds, respectively. Generally, the commonly expressed genes had higher expressions in GX74 compared to XY15 in CK and cold stress conditions. The expression changes in DEGs related to photosynthesis-antenna proteins, chlorophyll biosynthesis, and sugar biosynthesis-related pathways were consistent with the fructose and glucose levels in cotyledons. Compared to XY15, GX74 showed upregulation of a higher number of genes/transcripts related to arachidonic acid, pyruvic acid, arginine and proline biosynthesis, cell wall changes, reactive oxygen species scavenging, cold-responsive pathways, and phytohormone-related pathways. Taken together, our results provide a detailed overview of the cold stress responses in rapeseed cotyledons. [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. Study objectives were to compare the immune response, metabolism, and production following intramammary LPS (IMM LPS) administration in early and mid-lactation cows. Early (E-LPS; n = 11; 20 ± 4 DIM) and mid- (M-LPS; n = 10; 155 ± 40 DIM) lactation cows were enrolled in an experiment consisting of 2 periods (P). During P1 (5 d) cows were fed ad libitum and baseline data were collected, including liver and muscle biopsies. At the beginning of P2 (3 d) cows received 10 mL of sterile saline containing 10 µg of LPS from Escherichia coli O111:B4/mL into the left rear quarter of the mammary gland, and liver and muscle biopsies were collected at 12 h after LPS. Tissues were analyzed for metabolic flexibility, which measures substrate switching capacity from pyruvic acid to palmitic acid oxidation. Data were analyzed with the MIXED procedure in SAS 9.4. Rectal temperature was assessed hourly for the first 12 h after LPS and every 6 h thereafter for the remainder of P2. All cows developed a febrile response following LPS, but E-LPS had a more intense fever than M-LPS cows (0.7°C at 5 h after LPS). Blood samples were collected at 0, 3, 6, 9, 12, 24, 36, 48, and 72 h after LPS for analysis of systemic inflammation and metabolism parameters. Total serum Ca decreased after LPS (26% at 6 h nadir) but did not differ by lactation stage (LS). Circulating neutrophils decreased, then increased after LPS in both LS, but E-LPS had exaggerated neutrophilia (56% from 12 to 48 h) compared with M-LPS. Haptoglobin increased after LPS (15-fold) but did not differ by LS. Many circulating cytokines were increased after LPS, and IL-6, IL-10, TNF-α, MCP-1, and IP-10 were further augmented in E-LPS compared with M-LPS cows. Relative to P1, all cows had reduced milk yield (26%) and DMI (14%) on d 1 that did not differ by LS. Somatic cell score increased rapidly in response to LPS regardless of LS and gradually decreased from 18 h onwards. Milk component yields decreased after LPS. However, E-LPS had increased fat (11%) and tended to have increased lactose (8%) yield compared with M-LPS cows throughout P2. Circulating glucose was not affected by LPS. Nonesterified fatty acids (NEFA) decreased in E-LPS (29%) but not M-LPS cows. β-Hydroxybutyrate slightly increased (14%) over time after LPS regardless of LS. Insulin increased after LPS in all cows, but E-LPS had blunted hyperinsulinemia (52%) compared with M-LPS cows. Blood urea nitrogen increased after LPS, and the relative change in BUN was elevated in E-LPS cows compared with M-LPS cows (36% and 13%, respectively, from 9 to 24 h). During P1, metabolic flexibility was increased in liver and muscle in early lactating cows compared with mid-lactation cows, but 12 h after LPS, metabolic flexibility was reduced and did not differ by LS. In conclusion, IMM LPS caused severe immune activation, and E-LPS cows had a more intense inflammatory response compared with M-LPS cows, but the effects on milk synthesis was similar between LS. Some parameters of the E-LPS metabolic profile suggest continuation of metabolic adjustments associated with early lactation to support both a robust immune system and milk synthesis. [ABSTRACT FROM AUTHOR]

​​​​​​​Volatile organic compounds (VOCs) play a key role in tropospheric chemistry, giving rise to secondary products such as highly oxygenated organic molecules (HOMs) and secondary organic aerosols (SOAs). HOMs, a group of low-volatility gas-phase products, are formed through the autoxidation process of peroxy radicals (RO 2) originating from the oxidation of VOCs. The measurement of HOMs is made by a NO 3- ToFCIMS instrument, which also detects other species like small highly oxygenated VOCs (e.g., dicarboxylic acids) and sulfuric acid (H 2 SO 4). The instrument response to HOMs is typically estimated using H 2 SO 4 , as HOMs are neither commercially available nor easily synthesized in the laboratory. The resulting calibration factor is then applied to quantify all species detected using this technique. In this study, we explore the sensitivity of the instrument to commercially available small organic compounds, primarily dicarboxylic acids, given the limitations associated with producing known amounts of HOMs for calibration. We compare these single-compound calibration factors to the one obtained for H 2 SO 4 under identical operational conditions. The study found that the sensitivity of the NO 3- ToFCIMS varies depending on the specific type of organic compound, illustrating how a single calibration factor derived from sulfuric acid is clearly inadequate for quantifying all detected species using this technique. The results highlighted substantial variability in the calibration factors for the tested organic compounds, with 4-nitrocatechol exhibiting the highest sensitivity and pyruvic acid the lowest. The obtained sulfuric acid calibration factor agreed well with the previous values from the literature. In summary, this research emphasized the need to develop reliable and precise calibration methods for progressively oxygenated reaction products measured with a NO 3- chemical-ionization mass spectrometer (CIMS), for example, HOMs. [ABSTRACT FROM AUTHOR]

Background: Albendazole (ABZ) and atovaquone (ATO) achieve killing efficacy on Echinococcus granulosus (Egs) by inhibiting energy metabolism, but their utilization rate is low. This study aims to analyze the killing efficacy of ABZ-ATO loading nanoparticles (ABZ-ATO NPs) on Egs. Methods: Physicochemical properties of NPs were evaluated by ultraviolet spectroscopy and nanoparticle size potentiometer. In vitro experiments exmianed the efficacy of ATO, ABZ, or ATO-ABZ NPs on protoscolex activity, drug toxicity on liver cell LO2, ROS production, and energy metabolism indexes (lactic dehydrogenase, lactic acid, pyruvic acid, and ATP). In vivo of Egs-infected mouse model exmianed the efficacy of ATO, ABZ, or ATO-ABZ NPs on vesicle growth and organ toxicity. Results: Drug NPs are characterized by uniform particle size, stability, high drug loading, and − 21.6mV of zeta potential. ABZ or ATO NPs are more potent than free drugs in inhibiting protoscolex activity. The protoscolex-killing effect of ATO-ABZ NPs was stronger than that of free drugs. In vivo Egs-infected mice experiment showed that ATO-ABZ NPs reduced vesicle size and could protect various organs. The results of energy metabolism showed that ATO-ABZ NPs significantly increased the ROS level and pyruvic acid content, and decreased lactate dehydrogenase, lactic acid content, and ATP production in the larvae. In addition, ATO-ABZ NPs promoted a decrease in DHODH protein expression in protoscolexes. Conclusion: ATO-ABZ NPs exhibits anti-CE in vitro and in vivo, possibly by inhibiting energy production and promoting pyruvic acid aggregation. [ABSTRACT FROM AUTHOR]

Novel cathodic and anodic dual-emitting electrochemiluminescence (ECL) of Ru(bpy)32+ and α-keto acids system are studied for the first time. Based on their cathodic and anodic ECL intensity, α-keto acids including oxalate, glyoxylic acid, pyruvic acid, and phenylglyoxylic acid can be directly sensitively detected. The limits of detection (LOD) of oxalate, glyoxylic acid, pyruvic acid, and phenylglyoxylic acid are 31.25 nM, 23.26 µM, 36.36 µM, and 18.52 µM, respectively. Possible mechanism of ECL produced is also proposed. Electrochemical results show that the reduction of oxygen at the cathode to produce ·OH is a vital step for cathodic and anodic dual-emitting ECL. Furthermore, using the enhancement strategy of S2O82−/Ag+ as coreactant accelerators is proposed considering that decarboxylation of α-keto acids to produce acyl radical can be achieved via S2O82− or Ag+. Using the S2O82−/Ag+ enhancement strategy, the LOD of oxalate, glyoxylic acid, pyruvic acid, and phenylglyoxylic acid are improved and are 2.12 nM, 0.37 µM, 3.23 µM, and 0.28 µM, respectively. Coreactants of Ru(bpy)32+ with dual-emitting ECL are expanded, which includes additional substances with organic carboxylic acid characterized by the keto group in α-position. It also provides an effective way to enhance ECL and improve sensitivity. More importantly, cathodic and anodic dual-emitting ECL greatly improves the selectivity. [ABSTRACT FROM AUTHOR]

Mammalian spermatozoa rely on glycolysis and mitochondrial oxidative phosphorylation for energy leading up to fertilization. Sperm capacitation involves a series of well-regulated biochemical steps that are necessary to give spermatozoa the ability to fertilize the oocyte. Additionally, zinc ion (Zn2+) fluxes have recently been shown to occur during mammalian sperm capacitation. Semen from seven commercial boars was collected and analyzed using image-based flow cytometry before, after, and with the inclusion of 2 mM Zn2+ containing in vitro capacitation (IVC) media. Metabolites were extracted and analyzed via Gas Chromatography-Mass Spectrometry (GC-MS), identifying 175 metabolites, with 79 differentially abundant across treatments (p < 0.05). Non-capacitated samples showed high levels of respiration-associated metabolites including glucose, fructose, citric acid, and pyruvic acid. After 4 h IVC, these metabolites significantly decreased, while phosphate, lactic acid, and glucitol increased (p < 0.05). With zinc inclusion, we observed an increase in metabolites such as lactic acid, glucitol, glucose, fructose, myo-inositol, citric acid, and succinic acid, while saturated fatty acids including palmitic, dodecanoic, and myristic acid decreased compared to 4 h IVC, indicating regulatory shifts in metabolic pathways and fatty acid composition during capacitation. These findings underscore the importance of metabolic changes in improving artificial insemination and fertility treatments in livestock and humans. [ABSTRACT FROM AUTHOR]

Uveal melanoma (UM) is a leading intraocular malignancy with a high 5‐year mortality rate, and radiotherapy is the primary approach for UM treatment. However, the elevated lactic acid, deficiency in ROS, and hypoxic tumor microenvironment have severely reduced the radiotherapy outcomes. Hence, this study devised a novel CoMnFe‐layered double oxides (LDO) nanosheet with multienzyme activities for UM radiotherapy enhancement. On one hand, LDO nanozyme can catalyze hydrogen peroxide (H2O2) in the tumor microenvironment into oxygen and reactive oxygen species (ROS), significantly boosting ROS production during radiotherapy. Simultaneously, LDO efficiently scavenged lactic acid, thereby impeding the DNA and protein repair in tumor cells to synergistically enhance the effect of radiotherapy. Moreover, density functional theory (DFT) calculations decoded the transformation pathway from lactic to pyruvic acid, elucidating a previously unexplored facet of nanozyme activity. The introduction of this innovative nanomaterial paves the way for a novel, targeted, and highly effective therapeutic approach, offering new avenues for the management of UM and other cancer types. [ABSTRACT FROM AUTHOR]

We report primordial aqueous alteration signatures in water-soluble organic molecules from the carbonaceous asteroid (162173) Ryugu by the Hayabusa2 spacecraft of JAXA. Newly identified low-molecular-weight hydroxy acids (HO-R-COOH) and dicarboxylic acids (HOOC-R-COOH), such as glycolic acid, lactic acid, glyceric acid, oxalic acid, and succinic acid, are predominant in samples from the two touchdown locations at Ryugu. The quantitative and qualitative profiles for the hydrophilic molecules between the two sampling locations shows similar trends within the order of ppb (parts per billion) to ppm (parts per million). A wide variety of structural isomers, including α- and β-hydroxy acids, are observed among the hydrophilic molecules. We also identify pyruvic acid and dihydroxy and tricarboxylic acids, which are biochemically important intermediates relevant to molecular evolution, such as the primordial TCA (tricarboxylic acid) cycle. Here, we find evidence that the asteroid Ryugu samples underwent substantial aqueous alteration, as revealed by the presence of malonic acid during keto–enol tautomerism in the dicarboxylic acid profile. The comprehensive data suggest the presence of a series for water-soluble organic molecules in the regolith of Ryugu and evidence of signatures in coevolutionary aqueous alteration between water and organics in this carbonaceous asteroid. In this study, the authors report primordial aqueous alteration signatures in water-soluble organic molecules from the carbonaceous asteroid Ryugu. This provides evidence o coevolutionary aqueous alteration between water and organics in this asteroid. [ABSTRACT FROM AUTHOR]

Cotton is one of the main crops explored commercially, moving several sectors of the economy, generating employment and income. The soaking of seeds in organic substances is a promising alternative for the vital processes of plants. Pyruvate, for example, is a crucial element in cell respiration, influencing the growth and development of the culture. Given the above, the objective was to evaluate the morphophysiology of cotton genotypes submitted to pyruvate supplementation via seed pre-soaking as a reinforcement of the energy mechanisms of plants. The treatments resulted from the combination of two cotton genotypes (BRS Jade and Line MT 2009-152) and five concentrations of pyruvate (0, 11, 22, 33 and 44 mM) applied via seed presoaking, distributed in randomized blocks. In a 2 x 5 factorial scheme, with 4 replications, totaling 40 experimental units. Seedling emergence, initial plant growth, gas exchange and phytomass accumulation were evaluated. Pre-soaking seeds in a calcium pyruvate solution starting at a concentration of 11 mM increases the rate assimilation of CO2, while, for emergency variables, growth and dry mass accumulation varies between 11 and 22 mM, reinforcing the energetic mechanisms of cotton genotypes BRS Jade and MT 2009-152. Evidently, more studies will be needed to test and validate the adoption of this technology. [ABSTRACT FROM AUTHOR]

The reaction of thiosemicarbazide and sodium pyruvate has been thoroughly studied and the novel crystal form of pyruvic acid thiosemicarbazone (H2pt) and its sodium salt was obtained. Compounds were characterized by IR spectra, melting points, elemental analysis, conductometric measurements and single-crystal X-ray analysis. A detailed comparative analysis of crystal structures of these compounds is given, as well as comparison with some of the earlier known complexes containing H2pt. The two novel crystal structures exhibit notably different hydrogen bonding patterns, mutually and in comparison with previously reported crystal form of H2pt. All crystal structures are stabilized by extensive network of N--H...O, O--H...O and N--H...S hydrogen bonds. The cyclic hydrogen bonding motif involving the thioureido moieties of the ligand is the only one which repeats in each structure. [ABSTRACT FROM AUTHOR]

Conventional diagnostic tools for prostate cancer (PCa), such as prostate-specific antigen (PSA), transrectal ultrasound (TRUS), digital rectal examination (DRE), and tissue biopsy face, limitations in individual risk stratification due to invasiveness or reliability issues. Liquid biopsy is a less invasive and more accurate alternative. Metabolomic analysis of extracellular vesicles (EVs) holds a promise for detecting non-genetic alterations and biomarkers in PCa diagnosis and risk assessment. The current research gap in PCa lies in the lack of accurate biomarkers for early diagnosis and real-time monitoring of cancer progression or metastasis. Establishing a suitable approach for observing dynamic EV metabolic alterations that often occur earlier than being detectable by other omics technologies makes metabolomics valuable for early diagnosis and monitoring of PCa. Using four distinct metabolite extraction approaches, the metabolite cargo of PC3-derived large extracellular vesicles (lEVs) was evaluated using a combination of methanol, cell shearing using microbeads, and size exclusion filtration, as well as two fractionation chemistries (pHILIC and C18 chromatography) that are also examined. The unfiltered methanol–microbeads approach (MB-UF), followed by pHILIC LC-MS/MS for EV metabolite extraction and analysis, is effective. Identified metabolites such as L-glutamic acid, pyruvic acid, lactic acid, and methylmalonic acid have important links to PCa and are discussed. Our study, for the first time, has comprehensively evaluated the extraction and separation methods with a view to downstream sample integrity across omics platforms, and it presents an optimised protocol for EV metabolomics in PCa biomarker discovery. [ABSTRACT FROM AUTHOR]

13C-bicarbonate is a crucial measure of pyruvate oxidation and TCA cycle flux, but is challenging to measure due to its relatively low concentration and thus will greatly benefit from improved signal-to-noise ratio (SNR). To address this, we developed and investigated the feasibility of a 3D stack-of-spirals metabolite-specific balanced steady-state free precession (MS-bSSFP) sequence for improving the SNR and spatial resolution of dynamic 13C-bicarbonate imaging in hyperpolarized [1-13C]pyruvate studies. The bicarbonate MS-bSSFP sequence was evaluated by simulations, phantoms studies, preclinical studies on five rats, brain studies on two healthy volunteers and renal study on one renal cell carcinoma patient. The simulations and phantom results showed that the bicarbonate-specific pulse had minimal perturbation of other metabolites (

PurposeModel-constrained reconstruction with Fourier-based undersampling (MoReFUn) is introduced to accelerate the acquisition of dynamic MRI using hyperpolarized [1-13 C]-pyruvate.MethodsThe MoReFUn method resolves spatial aliasing using constraints introduced by a pharmacokinetic model that describes the signal evolution of both pyruvate and lactate. Acceleration was evaluated on three single-channel data sets: a numerical digital phantom that is used to validate the accuracy of reconstruction and model parameter restoration under various SNR and undersampling ratios, prospectively and retrospectively sampled data of an in vitro dynamic multispectral phantom, and retrospectively undersampled imaging data from a prostate cancer patient to test the fidelity of reconstructed metabolite time series.ResultsAll three data sets showed successful reconstruction using MoReFUn. In simulation and retrospective phantom data, the restored time series of pyruvate and lactate maintained the image details, and the mean square residual error of the accelerated reconstruction increased only slightly (

BackgroundThe heart has metabolic flexibility, which is influenced by fed/fasting states, and pathologies such as myocardial ischemia and hypertrophic cardiomyopathy (HCM). Hyperpolarized (HP) 13C-pyruvate MRI is a promising new tool for non-invasive quantification of myocardial glycolytic and Krebs cycle flux. However, human studies of HP 13C-MRI have yet to demonstrate regional quantification of metabolism, which is important in regional ischemia and HCM patients with asymmetric septal/apical hypertrophy.MethodsWe developed and applied methods for whole-heart imaging of 13C-pyruvate, 13C-lactate and 13C-bicarbonate, following intravenous administration of [1-13C]-pyruvate. The image acquisition used an autonomous scanning method including bolus tracking, real-time magnetic field calibrations and metabolite-specific imaging. For quantification of metabolism, we evaluated 13C metabolite images, ratio metrics, and pharmacokinetic modeling to provide measurements of myocardial lactate dehydrogenase (LDH) and pyruvate dehydrogenase (PDH) mediated metabolic conversion in 5 healthy volunteers (fasting & 30 min following oral glucose load).ResultsWe demonstrate whole heart coverage for dynamic measurement of pyruvate-to-lactate conversion via LDH and pyruvate-to-bicarbonate conversion via PDH at a resolution of 6 × 6 × 21 mm3 (13C-pyruvate) and 12 × 12 × 21 mm3 (13C-lactate, 13C-bicarbonate). 13C-pyruvate and 13C-lactate were detected simultaneously in the RV blood pool, immediately after intravenous injection, reflecting LDH activity in blood. In healthy volunteers, myocardial 13C-pyruvate-SNR, 13C-lactate-SNR, 13C-bicarbonate-SNR, 13C-lactate/pyruvate ratio, 13C-pyruvate-to-lactate conversion rate, kPL, and 13C-pyruvate-to-bicarbonate conversion rate, kPB, all had statistically significant increases following oral glucose challenge. kPB, reflecting PDH activity and pyruvate entering the Krebs Cycle, had the highest correlation with blood glucose levels and was statistically significant.ConclusionsWe demonstrate first-in-human regional quantifications of cardiac metabolism by HP 13C-pyruvate MRI that aims to reflect LDH and PDH activity.

Lactate is a mitochondrial substrate for many tissues including neuron, muscle, skeletal and cardiac, as well as many cancer cells, however little is known about the processes that regulate its utilization in mitochondria. Based on the close association of Hexokinases (HK) with mitochondria, and the known cardio-protective role of HK in cardiac muscle, we have investigated the regulation of lactate and pyruvate metabolism by hexokinases (HKs), utilizing wild-type HEK293 cells and HEK293 cells in which the endogenous HKI and/or HKII have been knocked down to enable overexpression of wild type and mutant HKs. To assess the real-time changes in intracellular lactate levels the cells were transfected with a lactate specific FRET probe. In the HKI/HKII double knockdown cells, addition of extracellular pyruvate caused a large and sustained decrease in lactate. This decrease was rapidly reversed upon inhibition of the malate aspartate shuttle by aminooxyacetate, or inhibition of mitochondrial oxidative respiration by NaCN. These results suggest that in the absence of HKs, pyruvate-dependent activation of the TCA cycle together with the malate aspartate shuttle facilitates lactate transformation into pyruvate and its utilization by mitochondria. With replacement by overexpression of HKI or HKII the cellular response to pyruvate and NaCN was modified. With either hexokinase present, both the decrease in lactate due to the addition of pyruvate and the increase following addition of NaCN were either transient or suppressed altogether. Blockage of the pentose phosphate pathway with the inhibitor 6-aminonicotinamide (6-AN), abolished the effects of HK replacement. These results suggest that blocking of the malate aspartate shuttle by HK may involve activation of the pentose phosphate pathway and increased NADPH production.

BackgroundDynamic hyperpolarized (HP)-13C MRI has enabled real-time, non-invasive assessment of Warburg-related metabolic dysregulation in glioma using a [1-13C]pyruvate tracer that undergoes conversion to [1-13C]lactate and [13C]bicarbonate. Using a multi-parametric 1H/HP-13C imaging approach, we investigated dynamic and steady-state metabolism, together with physiological parameters, in high-grade gliomas to characterize active tumor.MethodsMulti-parametric 1H/HP-13C MRI data were acquired from fifteen patients with progressive/treatment-naïve glioblastoma [prog/TN GBM, IDH-wildtype (n = 11)], progressive astrocytoma, IDH-mutant, grade 4 (G4AIDH+, n = 2) and GBM manifesting treatment effects (n = 2). Voxel-wise regional analysis of the cohort with prog/TN GBM assessed imaging heterogeneity across contrast-enhancing/non-enhancing lesions (CEL/NEL) and normal-appearing white matter (NAWM) using a mixed effects model. To enable cross-nucleus parameter association, normalized perfusion, diffusion, and dynamic/steady-state (HP-13C/spectroscopic) metabolic data were collectively examined at the 13C resolution. Prog/TN GBM were similarly compared against progressive G4AIDH+ and treatment effects.ResultsRegional analysis of Prog/TN GBM metabolism revealed statistically significant heterogeneity in 1H choline-to-N-acetylaspartate index (CNI)max, [1-13C]lactate, modified [1-13C]lactate-to-[1-13C]pyruvate ratio (CELval > NELval > NAWMval); [1-13C]lactate-to-[13C]bicarbonate ratio (CELval > NELval/NAWMval); and 1H-lactate (CELval/NELval > NAWMundetected). Significant associations were found between normalized perfusion (cerebral blood volume, nCBV; peak height, nPH) and levels of [1-13C]pyruvate and [1-13C]lactate, as well as between CNImax and levels of [1-13C]pyruvate, [1-13C]lactate and modified ratio. GBM, by comparison to G4AIDH+, displayed lower perfusion %-recovery and modeled rate constants for [1-13C]pyruvate-to-[1-13C]lactate conversion (kPL), and higher 1H-lactate and [1-13C]pyruvate levels, while having higher nCBV, %-recovery, kPL, [1-13C]pyruvate-to-[1-13C]lactate and modified ratios relative to treatment effects.ConclusionsGBM consistently displayed aberrant, Warburg-related metabolism and regional heterogeneity detectable by novel HP-13C/1H imaging techniques.

Metabolite-specific echo-planar imaging (EPI) sequences with spectral-spatial (spsp) excitation are commonly used in clinical hyperpolarized [1-13C]pyruvate studies because of their speed, efficiency, and flexibility. In contrast, preclinical systems typically rely on slower spectroscopic methods, such as chemical shift imaging (CSI). In this study, a 2D spspEPI sequence was developed for use on a preclinical 3T Bruker system and tested on in vivo mice experiments with patient-derived xenograft renal cell carcinoma (RCC) or prostate cancer tissues implanted in the kidney or liver. Compared to spspEPI sequences, CSI were found to have a broader point spread function via simulations and exhibited signal bleeding between vasculature and tumors in vivo. Parameters for the spspEPI sequence were optimized using simulations and verified with in vivo data. The expected lactate SNR and pharmacokinetic modeling accuracy increased with lower pyruvate flip angles (less than 15°), intermediate lactate flip angles (25° to 40°), and temporal resolution of 3 s. Overall SNR was also higher with coarser spatial resolution (4 mm isotropic vs. 2 mm isotropic). Pharmacokinetic modelling used to fit kPL maps showed results consistent with the previous literature and across different sequences and tumor xenografts. This work describes and justifies the pulse design and parameter choices for preclinical spspEPI hyperpolarized 13C-pyruvate studies and shows superior image quality to CSI.

This study aimed to investigate how intermittent hyperoxic exposure (three cycles of 21% O2 [10 min] and 30% O2 [15 min]) affects exercise performance in mice. Three hours after the acute exposure, there was an observed increase in mRNA levels of phosphofructokinase (Bayes factor [BF] ≥ 10), mitochondrial transcription factor‐A (BF ≥10), PPAR‐α (BF ≥3), and PPAR‐γ (BF ≥3) in the red gastrocnemius muscle (Gr). Four weeks of exercise training under intermittent (INT), but not continuous (HYP), hyperoxia significantly (BF ≥30) increased maximal exercise capacity compared to normoxic exercise‐trained (ET) group. INT group exhibited significantly higher activity levels of 3‐hydroxyacyl‐CoA‐dehydrogenase (HAD) in Gr (BF = 7.9) compared to ET group. Pyruvate dehydrogenase complex activity levels were significantly higher in INT group compared to ET group in white gastrocnemius, diaphragm, and left ventricle (BF ≥3). NT‐PGC1α protein levels in Gr (BF = 7.7) and HAD activity levels in Gr (BF = 6.9) and soleus muscles (BF = 3.3) showed a significant positive correlation with maximal work values. These findings suggest that exercise training under intermittent hyperoxia is a beneficial strategy for enhancing endurance performance by improving fatty acid and pyruvic acid utilization. [ABSTRACT FROM AUTHOR]

The electrochemical synthesis of α ${\alpha }$ ‐amino acids at room temperature and pressure is a sustainable alternative to conventional methods like microbial fermentation and Strecker synthesis. A custom‐built zero‐gap flow electrolyzer was used to study the electrosynthesis of alanine via the electrocatalytic reductive amination (ERA) of the corresponding biomass‐derivable α ${\alpha }$ ‐keto acid precursor – pyruvic acid (PA), and hydroxylamine (NH2OH) at very low pH. Non‐toxic, abundant, and easy to prepare TiO2/Ti electrocatalysts were utilized as the cathode. Three TiO2/Ti felt electrodes with different oxide thicknesses were prepared and their characterization results were correlated with their respective electrochemical performance in terms of Faradaic efficiency η ${\eta }$ , and partial current density j‾ ${\left|\overline{j}\right|}$. Cyclic voltammetry indicated a different electrocatalytic reduction process on hydrothermally treated electrodes, compared to thermally oxidized ones. Hydrothermally treated electrodes were also found to have the thickest porous anatase layer and achieved 50–75 % alanine conversion efficiencies. Optimization showed that the cell potential, reactant flow rate and the PA: NH2OH ratio were crucial parameters in determining the conversion efficiency. η ${\eta }$ and j‾ ${\left|\overline{j}\right|}$ were found to significantly decrease when an excess of is used and, an optimal alanine η ${\eta }$ of 75 % was achieved at 2.0 V applied cell potential and 10 mL/h reactant flow rate. [ABSTRACT FROM AUTHOR]

Using the previously engineered adipate-secreting Escherichia MG1655 lacIQ, ∆ackA-pta, ∆poxB, ∆ldhA, ∆adhE, PL-SDφ10-atoB, Ptrc-ideal-4-SDφ10-fadB, ∆fadE, PL-SDφ10-tesB, ∆yciA, Ptrc-ideal-4-SDφ10-fabI, PL-SDφ10-paaJ, ∆aceBAK, ∆glcB as the core strain, the derivatives capable of enhanced synthesis of the target compound from glucose via the reversed fatty acid β-oxidation pathway were obtained. The respective effect was achieved due to the intensification of the tricarboxylic acid cycle in the cells. Prevention of multiple cycle turnovers, resulting from the inactivation of succinate dehydrogenase, had no pronounced effect on the formation of adipic acid by the recombinant. Upon intensification of the cycle due to enhancing anaplerotic oxaloacetic acetic acid formation from phosphoenolpyruvate, resulting from the increased expression of the native ppc gene, the synthesis of adipic acid increased by 1.2-fold up to ~390 μM. Enabling the formation of oxaloacetate from pyruvic acid, by introducing heterologous Bacillus subtilis pyruvate carboxylase in the cells , resulted in a 1.5-fold intensification of the cycle, concomitantly with the proportional increase in adipic acid secretion to ~496 μM. Subsequent inactivation of sdhAB genes in the strain increased the secretion of the target compound only slightly, and the adipic acid titer reached ~520 μM. The obtained data indicated a direct dependence of the efficiency of adipic acid synthesis by the engineered strains on the degree of intensification of the tricarboxylic acid cycle. [ABSTRACT FROM AUTHOR]

Endophytic fungi exist in interdependent manner inside the host plant with potential to generate the identical bioactive secondary metabolites for which the host plant is recognized. Therefore, the present study aims to identify secondary metabolites, produced by the endophytic fungi isolated from the roots of Taxus wallichiana. Additionally, biological activities, namely antioxidant and antibacterial activity, are also evaluated. Five endophytic fungi i.e., GBPITWR_F1 (Penicillium sp.), GBPITWR_F1 (P. daleae), GBPITWR_F1 (Penicillium sp.), GBPITWR_F1 (Aspergillus versicolor), and GBPITWR_F1 (Aspergillus sp.), isolated from T. wallichiana roots, were used. Extraction of bioactive metabolites was done by maceration methods in four different solvents- hexane, chloroform, ethyl acetate, and methanol in sequential manner. These crude organic extracts were tested for phytochemicals and antioxidant and antibacterial activity. Results revealed the tendency of endophytic fungi to accumulate various bioactive compounds. Gallic acid was found maximum in GBPITWR_F5 (18.35 ± 2.65 mg/g), quercetin higher in GBPITWR_F1 (15.24 ± 2.28 mg/g); taxol content was present in two of the endophytes i.e., GBPITWR_F1 (0.31 ± 0.00 mg/g) and GBPITWR_F (5 0.68 ± 0.00 mg/g). All the endophytes exhibited production of seven important organic acids i.e., ascorbic acid, citric acid, lactic acid, mallic acid, oxalic acid, pyruvic acid, and succinic acid. Additionally, all the endophytes showed potential antioxidants activity- GBPITWR_F3 with ABTS and GBPITWR_F1 with DPPH with IC50 55.15 ± 3.28 μg/mL and 65.12 ± 4.29 μg/mL in ethyl acetate extracts, respectively. Moreover, all the endophytes showed antibacterial activity against Bacillus subtilis, B. megaterium, Escherichia coli, Serratia marcescens, Pseudomonas chlororaphis, and P. palleroniana. GC-MS analysis revealed the presence of phenols, fatty acids, aromatic dicarboxylic acid, and alkaloids in ethyl acetate extracts. The biotechnological, pharmaceutical, and agricultural industries may benefit from these endophytic fungi investigated for the production of a range of secondary metabolites and the antibiotic activity. [ABSTRACT FROM AUTHOR]

The human Solute Carrier (SLC) family member, monocarboxylate transporter 1 (MCT1), transports lactic and pyruvic acid across biological membranes to regulate cellular pH and metabolism. Proper trafficking of MCT1 from the endoplasmic reticulum to the plasma membrane hinges on its interactions with the membrane-bound chaperone protein, CD147. Here, using AlphaFold2 modeling and copurification, we show how a conserved signature motif located in the flexible N-terminus of MCT1 is a crucial region of interaction between MCT1 and the C-terminus of CD147. Mutations to this motif—namely, the thymic cancer linked G19C and the highly conserved W20A—destabilize the MCT1-CD147 complex and lead to a loss of proper membrane localization and cellular substrate flux. Notably, the monomeric stability of MCT1 remains unaffected in mutants, thus supporting the role of CD147 in mediating the trafficking of the heterocomplex. Using the auxiliary chaperone, GP70, we demonstrated that W20A-MCT1 can be trafficked to the plasma membrane, while G19C-MCT1 remains internalized. Overall, our findings underscore the critical role of the MCT1 transmembrane one signature motif for engaging CD147 and identify altered chaperone binding mechanisms between the CD147 and GP70 glycoprotein chaperones. [ABSTRACT FROM AUTHOR]

Floods induce hypoxic stress and reduce wheat growth. On the other hand, rice is a semi-aquatic plant and usually grows even when partially submerged. To clarify the dynamic differences in the cellular mechanism between rice and wheat under flooding stress, morphological and biochemical analyses were performed. Although the growth of wheat in the early stage was significantly suppressed due to flooding stress, rice was hardly affected. Amino-acid analysis revealed significant changes in amino acids involved in the gamma-aminobutyric acid (GABA) shunt and anaerobic/aerobic metabolism. Flood stress significantly increased the contents of GABA and glutamate in wheat compared with rice, though the abundances of glutamate decarboxylase and succinyl semialdehyde dehydrogenase did not change. The abundance of alcohol dehydrogenase and pyruvate carboxylase increased in wheat and rice, respectively. The contents of aspartic acid and pyruvic acid increased in rice root but remained unchanged in wheat; however, the abundance of aspartate aminotransferase increased in wheat root. These results suggest that flooding stress significantly inhibits wheat growth through upregulating amino-acid metabolism and increasing the alcohol-fermentation system compared to rice. When plant growth is inhibited by flooding stress and the aerobic-metabolic system is activated, GABA content increases. [ABSTRACT FROM AUTHOR]

A solid phase extraction-electrospray ionization-ion mobility spectrometry (SPE-ESI-IMS) method was developed to determine six organic acids in cucumber leaves. The multiplexing IMS using correlation technique was adopted to optimize the signal-to-noise ratio (SNR) and resolution. 90% methanol/water was selected to be the solvent, the flow rate was 120 µL·h−1, the stop frequency of ion gate was 5000 Hz, the ion gate opening period was 0.1 ms, the air flow velocity was 2.0 L·min−1, the electrospray voltage was 3.5 kV, and the drift tube temperature was 90 °C. The cucumber leaves were treated with ultrasound in 50% methanol/water. The analytes were subsequently eluted from an SPE cartridge with 0.1 mol·L−1 HCl, and the extract was neutralized to pH 2–3 with ammonia before freeze-drying. SPE-ESI-IMS enabled the effective determination of citric acid, fumaric acid, lactic acid, malic acid, pyruvic acid, and succinic acid based upon the drift time. The limits of detection were from 0.008 µg·mL−1 to 0.2 µg·mL−1, and the recoveries of spiked samples were from 87.00% to 107.20%. The convenient, sensitive, and efficient developed SPE-ESI-IMS method may be applicable for the determination of organic acids in leaves. [ABSTRACT FROM AUTHOR]