Monocarboxylic Acids Research Articles

Synthesis and optical properties of some 3D metal complexes based on β-dicarbonyl ferrocene derivatives

We obtained β-diketone – 1-ferrocenylbutanedione-1,3 by Claisen condensation. Ligands - hydrazones of monocarboxylic acids 1-ferrocenylbutanedione-1,3 (H2L) were synthesized by the interaction of carboxylic acid hydrazides with ferrocenoylacetone. The optical properties of all compounds synthesized in the work have been studied; based on the absorption spectra data, the values of the optical band gap were determined; it was shown that all the synthesized compounds are d-π type chromophores and have a band gap of 1,39–2,26 eV, i.e. they belong to narrow-gap semiconductors.

Construction of defective zirconium-based metal–organic frameworks for enhanced removal of toxic selenite: performance and mechanism studies

The development of effective adsorbents for the adsorption and removal of toxic selenite (SeO32−) from wastewater is urgently required but challenging. Herein, formic acid (FA), a monocarboxylic acid, was used as a template to construct serial defective Zr-Fumarate (Fum) -FA based on a green and facile preparation method. Physicochemical characterization shows that the defect degree of Zr-Fum-FA can be flexibly controlled by regulating the amount of FA to be added. Owing to rich defect units, the diffusion and mass transfer of guest SeO32− into the channel can be boosted. Particularly, Zr-Fum-FA-6 with the most defects exhibits superior adsorption capacity (519.6 mg g−1) and rapid adsorption equilibrium (∼200 min). The adsorption isotherms and kinetics can be well described by the Langmuir and pseudo-second-order kinetic models. Moreover, this adsorbent possesses excellent resistance towards co-existing ions, high chemical stability and good applicability in a broad pH range of 3–10. Thus, our study provides a promising adsorbent for SeO32−, and more importantly, it proposes a strategy for rationally tailoring the adsorption behavior of adsorbents via defect construction.

A Detailed Kinetic Analysis of the Environmentally Friendly Leaching of Spent Lithium-Ion Batteries Using Monocarboxylic Acid

It is essential to develop a leaching procedure that uses minimal acid consumption, is economical, recovers large amounts of metal, and has a minimal negative impact on the environment. In this paper, a viable hydrometallurgical method using acetic acid as a leachant is suggested for recovering critical metals from waste LCO-type batteries. Several leaching parameters were examined in order to optimize the leaching conditions. With 1.2 mol/L acetic acid, 7% H2O2, 90 °C, an S/L ratio of 10 g/L, and a 60 min leaching period, the maximum leaching efficiencies of Li (99.6%) and Co (95.6%) were attained. By investigating the different kinetic models, it was feasible to figure out the reaction’s pace, as well as the mechanism involved in the leaching process. It was found, through the comprehensive kinetic studies of the leaching process, that the surface chemical reaction controls the leaching mechanism for waste LCO-type batteries. The economic viability of the current leaching procedure in comparison to those of earlier approaches is also discussed.

In a zebrafish biomedical model of human Allan-Herndon-Dudley syndrome impaired MTH signaling leads to decreased neural cell diversity.

Maternally derived thyroid hormone (T3) is a fundamental factor for vertebrate neurodevelopment. In humans, mutations on the thyroid hormones (TH) exclusive transporter monocarboxylic acid transporter 8 (MCT8) lead to the Allan-Herndon-Dudley syndrome (AHDS). Patients with AHDS present severe underdevelopment of the central nervous system, with profound cognitive and locomotor consequences. Functional impairment of zebrafish T3 exclusive membrane transporter Mct8 phenocopies many symptoms observed in patients with AHDS, thus providing an outstanding animal model to study this human condition. In addition, it was previously shown in the zebrafish mct8 KD model that maternal T3 (MTH) acts as an integrator of different key developmental pathways during zebrafish development. Using a zebrafish Mct8 knockdown model, with consequent inhibition of maternal thyroid hormones (MTH) uptake to the target cells, we analyzed genes modulated by MTH by qPCR in a temporal series from the start of segmentation through hatching. Survival (TUNEL) and proliferation (PH3) of neural progenitor cells (dla, her2) were determined, and the cellular distribution of neural MTH-target genes in the spinal cord during development was characterized. In addition, in-vivo live imaging was performed to access NOTCH overexpression action on cell division in this AHDS model. We determined the developmental time window when MTH is required for appropriate CNS development in the zebrafish; MTH is not involved in neuroectoderm specification but is fundamental in the early stages of neurogenesis by promoting the maintenance of specific neural progenitor populations. MTH signaling is required for developing different neural cell types and maintaining spinal cord cytoarchitecture, and modulation of NOTCH signaling in a non-autonomous cell manner is involved in this process. The findings show that MTH allows the enrichment of neural progenitor pools, regulating the cell diversity output observed by the end of embryogenesis and that Mct8 impairment restricts CNS development. This work contributes to the understanding of the cellular mechanisms underlying human AHDS.

Removal of norfloxacin from high salinity wastewater by Hf-porphyrin MOF with missing linker defects: Insights into anion trapping and photoinduced charge transfer effects

Treatment of saline wastewater with advanced oxidation technologies has been an urgent challenge due to the inhibitory effect of coexisting ions on reactive oxygen species in real wastewater. Herein, monocarboxylic acids with varying acidity coefficient were employed to modulate the number of missing-linker defects in Hf-porphyrin MOFs (Hf-TCPP-X) to regulate their performance in removing norfloxacin (NFX) from complex aqueous matrices. The missing-linker defect density in Hf-MOFs promoted the removal efficiency of NFX from 8.5 % to 93.6 %. In various anion surroundings, the adsorption and photocatalysis performance of Hf-TCPP-FA with missing-linker defects was enhanced significantly. Quenching tests and the electron paramagnetic resonance (EPR) exhibited that O2∙−, 1O2, and ∙OH dominated NFX removal and their content rising in Hf-TCPP-FA/NaCl/visible-light (Hf-TCPP-FA/NaCl/vis) system. Density functional theory (DFT) calculations displayed that the adsorption energy of Hf-TCPP-FA for NFX decreased from −12.128 eV to −19.157 eV after adding Cl−. The missing-linker defects of catalysts facilitated the photoinduced charge transfer (PICT) under the visible-light irradiation and increased the number of active sites (Hf) in high salinity water. Additionally, favorable NFX removal efficiency could be sustained in Hf-TCPP-FA/visible-light (Hf-TCPP-FA/VIS) system from a wide pH range of aqueous solutions, high coexisting ion concentrations, and in the actual water matrices, and be performed well in cycling tests. This work suggests a promising route to tailor MOF-based photocatalysts by defect engineering and thus improve the removal performance of contaminants in highly saline water.

Sustainable recovery of lithium from spent LiFePO4 via proton circulation

Excessive chemical consumption and its concomitant secondary pollution have become persistent issues in the wet chemical recycling process of spent LiFePO4 batteries (sLFP). In this study, a prospective recycling strategy is proposed based on sustainable proton circulation between organic leachants, extractants, and strippants, whereby expensive organic leachants can be regenerated and secondary pollutants are reduced. The leaching dependence of the sLFP powder on the structure of the organic leachants is determined. Monocarboxylic acids with low pKa and short carbon chains exhibit preferable lithium leaching performance (98.7 % for formic acid), and the leaching behavior of metal impurities (Al, Cu) are coupled with organic acid complexation and solution pH. The direct separation of lithium from organic leachates is explored with acidic extractants for the first time. Benefitting from the buffering capacity toward protons and the salt-out effect of organic acid anions, Li element could be successfully extracted with di-(2-ethylhexyl) phosphoric acid and the organic acids can be significantly regenerated by proton exchange equilibrium. Dilute H3PO4 is employed to selectively strip Li and contribute protons to regenerate the extractant, where the separation factors of Li/Cu and Li/Al are 148.9 and 54.1, respectively. Through two-stage counter-current extraction and stripping processes, the extraction and stripping efficiency of Li could enhance to 98.62 % and 99.38 %, respectively. Thus, the Li overall yield in the leaching-extraction-stripping processes is calculated as 96.73 %, exhibiting promising prospects for proposed proton circulation strategy.

Differential Effects of Chronic Ethanol Use on Mouse Neuronal and Astroglial Metabolic Activity.

Chronic alcohol use disorder, a major risk factor for the development of neuropsychiatric disorders including addiction to other substances, is associated with several neuropathology including perturbed neuronal and glial activities in the brain. It affects carbon metabolism in specific brain regions, and perturbs neuro-metabolite homeostasis in neuronal and glial cells. Alcohol induced changes in the brain neurochemical profile accompany the negative emotional state associated with dysregulated reward and sensitized stress response to withdrawal. However, the underlying alterations in neuro-astroglial activities and neurochemical dysregulations in brain regions after chronic alcohol use are poorly understood. This study evaluates the impact of chronic ethanol use on the regional neuro-astroglial metabolic activityusing 1H-[13C]-NMR spectroscopy in conjunction with infusion of [1,6-13C2]glucose and sodium [2-13C]acetate, respectively, after 48h of abstinence. Besides establishing detailed 13C labeling of neuro-metabolites in a brain region-specific manner, our results show chronic ethanol induced-cognitive deficits along with a reduction in total glucose oxidation rates in the hippocampus and striatum. Furthermore, using [2-13C]acetate infusion, we showed an alcohol-induced increase in astroglial metabolic activity in the hippocampus and prefrontal cortex. Interestingly, increased astroglia activity in the hippocampus and prefrontal cortex was associated with a differential expression of monocarboxylic acid transporters that are regulating acetate uptake and metabolism in the brain.

A novel strategy of post defect modification (PDM) for synthesizing hydrophobic FA-UiO-66-CF3 with enhanced n-hexane vapor adsorption capacity under humidity

Volatile organic compounds (VOCs) are hard to recover due to the existence of large amounts of water vapor in practical conditions by adsorption method. Given the abundant functional groups of metal-organic frameworks (MOFs), especially –NH2 group, which can be easily functionalized to solve this problem. However, their pore apertures of the modified MOFs are constricted after post synthesis modification (PSM), leading to unsatisfied adsorption capacity under high humidity. In this work, we proposed a novel strategy of post defect modification (PDM) to synthesize high-performance hydrophobic MOFs for improving adsorption performance under humidity. Originally, the defect-rich UiO-66-NH2 was prepared by using different monocarboxylic acids (MA). In particular, the sample FA-UiO-66-NH2, obtained by the addition of formic acid (FA), exhibited strong n-hexane vapor adsorption ability (198 mg·g−1), which was 97% larger than the non-defective UiO-66-NH2. Afterwards, the defect-engineered FA-UiO-66-NH2 was decorated with –CF3 groups for improving its hydrophobicity, which showed superhydrophobicity with a water contact angle (WCA) of 151.6° and decreased (60%) water vapor adsorption capacity. Dynamic competitive adsorption experiments also indicated that the FA-UiO-66-CF3 sample is more superior competitive adsorption performances for n-hexane vapor than water vapor. Furthermore, we provide a novel strategy for constructing defect-engineered and functionalized MOFs, which will expand their application fields.

Investigation of reactive extraction of monocarboxylic acids with menthol-based hydrophobic deep eutectic solvent by response surface methodology

ABSTRACT The growing demand for producing organic acids by fermentative techniques has increased the significance of separating carboxylic acids from their fermentation broth with the reactive extraction process. Considering the environmental impacts, deep eutectic solvents can be considered as a potential green alternative for the replacement of volatile organic solvents commonly used in the extraction process. In this study, a new type of green solvent named hydrophobic deep eutectic solvent (HDES) based on decanoic acid as a hydrogen bond acceptor and menthol as a hydrogen bond donor was utilized for the reactive extraction of formic, acetic, and propionic acids from their aqueous solutions. The effect of initial acid concentration, HDES molar ratio, and tri-n-octyl amine (TOA) concentration on extraction efficiency was investigated. Modeling of the reactive extraction process was performed via a response surface methodology with a central composite design. Herein, the effect of the parameters of TOA concentration, HDES molar ratio, and initial acid concentration on the distribution coefficient was investigated. According to the results, it was reported that the most effective parameter on the extraction efficiency (%E) was the amount of extractant. The results of the experimental studies showed that the highest separation efficiency was obtained for 5% initial concentrations of formic, acetic, and propionic acids by using a mixture of 0.5 HDES molar ratio solvent and 1.9 mol/L TOA. The extraction efficiencies of these acids were found to be 88.71, 92.52, and 95.90 with ±0.1 standard deviation, respectively.

Disentangling the resistant mechanism of Fusarium wilt TR4 interactions with different cultivars and its elicitor application.

Fusarium wilt of banana, especially Tropical Race 4 (TR4) is a major factor restricting banana production. Developing a resistant cultivar and inducing plant defenses by elicitor application are currently two of the best options to control this disease. Isotianil is a monocarboxylic acid amide that has been used as a fungicide to control rice blast and could potentially induce systemic acquired resistance in plants. To determine the control effect of elicitor isotianil on TR4 in different resistant cultivars, a greenhouse pot experiment was conducted and its results showed that isotianil could significantly alleviate the symptoms of TR4, provide enhanced disease control on the cultivars 'Baxi' and 'Yunjiao No.1' with control effect 50.14% and 56.14%, respectively. We compared the infection processes in 'Baxi' (susceptible cultivars) and 'Yunjiao No.1' (resistant cultivars) two cultivars inoculated with pathogen TR4. The results showed that TR4 hyphae could rapidly penetrate the cortex into the root vascular bundle for colonization, and the colonization capacity in 'Baxi' was significantly higher than that in 'Yunjiao No.1'. The accumulation of a large number of starch grains was observed in corms cells, and further analysis showed that the starch content in 'Yunjiao No. 1' as resistant cultivar was significantly higher than that in 'Baxi' as susceptible cultivar, and isotianil application could significantly increase the starch content in 'Baxi'. Besides, a mass of tyloses were observed in the roots and corms and these tyloses increased after application with isotianil. Furthermore, the total starch and tyloses contents and the control effect in the corms of 'Yunjiao No.1' was higher than that in the 'Baxi'. Moreover, the expression levels of key genes for plant resistance induction and starch synthesis were analyzed, and the results suggested that these genes were significantly upregulated at different time points after the application of isotianil. These results suggest that there are significant differences between cultivars in response to TR4 invasion and plant reactions with respect to starch accumulation, tyloses formation and the expression of plant resistance induction and starch synthesis related genes. Results also indicate that isotianil application may contribute to disease control by inducing host plant defense against TR4 infection and could be potentially used together with resistant cultivar as integrated approach to manage this destructive disease. Further research under field conditions should be included in the next phases of study.

The effects of esketamine on the intestinal microenvironment and intestinal microbiota in mice.

This study aimed to investigate the impact of esketamine on the intestinal flora and microenvironment in mice using mRNA transcriptome sequencing and 16S rRNA sequencing. Ten female mice were randomly assigned to two groups. One group received daily intramuscular injections of sterile water, while the other group received esketamine. After 24days, the mice were sacrificed, and their intestinal tissues and contents were collected for 16S rRNA sequencing and mRNA transcriptome sequencing. The intergroup differences in the mouse intestinal flora were analyzed. Differentially expressed genes were utilized to construct ceRNA networks and transcription factor regulatory networks to assess the effects of esketamine on the intestinal flora and intestinal tissue genes. Esketamine significantly altered the abundance of intestinal microbiota, including Adlercreutzia equolifaciens and Akkermansia muciniphila. Differential expression analysis revealed 301 significantly upregulated genes and 106 significantly downregulated genes. The ceRNA regulatory network consisted of 6 lncRNAs, 44 miRNAs, and 113 mRNAs, while the regulatory factor network included 13 transcription factors and 53 target genes. Gene Ontology enrichment analysis indicated that the differentially expressed genes were primarily associated with immunity, including B-cell activation and humoral immune response mediation. The biological processes in the ceRNA regulatory network primarily involved transport, such as organic anion transport and monocarboxylic acid transport. The functional annotation of target genes in the TF network was mainly related to epithelial cells, including epithelial cell proliferation and regulation. Esketamine induces changes in gut microbiota and the intestinal microenvironment, impacting the immune environment and transport modes.

Молочна кислота як системний продукт метаболізму та біомаркер фізичного навантаження

This paper presents an up-to-date review of research data on the specific features of lactic acid metabolism and its role as an effector of vital regulatory mechanisms. Lactic acid is an alpha-hydroxy monocarboxylic acid. Physical loads of submaximal intensity and some diseases can cause dramatic increase of lactic acid content in the body fluids. The excessive lactate is removed from the working muscle and either metabolized by other tissues or excreted from the human body. Alteration of the lactate-pyruvate balance is one of the main markers of the development of cardiac hypertrophy and failure. The redistribution of lactate between the cells producing it and the cells that metabolize it is vital to maintain a stable pH level in tissues and hold lactate in the body since this compound is an important energy source as well as an effector of important regulatory mechanisms. The quantification of lactate is used to assess general physical capabilities of the human body, the intensity of physical load and the rate of recovery in physical rehabilitation. Specialized proteins, which refer to the group of monocarboxylate transporters, are involved in lactate excretion and absorption by cells. The presence of various types of transporters in cell membranes that differ in affinity to lactate and the direction of transport ensures a rapid redistribution of lactic acid throughout the body and regulates the intensity and direction of its metabolism according to the physiological needs. Efficient transfer and redistribution of lactate between different tissues of the body is essential, given the participation of lactate in several important regulatory mechanisms. As an effector, lactate is involved in the regulation of angiogenesis, differentiation of myosatellitocytes, regeneration of muscle fibers, polarization of macrophages and the course of inflammatory processes. Besides, lactate participates in epigenetic mechanisms of muscle tissue metabolism regulation. Therefore, lactate is one of the key metabolites in the human body.

Decreased β-hydroxybutyrate and ketogenic amino acid levels in depressed human adults.

β-hydroxybutyrate (BHB) is a major ketone body synthesized mainly in the liver mitochondria and is associated with stress and severity of depression in humans. It is known to alleviate depressive-like behaviors in mouse models of depression. In this study, plasma BHB, ketogenic and glucogenic amino acids selected from the Tohoku Medical Megabank Project Community-Based Cohort Study were analysed and measured using nuclear magnetic resonance spectroscopy. The Center for Epidemiologic Studies Depression Scale (CES-D) was utilized to select adult participants with depressive symptoms (CES-D ≥ 16; n = 5722) and control participants (CES-D < 16; n = 18,150). We observed significantly reduced plasma BHB, leucine, and tryptophan levels in participants with depressive symptoms. Using social defeat stress (SDS) mice models, we found that BHB levels in mice sera increased after acute SDS, but showed no change after chronic SDS, which differed from human plasma results. Furthermore, acute SDS increased mitochondrial BHB levels in the prefrontal cortex at 6 h. In contrast, chronic SDS significantly increased the amount of food intake but reduced hepatic mitochondrial BHB levels in mice. Moreover, gene transcriptions of voltage-dependent anion-selective channel 1 (Vdac1) and monocarboxylic acid transporter 1 (Mct1), major molecules relevant to mitochondrial biogenesis and BHB transporter, significantly decreased in the liver and PFC after chronic SDS exposure. These results provide evidence that hepatic and prefrontal mitochondrial biogenesis plays an important role in BHB synthesis under chronic stress and in humans with depressive symptoms.

Metal-free catalysis on the reactions of nitric acid with aliphatic aldehydes: A new potential source of organic nitrates

The photochemical reaction of peroxy radical (RO2·) and NO has been identified by field and forest studies as important source of organic nitrates (RONO2) in the atmosphere. However, this traditional pathway is not sufficient to explain the high concentration of RONO2. Hence, a new source of the tropospheric RONO2 from the dark reactions of nitric acid (HNO3) with aliphatic aldehydes (C1–C5) under catalysis is provided and examined for the first time by high-level quantum chemistry. The findings show that the reaction between HCHO and HNO3, which produces HOCH2ONO2, can be catalyzed by a series of metal-free catalysts (NH3, CH3NH2, CH3NHCH3, H2O, HNO3, H2SO4, HCOOH, HOOCCOOH). At 296 K, the effective rate constant for the bimolecular HNO3–HCHO reaction under the catalysis of CH3NH2 or CH3NHCH3 can be sufficiently accelerated by 5–8 order of magnitudes through this new loss pathway for HNO3 or HCHO to become competitive with the conventional loss pathway for their photochemical reactions with ·OH radical. Significantly, this new HOCH2ONO2 formation pathway from the dark reaction of HCHO with CH3NH3+NO3−/(CH3)2NH + NO3− was more favorable than the recognized source of RO2· with NO. Efficient catalysis performance of CH3NH2 and CH3NHCH3 is mainly attributed to their excellent proton receptivity capacity by activating the O–H bond of HNO3 to form stable organic nitrates (CH3NH3+NO3− and (CH3)2NH + NO3−) in the rate-determining step transition states. In the case of only considering the barrier, H2SO4 is the best catalyst among the investigated inorganic and organic acids, and dicarboxylic acid (HOOCCOOH) is stronger than monocarboxylic acid HCOOH in facilitating the RONO2 formation reaction. These new findings deepen our understanding on the unexpected source of organic nitrate and loss pathway of HNO3 or HCHO under catalysis in highly polluted regions.

A Dual-Signaling Electrochemical Aptasensor Based on an In-Plane Gold Nanoparticles-Black Phosphorus Heterostructure for the Sensitive Detection of Patulin.

Patulin (PAT), a type of mycotoxin existing in foodstuffs, is harmful to food safety and human health. Thus, it is necessary to develop sensitive, selective and reliable analytical methods for PAT detection. In this study, a sensitive aptasensor based on a dual-signaling strategy was fabricated, in which a methylene-blue-labeled aptamer and ferrocene monocarboxylic acid in the electrolyte acted as a dual signal, for monitoring PAT. To improve the sensitivity of the aptasensor, an in-plane gold nanoparticles-black phosphorus heterostructure (AuNPs-BPNS) was synthesized for signal amplification. Due to the combination of AuNPs-BPNS nanocomposites and the dual-signaling strategy, the proposed aptasensor has a good analytical performance for PAT detection with the broad linear range of 0.1 nM-100.0 μM and the low detection limit of 0.043 nM. Moreover, the aptasensor was successfully employed for real sample detection, such as apple, pear and tomato. It is expected that BPNS-based nanomaterials hold great promise for developing novel aptasensors and may provide a sensing platform for food safety monitoring.

Multiomics Analyses Reveal Sex Differences in Mouse Renal Proximal Subsegments.

Sex-dependent differences in kidney function are recognized but the underlying molecular mechanisms are largely unexplored. Advances in genomics and proteomic technologies now allow extensive characterization of differences between the same cell types of males and females. Multiomics integrating RNA-seq, ATAC-seq, and proteomics data to investigate differences in gene expression, chromatin accessibility, and protein expression in proximal tubules of male and female mice identified many sex-biased genes and proteins associated with kidney functions, including metabolic and transport processes. Sex differences may also arise from variations of the interaction between transcription factors and accessible chromatin regions. A comprehensive web resource is provided to advance understanding of sex differences in cells of the proximal tubule. Sex differences have been increasingly recognized as important in kidney physiology and pathophysiology, but limited resources are available for comprehensive interrogation of sex differences. RNA-seq and ATAC-seq of microdissected mouse proximal tubules and protein mass spectrometry of homogenized perfused mouse kidneys reveal differences in proximal tubule cells of males and females. The transcriptomic data indicated that the major differences in the proximal tubules between the sexes were in the S2/S3 segments, and most of the sex-biased transcripts mapped to autosomes rather than to the sex chromosomes. Many of the transcripts exhibiting sex-biased expression are involved in monocarboxylic acid metabolic processes, organic anion transport, and organic acid transport. The ATAC-seq method on microdissected tubules captured chromatin accessibility. Many of the more than 7000 differentially accessible DNA regions identified were in distal regions. Motif analyses revealed a lack of direct involvement of estrogen receptors or the androgen receptor (absence of canonical hormone response elements), suggesting an indirect regulatory role of sex hormones. Instead, analyses identified several transcription factors (TFs) ( Tead1 , Nfia/b , and Pou3f3 ) whose interplay with proximal tubule-specific TFs ( e.g. , Hnf1b , Hnf4a ) may contribute to sex differences. Finally, the whole-kidney proteome was correlated with the transcriptome, and many sex-biased proteins ( e.g. , Cyp2e1, Acsm2/3) were identified. Sex-dependent cis-regulatory elements interact with TFs in ways that lead to sex-biased gene expression in proximal tubule cells. These data are provided as a user-friendly web page at https://esbl.nhlbi.nih.gov/MRECA/PT/ .

Astrocytic lactate dehydrogenase A regulates neuronal excitability and depressive-like behaviors through lactate homeostasis in mice

Alterations in energy metabolism are associated with depression. However, the role of glycolysis in the pathogenesis of depression and the underlying molecular mechanisms remain unexplored. Through an unbiased proteomic screen coupled with biochemical verifications, we show that the levels of glycolysis and lactate dehydrogenase A (LDHA), a glycolytic enzyme that catalyzes L-lactate production, are reduced in the dorsomedial prefrontal cortex (dmPFC) of stress-susceptible mice in chronic social defeat stress (CSDS) model. Conditional knockout of LDHA from the brain promotes depressive-like behaviors in both male and female mice, accompanied with reduced L-lactate levels and decreased neuronal excitability in the dmPFC. Moreover, these phenotypes could be duplicated by knockdown of LDHA in the dmPFC or specifically in astrocytes. In contrast, overexpression of LDHA reverses these phenotypic changes in CSDS-susceptible mice. Mechanistic studies demonstrate that L-lactate promotes neuronal excitability through monocarboxylic acid transporter 2 (MCT2) and by inhibiting large-conductance Ca2+-activated potassium (BK) channel. Together, these results reveal a role of LDHA in maintaining neuronal excitability to prevent depressive-like behaviors.

Compositional Effect on the Low-Temperature Oxidation of Crude Oils Subjected to In Situ Combustion

This work shows the compositional effect on low-temperature oxidation of crude oils subjected to in situ combustion (ISC). Three heavy crudes were used in this study in which detailed information on the molecular species involved in ISC was obtained by ultra-high-resolution mass spectrometry. The oxidation was carried out on a mixture of 2% of crude oil in Ottawa sand in an isothermal cell using a batch system at 1500 psi at three conditions: (i) reservoir temperature of each crude oil, (ii) 180 °C, and (iii) 180 °C using a heterogeneous catalyst-type β-MnO2. The oil remaining after the reaction was extracted from the sand and characterized by FT-ICR MS using (+) atmospheric pressure photoionization and (−) electrospray ionization modes. The acidity of the oxidation products (extracts) and the composition of the produced carbon oxides were also monitored. A greater amount of carbon oxides produced, a lower extraction yield of organic matter in the sand after the reaction, and a higher acidity in the extracts, implied a higher reactivity. In the same sense, a higher reactivity was observed for the sample with the highest sulfur content and over the most aromatic compounds. The use of the catalyst at 180 °C promoted the oxidative reactions in two of three of the oils, as well as the formation of polyoxygenated acids over monocarboxylic acids for one of the oils, which implies that the application of this technology strongly depends on the composition of the oil.

Allosteric and substrate site effects of relevant amino acids on structural stability and flexibility of glutamate dehydrogenase-1 (GDH-1).

Mammalian GDH-1, which converts glutamate to alpha-ketoglutarate and ammonia while reducing NAD(P), is constitutively expressed in virtually all cells of the body. The extensive literature on GDH-1 suggests that functionally relevant GDH-1 structures may be distributed over a conformational flexibility landscape: polyhexamer, hexamer, trimer, monomer, monomer (unfolded), monomer (misfolded), polymer (disassembled). We have used both intrinsic (tryptophan) and extrinsic (ANS) fluorescent probes to study the dependence of the reversible hexamer to trimer dissociation on the concentrations of the denaturing agents urea and guanidine hydrochloride (GdnHCl). Dissociation at each denaturant concentration increases with increase in concentration and/or temperature, and these dependencies are shown to be affected by amino acids which bind to allosteric and/or substrate binding sites. Dissociation of the hexamer is accompanied by a large increase in the fluorescence of ANS due to binding to increase in exposed hydrophobic microdomains on the protein. In contrast, tryptophan fluorescence decreases due to increased exposure of tryptopan in the protein to the aqueous environment. Measurement were made of the influence of several known substrates and allosteric modifiers (i.e. a selection physiologically relevant monocarboxylic amino acids) on the GDH-1 hexamer to trimer transition. The observed effect of adding each amino acid is consistent with independent measurements of its binding affinity. From the temperature dependence of the fluorescence intensity changes for ANS we obtained activation parameters for the hexamer-trimer transitions. Our data are consistent with the hexamer/trimer transition in GDH-1 having significant regulatory function in vivo, perhaps contribution to/complementing allosteric regulation of the enzyme activity.

Effect of structure isomerism of pyridine monocarboxylic acids on thermodynamic properties of l-lysine complexation in aqueous buffer solution

The thermodynamic characteristics (lgKc, ΔcG, ΔcH, ΔcS) of complexation of l-lysine, a polar basic amino acid, with isomeric pyridine monocarboxylic acids (picolinic acid, nicotinic acid, isonicotinic acid) in buffer solution (pH 7.4) have been obtained at 298.15 K by calorimetry method. The results indicate the formation of molecular complexes between Lys and pyridine carboxylic acids (PyCOOH) with 1:1 stoichiometry in the buffer solution. The complexation of amino acid is influenced by position of –COOH group in the pyridine ring relative to the nitrogen atom. The binding affinity of Lys with PyCOOH isomers follows the order as PA < NA < INA. The measured density values were used to calculate the apparent molar and the partial molar volumes at infinite dilution for PyCOOH isomers in Lys buffer solutions. The results revealed formation of Lys complexes with above pyridine monocarboxylic acids. The positive transfer volumes for the PyCOOH isomers decrease in the series NA ≥ INA > PA. The effects of solute concentration and structure isomerism of PyCOOH on the volume properties were discussed in terms of predominant types of molecular interactions (hydrophilic, hydrophobic, ionic and zwitterionic) on the basis of co-spheres overlap model.