Search Results (12)

Background/Objectives: Temporal lobe epilepsy (TLE) often develops following an initial brain injury, where specific triggers lead to epileptogenesis—a process transforming a healthy brain into one prone to spontaneous, recurrent seizures. Although electroencephalography (EEG) remains the primary diagnostic tool for epilepsy, it cannot predict the risk of epilepsy after brain injury. This limitation highlights the need for biomarkers, particularly those measurable in peripheral samples, to assess epilepsy risk. This study investigated urinary metabolites in a rat model of TLE to identify biomarkers that track epileptogenesis progression across the acute, latent, and chronic phases and elucidate the underlying mechanisms. Methods: Status epilepticus (SE) was induced in rats using repeated intraperitoneal injections of lithium chloride–pilocarpine hydrochloride. Urine samples were collected 48 h, 1 week, and 6 weeks after SE induction. Nuclear magnetic resonance spectrometry was used for metabolomic analysis, and statistical evaluations were performed using MetaboAnalyst 6.0. Differences between epileptic and control groups were represented using the orthogonal partial least squares discriminant analysis (OPLS-DA) model. Volcano plot analysis identified key metabolic changes, applying a fold-change threshold of 1.5 and a p-value < 0.05. Results: The acute phase exhibited elevated levels of acetic acid, dihydrothymine, thymol, and trimethylamine, whereas glycolysis and tricarboxylic acid cycle metabolites, including pyruvic and citric acids, were reduced. Both the acute and latent phases showed decreased theobromine, taurine, and allantoin levels, with elevated 1-methylhistidine in the latent phase. The chronic phase exhibited reductions in pimelic acid, tiglylglycine, D-lactose, and xanthurenic acid levels. Conclusions: These findings highlight stage-specific urinary metabolic changes in TLE, suggesting distinct metabolites as biomarkers for epileptogenesis and offering insights into the mechanisms underlying SE progression. Full article

Background: To improve the solubility and permeability of Sparfloxacin (SPX) and enhance its antimicrobial activity in vitro, two unreported pharmaceutical crystalline salts were synthesized and characterized in this paper. One is a hydrated crystal of Sparfloxacin with Pimelic acid (PIA), another is a hydrated crystal of Sparfloxacin with Azelaic acid (AZA), namely, SPX-PIA-H₂O (2C₁₉H₂₃F₂N₄O₃·C₇H₁₀O₄·2H₂O) and SPX-AZA-H₂O (4C₁₉H₂₃F₂N₄O₃·2C₉H₁₄O₄·5H₂O). Methods: The structure and purity of two crystalline salts were analyzed using solid-state characterization methods such as single-crystal X-ray diffraction, powder X-ray diffraction, differential scanning calorimetry, thermogravimetric analysis, and infrared spectroscopy. Additionally, the interaction characteristics between two crystal salt molecules were examined by constructing Hirshfeld surfaces and mapping specific real-space functions through Hirshfeld surface analysis. The solubility under physiological conditions, diffusivity across simulated biological membranes, and in vitro antibacterial activity against specific bacterial strains of two crystalline salts were evaluated using established assays, including minimum inhibitory concentration (MIC) tests. Results: Single-crystal X-ray diffraction and Hirshfeld surface analysis indicate that SPX forms stable crystal structures with PIA through charge-assisted hydrogen bonds N1-H1e···O10 (1.721 Å, 173.24°), N5-H5a···O11 (1.861 Å, 169.38°), and with AZA through charge-assisted hydrogen bonds N5-H5B···O8 (1.810 Å, 154.55°), N4-H4B···O6 (1.806 Å, 174.97°). The binding sites of two crystalline salts were at the nitrogen atoms on the piperazine ring of SPX. Compared with SPX, the equilibrium solubility of the two crystalline salts was improved by 1.17 and 0.33 times, respectively, and the permeability of the two crystalline salts was increased by 26.6% and 121.9%, respectively. In addition, SPX-AZA-H₂O has much higher antibacterial activity on Pseudomonas aeruginosa and Bacillus subtilis than SPX. Conclusions: This research yielded the successful synthesis of two crystalline salts of Sparfloxacin (SPX), significantly improving its solubility and diffusivity, and bolstering its antibacterial efficacy against targeted bacterial species. These breakthroughs set the stage for innovative advancements in the realm of antimicrobial drug development. Full article

Polypropylene (PP) is one of the most commercially used thermoplastics, while a significant amount of PP is used in the form of fibers. In this study, the effects of modification of the filler on the thermal and mechanical properties of composite polypropylene/wollastonite drawn fibers were investigated. In this direction, the surface modification of wollastonite with various organic acids, such as myristic, maleic, malonic glutaric, pimelic, and suberic acid, and the use of two solvents were studied. The surface-modified wollastonite particles were used to produce composite polypropylene drawn fibers. The modification efficiency was found to be slightly better when a non-polar solvent (carbon tetrachloride) was used instead of a polar one (ethanol). FTIR experiments showed that myristic, maleic, malonic, and pimelic acid can strongly interact with wollastonite’s surface. However, the mechanical strength of the composite fibers was not increased compared to that of the neat PP fibers, suggesting inadequate interactions between PP and wollastonite particles. Furthermore, it was observed that the drawing process increased around 10% the crystallinity of all samples. Wollastonite modified with malonic acid acted as a nucleating agent for β-crystals. The onset decomposition temperature increased by 5–10 °C for all samples containing 2% wollastonite, either modified or not. The suggested modifications of wollastonite might be more suitable for less hydrophobic polymers. Full article

The widespread use of diesel fuel for transportation, industry, and electricity generation causes several environmental issues via an increase in the amount of sulfur compound emissions. Commercial diesel fuel must be free of sulfur-containing compounds since they can cause several environmental problems. Considering the currently available processes to eliminate sulfur compounds, oxidative desulfurization (ODS) is one of the effective means for this purpose. This work presented a simple, low cost, and efficient ODS system of high-sulfur diesel fuels using peroxide oxidation with the aid of citric, pimelic, and α-ketoglutaric acids. The aim of the study was to investigate the potential of these acids as hydrogen peroxide (H₂O₂) activators for ODS and to optimize the reaction conditions for maximum sulfur removal. The results showed that citric, pimelic, and α-ketoglutaric acids were effective catalysts for the desulfurization of high-sulfur diesel with an initial sulfur content of 2568 mg L⁻¹, achieving a sulfur removal efficiency of up to 95%. The optimized reaction conditions were found to be 0.6 g of carboxylic acid dosage and 10 mL of H₂O₂ at 95 °C. The desulfurization efficiency of the real diesel sample (2568 mg L⁻¹) was shown to be 27, 34, and 84.57%, using citric acid, α-ketoglutaric acid, and pimelic acid after 1h, respectively. The effectiveness of the oxidation process was characterized by gas chromatographic pulsed flame photometric detector (GC-PFPD) and Fourier-transform infrared spectroscopy (FTIR) techniques. The experimental results demonstrated that the developed system exhibited high efficiency for desulfurization of real high-sulfur diesel fuels that could be a good alternative for commercial application with a promising desulfurization efficiency. Full article

The purpose of studies was to analyse an impact of heterogeneous nucleation of modified isotactic polypropylene (iPP) on its tribological properties. The iPP injection molded samples, produced by mold temperature of 20 and 70 °C, were modified with compositions of two nucleating agents (NA’s), DMDBS creating α-form and mixture of pimelic acid with calcium stearate (PACS) forming β–phase of iPP, with a total content 0.2 wt.% of NA’s. A polymorphic character of iPP, with both, monoclinic (α) and pseudo-hexagonal (β) crystalline structures, depending on the NA’s ratio, was verified. The morphology observation, DSC, hardness and tribological measurements as test in reciprocating motion with “pin on flat” method, were realized, followed by microscopic observation (confocal and SEM) of the friction patch track. It was found that Shore hardness rises along with DMBDS content, independent on mold temperature. The friction coefficient (COF) depends on NA’s content and forming temperature—for upper mold temperature (70 °C), its value is higher and more divergently related to NA’s composition, what is not the case by 20 °C mold temperature. The height of friction scratches and the width of patch tracks due to its plastic deformation, as detected by confocal microscopy, are related to heterogeneous nucleation modified structure of iPP. Full article

A molecular umbrella composed of two O-sulfated cholic acid residues was applied for the construction of conjugates with cispentacin, containing a “trimethyl lock” (TML) or o-dithiobenzylcarbamoyl moiety as a cleavable linker. Three out of five conjugates demonstrated antifungal in vitro activity against C. albicans and C. glabrata but not against C. krusei, with MIC₉₀ values in the 0.22–0.99 mM range and were not hemolytic. Antifungal activity of the most active conjugate 24c, containing the TML–pimelate linker, was comparable to that of intact cispentacin. A structural analogue of 24c, containing the Nap-NH₂ fluorescent probe, was accumulated in Candida cells, and TML-containing conjugates were cleaved in cell-free extract of C. albicans cells. These results suggest that a molecular umbrella can be successfully applied as a nanocarrier for the construction of cleavable antifungal conjugates. Full article

Octacalcium phosphate (OCP) can incorporate various dicarboxylate ions in the interlayer spaces of its layered structure. Although not proven, these incorporated ions are believed to have a linear structure. In this study, the steric structures of twelve different dicarboxylate ions incorporated into OCP were investigated by comparing the experimentally determined interlayer distance of the OCP with the distance estimated using the molecular sizes of dicarboxylic acids calculated by considering their steric structures. The results revealed that the incorporated succinate, glutarate, adipate, pimelate, suberate, and aspartate ions possessed linear structures, whereas the incorporated azelate, sebacate, methylsuccinate, and malate ions exhibited bent structures. Further, the incorporated mercaptosuccinate ions featured linear, bent, other types of structures. Moreover, the steric structure of the incorporated malonate ion significantly differed from those of other dicarboxylate ions. The computational approach employed in this study is expected to deepen our understanding of the steric structures of dicarboxylate ions incorporated in the OCP interlayer spaces. Full article

We examined the effects of two direct-fed microbial (DFM) products containing multiple microbial species and their fermentation products on ruminal metatranscriptome and carboxyl-metabolome of beef steers. Nine ruminally-cannulated Holstein steers were assigned to 3 treatments arranged in a 3 × 3 Latin square design with three 21-d periods. Dietary treatments were (1) Control (CON; basal diet without additive), (2) Commence (PROB; basal diet plus 19 g/d of Commence), and (3) RX3 (SYNB; basal diet plus 28 g/d of RX3). Commence and RX3 are both S. cerevisiae-based DFM products containing several microbial species and their fermentation products. Mixed ruminal contents collected multiple times after feeding on day 21 were used for metatranscriptome and carboxyl-metabolome analysis. Partial least squares discriminant analysis revealed a distinct transcriptionally active taxonomy profiles between CON and each of the PROB and SYNB samples. Compared to CON, the steers fed supplemental PROB had 3 differential (LDA ≥ 2.0; p ≤ 0.05) transcriptionally active taxa, none of which were at the species level, and those fed SYNB had eight differential (LDA > 2.0, p ≤ 0.05) transcriptionally active taxa, but there was no difference (p > 0.05) between PROB and SYNB. No functional microbial genes were differentially expressed among the treatments. Compared with CON, 3 metabolites (hydroxylpropionic acid and 2 isomers of propionic acid) were increased (FC ≥ 1.2, FDR ≤ 0.05), whereas 15 metabolites, including succinic acid and fatty acid peroxidation and amino acid degradation products were reduced (FC ≤ 0.83, FDR ≤ 0.05) by supplemental PROB. Compared with CON, 2 metabolites (2 isomers of propionic acid) were increased (FC ≥ 1.2, FDR ≤ 0.05), whereas 2 metabolites (succinic acid and pimelate) were reduced (FC ≤ 0.83, FDR ≤ 0.05) by supplemental SYNB. Compared to SYNB, supplemental PROB reduced (FC ≤ 0.83, FDR ≤ 0.05) the relative abundance of four fatty acid peroxidation products in the rumen. This study demonstrated that dietary supplementation with either PROB or SYNB altered the ruminal fermentation pattern. In addition, supplemental PROB reduced concentrations of metabolic products of fatty acid peroxidation and amino acid degradation. Future studies are needed to evaluate the significance of these alterations to ruminal fatty acid and amino acid metabolisms, and their influence on beef cattle performance. Full article

Matrix-induced signal suppression or enhancements are known phenomena in electrospray ionization mass spectrometry. Very few studies report on method development for organic aerosols analyses with the evaluation of the matrix effects. The matrix effects lead to errors in the quantification of the analytes and affect the detection capability, precision, and accuracy of an analysis method. The present study reports on the matrix effects in the analysis of organic chemical compounds present in atmospheric aerosol particles collected on quartz filters. A total number of 19 analytes, including different classes of organic compounds, such as monoaromatic phenols and derivatives (e.g., catechol, 4-methylcatechol, 3-methoxycatechol, 4-nitrocatechol, 4-nitrophenol, 2,4-dinitrophenol, 2,6-dimethyl-4-nitrophenol), carboxylic acids (terebic acid, adipic acid, pimelic acid, phthalic acid, vanillic acid), and sulfonic acids (e.g., camphor-10-sulfonic acid), was investigated by high-performance liquid chromatography coupled to electrospray ionization time-of-flight mass spectrometry (HPLC/ESI-ToF-MS). The HPLC and ESI set-up parameters used in this study were previously optimized for the investigated compounds. Different volumes of a standard mixture were added to sample extracts, with final solutions concentrations in the 50–1500 μg L⁻¹ range. For the investigated concentration range, the observed matrix effect was independent of the standard concentration level. For quartz filter extracts, the average matrix effect determined on a concentration-based method was 109.5 ± 6.1%. Both signal suppression and enhancement effects were observed for different compounds. For other analytes, the influence of the matrix effect is variable, suggesting that the use of an internal standard is not sufficient for the matrix effects correction. Competition between analyte ions and matrix components in the gas-phase ionization processes occurring in electrospray might explain signal suppression while generated coeluted isobaric compounds might induce signal enhancement. Full article

Rate constants for the aqueous-phase reactions of the hydroxyl radical with the dicarboxylic acids, succinic acid and pimelic acid were determined using the relative rate technique over the temperature range 287 K ≤ T ≤ 318 K and at pH = 2.0, 4.6 or 4.9 and 8.0. OH radicals were generated by H₂O₂ laser flash photolysis while thiocyanate was used as a competitor. The pH values were adjusted to obtain the different speciation of the dicarboxylic acids. The following Arrhenius expressions were determined (in units of L mol⁻¹ s⁻¹):  succinic acid, k(T, AH₂) (2.1 ± 0.1) × 10¹⁰ exp[(−1530 ± 250 K)/T], k(T, AH⁻) (1.8 ± 0.1) × 10¹⁰ exp[(−1070 ± 370 K)/T], k(T, A²⁻) (2.9 ± 0.2) × 10¹¹ exp[(−1830 ± 350 K)/T] and pimelic acid, k(T, AH₂) (7.3 ± 0.2) × 10¹⁰ exp[(−1040 ± 140 K)/T], k(T, AH⁻) (1.8 ± 0.1) × 10¹¹ exp[(−1200 ± 240 K)/T], k(T, A²⁻) (1.4 ± 0.1) × 10¹² exp[(−1830 ± 110 K)/T]. A general OH radical reactivity trend for dicarboxylic acids was found as k(AH₂) < k(AH⁻) < k(A²⁻). By using the pH and temperature dependent rate constants, source and sinking processes in the tropospheric aqueous phase can be described precisely. Full article

The crystalline structure of two biodegradable odd-odd polyesters (i.e., poly(nonamethylene pimelate) (PES 9,7) and poly(nonamethylene azelate) (PES 9,9)) was investigated by means of electron and X-ray diffraction of single crystals and oriented fibers, respectively. Truncated rhombic crystals were obtained with an aspect ratio that was strongly depended on the supercooling degree. The crystalline structure of both homopolyesters was defined by an orthorhombic P21ab space group and a large unit cell containing four molecular segments with an all-trans conformation. Nevertheless, the structure in the chain axis projection was equivalent to a simpler cell containing only two segments. Crystalline lamellae were effectively degraded by lipases, starting the enzymatic attack on the lamellar surfaces. The random copolymer constituted by an equimolar amount of pimelate and azelate units (COPES 9,7/9) crystallized according to regular lamellae with a similar molecular arrangement in the chain axis projection. The structure of this copolymer was preferably conditioned by the azelate component as could be deduced from both, diffraction and spectroscopic data. Analysis of small angle X-ray scattering patterns pointed out that less crystalline lamellae with higher amorphous thickness had developed in the copolymer. This feature was interpreted as a consequence of the preferential incorporation of pimelate comonomer units in the folding surface. Full article

Friedreich’s ataxia (FRDA) is caused by transcriptional repression of the nuclear FXN gene encoding the essential mitochondrial protein frataxin. Based on the hypothesis that the acetylation state of the histone proteins is responsible for gene silencing in FRDA, previous work in our lab identified a first generation of HDAC inhibitors (pimelic o-aminobenzamides), which increase FXN mRNA in lymphocytes from FRDA patients. Importantly, these compounds also function in a FRDA mouse model to increase FXN mRNA levels in the brain and heart. While the first generation of HDAC inhibitors hold promise as potential therapeutics for FRDA, they have two potential problems: less than optimal brain penetration and metabolic instability in acidic conditions. Extensive optimization focusing on modifying the left benzene ring, linker and the right benzene ring lead to a novel class of HDAC inhibitors that have optimized pharmacological properties (increased brain penetration and acid stability) compared to the previous HDAC inhibitors. This article will describe the chemical synthesis and pharmacological properties of these new HDAC inhibitors. Full article