Search Results (1,280)

Background: Cefepime/enmetazobactam (FEP/META) is a novel fixed-dose β-lactam/β-lactamase inhibitor combination. The objective was to study the physicochemical stability of the approved daily dose in polypropylene syringes and elastomeric devices over a 24 or 72 h period to understand the feasibility of using FEP/META in prolonged infusions and its use for outpatient parenteral antibiotic therapy (OPAT). Methods: Solutions of FEP/META were prepared in 0.9% NaCl or 5% dextrose (D5W) and stored in syringes (6 g/1.5 g/48 mL) or silicone and polyisoprene elastomeric devices (EDs) at 6 g/1.5 g/120 mL and 6 g/1.5 g/240 mL: syringes were tested at 22–25 °C over a 24 h period, polyisoprene EDs at 2–8 °C over 72 h period, and silicone and polyisoprene EDs at 32 °C over a 24 h period. The solution was considered stable if it retained more than 90% of its initial concentration (Ci), no pH variation (±1 unit), no significant visual change, and with compliant subvisual examination. Liquid Chromatography–Electrospray Ionization–Quadrupole Time-of-Flight–Mass Spectrometry was utilized to identify intermediate degradation products. Results: At the daily dose, FEP/META retained >90% of its Ci up to 12 h in 0.9% NaCl and 24 h in D5W when stored in syringes. In silicone ED, stability was enhanced up to 24 h in D5W at all concentrations. The solution was chemically stable for 24 h when stored in polyisoprene ED in 0.9% NaCl at 2–8 °C. Conclusions: FEP/META combination showed prolonged stability with physicochemical integrity up to 12–24 h in all containers and conditions. It appears to be stable for prolonged infusions and for OPAT. Full article

Bovine Parainfluenza Virus Type 3 (BPIV3) is a critical pathogen in the Bovine Respiratory Disease Complex (BRDC), leading to significant economic losses in the cattle industry. However, the metabolic reprogramming induced by BPIV3 in cattle remains poorly understood. This study aimed to investigate the impact of BPIV3 infection on the serum metabolome of Simmental cattle using untargeted metabolomics and ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS/MS). The results revealed significant alterations in the lipidome, including the upregulation of phosphatidylcholine (PC) and phosphatidylglycerol (PG), and the downregulation of phosphatidylinositol (PI). Sphingolipid metabolism also showed considerable changes, with increased levels of Trihexosylceramide and D-erythro-Sphingosine C-17. Furthermore, metabolic pathway analysis identified enriched pathways related to lipid metabolism, amino acid metabolism, and energy sensing. These findings suggest that BPIV3 infection induces substantial shifts in lipid metabolism, which may facilitate viral replication and immune evasion. Our results provide a deeper understanding of the metabolic changes in BPIV3-infected cattle and propose potential targets for therapeutic intervention. Full article

Background: Distinguishing between osteoarthritis (OA), rheumatoid arthritis (RA), and psoriatic arthritis (PsA) remains challenging despite different underlying mechanisms. Synovial fluid reflects metabolic changes within affected joints, yet comprehensive metabolomic comparisons across these conditions are limited. We aimed to identify disease-specific metabolic signatures in synovial fluid that could improve differential diagnosis and reveal therapeutic targets. Methods: We collected synovial fluid from 39 patients (20 OA, 5 RA, and 14 PsA) during routine knee arthrocentesis between January 2023 and February 2024. Following metabolite extraction, we performed untargeted metabolomic profiling using quadrupole time-of-flight liquid chromatography–mass spectrometry (Q-TOF LC/MS). Data underwent multivariate statistical analysis, including principal component analysis (PCA) and partial least squares–discriminant analysis (PLS-DA), to identify discriminatory metabolites. Results: While unsupervised analysis showed overlap between groups, supervised PLS-DA achieved clear metabolic separation. RA samples showed elevated itaconic acid, indicating inflammatory macrophage activation, and increased O-acetylserine, suggesting altered one-carbon metabolism. Hypoxanthine was decreased, which reflected severe metabolic stress. PsA exhibited the unique elevation of 4,4-dimethylcholestane and 2-oxoarginine. These metabolites have previously been unreported in this disease. OA demonstrated increased hippuric acid and indoleacetic acid, which are both gut microbiota products, supporting the gut–joint axis hypothesis. Conclusions: Each arthritis type displayed distinct metabolic fingerprints in synovial fluid. Candidate discriminatory metabolites, including gut-derived metabolites in OA and specific lipid alterations in PsA, open new diagnostic and therapeutic avenues. Given the limited RA sample size (n = 5), RA-related results should be viewed as exploratory and requiring validation in larger independent cohorts. These metabolites may, after rigorous validation in larger and independent cohorts, contribute to multi-metabolite biomarker panels for earlier diagnosis and to the rational design of targeted therapeutics addressing disease-specific metabolic disruptions. Full article

Recently, some cases of intentional animal poisoning using Carbofuran (CF) occurred in the Czech Republic, although CF is no longer available in the EU market. The present study describes a novel non-targeted analysis (NTA) workflow developed to possibly characterize 13 CF formulations from various sources to be certainly identified in real samples. Furthermore, a detection and quantification method for CF was developed for analyzing three animal samples, obtained from dead animals. The analyses were conducted using the liquid electron ionization (LEI) interface coupled with a quadrupole time-of-flight (QTOF) mass spectrometer, allowing the simultaneous characterization of the formulation’s volatile and low-volatile fractions. Almost all compounds detected in the different formulations were identified by comparing the experimental spectra with the NIST library at high probability values (95–99.38%). Determination of molecular ions, followed by MS/MS analysis, was performed to confirm compound identities at a high level of confidence. The quantification method for CF was successfully validated, showing negligible matrix effects (107%). CF was detected in two out of the three real samples. Only 3-keto-carbofuran was detected in one of the real samples; without any other marker, it was not possible to identify the specific formulation used in the three poisoning cases. Full article

Mycotoxin contamination in agricultural products poses a serious challenge to food safety, severely threatening human and animal health and causing significant economic losses. This study aimed to investigate the degradation and detoxification capabilities of Trichoderma reesei GG-T40 against two representative mycotoxins—aflatoxin B₁ (AFB₁) and zearalenone (ZEN). The results showed that the degradation rates of AFB₁ and ZEN by this strain reached 98.6% and 88.4%, respectively. Using ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF MS), the degradation products were systematically characterized, leading to the identification of six AFB₁ degradation products (C₁₇H₁₄O₇, AFD₁: C₁₆H₁₄O₅, C₁₁H₁₀O₄, C₁₄H₁₆O₄, C₁₅H₁₀O₄, and C₁₇H₁₄O₅) and two ZEN degradation products (α-ZOL and β-ZOL). Toxicity evaluation revealed that the key toxic structures of AFB₁ were disrupted, significantly reducing or even eliminating the toxicity of its degradation products; ZEN was mainly converted into β-ZOL (accounting for 91.5%), which has lower estrogenic activity. Further toxicological experiments in mice confirmed that the degradation products were non-toxic and non-pathogenic under actual testing conditions, demonstrating systematic verification of their safety. In conclusion, T. reesei GG-T40 can efficiently and safely degrade AFB₁ and ZEN, showing great potential for developing green control technologies for mycotoxin contamination in food and feed raw materials, with important application value for ensuring food safety. Full article

Background: Branched-chain amino acids (BCAAs) are popular as sports supplements due to their ability to enhance performance and recovery. However, the full spectrum of metabolic alterations triggered by acute supplementation with BCAAs in conjunction with exercise remains incompletely understood. Methods: A randomized crossover trial was conducted in 8 healthy active young males, who received either BCAA or placebo supplementation for three consecutive days prior to a high-intensity cycling test. Plasma samples were collected pre- and post-exercise and analyzed by ultra-high-performance liquid chromatography–quadrupole time-of-flight mass spectrometry, followed by correlation and enrichment analyses. Results: Acute BCAA supplementation was significantly associated with enhanced fat oxidation and attenuated post-exercise increases in plasma ammonia, creatine kinase, and lactate dehydrogenase, suggesting the potential improvements in energy supply and membrane stability. Metabolomics analysis identified differential metabolites primarily involved in lipid, amino acid, and glucose metabolism. Pathway enrichment revealed coordinated regulation of fatty acid oxidation (FAO) and tryptophan-related pathways. Correlation analysis further showed that changes in metabolite profiles were strongly associated with biochemical outcomes, particularly linking enhanced fat oxidation and ammonia clearance with BCAA intake. Conclusions: Short-term BCAA supplementation could enhance FAO and membrane stability via coordinated regulation of lipid and amino acid metabolism post exercise, supporting its potential role as a precision nutrition strategy. Full article

Background: Oxazolidinone derivatives are a novel class of synthetic antibacterial agents, characterized by a five-membered heterocyclic ring containing oxygen and nitrogen and a carbonyl functionality at position 2. This pharmacophore is responsible not only for antibacterial activity but also for a variety of other biological activities, including anticancer activity, anticoagulant activity, and several others. A series of novel oxazolidinone derivatives containing a hydroxamic acid moiety were synthesized in our laboratories and identified as potent inhibitors of the enzyme 5-lipoxygenase (5-LO), a key enzyme involved in the biosynthesis of leukotrienes (LTs). LTs are proinflammatory mediators implicated in allergic and inflammatory diseases. Currently, zileuton is the only FDA-approved 5-LO inhibitor, emphasizing the need to develop new agents for the treatment of such diseases. This project aims to develop validated stability-indicating analytical methods for the four most potent novel 5-(hydroxamic acid)methyl oxazolidinone derivatives (PH-211, PH-247, PH-249, and PH-251). Methods: The compounds were analyzed using Waters Acquity Ultra-High-Performance Liquid Chromatography (UHPLC-UV) with an ultraviolet detector to determine their stability in human plasma and under various forced degradation conditions, including acidic, basic, oxidative, and thermal conditions. Liquid chromatography–quadrupole time-of-flight mass spectrometry (LC-QToF-MS) was used to identify possible degradation products. Results: The compounds were found to be stable in human plasma and under thermal degradation conditions with high extraction recoveries (82–90%) but unstable in acidic, basic, and oxidative conditions. Conclusions: The findings show that the compounds are stable in biological conditions; they hold promise for the treatment of inflammatory and allergic diseases. Full article

The gut microbiome evolves in response to host development, health state, lifestyle, nutrition, and microbial interactions. The survival of gut microbiota depends on its ability to utilize its host-indigestible complex oligosaccharides. Certain gut microbes produce glycosidases that cleave N-glycoproteins to release N-glycans that are then used as a carbon source. However, commercial glycosidases are inefficient and, thus, require improved deglycosylation strategies to study their functions and scale up their production. Therefore, the main objective of this study was to recombinantly produce and characterize the novel endo-β-N-acetylglucosaminidase 2 (EndoBI-2) from Bifidobacterium longum subsp. infantis (B. infantis) and to evaluate its enzymatic performance for controlled N-glycan release. Furthermore, the optimum reaction conditions for EndoBI-2 were investigated on model glycoprotein RNAse B using model glycoprotein. The released N-glycans were profiled by hydrophilic interaction liquid chromatography-fluorescence detection-quadrupole time-of-flight tandem mass spectrometry (HILIC-FLD-QTOF-MS/MS). We demonstrated that EndoBI-2 possesses a strong temperature tolerance and efficiently cleaves N-glycans under mild reaction conditions, exhibiting high activity at pH 5. These findings highlight EndoBI-2 as a robust and efficient biocatalyst for the production of bioactive N-glycans from diverse N-glycoproteins, with potential applications in glycobiotechnology. Full article

Background: The intestinal microflora is a population of microorganisms that resides in the human gastrointestinal tract and is important in maintaining metabolic and immune homeostasis in the body. Bacteria residing in the intestine produce short-chain fatty acids (SCFAs), which communicate with, among other things, the brain–gut axis—disorders of which are one of the causes of MS-like pathologies. A particular property of SCFAs is the induction of regulatory T cells, which are finding their way into pioneering therapies for MS patients. The aim of the study is to evaluate SCFA secretion in patients with multiple sclerosis from the West Pomeranian region depending on the genotypes of rs778986 and rs3894326 polymorphisms of the FUT3 gene. Methods: The study group included 47 patients clinically diagnosed with MS. Genotyping was performed by real-time PCR using TaqMan probes. Analysis of short-chain fatty acids in faeces was performed on a quadrupole mass spectrometer coupled to a time-of-flight (QTOF) analyser coupled to an AB Sciex high-performance liquid chromatograph (UHPLC). Results: Statistical analysis did not reveal any statistically significant differences in the prevalence of the studied polymorphisms in MS patients compared to the healthy control group. It was observed that the intestinal microflora and SCFA production in MS patients may be disturbed, while the studied FUT3 gene polymorphisms probably do not have a significant effect on their concentrations. A statistical tendency towards higher caproic acid content in heterozygotes of the rs778986 polymorphism and higher valeric acid secretion in homozygotes of rs3894326 was demonstrated. Conclusions: In summary, the studied FUT3 gene polymorphisms are not overrepresented in patients with MS. The rs778986 FUT3 polymorphism may affect the caproic acid content in the faeces of patients with MS, and the rs3894326 polymorphism may affect valeric acid secretion. Due to the small sample size and sparse genotype groups, the study has limited power and negative findings may reflect Type II error; replication in larger cohorts is warranted. Full article

Geographical origin constitutes one of the key factors that exert an influence on chemical compounds of Lonicerae japonicae flos (LJF). The present research was designed to explore differences among volatile organic compounds (VOCs) and non-VOCs among LJF samples from four geographical origins. Selection of 32 LJF samples with similar genetic backgrounds was performed using simple sequence repeat markers. Headspace solid-phase microextraction gas chromatography-mass spectrometry (HS-SPME-GC-MS) and headspace-gas chromatography-ion mobility spectrometry (HS-GC-IMS) were utilized to analyze VOCs, while non-VOCs were detected via ultra-high-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry (UPLC-Q-TOF-MS). Multivariate statistical analyses were applied to screen differential compounds. The results indicated that HS-SPME-GC-MS and HS-GC-IMS identified 80 and 57 VOCs, respectively, with 34 key differential VOCs screened out, exhibiting significant variations among origins. For non-VOCs, 130 compounds were identified, with 19 key differential compounds showing geographical differences. This study further facilitates a comprehensive understanding of the chemical composition of LJF from different origins. Full article

Background/Objectives: Pregnancy represents a unique physiological state marked by extensive metabolic adaptations, particularly in lipid pathways essential for maternal adjustments, fetal development, and postpartum recovery. This study aimed to explore these changes through untargeted lipidomic profiling. Methods: This observational, comparative, non-interventional clinical study included 107 women, of which 65 were in the third trimester of pregnancy (mean age 27.9 ± 5 years) and 42 were in the early postpartum period (≤7 days, mean age 28.9 ± 5.9 years). Inclusion criteria were singleton, term pregnancies (37–41 weeks) with neonates weighing > 2500 g and no associated pregnancy-related pathologies; exclusion criteria included multiple gestation, use of lipid-altering medications, maternal age > 40 years, or diagnosed pregnancy complications. Plasma samples were analyzed using High-Performance Liquid Chromatography–Quadrupole Time-Of-Flight–Electrospray Ionization (positive mode)–Mass Spectrometry, data were processed with MetaboAnalyst 6.0 using multivariate and univariate analyses (Partial Least Squares–Discriminant Analysis, Volcano Plot, Random Forest, Receiver Operating Characteristic analysis), with statistical significance set at p < 0.05. Results: Multivariate analysis demonstrated a clear separation between groups with high predictive accuracy as reflected by strong classification metrics (Accuracy = 0.90, R² = 0.75, Q² = 0.68). Several discriminative lipids were consistently identified across statistical models, including 2-Methoxyestrone (AUC = 0.861), Eicosanedioic acid (AUC = 0.854), and Pregnenolone sulfate (AUC = 0.843). These biomarkers were further categorized into five major lipid classes: steroid hormones, long-chain fatty acids, lysophospholipids, ceramides/sphingolipids, and glycerolipids. Conclusions: Untargeted lipidomic profiling revealed distinct metabolic signatures that differentiate late pregnancy from early post-partum states. The identification of robust lipid biomarkers with high discriminative performance highlights their potential utility in maternal health monitoring, obstetric risk assessment, and postpartum recovery surveillance. Full article

Idiopathic steroid-sensitive nephrotic syndrome (ISSNS) is the most common glomerular disease in children, yet its molecular mechanisms and lipid-mediated pathophysiology remain poorly understood. In this study, we performed comprehensive non-targeted metabolomic analysis of serum samples obtained from children with ISSNS during both the nephrotic and remission phases to identify metabolic alterations associated with disease status. Using liquid chromatography–quadrupole time-of-flight mass spectrometry (LC-QTOF-MS), we profiled low-molecular-weight metabolites and identified significant alterations in several lipid classes, including sphingolipids, glycerophospholipids, and lysophospholipids. Several sphingomyelin and phosphatidylcholine species showed strong correlations with total cholesterol levels, reflecting lipid alterations consistent with the hyperlipidemic state that characterizes ISSNS. In contrast, oxidized phosphatidylcholines may more specifically reflect oxidative membrane injury and glomerular permeability changes associated with disease status. These findings highlight membrane lipid remodeling as a key feature of active disease and suggest potential lipid-based biomarkers for disease monitoring and therapeutic evaluation in pediatric ISSNS. This study provides a metabolomic framework for understanding lipid-driven mechanisms of ISSNS pathophysiology. Full article

The transition to sustainable aviation fuel (SAF) is critical for reducing the carbon footprint of the aviation sector while ensuring compatibility with current engines and infrastructure. Regulatory constraints, such as ASTM D7566, currently limit SAF blending to 50% in commercial flights, emphasizing the need for accurate evaluation of SAF properties to enable broader adoption. This review presents an updated overview of fuel studies evaluating key thermophysical and transport properties of hydrocarbon-based SAFs—including density, viscosity, specific energy, flash point, and thermal stability—with particular emphasis on molecular dynamics (MD) simulations. Among the MD simulations, the OPLS-AA force field demonstrates high accuracy in modeling liquid-phase hydrocarbons and shows strong agreement with experimental data. Coupled with MD engines like LAMMPS and GROMACS, it enables scalable and efficient simulations of SAF blends. Emerging research trends highlight integrative approaches that combine classical MD and machine learning (ML) in fuel property prediction, and force-field optimization to improve predictive capability. Future research in fuel is moving toward multi-force-field coupling using reactive frameworks such as ReaxFF for studying pyrolysis and oxidation, and data-driven experiments with in situ simulation feedback loops to accelerate SAF design and facilitate wider implementation in aviation. Full article

Ziziphi Spinosae semen (ZSS) is renowned for its rich nutritional composition and is traditionally consumed in China, Japan, and Korea, where it is widely incorporated into both medicinal diets and daily cuisine. To address the lack of systematic research comparing raw and fried ZSS, this study aimed to elucidate the compositional and functional changes induced by the frying process. This study systematically compared the chemical profiles and antioxidant activities of ZSS and fried ZSS using ultra-performance liquid chromatography–quadrupole–time-of-flight mass spectrometry (UPLC–Q–TOF–MS) and gas chromatography–ion mobility spectrometry (GC–IMS). A total of 92 non-volatile compounds and 43 volatile organic compounds (VOCs) were identified. Frying significantly promoted the formation of polar compounds such as flavonoids and saponins and increased the content of aldehydes and alcohols, thereby generating aromas characteristic of Maillard reactions and lipid oxidation. Principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) clearly distinguished the two groups in terms of their chemical composition and flavor characteristics. In addition, 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2′-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) assays demonstrated that the antioxidant capacity of fried ZSS was significantly higher than that of the raw sample (p < 0.05). These results indicate that the frying process reshapes the chemical properties and bioactivity of ZSS via multiple pathways, including glycoside hydrolysis, lipid oxidation, and Maillard reactions. Overall, this study establishes a scientific foundation for the development of functional foods derived from ZSS. Full article

Prosthechea karwinskii is an orchid endemic to Mexico used for medicinal purposes. The objective of this study was to determine the anticoagulant potential ex vivo of the extract isolated using green solvents. Coagulometric assays were performed to evaluate the anticoagulant activity: activated partial thromboplastin time (APTT), prothrombin time (PT), and thrombin time (TT). For each assay, different concentrations of the extract were evaluated (0.5, 1.0, 1.5, 2.5, 3.5, 4.5, 5.5, 7.5, and 8.5 mg/mL) using platelet-poor plasma from healthy donors. The P. karwinskii leaves extract showed an anticoagulant effect by significantly prolonging (p < 0.05) the APTT and TT from a concentration of 3.5 and 2.5 mg/mL, respectively, compared to basal. The anticoagulant activity was concentration dependent. In addition, the hydroethanolic extract of P. karwinskii leaves inhibited factor XI activity by 86.10 ± 2.3%. The compounds in the extract were identified by ultra-high-performance liquid chromatography coupled with electrospray ionization and quadrupole time-of-flight mass spectrometry (UPLC-ESI-qTOF-MS/MS). The compounds identified were quinic acid, malic acid, succinic acid, L (-)-phenylalanine, guanosine, neochlorogenic acid, chlorogenic acid, rutin, kaempferol-3-O-rutinoside, azelaic acid, sebacic acid, pinellic acid, and embelin. Full article