Search Results (2,693)

Background/Objective: Sacubitril/Valsartan are a combination drug approved for heart failure treatment, known to enhance natriuretic peptide activity and inhibit the renin–angiotensin–aldosterone system (RAAS). While its clinical efficacy is well-established, its broader impact on human metabolism remains insufficiently characterized. This study aimed to explore the time-resolved metabolic changes induced by Sacubitril/Valsartan in healthy individuals using an untargeted metabolomics approach. Methods: Fourteen healthy male volunteers received a single oral dose of Sacubitril/Valsartan (200 mg; 97.2 mg Sacubitril and 102.8 mg Valsartan) across two phases separated by a two-week washout period. Plasma samples were collected at eight individualized time points based on pharmacokinetic profiles. Metabolites were extracted and analyzed using high-resolution liquid chromatography–mass spectrometry (LC-QToF HRMS). Data processing included peak alignment, annotation via HMDB and METLIN, and statistical modeling through multivariate (PLS-DA, OPLS-DA) and univariate (ANOVA with FDR correction) analyses. Results: Out of 20,472 detected features, 13,840 were retained after quality filtering. A total of 315 metabolites were significantly dysregulated (FDR p < 0.05), of which 31 were confidently annotated as endogenous human metabolites. Among these, key changes were observed in the pyrimidine metabolism pathway, particularly elevated levels of uridine triphosphate (UTP) associated with cellular proliferation and metabolic remodeling. OPLS-DA models demonstrated clear separation between pre-dose and Cmax samples (R²Y = 0.993, Q² = 0.768), supporting the robustness of the time-dependent effects. Conclusions: This is the first study to characterize the dynamic metabolomic signature of Sacubitril/Valsartan in healthy humans. The findings reveal a distinctive perturbation in pyrimidine metabolism, suggesting possible links to drug mechanisms relevant to cardiac cell cycle regulation. These results underscore the utility of untargeted pharmacometabolomics in uncovering systemic drug effects and highlight potential biomarkers for monitoring therapeutic response or guiding precision treatment strategies in heart failure. Full article

Heliotropium procumbens, a Boraginaceae species native to Panama, has remained largely unexplored regarding its nitrogen-containing metabolites, including pyrrolizidine alkaloids (PAs). In the current study, a comprehensive phytochemical investigation of its aerial parts is presented using HPLC-DAD-IT-MS, UHPLC–HRMS, and GC-MS primarily to profile its PA composition. A total of twelve PAs and N-oxides (PANOs) were identified, along with two phenolamides—including N¹, N¹⁰-diferuloylspermidine, which is biosynthetically related to PAs—and the distinctive metabolite heliotropamide. The detected PAs included unsaturated necines, primarily monoesters of retronecine and heliotridine, as well as saturated PAs such as a platynecine-type PA and the less commonly encountered triol necines and their N-oxides. Among these, helifoline-N-oxide was isolated and structurally elucidated by NMR spectroscopy for the first time as a natural product. Comparison with the chemodiversity of PAs within the Heliotropium genus revealed a high degree of diversity in H. procumbens, which can be attributed both to the species’ inherent biosynthetic capacity for chemical variation and to the more comprehensive and extensive studies conducted on it, which naturally enrich the apparent diversity observed. This work expands the phytochemical knowledge of H. procumbens and contributes to a broader understanding of PA diversity in the genus, offering new insights into their potential ecological and toxicological significance. Full article

Peach (Prunus persica) leaves, usually discarded in traditional Chinese medicine, were explored as a source of laxative agents. Using zebrafish larvae for bioactivity-guided fractionation, we isolated a single active flavanone that was identified by NMR and HR-MS as Sakuranetin. In vivo assays demonstrated that Sakuranetin (10–25 µM) accelerated intestinal transit in a dose-dependent fashion; at 25 µM, 64.8% of the fluorescent intestinal content was expelled. Untargeted LC-MS metabolomic analysis revealed significant perturbations in serine biosynthesis and N-glycan precursor biosynthesis, suggesting energetic rewiring of enterocytes. RNA-Seq analysis highlighted gnat1 as the most responsive gene, and molecular docking predicted a stable Sakuranetin–Gnat1 complex with a binding free energy of −8.7 kcal/mol. Concurrent down-regulation of rho transcripts indicated suppression of inflammatory signaling that often accompanies constipation. Our findings identified Sakuranetin as a potent promoter of gut motility and position the otherwise wasted peach leaves as an untapped botanical resource for developing anti-constipation therapeutics. Full article

Considering the importance of free amino acids (FAAs) and biogenic amines (BAs) in the production of fermented beverages (FB), the interest in the quantification of these compounds has been growing. So far, most of the analytical methods developed entail a derivatization step. While this technique allows for the detection of several compounds, it is often associated with scarce accuracy and poor resolution. To counteract the drawbacks, in this study, we aimed to develop a fast, simple, and effective method that combines the use of ultra-high-performance liquid chromatography (UHPLC) and high-resolution mass spectrometry (HRMS) to quantify underivatized FAAs and BAs in FBs. The method was successfully developed and validated: it allowed for the accurate and precise quantification of 20 FAAs—including leucine and isoleucine—and 12 BAs in just 12 min. Its applicability was demonstrated on commercial samples of wines, beers, ciders, saké, and vinegars. Full article

In the last 30 years, many scholars have proposed multilevel regulatory systems that go beyond the mere management of duties, tariffs, and non-tariff barriers, seeking instead to promote ethical, environmental, and social principles in international trade. A literature review shows that no detailed studies have examined whether, or how, sustainable human resource management (SHRM) practices can contribute to the development of effective international trade governance models. The role of human resource management (HRM) in major international trade agreements proposed by the World Trade Organization, USA, and EU is analyzed and discussed. Adopting a narrative review method, this study formulates and discusses six propositions on the potential contribution of SHRM practices to enhancing the effectiveness of international trade governance. A model to carry out a construct and criterion validation of such SHRM practices to increase the efficacy of international trade governance is proposed. Finally, critical issues arising from the constraints imposed by the current international context—marked by high levels of uncertainty and conflict—are analyzed. This analysis provides a realistic assessment of the actual contribution of SHRM practices to the effective governance of international trade. Full article

Background: It has been shown previously that thienobenzo-1,2,3-triazoles exhibit very good selective inhibition toward butyrylcholinesterase (BChE), while the same derivatives converted into salts also display inhibitory activity against acetylcholinesterase (AChE), enzymes relevant to Alzheimer’s disease therapy. They show even better BChE inhibition potential than neutral analogs. Methods: This study presents the synthesis and biological evaluation of a novel series of charged thienobenzo-1,2,3-triazolinium salts (1–17) as inhibitors of AChE and BChE. The basic skeleton of the targeted compounds was synthesized via a photochemical method and subsequently converted into corresponding bromide salts. Their structures were confirmed using NMR and HRMS analyses. Results: In vitro testing showed that all synthesized compounds exhibit moderate to strong BChE inhibition and, to a lesser extent, AChE inhibition. Compounds 8 and 11 emerged as the most potent AChE inhibitors (IC₅₀ ~ 2.6–3.2 µM), while compounds 1, 2, and 8 demonstrated excellent and selective BChE inhibition (IC₅₀ ~ 0.3–0.4 µM), outperforming the reference drug galantamine. Anti-inflammatory evaluation revealed limited activity, with compound 17 slightly reducing LPS-induced TNF-α production at the highest tested concentration. Conclusions: These findings highlight the role of the electric charge and substituent type in modulating biological activity and confirm the therapeutic potential of these molecules as dual cholinesterase inhibitors for further development in neurodegenerative disease treatment. Full article

Background: Breast cancer continues to pose a significant global health challenge despite advances in early detection and targeted therapies. The development of novel chemotherapeutic agents remains crucial, particularly those with selective cytotoxicity toward specific breast cancer subtypes. Methods: A series of ten hybrid indolyl-methylidene phenylsulfonylhydrazones and one bis-indole derivative were designed, synthesized, and structurally characterized using NMR and high-resolution mass spectrometry (HRMS). Prior to synthesis, in silico screening was performed to assess drug likeness and ADME-related properties. Single-crystal X-ray diffraction was conducted for compound 3e. The cytotoxic potential of the synthesized compounds was evaluated using the MTT assay against MCF-7 (ER-α⁺) and MDA-MB-231 (triple-negative) breast cancer cell lines. Additionally, quantitative structure–activity relationship (QSAR) analysis was conducted to identify key structural features contributing to activity. Results: Most compounds exhibited selective cytotoxicity against MCF-7 cells. Notably, compound 3b demonstrated the highest potency with an IC₅₀ of 4.0 μM and a selectivity index (SI) of 20.975. Compound 3f showed strong activity against MDA-MB-231 cells (IC₅₀ = 4.7 μM). QSAR analysis revealed that the presence of a non-substituted phenyl ring and specific indolyl substituents (5-methoxy, 1-acetyl, 5-chloro) significantly contributed to enhanced cytotoxic activity and ligand efficiency. Conclusion: The synthesized phenylsulfonylhydrazone hybrids exhibit promising and selective cytotoxicity, particularly against ER-α⁺ breast cancer cells. Structural insights from QSAR analysis provide a valuable foundation for the further optimization of this scaffold as a potential source of selective anticancer agents. Full article

Artificial intelligence (AI) is transforming organizational functions across sectors; however, its application to human resource management (HRM) within healthcare remains underexplored. This study aims to unpack the black-box nature of AI capability’s impact on HR functions within China’s healthcare sector, a domain undergoing rapid digital transformation, driven by national innovation policies. Grounded in resource-based theory, the study conceptualizes AI capability as a multidimensional construct encompassing tangible resources, human resources, and organizational intangibles. Using a structural equation modeling approach (PLS-SEM), the analysis draws on survey data from 331 professionals across five hospitals in three Chinese cities. The results demonstrate a strong, positive, and statistically significant relationship between AI capability and HR functions, accounting for 75.2% of the explained variance. These findings indicate that AI capability enhances HR performance through smarter recruitment, personalized training, and data-driven talent management. By empirically illuminating the mechanisms linking AI capability to HR outcomes, the study contributes to theoretical development and offers actionable insights for healthcare administrators and policymakers. It positions AI not merely as a technological tool but as a strategic resource to address talent shortages and improve equity in workforce distribution. This work helps to clarify a previously opaque area of AI application in healthcare HRM. Full article

Polycyclic aromatic hydrocarbon (PAH) derivatives, specifically azaarenes and nitrated and oxygenated PAHs, are emerging contaminants of concern due to their increased toxicity and persistence compared to the parent PAHs. Despite their toxicity, their simultaneous analysis in complex matrices, such as in fumes emitted from bituminous mixtures, remains challenging due to limitations of conventional analytical techniques. To address this, an advanced methodology was developed using Ultra-High-Performance Liquid Chromatography coupled with High-Resolution Mass Spectrometry (UHPLC-HRMS Orbitrap Eclipse) equipped with an APCI source for the simultaneous identification and quantification of 14 PAH derivatives. Chromatographic and ionization parameters were optimized to ensure maximum sensitivity and selectivity. Following ICH Q2(R2) guidelines, the method was validated, demonstrating excellent linearity (R² > 0.99), high mass accuracy (≤5 ppm), strong precision (<15%), and excellent sensitivity. Limits of detection (LODs) ranged from 0.1 µg L⁻¹ to 0.6 µg L⁻¹ and limits of quantification (LOQs) ranged from 0.26 µg L⁻¹ to 1.87 µg L⁻¹. The validated method was successfully applied to emissions from asphalt pavement materials collected on quartz filters under controlled conditions, enabling the identification and quantification of all 14 targeted compounds. These results confirm the method’s robustness and suitability for trace-level analysis of PAH derivatives in complex environmental matrices. Full article

Background: Recently, extensive use of antibiotics has increased the amount of antibiotic residues in the natural water environment. Methods: This study presents an experimental investigation into the degradation of penicillins, tetracyclines, streptomycin and chloramphenicol in aqueous solutions when exposed to 1 MeV accelerated electrons with doses of 0.1, 1, 3 and 7 kGy using HPLC-HRMS analysis. Results: It was found that electron beam irradiation with a dose of 7 kGy ensures 98–99% removal of antibiotics, with the initial concentrations ranging from 15 mg/L to 30 mg/L depending on the class of antibiotic. The mathematical model proposed in the study, which estimates the dose dependencies of the relative concentrations of antibiotics and their degradation products in aqueous solutions, reveals different decomposition rates of antibiotics of different classes due to the different radiosensitivities of antibiotics. It has been found that tetracycline has a considerably higher radiation–chemical yield compared to the other antibiotics when exposed to accelerated electrons. Conclusions: Using density functional theory in combination with the mathematical model, we have developed a novel approach to establishing a quantitative irradiation marker of antibiotic degradation as a result of irradiation, which involves finding the degradation product whose formation requires a minimum number of ionization events. Using such an approach, it is possible to establish the extent of antibiotic degradation in water after irradiation with different doses and find the optimal irradiation doses for industrial water treatment. Full article

This investigation explored the chemical constituents and biological activities of the steam-distilled oil of L. usitatissimum (SDOLU), employing sophisticated techniques including LC-HRMS, GC-MS, and GC-FID. The analysis identified a diverse array of 17 phenolic compounds, with linoleoyl chloride (64.05%) and linoleic acid (10.39%) as the major fatty acid components. The SDOLU demonstrated remarkable antioxidant capacity, effectively neutralizing free radicals in both DPPH^• (IC₅₀: 19.80 μg/mL) and ABTS^•+ (IC₅₀: 57.75 μg/mL) scavenging assays, alongside robust electron-donating activity in reducing ability tests. Moreover, the SDOLU showed significant inhibition of key enzymes implicated in metabolic and neurodegenerative disorders, including α-amylase (IC₅₀: 531.44 μg/mL), acetylcholinesterase (IC₅₀: 13.23 μg/mL), and carbonic anhydrase II (IC₅₀: 281.02 μg/mL). Collectively, these results highlight the SDOLU as a valuable natural source of multifunctional bioactivities with potential applications in combating oxidative stress and enzyme-related global diseases. Further studies are warranted to validate its therapeutic efficacy and expand its industrial utilization. Full article

This study explores the relationship between digital human resource management (HRM) practices, organizational culture, and employees’ perceived digital competence within Greek organizations. While digitalization has become a central priority in human resource management (HRM), there is still limited understanding of how cultural context shapes the effectiveness of digital HR interventions. Using a quantitative approach, data were collected via an online questionnaire from 257 employees across various sectors. The research employed the method of Partial Least Squares Structural Equation Modeling (PLS-SEM) and Multi-Group Analysis (MGA) to examine the structural relationships between digital HRM practices—such as e-learning, onboarding, and performance management—and digital competence, taking into account different organizational culture profiles. The results show that digital HRM practices have a positive, but modest, impact on employees’ digital skills, with e-learning emerging as the most influential factor. Importantly, the effect of HRM practices varies significantly according to the cultural environment: supportive and innovative cultures foster stronger development of digital competence compared to hierarchical settings. The findings underline the necessity for organizations to adapt digital HR strategies to their specific cultural context and not to rely solely on technological solutions. This research contributes to the growing literature by demonstrating the interplay between technology and culture in shaping employees’ digital capabilities and suggests that a balanced focus on both is essential for successful digital transformation. Full article

The phytochemical profiles, antioxidant capacities, mineral composition, and antibacterial activities of Zingiber officinale (Z. officinal) and Piper nigrum (P. nigrum) were explored through aqueous, ethanolic, and methanolic extractions. The extracts were analyzed for polyphenols, flavonoids, and tannins, and their antioxidant potential was assessed using the DPPH assay. UPLC-HRMS identified major bioactive compounds, including 6-gingerol and shogaol in Z. officinale, and piperine and piperlonguminine in P. nigrum. Mineral analysis showed that P. nigrum was particularly rich in essential elements, including calcium (Ca), magnesium (Mg), and iron (Fe). In antibacterial testing, P. nigrum demonstrated wider zones of inhibition against E. coli, whereas Z. officinale was more active at lower concentrations, showing MICs as low as 3.91 µg/mL against Salmonella and S. aureus. PCA analysis revealed strong correlations between phenolic content and biological effects. These results underscore the potential of both spices as effective natural agents for use in food preservation and health-promoting applications. Full article

The widespread emergence of resistant pathogenic microorganisms are diminishing the effectiveness of existing antimicrobial drugs, posing an enormous threat to global public health. This phenomenon, known as antimicrobial resistance (AMR), is primarily driven by the misuse and overuse of antimicrobial drugs. Natural product researchers around the globe, in response to antibiotics resistance, are searching for new antimicrobial lead compounds from unexplored or underexplored ecological niches such as the marine environment. In order to isolate new antimicrobial lead compounds, two Streptomyces spp. were isolated from marine sediment samples by a serial dilution technique and subsequently cultured in modified Bennett’s broth medium. Repeated chromatographic steps of ethyl acetate (EtOAc) extracts obtained from the culture broth led to the isolation of a new compound with an unusual chemical skeleton, streptopiperithiazol (1), and a synthetically known (2) compound. These compounds were characterized by the extensive analysis of 1D and 2D spectroscopic as well as HRMS data. The absolute configuration of 1 was unresolved due to limited yield and lack of proper facilities for taking CD and ECD spectra. In vitro activity study of compounds 1 and 2 revealed that these compounds had better activity against Gram-positive bacteria than Gram-negative bacteria and yeast. Full article

In this study, phenolic compounds of methanol extracts obtained from the leaves and branches of Satureja aintabensis P.H. Davis and Satureja spicigera (K. Koch) Boiss. species were determined as mg/kg extract using the liquid chromatography high resolution mass spectrometry technique. The in vitro inhibitory effects of these extracts against enzymes associated with neurodegenerative Alzheimer’s disease (AD) were also evaluated. The relationship between secondary metabolite structures and biological activities was discussed. The major components of S. aintabensis were determined as hesperidin (6.465% of the extract; 64.65 g/kg), syringic acid (5.964% of the extract; 59.64 g/kg), rosmarinic acid (5.248% of the extract; 52.48 g/kg) and naringenin (0.395% of the extract; 3946.84 mg/kg), while syringic acid (3.081% of the extract; 30.81 g/kg), rosmarinic acid (2.757% of the extract; 27.57 g/kg), hesperidin (1.723% of the extract; 17.23 g/kg), and luteolin-7-O-rutinoside (1.682% of the extract; 16.82 g/kg) were determined in S. spicigera. AChE and BChE enzyme inhibition of the extracts were analyzed. The species showed moderate inhibition against AChE enzyme and low inhibition against BChE enzyme. The antioxidant properties of both plant extracts were evaluated by measuring three radical scavenging capacities and the ability to reduce Fe³⁺, and Cu²⁺ ions. S. aintabensis showed better antioxidant capacity in all methods except DPPH scavaging assay. These data clearly show that both species, especially S. aintabensis, have emerged as a new and important natural source of hesperidin, syringic acid and rosmarinic acid and an antioxidant agent for pharmaceutical and nutraceutical applications. Full article