Search Results (1,072)

Arugula leaves (Diplotaxis tenuifolia L. and Eruca sativa L.) are a must-have ingredient in ready-to-eat salads, as they are prized for their appearance, taste, and flavor. The nutraceutical properties of this leafy vegetable are attributed to the presence of valuable secondary metabolites, such as phenolic acids and glucosinolates. Using UHPLC-Q-Orbitrap HRMS analysis and ion chromatography, we characterized the content of phenolic acids, glucosinolates, nitrates, and organic acids in organic arugula [Diplotaxis tenuifolia (L.) DC] and evaluated how the foliar application of three different non-microbial biostimulants (a seaweed extract, a vegetable protein hydrolysate, and a tropical plant extract) modulated the expression of these. Although the application of vegetable protein hydrolysate increased, compared to control plants, the nitrate content, the application of the same biostimulant increased the total content of glucosinolates and phenolic acid derivatives by 5.2 and 17.2%. Specifically, the foliar application of the plant-based biostimulant hydrolyzed protein significantly increased the content of glucoerucin (+22.9%), glucocheirolin (+76.8%), and ferulic acid (+94.1%). The highest values of flavonoid derivatives (173.03 μg g⁻¹ dw) were recorded from plants subjected to the exogenous application of seaweed extract. The results obtained underscore how biostimulants, depending on their origin and composition, can be exploited not only to improve agronomic performance but also to enhance the nutraceutical content of vegetables, guaranteeing end consumers a product with premium quality characteristics. Full article

The Citrus tristeza virus (CTV), a member of the Closterovirus genus, is considered a serious threat to citrus trees grafted onto sour orange (SO) rootstock. In the Mediterranean area, the most prevalent CTV strains are VT and T30. The VT strain includes both mild and severe isolates, some of them associated with seedling yellows (SY) syndrome. Mild CTV-VT isolates that do not induce SY symptoms (no-SY) show minor variations in their Orf1a, p23, and p33 genes, with a single nucleotide polymorphism at position 161 of the p23 gene. These isolates can repress superinfection with homologous severe isolates. The aim of this study was to investigate the mechanism of cross-protection by means of biological indexing, real-time RT-PCR high-resolution melting (HRM), and p23 gene amplicon sequencing. Four no-SY CTV-VT isolates were inoculated onto SO seedlings and Hamlin sweet orange trees grafted on SO. These plants were later challenged with two homologous CTV-VT SY isolates and remained asymptomatic. The biological evaluation of the infection process in superinfected plants was investigated via inoculation of the bark on SO seedlings that were also asymptomatic. A parallel HRM analysis of midvein RNA extracts revealed that the melting temperature (Tm) of the no-SY isolates was statistically lower than that of the SY isolates. The Tm values of RNAs extracts from superinfected plants were not statistically different from those of the no-SY isolates. This suggests that the SY isolates failed to establish infection or replicate in plants pre-inoculated with no-SY isolates. This blockage of replication resembles superinfection exclusion, with attractive perspectives to prevent SY damage in field applications. Full article

Background: Natural products play a crucial role in cancer treatment due to their ability to selectively target cancer cells. Andrographolide, a major constituent of Andrographis paniculata, exhibits potential anticancer properties. Considering the pharmacological importance of nitrogen-based heteroaromatic scaffolds, particularly pyrazole motifs, this study aimed to integrate the pyrazole pharmacophore with the andrographolide scaffold to develop novel therapeutic candidates. Methods: Twenty novel 3,19-(N-phenyl-3-aryl-pyrazole) acetals of andrographolide and isoandrographolide were synthesized and characterized using UV-Vis, FT-IR, NMR, and HRMS. Initial anticancer screening was conducted by the National Cancer Institute (NCI), USA, against 60 human cancer cell lines. The most promising compound, 1f (R = 4-F), was selected for further biological evaluation in the MDA-MB-231 breast cancer cell line. Results: The MTT assay results demonstrated that compound 1f exhibited strong, dose-dependent anti-proliferative effects. The apoptosis analysis of 1f revealed a time-dependent increase in apoptotic cells, and cell cycle studies indicated S phase arrest in MDA-MB-231 cells. Antioxidant activity via the DPPH assay identified compounds 1b (R = 3-NO₂) and 2b (R = 3-NO₂) as the most effective radical scavengers. The most active compounds were also evaluated for drug-likeness using in silico Lipinski’s rule assessments. Conclusions: The synthesized 3,19-(N-phenyl-3-aryl-pyrazole) acetals of andrographolide and isoandrographolide exhibited promising anticancer and antioxidant properties. Among them, compound 1f showed the most significant activity, supporting its potential as a lead candidate for further anticancer drug development. Full article

This study explores how Human Resource Management (HRM) can help organizations to face the challenges of digital transformation, focusing on reducing digital inequalities and improving employee performance. As digital tools become more important in workplaces, many employees still experience digital exclusion, which affects not only their productivity but also their sense of fairness and inclusion, as well. To investigate these issues, quantitative research was conducted using a structured questionnaire distributed online to employees across EU-based companies. The data were analyzed through PLS-SEM, including IPMA and mediation analysis, to understand the relations between HRM practices, digital skills, and perceptions of organizational justice. The findings show that HRM strategies have a significant impact on bridging the digital divide, especially by promoting digital adaptability and supporting inclusive work environments. Inclusion was also found to mediate the relation between HRM and employee performance. This research offers practical suggestions, like using Key Performance Indicators (KPIs) to monitor digital participation and encouraging continuous learning. The study adds value by connecting digital empowerment with HRM policies in a way that supports both organizational efficiency and equality. Future research could focus on specific sectors or use longitudinal data to better capture how digital inclusion develops over time. Full article

Background: Hydroxyl and amino compounds play a significant role in defining the flavor and quality of sauce-flavor Baijiu, yet their comprehensive analysis remains challenging due to limitations in detection sensitivity. In this study, we developed a novel bromine isotope labeling approach combined with ultra-high performance liquid chromatography–high-resolution mass spectrometry (UHPLC-HRMS) to achieve high-coverage profiling of these compounds in sauce-flavor Baijiu. Methods: The method employs 5-bromonicotinoyl chloride (BrNC) for rapid (30 s) and mild (room temperature) labeling of hydroxyl and amino functional groups, utilizing bromine’s natural isotopic pattern (Δm/z = 1.998 Da) for efficient screening. Annotation was performed hierarchically at five confidence levels by integrating retention time, accurate mass, and MS/MS spectra. Results: A total of 309 hydroxyl and amino compounds, including flavor substances (e.g., tyrosol and phenethyl alcohol) and bioactive compounds (e.g., 3-phenyllactic acid), were identified in sauce-flavor Baijiu. The method exhibited excellent analytical performance, with wide linearity (1–4 orders of magnitude), precision (RSD < 18.3%), and stability (RSD < 15% over 48 h). When applied to sauce-flavor Baijiu samples of different grades, distinct compositional patterns were observed: premium-grade products showed greater metabolite diversity and higher contents of bioactive compounds, whereas lower-grade samples exhibited elevated concentrations of acidic flavor compounds. Conclusions: These results demonstrate that the established method is efficient for the comprehensive analysis of hydroxyl and amino compounds in complex food matrices. The findings provide valuable insights for quality control and flavor modulation in sauce-flavor Baijiu production. Full article

Colonization of plant tissues by bacterial endophytes might lead to qualitative and quantitative changes in secondary metabolites (SMs). In this work, in vitro co-culture experiments were performed using cell suspensions of the medicinal plant Alkanna tinctoria and eight of its bacterial endophytes. An untargeted metabolomics approach using Ultra-High-Performance Liquid Chromatography High-Resolution Mass Spectrometry (UHPLC-HRMS) was employed to investigate plant–microbe interactions. Hierarchical clustering analysis and principal component analysis highlighted significant modifications of specific regulation patterns in SM production, caused by bacterial endophytes. The annotation step lead to the identification of 32 stimulated compounds in A. tinctoria cell suspensions. Among them, 3′-hydroxy-14-hydroxyshikonofuran H (5), 8′-decarboxy-rosmarinic acid (18), 8‴-decarboxy-salvianolic B (23), 8″-8‴-didecarboxy-salvianolic acid B (26) were putatively identified for the first time. Our findings highlight that employing selected microbial inoculants under controlled conditions can be an effective strategy for enhancing or stimulating the production of specific high-value metabolites. Full article

Background: Endometrial cancer (EC) is the sixth most common cancer among women globally, with an estimated 420,000 new cases diagnosed annually. Methods: This study comprised patients with endometrial cancer (EC) (n = 17), hyperplasia (HY) (n = 17), and controls (CO) (n = 20). Tissue was collected from the endometrium of all 54 patients, including patients with HY, EC, and CO, who underwent total hysterectomy. EC and HY diagnoses were confirmed based on histological examination. Untargeted metabolomics profiling was conducted using LC-HRMS. The partial least squares discriminant analysis (PLS-DA) and orthogonal partial least squares discriminant analysis (OPLS-DA) models were used for univariate and multivariate statistical analysis. The fitness of the model (R2Y) and predictive ability (Q2) were used to create OPLS-DA models. ROC analysis was carried out, followed by network analysis using Ingenuity Pathway Analysis. Results: The top metabolites that can discriminate EC and HY from CO were identified. This revealed a decrease in the levels of the lipid species, specifically phosphatidic acid (PA) (PA (14:1/14:0), PA(10:0/17:0), PA(18:1-O(12,13)/12:0)), PG(a-13:0/a-13:0), ganglioside GA1 (d18:1/18:1), PS(14:1/14:0), TG(20:0/18:4/14:1), and CDP-DG(PGF2alpha/18:2), while the levels of 3-Dehydro-L-gulonate, Uridine diphosphate-N-acetylglucosamine, ganglioside GT2 (d18:1/14:0), gamma-glutamyl glutamic acid and oxidized glutathione were increased in cases of EC and HY as compared to CO. Bioinformatics analysis, specifically using Ingenuity Pathway Analysis (IPA), revealed distinct pathway enrichments for EC and HY. For EC, the most highly scored pathways were associated with cell-to-cell signaling and interaction, skeletal and muscular system development and function, and small-molecule biochemistry. In contrast, HY cases showed the highest scoring pathways related to inflammatory disease, inflammatory response, and organismal injury and abnormalities. Conclusions: Developing sensitive biomarkers could improve diagnosis and guide treatment decisions, particularly in identifying which patients with HY may safely avoid hysterectomy and be managed with hormonal therapy. Full article

Background/Objectives: One of the plants found in Indonesian forests that has potential as an herbal medicine is andaliman (Zanthoxylum acanthopodium DC.). The fruit of Z. acanthopodium contains phenolic compounds that are known to modulate the immune response. The purpose of this study is to determine the extract profile and immunomodulatory activity of Z. acanthopodium fruit and to develop a soft capsule formulation of the extract in the form of emulsion, which stabilizes and acts as an immunomodulatory candidate. Methods: Extract profiling was conducted by liquid chromatography UHPLC–HRMS, and the predicted molecular structure was then used to search for the name of the compound using the mzcloud database. Immunomodulatory activity of the extract and its emulsion was assessed using a lymphocyte viability assay. The extract emulsion to be encapsulated as a soft capsule was developed by employing different types of oil and solubilizer in the oil phase, and a water phase containing the extract and two types of emulsifiers. Results: The chemical composition of andaliman extract was analyzed, including total phenolic content (4%), total flavonoid content (0.35%), and quercetin content (0.13%). Based on LC-HRMS analysis, eleven compounds derived from the ethanolic extract of andaliman were identified as potential immunomodulatory agents. The F3.3F formulation, which contains 30% MCT oil phase with solubilizer lauroyl-PEG-32 glycerides and a water phase with 35% Polysorbat (Tween) 80 emulsifier, provided the most stability. This stability is attributed to the presence of the Tween 80 emulsifier, which has superior wetting and washing functions, strong detergency, and good emulsifying properties compared to the PEG emulsifier used in formulation F3.3E. The survival rates in the lymphocyte cell viability test results indicate that treatment with andaliman extract (173.697% at 15.625 ppm; 174.923% at 31.25 ppm; 168.457% at 62.5 ppm) was better than treatment with kojic acid (144.375% at 15.625 ppm; 137.891% at 31.25 ppm; 146.345% at 62.5 ppm), used as the immunomodulatory agent standard. Conclusions: This study highlights the potential of andaliman extract as an immunomodulatory agent to be developed as an emulsion in a soft capsule. Full article

The current study evaluated the anticonvulsant properties of ethanolic extracts from Morus alba, Angelica archangelica, Passiflora incarnata, and Valeriana officinalis using integrated phytochemical, in vivo, biochemical, and computational approaches. Phytochemical analysis by UHPLC-HRMS/MS revealed the presence of various bioactive compounds, notably flavonoids such as isorhamnetin, quercetin, and kaempferol. In an electroshock-induced seizure model, Morus alba extract (MAE, 100 mg/kg) demonstrated significant anticonvulsant effects, reducing both seizure duration and incidence, likely mediated by flavonoid interactions with GABA-A and 5-HT3A receptors, as suggested by target prediction and molecular docking analyses. The extracts of Angelica archangelica (AAE, 100 mg/kg) and Passiflora incarnata (PIE, 50 mg/kg) exhibited moderate, non-significant anticonvulsant activities. At the same time, Valeriana officinalis (VOE, 50 mg/kg) displayed considerable antioxidant and anti-inflammatory properties but limited seizure protection. All extracts significantly reduced brain inflammation markers (TNF-α) and enhanced antioxidant defenses, as indicated by total thiols. Molecular docking further supported the interaction of key phytochemicals, including naringenin and chlorogenic acid, with human and mouse 5-HT3A receptors. Overall, Morus alba extract exhibited promising therapeutic potential for epilepsy management, warranting further investigation into chronic seizure models and optimized dosing strategies. Full article

Objectives: This study aims to investigate the impact of Gossypol on human cervical cancer cells and elucidate its mechanism of action to establish a foundation for further clinical investigations. Methods: Cell proliferation, migration, and invasion were evaluated through CCK−8, wound healing, and Transwell assays. Fe₃O₄-BP-Gossypol (Fe₃O₄@Gossypol) conjugates were synthesized by linking Fe₃O₄ with Gossypol using benzophenone crosslinking. Successful conjugation was confirmed through scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FT-IR), and ultraviolet–visible spectrophotometry (UV-Vis). Subsequent to co-incubation with HeLa cell lysates, Fe₃O₄@Gossypol complexes facilitated the magnetic enrichment and purification of target proteins, which were identified using high-resolution mass spectrometry (HR-MS). The identified targets underwent KEGG pathway and GO analyses, followed by molecular docking with Gossypol. HeLa cells were exposed to Gossypol at concentrations of 7.48, 14.96, and 29.92 μmol·L⁻¹ for 48 h, and protein expression levels were quantified via Western blotting. Results: Gossypol notably suppressed cervical cancer cell proliferation, migration, and invasion. The integration of target fishing, network pharmacology, and molecular docking highlighted PIK3R2, MAPK1, and GRB2 as potential therapeutic targets. Western blot analysis revealed a dose-dependent reduction in PIK3R2, GRB2, and MAPK1 expression in Gossypol-treated groups compared to controls (p < 0.05). Conclusions: Gossypol may exhibit anti-cervical cancer effects by modulating the PI3K/AKT signaling pathway. Full article

Organizational behavior examines the interactions of individuals and groups within businesses, while human resource management (HRM) focuses on enhancing workforce efficiency through recruitment, training, and employee relations. The success of an organization depends on the relationship between employee engagement and performance, as engaged individuals enhance productivity and innovation. This study aims to conduct a comprehensive bibliometric analysis of the academic research on the relationship between artificial intelligence (AI), employee engagement, and performance. This study highlights trends, countries, sources, and keywords in this field. The authors analyzed 11,291 articles in the first phase, 42,358 articles were analyzed in the second phase, and 606 articles were analyzed in the third phase. This study highlights the growth of the research in this area and identifies the most productive years and regional contributions. The citation analysis is used to identify the relevant research and renowned authors. This study also addresses ethical concerns related to the implementation of artificial intelligence (AI) in the workplace. This study indicates theme variations among national contributions, highlighting differing socio-cultural and theoretical perspectives on AI adoption in HRM, from behavioral leadership models to efficiency-oriented frameworks. In summary, this bibliometric study provides valuable insights into the evolution of the research topics related to AI’s impact on employee engagement and productivity, spanning multiple disciplines, such as psychology, organizational behavior, and computer science. It is relevant for the researchers, practitioners, and businesses interested in understanding and utilizing AI in the workplace. Full article

Pyridine derivatives are widely distributed in nature and have valuable pharmacological properties. The pyridine core can be found in drugs such as sorafenib, zapiclone or prothipendyl. Dipyridothiazines are derivatives of phenothiazines that exhibit valuable anticancer, antioxidant and immunomodulatory activities. In this study, we present the synthesis and preliminary in vitro analysis of anticancer activity towards melanotic (COLO829, G361) and amelanotic (A375, C32) melanoma cells and normal human fibroblasts (HDF) of a series of new tricyclic diazaphenothiazines containing a pyridine scaffold in their structure. The structures of these new molecules was confirmed using spectral techniques, including ¹H NMR, ¹³C NMR, 2D NMR and HRMS. An in vitro panel of experiments was assessed using the WST-1 assay and cytometric techniques. The two most promising compounds were analyzed for their effect on intracellular GSH levels, mitochondrial membrane potential and their ability to initiate DNA fragmentation to determine the potential mechanism of both cytotoxic and proapoptotic activity. The conducted studies confirmed the ability of the new 3-methyl-1,6-diazaphenothiazines to induce apoptosis in cancer cells, especially in terms of inducing initial as well as late-phase apoptosis. Moreover, the studied compounds were found to induce redox imbalance (evidenced by GSH depletion) in the analyzed melanoma cells, which may be an important factor that directs melanoma cells towards cell death signaling pathways. Full article

Over the past decade, microbial natural products research has witnessed a transformative “deep-mining era” driven by key technological advances such as high-throughput sequencing (e.g., PacBio HiFi), ultra-sensitive HRMS (resolution ≥ 100,000), and multi-omics synergy. These innovations have shifted discovery from serendipitous isolation to data-driven, targeted mining. These innovations have transitioned discovery from serendipitous isolation to data-driven targeted mining. Genome mining pipelines (e.g., antiSMASH 7.0 and DeepBGC) can now systematically discover hidden biosynthetic gene clusters (BGCs), especially in under-explored taxa. Metabolomics has achieved unprecedented accuracy, enabling researchers to target novel compounds in complex extracts. Integrated strategies—combining genomic prediction, metabolomics analysis, and experimental validation—constitute new paradigms of current “deep mining”. This review provides a systematic overview of 185 novel microbial natural products discovered between 2018 and 2024, and dissects how these technological leaps have reshaped the discovery paradigm from traditional isolation to data-driven mining. Full article

Aletris spicata (Thunb.) Franch. (AS), a traditional edible and medicinal plant for treating asthma, was investigated for its therapeutic mechanisms. Liquid chromatography-high-resolution tandem mass spectrometry (LC-HRMS/MS) analysis identified 33 compounds in AS. In ovalbumin (OVA)-induced asthmatic mice, AS significantly reduced inflammatory cells (neutrophils, lymphocytes, eosinophils) in bronchoalveolar lavage fluid (BALF) and decreased IL-4, IL-5, IL-13, TNF-α, and serum IgE while increasing IFN-γ. AS alleviated lung and intestinal inflammation, reduced ROS and MDA levels, and enhanced SOD activity. Immunohistochemistry and Western blot revealed AS upregulated Nrf2/HO-1 expression and inhibited NF-κB p65 nuclear translocation. Gut microbiota studies demonstrated AS restored intestinal flora homeostasis by modulating the richness, diversity, and composition. Spearman correlation analysis identified significant relationships between oxidative stress markers, inflammatory cytokines, and specific gut bacteria. These findings indicate that AS mitigates asthma through antioxidant effects (Nrf2/HO-1 pathway), anti-inflammatory actions (NF-κB pathway), and gut microbiota modulation. The study provides a scientific basis for developing AS as a natural anti-asthma treatment or functional food. The multi-target mechanism involving oxidative stress, inflammation, and gut flora highlights AS’s comprehensive therapeutic potential for asthma management. Full article

Chemical analysis of the hydroethanolic Hypericum repens L. extracts was performed using the LC/Q-TοF/HRMS technique. The majority of compounds identified belonged to phenolics, particularly flavonoids. The extract was also studied for its possible bioactivities, demonstrating high antioxidant properties compared to the control (IC₅₀ values ranging from 4.6 to 9.42 μg/mL). Significant antibacterial activity was also detected against Escherichia coli, Staphylococcus aureus, Enterococcus faecalis, and Salmonella enteritidis, with MIC values from 125 to 625 μg/mL. S. aureus presented the highest susceptibility among all bacteria tested. Additionally, the extract showed very mild anticholinesterase activity in the AChE and BChE inhibition assays. These findings provide the first insights into the phytochemical composition, as well as the antioxidant, antimicrobial, and anticholinesterase activities of H. repens extract, suggesting that the endemic Cyprus H. repens is a valuable natural rich source of bioactive compounds with a potentially broad range of bioactivities. Full article