Search Results (6,219)

Background/Objectives: This study aimed to synthesize a novel, high-molecular-weight acyclic heterocyclic compound, compound 5, via a one-pot reaction between Trichloroisocyanuric acid (TCCA) and ethanolamine, and evaluate its anticancer, antioxidant, and antifungal activities. Methods: Its complex tetrameric structure, assembled through N-N linkages, was unequivocally confirmed by a full suite of spectroscopic techniques including IR, ¹H & ¹³C NMR, ²D-NMR, and high-resolution mass spectrometry (LC/Q-TOF/MS). The MTT assay was used to assess the anticancer activity of compound 5 against four different human cancer cell lines. Results: The findings indicate that human colon (HT29) and ovarian (OVCAR3) cancer cells were sensitive to the treatment, whereas brain (glioblastoma) (T98G) cancer cells were resistant. The most pronounced cytotoxic effect was observed in pancreatic (MiaPaCa2) cancer cells. Notably, compound 5 exhibited potent antifungal properties, achieving 100% inhibition of the pathogenic water mould Saprolegnia parasitica zoospores at 100 µM after 10 min. Molecular docking studies corroborated the biological data, revealing a high binding affinity for key cancer and fungal targets (Thymidylate Synthase and CYP51), providing a strong mechanistic basis for its observed activities. Conclusions: These findings establish compound 5 as a promising dual-action agent with significant potential as both a targeted anticancer lead and an eco-friendly antifungal for applications in aquaculture. Full article

MicroRNA-22 (miR-22) is a negative regulator of mitochondrial biogenesis, as well as lipid and glucose metabolism, in metabolically active tissues. Silencing miR-22 holds promise as a potential treatment of obesity and metabolic syndrome, as it restores metabolic capacity—enhancing oxidative metabolism—and reduces ectopic fat accumulation in chronic obesity, a driver of impaired metabolic flexibility and muscle mass loss. Intramuscular adipose accumulation and defective mitochondrial function are features associated with obese-mediated muscle atrophy and hallmarks of neuromuscular disorders such as Duchenne muscular dystrophy. Therefore, miR-22 could represent a compelling molecular target to improve muscle health across various muscle-wasting conditions. This study describes a pharmacological strategy for the inhibition of miR-22 in skeletal muscle by employing a mixmer antisense oligonucleotide (ASO, anti-miR-22). Administration of the ASO in a mouse model of obesity positively modulated myogenesis while protecting dystrophic mice from muscle function decline, enhancing fatigue resistance, and limiting pathological fibrotic remodeling. Mechanistically, we show that anti-miR-22 treatment promotes derepression of genes involved in mitochondrial homeostasis, favoring oxidative fiber content regardless of the disease model, thus promoting a more resilient phenotype. Furthermore, we suggest that miR-22 inhibition increases autophagy by transcriptional activation of multiple negative regulators of mammalian target of rapamycin (mTOR) signaling to decrease immune infiltration and fibrosis. These findings position miR-22 as a promising therapeutic target for muscle atrophy and support its potential to restore muscle health. Full article

Pea starch, often obtained as a by-product of pea protein isolation, is increasingly available and economically attractive. Consequently, the industry is seeking new applications of pea starch, both in its native and modified forms. This paper highlights the topic of pea and potato starch oxidation with ozone in aqueous suspension and evaluates the effect of process time, retention volume and solids content on pasting, texture, and flow behavior, benchmarking against a commercial hypochlorite-oxidized product. Moreover, obtained preparations were studied for their molecular mass distribution and hydrodynamic parameters. It was found that the oxidation of both potato and pea starch with ozone in an aqueous suspension is an effective method of obtaining this type of starch preparations. The extent of modification was dependent on all variables considered in the research. The depolymerization of both starch varieties progressed gradually, but the oxidation effects were more noticeable for potato starch compared to pea starch, which was found to be related to the gelling characteristic of those preparations. Full article

This paper reports a novel effort to estimate and evaluate the coefficients of Hg transfer across the water/air interface in lakes such as Cane Creek Lake (CCL, Cookeville, TN, USA). This was accomplished by calculating the coefficients (k_w) using the Two-Thin Film (TTF) Model for Hg transfer together with the field-measured data of Hg emission flux (F), dissolved gaseous mercury concentration (DGM), air Hg concentration (C_a), and water temperature for Henry’s coefficient (K_H) obtained from a separate field study at the CCL. The daily mean k_w values range from 0.045 to 0.21 m h⁻¹, with the min. at 0.0025–0.14 and the max. at 0.079–0.41 m h⁻¹, generally higher for the summer, and from 0.0092 to 0.15, with the min. at 0.0032–0.033 and the max. at 0.017–0.31 m h⁻¹, generally lower for the fall and winter, exhibiting an apparent seasonal trend. The highest k_w values occur in August (mean: 0.21, max.: 0.41 m h⁻¹). Our k_w results add to and enrich the aquatic interfacial Hg transfer coefficient database and provide an alternative avenue to evaluate and select the coefficients for the TTF Model’s application. The k_w results are of value in gaining insights into the Hg transfer actually occurring across the water/air interface under environmental influences (e.g., wind/wave, solar radiation). Our k_w results do not show a clear, consistent correlation of k_w with wind/wave effect, nor sunlight effect, in spite of some correlations in sporadic cases. Generally, the k_w values do not exbibit the trends prescribed by the model sensitivity study. The comparisons of our k_w results with those obtained using wind-based transfer models (the Liss/Merlivat Model, the Wanninkhof Model, and the modified linear model) show that they depart from each other. The findings of this study indicate that the TTF Model has limitations and weaknesses. One major assumption of the TTF Model is the equilibrium of the Hg distribution between the air and water films across the water/air interface. The predominant oversaturation of DGM shown by our DGM data evidently challenges this assumption. This study suggests that aquatic interfacial Hg transfer is considerably more complicated, involving a group of factors, more than just wind and wave. Full article

An integrative approach combining network pharmacology, molecular docking, and cellular assays was used to elucidate the potential mechanisms by which the n-butanol extract of Biebersteinia heterostemon ameliorates type 2 diabetes mellitus (T2DM). Chemical constituents of the n-butanol extract were identified via ultra-high-performance liquid chromatography coupled with Q-Exactive Orbitrap mass spectrometry. Active compounds and T2DM-related targets were retrieved from public databases, and intersecting targets were identified. Protein–protein interaction (PPI) networks were constructed using the STRING database, while Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed via the DAVID database. A comprehensive “drug–compound–target–disease–pathway” network was established, and molecular docking was conducted to evaluate binding affinities of key compounds to core targets. Functional validation was performed in insulin-resistant cell models. Network pharmacology analysis identified 37 active constituents within the extract and 222 overlapping targets associated with T2DM. GO enrichment indicated involvement in protein phosphorylation, MAPK cascade activation, and negative regulation of apoptosis. Key signaling pathways included PI3K/AKT and lipid and atherosclerosis pathways. Molecular docking revealed strong binding affinities (binding energies ≤ −9.3 kcal·mol⁻¹) between core compounds—such as cheilanthifoline, glabridin, acetylcorynoline, skullcapflavone II, liquiritigenin, and dinatin—and pivotal targets including GAPDH, AKT1, TNF, SRC, EGFR, and PPARγ. In vitro experiments demonstrated that the extract significantly enhanced glucose uptake and glycogen synthesis in insulin-resistant cells, while suppressing oxidative stress and the expression of pro-inflammatory mediators such as TNF-α, MMP9, and IL-6. Collectively, B. heterostemon shows potential as an effective intervention for T2DM by targeting key molecular pathways, improving insulin sensitivity, and mitigating oxidative stress and inflammation in insulin-resistant cells. Full article

Photodynamic therapy (PDT) has evolved considerably over the past decades, progressing from first-generation porphyrins to second- and third-generation photosensitizers, including nanocarrier-based systems with improved selectivity and bioavailability. In parallel, matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF MS) has become a gold standard for the characterisation of complex biomolecules, enabling precise determination of molecular mass, purity and stability. This narrative review explores the intersection of these two fields, focusing on how MALDI-TOF MS supports the development, characterisation and clinical application of photosensitizers used in PDT. Literature searches were performed across PubMed, Web of Science, Scopus and Base-search, followed by targeted retrieval of studies on MALDI and PDT applications. Findings indicate that MALDI-TOF MS plays a crucial role at multiple stages: confirming the synthesis and chemical integrity of novel photosensitizers, monitoring their metabolic stability in biological systems and characterising photodegradation products after PDT. Moreover, MALDI imaging mass spectrometry (MALDI-IMS) enables spatial mapping of photosensitizer distribution in tissues, while rapid pathogen identification by MALDI-TOF supports antimicrobial PDT applications. Collectively, the evidence highlights that MALDI-MS is not only a tool for molecular characterisation but also a versatile analytical platform with a direct translational impact on PDT. Its integration with other omics and multimodal imaging approaches is expected to enhance the personalization and clinical effectiveness of photodynamic therapy. Full article

Ozonation is an emergent green technology that modifies the chemical composition and bioactivity of natural oils, creating new opportunities for functional and biomedical use. In this study, the chemical changes and in vitro activities of lettuce (Lactuca sativa) oil before and after ozonation were evaluated. Gas chromatography–mass spectrometry (GC–MS) revealed an increase in both the number and diversity of constituents in ozonated oil, with (Z)-13-docosenamide and trans-13-octadecenoic acid as predominant components. Fourier-transform infrared (FTIR) spectra showed overall similarity between native and ozonated oils, but with three additional characteristic bands in the ozonated sample. Bioassays demonstrated that ozonation enhanced anti-Helicobacter pylori activity (inhibition zone 21.3 ± 0.3 mm), supported bactericidal effects, and improved antibiofilm and antihemolytic properties. The antioxidant capacity of ozonated oil was modestly increased (IC₅₀ = 3.95 ± 0.4 µg/mL), while butyrylcholinesterase inhibition was more markedly enhanced (IC₅₀ = 2.58 ± 0.6 µg/mL), compared to that of the non-ozonated oil (IC₅₀ = 6.14 ± 0.3 µg/mL and IC₅₀ = 4.38 ± 0.4 µg/mL, respectively). Molecular docking suggested strong interactions of major ozonation-derived compounds with human BuChE and H. pylori urease, providing mechanistic support for the observed activities. Overall, these results indicate that ozonation modestly but consistently enhances the biological potential of lettuce oil through compositional shifts, highlighting its promise for development as a safe functional food ingredient with possible biomedical applications. Full article

Despite the long history of beech (Fagus sylvatica L.) red heartwood research, there has been no experimental proof on the structure of the chromophores yet. For the first time, using high-performance liquid chromatography/diode array detection/multistage electrospray ionization mass spectrometry, it was evidenced that red heartwood chromophores are water/methanol solvent extractable high molecular weight (400–2200 Da) compounds, which are polymerized, transformed, and oxidized products of (epi)catechin and taxifolin. Acid soluble non-extractable polyphenols (flavonoids, tannins) were not evidenced in the cell wall structure, while alkaline soluble compounds (ferulic acid, dehydrodiferulic acid, p-coumaric acid) have been identified for the first time from the sapwood/red heartwood boundary tissues: these supposedly play a role in the structural reinforcement of the cell wall structure and in the antioxidant protection and have a lesser role in color formation. Results on the structure of chromophores and on cell wall composition may enhance color homogenization technologies and contribute to a better utilization of red-heartwooded timber in the future. Full article

Background: Recombinant monoclonal antibodies (mAbs) represent the fastest-growing sector of the biopharmaceutical industry, with their efficient expression being a key technological factor for scalability. Objectives: In this study we compared the performance of two bicistronic vectors, which alternate the positions of the light and heavy chain coding genes, employing a wild-type Encephalomyocarditis virus (EMCV) IRES functional element to drive expression of the second gene. Methods: Using two neutralizing anti-SARS-CoV-2 IgG1 antibodies as model molecules, we conducted transient transfections in the commercially available ExpiCHO^TM platform. Following protein A affinity purification and quantification, vectors positioning the light chain as the first cistron consistently yielded higher expression levels than those with the heavy chain upstream. To confirm the quality attributes of the mAbs, we applied a comprehensive analytical workflow, including SDS-PAGE and Western blot for molecular mass and purity, circular dichroism for secondary structure, intrinsic tryptophan fluorescence for tertiary structure, and SEC-HPLC for quaternary structure and aggregate detection. Additionally, we assessed binding affinity to the target using spot blot and surface plasmon resonance, analyzed N-glycosylation profiles by HILIC-HPLC and mass spectrometry, and examined molecular structure by transmission electron microscopy. Results and Conclusions: Together, these results provide insight into the impact of gene positioning within bicistronic vectors on mAb expression efficiency and quality, supporting optimization strategies for scalable recombinant antibody production. Full article

Background: Histone post-translational modifications (PTMs) play a pivotal role in the regulation of chromatin structure and gene expression, making them key targets in structural and epigenetic research. Synthetic histone peptides bearing specific PTMs are essential tools for elucidating the molecular mechanisms of histone function and protein–histone interactions. Methods: We synthesized histone H4 tail peptides containing site-specific lysine modifications using solid-phase peptide synthesis (SPPS). The correct synthesis of the peptides was confirmed by their molecular weights using a mass spectrometer. Results: An improved high-performance liquid chromatography (HPLC) method was developed to efficiently separate peptides with one modification difference. In alignment with green chemistry principles, we evaluated ethanol and isopropanol as an alternative organic solvent to acetonitrile in the mobile phase. The optimized HPLC method using acetonitrile enabled effective resolution of closely related peptide species, providing peptides suitable for downstream applications requiring high purities such as structural biology. Conclusions: This study presents a strategy for the purification of histone PTM peptides, emphasizing both analytical performance and sustainability. Further investigation must be undergone to develop high-precision purification using green chemicals. Full article

Gliomas are aggressive brain tumours with diverse histological and molecular features, complicating accurate diagnosis and treatment. Dysregulated lipid metabolism contributes to glioma progression, and analysing lipid profiles in plasma and tissue may enhance diagnostic and prognostic accuracy. This study investigated lipid dysregulation to identify key lipid signatures that distinguish glioma from other brain diseases and examined the associations between lipid biomarkers in glioma tissue and plasma. Biospecimens from 11 controls and 72 glioma patients of varying grades underwent lipidomic profiling using liquid chromatography-mass spectrometry. Univariate and multivariate analyses identified differentially abundant lipids, and correlation analysis evaluated the associations between tissue and plasma biomarkers. Lipidomic analysis revealed distinct lipid profiles in the tissues and plasma of glioma patients compared to those of controls. Prominent lipid metabolites in glioma tissues included LPC 21:3 (AUC = 0.925), DG 43:11 (AUC = 0.906), and PC 33:1 (AUC = 0.892), which served as effective biomarkers. Conversely, in plasma, lipid metabolites such as phosphatidylethanolamine (PE 21:3, AUC = 0.862), ceramide-1-phosphate (CerP 26:1, AUC = 0.861), and sphingomyelin (SM 24:3, AUC = 0.858) were identified as the most promising lipid biomarkers. Significant positive and negative correlations were observed between the tissue and plasma lipid biomarkers of glioma patients. Lipidomic profiling revealed aberrant lipid classes and pathways in glioma tissues and plasma, enhancing understanding of glioma heterogeneity and potential clinical applications. Full article

Jets and outflows are key components of low-mass star formation, regulating accretion and shaping the surrounding molecular clouds. These flows, traced by molecular species at (sub)millimeter wavelengths (e.g., CO, SiO, SO, H₂CO, and CH₃OH) and by atomic, ionized, and molecular lines in the infrared (e.g., H₂, [Fe II], [S I]), originate from protostellar accretion disks deeply embedded within dusty envelopes. Jets play a crucial role in removing angular momentum from the disk, thereby enabling continued mass accretion, while directly preserving a record of the protostar’s outflow history and potentially providing indirect insights into its accretion history. Recent advances in high-resolution, high-sensitivity observations, particularly with the James Webb Space Telescope (JWST) in the infrared and the Atacama Large Millimeter/submillimeter Array (ALMA) at (sub)millimeter wavelengths, have revolutionized studies of protostellar jets and outflows. These instruments provide complementary views of warm, shock-excited gas and cold molecular component of the jet–outflow system. In this review, we discuss the current status of observational studies that reveal detailed structures, kinematics, and chemical compositions of protostellar jets and outflows. Recent analyses of mass-loss rates, velocities, rotation, molecular abundances, and magnetic fields provide critical insights into jet launching mechanisms, disk evolution, and the potential formation of binary systems and planets. The synergy of JWST’s infrared sensitivity and ALMA’s high-resolution imaging is advancing our understanding of jets and outflows. Future large-scale, high-resolution surveys with these facilities are expected to drive major breakthroughs in outflow research. Full article

The adrenal glands are central to the stress response in cetaceans, yet their morphological and molecular changes under chronic stress remain poorly described. We investigated adrenal histology and protein composition in stranded common dolphins (Delphinus delphis) to assess whether post-mortem material can provide insights into stress physiology. Adrenal glands from 58 dolphins recovered along the Irish coast during a period of reported nutritional stress in the species were analyzed for adrenal mass, cortex-to-medulla (C:M) ratios, and cortical cell density. Additionally, two archival formalin-fixed, paraffin-embedded (FFPE) tissues were included in a pilot trial to assess the feasibility of protein extraction and mass spectrometry analysis. While adrenal mass did not differ significantly between stress types, chronically stressed dolphins exhibited significantly higher C:M ratios and cortical mass, consistent with cortical hypertrophy. Protein extraction from FFPE tissues was feasible, with the in-gel digestion method yielding more proteins (136) than the filter-aided sample preparation method (22). These findings demonstrate that histological and proteomic approaches can detect stress-related signatures in dolphins and highlight the potential of archival tissues for retrospective biomarker discovery. Full article

Platelet-rich plasma (PRP) has gained attention in regenerative medicine due to its bio-active proteins with tissue-healing potential. However, heterogeneity in PRP composition remains a major challenge for reproducibility and standardization. Given that body mass index (BMI) affects systemic blood parameters, we investigated whether BMI affects the cellular and molecular composition of PRP. Seventy-three participants were stratified into normal weight, overweight, and obese groups. PRP was prepared using a double-syringe system, and platelet activation was induced by freeze–thaw cycles. Whole blood and PRP cell counts were analyzed, and IL6, IGF1, HGF, and PDGF-BB levels in PRP were quantified by ELISA. Platelet enrichment and levels of IGF1, HGF, and PDGF-BB in PRP did not significantly differ between BMI groups. In contrast, IL6 concentrations were higher in normal-weight compared to overweight and obese individuals. Moreover, BMI-related associations emerged between platelet counts and PDGF-BB, and between PRP proteins and sex or caffeine intake, suggesting a more complex BMI-specific modulation of PRP composition. In conclusion, our findings support considering BMI as a relevant factor in PRP therapy. Incorporating BMI into PRP standardization strategies could improve reproducibility and support personalized regenerative approaches. Full article

The effects of the La₂O₃/Al₂O₃ mass ratio (L/A-ratio) in electroslag on La yield and the cleanliness of La-containing H13 steel, as well as slag properties were investigated. The slag–steel interaction experiments between slags bearing varying L/A-ratios based on 50wt%CaF₂-20wt%CaO-Al₂O₃-La₂O₃ slag and La-containing H13 steel were conducted. The molecular dynamics (MD) simulation was used to estimate the viscosity, electrical conductivity, and structure of the slag. The results show that La yield increases from 5.3% to 63.2% with L/A-ratio increasing from 0.2 to 5.0 due to the increasing La₂O₃ activity and decreasing Al₂O₃ activity of slag. Thermodynamic analysis indicates that La₂O₃ content should be higher than 23.9 wt% to ensure desirable La treatment effect. The desulfurization and deoxidation ability of slag are enhanced with increasing L/A-ratio. In addition, the phosphorus and arsenic content in steel decrease when the L/A-ratio reaches 5.0, and the removal rates are 20.0% and 33.3%, respectively. This is attributed to the formation of La-O-As-S-P inclusions. The MD simulation results indicate that the increasing L/A-ratio leads to a decrease in viscosity and increase in electrical conductivity. The mechanism is that the increasing concentration of free oxygen simplifies the aluminate network and increases the mobility of ions in slag. Full article