Search Results (240)

The sustainable recovery of valuable metals such as Cu and Co from ores is a pressing need considering environmental and economic challenges. Therefore, this study evaluates the effectiveness of deep eutectic solvents (DESs) as alternative leaching agents for Cu and Co extraction. Four DESs were prepared using choline chloride (ChCl) as a hydrogen bond acceptor (HBA) and oxalic acid (OA), ethylene glycol (EG), urea (U) and thiourea (TU) as hydrogen bond donors (HBDs). Leaching experiments were conducted with DESs supplemented with 30 wt.% water at varying temperatures, various solid-to-liquid ratios, and time durations. The ChCl:OA DES demonstrated the highest leaching efficiencies among the DESs tested on pure CuO and CoO, achieving 89.2% for Cu and 92.4% for Co (60 °C, 400 rpm, 6 h, −75 + 53 µm particle size, and 1:10 solid-to-liquid ratio). In addition, the dissolution kinetics, analysed using the shrinking core model (SCM), showed that the leaching process was mainly controlled by surface chemical reactions. The activation energy values for Cu and Co leaching were 46.8 kJ mol⁻¹ and 51.4 kJ mol⁻¹, respectively, supporting a surface chemical control mechanism. The results highlight the potential of ChCl:OA as a sustainable alternative for metal recovery. Full article

Background: Hypertension is a serious global health issue affecting over one billion adults and leading to severe complications if left unmanaged. Despite medical advancements, only a fraction of patients effectively have their hypertension under control. Among the factors that hinder adherence to hypertensive drugs are the debilitating side effects of the drugs. The lack of adherence results in poorer patient outcomes as patients opt to live with their condition, instead of having to deal with the side effects. Hence, there is a need to discover new hypertension drug molecules with better side effects to increase patient treatment options. To this end, computational methods such as artificial intelligence (AI) have become an exciting option for modern drug discovery. AI-based computational drug discovery methods generate numerous new lead antihypertensive drug molecules. However, predicting their potential side effects remains a significant challenge because of the complexity of biological interactions and limited data on these molecules. Methods: This paper presents a machine learning approach to predict the potential side effects of computationally synthesised antihypertensive drug molecules based on their molecular properties, particularly functional groups. We curated a dataset combining information from the SIDER 4.1 and ChEMBL databases, enriched with molecular descriptors (logP, PSA, HBD, HBA) using RDKit. Results: Gradient Boosting gave the most stable generalisation, with a weighted F1 of 0.80, and AUC-ROC of 0.62 on the independent test set. SHAP analysis over the cross-validation folds showed polar surface area and logP contributing the largest global impact, followed by hydrogen bond counts. Conclusions: Functional group patterns, augmented with key ADMET descriptors, offer a first-pass screen for identifying side-effect risks in AI-designed antihypertensive leads. Full article

The oral epithelium is essential for maintaining oral health and plays a key role in the onset and progression of periodontitis. It serves as both a mechanical and immunological barrier and possesses antimicrobial activity. Vitamin D₃, a hormone with known immunomodulatory functions, may influence oral epithelial responses. This study investigated the effects of two vitamin D₃ metabolites on key immunological and antimicrobial functions of oral epithelial cells, both under basal conditions and during bacterial challenge. Ca9-22 oral epithelial cells were treated with 1,25(OH)₂D₃ or 25(OH)D₃ in the presence or absence of Tannerella forsythia, Fusobacterium nucleatum, or Porphyromonas gingivalis. Inflammatory responses were assessed by measuring gene and protein expression of IL-1β and IL-8. Antimicrobial activity was evaluated via expression of LL-37, hBD-2, and hBD-3, as well as direct bacterial killing assays. Expression of epithelial integrity markers E-cadherin and ICAM-1 was also analyzed. Vitamin D₃ metabolites reduced IL-8 expression and significantly increased LL-37 expression and production in Ca9-22 cells. Both forms enhanced antimicrobial activity against all tested pathogens and modulated epithelial integrity markers. Vitamin D₃ positively regulates antimicrobial and barrier functions in oral epithelial cells, suggesting a potential role in supporting oral health and preventing periodontitis progression. Full article

Marathon running exerts physical stress and may lead to transient immune dysregulation, increasing susceptibility to airway inflammation and exercise-induced bronchoconstriction (EIB). This study investigated systemic levels of antimicrobial peptides in athletes and their association with EIB. Serum concentrations of angiogenin, human beta-defensin 2 (hBD-2), major basic protein (MBP), S100A8, and S100A8/A9 were measured in 34 marathoners and 36 half-marathoners at baseline, immediately after a race, and seven days postrace using enzyme-linked immunosorbent assays and compared with 30 sedentary controls. Lung function was assessed by spirometry to identify bronchoconstriction. Levels of hBD-2 and S100A8/A9 were significantly elevated postrace in runners compared to baseline and controls, returning to baseline during recovery. During recovery, S100A8 levels remained slightly elevated in marathoners with EIB. Similarly, human beta-defensin 2 was modestly increased in runners who developed bronchoconstriction. Notably, S100A8 levels correlated negatively with lung function parameters, including forced expiratory volume and mid-expiratory flows. These findings suggest that endurance running induces systemic inflammatory responses and modulates innate immune peptides, particularly in individuals prone to bronchoconstriction. These peptides may serve as biomarkers of respiratory stress and help guide personalized strategies in endurance sports. Full article

Until recently, it was believed that bacterial translocation occurs as a result of leaky gut syndrome or sepsis. To confirm or exclude the process of bacterial translocation, biomarkers can be used. One such biomarker is defensins, which indicate immune activity, as defensins are cationic peptides with antibacterial properties produced by intestinal epithelial cells. Also, fatty acid-binding proteins (I-FABP and L-FABP) can serve as useful serological markers for intestinal epithelial damage, indicating impaired intestinal permeability or organ damage, as high concentrations of them are found in tissues and low concentrations in blood serum. In the context of obesity, the integrity of the intestinal barrier, which can be disrupted by dietary fat, leads to increased intestinal permeability. Since bacterial translocation and microbiota contribute to obesity and Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) associated with metabolic dysfunction, intestinal barrier markers can be used to study the role of the gut–liver axis. The aim of this study was to gain insight into the pathogenesis of MASLD and examine the impact of bacterial translocation markers and intestinal and hepatic fatty acid-binding proteins (I-FABP and L-FABP) in children with MASLD. Method: We examined 60 children with MASLD and overweight/obesity (MASLD was diagnosed based on increased liver echogenicity in ultrasound and elevated ALT activity), aged 14.5 years (range 8.5 to 15.8); 33 children with overweight/obesity without MASLD, aged 13.0 years (range 11.4 to 15.8); and 16 healthy controls aged 11.0 years (range 7.0 to 16.2). Defensin, I-FABP, and L-FABP levels were measured using commercial kits: ELISA kits (Drg Medtek) were used to assess α-5 and α-6 defensin concentrations (HBD5, HBD6). I-FABP and L-FABP concentrations were measured using commercial ELISA kits (Hycult Biotech Inc., Wayne, PA, USA). ANOVA analysis was used to compare results across the three study groups. Results: A significant difference was found for the following tests among children with MASLD, obesity, and healthy controls: defensin 6 (14.4 ng/mL vs. 6.13 ng/mL vs. 17.2 ng/mL, respectively), L-FABP (9168 pg/mL vs. 7954 pg/mL vs. 7620 pg/mL, respectively), and I-FABP (272 pg/mL vs. 321 pg/mL vs. 330 pg/mL, respectively). No differences were found in defensin 5 levels (median 567.2 pg/mL vs. 485.7 pg/mL vs. 601.8 pg/mL). No differences were observed in cholesterol levels (HDL, LDL) or triglyceride concentrations, as well as apolipoprotein levels. Conclusions: Based on our study, it was concluded that inflammation and intestinal barrier damage lead to increased L-FABP levels, as it is released from enterocytes in response to oxidative stress or tissue damage. Defensin 6 may indirectly affect L-FABP through microbiota regulation and protection of the intestinal barrier. Defensin 6 also exerts antimicrobial activity and may accompany liver inflammation, with its increased concentration in comparison to obesity explained by the activation of defense mechanisms. Full article

In this work, we present a study on the thermal/transport properties of a novel deep eutectic solvent (DES) obtained by using N-methyltrifluoroacetamide (FNMA) as the hydrogen bond donor (HBD) and lithium bis(trifluoromethanesulfonyl)imide (LiTFSI) as the hydrogen bond acceptor (HBA). The binary phase diagram, thermal stability, flammability, viscosity and ionic conductivity of the as-prepared DESs were investigated at atmospheric pressure. The binary phase diagram shows a range of eutectic molar ratios (x_LiTFSI = 0.2~0.33), with the lowest deep eutectic temperature of −84 °C. At x_LiTFSI = 0.2 (i.e., FNMA:LiTFSI = 4:1 and denoted as DES-4:1). The as-prepared DES composition exhibits high thermal stability (onset temperature of weight loss = 78 °C), a low viscosity (η = 48.9 mPa s at 25 °C), relatively high ionic conductivity (σ = 0.86 mS cm⁻¹ at 25 °C) and non-flammability. The transport properties, including ionic conductivity and viscosity, as a function of temperature are in accordance with the Vogel–Fulcher–Tammann (VFT) equations. With increasing molar ratio of HBD vs. HBA, the viscosity decreases, and the ionic conductivity increases at a given temperature between 25 °C and 80 °C. The roughly equal pseudo-activation energies for ion transport and viscous flow in each composition imply a strong coupling of ion transport and viscous flow. Walden plots indicate vehicular transport as the main ion transport mechanism for the DES-4:1 and DES-3:1 compositions; meanwhile, it was confirmed that the ionic conductivity and viscous flow are strictly coupled. The present work is expected to provide strategies for the development of wide-temperature-range and safer electrolytes with low salt concentrations. Full article

The rolling system for stainless steel, particularly in the production of diamond plates, represents a complex industrial control scenario. The process requires precise load distribution to effectively manage pattern height, due to the high strength, hardness, and required dimensional accuracy of the material. This paper addresses the limitations of offline methods, which include heavy reliance on initial conditions, intricate parameter settings, susceptibility to local optima, and suboptimal performance under stringent constraints. A Multi-Objective Adaptive Rolling Iteration method that incorporates local constraints (MOARI-LC) is proposed. The MOARI-LC method simplifies the complex multi-dimensional nonlinear constrained optimization problem of load distribution, into a one-dimensional multi-stage optimization problem without explicit constraints. This simplification is achieved through a single variable cycle iteration involving reduction rate and rolling equipment selection. The rolling results of HBD-SUS304 show that the pattern height to thickness ratio obtained by MOARI-LC is 0.20–0.22, which is within a specific range of dimensional accuracy. It outperforms the other two existing methods, FCRA-NC and DCRA-GC, with results of 0.19~0.24 and 0.15~0.25, respectively. MOARI-LC has increased the qualification rate of test products by more than 25%, and it has also been applied to the other six industrial production experiments. The results show that MOARI-LC can control the absolute value of the rolling force prediction error of the downstream stands of the hot strip finishing rolls within 5%, and the absolute value of the finished stand within 3%. These results validate the scalability and accuracy of MOARI-LC. Full article

Natural deep eutectic solvents (NADESs) are a sustainable, green option for extraction and reaction media in biorefineries and various chemical and biotechnological applications. Particularly, enzymatic reactions profit from NADES applications, as these solvents help to maintain high substrate solubility while improving both enzyme stability and efficiency. Recent studies confirmed that NADESs can perform multiple functions simultaneously, as reaction media for biocatalytic conversions, but also as substrates and catalysts for reactions, fulfilling the role of a reactive solvent. This study reports the beneficial effect of designed reactive natural deep eutectic solvents (R-NADESs) on the esterification activity and thermal stability of free and immobilized lipases in the synthesis of polyol- and carbohydrate-based biosurfactants. We manufactured and characterized 16 binary and ternary R-NADES systems with choline chloride (ChCl) as the hydrogen bond acceptor (HBA) and carbohydrate polyols; mono-, di-, and oligosaccharides; urea (U); N-methyl urea (MU); and water as the hydrogen bond donors (HBDs), in different combinations and molar ratios, most of which are reported for the first time in this paper. We determined their physicochemical, thermal, and molecular properties, including among others viscosity, polarizability, and the number of hydrogen bonds, and we showed that these properties are controlled by composition, molar ratio, molecular properties, temperature, and water content. Many lipases, both native and immobilized, showed high stability and remarkable catalytic performance in R-NADESs during esterification reactions. Full article

This study investigates the structural and transport properties of SDS, CTAB, and SB3-12 micelles in three deep eutectic solvents (DESs), Ethaline, Glyceline, and Reline, using molecular dynamics (MD) simulations. The influence of solvent composition on micelle morphology, interactions, and dynamics was explored, revealing key differences driven by the DES environment. Structural analyses, including eccentricity and radius of gyration, demonstrated that micelle shape and compactness vary significantly depending on the solvent. In Ethaline and Reline, larger micelles showed significant deviations from spherical shapes, while micelles in Glyceline became more spherical and compact, particularly those formed by SB3-12. Radial distribution functions highlighted different levels of micelle–solvent interactions, with SDS showing strong interactions with HBD components and SB3-12 exhibiting prominent self-interaction. According to hydrogen bonding analysis, micelles slightly disrupt the DES hydrogen bond network, with SB3-12 establishing the most significant hydrogen bond connections. The transport property analysis revealed that larger micelles have lower diffusion coefficients, whereas smaller micelles enhance DESs’ component mobility. These findings advance the understanding of micelle behavior in DESs and also help in the optimization of DES–surfactant systems for applications such as electrodeposition, nanomaterial templating, and drug delivery. Future research will focus on surfactant interactions with surfaces to further improve these applications. Full article

Natural hydrophobic deep eutectic solvents (NaHDESs), composed of natural components like menthol, fatty acids, and organic acids, are sustainable alternatives to conventional solvents for extracting carotenoids from agro-industrial by-products. This study assessed the performance of nine NaHDESs for extracting β-carotene from pumpkin peels, identifying DL-menthol/lactic acid (1:2) as the most effective solvent, achieving a yield of 0.823 ± 0.019 mg/mL of β-carotene, corresponding to 93.95% of the yield obtained using acetone. Optimization through Box–Behnken design (BBD) and response surface methodology (RSM) established ideal extraction conditions: a molar ratio of HBA:HBD at 1:4, a solvent-to-sample ratio of 26:1, and an extraction time of 30 min. These conditions maximized β-carotene recovery while minimizing energy consumption and process costs. Using NaHDESs facilitates the valorization of food waste, achieving extraction efficiencies of up to 25.05% of the theoretical carotenoid content in pumpkin peels. Their high performance and environmentally friendly profile underscore the potential of NaHDESs as sustainable alternatives to conventional solvents. Full article

Background: Numerous studies have shown the presence of multiple defence factors in placental tissue, although their role is partially understood; therefore, the aim of this study was to evaluate the expression of nuclear factor-kappa B (NF-κB); human beta-defensin 2, 3, and 4 (HBD-2,3,4); cathelicidine (LL-37); heat shock protein 60 (HSP60); and interleukin 10 (IL-10) in dissimilar gestational week placental tissue and display correlations between immunoreactive cells. Methods: A total of 15 human placental tissue samples were acquired from mothers with different gestational weeks: 28, 31, and 40. Routine staining and immunohistochemistry for the samples were executed. The evaluation of data was performed with semi-quantitative methods, and, for statistical analysis, the Kruskal–Wallis test was used. Spearman’s rank correlation was used for calculating correlations. Results: NF-κB, HBD- 2,3,4, HSP60, and IL-10 expression were discovered in every examined placental tissue cell type. LL-37 expression was found only in Hofbauer cells. A rise in expression with higher gestational weeks was noted in LL-37-positive Hofbauer cells (p = 0.03), HBD-3-positive cytotrophoblasts (p = 0.007), endothelial cells (p = 0.024), extraembryonic mesodermal cells (p = 0.004), and HBD-4-positive endothelial cells (p = 0.001). Numerous statistically significant moderate and strong positive correlations between defence factors were discovered. Conclusions: The persistence of Hofbauer cell accumulations underlines the growing significance of placental macrophages in placental protection. The expression of positive defence factors and a rise in expression in tissue protection factors (HBD-3, LL-37, HBD-4) in higher gestational weeks may indicate these factors as the most significant protectors of the placenta in ontogenetic aspects. The high number of statistically significant positive and negative correlations between positive cells show a strong network to sustain distressed placental growth and therefore pregnancy. Full article

Background/Objectives: The physiological basis underlying symptomatic versus asymptomatic premature ventricular contractions (PVCs) remains poorly understood. However, symptomatic PVCs can significantly impair quality of life. In patients without structural heart disease, symptom intensity is crucial for guiding management strategies and determining the need for medical or surgical intervention. In this study, we aimed, for the first time, to examine the associations between PVC symptoms and cardiac interoception. Methods: This study included 34 participants with PVCs (20 women; median age = 42 years; 17 participants had asymptomatic PVCs) without concomitant disorders. Interoception was assessed through interoceptive accuracy (IA) probed by two behavioral tests—mental tracking (MT) and heartbeat detection (HBD)—and the neurophysiological marker of cardiac interoception, the heartbeat-evoked potentials (HEPs). Symptom intensity scores reported by patients served as the response variable in the regression analysis, with IA and HEP as predictors. Other factors such as sex, age, percent of body fat, trait anxiety, and alexithymia were added to the models as confounding variables. Results: IA_MT was significantly higher in patients with symptomatic PVCs. IA_MT and HEP modulation for the HBD task were associated with symptom intensity. A combined regression model incorporating both metrics showed the highest predictive accuracy for symptom severity. Adding confounding variables improved model quality (lower AIC); however, only the male sex emerged as a significant negative predictor for symptom intensity. Conclusions: Our findings confirm a significant association between interoception and PVC symptom severity. Integrating behavioral and neurophysiological interoception measures enhances symptom prediction accuracy, suggesting new ways to develop diagnostic and non-invasive treatment strategies targeting interoception in PVC management. Full article

Background/Objectives: Human β-defensin 2 (HBD2) is a protein that plays an important role in activating the immune system by modulating spinal pathways and the inflammatory response. According to previous research, HBD2 was proven to be important in chronic spontaneous urticaria (CSU) (their values were significantly elevated in CSU patients, with a significant correlation between HBD2 levels and the percentage of peripheral basophils, suggesting that elevated HBD2 levels may be a potential marker of basophil and mast cell activation), which led us to additional research on the HBD2 molecule in isolated chronic angioedema. The aim of this research is to examine HBD2 values in the saliva and serum of patients with isolated angioedema, as a potential biomarker of the disease. Methods: This cross-sectional study involved a total of 102 participants, involving three groups: 33 patients with isolated chronic non-hereditary angioedema (AE) (defined as sudden onset of localized edema without chronic urticaria), 33 patients with angioedema associated with chronic urticaria (CU+AE), and 35 healthy participants (controls, CTRL). They provided a saliva sample to determine HBD2 levels using an ELISA (Enzyme-Linked Immunosorbent Assay). Subsequently, a peripheral blood sample (serum) was taken from the participants to determine HBD2 levels using the same ELISA. Results: Salivary HBD2 levels were significantly higher in those with CU+AE than in the CTRL (p = 0.019). While salivary HBD2 values differed between those with angioedema and CTRL, the serum HBD2 values did not. Also, no correlation between the levels of HBD2 in saliva and serum was found. Conclusions: Since we found that salivary HBD2 values were significantly higher in those with CU+AE than in CTRL, this points to a possible role of the HBD2 molecule in pathogenesis of AE (namely, that it induces degranulation in mast cells and vascular permeability, and has antimicrobial properties) Therefore, more research is needed to determine how reliable salivary HBD2 measurement is, as well as its significance. Full article

Today, Candida albicans is still the most common cause of both local and life-threatening systemic candidiasis. The spread of resistant fungal strains has resulted in an urgent need to search for new promising antimycotics. Here, we investigated the antifungal action of the tobacco defensin NaD1 against susceptible and resistant to azoles and echinocandins strains of C. albicans. We demonstrated that NaD1 was equally effective and fungicidal against all tested strains. The MIC and MFC values were 6.25 and 12.5 µM, respectively. We showed for the first time that NaD1 could act synergistically not only with caspofungin but also with human host defense antimicrobial peptides cathelicidin LL-37 and β-defensin-2 (HBD2) against susceptible and resistant fungal strains. Using flow cytometry, we demonstrated that NaD1 in combinations with LL-37 or HBD2 can reinforce each other by enhancing membrane disruption. Using the Caco-2 cell monolayer model, we demonstrated that NaD1 impaired the adhesion of C. albicans cells to the human epithelium. Moreover, NaD1 inhibited the formation of fungal biofilms in Sabouraud broth and less markedly in nutrient-rich RPMI-1640 medium, and enhanced the antibiofilm activity of caspofungin. Thus, we hypothesized that NaD1 might affect the development of candidiasis in vivo, including that caused by resistant fungal strains. Full article

Background: Hypertension affects 32% of adults worldwide, leading to a significant global consumption of cardiovascular medications. Atenolol, a β-adrenergic receptor blocker, is widely prescribed for cardiovascular diseases such as hypertension, angina pectoris, and myocardial infarction. According to the Biopharmaceutics Classification System (BCS), atenolol belongs to Class III, characterized by high solubility but low permeability. Currently, atenolol is commercially available in oral formulations. Increasing attention is being directed towards developing cost-effective transdermal delivery systems, due to their ease of use and better patient compliance. Eutectogels represent next-generation systems that are attracting great interest in the scientific community. Typically obtained from deep eutectic solvents (DESs) combined with gelling agents, these systems exhibit unique properties due to the intrinsic characteristics of DESs. Methods: In this study, a DES based on choline chloride as a hydrogen bond acceptor (HBA) and propylene glycol as a hydrogen bond donor (HBD) was explored to enhance the topical delivery of atenolol. The solubility of atenolol in the DES was evaluated using spectroscopic and thermodynamic measurements which confirmed the formation of hydrogen bonds between the drug and DES components. Additionally, the safety of the DES was assessed in a cell viability assay. Subsequently, we formulated eutectogels with different concentrations using animal gelatin and Tego Carbomer 140, and characterized these formulations through rheological measurements, swelling percentage, and permeation studies with Franz cells. Results: These novel eutectogels exhibit superior performance over conventional hydrogels, with a release rate of approximately 86% and 51% for Carbomer- and gelatin-based eutectogels, respectively. In contrast, comparable hydrogels released only about 27% and 35%. Conclusions: These findings underscore the promising potential of eutectogels for the transdermal delivery of atenolol. Full article