Search Results (69,054)

Metformin, widely prescribed for type 2 diabetes mellitus (T2D), has emerged as a systemic immunomodulator with effects that extend far beyond glycemic control. Recent advances in immunometabolism reveal that metformin modulates innate immune responses through coordinated cellular metabolic reprogramming and epigenetic modification, which collectively modulate the functional phenotype of innate immune cells. This narrative review summarizes current evidence regarding the immunomodulatory effects of metformin on the innate immune system, with a focus on immunometabolism and epigenetic regulation. It explores how metformin modulates innate immunity by altering cellular energy sensing, mitochondrial function, and nutrient utilization. Such metabolic changes and alterations further reshape chromatin structure and architecture, as well as transcriptional profiles and programs. Through the regulation of glycolysis, fatty acid oxidation, and histone modification landscapes, metformin regulates the phenotypes of innate immune cells, which can be pro-inflammatory, tolerogenic, or homeostatic. This conceptual framework presents a new understanding of metformin. As well as acting as an anti-inflammatory agent, it may regulate immune memory. Full article

Soil salinization poses a significant global challenge to agriculture and the environment, leading to decreased soil fertility and hindered crop growth. Therefore, the development of effective and environmentally friendly soil improvement strategies is crucial for sustainable agriculture. In this study, a range of eco-friendly, versatile, and highly absorbent hydrogels for soil enhancement were created using itaconic acid (IA) as a hydrophilic monomer. Furthermore, their effectiveness and application in agriculture were thoroughly evaluated. The nano-iron-loaded IA-based hydrogels (nano-iron (III) oxide (nano-Fe₂O₃)/Poly itaconic acid (PIA)-Acrylamide (AM)/Sodium alginate (SA)) hydrogels demonstrated exceptional water absorption and retention capabilities. They exhibited remarkable soil conditioning properties by leveraging carboxyl groups for electrostatic adsorption of saline ions and the porous structure created by the crosslinked network. These features not only significantly facilitated gradual regulation of pH levels and salinity but also effectively enhanced organic matter in saline–alkali soil. Meanwhile, nano-Fe₂O₃ simultaneously served to stabilize the hydrogel structure and enhance crop nutrient absorption. Wheat cultivation trials demonstrated that the hydrogels notably enhanced the growth of 7-day-old wheat seedlings. The degradation rates of the hydrogels can be adjusted by varying the IA amount, allowing for the continuous release of small organic molecules to enhance soil quality, aligning with various crop growth cycles. Overall, these hydrogels function as environmentally friendly and versatile soil conditioners, offering significant potential for enhancing agricultural soil quality and expanding into related fields. Full article

Usnic acid (UA), a prominent lichen secondary metabolite, exhibits a unique dual therapeutic profile in dermatology, though its clinical translation is limited by systemic hepatotoxicity and poor solubility. This review comprehensively evaluates the topical efficacy, molecular mechanisms, and advanced formulation strategies of UA enantiomers and UA-rich extracts. A literature search across PubMed, Scopus, and Google Scholar identified 36 original publications focusing on anti-melanoma activity, photoprotection, and tissue regeneration. In vitro studies demonstrate that UA induces apoptosis in resistant melanoma cell lines (A375, HTB-140) via extrinsic/intrinsic pathways, with (−)-UA effectively overcoming doxorubicin resistance. Conversely, in non-cancerous models, low concentrations of UA accelerate wound and burn healing by upregulating vascular endothelial growth factor (VEGF), stimulating fibroblast proliferation, and optimizing extracellular matrix remodeling while preventing hypertrophic scarring. To mitigate skin sensitization and systemic risks, advanced drug delivery systems—including liposomes, nanoemulsions, chitosan nanogels, and electrospun scaffolds—have been developed, significantly enhancing skin permeability and localized dermal retention. Ultimately, the development of bio-functionalized smart dressings and targeted nano-formulations represents the most viable path toward unlocking the full clinical potential of UA in modern dermatological and oncological care. Full article

This study evaluated the effects of dietary inclusion of free and protected acid protease on productive performance, milk composition, metabolic profile, nutrient digestibility, and ruminal environment in lactating Jersey cows. Fifteen multiparous cows (67 ± 7.5 days in milk; 27.5 ± 3.5 kg/day) were assigned to a 3 × 3 Latin square (5 squares) design with 21-day periods. Treatments consisted of: control (no enzyme), free protease (4.4 g/day), and protected protease (4.4 g/day). The protected form was developed using alginate-based encapsulation to enhance enzyme stability under ruminal conditions. Protease inclusion did not affect dry matter intake, milk yield, or feed efficiency (p > 0.05). However, free protease increased lactation persistency (p = 0.05) and improved fat-corrected and energy-corrected milk yields (p ≤ 0.02), with intermediate responses observed for protected protease. Milk fat and protein contents were higher in enzyme-fed cows (p ≤ 0.05), while other compositional parameters remained unchanged. Apparent crude protein digestibility was greater in cows receiving free protease (p = 0.037), with no effects on dry matter or fiber digestibility. Protease intake increased total volatile fatty acid concentrations and major fermentation products (acetate, propionate, and butyrate; p ≤ 0.01), indicating enhanced ruminal fermentation. Blood metabolites showed increased total protein and globulin levels in cows fed free protease (p ≤ 0.05), suggesting improved protein metabolism. Microbiota analysis revealed no differences in alpha or beta diversity; however, specific microbial taxa and predicted metabolic pathways were modulated by treatments, particularly in post-ruminal compartments. In conclusion, exogenous protease, especially in free form, improved protein utilization and corrected milk production without disrupting microbial stability. These findings highlight the potential of protease as a nutritional strategy to enhance efficiency in dairy systems through targeted modulation of ruminal function and nutrient metabolism. Full article

Edible insects are increasingly recognized as a viable alternative protein source, offering a potentially sustainable approach to addressing global food security challenges. This narrative review critically examines the nutritional composition, environmental advantages, techno-functional attributes, and potential applications of insect-based proteins within human food systems. Edible insects are characterized by high protein content, favourable essential amino acid profiles, and appreciable levels of key micronutrients, rendering them nutritionally comparable to conventional livestock-derived proteins. Moreover, insect production systems generally require substantially lower inputs of land, water, and feed, resulting in comparatively lower greenhouse gas emissions and reduced overall environmental burden. Despite these advantages, broader adoption remains constrained by challenges related to regulatory heterogeneity, food safety concerns, and limited consumer acceptance. Overall, the available evidence suggests that edible insects can function as a nutritionally adequate and environmentally sustainable complementary protein source; however, significant variability in nutrient composition, limitations in standardized safety assessment, and socio-cultural barriers currently restrict their large-scale integration into mainstream food systems. In addition, inconsistencies in analytical methodologies and reliance on in vitro data further complicate cross-study comparisons and translational relevance. Future research should focus on standardization of rearing and processing conditions, harmonization of evaluation frameworks (e.g., protein quality indices), comprehensive safety assessments, and well-designed clinical studies to validate nutritional and functional benefits, alongside the development of effective strategies to improve consumer acceptance and support regulatory alignment across regions. Full article

In Chile, Eucalyptus globulus stands out as a significant forest species, yielding around 2 million tonnes of bark; this by-product is a valuable source of phenolic compounds. This research evaluated the valorization of E. globulus bark using alkali-assisted extraction (AAE) and obtained extracts intended to protect the wood against fungal degradation and ultraviolet (UV) radiation. The chemical and thermal properties of the extracts were characterized using total phenolic content (TPC), antioxidant capacity, FTIR spectroscopy, LC-LTQ-Orbitrap-MS, and thermal analyses (TGA and DSC). Pine wood samples were impregnated using the Bethel process, and their absorption, retention, leaching, UV resistance, gloss, and antifungal efficacy were evaluated. The AAE showed an extraction yield of 8.79%, almost double that of aqueous extraction, with a phenolic content of 970 mg GAE/100 g dry bark and good antioxidant capacity. The MS/MS analysis tentatively identified low-molecular-weight organic acids, phenolic acids, a hydrolyzable tannin derivative, ellagic acid, methylated flavonol glycosides, and an iridoid non-phenolic metabolite. Thermal analysis indicated greater stability of the alkaline extracts, with a mass loss of less than 10% up to 200 °C, and significant degradation between 220 and 300 °C. Leaching tests showed a lower release of polyphenols from alkali-treated wood, indicating reduced mobility and/or greater retention of the extractives within the wood structure. Biological assays demonstrated effective inhibition of stain fungi and strong resistance to brown rot. Furthermore, UV aging tests showed less color change (Delta E*) and greater resistance to surface degradation. These results demonstrate the potential of alkaline extracts from E. globulus bark as sustainable additives for wood protection. Full article

Sustainable management of permanent grasslands requires evidence-based selection of fertilization practices that support long-term soil organic matter quality and ecosystem function. This study addresses the need to identify optimal agricultural practices in permanent grasslands and the effects of organic and inorganic fertilizers on soil humic substances (HS) composition and stability. Grassland plots were amended after cutting with mineral fertilizer (NPK), farmyard manure (FYM), cattle slurry (CS), or digestate (DIG), and humic acids (HA) were isolated using the standard International Humic Substances Society procedure. The elemental composition, total carbon and nitrogen contents, C/N ratio, and selected biogenic elements were determined using routine laboratory methods, while infrared spectroscopy, fluorescence excitation–emission matrix analysis, and electron paramagnetic resonance spectroscopy were applied to characterize chemical structure and semiquinone radical concentrations. Principal component analysis (PCA) indicated distinct clustering of fertilization treatments, which was supported by a statistically significant effect (p < 0.05) based on ANOVA. The results suggest that the fertilization regime was associated with variation in HS composition and radical abundance. DIG and NPK treatments showed lower O/C ratios and radical concentrations, potentially reflecting more reduced humic acids. In contrast, FYM and CS treatments tended to exhibit higher radical concentrations and O/C ratios. These findings highlight the importance of fertilizer type in shaping soil organic matter dynamics in managed grassland ecosystems and provide a scientific basis for the development of sustainable soil management strategies and environmentally sound fertilization practices in permanent grassland systems. Full article

Background and Objectives: Ticagrelor reduces ischemic events in acute coronary syndrome (ACS) but increases bleeding risk. Clinical predictors of bleeding are well established; the contribution of cytochrome P450 polymorphisms involved in ticagrelor metabolism remains uncertain, with conflicting reports in the literature. We examined the association of CYP3A4* 22 (rs 35599367), CYP3A5* 3 (rs 776746), and CYP4F2 (rs3093135) with bleeding in a Serbian ACS cohort. Materials and Methods: This prospective, single- center observational study enrolled 105 consecutive ACS patients undergoing percutaneous coronary intervention (PCI) or medical management after coronary angiography and receiving dual antiplatelet therapy (DAPT) with acetylsalicylic acid and ticagrelor at the University Clinical Center Niš between January 2024 and the end of May 2025. Bleeding events occurring during the index hospitalization and the six-month follow-up were classified according to the Bleeding Academic Research Consortium (BARC) criteria. Genotyping used TaqMan assays. Associations with bleeding were assessed using Firth’s penalized logistic regression, with multivariable adjustment for age and renal function. Severity-stratified analyses and gradient-boosted machine learning (XGBoost with SHAP) were performed as exploratory analyses. Results: Thirteen patients (12.4%) experienced bleeding (nine minor [BARC 1/2], four major [BARC 3/5]). Age ≥ 75 years (univariable OR 7.62, p = 0.001) and eGFR < 60 mL/min/1. 73 m ² (OR 3.68, p = 0.006) were the strongest predictors. CYP3A5 *1 carrier status was univariably associated with bleeding (OR 4.16, p = 0.043) but did not remain significant after adjustment for age and renal function, and *1 carriers were significantly older and more likely to have impaired renal function. No genotype was associated with major (BARC 3/5) bleeding. The apparent effect was concentrated in minor bleeding (BARC 1/2 rate: 30.8% versus 5.5%), with no major events among *1 carriers. CYP 3 A 4* 22 (OR 1.37, p = 0.109) and CYP 4 F 2 (OR 1.17, p = 0.111) showed no association. Machine-learning analyses confirmed eGFR and age as the dominant predictors. Conclusions: In this Serbian ACS cohort, clinical factors—particularly advanced age and impaired renal function—dominated the prediction of bleeding risk. The CYP3A5 signal was largely explained by baseline imbalances in age and renal function. CYP 3 A 4* 22 and CYP 4 F 2 polymorphisms did not contribute additional predictive information. Preemptive genotyping for these variants is unlikely to materially improve bleeding-risk assessment beyond standard clinical evaluation in patients of this type. Full article

Admiralty brass, commonly used in heat exchangers, is particularly susceptible to corrosion in acidic media such as those used in industrial cleaning. To mitigate this problem, the present study evaluated Musa acuminata (banana) peel and Lupinus mutabilis Sweet (Andean lupine) extracts as sustainable, low-toxicity corrosion inhibitors for admiralty brass in 0.5 M HCl. Six extracts were prepared using different solvents and characterized by qualitative and semi-quantitative phytochemical analyses (phenols, flavonoids, alkaloids). M. acuminata extracts were rich in phenolic compounds, while L. mutabilis extracts contained high levels of quinolizidine alkaloids. A comparative electrochemical screening of the agro-industrial waste-derived extracts revealed that the inhibition efficiency of M. acuminata extracts reached up to 43.6%, whereas the debittering wastewater extract of L. mutabilis (E6) achieved a maximum efficiency of 85.5% at 2000 ppm. A preliminary techno-economic analysis indicated the feasibility of industrial-scale production of the L. mutabilis-based inhibitor, yielding a net present value (NPV) of USD 9.48 million, an internal rate of return (IRR) of 27.3%, and a payback period of 6.7 years. These results demonstrate that agro-industrial residues can be valorized into effective and profitable green corrosion inhibitors, aligning with circular economy and sustainable chemistry principles. Full article

Diabetes mellitus (DM) is a complex metabolic disorder characterized by chronic hyperglycemia and represents a major global public health concern due to its rapidly increasing prevalence. Although current pharmacological therapies effectively achieve glycemic control, their long-term use is limited by adverse effects, high costs, patient compliance issues, and increasing interest in safer, multi-targeted therapeutic strategies. In this context, plant-derived bioactive compounds have gained attention as complementary or alternative approaches to metabolic disease management. Gymnema sylvestre (Retz.) R.Br. ex Sm (GS), traditionally known as “gurmar” (“sugar destroyer”), is one of the most extensively studied medicinal plants with significant antidiabetic potential. This review evaluates the antidiabetic effects of G. sylvestre, focusing on its phytochemical composition, molecular mechanisms, and impact on diabetes-related complications. Major bioactive constituents, including triterpenoid saponins (gymnemic acids), gurmarin-like peptides, flavonoids, and sterols, regulate glucose homeostasis, inhibit intestinal glucose absorption, preserve pancreatic β-cell function, stimulate insulin secretion, modulate lipid metabolism, and suppress inflammatory signaling pathways. Experimental and clinical evidence indicates that G. sylvestre modulates oxidative stress and inflammation associated with complications such as nephropathy, neuropathy, retinopathy, vascular dysfunction, and dyslipidemia. This review adopts a mechanism-oriented framework integrating phytochemical structure–molecular target–metabolic outcome relationships and discusses emerging strategies, including nanotechnology-based delivery systems, molecular docking, and multi-component phytotherapy. Overall, G. sylvestre represents a promising multi-target phytotherapeutic agent, highlighting directions for future mechanistic and clinical research. Full article

Bile acids are important for lipid digestion and metabolic regulation, but the roles of individual bile acids in crustaceans remain unclear. This study evaluated the effects of six dietary monomeric bile acids on growth and lipid metabolism in juvenile Pacific white shrimp. Juvenile shrimp (2.5 g) were fed a basal diet or the same diet supplemented with 0.04% bile acid (cholic acid, hyodeoxycholic acid, chenodeoxycholic acid, deoxycholic acid, ursodeoxycholic acid, or hyocholic acid) for 8 weeks. Each treatment was assigned to three replicate 100-L tanks, with 30 shrimp per tank. Dietary monomeric bile acids did not significantly affect growth performance, body composition, or muscle fatty acid composition. Compared with the control group, chenodeoxycholic acid, deoxycholic acid, and hyocholic acid significantly reduced the hemolymph triglyceride levels, while cholic acid, chenodeoxycholic acid, and hyocholic acid lowered the hepatopancreatic lipid levels. All bile acid treatments reduced the hepatopancreatic malondialdehyde content compared with the control group. Expression of genes related to bile acid transport, sterol metabolism, and lipid catabolism was generally upregulated by bile acids, indicating enhanced bile acid circulation and lipid turnover. In conclusion, monomeric bile acids mainly regulate lipid metabolism and oxidative status rather than directly promoting growth under the present dietary condition, with chenodeoxycholic acid, cholic acid, and deoxycholic acid showing relatively stronger effects. Full article

Objective: Glutamic acid decarboxylase 65 (GAD65) antibody-associated epilepsy often presents as chronic focal epilepsy, usually with temporal lobe predominance, marked drug resistance, and inconsistent response to first-line immunotherapy. We assembled a large, harmonized, and literature-derived patient-level cohort to examine whether immunotherapy timing and regimen composition were associated with seizure outcome and to identify clinically meaningful prognostic signals. Methods: We performed a literature-derived patient-level analysis of 375 unique published cases linked to 132 contributory source publications from an audited full-text register of 166 reviewed studies. Descriptive analyses used the whole cohort. Treatment-response analyses assessed seizure outcome at the first evaluable post-immunotherapy assessment and at the last follow-up. Good seizure outcome was defined as seizure freedom and/or ≥50% seizure reduction. The primary timing comparison contrasted early treatment, defined as immunotherapy within 6 months of symptom onset, with late treatment, defined as immunotherapy after more than 12 months; four cases treated in the intermediate >6 to ≤12 month window were retained for descriptive timing summaries but excluded from the primary comparison. Statistical testing used the Fisher exact, Chi-square, Mann–Whitney U, and prespecified clustered logistic sensitivity analyses where appropriate. Results: The pooled phenotype was predominantly female, usually temporal-lobe-based, and frequently drug-resistant, with common autoimmune comorbidity and heterogeneous MRI abnormalities. Among timing-evaluable treated cases, earlier immunotherapy showed a class-specific, exploratory signal rather than a uniform regimen-independent effect. In rituximab/CD20-directed regimens, early treatment was associated with a higher rate of good seizure outcome than late treatment at both the first post-immunotherapy assessment and last follow-up (93.8% vs. 50.0%; risk difference [RD]: 43.8 percentage points; 95% CI: 7.7 to 72.7). A similar pattern was observed in the broader escalation group (94.4% vs. 55.6%; RD: 38.9 percentage points; 95% CI: 6.3 to 68.1). By contrast, steroid-containing regimens showed no clear early-versus-late advantage (84.6% vs. 88.2%; RD: −3.6 percentage points; 95% CI: −18.4 to 20.1). Shorter epilepsy duration before immunotherapy and absence of established drug resistance were the most clinically meaningful favorable baseline features. Significance: In GAD65 antibody-associated epilepsy, the therapeutic window may be most relevant for escalation strategies rather than for steroid-containing first-line regimens. However, these class-specific findings are exploratory and hypothesis-generating. They derive from non-randomized, literature-derived data and may reflect treatment intensity, center practice, publication era, and confounding by indication rather than isolated regimen superiority. Prospective collaborative registries with standardized longitudinal seizure outcome measures are needed to validate these observations. Full article

Generative artificial intelligence (AI) is transforming biological and medical research and data analysis. Beyond analyzing existing information, these models can learn complex patterns and generate new data such as realistic protein sequences, genetic variants, or clinical notes. In molecular biology, language-like sequence models can read and generate DNA, RNA, and amino acid sequences to predict genetic variant effects, design new proteins, and explore molecular functions. In medicine, large language models (LLMs) trained on biomedical literature and electronic health records (EHRs) can summarize clinical findings, identify patterns, and provide decision support for clinicians and healthcare providers. Additionally, synthetic data generation can help protect patient privacy and augment existing disease datasets. While these advances make tasks that were previously impractical possible at scale, they also carry major risks, including producing convincing but incorrect results, reflecting hidden biases in the training data, and underperforming when real-world conditions change. Full article

Organic citrus production in semi-arid Mediterranean regions is increasingly challenged by water scarcity, soil degradation, and rising phytosanitary pressure associated with climate change. This study evaluated different sustainable management strategies under commercial organic citrus production conditions in the Andarax Valley (Almería, southeastern Spain). Two complementary field trials were conducted: (i) the assessment of four weed management systems—shallow tillage, mechanical mowing, sown cover crop, and partial manual mowing—and (ii) the comparison of four mass-trapping systems for the control of Ceratitis capitata. Fruit quality parameters, yield performance, and trapping efficacy were evaluated under commercial organic farming conditions. Weed management treatments did not significantly affect internal fruit quality parameters, including juice content, total soluble solids, titratable acidity, and maturity index, which were mainly determined by cultivar-related factors. In contrast, yield showed significant responses to treatment, growing season, and cultivar. The sown cover crop treatment (T3) produced the highest mean yields in both growing seasons, reaching 56.6 and 72.9 kg tree⁻¹ in seasons 1 and 2, respectively. In the mass-trapping trial, the liquid trap baited with hydrolyzed protein (R-9) showed the highest capture efficacy (0.060 flies trap⁻¹ day⁻¹), significantly outperforming the control treatment (0.014 flies trap⁻¹ day⁻¹) and the other evaluated trapping systems. Conversely, dry trap models (A-9 and V-8) recorded significantly lower capture rates (FTD < 0.01), which may be associated with lower retention efficiencies documented in the literature for dry-killing designs. All treatments exhibited high female selectivity (>94%). In addition, a pronounced edge effect was detected, with significantly higher captures concentrated along the orchard perimeter. Overall, the results support the integration of functional cover crops and perimeter mass-trapping strategies as sustainable tools to improve resilience and pest management in Mediterranean organic citrus production systems. Full article

3D-printed continuous carbon fiber-reinforced polylactic acid (CF/PLA) composites combine the high load-bearing capability of continuous fibers with the structural design freedom of additive manufacturing, showing broad application prospects in lightweight complex structures. However, the chemically inert surface of carbon fibers and their insufficient interfacial compatibility with the PLA matrix lead to inefficient interfacial load transfer, thereby limiting the mechanical performance of the composites. In this study, a waterborne polyurethane (WPU)-based sizing treatment was applied to carbon fibers to enhance the fiber–matrix interface of 3D-printed continuous CF/PLA composites. The WPU sizing layer increased fiber-bundle cohesion and introduced a transition region between CF and PLA through possible hydrogen bonding, dipolar interactions, and physical adhesion. When the nominal WPU concentration was 5 wt%, the apparent interfacial shear strength reached 1.31 MPa, representing an improvement of approximately 65% compared with ACF/PLA. The three-point flexural strength reached 69.76 MPa, which was 55.3% higher than that of the ACF/PLA composite. These results indicate that WPU sizing is an effective and scalable interfacial regulation strategy for improving the mechanical properties of 3D-printed continuous CF/PLA composites. Full article