Search Results (48,191)

Ferulic acid (FA) is a bioactive compound known for its potent antioxidant and anti-inflammatory properties; however, its poor water solubility significantly limits its bioavailability and therapeutic potential. In this study, a solid dispersion of FA (FA-SD) was developed using Eudragit^® EPO via the solvent evaporation method, achieving a 24-fold increase in solubility (42.7 mg/mL) at a 1:3 drug-to-polymer ratio. Expandable gastroretentive films were subsequently formulated using starches from Hom-Nil rice, glutinous rice, and white rice, combined with chitosan as the primary film-forming agents, via the solvent casting technique. Hydroxypropyl methylcellulose (HPMC) K100 LV was incorporated as an adjuvant to achieve controlled release. At optimal concentrations (3% w/w starch, 2% w/w chitosan, and 2% w/w HPMC), the films exhibited favorable mechanical properties, swelling capacity, and unfolding behavior. Sustained release of FA over 8 h was achieved in formulations containing HPMC with either Hom-Nil or glutinous rice starch. Among the tested formulations (R6, G6, and H6), those incorporating Hom-Nil rice starch demonstrated the most significant antioxidant (10.38 ± 0.23 μg/mL) and anti-inflammatory (9.26 ± 0.14 μg/mL) effects in murine macrophage cell line (RAW 264.7), surpassing the activities of both free FA and FA-SD. These results highlight the potential of anthocyanin-rich pigmented rice starch-based expandable films as effective gastroretentive systems for enhanced FA delivery Full article

Mining and metallurgical activities negatively impact ecosystems due to the release of potentially toxic elements (PTEs). This study assesses PTE pollution and accumulation in native plant species that have spontaneously colonized a historical mining site (Michaly, site A) and a nearby metallurgical smelter site (Varvara, site B) on the Lavreotiki Peninsula, Attika, Greece. Soils were analyzed for As, Cd, Co, Cr, Cu, Fe, Mn, Ni, Pb, Sb, and Zn. A total of 89 native plant taxa across 28 families were identified. The aerial parts from dominant species were analyzed for PTE concentrations, and bioconcentration factors (BCFs) were calculated. One-way ANOVA and principal component analysis (PCA) using R were used for statistical evaluation. Soils at both sites showed elevated As, Cd, Cr, Cu, Ni, Pb, Sb, and Zn; Mn was high only at site B, while Co and Fe remained at background levels. Several plant species, especially at Michaly, had elevated concentrations of As, Cd, Co, Cr, Fe, Pb, Sb, and Zn in their aerial parts. BCFs indicated general PTE exclusion from aerial parts, particularly at site B. Native vegetation on these contaminated sites shows resilience and PTE exclusion, highlighting their potential for phytoremediation, especially phytostabilization, and ecological restoration in similarly polluted Mediterranean environments. Full article

Physical conditions in grain storage environments influence trophic interactions between predators and their prey and can affect the effectiveness of biocontrol agents. The study aimed to assess the potential of Xylocoris flavipes (Reuter) (Hemiptera: Anthocoridae), to manage Liposcelis decolor (Pearman) (Psocodea: Liposcelididae). Liposcelis decolor population suppression and X. flavipes progeny production were assessed at five predator–prey (P-P) ratios (0:240, 1:240, 2:240, 3:240, and 5:240), four temperatures (20, 24, 28, and 32 °C), and three relative humidities (RH) (63, 75, and 85%) over 40 days at 0:24 (L:D) photoperiod in the laboratory. Compared with the Control P-P ratio of 0:240 (no predators), prey suppression >97% was achieved across all predator release ratios. At 32 °C and 75% RH, which are the optimal conditions for L. decolor, 3985.13 ± 255.45 prey survived in the Control P-P ratio compared with 19.85 ± 2.47–115.73 ± 8.99 found for the four P-P ratios with the predator, representing prey reduction of 97.10–99.50%. Temperature influenced X. flavipes progeny production, which was greatest at 28 °C and a P-P ratio of 1:240. Suppression caused by X. flavipes demonstrates its potential as a biological control agent to manage psocid infestations in stored commodities. Full article

Background: Nephrolepis exaltata (sword fern) possesses a considerable amount of phytochemicals and different biological activities. The current study investigates the anti-biofilm potential of greenly synthesized bimetallic nanoparticles of Nephrolepis exaltata leaf methanol extract (NEME-MnO₂-MgO BNPs). Methods: The NEME was subjected to UPLC/MS analysis, followed by characterization of its NPs by size, zeta potential, FTIR, entrapment efficiency, and release. Then, antioxidant, antimicrobial and antibiofilm assays were employed, followed by in silico studies. Results: The UPLC/MS analysis of NEME led to the tentative identification of 27 metabolites, mostly phenolics. The MnO₂-MgO BNPs presented a uniform size and distribution and exhibited IC₅₀ values of 350 and 215.6 μg/mL, in the DPPH and ABTS assays, respectively. Moreover, the NPs exhibited antimicrobial and anti-biofilm efficacies against Pseudomonas aeruginosa, Klebsiella pneumonia (ATCC-9633), Staphylococcus aureus (ATCC-6538), Escherichia coli, Bacillus cereus, and C. albicans, with MIC values of 250–500 μg/mL. The MnO₂-MgO BNPs inhibited Candida albicans biofilms with a % inhibition of 66.83 ± 2.45% at 1/2 MIC. The network pharmacology highlighted epigallocatechin and hyperoside to be the major compounds responsible for the anti-biofilm potential. The ASKCOS facilitated the prediction of the redox transformations that occurred in the green synthesis, while the docking analysis revealed enhanced binding affinities of the oxidized forms of both compounds towards the outer membrane porin OprD of P. aeruginosa, with binding scores of −4.6547 and −5.7701 kcal/mol., respectively. Conclusions: The greenly synthesized Nephrolepis exaltata bimetallic nanoparticles may provide a promising, eco-friendly, and sustainable source for antimicrobial agents of natural origin with potential biofilm inhibition. Full article

Background/Objectives: Adapalene is a synthetic retinoid used as a treatment for acne vulgaris. In this study, we attempted to evaluate the dermal pharmacokinetics of adapalene utilizing experimental and in silico tools. Methods: We utilized three over the counter (OTC) adapalene gels to evaluate local dermal pharmacokinetics. A data-driven, robust, mechanistic dermal physiologically based pharmacokinetic (PBPK) model was developed by integrating the physicochemical properties of adapalene, the formulation attributes of the gels, and the biophysical aspects of dermal absorption. The dermal PBPK model was validated against experimental data using in vitro release studies and in vitro permeation studies with human cadaver skin. A clinical study was performed to evaluate the effects of adapalene from the three gel formulations. The impact of adapalene delivery from three gels on the stratum corneum (SC) thickness, pilosebaceous unit area, keratinocyte number, and epidermal thickness was captured using a non-invasive technique, line-field confocal optical coherence tomography (LC–OCT). These responses were evaluated using an Emax model. Results: The dermal PBPK model has successfully predicted adapalene penetration profiles across different gel formulations. The model accuracy, in predicting drug release and permeation characteristics, was confirmed using the experimental data. Clinical evaluation revealed formulation-dependent differences in adapalene’s effects on measured skin parameters, with distinct pharmacodynamic profiles observed for each gel formulation. Conclusions: The overall study gave us a detailed insight into potential effects of formulation on the dermal pharmacokinetics and pharmacodynamics of adapalene using three marketed gels. Full article

MRGPRX2 (Mas-related G protein-coupled receptor member X2) is implicated in mast cell (MC)-driven disorders due to its ability to bind diverse ligands, which may be G-protein-biased or balanced, with the latter activating both G-proteins and the β-arrestin pathway. Icatibant, a peptide drug, produces injection-site reactions in most patients and is used experimentally to probe MRGPRX2 function in skin tests. While reported to be G-protein-biased, it is unknown how skin MCs respond to icatibant, although these are the primary target cells during therapy. We therefore compared responses to icatibant with those induced by the balanced agonist substance P (SP) in skin MCs. Degranulation and desensitization were assessed via β-hexosaminidase release, receptor internalization by flow cytometry, and downstream signaling by immunoblotting. Skin MCs degranulated in response to SP and icatibant, relying on Gi proteins and calcium channels; Gq and PI3K (Phosphoinositide 3-kinase) contributed more strongly to exocytosis following icatibant, while JNK (c-Jun n-terminal kinase) was more relevant for SP. Both agonists activated ERK, PI3K/AKT, and (weakly) p38. Surprisingly, and in contrast to the LAD2 (Laboratory of Allergic Diseases 2 mast cell line) MC line, icatibant was at least as potent as SP in eliciting MRGPRX2 internalization and (cross-)desensitization in skin MCs. These findings suggest that icatibant functions differently in primary versus transformed MCs, acting as a fully balanced ligand in the former by triggering not only degranulation but also receptor internalization and desensitization. Therefore, not only the ligand but also the MRGPRX2-expressing cell plays a decisive role in whether a ligand is balanced or biased. These findings are relevant to our understanding of icatibant’s clinical effects on edema and itch. Full article

Privacy risk mining, a crucial domain in data privacy protection, endeavors to uncover potential information among datasets that could be linked to individuals’ sensitive data. Existing anonymization and privacy assessment techniques either lack quantitative granularity or fail to adapt to dynamic, heterogeneous data environments. In this work, we propose a unified two-phase linkability quantification framework that systematically measures privacy risks at both the inter-dataset and intra-dataset levels. Our approach integrates unsupervised clustering on attribute distributions with record-level matching to compute interpretable, fine-grained risk scores. By aligning risk measurement with regulatory standards such as the GDPR, our framework provides a practical, scalable solution for safeguarding user privacy in evolving data-sharing ecosystems. Extensive experiments on real-world and synthetic datasets show that our method achieves up to 96.7% precision in identifying true linkage risks, outperforming the compared baseline by 13 percentage points under identical experimental settings. Ablation studies further demonstrate that the hierarchical risk fusion strategy improves sensitivity to latent vulnerabilities, providing more actionable insights than previous privacy gain-based metrics. Full article

Background and purpose: Vulvovaginal candidiasis (VVC), caused by Candida albicans (C. albicans), is exacerbated by oxidative stress and uncontrolled inflammation. Pathogens like C. albicans generate reactive oxygen species (ROS) to enhance virulence, while host immune responses further amplify oxidative damage. This study investigates the antioxidant and antifungal properties of Hyssopus cuspidatus Boriss volatile extract (SXC), a traditional Uyghur medicinal herb, against fluconazole-resistant VVC. We hypothesize that SXC’s bioactive volatiles counteract pathogen-induced oxidative stress while inhibiting fungal growth and inflammation. Methods: GC-MS identified SXC’s major bioactive components, while broth microdilution assays determined minimum inhibitory concentrations (MICs) against bacterial/fungal pathogens, and synergistic interactions with amphotericin B (AmB) or fluconazole (FLC) were assessed via time–kill kinetics. Anti-biofilm activity was quantified using crystal violet/XTT assays, and in vitro studies evaluated SXC’s effects on C. albicans-induced cytotoxicity (LDH release in A431 cells) and inflammatory responses (cytokine production in LPS-stimulated RAW264.7 macrophages). A murine VVC model, employing estrogen-mediated pathogenesis and intravaginal C. albicans challenge, confirmed SXC’s in vivo effects. Immune modulation was assessed using ELISA and RT-qPCR targeting inflammatory and antioxidative stress mediators, while UPLC-MS was employed to profile metabolic perturbations in C. albicans. Results: Gas chromatography-mass spectrometry identified 10 key volatile components contributing to SXC’s activity. SXC exhibited broad-spectrum antimicrobial activity with MIC values ranging from 0.125–16 μL/mL against bacterial and fungal pathogens, including fluconazole-resistant Candida strains. Time–kill assays revealed that combinations of AmB-SXC and FLC-SXC achieved sustained synergistic bactericidal activity across all tested strains. Mechanistic studies revealed SXC’s dual antifungal actions: inhibition of C. albicans hyphal development and biofilm formation through downregulation of the Ras1-cAMP-Efg1 signaling pathway, and attenuation of riboflavin-mediated energy metabolism crucial for fungal proliferation. In the VVC model, SXC reduced vaginal fungal burden, alleviated clinical symptoms, and preserved vaginal epithelial integrity. Mechanistically, SXC modulated host immune responses by suppressing oxidative stress and pyroptosis through TLR4/NF-κB/NLRP3 pathway inhibition, evidenced by reduced caspase-1 activation and decreased pro-inflammatory cytokines (IL-1β, IL-6, TNF-α). Conclusions: SXC shows promise as a broad-spectrum natural antimicrobial against fungal pathogens. It inhibited C. albicans hyphal growth, adhesion, biofilm formation, and invasion in vitro, while reducing oxidative and preserving vaginal mucosal integrity in vivo. By disrupting fungal metabolic pathways and modulating host immune responses, SXC offers a novel approach to treating recurrent, drug-resistant VVC. Full article

Carbon dioxide (CO₂) released from natural or even anthropogenic sources may lead to an increase in the average global temperature and ultimately a climate shift. Thus, protecting the environment by reducing CO₂ concentration is a global concern. The recent approach of integrating CO₂ through capture, utilization, and storage seems to be an effective eradication technique. Even though a wide range of CO₂ capture strategies have been successfully adopted, there is an urgent need to compare these based on their advantages and weaknesses to define the development direction for future perspectives. Several materials have been used for capturing CO₂. Thus, we have elaborated and compared the current state of CO₂ capture strategies, including post-combustion CO₂ capture and direct air CO₂ capture. Strategies adopted under post-combustion CO₂ capture, including liquid- and solid-based sorbents, membrane-based separators, and electrochemical reduction, have been explained in detail, including their advantages, weaknesses, and potential risks. Thus, this review presents a thorough analysis of CO₂ capture in terms of material developments and manufacturing techniques, with some research gaps for future development. Full article

China’s major function-oriented zoning (MFOZ) serves as a crucial policy instrument for functional regulation of land use, playing a significant role in the latest territorial spatial planning. Studies on the implementation of MFOZ have been conducted since its release in 2012, but there is a lack of comprehensive methods to assess the effectiveness of its implementation. In China, the newly initiated City Examination provides novel technical support for verifying MFOZ planning, addressing the gap in comprehensive evaluation methodologies and channels. This study proposes a comprehensive urban assessment framework and a major function classification approach based on City Examination data, enabling the identification of implementation deviations in MFOZ planning based on the current urban conditions reflected by City Examination. The methodology incorporates dimensionality reduction, multi-indicator clustering, entropy-weighted overlays, and natural break classification techniques and examines the degree of strategic deviation in China’s MFOZ through a comprehensive and systematic assessment. Due to the timeliness and long-term nature City Examination data, the method allows for the long-time dynamic tracking and evaluation of the real-time progress in MFOZ. Empirical analysis of Hubei Province revealed that 77.9% of its urban development aligns with the 2011 MFOZ scheme while demonstrating discernible deviation types and hierarchical discrepancies, with geographically clustered patterns observed among cities exhibiting such deviations. Full article

Preeclampsia (PE) is not merely a pregnancy complication but a clinical manifestation of underlying vascular dysfunction with long-term health implications. It is diagnosed after 20 weeks of gestation as new-onset hypertension with proteinuria or organ involvement. The condition arises from impaired placental development, particularly defective spiral artery remodeling, which leads to placental ischemia and the release of antiangiogenic factors such as soluble fms-like tyrosine kinase-1 (sFlt-1) and soluble endoglin (sEng). These circulating factors contribute to systemic endothelial dysfunction, resulting in hypertension, inflammation, and multiorgan stress. Histopathological findings, including acute atherosis and abnormal vascular remodeling, further reflect the cardiovascular damage underlying PE. This review synthesizes emerging evidence on the vascular and histological mechanisms of PE, highlighting novel biomarkers such as microRNAs and neprilysin, and the potential of advanced diagnostic tools, including machine learning. Importantly, PE is now recognized not only as an obstetric disorder but also as an early marker of future cardiovascular disease. This paradigm shift emphasizes the need for personalized prevention strategies, close surveillance of high-risk women, and long-term cardiovascular follow-up. Pregnancy thus represents a critical window for early detection and intervention in women’s cardiovascular health. Full article

In 2024, the Americas experienced the largest dengue outbreak on record and Brazil was among the worst affected countries, reporting 6.6 million cases and 6200 deaths. We report the long-term entomological and epidemiological effectiveness of city-wide deployment of wMel-strain Wolbachia-infected Aedes aegypti in Niterói, a city of half a million people in Rio de Janeiro state, where Wolbachia releases across three-quarters of the urban population in 2017–2019 were expanded to remaining populated areas in 2023. wMel was durably established at ≥95% prevalence in Ae. aegypti populations throughout Niterói four years post-release, and up to seven years in the earliest release sites. Notified dengue case incidence in Niterói was 89% lower following Wolbachia releases, compared to the 10-year pre-intervention period of 2007–2016. Dengue incidence in Niterói in 2024, during a period of record high incidence in Brazil and the region, was 374 per 100,000 population, substantially lower than overall in Rio de Janeiro state (1884 per 100,000) and nationwide in Brazil (3157 per 100,000). Our findings show that city-wide Wolbachia coverage in Niterói provided sustained population-level reduction in dengue incidence throughout the five years post-intervention, including during the 2024 epidemic surge, averting an estimated three-quarters of the dengue case burden that may otherwise have been expected in Niterói in 2024. Full article

This study examined the ultrasound pretreatment (UP) and simultaneous ultrasound (US) effects on the structural–functional features of collagen peptides in Chinemys reevesii skin collagen hydrolysates (CCHs) using a composite protease system (Trypsin: Alkaline protease, 1:1). Structural characterization revealed that UP induced the unfolding of collagen molecules, evidenced by reduced disulfide bond content and the concomitant increase in surface hydrophobicity. Consequently, ultrasound pretreatment-assisted enzymatic hydrolysis (UPH) significantly enhanced the yield of low-molecular-weight components (<0.18 kDa) and hydrophobic amino acids, which rose by 3.03% and 4.89% compared to the results of conventional enzymatic treatment (CE). UPH showed higher antioxidant activity than CE and WUH over CE and whole-process ultrasound-assisted hydrolysates (WUH). At 5 mg/mL, it displayed an ABTS radical scavenging rate of 87.59%, a DPPH scavenging rate of 53.37%, and the highest reducing power. However, WUH induced peptide reaggregation due to prolonged ultrasonication, thus exhibiting moderately lower antioxidant activity than UPH. These findings suggest that UP is an effective strategy to optimize the structure and composition of CCHs, outperforming both CE and WUH in facilitating the release of antioxidant peptides and improving antioxidant capacity. Full article

The alpine marmot (Marmota marmota) once vanished from Romania’s Carpathian Mountains, but a reintroduction initiative launched in 1973 has since fostered population recovery. This study evaluates the long-term success of those efforts and explores the feasibility of further reintroductions. Population data from 2004 to 2025 across the Rodna, Retezat, and Făgăraș Mountains show a steady growth trend, culminating in a national population of approximately 815 individuals by 2025. Habitat quality was assessed using a Habitat Suitability Index, identifying robust colonies that could serve as donor populations. Additionally, an Ecological Diagnostic Key was developed to evaluate 27 potential reintroduction sites in the Țarcu, Ciucaș, and Bucegi Mountains. Findings reveal that 61 ha are suitable for reintroduction, with 40.5 ha rated as highly suitable. The study proposes a phased reintroduction strategy, combining individuals from established Romanian colonies with genetically diverse founders from Western Europe. It emphasizes soft-release protocols and calls for mitigation of anthropogenic pressures. This research supports a broader conservation framework that integrates habitat evaluation, demographic stability, and genetic health to enhance the alpine marmot’s persistence and expansion in Romania. Full article

This study presents a general overview of the important problem of pharmaceutical pollutants, aiming to draw attention to the global danger they represent and the need for concrete solutions for their remediation. Here, we summarize the available advanced knowledge on the occurrence and fate of pharmaceutical residues in the environment, particularly in water effluents, since they need a special approach when one takes into account the increasing consumption of medicines by both humans and animals, that might be discharged in aqueous systems and bio-accumulated in aquatic flora and fauna. This review details the presence of pharmaceutical wastes in water sources; their trajectories from production to consumption and release in household taps; their concentrations in natural water; methods for monitoring them; their risks; and their worldwide impacts. Adequate methods and advanced removal techniques for selected contaminants or classes of pharmaceutical compounds are discussed, together with their remediation potential and strategies. Local and global limiting proposals for these types of contaminants and concrete solutions for their remediation are recommended. Full article