Search Results (455)

Ultraviolet (UV) radiation is a main environmental factor responsible for skin damage, leading to oxidative stress, inflammation, and impairment of the skin barrier function. Furthermore, many components in sunscreen may accumulate in aquatic systems, causing environmental pollution. Therefore, the identification of novel natural bioactives that counteract these effects and can be useful as effective adjuvants in sunscreen formulations is of particular interest. Morin (1), a natural flavonoid, represents an attractive scaffold for modifications to enhance its biological activity. Herein, we aimed to investigate the effects of combining the flavonoid 1 and its derivative, morin semicarbazone (2), with the carotenoid fucoxanthin (FX) on UVB-exposed HaCaT keratinocytes. All compounds exhibited higher radical scavenging activity compared to Trolox. In this cell model, the phenolic–carotenoid combinations provided greater photoprotection than individual compounds, significantly enhancing cell viability and reducing necrosis, FX-2 emerged as the most potent combination, as evidenced by a marked reduction in reactive oxygen species (ROS) and malondialdehyde (MDA) levels, likely mediated through the activation of the nuclear factor erythroid 2-related factor 2/Heme oxygenase-1 (Nrf2/HO-1) signaling pathway. Furthermore, the tested treatments exerted enhanced anti-inflammatory effects by significantly reducing interleukin-6 (IL-6), cyclooxygenase 2 (COX-2), and matrix metalloproteinase-9 (MMP-9) mediators, with FX-2 being the most active combination. In conclusion, our findings highlight the protective effects of the combinations of these phenolics with the carotenoid FX against UVB radiation and support their potential application as natural active ingredients in sunscreen formulations. Full article

Background: Achieving and maintaining therapeutic anticoagulation with unfractionated heparin in critically ill patients is challenging due to biologic variability, heparin resistance, and limitations of activated partial thromboplastin time (aPTT) monitoring. Argatroban, a direct thrombin inhibitor, provides antithrombin-independent anticoagulation with more predictable pharmacokinetics, but real-world data describing its anticoagulation stability in the intensive care unit (ICU) remain limited. Objective: This study aimed to compare anticoagulation stability between continuous intravenous argatroban and unfractionated heparin in critically ill patients using time in therapeutic range (TTR) based on aPTT as the primary performance metric. Methods: A retrospective cohort study was conducted in the ICU and step-down unit of Hôpital Montfort (Ottawa, ON, Canada) between January 2016 and December 2024. Adult patients receiving continuous intravenous argatroban or unfractionated heparin for systemic anticoagulation were included. All aPTT values obtained during active infusion were extracted, and TTR was calculated using linear interpolation between consecutive measurements. Continuous variables were summarized as medians with interquartile ranges and compared using the Wilcoxon rank-sum test; categorical TTR strata were compared using Fisher’s exact test. Results: Sixty-eight patients met the inclusion criteria, contributing 9 argatroban and 61 heparin infusion courses. Argatroban demonstrated a higher median TTR than heparin (83.3% [IQR 82.0–90.7] vs. 47.5% [32.9–62.4]; p < 0.001), with a moderate-to-large effect size (r = 0.51). Median aPTT values were similar between groups, but argatroban showed narrower dispersion and fewer prolonged subtherapeutic periods. A majority of heparin courses (56.5%) spent <50% of time within range, whereas no argatroban courses fell into this category. Conversely, 33.3% of argatroban courses achieved ≥90% TTR compared with none in the heparin group. Conclusions: In this real-world ICU cohort where argatroban was used for suspected or confirmed HIT, argatroban was associated with higher TTR than unfractionated heparin. These findings support the use of time-dependent metrics to evaluate anticoagulation quality and warrant prospective studies in more homogeneous populations. Full article

This research considers, by a conceptual and philosophical–legal perspective, the tensions between the interest of harmonization of intellectual property and the protection of Intangible Cultural Heritage. Starting from the fact that the harmonization of IP has been promoted as a strategy of global legal integration, normative predictability, and legal certainty for transnational economic agents, this study underpins the challenges that cross this intention. ICH is also observed as a legal category grounded on collective, dynamic, and culturally situated logics. The article briefly remarks a critical reading regarding possible conceptual incompatibilities between these regimes, showing through pensée complexe that such tensions stem from deeper divergences, associated with the predominance of a unidimensional and reductive view of the relationship between IP and ICH. Full article

Pre-fattening (also referred to as nursery culture) of Manila clam is a priority for this sector of aquaculture, as it allows hatchery-produced seed (1–3 mg) to reach sowable juvenile sizes of 30–100 mg and reduces reliance on natural juvenile recruitment. This study evaluated the efficiency of two early pre-fattening systems, both in economic terms and in product quality: conventional upwelling units (a high-density system) and flat-bottom tanks (a mid-density system), the latter tested with and without a sand layer. The 51-day trial was conducted under autumn environmental conditions (temperature 13–25.8 °C; salinity 25–28 ppt; chlorophyll-a 3–24 µg/L), starting with 1.34 mg seed maintained under a water flow rate ≥ 15–20 mL/min/g. In upwelling units, the initial density was ~216 ind./cm². Four grading events produced four size classes, with total mean weights ranging from 6.4 mg in the smallest (tails) to 46.3 mg in the largest (heads). The overall population mean size was 19.0 mg, with a specific growth rate (SGR) of 5.2%/day and mortality of 17.6%. Flat-bottom tanks, stocked at ~30 ind./cm², achieved higher growth (overall weighted mean: 28.0 mg; SGR ~6%/day), but exhibited higher mortality (26.0% on average), with no significant effect from the presence of bottom sand. Overall, flat-bottom systems showed promising growth performance with reduced labor requirements, suggesting that this system could represent a viable alternative to upwelling. However, the associated rearing protocol could still be improved by optimizing stocking density and water exchange rates. Full article

Background/Objectives: Pharmacogenomics (PGx) enables personalized therapy by identifying genetic variants that influence drug response. Despite the advantages of next-generation sequencing (NGS), few clinically validated, guideline-aligned panels comprehensively detect common, rare, and structurally complex pharmacogenetic variants. Methods: We developed and analytically validated Action PharmaKitDx, a targeted NGS panel covering 335 pharmacogenes, including all priority genes recommended by CPIC, DPWG, and CPNDS. Performance was assessed using Coriell HapMap and GeT-RM reference materials across multiple library preparation workflows and Illumina platforms. Clinical feasibility was evaluated in 41 patient samples from diverse specialties. Results were compared with established reference methods, including PCR-based assays, STR analysis, Sanger sequencing, and whole-exome sequencing. Results: Analytical validation: More than 99% of target bases achieved ≥30× coverage. Analytical accuracy, sensitivity, specificity, and positive predictive value exceeded 99.3%, with repeatability and reproducibility >99.7%. Concordance with GeT-RM haplotypes reached 98% after star-allele harmonization. The panel accurately detected complex variants, including CYP2D6 copy-number changes and hybrid alleles. Clinical validation: Full concordance with prior genotyping was observed in clinical samples. Beyond the initial testing indication, each sample harbored a mean of six actionable variants (range 2–10). Thirty-six rare (minor allele frequency <1%) potentially actionable variants were additionally identified. Conclusions: Action PharmaKitDx demonstrates high analytical performance and broad clinical applicability, supporting its implementation as a scalable solution for comprehensive pharmacogenetic testing and precision prescribing. Full article

Peroxisome proliferator-activated receptor γ (PPARγ), encoded by the PPARG gene on chromosome 3p25.2 in humans, is a ligand-dependent transcription factor that belongs to the nuclear receptor family. In various tissues, PPARγ controls cell differentiation, proliferation, or fusion. Its essential role in the development and functions of the placenta is now well established. To date, the specific functions of its RNA isoforms, encoded by ten exons, in trophoblast biology, including cell fusion and invasion, remain unknown. As translation is mainly regulated by the 5′UTR sequences of mature mRNA, this region was analyzed, and four previously unreported exonic sequences were revealed. Their expressions were confirmed and quantified in villous cytotrophoblasts from term placenta and in chorionic villi from both first-trimester and term placenta. Distinct expression patterns were observed: one exon showed weak expression in placental and chorionic cells, another exhibited stable expression throughout pregnancy, while two exons specific to villous cytotrophoblasts displayed increased expression during the first trimester, suggesting a role in oxygen-responsive mechanisms. Among these, one may be involved in villous trophoblast differentiation. These findings demonstrate that the PPARG gene is composed of 14 exons and is highly regulated depending on cell type and the stage of cell differentiation. Full article

Systemic risk in banking systems arises from losses transmitted through networks of contractual exposures. Yet, most widely used measures rely on market-implied volatility and equity prices rather than structural balance sheet fragilities. This paper develops a flow network framework that models systemic risk as a capacity-constrained loss-diffusion process governed by flow conservation, contractual seniority, and interbank topology. Using regulatory balance sheet data for four major U.S. banks across six quarters of the 2007–2008 financial crisis, we simulate millions of unit-consistent cascade scenarios to characterize the distribution of bank failures and aggregate losses. Despite severe macro-financial stress, the system remains in a subcritical contagion regime, exhibiting frequent single-bank failures, virtually no multi-bank cascades, and quasi-stationary aggregate losses concentrated around USD 420–430B.We extend the model to a stochastic setting in which the initial shock magnitude is randomized while propagation mechanics remain deterministic. The resulting loss distribution remains tightly concentrated and scales approximately linearly with shock size, suggesting that uncertainty in shock realizations does not induce nonlinear cascade amplification. Applying an efficient network benchmark, we estimate that 10–23% of expected systemic loss is attributable to suboptimal network architecture, implying potential gains from structural policy intervention. A comparison with SRISK reveals early divergence and convergence only at peak stress, highlighting the complementary roles of structural and market-based systemic risk measures. Finally, a graph neural network trained on synthetic flow network data fails to reproduce threshold-driven cascade dynamics, underscoring the importance of considering network structures vis-à-vis data-driven approaches. Full article

Knowledge of the trace element contents of petroleum can improve crude oil exploration and refining and aid environmental studies. Analytical challenges prompt experimentation with various digestion methods and analytical techniques, but the assessment of the efficiency of applied methodologies is hindered by the scarcity of multi-element standard reference materials. In this study, NIST SRM 1634c residual fuel oil and NIST RM 8505 crude oil were subjected to (i) hotplate acid digestion and (ii) one, two or three cycles of microwave acid digestion, and analyzed by ICP-MS. Comparison with the few available certificate values shows optimum recoveries for both reference materials with two and three cycles of microwave digestion. Hotplate digestion can also efficiently decompose petroleum, although this procedure requires more time and reagents than the microwave digestion. To better characterize the trace element composition of the two reference materials for future use in the community, we integrate our new results with a comprehensive compilation of published trace element data for both petroleum samples. Finally, we show that the V/Ni and V/(V + Ni) ratios commonly used for oil–oil and oil–source rock correlations remain sufficiently close to the expected ratios even in cases of incomplete digestion with lower recoveries for both elements. Full article

This study systematically maps how artificial intelligence (AI) has been applied within finite-element (FE)-based structural engineering. A corpus of 5995 unique English-language publications was compiled and classified by discipline, with 3345 relevant papers further categorized by application group. A representative subset of 372 studies underwent detailed full-text classification across seven analytical dimensions covering AI methods, element formulations, materials, and structural objects. The analysis reveals rapid growth after 2015, including a pronounced expansion of surrogate modeling and data-driven prediction methods. The disciplinary composition of the literature has also evolved, with structural engineering studies becoming more prominent in recent years relative to earlier decades. Optimization & Design remains the largest application area across the full dataset, while Structural Performance Prediction and FEM Acceleration/Surrogate Modeling show the fastest growth, reflecting increasing emphasis on predictive, solver-efficient, and hybrid physics–data approaches. These findings indicate a maturing field in which AI is increasingly embedded across all stages of FE-based analysis and design. This study provides a structured overview of methodological patterns, identifies emerging hybrid strategies, and highlights opportunities for future research and industrial integration. Full article

This study examines the social, economic and cultural impacts that Latin American women face due to climate-induced displacement, considering these impacts as arenas of conflict and negotiation. Using an intersectional framework, the study analyses how climate disasters exacerbate structural inequalities rooted in patriarchal systems, thereby constraining women’s adaptive capacity while simultaneously catalysing resistance strategies. Through a comparative analysis of Bangladesh and the Dry Corridor in Central America using a Gender Vulnerability Index (GVI), the study reveals that displaced women navigate contested spaces, disputing access to resources, legal recognition and territorial belonging, while constructing transnational solidarity networks and cooperative economies. The emergence of women climate refugees challenges international legal frameworks, exposing critical gaps in protection regimes. The findings emphasise the need for gender-responsive policies that recognise women as transformative agents who negotiate power asymmetries in contexts of environmental crisis, not merely as vulnerable populations. This research contributes to our understanding of the nexus between climate change, gender and migration by foregrounding the dialectic of domination and agency in Latin American displacement processes. Full article

Background/Objectives: Acetaminophen (paracetamol or APAP) overdose is a major cause of acute liver injury mediated by oxidative stress, inflammation, and hepatocellular necrosis. The present study investigates the in vivo hepatoprotective potential of morin (M), lignin nanoparticles (LN), and morin-encapsulated lignin nanoparticles (LMN) against APAP-induced hepatotoxicity in mice. The specific goal was to determine whether LMN could strengthen hepatic antioxidant and anti-inflammatory defenses prior to toxic insult, which aligns with a prophylactic model rather than a post-injury clinical rescue approach. This study was guided by the primary hypothesis that LMN pretreatment would markedly reduce APAP-induced hepatic injury. Methods: Experimental groups included control, APAP, M, LN, LMN, M+APAP, LN+APAP, and LMN+APAP treatments. Serum hepatic biomarkers, oxidative stress parameters, and inflammatory cytokines were analyzed to assess protective responses. Results: APAP exposure markedly elevated aspartate aminotransferase (AST) and alkaline phosphatase (ALP) levels, indicating severe hepatic dysfunction, accompanied by increased lipid peroxidation and pro-inflammatory cytokine production. LMN+APAP treatment significantly restored hepatic enzyme levels to approximately normal values and suppressed malondialdehyde (MDA) formation, while enhancing superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activities. LMN also downregulated interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), and interleukin 1β (IL-1β), while upregulating interleukin 10 (IL-10), suggesting effective attenuation of inflammatory signaling. Correlation analyses demonstrated positive interactions between MDA, cytokines, and hepatic enzymes, whereas antioxidant enzyme levels were inversely correlated with liver injury markers. Histopathological analysis revealed that treatment with LMN enhanced hepatoprotection, demonstrating predominantly mild, reversible lesions and suggesting a synergistic antioxidant and immunomodulatory effect. Conclusions: It could be concluded that LMN provided superior hepatoprotection compared to M or LN. These findings establish LMN as a promising bio-based nanotherapeutic agent for mitigating drug-induced hepatotoxicity through coordinated antioxidant and anti-inflammatory mechanisms. Full article

Flavonoids, natural organic compounds from the polyphenolic group with broad bioactive and pharmaceutical properties, are strong ligands for many metal ions. This work describes the formation of the complex between Zn(II) and morin. The synthesized compound is characterized using three analytical techniques, i.e., ¹H NMR, IR, and thermal gravimetric analysis. Importantly, the complex was successfully obtained in the form of a solid, which enables its further physicochemical and structural characterization. Physicochemical characterization of the Morin-Zn complex was performed by steady-state and time-resolved spectroscopy. The absorption spectrum of the complex contains two main bands at ca. 407–415 nm and ca. 265 nm, and the complex emits yellow-green light with higher intensity than the free ligand. In the next step, morin and zinc complex were dispersed in a PMMA (poly (methyl methacrylate)) polymer matrix, and respective thin layers were produced. The studied thin films were deposited on silicon substrates by using the spin-coating method and characterized by X-ray photoelectron spectroscopy (XPS), Atomic Force Microscopy (AFM), Spectroscopic Ellipsometry (SE), UV-VIS spectroscopy, and photoluminescence (PL). The absorption of thin layers showed, similarly to solutions, the presence of two transitions: π→π* and n→π*, and a bathochromic shift for the morin-zinc complex compared to morin. The photoluminescence of the complex thin film showed two bands, the first in the range of 380–440 nm corresponding to PMMA, and the second with a maximum at 490 nm, derived from the synthesized compound. Full article

Background/Objectives: High fructose consumption is a significant risk factor for glomerular podocyte injury. This study aimed to identify the underlying mechanism of fructose-induced podocyte injury and explore the protective effect of the natural polyphenol morin. Methods: In vivo, high-fructose-diet-fed rats were used to evaluate podocyte injury through ultrastructural structure analysis, urinary albumin-to-creatinine ratio (UACR), and synaptopodin expression. In vitro, adenosine 5′-monophosphate deaminase (AMPD) expression and activity, mitochondrial function, and glycolytic flux were measured in mouse podocyte clone-5 (MPC5) exposed to 5 mM fructose, with molecular docking and siRNA interference assays validating morin’s regulatory role. Results: High fructose significantly increased AMPD activity in the purine nucleotide cycle (PNC), leading to mitochondrial dysfunction and a compensatory activation of glycolysis in podocytes. Morin effectively mitigated podocyte injury and suppressed the upregulation of AMPD activity, potentially through targeting AMPD2, as evidenced by molecular docking, which demonstrated a strong binding affinity between morin and AMPD2. Similarly, AMPD2 knockdown markedly alleviated mitochondrial impairment and glycolysis activation, confirming the pivotal role of AMPD2 in fructose-induced podocyte injury. In high-fructose-diet-fed rats, morin substantially improved ultrastructural damage, as shown by reduced podocyte foot process effacement, decreased UACR, restored glomerular synaptopodin expression, and suppressed AMPD activity in the renal cortex. Conclusions: Morin alleviated high-fructose-induced podocyte injury by inhibiting AMPD activity in the PNC, highlighting AMPD2 as a potential therapeutic target for podocyte injury caused by high fructose intake. This study provides novel mechanistic insights into how morin counteracts mitochondrial energy disturbance in podocyte injury. Full article

Background/Objectives: The breast cancer care continuum is associated with a physical and emotional burden resulting in significant needs for rehabilitation. A growing concern has been the underutilization of rehabilitation services, even when they are accessible, highlighting that several women’s needs remain unmet. The aim of this study was to investigate breast cancer patients’ physical and psychological rehabilitation needs and experiences, and to document the barriers encountered throughout the breast cancer care continuum. Methods: A cross-sectional study consisting of a self-reported online survey was conducted. Women aged 18 years and over with a diagnosis of breast cancer, who underwent breast surgery in the last 5 years in Quebec province, Canada, were eligible for this study. A questionnaire was developed by research team members, and content validity was evaluated by an expert group including professionals in rehabilitation, oncological care, and two patient partners. The questionnaire was completed once by each participant on the online platform Qualtrics ©. Closed-ended and open-ended questions were used to collect information on (1) sociodemographic characteristics, (2) clinical profiles, (3) rehabilitation needs, and (4) rehabilitation experiences. Results: The sample included participants from all 17 administrative regions of the Quebec province, 78.0% of whom lived in urban areas. Four hundred and four participants (78.4%) expressed rehabilitation needs, but only two hundred and forty-five participants (47.2%) reported the use of rehabilitation services. A lack of awareness of the service’s availability, the fact that the service was not prescribed or recommended, and financial constraints were cited as major barriers to accessing rehabilitation services. Conclusions: Breast cancer patients expressed significant needs for rehabilitation services but demonstrated low utilization rates, reflecting barriers to rehabilitation. Addressing the fragmented integration of rehabilitation services into the breast cancer care continuum and inequities in access based on social determinants of health should be prioritized. Full article

This study investigates and compares different molecular mutation strategies to optimize their application as genetic algorithm operators in drug design. We evaluated five distinct mutation methods—Graph-Based Genetic Algorithm, Graph-Based Generative Model, SmilesClickChem, SELFIES Token, and SMILES Token Mutation—by assessing their computational efficiency, validity, and impact on molecular complexity and structural conservation. Our results reveal that the Graph-Based Genetic Algorithm achieves the highest molecular validity (96.5%) while maintaining computational efficiency, making it ideal for rapid iterative drug discovery. SmilesClickChem and Graph-Based Generative Model tend to increase molecular complexity, whereas SF-T simplifies molecular structures, suggesting different applications in lead optimization. Additionally, we analyzed mutation-induced changes in pIC50 potency and found that SELFIES Token caused the most substantial shifts in bioactivity, particularly in SRC-targeted molecules. These findings underscore the importance of selecting the appropriate mutation strategy to balance validity, structural diversity, and computational cost in AI-driven drug design. Our insights help refine evolutionary algorithms for molecular generation and optimize candidate selection in early-stage drug discovery. Full article