Search Results (123)

The place and people of Waiʻanae, Hawaiʻi, are rich in connection with ʻāina (natural environment) and culture. Counter to this strengths-based approach, metrics and narratives imposed by outside systems assess many communities like ours as “sick”, “poor”, or “unwell”. This paper details our community’s approach to defining “well-being” around the values specific to our place, overseen by a council of community leaders with decades of experience supporting youth. The development was a mixed methods process including formal focus groups, informal community conversations, review of existing models, and collaboration with a professional artist. Centering community was the priority through each phase, engaging youth, parents, cultural practitioners, healthcare providers, and educators. Our community built the Kaiona Framework around the moʻolelo (traditional story) of Kaiona who helps the lost find home through empathy and compassion. Well-being is grounded in connection to, in relationship with, and in service to ʻāina. The child is at the center of our work, but inseparable from the family, community, and wider nation of people. Wellness comprises four values vital to our community: mauli ola, a balanced state of physical, mental, emotional, spiritual, and environmental health; waiwai, abundance and prosperity; pilina, mutually sustaining relationships; and ea, self-determination and agency. Full article

A point-of-care (POC) HIV drug resistance (HIV-DR) test is needed for low- and middle-income countries (LMICs). Oligonucleotide Ligation Assay (OLA)-Simple, designed as a near-POC HIV-DR test, was assessed for its overall usability in Kenya by technicians with and without molecular laboratory PCR experience. Further, its diagnostic accuracy was evaluated by PCR-experienced technicians utilizing 147 plasma samples with known Sanger sequence genotypes—based on seven major HIV-DR mutations of nucleotide and non-nucleoside reverse transcriptase inhibitors. Thirteen laboratory technicians were recruited, including five with prior PCR experience. Twelve technicians completed the training and attained OLA-Simple testing competency, ten of whom were able to perform the OLA-Simple test within 6 h. Technicians’ survey feedback indicated the user-friendliness of OLA-Simple, citing straightforward reagent reconstitution, concise instructions in prompts, and a shorter sample-to-result test time compared to standard genotyping assays. Of the 147 archived plasma samples tested, 132 (90%) yielded interpretable results. OLA-Simple assay demonstrated a sensitivity of 97.3% (95% CI 94.5, 98.9), a specificity of 97.2% (95% CI 95.5, 98.3), and a percent agreement of 97.1% (95% CI 95.9, 98.2) compared to Sanger sequencing. This evaluation found that OLA-Simple was user-friendly among intended end-users and performed well. LMIC HIV programs would benefit from strategizing on case-use scenarios for such near-POC HIV-DR assays to improve HIV outcomes. Full article

The objective of this study was to develop multifunctional chitosan (CT) derivatives by conjugating oleic acid (OLA) and caffeic acid (CAF) to improve water solubility at neutral pH, enhance interfacial activity, and provide antioxidant protection in oil-in-water emulsions. Two CAF-incorporation strategies—1-(3-dimethylaminopropyl)-3-ethylcarbodiimide·HCl/N-hydroxysuccinimide (EDC/NHS)-mediated amide coupling and ascorbic acid/H₂O₂-initiated free radical grafting—were employed to functionalize the CT–OLA backbone. The CT–OLA–CAF conjugates generated via the free radical pathway exhibited markedly lower viscosity and interfacial tension than those produced through EDC/NHS coupling, thereby highlighting the respective advantages and limitations associated with these two synthesis approaches. Chemically, CAF incorporation substantially enhanced the antioxidant capacity of the conjugates—surpassing that of both CT and CT—OLA and conferred excellent protection to photo-oxidatively labile β-carotene in o/w emulsions. Full article

Over the past decade, trait data collection and mobilisation have expanded significantly, yet much of this data remains only partially compliant with FAIR principles. A major challenge lies in the inconsistent use of standards for harmonising heterogeneous trait data, along with the diversity, redundancy, and poor alignment of semantic artefacts developed to address this challenge. This study presents an approach to enhance the interoperability of the Trait Thesauri developed within the LifeWatch Italy research infrastructure for annotating and standardising trait data and metadata of aquatic organisms. This approach combines manual and automated alignment techniques, tested within the 2023 Ontology Alignment Evaluation Initiative. Domain experts manually aligned the Phytoplankton, Zooplankton, Macroalgae, Macrozoobenthos, and Fish trait thesauri, while five matching tools, LogMap, LogMapKG, LogMapLt, Matcha, and OLaLa, were tested for automated mappings. Both approaches revealed significant overlap among thesauri: Manual mapping identified 160 cross-thesauri correspondences and served as a benchmark for evaluating automated matching systems. Automated tools showed variable performance, with OLaLa achieving the best automated alignment results, with an F-measure of 0.93. Challenges in alignment included varying linguistic expressions and differing levels of concept specificity. The results highlight the importance of combining automation with expert validation to ensure mapping quality and allowed the development of a unified Trait Thesaurus, which integrates approximately 500 harmonised concepts, reducing redundancy and enhancing FAIR compliance in ecological and trait-based research. Full article

Autonomous vehicles need to explain their actions to improve reliability and build user trust. This study focuses on enhancing the transparency and explainability of the decision-making process in such systems. A module named XAI-Interpreter is developed to identify and highlight the most influential factors in driving decisions. The module combines two complementary methods: Learned Attention Weights (LAW) and Object-Level Attention (OLA). In the LAW method, images captured from the ego vehicle’s front and rear cameras in the CARLA simulation environment are processed using the Faster R-CNN model for object detection. GRAD-CAM is then applied to generate visual attention heatmaps, showing which regions and objects in the images affect the model’s decisions. The OLA method analyzes nearby dynamic objects, such as other vehicles, based on their size, speed, position, and orientation relative to the ego vehicle. Each object receives a normalized attention score between 0 and 1, indicating its influence on the vehicle’s behavior. These scores can be used in downstream modules such as planning, control, and safety. The module is currently tested in simulation. Future work will involve deploying the system on real vehicles. By helping the vehicle focus on the most critical elements in its surroundings, the Explainable Artificial Intelligence (XAI)-Interpreter supports more transparent and explainable autonomous driving systems. Full article

Harnessing Europe’s strong wave energy could support net-zero emissions goals, but extreme ocean loads still make wave energy expensive and delay the rollout of commercial wave-energy converters (WECs). To address this, the twin-floater CECO WEC has been redesigned into a single-pivot device called the Pivoting WEC (PWEC), which includes a passive duck diving survival mode to reduce extreme wave impacts. Its performance is evaluated using detailed wave simulations based on Reynolds-Averaged Navier–Stokes (RANS) equations and the Volume-of-Fluid (VoF) method in OpenFOAM-olaFlow, which is validated with data from small-scale (1:20) wave tank experiments. Extreme non-breaking and breaking waves are simulated based on 100-year hindcast data for the case study site of Matosinhos (Portugal) using a modified Miche criterion. These are validated using data of surface elevation and force sensors. Wave height errors averaged 5.13%, and period errors remain below 0.75%. The model captures well major wave loads with a root mean square error down to 47 kN compared to a peak load of 260 kN and an R² up to 0.80. The most violent plunging waves increase peak forces by 5 to 30% compared to the highest non-breaking crests. The validated numerical approach provides accurate extreme load predictions and confirms the effectiveness of the PWEC’s passive duck diving survival mode. The results contribute to the development of structurally resilient WECs, supporting the progress of WECs toward higher readiness levels. Full article

This study investigated the degradation and disintegration behavior of novel biobased multilayered films composed of poly(lactic acid) (PLA) and poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) during controlled composting tests performed at the laboratory scale. The compostability of monolayer PLA and PHBV films, hot-pressed bilayers, and coextruded multilayer films produced in industrial or semi-industrial settings was systematically evaluated. Materials supplied by Fraunhofer LBF (Darmstadt, Germany) were tested as specified by the EVS-EN standard ISO 14855-1:2012 and EVS-EN ISO 20200:2016 standards. Composting took place in sealed, aerated vessels at 58 ± 2 °C with 50 ± 5% moisture and >6% oxygen. Biodegradation was measured via CO₂ evolution, and disintegration was assessed visually and physically. PLA-1OLA films achieved 98.59% biodegradation and 91.13% disintegration. PHBV-5OLA and multilayer PLA-1OLA/PHBV-5OLA films showed biodegradation rates of 85.49% and 73.14%, with disintegration degrees of 89.93% and 79.18%, respectively. However, modified multilayer structures displayed slightly reduced compostability compared with pure compounds, likely due to the influence of additional components. To meet the 90% biodegradability threshold required by EVS-EN 13432:2003, increasing the PLA-1OLA content is recommended. This study introduces a novel combination of biobased polymers and plasticizers in multilayer formats, offering a deeper understanding of structure–property–degradation relationships. Its significance lies in advancing the design of sustainable packaging materials that balance functionality with environmental compatibility. Full article

As offshore wind energy industry advances into deeper water recently, jacket foundations become one of the predominant support structure types for far-sea wind farms. To ensure the safety and reliability of offshore wind turbine (OWT) jacket foundations in the complex environments of far-seas, the investigation of their resistance capabilities to extreme ocean wave is essential. In this study, the OWT jacket foundations in the sea area of Cangnan and Lianjiang are adopted to conduct a typical case study. This study employs a full-scale jacket foundation to carry out some full-scenario, large-scale hydrodynamic numerical simulations considering the combined action of wave and current. It is revealed that for OWT jacket foundations in Cangnan and Lianjiang, China, under an extreme condition with approximately 26 m wave height and 18 s wave period, the peak wave impact and horizontal force on the jacket foundation are approximately 190 kPa and 18,000 kN, respectively. Furthermore, this study discusses the wave profile evolution characteristics around the jacket foundation and the correlation between wave run-up and wave height. These findings provide a good case study and technical reference for the full-scale fine simulation of wave forces on OWT jacket foundations in far-sea areas. Full article

In this study, multicomponent PLA-based biocomposites were developed. In particular, both native fibrous cellulose and cellulose with modified morphology obtained through ball milling treatments were incorporated into the polyester matrix in combination with an oligomeric plasticizer, specifically a lactic acid oligomer (OLA). The resulting materials were analyzed in terms of their morphology, thermal and mechanical properties over time, water vapor permeability, and degradation under soil burial conditions in comparison to neat PLA and unplasticized PLA/cellulose composites. The cellulose phase significantly affected the mechanical properties and enhanced their long-term stability, addressing a common limitation of PLA/plasticizer blends. Additionally, water vapor permeability increased in all composites. Finally, the ternary systems exhibited a significantly higher degradation rate in soil burial conditions compared to PLA, evidenced by larger weight loss and reduction in the molecular weight of the PLA phase. The degradation rate was notably influenced by the morphology of the cellulose phase. Full article

Background: Olanzapine (Ola) is a second-generation antipsychotic with clinical utility limited by poor brain bioavailability due to blood–brain barrier restriction, hepatic first-pass metabolism, and systemic side effects. This study aimed to develop and optimize a novel intranasal polymersome-based nanocarrier (Poly_Ola) to enhance brain targeting, therapeutic efficacy, and safety of Ola. Methods: Poly_Ola was prepared using poloxamer 401 and optimized through a Box–Behnken Design to minimize particle size and maximize entrapment (EE%) and loading efficiency (LE%). The formulation was characterized by size, morphology, drug release, and serum stability. In vivo studies in adult male Sprague-Dawley rats assessed pharmacokinetics (plasma and brain concentrations), pharmacodynamic efficacy in a ketamine-induced schizophrenia model, and systemic safety markers including metabolic, hepatic, and testicular oxidative stress indicators. Results: Optimized Poly_Ola exhibited a particle size of 78.3 ± 4.5 nm, high EE% (91.36 ± 3.55%), and sustained in vitro drug release. It remained stable in serum for 24 h. Intranasal administration significantly improved brain delivery of Ola, achieving a 2.7-fold increase in C_max and a 5.7-fold increase in AUC compared to oral dosing. The brain T_max was 15 min, with high drug-targeting efficiency (DTE% = 365.38%), confirming efficient nose-to-brain transport. Poly_Ola-treated rats showed superior antipsychotic performance, reduced extrapyramidal symptoms, and improved systemic safety evidenced by mitigated weight gain, glycemic control, normalized liver enzymes, and reduced oxidative stress. Conclusions: Poly_Ola offers a safe and effective intranasal delivery platform for Ola, enabling targeted brain delivery and improved management of schizophrenia with reduced peripheral toxicity. Full article

Moringa oleifera (MO) is a prominent plant in traditional medicine, widely recognized for its phytochemicals with anti-inflammatory properties. Liver fibrosis characterized by chronic inflammation and excessive extracellular matrix deposition may benefit from the therapeutic properties of MO. This report focuses on the potential of oleamide (OLA), a bioactive compound identified from MO, in mitigating liver fibrosis. The anti-fibrotic effects of OLA were evaluated by assessing the production of pro-inflammatory cytokines, gelatinase activity and the expression of genes and proteins associated with the TGF-β/SMAD2/3 pathway. The LX-2 human hepatic stellate cell line, in conjunction with TGF-β1, was employed to model fibrotic conditions. OLA treatment significantly reduced the production of pro-fibrotic effectors in the activated LX-2 cells. Molecular docking analysis demonstrated a high binding affinity of OLA to key proteins in the TGF-β/SMAD2/3 pathway, while qRT-PCR and Western blotting revealed that OLA suppressed the expression of COL1A1, COL4A1, SMAD2, SMAD3, SMAD4, MMP2, MMP9, ACTA2 and TIMP1. These findings indicate that OLA effectively attenuates the pro-inflammatory responses induced by TGF-β1 and inhibits the activation of LX-2 cells. Collectively, OLA holds significant potential as a therapeutic agent for the prevention and treatment of liver fibrosis via the modulation of the TGF-β/SMAD2/3 signaling pathway. Full article

Resistance to PARP inhibitors (PARPi), such as olaparib (OLA), is a major challenge in ovarian cancer treatment. In this study, we investigated the combination effect of PARPi and gukulenin A (GUA), a bis-tropolone tetraterpenoid isolated from the marine sponge Phorbas gukhulensis. We found that GUA at a mildly cytotoxic dose synergistically enhanced OLA-induced cytotoxicity in human ovarian cancer cells. The combination treatment significantly increased reactive oxygen species (ROS) levels and lipid peroxidation, leading to ferroptotic rather than apoptotic cell death. Network pharmacology and gene ontology (GO) enrichment analyses revealed oxidative stress-related pathways as key mediators of this effect. Inhibition of NADPH oxidase (NOX) reversed combination-induced cell death, while ferrostatin-1 (FER-1), a ferroptosis inhibitor, significantly reduced lipid peroxidation and cytotoxicity. Additionally, GUA and OLA treatment suppressed ERK1/2 activation, and ERK overexpression attenuated the combination-induced cell death. Collectively, these findings suggest that marine-derived GUA enhances PARPi efficacy in ovarian cancer cells by inducing ferroptosis through oxidative stress and ERK pathway modulation. Full article

Electrochemical enzyme biosensors are extensively utilized in clinical analysis and environmental monitoring, yet achieving effective enzyme immobilization while maintaining high activity remains a challenge. In this work, we developed a flow-through enzyme biosensor system using a 3D-printed flow-through electrochemical cell fabricated from commercially available poly (lactic acid). After modification with thiacalixarene-functionalized oligo (lactic acids) (OLAs), the material enabled efficient immobilization of uricase on the inner surface of a replaceable reactor of the cell. Swelling and hydrolytic stability of OLAs in cone, partial cone, and 1,3-alternate conformations were studied, with 1,3-alernate conformation demonstrating superior stability and enzyme immobilization performance. The use of OLAs enhanced immobilization efficiency by over 30% and protected the reactor from swelling, hydrolytic degradation, and enzyme loss. The biosensor was validated for amperometric uric acid determination, with a screen-printed carbon electrode modified with carbon black and Prussian Blue. This modification reduced the cathodic potential for uric acid detection to –0.05 V. The biosensor exhibited a linear detection range of 10 nM to 30 μM with a detection limit of 7 nM, and it performed effectively in artificial urine and synthetic blood plasma. The novel cell design, featuring easy assembly and low-cost replaceable parts, makes this biosensor a promising candidate for routine clinical analysis and other practical applications. Full article

The aim of this study was to investigate the promotion of linoleic acid (OLA)-induced myofibrillar protein (MP) oxidation by boiling treatment. The effect of the boiling treatment on grass carp MP oxidation induced by OLA was investigated. The total sulfhydryl content, fluorescence intensity, and amino acid content were reduced with the increasing OLA concentration after the boiling treatment, while the boiled oxidized MP’s carbonyl content (4.76 ± 0.14 nmol/mg) was 2.14 times higher than that of the native MP (2.22 ± 0.02 nmol/mg) at an OLA concentration of 10 mM. Additionally, the secondary structure of MP became more disordered, shifting from an α-helix to random coils and β-turns. When the concentration of OLA was higher than 5 mM, both the surface hydrophobicity and water holding capacity (WHC) decreased with the increasing OLA concentration. Furthermore, the boiling treatment led to a reduction in immobile water and an increase in free water content in the MP gel. These findings establish a theoretical basis for regulating MP oxidation to improve fish quality during boiling. Full article

Background: Olaparib (OLA) and regorafenib (REG) are metabolized by the CYP3A4 isoenzyme of cytochrome P450. Both drugs are also substrates and inhibitors of the membrane transporters P-glycoprotein and BCRP. Therefore, the potential concomitant use of OLA and REG may result in clinically relevant drug–drug interactions. Knowledge of the influence of membrane transporters and cytochrome P450 enzymes on the pharmacokinetics of drugs makes it possible to assess their impact on the efficacy and safety of therapy. Purpose: The study aimed to evaluate the bilateral pharmacokinetic interactions of OLA and REG and its active metabolites after a single administration in healthy rats. Methods: The study was performed in male Wistar rats (n = 24) randomly divided into three groups: one study group, I_REG+OLA (n = 8), received REG with OLA, and two control groups, II_REG (n = 8) and III_OLA (n = 8), received REG and OLA, respectively. The concentrations of OLA, REG, REG-N-oxide (M-2), and N-desmethyl-REG-N-oxide (M-5) were determined by ultra-performance liquid chromatography–tandem mass spectrometry (UPLC-MS/MS). The values of the pharmacokinetic parameters of OLA, REG, M-2, and M-5 were determined by non-compartmental analysis with linear interpolation. Results: After OLA administration, the pharmacokinetic parameters of REG (AUC_0–∞, t_max, and t_0.5) increased significantly by 3.38-, 2.66-, and 1.82-fold, respectively. On the other hand, REG elimination parameters, i.e., k_el and Cl/F, were significantly reduced in the study group by 1.77- and 1.70-fold, respectively. In the study group, C_max and AUC_0–t values were also 7.22- and 8.86-fold higher for M-2 and 16.32- and 17.83-fold higher for M-5, respectively. The Metabolite M-2/Parent and Metabolite M-5/Parent ratios for C_max and AUC_0–t increased by 6.52-, 10.74-, 28-, and 13-fold, respectively. After administration of OLA with REG, the C_max, AUC_0–t, and AUC_0–∞ of OLA increased by 2.0-, 3.4-, and 3.4-fold, respectively, compared to the control group. Meanwhile, Cl/F and Vd/F of OLA were significantly decreased in the presence of REG. Conclusions: OLA was shown to significantly affect the pharmacokinetics of REG and its active metabolites M-2 and M-5 in rats after co-administration of both drugs. There was also a significant effect of REG on the pharmacokinetics of OLA, which may have clinical relevance. The AUC ratios (study group/control group) were 3.41 and 3.39 for REG and OLA, respectively, indicating that REG and OLA were moderate inhibitors in this preclinical study. The results obtained need to be confirmed in clinical studies. This study may provide guidance on the safety of using both drugs in clinical practice. Full article