Search Results (559)

The increasing prevalence of antibiotic resistance and the limited availability of antiviral therapeutics for pathogens such as human respiratory syncytial virus (hRSV) underscore the need for novel, plant-derived antimicrobial substances. In this study, we evaluated the antiproliferative, antibacterial, and antiviral activities of aqueous leaf extracts from two plants commonly found in North America, Osage orange (M. pomifera) and spearmint (M. spicata). Both extracts exhibited no significant cytotoxic or morphologic impact on HEp-2 human cancer cells up to 25 mg/mL. However, both extracts demonstrated strong dose-dependent antibacterial activity, significantly inhibiting replication of E. coli and S. aureus at concentrations ≥ 1 mg/mL. Antiviral assays revealed that both extracts inhibited hRSV infectivity, with spearmint extract showing higher potency (EC₅₀ = 1.01 mg/mL) compared to Osage orange (EC₅₀ = 3.85 mg/mL). Gas chromatography–mass spectrometry (GC-MS) identified three major extract constituents: 3-hydroxybenzyl alcohol, 4-hydroxybenzyl alcohol (Osage orange), and R-(-)-carvone (spearmint). Among these, only carvone significantly inhibited hRSV in vitro, suggesting its key role in spearmint’s antiviral activity. These findings highlight the therapeutic potential of Osage orange and spearmint leaf extracts, particularly as sources of water-soluble compounds with antimicrobial properties, and support further investigation into their mechanisms of action and broader clinical relevance. Full article

Payments for Watershed services (PWSs) have been emerging as a critical tool for environmental governance in watershed, yet their comparative effectiveness across implementation models has remained poorly understood. Based on a comparative analysis of Eco-Compensation (EC) and Payments for Ecosystem Services (PESs) frameworks, examining both theoretical foundations and implementation practices, this study aims to quantitatively assess and compare the effectiveness of two dominant PWSs models—the EC-like model (Phase I: October 2008–April 2017) and the PESs-like model (Phase II: 2017–December 2021). Using the Liaohe River in China as a case study, utilizing ecosystem service value (ESV) as an indicator and employing the corrected unit-value transfer method, we compare the effectiveness of different PWSs models from October 2008 to December 2021. The results reveal the following: (1) Policy Efficiency: The PESs-like model demonstrated significantly greater effectiveness than the EC-like model, with annual average increases in ESV of 3.23 billion CNY (491 million USD) and 1.79 billion CNY (272 million USD). (2) Functional Drivers: Water regulation (45.1% of total ESV growth) and climate regulation (24.3%) were dominant services, with PESs-like interventions enhancing multifunctionality. (3) Stakeholder Impact: In the PESs-like model, the cities implementing inter-county direct payment showed higher growth efficiency than those without it. The operational efficiency of PWSs increases with the number of participating stakeholders, which explains why the PESs-like model demonstrates higher effectiveness than the EC-like model. Our findings offer empirical evidence and actionable policy implications for designing effective PWSs models across global watershed ecosystems. Full article

Cardiovascular disease encompasses a wide group of conditions that affect the heart and blood vessels. Of these diseases, cardiomyopathies and arrhythmias specifically have been well-studied in their relationship to cardiac dyads, nanoscopic structures that connect electrical signals to muscle contraction. The proper development and positioning of dyads is essential in excitation–contraction (EC) coupling and, thus, beating of the heart. Three proteins, namely CMYA5, JPH2, and BIN1, are responsible for maintaining the dyadic cleft between the T-tubule and junctional sarcoplasmic reticulum (jSR). Various other dyadic proteins play integral roles in the primary function of the dyad—translating a propagating action potential (AP) into a myocardial contraction. Ca²⁺, a secondary messenger in this process, acts as an allosteric activator of the sarcomere, and its cytoplasmic concentration is regulated by the dyad. Loss-of-function mutations have been shown to result in cardiomyopathies and arrhythmias. Adeno-associated virus (AAV) gene therapy with dyad components can rescue dyadic dysfunction, which results in cardiomyopathies and arrhythmias. Overall, the dyad and its components serve as essential mediators of calcium homeostasis and excitation–contraction coupling in the mammalian heart and, when dysfunctional, result in significant cardiac dysfunction, arrhythmias, morbidity, and mortality. Full article

Endometrial cancer (EC) is the most common gynecological malignancy in developed countries. Risk factors for EC include metabolic alterations (obesity, metabolic syndrome, insulin resistance), hormonal imbalance, age at menopause, reproductive factors, and inherited conditions, such as Lynch syndrome. For the inherited forms, several genes had been implicated in EC occurrence and development, such as POLE, MLH1, TP53, PTEN, PIK3CA, PIK3R1, CTNNB1, ARID1A, PPP2R1A, and FBXW7, all mutated at high frequency in EC patients. However, gene function impairment is not necessarily caused by mutations in the coding sequence of these and other genes. Gene function alteration may also occur through post-transcriptional control of messenger RNA translation, frequently caused by microRNA action, but transcriptional impairment also has a profound impact. Here, we review how chromatin modifications change the expression of genes whose impaired function is directly related to EC etiopathogenesis. Chromatin modification plays a central role in EC. The modification of chromatin structure alters the accessibility of genes to transcription factors and other regulatory proteins, thus altering the intracellular protein amount. Thus, DNA structural alterations may impair gene function as profoundly as mutations in the coding sequences. Hence, its central importance is in the diagnostic and prognostic evaluation of EC patients, with the caveat that chromatin alteration is often difficult to identify and needs investigations that are specific and not broadly used in common clinical practice. The different phases of the healthy endometrium menstrual cycle are characterized by differential gene expression, which, in turn, is also regulated through epigenetic mechanisms involving DNA methylation, histone post-translational modifications, and non-coding RNA action. From a medicolegal and policy-making perspective, the implications of using epigenetics in cancer care are briefly explored as well. Epigenetics in endometrial cancer is not only a topic of biomedical interest but also a crossroads between science, ethics, law, and public health, requiring integrated approaches and careful regulation. Full article

Due to widespread use of silver nanoparticles (AgNPs), the assessment of their potential harm to microalgal photosynthesis is crucial, as microalgae, together with cyanobacteria, contribute to approximately 50% of global oxygen production. This study investigated photosynthetic pigments, photosynthetic rate, chlorophyll a fluorescence, and the expression of photosynthesis-related genes and proteins in green alga Chlorella vulgaris after 72 h exposure to citrate- and cetyltrimethylammonium bromide (CTAB)-stabilized AgNPs, as well as silver ions (AgNO₃), at concentrations allowing 75% cell survival (EC₂₅). All treatments impaired photosynthetic performance. The most pronounced decreases in chlorophyll fluorescence parameters and photosynthetic rate, alongside elevated energy dissipation, were observed after exposure to AgNP-CTAB and AgNO₃. AgNP-citrate had milder effects and induced compensatory responses, reflected in an increased performance index and upregulation of photosynthesis-related proteins. AgNP-CTAB induced the strongest downregulation of gene and protein expression, likely due to its higher EC₂₅ concentration and cationic surface promoting interaction with photosynthetic structures. Although AgNO₃ caused fewer molecular changes, it significantly disrupted photosynthetic function, suggesting a direct effect of Ag⁺ ions on photosynthesis-related proteins. Overall, the results highlight the role of AgNPs’ surface coatings and dosage in determining their phytotoxicity, with photosystem disruption and oxidative stress emerging as key mechanisms of action. Full article

Background: Interprofessional collaboration (IPC) is considered fundamental for integrated, high-quality woman-centered care. This study analyzes concordance/differences in the perspectives of midwives and physicians on IPC and Equitable Communication (EC) in prenatal/postpartum (PPC) and birth care (BC). Methods: The short form of the ICS Scale (ICS-R with eight items) adapted for the midwifery context, and the EC scale (three items) were completed by 293 midwives and 215 physicians in Germany. Profession- and the setting-specific differences were analyzed using t-tests and ANOVA with repeated measurements. Confirmatory factor analysis with nested model comparisons test the fairness of the scales. Results: Midwives’ ratings of all IPC aspects were systematically lower than physicians’ in both care settings (variance component professional group: η²_p = 0.227/ 0.318), esp. for EC (d = 1.22–1.41). Both groups rated EC higher in BC. The setting effect was less pronounced among physicians for the ICS-R items than among midwives. Violations of test fairness reveal validity deficiencies when using the aggregated EC sum score for group comparisons. Conclusions: Fundamental professional differences were found in the IPC assessment between physicians and midwives. The results enhance the understanding of IPC dynamics and provide starting points for action to leverage IPC’s potential for woman-centered care. Full article

With the rapid progression of global industrialization and urbanization, emerging contaminants (ECs) have become pervasive in environmental media, posing considerable risks to ecosystems and human health. While multidisciplinary evidence continues to accumulate regarding their environmental persistence and bioaccumulative hazards, critical knowledge gaps persist in understanding their spatiotemporal distribution, cross-media migration mechanisms, and cascading ecotoxicological consequences. This review systematically investigates the global distribution patterns of ECs in aquatic environments over the past five years and evaluates their potential ecological risks. Furthermore, it examines the performance of various treatment technologies, focusing on economic cost, efficiency, and environmental sustainability. Methodologically aligned with PRISMA 2020 guidelines, this study implements dual independent screening protocols, stringent inclusion–exclusion criteria (n = 327 studies). Key findings reveal the following: (1) Occurrences of ECs show geographical clustering in highly industrialized river basins, particularly in Asia (37.05%), Europe (24.31%), and North America (14.01%), where agricultural pharmaceuticals and fluorinated compounds contribute disproportionately to environmental loading. (2) Complex transboundary pollutant transport through atmospheric deposition and oceanic currents, coupled with compound-specific partitioning behaviors across water–sediment–air interfaces. (3) Emerging hybrid treatment systems (e.g., catalytic membrane bioreactors, plasma-assisted advanced oxidation) achieve > 90% removal for recalcitrant ECs, though requiring 15–40% cost reductions for scalable implementation. This work provides actionable insights for developing adaptive regulatory frameworks and advancing green chemistry principles in environmental engineering practice. Full article

Estrogens regulate many physiological processes in the human body, including the cardiovascular system. Importantly, Estradiol (E2) exerts its vascular protective actions, in part, by promoting endothelial repair via induction of endothelial cell (EC) proliferation, migration and angiogenesis. Recent evidence that microRNAs (miRNAs) play an important role in vascular health and disease as well as in regulating Estrogen actions in many cell types. We hypothesize that E2 may mediate its vascular protective actions via the regulation of miRNAs. Following initial screening, we found that E2 downregulates the levels of miR-193a-3p in ECs. Moreover, miR-193a-3p downregulation by miR-193a-3p-antimir mimicked the effects as E2 on EC growth, migration, and capillary formation. Restoring miR-193a-3p levels with mimics after E2 treatment abrogated the vasculogenic actions of E2, suggesting a key role of miR-193a-3p in E2-mediated EC-growth-promoting effects. We further investigated the cellular mechanisms involved and found that miR-193a-3p inhibits angiogenesis by blocking phosphoinositide-3-kinase (PI3K)/Akt-vascular endothelial growth factor (VEGF) and Activin receptor-like kinase 1 (ALK1)/SMAD1/5/8 signaling in ECs, both pathways that are important in E2-mediated vascular protection. Additionally, using reverse transcription polymerase chain reaction (RT-PCR), we demonstrate that E2 downregulates miR-193a-3p in ECs via Estrogen Receptor (ER)α, but not ERβ or G protein-coupled estrogen receptor (GPER). Moreover, these actions occur post-transcriptionally, as the expression of pri-miR-193a-3p was not affected. The anti-angiogenic actions of miR-193a-3p were also observed in in vivo Matrigel implant-based capillary formation studies in ovariectomized mice where E2 induced capillary formation, and these effects were abrogated in the presence of miR-193a-3p, but not in the control mimic. Assessment of miR-193a-3p levels in plasma collected from in vitro fertilization (IVF) subjects with low and high E2 levels showed significantly lower miR-193a-3p levels in responders during the high E2 period. Hence, our findings provide the first evidence that miR-193a-3p mimic inhibits angiogenesis whereas its antimir is angiogenic. Importantly, E2 mediates its regenerative actions on ECs/capillary formation by downregulating endogenous miR-193a-3p expression. Both miR-193a-3p mimic or antimir may represent important therapeutic molecules to prevent or to induce endothelial function in treating pathophysiologies associated with capillary growth. Full article

Estradiol (E2) plays an important role in cell proliferation and certain brain functions. To reveal its mechanism of action, its detectability is essential. Only a few fluorescent-labeled hormonally active E2s exist in the literature, and their mechanism of action usually remains unclear. It would be of particular interest to develop novel labeled estradiol derivatives with retained biological activity and improved optical properties. Due to their superior optical characteristics, aza-BODIPY dyes are frequently used labeling agents in biomedical applications. E2 was labeled with the aza-BODIPY dye at its phenolic hydroxy function via an alkyl linker and a triazole coupling moiety. The estrogenic activity of the newly synthesized fluorescent conjugate was evaluated via transcriptional luciferase assay. Docking calculations were performed for the classical and alternative binding sites (CBS and ABS) of human estrogen receptor α. The terminal alkyne function was introduced into the tetraphenyl aza-BODIPY core via selective formylation, oxidation, and subsequent amidation with propargyl amine. The conjugation was achieved via Cu(I)-catalyzed azide–alkyne click reaction of the aza-BODIPY-alkyne with the 3-O-(4-azidobut-1-yl) derivative of E2. The labeled estrogen induced a dose-dependent transcriptional activity of human estrogen receptor α with a submicromolar EC₅₀ value. Docking calculations revealed that the steroid part has a perfect overlap with E2 in ABS. In CBS, however, a head-tail binding deviation was observed. A facile, fluorescent labeling methodology has been elaborated for the development of a novel red-emitting E2 conjugate with substantial estrogenic activity. Docking experiments uncovered the binding mode of the conjugate in both ABS and CBS. Full article

As mainstream solvers for black-box optimization problems, evolutionary computation (EC) methods struggle with finding desired optima of lower attractiveness. Researchers have designed benchmark problems for simulating this scenario and proposed a large number of niching methods for solving those problems. However, factors causing the difference in attractiveness between local optima are often coupled in existing benchmark problems, which makes it hard to clarify the primary contributors. In addition, niching methods are carried out using a combination of several niching techniques and reproduction operators, which enhances the difficulty of identifying the essential effects of different niching techniques. To obtain an in-depth understanding of the above issue, thus offering actionable insights for optimization tasks challenged by the multimodality, this paper uses continuous optimization as an entry point and focuses on analyzing differential behaviors of EC methods across different basins of attraction. Specifically, we quantitatively investigate the independent impacts of three features of basins of attraction via corresponding benchmark scenarios generated by Free Peaks. The results show that the convergence biases induced by the difference in distribution only occur in EC methods with less uniform reproduction operators. On the other hand, convergence biases induced by differences in size and average fitness, both of which equate to the difference in size of superior region, pose a challenge to any EC method driven by objective functions. As niching methods limit survivor selection to specified neighborhoods to mitigate the latter biases, we abstract five niching techniques from these methods by their definitions of neighborhood for restricted competition, thus identifying key parameters that govern their efficacy. Experiments confirm these parameters’ critical roles in reducing convergence biases. Full article

To identify fungicide lead compounds with novel scaffold and high efficacy, a library of 4,5-dihydrotetrazolo [1,5-a]thieno [2,3-e]pyridine derivatives, consisting of 10 newly synthesized compounds and 12 previously reported compounds, was evaluated for their potential as fungicide agents. In vitro bioassay results indicated that some target compounds exhibited certain antifungal activity against the tested fungi at a concentration of 50 μg/mL. Especially, compounds I-1, I-5, I-7, and I-12 demonstrated promising antifungal activity against C. arachidicola, R. solani, and S. sclerotiorum, with EC₅₀ values ranging from 4.61 to 6.66 μg/mL. Additionally, transcriptome analysis revealed that the molecular mode of action of compound I-12 involves the inhibition of nitrogen metabolism and the proteasome pathway. The present work demonstrates that 4,5,6,7-tetrahydrothieno [3,2-b] pyridine represents a promising lead scaffold and provides important theoretical foundations and innovative perspectives for the development of novel and highly efficient fungicides. Full article

Blending child-led exploration with purposeful teacher guidance and clearly defined learning goals, playful learning has been promoted as a promising approach for introducing computational thinking (CT) in early childhood education (ECE). However, there is a lack of practical guidance for teachers on how to design and implement playful CT learning effectively. To address this gap, we conducted a collaborative action research project and asked these two questions: (1) How can teachers effectively prepare and design a playful learning CT program using tangible CT toys? (2) How do teachers facilitate playful learning in the CT program? Through iterative cycles of planning, acting, observing, and reflecting, the first and second authors (teacher-researchers) designed and implemented their CT programs in a preschool classroom and an afterschool program respectively, and collected data including video recordings of sessions, participant-generated artifacts, program documentation, and anecdotal reflection notes. Based on our thematic analysis of the data, we identified practical principles for selecting CT toys, three key themes for CT program design and preparation—interest, ownership, and application, and two forms of teacher scaffolding during implementation: embodied approach and storytelling as scaffolding and assessment. The findings highlight practical ways that teachers can enhance children’s engagement, problem-solving skills, and conceptual understanding of CT, while also promoting autonomy and creativity through coding and storytelling. Full article

Apple scab, caused by Venturia inaequalis, remains a major challenge for apple production in Morocco, where disease management heavily depends on fungicide applications. However, increasing reports of resistance have raised concerns about the long-term efficacy of commonly used products and the economic sustainability of apple orchards. In this study, we evaluated the sensitivity of five V. inaequalis isolates from the Fes-Meknes region, a key apple-producing area in Morocco, to three fungicides: difenoconazole, trifloxystrobin, and thiophanate-methyl. The identity of the isolates was confirmed based on both morphological characteristics and by molecular analysis of the ITS region. In vitro and in vivo assays revealed significant differences in isolate responses. Difenoconazole consistently showed the highest efficacy, with EC₅₀ values ranging from 0.05 to 1.46 µg/mL, and preventive applications reducing disease severity by up to 85.8% at 10 µg/mL. In contrast, trifloxystrobin and thiophanate-methyl exhibited much higher EC₅₀ values (2.94–29.62 µg/mL and 14.84–1237.20 µg/mL, respectively), indicating widespread resistance, particularly to thiophanate-methyl, whose curative and preventive efficacy rarely exceeded 44%. Preventive treatments were significantly more effective than curative applications for all fungicides tested. These findings highlight the urgent need to revise apple scab management strategies in Morocco, including the rotation of fungicides with different modes of action and the integration of non-chemical approaches. Broader sensitivity monitoring and the use of molecular diagnostics are recommended to better inform sustainable disease control programs. Full article

Background: High-intensity actions like accelerations and decelerations, often performed unilaterally, are crucial in elite female football but increase the risk of interlimb asymmetries and injury. Flywheel resistance training enhances eccentric strength, yet limited research has assessed how different inertial loads affect mechanical outputs in unilateral exercises. Purpose: This study investigated how two inertial loads (0.107 kg·m² and 0.133 kg·m²) influence power, acceleration, speed, and asymmetry during unilateral hip extensions in elite female footballers. Methods: Eighteen professional players (27 ± 4 years, 59.9 ± 6.5 kg, 168.2 ± 6.3 cm, BMI 21.2 ± 1.8) completed unilateral hip extensions on a conical flywheel under both inertia conditions. A rotary encoder measured peak/average power, acceleration, speed, and eccentric-to-concentric (E:C) ratios. Bilateral asymmetries between dominant (DL) and non-dominant (NDL) limbs were assessed. Paired t-tests and Cohen’s d were used for analysis. Results: Higher inertia reduced peak and mean acceleration and speed (p < 0.001, d > 0.8). Eccentric peak power significantly increased in the NDL (p < 0.001, d = 3.952). E:C ratios remained stable. Conclusions: Greater inertial loads reduce movement velocity but increase eccentric output in the NDL, offering potential strategies to manage neuromuscular asymmetries in elite female football players. Full article

As global environmental challenges intensify, there is an increasing need to equip younger generations with the knowledge, values, and sense of responsibility necessary for a sustainable future. This study explores how environmental citizenship education (ECE), implemented through a nature-based learning program within a Nature and Science School (NSS) in Türkiye, was experienced and interpreted by primary school pupils in relation to their development of understanding of sustainability and environmental citizenship. NSSs, integrated into the formal education system by the Turkish Ministry of National Education, offer inquiry-driven and experiential learning in natural settings. The study took place in Talat Göktepe Grove, a biodiverse site including forest and marine ecosystems, where a four-month ECE program was conducted. A holistic single-case study design was employed, drawing on pupil diaries and semi-structured interviews. A total of 88 pupils engaged in structured outdoor activities addressing biodiversity, sustainability, and the climate crisis. Initially, pupils described environmental citizenship through individual actions. Over time, their perspectives expanded to include civic participation, environmental rights, and collective responsibility. Their reflections also revealed a more nuanced understanding of sustainability, encompassing concepts such as ecosystem balance, renewable energy, and environmental justice. The study provides insight into how nature-based education may support meaning-making around environmental citizenship and sustainability in early education. Full article