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Development of a blended MOOC implementation model for English language learning: An interpretive structural modeling approach
The integration of Massive Open Online Courses (MOOCs) into traditional English language education has created new opportunities for scalable, flexible, and inclusive learning. However, existing studies on MOOCs and blended learning remain largely descriptive and lack a structured framework that prioritizes key implementation elements for effective integration into formal education. This study develops a structured implementation model for blended MOOCs (bMOOCs) tailored to undergraduate English as a Foreign Language (EFL) instruction. This gap is particularly evident in specific contexts such as Vietnam, where institutional conditions, technological readiness, and learner characteristics significantly influence implementation effectiveness. Using the Interpretive Structural Modelling (ISM), the research identifies and validates 20 key sub-indicators grouped into three interconnected phases: planning, implementation, and evaluation. The model emphasizes the importance of analyzing learners’ backgrounds and motivations, setting clear learning objectives, and selecting appropriate materials and technologies. During implementation, the focus shifts to effective instructional strategies, learner participation, and technical support. The evaluation phase prioritizes formative assessment and timely feedback to promote continuous improvement and engagement. This learner-centered approach addresses common challenges in blended learning environments. The model offers practical guidance for stakeholders in EFL education, such as administrators, educators, and curriculum developers, seeking to enhance English language education through blended MOOCs. Practical implications for the implementation of blended MOOCs in EFL instruction are also addressed to enhance the quality of English language instruction in the digital age.
Nationwide survey reveals gender disparities in cardiovascular awareness and lifestyle behaviors among polish adolescents aged 18 years
Constitutive activation of a hybrid two-component regulator reveals cross-regulation of polysaccharide utilization genes in Bacteroides
Fossil fuel emissions dominate Northern Hemisphere CO2 seasonal cycle trends under mitigation scenarios
Abstract Variations in the atmospheric CO 2 seasonal cycle across the Northern Hemisphere have historically been dominated by terrestrial ecosystems, making ground-based observations a reliable proxy for terrestrial carbon dynamics. However, whether this dominance will persist in the future remains uncertain. Here we combine atmospheric transport modeling with factorial simulations to assess and attribute future changes in the CO 2 seasonal cycle through 2100. We show that the dominant drivers of these changes shift fundamentally across scenarios. Under the high-emission scenario (SSP5-8.5), strengthening land sinks dominate and amplify CO 2 seasonal variability, preserving ground-based observations as a reliable terrestrial proxy. In contrast, under the low-emission scenario (SSP1-2.6), CO 2 seasonal amplitude declines widely, driven primarily by reduced fossil fuel emissions and their dampened seasonality. Consequently, established ground-based CO 2 observations may no longer reliably track terrestrial carbon dynamics under mitigation pathways, underscoring the need for new approaches for monitoring and climate policy verification.
Synthesis and Structures of Formal Ni(I/II/III) Imido Complexes
A network pharmacology-based approach and molecular docking study to explore the therapeutic potential of a nutraceutical formula (Vernolac) in the treatment of cancer
Vernolac is a commercially available polyherbal nutraceutical capsule containing Vernonia zeylanica aerial parts, Nigella sativa seeds, Hemidesmus indicus roots, Leucas zeylanica aerial parts, and Smilax glabra rhizome. Herbal formulations, organic extracts, and isolated phytochemicals from these plants have demonstrated anticancer properties. However, the mechanisms underlying Vernolac’s anticancer activity as a polyherbal formulation remain largely unexplored. This study utilized an integrative network pharmacology-based approach, supported by in vitro experiments, to investigate Vernolac’s anticancer potential. Phytochemicals were retrieved from databases, screened for drug-likeness and oral bioavailability using SwissADME, yielding 155 drug-like compounds, and their protein targets were predicted using SwissTargetPrediction. The intersection of phytochemical targets with cancer-related targets from GeneCards identified 137 common targets. Protein-protein interaction analysis using STRING and Cytoscape revealed fourteen key hub nodes, including AKT1, BCL2, CASP3, CTNNB1, EGFR, ESR1, GAPDH, HSP90AA1, HSP90AB1, IL6, JUN, SRC, STAT3, and TNF. Network analyses highlighted key phytochemicals, including vernolactone, thymoquinone, quercetin, nigellidine, α-hederin, and carvacrol. GC–MS profiling of the supercritical CO 2 extract of Vernolac revealed a diverse phytochemical composition enriched with terpenes, fatty acids, and sterols, including the key constituents stigmasterol, thymoquinone, and carvacrol. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses revealed significant enrichment of the identified targets across multiple cancer pathways. Molecular docking and dynamics simulations identified novel target-ligand interactions, such as vernolactone-β-catenin and α-hederin-CDK4. The Sulforhodamine B assay demonstrated selective antiproliferative activity of Vernolac extract against cancerous cell lines MCF-7 (IC 50 = 54.01 ± 0.02 μg/mL), Caco-2 (IC 50 = 85.52 ± 0.13 μg/mL), NTERA-2 cl.D1 (IC 50 = 42.41 ± 0.06 μg/mL), and non-cancerous MCF-10A (IC 50 = 803.5 ± 0.03 μg/mL). Collectively, network analysis suggests that phytochemicals in Vernolac may exert anticancer effects through multiple cancer-related pathways, including those associated with apoptosis, immune modulation, oxidative stress, inflammation, and cell proliferation. Furthermore, the identified targets and enriched pathways suggest a potential role in modulating drug resistance and treatment response, providing a computational basis for its application as an adjunct to conventional cancer therapies and warranting further investigation in preclinical and clinical settings.
Consensus-based radiographic threshold for identifying vertical periodontal bone loss: an international observer study
The landscape for therapeutic cancer vaccines
Restoring cortical disinhibition improves Huntington’s disease phenotypes
Abstract Huntington’s disease (HD) is a devastating movement disorder without a cure at present 1 . Although the monogenic basis of HD is well defined 2 , the complex downstream effects that underlie behavioural symptoms are poorly understood. These effects include cortical dysfunction 3,4 , yet the roles of specific cortical neuronal subtypes in HD symptoms remain largely unexplored. Here we used longitudinal in vivo two-photon calcium imaging to examine the activity of three cortical inhibitory neuron (IN) subtypes and excitatory corticostriatal (CStr) projection neurons in the motor cortex of the transgenic R6/2 HD mouse model throughout disease progression. We found that motor deficits in R6/2 mice were accompanied by neuron subtype-specific abnormalities in movement-related activity. This included marked hypoactivity of vasoactive intestinal peptide (VIP)-INs and CStr neurons, which was also observed in the knock-in zQ175DN HD mouse model. Optogenetic activation of VIP-INs in R6/2 mice restored healthy levels of activity in VIP-INs and their downstream CStr neurons and ameliorated motor deficits in R6/2 mice; behavioural improvements persisted for days after stimulation. Our findings highlight cortical INs as a potential therapeutic target for HD.
Cyclic GMP-dependent activation of Ca2+ release from the ER and digestive vacuole at distinct phases of intraerythrocytic Plasmodium falciparum development
Tectonically driven integration of the 4.8 Ma Colorado River USA tracked with detrital sanidine and fish genetics
Fast Interfacial Hole Consumption Suppresses Space–Charge Layer Trap Filling in BiVO <sub>4</sub> Photoanodes
Determining optimal practices for foal weaning – A protocol for a systematic review and network meta-analysis
Background Weaning is a stressful time in a foal’s ( Equus caballus ) life. As humans artificially manage weaning in domestic horses, it provides an opportunity to safeguard horse welfare early in life, with potential long-term benefits. While numerous studies have examined the effects of different weaning and management interventions on foal stress, optimal weaning practices have yet to be identified. Overall purpose of the study: To identify which weaning interventions and management practices have the greatest potential to improve foal welfare based on physiological and behavioural outcomes. Research questions: (1) What physiological and behavioural changes occur in foals in response to artificial weaning? (2) Do different interventions during weaning produce different physiological and behavioural outcomes in foals? (3) How do study-level characteristics explain heterogeneity in foal outcomes during weaning, and which impact welfare outcomes across different interventions? (4) Which interventions, management practices, or combinations thereof most effectively optimise foal welfare during weaning? Methodology Six databases were searched on 24 August 2025. Database search strings were based on the Population-Intervention-Comparator-Outcome (PICO) framework and were PRESS-reviewed. Additional studies, including grey literature, will be identified through dissertation databases, ScienceDirect, Google Scholar, and by hand-searching the reference lists of included studies and narrative reviews, to ensure a comprehensive search. Articles will be selected based on predefined eligibility criteria. Two reviewers will independently conduct title/abstract and full-text screening, data extraction, and assess risk of bias and confidence in the evidence (GRADE and CINeMA). Results will be synthesised through pairwise and Bayesian network meta-analysis using R Statistical Software. Conclusion This systematic review will be the first to investigate foal welfare during artificial weaning, and the findings are expected to provide evidence-based recommendations to improve foal welfare. This paper outlines the protocol that will be used and does not contain any empirical results. Registration This systematic review protocol was registered on the Open Science Framework (OSF) on 19 May 2025 ( https://doi.org/10.17605/OSF.IO/DJWQY ).
When and how to partition airspace: a data-driven control framework for dynamic airspace sectorization based on multi-objective receding horizon optimization
Casdatifan shows durable response linked to HIF-2α biology in kidney cancer
Abstract Clear cell renal cell carcinoma (ccRCC) is largely driven by the transcription factor hypoxia-inducible factor 2α (HIF-2α) 1 . Here we show that monotherapy with casdatifan—an orally bioavailable, potent and selective HIF-2α inhibitor 2 —produces meaningful, durable antitumour activity with manageable safety in individuals with refractory metastatic ccRCC. Dose-expansion data from the ARC-20 study ( NCT05536141 ) are presented, including for the 100 mg once daily (QD) cohort ( n = 32) and the total cohort ( n = 127). Treatment discontinuation from casdatifan-related adverse events was infrequent (3%), and class-effect toxicities included anaemia and hypoxia. The confirmed objective response rates (ORRs) were 35% (95% confidence intervals (CI) = 19–55%; 100 mg QD) and 31% (95% CI = 23–40%; total); median progression-free survival (PFS) was not estimable (95% CI = 5.7–not estimable; 100 mg QD) and 12.2 months (9.4–20.6; total). Greater maximal reductions in serum erythropoietin were associated with improved clinical outcomes, including a higher ORR ( P = 0.001), lower rates of progressive disease ( P = 0.003) and longer PFS ( P = 0.006). Erythropoietin expression was restricted to cancer cells and was significantly higher at the mRNA level in patients with clinical benefit. Concordantly, HIF-2α protein expression and HIF-2α expression signature were associated with prolonged PFS. Overall, our findings show that casdatifan achieves meaningful, durable responses with manageable safety. These data establish a link between on-target HIF-2α pathway modulation, tumour biology and clinical efficacy.
TGF-β2 drives lipid droplet accumulation in chondrocytes through the TβRI/p-Smad3/Fabp5 axis
Voltage imaging of CA1 pyramidal cells and SST+ interneurons reveals stability and plasticity mechanisms of spatial firing
A ROS-Responsive DNA Nanodevice for Targeted Cytosolic siRNA Delivery in Metabolic Dysfunction-Associated Steatohepatitis
Short- and long-term scaling behavior of blood pressure and pulse arrival time during sleep in healthy controls and patients with obstructive sleep apnea
Obstructive sleep apnea (OSA) is characterized by recurrent respiratory events that trigger autonomic arousals and blood pressure (BP) surges, contributing to elevated cardiovascular risk. Photoplethysmography (PPG)-derived timing markers such as pulse arrival time (PAT) are frequently used as noninvasive surrogates of BP dynamics, yet their interpretation is confounded by the pre-ejection period and peripheral vascular effects. Here, we used detrended fluctuation analysis (DFA) to quantify short- and long-term scaling exponents of continuous blood pressure (Portapres), PPG-, and PAT-derived signals across sleep stages in healthy individuals and patients with OSA. Directly measured systolic and diastolic BP exhibited a robust short- to long-term crossover across all sleep stages, with elevated short-range exponents ( α 1 > 1 ) and lower long-range exponents ( α 2 < 1 ), reflecting well-organized autonomic and vascular control. In OSA, this crossover persisted but was visibly attenuated, consistent with reduced short-term adaptability of cardiovascular regulation. In contrast, PAT-based indices showed substantially weaker short-range correlations and minimal crossover structure. Systolic PAT displayed almost no separation between α 1 and α 2 , and PPG-derived measures exhibited scaling patterns that differed fundamentally from BP. Across modalities, PAT (whether derived from BP or PPG) failed to reproduce the multiscale organization characteristic of beat-to-beat BP dynamics. Group comparisons further identified systolic BP scaling, particularly the short-range exponent α 1 , as the most sensitive marker of cardiovascular dysregulation in OSA, whereas PAT and PPG provided complementary but physiologically distinct information related to peripheral vascular and autonomic modulation. These findings demonstrate that PAT and PPG timing measures should not be used as surrogates for BP in fractal or scaling analyses and underscore the unique diagnostic value of BP-derived scaling behavior for assessing cardiovascular regulation during sleep.