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ARNT-dependent HIF-2α signalingprotects cardiac microvascular barrierintegrity and heart function postmyocardial infarction
No full textMyocardial infarction (MI) compromises the cardiac microvascular endothelial barrier, increasing leakage and inflammation. HIF2α, predominantly expressed in cardiac endothelial cells during ischemia, has an unclear role in barrier function during MI. Here, we show that inducible, adult endothelial-specific deletion of Hif2α in mice leads to increased mortality, cardiac leakage, inflammation, reduced heart function, and adverse remodeling after MI. In parallel, human cardiac microvascular endothelial cells (HCMVECs) lacking HIF2α display impaired barrier integrity, reduced tight-junction proteins, increased cell death, and elevated IL-6 levels, effects that are alleviated by overexpressing ARNT, a key partner of HIF2α under hypoxic conditions. Interestingly, ARNT, but not HIF2α, directly binds the IL-6 promoter to suppress its expression. These findings suggest the HIF2α/ARNT axis as a protective mechanism in heart failure post-MI and identify potential therapeutic targets to support cardiac function
Investigating the link between an ePortfolio and nursing students’ self-efficacy: a protocol of a sequential explanatory mixed method study
No full textThe global pandemic pushed universities to adopt online platforms for academic continuity, but capturing clinical practice evidence was challenging. ePortfolio pedagogy emerged as a solution, integrating technology, reflection, and assessment to support nursing students' development. This approach enhances digital literacy, lifelong learning, and professional growth by facilitating communication and collaboration. A PhD-funded study at Queen’s University Belfast, using a mixed methods sequential explanatory design, explores the understanding and impact of ePortfolios on nursing students, lecturers, and practice staff. The study, ethically approved by the Faculty of Medicine, Health & Life Sciences, aims to evaluate ePortfolio technology's effect on curriculum delivery and student performance. Initial results are expected in 2026, focusing on its impact within nursing and higher education
BioStructNet: structure-based network with transfer learning for predicting biocatalyst functions
No full textEnzyme–substrate interactions are essential to both biological processes and industrial applications. Advanced machine learning techniques have significantly accelerated biocatalysis research, revolutionizing the prediction of biocatalytic activities and facilitating the discovery of novel biocatalysts. However, the limited availability of data for specific enzyme functions, such as conversion efficiency and stereoselectivity, presents challenges for prediction accuracy. In this study, we developed BioStructNet, a structure-based deep learning network that integrates both protein and ligand structural data to capture the complexity of enzyme–substrate interactions. Benchmarking studies with different algorithms showed the enhanced predictive accuracy of BioStructNet. To further optimize the prediction accuracy for the small data set, we implemented transfer learning in the framework, training a source model on a large data set and fine-tuning it on a small, function-specific data set, using the CalB data set as a case study. The model performance was validated by comparing the attention heat maps generated by the BioStructNet interaction module with the enzyme–substrate interactions revealed from molecular dynamics simulations of enzyme–substrate complexes. BioStructNet would accelerate the discovery of functional enzymes for industrial use, particularly in cases where the training data sets for machine learning are small.<br/
Evaluating and improving the connectivity of China's protected area networks for facilitating species range shifts under climate change
No full textContemporary climate change is causing spatial redistributions of many species, potentially undermining the effectiveness of existing protected areas (PAs). This raises concerns about whether current PAs are connected enough to capture climate-induced range shifts and how to expand PAs to support this ecological process. Hence, we conducted a national-scale assessment of climate connectivity for the terrestrial PAs across mainland China. We found that most PAs are structurally connected to cool ones through low human impact (LHI) areas along temperature gradients. The connected PA networks could enable species to migrate and avoid an average climate warming of 2.9 °C under moderate emission scenario. Nevertheless, less than half (46.2%) of the PAs have achieved successful climate connectivity. To facilitate climate-induced range shifts, we identified priority areas for conservation based on their importance in supporting connections between PAs. Our study provides spatially explicit assessments of the connectivity of PA networks for range shifts and emphasizes the necessity to consider climate connectivity in the planning of PAs at regional scales
Environmental and biological factors of relevance to shellfish production in Northern Ireland: insights from 20 years of regional monitoring data
No full textA historical analysis was conducted to evaluate monitoring data in the coastal and estuarine waters of Northern Ireland over the 20-year period between 2001 and 2022 to identify current and emerging concerns and gaps in analysis relative to the sustainability of the aquaculture industry. The effects of biological factors such as the presence of harmful algal bloom phytoplankton and marine biotoxins, and environmental factors such as chemical contamination and the water quality on shellfish production were analysed. The influence of key meteorological factors, such as sea temperature, rainfall and sunshine hours, on the levels of environmental factors was also examined. The evaluation included a socio–economic perspective, exploring the impact of the shellfish industry on the Northern Irish economy and the surrounding communities. The article examined the challenges faced by shellfish producers in terms of regulatory compliance and market access, and provides suggestions for comprehensive environmental monitoring strategies, in particular improved sampling plans to be employed to address these challenges. Overall, the compilation analysis discovered that while the shellfish industry in Northern Ireland faces a number of challenges, it remains a valuable source of local employment and income, and has the potential for growth in the coming years. The findings presented will be of interest to researchers and policymakers in the aquaculture industry, and presents a valuable historical contribution on the evaluation of chemical and microbiological contaminants affecting shellfish production that may be useful for other production areas.<br/
Effects of water and sediment chemistry variables on aquatic macroinvertebrate community structuring in a subtropical Austral river system
No full textRiverine physical and chemical characteristics are influencing ecosystem integrity while shaping and impacting species richness and diversity. Changes in these factors could potentially influence community structuring through competition, predation and localised species extinctions. In this study, eight sampling sites over multiple seasons were assessed along the streams draining the City of Nelspruit, South Africa, to examine river health based on water and sediment quality, while using macroinvertebrates as bioindicators for pollution. All water variables with the exception for salinity were found to be significantly different among seasons, with sites having significant differences among all water variables. All sediment chemistry variables were also found to be significantly different among sites and seasons, with the exception of K for sites and Zn and Ca for seasons. The PCA factor loadings and two-cluster analysis identified two groupings, i.e. group 1 that consisted of all metals apart from K and Na and group 2 with K and Na metals. A total of 4470 macroinvertebrate taxa were identified, with Crustacea Caridina nilotica and Diptera Chironominae being dominant across seasons, with macroinvertebrate communities being found to be significantly different among sites and seasons. The most common functional feeding groups across sites were the collector–gatherers (52.2%), followed by collector–filters (26.8%), predators (16.4%), scrapers (4.4%) and shredders (0.1%). Boosted regression trees indicated that high variation in species richness occurred with change in resistivity, P, water pH, ORP, conductivity and S concentrations. These results evidence a strong linkage among the sediment, water quality, substratum embeddedness and habitat structure and community structure. It is important to protect the integrity of aquatic ecosystems through effective monitoring due to the increasing water and sediment quality pressures that arise from various anthropogenic activities.<br/
Role of the extracellular matrix in cancer: insights into tumor progression and therapy
No full textThe extracellular matrix (ECM) serves not only as a structural scaffold but also as an active regulator of cancer progression, profoundly influencing tumor behaviour and the tumor microenvironment (TME). This review focuses into the pivotal role of ECM alterations in facilitating tumor metastasis and explores therapeutic strategies aimed at counteracting these changes. We analyse targeted interventions against collagen, including approaches to inhibit its biosynthesis and disrupt associated signalling pathways critical for tumor architecture and cell migration. Additionally, therapies addressing hyaluronan are reviewed, highlighting methods to suppress its synthesis and enzymatic strategies to degrade it, thereby mitigating its tumor-promoting effects. The discussion extends to innovative approaches for modulating ECM stiffness, focusing on the roles of cancer-associated fibroblasts and lysyl oxidases, which are key contributors to ECM remodelling and mechanical signalling. By strategically modifying these ECM components, these interventions aim to enhance the efficacy of existing cancer treatments, tackle resistance mechanisms, and achieve more durable therapeutic outcomes. Insights from recent studies and clinical trials highlight the promise of these strategies in overcoming treatment resistance and improving patient outcomes. Advancing our understanding of ECM biology leads to the development of innovative and more effective cancer therapies.<br/
Formulation and evaluation of PVA-based composite hydrogels: physicochemical, leachables, and in vitro immunogenicity studies
No full textThis study explores the formulation and characterization of poly(vinyl alcohol) (PVA)-based composite hydrogels synthesized through solid-state crosslinking. Comprehensive assessments were conducted on their physicochemical properties, leachables, and immunogenicity. Swelling experiments demonstrated that the incorporation of poly(vinylpyrrolidone) (PVP) enhanced water retention, while chitosan had a minimal effect on swelling behavior. Qualitative analysis of leachables identified water-soluble components, including dehydrated PVA and PVP. Fourier-transform infrared (FTIR) spectroscopy confirmed the formation of ester bonds and indicated increased hydrogen bonding post-crosslinking. Thermal stability was validated by differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA), with decomposition observed at 320–330 °C. X-ray diffraction (XRD) analysis revealed enhanced crystallinity following crosslinking. Solid-state nuclear magnetic resonance (NMR) further confirmed chemical changes consistent with the results from other characterization techniques. In vitro assays using DC2.4 mouse dendritic cells showed that hydrogel extracts inhibited cell proliferation without causing cytotoxicity or triggering significant immune responses. These findings highlight the hydrogels’ biocompatibility and stability, supporting their potential for biomedical applications.<br/
Pan-cancer drivers of metastasis
No full textMetastasis remains a leading cause of cancer-related mortality, irrespective of the primary tumour origin. However, the core gene regulatory program governing distinct stages of metastasis across cancers remains poorly understood. We investigate this through single-cell transcriptome analysis encompassing over two hundred patients with metastatic and non-metastatic tumours across six cancer types. Our analysis revealed a prognostic core gene signature that provides insights into the intricate cellular dynamics and gene regulatory networks driving metastasis progression at the pan-cancer and single-cell level. Notably, the dissection of transcription factor networks active across different stages of metastasis, combined with functional perturbation, identified SP1 and KLF5 as key regulators, acting as drivers and suppressors of metastasis, respectively, at critical steps of this transition across multiple cancer types. Through in vivo and in vitro loss of function of SP1 in cancer cells, we revealed its role in driving cancer cell survival, invasive growth, and metastatic colonisation. Furthermore, tumour cells and the microenvironment increasingly engage in communication through WNT signalling as metastasis progresses, driven by SP1. Further validating these observations, a drug repurposing analysis identified distinct FDA-approved drugs with anti-metastasis properties, including inhibitors of WNT signalling across various cancers.<br/