Search Results (569)

The building sector plays a key role in the transition toward climate neutrality, with national regulations across the EU requiring the construction of nearly zero-energy buildings (nZEBs). However, while energy performance has been extensively studied, less attention has been given to the problem of ensuring user comfort—both indoors and in the surrounding outdoor areas—under nZEB design constraints. This gap raises two key research objectives: (1) to evaluate whether a well-designed nZEB with extensive glazing maintains acceptable indoor thermal comfort and (2) to assess whether residents experience greater outdoor thermal comfort and satisfaction in small, sun-exposed private gardens or in larger, shaded communal green spaces. To address these objectives, a newly built residential estate near Kraków (Poland) was analyzed. The investigation included simulation-based assessments during the design phase and in situ measurements during building operation, complemented by a user survey on spatial preferences. Indoor comfort was evaluated for rooms with large glazed façades, as well as rooms with standard-sized windows, while outdoor comfort was assessed in both private gardens and a shared green courtyard. Results show that shading the southwest-oriented glazed façade with an overhanging terrace provided slightly lower temperatures in ground-floor rooms compared to rooms with standard unshaded windows. Outdoors, users experienced lower thermal comfort in small, unshaded gardens than in the larger, vegetated communal area (pocket park), which demonstrated greater capacity for temperature moderation and thermal stress reduction. Survey responses further indicate that potential future residents prefer the inclusion of a shared green–blue infrastructure area, even at the expense of building some housing units in semi-detached form, instead of maximizing the number of detached units with unshaded individual gardens. These findings emphasize the importance of addressing both indoor and outdoor comfort in residential nZEB design, showing that technological efficiency must be complemented by user-centered design strategies. This integrated approach can improve the well-being of residents while supporting climate change adaptation in the built environment. Full article

Cellular plasticity enables cells to dynamically adapt their phenotype in response to environmental cues, a process central to development, tissue repair, and disease. Among the most studied plasticity programs is epithelial–mesenchymal transition (EMT), a transcriptionally controlled process by which epithelial cells acquire mesenchymal traits. Originally described in embryogenesis, EMT is now recognized as a key driver in both tumor progression and fibrotic remodeling. In cancer, EMT and hybrid epithelial/mesenchymal (E/M) states promote invasion, metastasis, stemness, therapy resistance, and immune evasion. In fibrotic diseases, partial EMT (pEMT) contributes to fibroblast activation and excessive extracellular matrix deposition, sustaining organ dysfunction mainly in the kidney, liver, lung, and heart. This review integrates recent findings on the molecular regulation of EMT, including signaling pathways (TGF-β, WNT, NOTCH, HIPPO), transcription factors (SNAIL, ZEB, TWIST), and regulatory layers involving microRNAs and epigenetic modifications. Moreover, we discuss the emergence of pEMT states as drivers of phenotypic plasticity, functional heterogeneity, and poor prognosis. By comparing EMT in cancer and fibrosis, we reveal shared mechanisms and disease-specific features, emphasizing the translational relevance of targeting EMT plasticity. Finally, we explore how cutting-edge technologies, such as single-cell transcriptomics and lineage tracing, are reshaping our understanding of EMT across pathological contexts. Full article

Background: A range of cancer cells are significantly inhibited by FTY720. It is unknown, nevertheless, how FTY720 influences the onset of non-small cell lung cancer (NSCLC). Using bioinformatics techniques, we analyzed and the possible molecular mechanisms and targets of FTY720 for the treatment of NSCLC. Methods: DEGs (Differentially expressed genes) were acquired by differential analysis of the dataset GSE10072. Obtained FTY720 target genes and NSCLC disease genes from databases such as Swiss-TargetPrediction and GeneCard. Subsequently, target and disease genes, as well as DEGs, were merged for Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, gene ontology (GO), and protein interaction analysis. The overlapping genes of DEGs and target genes, and disease genes were also obtained separately and subjected to survival as well as expression analyses. We constructed the regulatory network of miRNAs and transcription factors (TFs) on hub genes. Finally, the immune cell association of hub genes was evaluated using the ssGSEA method, molecular docking of FTY720 to hub genes was carried out utilizing Autodock, and molecular dynamics simulations were conducted. Results: In this study, 444 DEGs, 232 target genes of FTY720, and 466 disease genes were obtained. Moreover, a total of 1062 genes were obtained by removing duplicate values after merging, among which PIK3R1, Akt1, and S1PR1 had the highest DEGREE values in the protein interactions network, and these genes were primarily enriched in MAPK, PI3K-Akt signaling pathways, with the PI3K-Akt signaling pathway being the most prominent. Among the overlapping genes, three potential targets of FTY720 for NSCLC treatment were found: S1PR1, ZEB2, and HBEGF. ZEB2 and S1PR1 were determined to be hub genes and to significantly affect NSCLC prognosis by survival analysis. Furthermore, hsa-miR-132-3p, hsa-miR-192-5p, and hsa-miR-6845-3p were strongly associated with FTY720 for the treatment of NSCLC; CTBP1 (carboxy-terminal binding protein 1), EZH2 (protein lysine N-methyltransferase), and ZNF610 (zinc-finger protein 610) may all influence the expression of ZEB2 and S1PR1. Hub genes had a substantial negative link with memory B cells and a significant positive correlation with memory CD8 T cells and Th17 helper T cells. The molecular docking and kinetic simulation results of FTY720 with the two hub genes indicate that the protein-ligand complex has good stability. Conclusion: Our research indicates that FTY720 may inhibit NSCLC via possible targets ZEB2 and S1PR1, further laying the theoretical foundation for the utilization of FTY720 in NSCLC treatment. Full article

This article analyses the possibility of using Li-ion batteries removed from battery electric vehicles (BEVs) as short-term energy storage devices in a near-zero energy building (nZEB) in conjunction with a rooftop photovoltaic (PV) system. The technical and economic feasibility of this solution was compared to that of a standard commercial LIB (Lithium-Ion battery) BESS Battery Energy Storage System). Two generations of the same BEV model battery were tested to analyse their suitability for powering a building. The necessary changes to the setup of such a battery for building power supply purposes were analysed, as well as its suitability. As a result, analyses of profitability over the predicted life span and NPV (net present value) of SLEVBs (second-life BEV batteries) for building power were carried out. The study also conducted preliminary research on the effectiveness of such projects and their pros and cons in terms of security. The author calculates the profitability of a ready-made PV BESS with a set of SLEVBs, estimating the payback periods for such investments relative to electricity prices in Poland. The article concludes on the potential of SLEVBs to support self-consumption in nZEB buildings and its environmental impact on the European circular economy. Full article

Background: Breast cancer is a complex, multifactorial malignancy characterized by the uncontrolled proliferation of epithelial cells, with certain subtypes exhibiting resistance to conventional therapies. Plant-derived essential oils have been proposed as potential anticancer agents due to their bioactive compounds. Recent studies have demonstrated that Decatropis bicolor essential oil exhibits activity against breast cancer, attributed to diverse secondary metabolites such as δ-cadinene. Aberrant expression of adhesion and invasion proteins, including MMPs, CD44, N-cadherin, and ZEB-2, are key signs of breast cancer progression and metastasis; they represent relevant molecular targets. Objectives: To investigate the interaction of δ-cadinene with these proteins using in silico approaches and in vitro evaluations. Methods: In silico analyses were conducted to assess the interaction and stability of δ-cadinene with target proteins. In vitro assays, including cytotoxicity, morphological analysis, and cell invasion assays, were performed using MDA-MB-231 and MCF10-A cell lines. Results: Interaction analysis suggest that δ-cadinene interacts with key catalytic residues in MMP-2, sharing features with Quercetin. Blind docking revealed a second high-affinity site in the Fibronectin type II domain. Molecular dynamics simulations confirmed the stability of these complexes. In vitro studies showed that δ-cadinene significantly reduced MDA-MB-231 cell viability in a concentration-dependent manner, without affecting MCF10-A cells, and significantly inhibited invasion and MMP-2 activity after 24 h. Conclusions: δ-cadinene exhibits selective cytotoxic and anti-invasive activity in MDA-MB-231 cells, likely through dual inhibition of the catalytic and adhesion domains of MMP-2. These findings support δ-cadinene as a potential candidate for future therapeutic development in metastatic breast cancer. Full article

Background: Epithelial-mesenchymal transition (EMT) is prevalent in human cancer and facilitates tumor metastasis and therapy resistance by enhancing cancer cell motility, invasiveness, survival, and immune evasion. However, the molecular mechanisms underlying the cellular changes during EMT remain largely elusive, making it challenging to simultaneously target these diverse malignant phenotypes. Results: Here, we show that the EMT-inducing ZEB transcription factors directly repressed WWC1 (also known as KIBRA), a key upstream activating component of the Hippo signaling pathway. The EMT program thus inherently downregulated WWC1, leading to impaired Hippo signaling and constitutive activation of the downstream effector and transcriptional coactivator YAP. The YAP-dependent transcriptional program promotes manifold cellular phenotypes that resemble those induced during EMT. Indeed, pharmacological inhibition of YAP suppressed EMT-stimulated cell migration and invasion, apoptosis resistance, and cell size growth, identifying active YAP as a common essential mediator of multiple EMT-associated phenotypes. Moreover, YAP activation directly induced transcription of B7 family immune checkpoint proteins VSIR (VISTA) and PD-L2, and rendered cancer cells resistant to effector CD8 T cells. Conclusions: Collectively, the results suggest that EMT intrinsically activates YAP by repressing WWC1, providing a non-genetic mechanism for pervasive YAP activation in cancer. Activated YAP, in turn, critically contributes to diverse EMT-enhanced malignant phenotypes and immune evasion. Therefore, pharmacological targeting of YAP may suppress various EMT-associated malignant properties and improve the efficacy of anti-PD-1 immunotherapy, offering a promising therapeutic strategy against cancer cells exhibiting EMT characteristics. Full article

Cisplatin resistance remains a major therapeutic challenge in oral squamous cell carcinoma (OSCC), leading to treatment failure and poor outcomes. This study aimed to generate and characterize cisplatin-resistant OSCC models to elucidate resistance mechanisms. Two resistant OSCC cell lines (SCC-9R and HSC-3R) were developed through gradual dose escalation. Parental and resistant cells were analyzed via RNA-seq and gene set enrichment analysis, and validated through RT-qPCR, Western blot, immunofluorescence, and gelatin zymography. Functional assays, including 2D and 3D migration and invasion models, assessed phenotypic changes. A multi-omics analysis revealed molecular alterations in resistant cells, including 305 differentially expressed genes (DEGs) in HSC-3R (187 upregulated) and 782 in SCC-9R (298 upregulated) versus parental lines, with enrichment for extracellular matrix organization (p < 0.001) and consistent epithelial–mesenchymal transition (EMT) activation (p < 0.001), demonstrated by the upregulation of ZEB1, ZEB2, Vimentin, and TWIST1, and E-cadherin suppression. Functional validation confirmed an aggressive phenotype, including increased migration (p < 0.05), invasion (p < 0.01), and elevated MMP-2 (p < 0.01) and MMP-9 (p < 0.001) activity. Findings were verified in 3D spheroid models. Overall, cisplatin resistance in OSCC involves EMT, inflammatory signaling, and metabolic adaptation. The consistency of these features across both models supports the robustness of this in vitro system and reveals targets for therapeutic intervention. Full article

This study presents a simulation-based analysis of a steel modular building that integrates technologies that support the energy transition in the built environment. The focus is placed on the implementation of building-integrated photovoltaics (BIPVs), with photovoltaic modules incorporated into the façade and balcony railings. Several modern photovoltaic façade systems were examined. In addition, the study considers the application of photovoltaic glazing enhanced with active quantum coatings. Seven distinct BIPV modules were analysed, each characterised by unique features, with particular emphasis on the influence of colour in tinted variants. A performance degradation analysis was conducted for railing-mounted modules with varying glass tints. The simulation results were correlated with the building’s electricity demand. Full article

The decarbonization of the energy sector drives the implementation of building-integrated and building-applied photovoltaic (BIPV–BAPV) systems. However, these systems face space and design limitations in urban environments. This study proposes an innovative methodology for the design and sizing of urban photovoltaic systems, considering diverse distributions and introducing metrics that link performance to occupied area. The methodology was applied to a university building in southern Spain, comparing the performance of rooftop photovoltaic (RTPV) and facade-applied photovoltaic (FAPV) systems. FAPV showed a larger useful area, resulting in similar self-sufficiency indices (RTPV: 22%, FAPV: 21%) and a 5% higher total emission reduction compared to the RTPV system. The proposed metrics demonstrate that FAPV outperforms RTPV both in final yield (49 vs. 21 kWh/kWp·m²) and total emission reduction (3.1 vs. 1.3 kgCO2eq/kWp·m²) normalized by installed power and occupied area. These complementary metrics are crucial for evaluating and selecting optimal photovoltaic configurations with varying generation densities and efficiencies, driving urban decarbonization and the creation of Zero Energy Buildings (ZEBs). Full article

Renal cell carcinoma (RCC) has a well-established propensity to form grossly visible tumour thrombi; however a comprehensive understanding of the underlying mechanisms is still lacking. The epithelial–mesenchymal transition (EMT) has been implicated in the progression of many carcinomas, including RCC; however, its exact role in the formation of venous tumour thrombi remains unclear. This study aims to explore the involvement of the EMT in venous invasion in RCC. In 14 patients with WHO/ISUP grade 2/3 clear cell RCC with venous invasion, the expression of main EMT markers (the miR-200 family, miR-205, SNAI1/2, TWIST1, ZEB2, and CDH1) was analyzed by qPCR in the selected tumour regions—the tumour centre (TC), the tumour periphery (TP), the venous tumour thrombus (VTT)—and compared to the corresponding non-neoplastic kidney tissue (N). Expression of E-cadherin, N-cadherin, and ZEB2 was analyzed immunohistochemically. The miR-200 family was downregulated in all areas examined compared to the corresponding N. When comparing the VTT with the TC, upregulation of miR-200c and miR-429 was observed. CDH1 was downregulated when the TP was compared with N, while SNAI2 was downregulated in all tumour regions. There was a strong correlation between the expression of all members of the miR-200 family. Our results demonstrate the presence of distinct molecular signatures between the selected ccRCC regions. The upregulation of two miRNAs in the VTT compared to the TC and their correlation with CDH1 expression could indicate a reversal of the EMT towards a more epithelial cell state in the VTT. Full article

Achieving zero-energy buildings (ZEBs) requires the appropriate planning of renewable energy systems, particularly photovoltaic (PV) systems, from the early design stage (EDS). Conventional PV system design tools have limitations, including insufficient integration with the architectural design process, complex operability, and inability to adequately reflect the characteristics of the EDS. In this study, we developed a PV system optimization tool based on SketchUp, which is widely used in the EDS. The developed tool inputs the building’s 3D modeling information and derives an optimal layout plan that minimizes the number of PV modules while achieving the target energy self-sufficiency rate (ESR) via particle swarm optimization. To verify the performance of the developed tool, a comparative analysis with the System Advisor Model (SAM) was performed, resulting in high accuracy with a maximum relative error of 2.25% in 15 verification cases. Through case studies of 20 different building masses, optimal PV layout plans that stably achieved a target ESR of 20% were successfully derived for diverse mass cases. This tool enables architects to perform preliminary sizing and performance evaluations of PV systems in the EDS without the support of engineers and provides an environment for the integrated consideration of energy performance and esthetics through the presentation of visualized results to support more effective decision-making in the EDS of ZEB projects. Full article

Postpartum metritis in dairy cows compromises reproductive performance and leads to substantial economic losses. This study investigated the molecular mechanisms underlying metritis by integrating high-throughput circulating microRNA (miRNA) profiling with systems-level bioinformatics. Previously, 30 differentially expressed miRNAs, 16 upregulated and 14 downregulated, were identified in metritis-affected cows compared to healthy controls. Building on these findings, this study predicted miRNA target genes and constructed regulatory networks involving miRNAs, mRNAs, circRNAs, lncRNAs, and snRNAs, alongside protein–protein interaction networks. Functional annotation and KEGG pathway analysis revealed that upregulated miRNAs influenced genes involved in immune activation, apoptosis, and metabolism, while downregulated miRNAs were associated with angiogenesis, immune suppression, and tissue repair. Hub genes such as AKT3, VEGFA, and HIF1A were central to immune and angiogenic signaling, whereas UBE3A and ZEB1 were linked to immune inhibition. Interferon-stimulated genes (e.g., ISG15, RSAD2, CXCL chemokines) were shown to regulate solute carriers, contributing to immune dysregulation. Key pathways included PI3K-Akt, NF-κB, JAK-STAT, insulin resistance, and T cell receptor signaling. Noncoding RNAs such as NEAT1, KCNQ1OT1, and XIST, along with miRNAs like bta-miR-15b and bta-miR-148a, emerged as pro-inflammatory regulators, while bta-miR-199a-3p appeared to exert immunosuppressive effects. These findings offer new insights into the complex regulatory networks driving metritis and suggest potential targets for improving fertility in dairy cows. Full article

CD26 (dipeptidyl peptidase-4) is a marker of colorectal cancer stem cells with high metastatic potential and resistance to therapy. Although CD26 expression is known to be associated with tumor progression, its functional involvement in epithelial-mesenchymal transition (EMT) and metastasis remains to be fully elucidated. In this study, we aimed to investigate the effects of a monoclonal anti-CD26 antibody on EMT-related phenotypes and metastatic behavior in colorectal cancer cells. We evaluated changes in EMT markers by quantitative PCR and Western blotting, assessed cell motility and invasion using scratch wound-healing and Transwell assays, and examined metastatic potential in vivo using a splenic injection mouse model. Treatment with the anti-CD26 antibody significantly increased the expression of the epithelial marker E-cadherin and reduced levels of EMT-inducing transcription factors, including ZEB1, Twist1, and Snail1, at the mRNA and protein levels. Functional assays revealed that the antibody markedly inhibited cell migration and invasion in vitro without exerting cytotoxic effects. Furthermore, systemic administration of the anti-CD26 antibody significantly suppressed the formation of liver metastases in vivo. These findings suggest that CD26 may contribute to the regulation of EMT and metastatic behavior in colorectal cancer. Our data highlight the potential therapeutic utility of CD26-targeted antibody therapy for suppressing EMT-associated phenotypes and metastatic progression. Full article

Endometriosis is a disease characterized by the presence of endometrial glands and stroma outside of the uterine corpus, often clinically presenting with pain and/or infertility. Ectopic lesions exhibit features characteristic of epithelial-to-mesenchymal transition (EMT), a process in which epithelial cells lose polarity and acquire mesenchymal traits, including migratory and invasive capabilities. During the process of EMT, epithelial traits are downregulated, while mesenchymal traits are acquired, with cells developing migratory ability, increasing proliferation, and resistance to apoptosis. EMT is promoted by exposure to hypoxia and stimulation by transforming growth factor-β (TGF-β), platelet-derived growth factor (PDGF), and estradiol. Signaling pathways that promote EMT are activated in most ectopic lesions and involve transcription factors such as Snail, Slug, ZEB-1/2, and TWIST-1/2. EMT-specific molecules present in the serum of women with endometriosis appear to have diagnostic potential. Strategies targeting EMT in animal models of endometriosis have demonstrated regression of ectopic lesions, opening the door for novel therapeutic approaches. This review summarizes the current understanding of the role of EMT in endometriosis and highlights potential targets for EMT-related diagnosis and therapeutic interventions. Full article

Understanding and forecasting energy consumption patterns is crucial for improving energy efficiency and human well-being, especially in diverse infrastructures like Spain. This research addresses a significant gap in energy demand forecasting across three building types by comparing six machine learning algorithms: Artificial Neural Networks, Random Forest, XGBoost, Radial Basis Function Network, Autoencoder, and Decision Trees. The primary aim is to identify the most effective model for predicting energy consumption based on historical data, contributing to the relationship between energy systems and urban well-being. The study emphasizes challenges in energy use and advocates for sustainable management practices. By forecasting energy demand over the next three years using linear regression, it provides actionable insights for energy providers, enhancing resilience in urban environments impacted by climate change. The findings deepen our understanding of energy dynamics across various building types and promote a sustainable energy future. Stakeholders will receive targeted recommendations for aligning energy production with consumption trends while meeting environmental responsibilities. Model performance is rigorously evaluated using metrics like Squared Mean Root Percentage Error (RMSPE) and Coefficient of Determination (R²), ensuring robust analysis. Training times for models in the LUCIA building ranged from 2 to 19 s, with the Decision Tree model showing the shortest times, highlighting the need to balance computational efficiency with model performance. Full article