Search Results (6,208)

Polyetheretherketone (PEEK), a high-performance thermoplastic, is utilized in bone tissue engineering due to its elastic modulus resembling that of human cortical bone. However, toxicological studies on PEEK remain limited. PEEK disrupts bone homeostasis by recruiting macrophages and inducing the aggregation of foreign body multinucleated giant cells, ultimately leading to bone resorption. The lack of effective therapeutic approaches underscores the importance of identifying novel treatments. This study systematically investigated the potential molecular mechanisms underlying PEEK-induced bone resorption using network toxicology, molecular docking techniques, and molecular dynamics simulations. We first conducted a network-based toxicological assessment based on the molecular structure of PEEK. By integrating and screening targets from multiple databases, we identified 139 potential targets associated with PEEK-induced bone resorption and constructed an interaction network diagram of these targets. Gene Ontology (GO)/KEGG enrichment analysis revealed that PEEK may induce bone resorption through pathways such as the PI3K-AKT signaling pathway and TNF signaling pathway. Further analysis using STRING and Cytoscape 3.9.0 software identified 53 core targets, including MAPK3, TNF, IL-6, AKT1, IL-1β, EGFR, and MMP9. We found that enriched highly correlated pathways encompassed core targets, supporting the scientific hypothesis that PEEK induces bone resorption. Furthermore, molecular docking and molecular dynamics simulation results confirmed that PEEK exhibits strong binding affinity with core targets, forming stable complexes. In summary, this study not only reveals the potential biological mechanisms underlying PEEK-induced bone resorption but also provides new evidence for future prevention and treatment of PEEK-induced bone imbalance. Full article

Digital transformation in higher education has increasingly shifted from a technology-centered agenda toward a multidimensional institutional process involving governance, quality assurance, process redesign, and data-driven decision-making. This study proposes and operationalizes an analytical framework for examining digital transformation in universities through an interactive Human–Machine Interface developed in Python. The framework is structured around three complementary methodological cores: ontology-based modeling, statistical reliability analysis, and multiobjective optimization. The ontology module organizes the semantic structure of digital transformation dimensions, revealing their relational hierarchy and structural relevance. The statistical module evaluates internal consistency and distributional behavior through Cronbach’s alpha, corrected item–total correlation, and density-based inspection. The optimization module formulates intervention selection as a constrained multiobjective problem, allowing the identification of efficient portfolios under cost, readiness gain, equity, and feasibility criteria. The analytical environment also incorporates interactive dashboards, VOSviewer-style relational exploration, and exportable high-resolution figures. Results show that digital transformation readiness is heterogeneous across groups, that governance-oriented dimensions occupy a central semantic role, and that institutional intervention planning benefits from Pareto-efficient decision support rather than single-criterion ranking. The study contributes a coherent bridge between conceptual models of digital transformation and an operational analytical environment capable of supporting institutional diagnosis, evidence-based prioritization, and strategic planning in regulated higher education settings. Full article

Background/Objectives: Psoriasis is a chronic immune-mediated skin disease, with plaque psoriasis being its most prevalent form. Although biologic therapies have significantly improved outcomes for patients with moderate to severe disease, certain anatomical regions often remain resistant to treatment. Given the observed variability in treatment response depending on lesion location, we aimed to explore anatomical site-specific differences in the skin transcriptome. Methods: Using a non-invasive tape-stripping technique, we collected and analyzed 44 psoriatic plaque samples from the scalp, trunk, upper extremities, and lower extremities, followed by differential gene expression and gene ontology analysis. Moreover, we included 80 samples obtained from healthy skin biopsies (GSE54456) to conduct an inflammation-controlled approach. We used two different approaches, an intra-disease approach, in which anatomically different sites were compared, and an inflammation-controlled approach, in which the inflammation bias was reduced. Results: Our findings indicate distinct molecular signatures and biological pathways across different anatomical sites, including differential expression of SERPINB7 and miRNAs such as miR-205 and miR-203a, along with different pathways. Furthermore, our results emphasized the heterogeneity of psoriasis and suggested that site-specific molecular mechanisms may contribute to variations in disease manifestation and treatment response. Conclusions: This study highlights the need for more personalized, site-specific therapeutic strategies. It should be considered an exploratory pilot study, and larger studies with paired samples from multiple anatomical sites within the same patients are needed to validate the identified transcriptomic signatures. Full article

This article analyzes how twentieth- and twenty-first-century Afro-Colombian women poets from the Pacific region challenge and reframe the feminization of the land and the naturalization of the Black female body within colonial and Eurocentric epistemologies. Drawing on a framework that conceptualizes body, territory, spirituality, and community as an interdependent continuum, the article conducts close textual analysis to demonstrate how these poets construct territory and the Black female body as sentient sites. These sites are simultaneously shaped by historical violence, forced displacement, extractive economies, and racialized gender constructs, while preserving ancestral knowledge and collective memory. The findings show that Valencia Córdoba develops the body–territory through metaphor and anaphora as a generative space; Grueso Romero deploys orality and the sea as transatlantic archives of ancestry and identity; and Truque articulates urban displacement as an ontological rupture that affects memory and Black subjectivity. Ultimately, the article advances the concept of body–territory as a decolonial aesthetic and analytical tool through which Afro-Colombian women’s poetry articulates environmental justice, gendered racialization, and forms of resistance within the Afrodiasporic diaspora. Full article

Automated compliance checking (ACC) integrated with Building Information Modeling (BIM) requires regulatory texts that can be translated into machine-executable rules. Existing studies have largely focused on rule extraction techniques and ontology-based modeling within single jurisdictions, leaving the upstream question of regulatory readiness underexplored. This study introduces a clause-level framework for assessing the formalizability of building regulations and applies it to four documents covering accessibility and fire safety in the United Kingdom and Kazakhstan. The corpus was decomposed into 2361 enforceable clauses, classified using a ten-category semantic taxonomy, and evaluated against four formalizability criteria: explicit scope, measurable requirement, deterministic outcome, and design-stage data availability. Clauses were classified as formalizable only when satisfying all four criteria simultaneously. UK documents reached 85% formalizability for accessibility and 90% for fire safety, compared with 77% and 51% for the corresponding Kazakh standards. The largest gap was observed in fire safety, where the Kazakh corpus contained fewer BIM-oriented and spatially explicit checks and a higher share of clauses lacking evidential specification. The proposed framework supports clause-level diagnosis of regulatory automation readiness, and a four-stage roadmap links linguistic structure to digital maturity in both jurisdictions. Full article

This paper presents a process-centric ontology for the semantic representation of cyber–physical systems (CPSs) within knowledge-based production planning (KPP). The approach integrates physical systems (PSs), cyber systems (CSs), and CPSs into a unified semantic model based on a three-layer classification. The ontology was implemented using OWL and integrated into a Neo4j-based graph architecture to support semantic querying and process modeling. The evaluation was conducted using prototypical manufacturing scenarios, including semiconductor and mechanical engineering domains. Validation included (i) consistency checking using the HermiT reasoner, (ii) execution of SPARQL queries for retrieving CPS-related process information, and (iii) integration into a three-stage planning model. The results show that the ontology enables consistent semantic representation and cross-domain querying of CPS-based production processes. The work provides a validated proof-of-concept and establishes a foundation for future research on ontology-based production systems. Full article

Human follicular development depends on coordinated communication between granulosa cells (GCs) and oocytes through endocrine cues, direct contacts, and extracellular vesicles (EVs). Exosomes are key EV mediators of intrafollicular signaling, but their cargo and functions in gonadotropin-stimulated GCs remain poorly defined. The human granulosa-like tumor cell line KGN was used to investigate exosome secretion and protein composition following human chorionic gonadotropin (hCG) stimulation. Exosomes were isolated by ultracentrifugation, characterized via nanoparticle tracking analysis (NTA), Scanning Electron Microscopy (SEM) and Western blotting, and analyzed using high-resolution mass spectrometry. Comparative proteomics integrating exosomal profiles with the whole secretome were performed, followed by bioinformatic analyses of protein networks, gene ontology, and pathway enrichment. hCG reshaped exosomal cargo, identifying 59 proteins enriched in exosomes, including Integrin α3 (ITGα3), Galectin-3-binding protein (LGALS3BP), tetraspanins (CD63, CD151), and proteasome subunits. Functional enrichment indicated roles in extracellular matrix remodeling, integrin signaling, proteostasis, and steroidogenesis. Comparison with the secretome revealed distinct protein distributions, supporting selective exosomal packaging. Western blot confirmed increased ITGα3 and LGALS3BP levels in exosomes upon hCG treatment. In conclusion, hCG modulates exosome cargo composition in granulosa cells, uncovering a novel mechanism of extracellular regulation. Full article

Ongoing processes appear to be both open-ended and, in an important sense, complete. In the context of the Growing Block Theory of time, this combination generates a tension: if a process is genuinely ongoing, it seems incomplete; yet if it is complete, it appears closed and no longer directed at a non-existent future. This paper argues that this tension is only apparent. Building on Stout’s conception of occurrent continuants and on the distinction between temporal existence and temporal location central to Growing Block accounts, I examine two hybrid views according to which a process, considered as ongoing, and processes, considered as having gone on, fall under different categories of persistence. I argue that both versions of the hybrid view ultimately fail to account for the relation between dynamic existence and temporal location in a growing universe. As an alternative, I propose understanding ongoing processes as temporally expanding wholes with open boundaries. In this view, an ongoing process is always complete, though not completed, because its boundary at the edge of becoming is dynamically open rather than a genuine temporal part. This account preserves the motivations behind hybrid views while avoiding their ontological costs. Full article

Background: Ovarian cancer (OVCA) remains the most lethal gynecologic malignancy, with poor prognosis largely due to late-stage diagnosis and therapy resistance. Pyroptosis, a pro-inflammatory form of programmed cell death, has recently emerged as a regulator of tumor progression and immune regulation. This study aimed to systematically profile pyroptosis-related genes and identify robust biomarkers for OVCA. Methods: Microarray data from the GSE54388 dataset were analyzed to characterize pyroptosis-related gene expression. Immune cell infiltration was assessed using xCell, and pathway enrichment was performed via Gene Set Enrichment Analysis (GSEA). Weighted Gene Co-expression Network Analysis (WGCNA) identified hub genes, followed by Gene Ontology (GO) and Reactome enrichment. Machine learning algorithms (Support Vector Machine, XGBoost, and Generalized Linear Model) were employed for feature selection and biomarker identification. Validation was conducted across independent bulk and scRNA-seq datasets, with GEPIA2 used to compare OVCA and normal samples and KMplot for survival analysis. Results: OVCA samples showed significantly reduced infiltration of CD4⁺ and CD8⁺ T cells, mast cells, monocytes, neutrophils, and immature dendritic cells compared to normal samples. GSEA revealed enrichment of cell cycle-related pathways, implicating pyroptosis-related genes as key regulators of mitotic progression. From 1097 differentially expressed genes, 22 pyroptosis-related DEGs (PYRDEGs) were identified, with nine hub genes (CASP1, CEP55, CHMP4C, HTRA1, IL18, MELK, PKM, PTX3, TNFSF13B) strongly associated with OVCA. Functional enrichment linked these genes to cytokinesis, inflammasome activity, and immune signaling. Machine learning consistently identified CEP55 as the core biomarker, demonstrating high diagnostic accuracy (AUC up to 0.972) and significant upregulation in OVCA samples. Correlation analysis linked CEP55 expression to altered immune cell populations, including positive associations with Th1 and class-switched memory B-cells and negative associations with iDCs, Tregs, and M2 macrophages. CEP55 was highly expressed across bulk and scRNA-seq datasets (cancer epithelial and CD8+ TEMRA cells) and negatively correlated with overall survival (OS) and progression-free survival (PFS). Conclusions: Pyroptosis-related genes play pivotal roles in OVCA pathogenesis. CEP55 emerges as a promising biomarker for early detection and a potential therapeutic target, bridging cell cycle regulation with immune modulation. Full article

Digital identity is increasingly treated as foundational infrastructure for digital economies and public services, yet national approaches remain fragmented and difficult to compare. This study presents a PRISMA-guided systematic artefact-based review of government digital identity programmes, using programme-relevant government artefacts as the review corpus, including strategies, trust frameworks, guidance, service documentation, and identity-enabled public-service materials. Adapting an NLP pipeline for large-scale digital identity text analysis, the study identifies recurring themes, constructs comparative programme profiles, and operationalises three artefact-based measures: alignment, transparency, and maturity. Rather than assessing innovation performance or operational system quality directly, it examines the documentary layer through which programmes are described, justified, and made comparable. The analysis reveals substantial variation in how highly digitalised societies articulate governance, trust, interoperability, security, privacy, and service delivery. The review contributes a repeatable artefact-based framework for cross-jurisdictional comparison and provides a baseline for ontology development and future triangulation against citizen perception, expert assessment, and technical evaluation. Full article

Inherited ichthyoses are clinically and genetically heterogeneous disorders of cornification caused by disruption of epidermal barrier genes involved in keratinization and lipid homeostasis. Pathogenic variants in more than 50 genes have been implicated in nonsyndromic ichthyosis vulgaris (IV) and autosomal recessive congenital ichthyosis (ARCI). Here, we investigated the genetic basis of ichthyosis in four consanguineous Pakistani families presenting with IV or ARCI phenotypes. Exome sequencing followed by segregation analysis identified pathogenic variants in four established ichthyosis-associated genes: CYP4F22, FLG, ALOX12B, and NIPAL4. Identified variants include one novel nonsense allele of CYP4F22 (c.296G>A; p.Trp99*) and three known variants previously not reported in the Pakistani population. These known variants include a nonsense change in FLG, a frameshift allele of ALOX12B, and a missense variant in NIPAL4. Standardized phenotypic annotation using Human Phenotype Ontology terms revealed overlapping but variable clinical features across families, consistent with known genotype–phenotype heterogeneity in inherited ichthyosis. In silico protein modeling using AlphaFold2 and Ramachandran plot analysis predicted structural perturbations associated with the identified variants, supporting their pathogenic relevance. Publicly available scRNAseq datasets revealed greater heterogeneity of keratinocyte-associated expression patterns of these ichthyosis-associated genes in aging samples. Collectively, our findings expand the allelic and phenotypic spectrum of inherited ichthyosis in the Pakistani population and highlight the utility of comprehensive genetic analysis in consanguineous families for accurate molecular diagnosis, genetic counseling, and disease epidemiology. Full article

Background/Objectives: Lens development is an essential component of visual-system development during fish embryogenesis, yet its transcriptional timing remains poorly characterized in European seabass (Dicentrarchus labrax). This study aimed to provide a stage-resolved transcriptomic characterization of lens-associated gene expression in D. labrax embryos and to relate these patterns to classical embryological stages. Methods: Publicly available RNA-seq data from embryos at the mid-gastrula, late somitogenesis, and hatching stages were analyzed. A targeted lens-associated gene set was defined using Gene Ontology annotations, with emphasis on genes assigned to the structural constituent of the eye lens category. Expression patterns were examined using normalized counts, variance-stabilized data, principal component analysis, and pairwise differential expression analysis. Results: Lens-associated genes displayed clear stage-dependent expression dynamics. Principal component analysis separated samples primarily by developmental stage, with the first two components explaining 89.3% of the total variance. The strongest biological shift occurred between mid-gastrula and late somitogenesis, when transcripts encoding β-crystallins and lens-fiber architecture components increased markedly. Among the most pronounced changes were the induction of crybb1l3 and cryba4, along with increased expression of membrane and cytoskeletal genes, such as the lim2 paralogs and bfsp1. By hatching, this structural-gene expression pattern was partly maintained, while specific crystallin-related loci, including crybg1a, showed further stage-associated increases. Conclusions: These findings define stage-specific patterns of lens-associated gene expression in D. labrax embryos and indicate that lens-associated structural gene expression is most pronounced during late somitogenesis among the stages analyzed. This work provides a useful reference for future studies of visual development in European seabass and for aquaculture-oriented investigations of early sensory ontogeny. Full article

Background/Objectives: Childhood interstitial lung disease (chILD) represents a heterogeneous group of rare pulmonary disorders. Practical diagnostic approaches tested for feasibility and impact in comprehensive cohorts are lacking. We aimed to assess a simple etiologically focused classification approach, clarify the role of genetic testing and quantify the impact of non-pulmonary organ manifestations. Methods: We hypothesized that chILD can be classified in a clinically meaningful and versatile way by answering three questions: Which children have an etiological chILD diagnosis due to (1) identified (exposure-related) cause/lung injury, or (2) systemic disease? (3) In how many children without an etiological diagnosis can a genetic cause be identified? We also calculated the predictive value of non-pulmonary organ involvement for underlying systemic conditions. Results: Among 1693 patients, 24.7% were grouped as ILD related to exposure, 22.7% as ILD with systemic condition, 16.6% as ILD with genetic diagnosis of systemic disease, 10.0% as ILD with genetic diagnosis affecting the lungs only, and 25.8% as ILD without genetic diagnosis. The average genetic diagnostic yield was 50.8%, with higher rates in interstitial pneumonia (61.4%) or pulmonary alveolar proteinosis (87.1%). The presence of ≥two non-pulmonary organ manifestations increased the likelihood of an underlying systemic disease by three to five-fold. Conclusions: An etiological diagnostic strategy effectively classifies chILD and guides genetic testing. Exome or genome sequencing should be considered if ≥two non-pulmonary organs are involved or if the initial diagnosis becomes uncertain due to an unusual disease course or signs of a second underlying condition. Full article

Soybean (Glycine max (L.) Merr.) is a globally crucial food crop and a model plant for studying symbiotic nitrogen fixation in legumes. Triacontanol (TRIA) is a natural plant growth regulator that enhances photosynthetic efficiency, stress tolerance, antioxidant enzyme activities and yield in crops. However, its regulatory role in nodulation and nitrogen fixation in legumes remains unclear. In this study, soybean seedlings inoculated with Bradyrhizobium japonicum strain USDA110 were treated with different concentrations of TRIA (0, 0.33, 0.5, 1 and 2 μg/mL). Then, oxidative stress indicators and comparative transcriptomic analysis were performed to check the oxidative status and screen the candidate genes under TRIA treatment. Our results showed that the 0.5 μg/mL TRIA treatment produced the greatest nodule number. TRIA treatment significantly induced antioxidant responses in soybean roots. Comparative transcriptome identified 867 differentially expressed genes (DEGs), Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses of DEGs revealed that a large number of genes were enriched in pathways related to oxidative activity. Combined with the expression pattern, we identified a Glutathione S-Transferase family gene, GmHSP26 (Glyma.07G139700), whose expression was induced by both TRIA and rhizobial infection, with its promoter activity was activated throughout the entire process of nodule development. Further function study using overexpression and gene editing proved that GmHSP26 was a positive regulator of soybean nodulation. Collectively, this study identifies the optimal TRIA concentration for promoting soybean nodulation, reveals the function and mechanism of GmHSP26 in response to TRIA-regulated nodulation, and provides a theoretical basis and genetic resource for enhancing nodulation and nitrogen fixation in leguminous crops through exogenous growth regulators. Full article

Multisystemic eosinophilic epitheliotropic disease (MEED) is a rare and severe equine disorder characterized by chronic eosinophilic inflammation, epithelial disruption, and multi-organ involvement, with an undefined genetic basis. We performed the high-depth (~40×) whole-genome sequencing of an affected horse and compared it to 40 control genomes. Over 6.3 million variants were identified, with moderate- and high-impact variants enriched in low-frequency categories, including rare and private variants absent from the controls. The affected horse was dominated by missense mutations, with relatively few high-impact variants, consistent with the distributed protein-altering effects rather than a single highly penetrant mutation. Gene prioritization and pathway analyses highlighted the disruption of cytoskeletal organization, microtubule dynamics, epithelial integrity, and immune regulation. The network analysis further revealed the interconnected structural and inflammatory pathways, suggesting a link between an impaired epithelial barrier function and immune homeostasis. Together, these findings provide the first population genomic insight into MEED and support a model in which cumulative mutations contribute to the epithelial instability and persistent inflammation characteristic of the disease. Full article