Search Results (1,833)

Organoids are self-organizing multicellular structures generated in vitro that recapitulate the micro-architecture and function of an organ. They are commonly derived from stem cells but can also emerge from pieces of proliferative tissues. Organoid technology has opened novel ways to model development and disease, but it is not without challenges. Computational models of organoids have been established to elucidate organoid growth and facilitate the optimization of organoid cultures. This article is a systematic review of in silico organoid models constructed at single-cell or subcellular resolution. PubMed, Scopus, and Web of Science were searched for original papers published in peer-reviewed journals before 26 September 2025, yielding 439 records after deduplication. Two independent reviewers screened their titles and abstracts, retrieved 84 papers for full-text scrutiny, and identified 32 papers that met the inclusion criteria. They were grouped by organoid type: 12 intestinal, 1 airway, 2 pancreas, 3 neural, 1 kidney, 1 inner cell mass, 9 tumor, and 3 generic. The analysis of these works revealed that computer simulations guided experimental work. Parsimonious computational models provided insights into diverse organoid behaviors, such as the rotation of airway organoids, size oscillations of pancreatic organoids, epithelial patterning of neural tube organoids, or nephron segment formation in kidney organoids. Generally, a deep understanding was achieved through combined in silico and in vitro investigations (e.g., optic cup morphogenesis). Recent research trends suggest that next-generation computational models of organoids may emerge from a more detailed understanding of the complex regulatory circuits that govern stem cell fate, and machine-learning-based, high-throughput imaging of organoids. Full article

The fish liver, as the main detoxification organ, is highly susceptible to xenobiotic exposure, often resulting in various hepatopathies. The cytochrome P450 system plays a central role in xenobiotic metabolism, with cytochrome P450 reductase (CYPOR) supplying the electrons required for CYP enzyme activity. This study aimed to evaluate the relationship between the ecological state of a reservoir and fish health, including CYPOR levels, through hematological, bacteriological, and histological analyses. Samples of water and fish were collected from 12 littoral sites of Lake Ladoga. A total of 1360 specimens of fish from carp (Cyprinidae) and perch (Percidae) families were examined. For histological examination and CYPOR level determination, we selected 40 specimens using a blind randomization method. This sample size was sufficient for statistical analyses. Hematological smears were stained with azure eosin; bacteriological cultures were grown on multiple media; liver samples were stained with hematoxylin and eosin and Sudan III. CYPOR levels in liver homogenates were measured by ELISA-test. Physical and hydrochemical analyses indicated a high pollution level in the littoral zones. Isolated bacterial species were non-pathogenic but exhibited broad antibiotic resistance. Hematological evaluation revealed erythrocyte vacuolization and anisocytosis. Histological analysis showed marked fatty degeneration in hepatocytes, indicating toxic damage. CYPOR concentrations ranged from 0.3–0.4 ng/mL in healthy fish to 5–6 ng/mL in exposed specimens, showing strong correlation between environmental influence and enzyme activity. These findings demonstrate the potential of CYPOR as a sensitive biomarker for biomonitoring programs. The integrated methodological approach provides a model for assessing aquatic ecosystem health and identifying zones requiring priority remediation. Full article

Remote Indigenous communities experience persistent inequities in access to fresh and nutritious foods due to the fragility of perishable food supply chains (PFSCs). Disruptions across procurement, transportation, storage, retail, and limited local production restrict access to perishable foods, contributing to food insecurity and diet-related health risks. This scoping literature review synthesizes evidence from 84 peer-reviewed, grey, and unpublished sources across fourteen countries to map PFSC management (PFSCM) challenges affecting food access in remote Indigenous communities worldwide and to synthesize reported practices implemented to address these challenges. PFSCM challenges were identified across all supply chain levels, and five categories of reported practices emerged: PFSC redesign strategies, forecasting and decision-support models, technological innovations, collaboration and coordination mechanisms, and targeted investments. These findings informed the development of a multi-scalar conceptual framework comprising seven interconnected PFSCM clusters that organize how reported practices are associated with multiple food access dimensions, including quantity, affordability, quality, safety, variety, and cultural acceptability. This review contributes an integrative, system-oriented synthesis of PFSCM research and provides a conceptual basis to support future scholarly inquiry, comparative inquiry, and policy-relevant discussion of food access and health equity in remote Indigenous communities. Full article

Atherosclerosis remains a leading cause of cardiovascular mortality despite advances in pharmacological and interventional therapies. Current treatment approaches face limitations including systemic side effects, inadequate local drug delivery, and restenosis following vascular interventions. Gel-based technologies offer unique advantages through tunable mechanical properties, controlled degradation kinetics, high drug-loading capacity, and potential for stimuli-responsive therapeutic release. This review examines gel platforms across multiple scales and applications in atherosclerosis research and intervention. First, gel-based in vitro models are discussed. These include hydrogel matrices simulating plaque microenvironments, three-dimensional cellular culture platforms, and microfluidic organ-on-chip devices. These devices incorporate physiological flow to investigate disease mechanisms under controlled conditions. Second, therapeutic strategies are addressed through macroscopic gels for localized treatment. These encompass natural polymer-based, synthetic polymer-based, and composite formulations. Applications include stent coatings, adventitial injections, and catheter-delivered depots. Natural polymers often possess intrinsic biological activities including anti-inflammatory and immunomodulatory properties that may contribute to therapeutic effects. Third, nano- and microgels for systemic delivery are examined. These include polymer-based nanogels with stimuli-responsive drug release responding to oxidative stress, pH changes, and enzymatic activity characteristic of atherosclerotic lesions. Inorganic–organic composite nanogels incorporating paramagnetic contrast agents enable theranostic applications by combining therapy with imaging-guided treatment monitoring. Current challenges include manufacturing consistency, mechanical stability under physiological flow, long-term safety assessment, and regulatory pathway definition. Future opportunities are discussed in multi-functional integration, artificial intelligence-guided design, personalized formulations, and biomimetic approaches. Gel technologies demonstrate substantial potential to advance atherosclerosis management through improved spatial and temporal control over therapeutic interventions. Full article

Traditional Turkish marbling (Ebru) art is an intangible cultural heritage characterized by highly asymmetric, fluid, and non-reproducible patterns, making its long-term preservation and large-scale dissemination challenging. It is highly sensitive to environmental conditions, making it enormously difficult to mass produce while maintaining its original aesthetic qualities. A data-driven generative model is therefore required to create unlimited, high-fidelity digital surrogates that safeguard this UNESCO heritage against physical loss and enable large-scale cultural applications. This study introduces a deep generative modeling framework for the digital reconstruction of traditional Turkish marbling (Ebru) art using a Deep Convolutional Generative Adversarial Network (DCGAN). A dataset of 20,400 image patches, systematically derived from 17 original marbling works, was used to train the proposed model. The framework aims to mathematically capture the asymmetric, fluid, and stochastic nature of Ebru patterns, enabling the reproduction of their aesthetic structure in a digital medium. The generated images were evaluated using multiple quantitative and perceptual metrics, including Fréchet Inception Distance (FID), Kernel Inception Distance (KID), Learned Perceptual Image Patch Similarity (LPIPS), and PRDC-based indicators (Precision, Recall, Density, Coverage). For experimental validation, the proposed DCGAN framework is additionally compared against a Vanilla GAN baseline trained under identical conditions, highlighting the advantages of convolutional architectures for modeling marbling textures. The results show that the DCGAN model achieved a high level of realism and diversity without mode collapse or overfitting, producing images that were perceptually close to authentic marbling works. In addition to the quantitative evaluation, expert qualitative assessment by a traditional Ebru artist confirmed that the model reproduced the organic textures, color dynamics, and compositional asymmetrical characteristic of real marbling art. The proposed approach demonstrates the potential of deep generative models for the digital preservation, dissemination, and reinterpretation of intangible cultural heritage recognized by UNESCO. Full article

Nucleic acids are essential dietary components with diverse physiological functions. Numerous studies have focused on the biological functions of nucleotides, nucleosides, and functional RNAs such as microRNAs. However, the nutritional value of ribosomal RNA (rRNA)-derived oligonucleotides, which are likely the predominant nucleic acid-derived components in foods, remains largely unexplored. Here, yeast was used as a food-associated eukaryotic model organism to investigate the uptake and utilization of rRNA-derived oligonucleotides. Yeast efficiently utilized short RNA oligonucleotides (approximately 5–30 nt) as nutrient sources, supporting robust cell growth. Confocal microscopy confirmed rapid uptake of Cy5-labeled RNA oligonucleotides by yeast cells. Proteomic analysis further revealed marked upregulation of proteins involved in endocytosis and autophagy in yeast cultured with RNA oligonucleotides. Collectively, these findings demonstrate that yeast can internalize and metabolize rRNA-derived oligonucleotides as efficient nutrient sources, likely through coordinated endocytic and autophagic pathways. This study highlights the nutritional potential of rRNA-derived oligonucleotides and provides a foundation for their future application in functional foods and fermentation systems. Full article

A strong safety culture is essential for managing human factors in complex systems and constitutes a strategic resource for supporting the sustainable operation of organizations. However, conventional approaches remain limited by unclear conceptual boundaries and a lack of mechanisms linking safety culture with other organizational safety elements. To address these gaps, this study develops a sustainable safety culture construction method grounded in accident causation theory. Using the 24Model, we establish a concise “culture–system–ability–acts” framework that operationalizes the pathways through which safety culture shapes organizational safety performance. The method integrates four components: conceptual clarification of safety culture, quantitative assessment, factor identification based on the 24Model, and Bayesian network analysis to quantify interdependencies among culture, systems, ability, and acts. Empirical evidence from coal mining enterprises shows that safety culture influences safety performance indirectly by shaping system implementation quality, workers’ safety ability, and safety-related actions. Enhancing “demand of safety training” substantially mitigated system deficiencies related to ineffective implementation of procedures, failure in enforcing procedures, lack of qualifications, and insufficient supervision. Improved training also strengthened workers’ knowledge of accident cases, consequences of violations, and technical standards, thereby reducing competence-related gaps and promoting more consistent safety supervision behaviors. Sensitivity analysis highlights the importance of reinforcing “safety responsibilities of line departments” and improving the dissemination of safety knowledge, particularly accident case knowledge. Overall, the findings empirically validate the dynamic “culture–system–ability–acts” transmission mechanism of the 24Model and provide a structured, quantitative pathway for advancing sustainable safety culture development. Full article

Fungal endophytes have emerged as a promising source of bioactive compounds with potent antifungal properties for plant disease management. This study aimed to isolate and characterize fungal endophytes from Antillean avocado (Persea americana var. americana) trees in the Colombian Caribbean, capable of producing bio-fungicide metabolites against Fusarium solani and Fusarium equiseti. For this, dual culture assays, liquid-state fermentation of endophytic isolates, and metabolite extractions were conducted. From 88 isolates recovered from leaves and roots, those classified within the Diaporthe genus exhibited the most significant antifungal activity. Some of their organic extracts displayed median inhibitory concentrations (IC₅₀) approaching 200 μg/mL. To investigate the mechanism of action, in silico studies targeting chitin synthase (CS) were performed, including homology models of the pathogens’ CS generated using Robetta, followed by molecular docking with Vina and interaction fingerprint similarity analysis of 15 antifungal metabolites produced by Diaporthe species using PROLIF. A consensus scoring strategy identified diaporxanthone A (12) and diaporxanthone B (13) as the most promising candidates, achieving scores up to 0.73 against F. equiseti, comparable to the control Nikkomycin Z (0.82). These results suggest that Antillean avocado endophytes produce bioactive metabolites that may inhibit fungal cell wall synthesis, offering a sustainable alternative for disease management. Full article

Background/Objectives: Advanced 3D cell culture techniques enhance the physiological relevance of in vitro models, while supporting the 3Rs principles (Reduction, Refinement, and Replacement) of animal experimentation. In this context, 3D collagen-based systems mimic key extracellular matrix properties, enabling more accurate cellular organization and phenotype. However, changes in culture dimensionality can affect RT-qPCR reference gene stability, underscoring the need for careful validation when combining 2D and 3D systems. Methods: AML12 cells were cultured for 7 days under different 2D and collagen-based 3D conditions. The expression stability of nine candidate housekeeping genes was systematically evaluated using established algorithms (BestKeeper, NormFinder, geNorm, RefFinder, and ΔCt method), followed by inter-group statistical and correlation analyses of raw Ct values. Albumin gene expression was used as a target gene. Results: Although all candidate genes initially met acceptable variability thresholds, a stepwise, exclusion-based analysis revealed distinct performance differences. Hprt, Ppia, and Actb emerged as the most stable, showing no intra-group variability or interaction with Albumin expression. Nevertheless, Ywhaz and Rplp0, despite their high stability, were compromised by significant correlation with Albumin. Furthermore, Ywhaz showed significant downregulation under 3D culture conditions. B2M, Gapdh, 18S, and Hmbs exhibited increased variability, likely reflecting metabolic and microenvironmental heterogeneity associated with prolonged 2D cultivation of AML12 cells. Conclusions: Overall, this study highlights the importance of context-dependent, exclusion-based reference gene validation when comparing 2D and 3D models, and demonstrates a new approach for reliable gene expression normalization in complex in vitro culture systems. Full article

Digital cultural-heritage (DCH) platforms are integral to achieving UN SDG Target 11.4, yet their long-term sustainability is compromised by a systemic vulnerability: the rapid decay of user engagement once the initial “novelty effect” fades. To address the theoretical anomaly of the “null effect” regarding value perception found in prior studies, this paper develops a competitive dual-path model to determine whether information-centric or experience-centric strategies effectively foster sustainable continuance intention. Drawing on the stimulus–organism–response (S-O-R) framework, interactivity is modelled as a high-order managerial investment. A quantitative survey of 407 DCH users was analysed using covariance-based structural equation modelling (CB-SEM). The results resolve the strategic dilemma: while interactivity enhances both pathways, a chi-square difference test $\left(\Delta {\chi }^2\left(1\right)=26.207\right.$, p < 0.001) confirms that affective value exerts a significantly stronger impact on cultural identity than epistemic value, supporting the affective primacy hypothesis. Crucially, cultural identity serves as the essential mediator that translates user experience into “emotional stickiness.” By demonstrating that narrative-driven affective engagement is superior to mere information dissemination, this study provides a validated blueprint for virtual–real symbiosis. The findings offer actionable guidance for managers to build digital resilience and safeguard heritage transmission across generations. Full article

In plant tissue culture, the middle cell layer of the callus is crucial for establishing pluripotency and serves as the foundation for subsequent organ regeneration. Although several root apical stem cell regulators have been implicated in maintaining callus pluripotency, how they functionally coordinate to control the formation and proliferation of the middle callus layer remains unclear. Here, we identify a reciprocal transcriptional activation between the root stem cell regulators WOX5/7 and SCR in the middle callus layer of Arabidopsis. We further show that WOX5/7 and SCR form protein complexes that mutually enhance their transcriptional activities. Transcriptomic analysis reveals that WOX5/7 and SCR co-regulate a subset of cell cycle-related genes, explaining the reduced mitotic activity observed in the callus of wox5 wox7 double mutants and scr mutants. Together, these findings support a model in which WOX5/7 and SCR establish a reciprocal positive feedback loop in the middle cell layer that drives the robust callus proliferation by promoting cell cycle progression. Full article

The purpose of this study was to develop and validate an integrated model explaining how AI-enabled knowledge integration and digital ecosystem connectivity influence knowledge innovation capability through the mediating role of knowledge agility and the moderating roles of digital trust and organizational learning culture. Grounded in the Knowledge-Based View (KBV) and Dynamic Capability Theory (DCT), this research seeks to understand how technological and cultural enablers jointly drive exploratory, exploitative, and adaptive innovation. A quantitative cross-sectional research design was employed, and data were collected from 243 professionals working in knowledge-intensive organizations. Measurement scales were adapted from previous studies, and data analysis was conducted through structural equation modeling, using SmartPLS 4. Reliability, validity, and path analyses were performed to test the hypothesized relationships among constructs. The results indicated that AI-enabled knowledge integration and digital ecosystem connectivity significantly enhance knowledge agility, which in turn positively affects knowledge innovation capability. The mediation tests confirmed the role of knowledge agility, while digital trust and organizational learning culture were confirmed to strengthen the relationship between knowledge agility and innovation capability. This study contributes to theory by integrating technological, organizational, and cultural perspectives into a unified model of digital innovation. Practically, it guides organizations in leveraging AI systems, digital connectivity, and learning culture to foster sustainable innovation. Full article

The liver is the central organ in metabolism; however, modeling hepatic diseases remains limited by current experimental models. Animal models frequently fail to predict human liver physiology, while primary hepatocytes rapidly dedifferentiate in culture. We performed comprehensive transcriptomic profiling of induced pluripotent stem cells (iPSCs) differentiation into hepatocyte-like cells (HLCs) under two-dimensional (2D) and three-dimensional (3D) culture conditions. RNA sequencing analysis revealed the sequential activation of lineage-specific markers across major developmental stages: definitive endoderm (FOXA2, SOX17, CXCR4, CER1, GATA4), posterior foregut (PROX1, GATA6), and hepatoblasts (HNF4A, AFP). Comparative analysis demonstrated a markedly enhanced hepatic gene expression of 3D organoids, as demonstrated by a 33-fold increase in HNF4A expression and elevated levels of mature hepatocyte markers, including ALB, SERPINA1, and UGT2B15. However, the 3D cultures retained fetal characteristics (290-fold higher AFP expression) and exhibited significantly impaired metabolic function, with CYP3A4 expression levels reduced by 2000-fold compared to the adult human liver. This partial maturation was further supported by a moderate correlation with adult liver tissue (ρ = 0.57). We demonstrated high reproducibility across five biologically distinct iPSCs lines, including those derived from patients with rare monogenic disorders. The establishment of quantitative benchmarks provides a crucial tool for standardizing in vitro liver models. Furthermore, we delineate the specific limitations of the current model, highlighting the need for further protocol optimization to enhance metabolic maturation and P450 enzyme activity. Functional validation of metabolic activity (CYP enzyme assays, albumin secretion) was not performed; therefore, conclusions regarding hepatocyte functionality are based on transcriptomic evidence. Full article

Understanding the formation logic and spatial organization of vernacular settlements requires analytical approaches that capture both morphological structures and the cognitive rules underlying residents’ interactions with space. However, existing research on rural spatial patterns has paid limited attention to the perceptual and cognitive mechanisms through which spatial genes are recognized, maintained, and reproduced. This gap limits the development of generalizable and bottom-up methods for interpreting and transmitting rural spatial characteristics. To address this gap, this study proposes a cognition-driven analytical framework supported by spatial analysis for rural space gene extraction and transmission. The framework consists of five interrelated components: environmental cognition, spatial element identification, system coupling, space gene extraction, and transmission mechanisms. The Guanzhong Region in Northwest China is selected as a representative case to examine the multi-scale spatial structure of vernacular settlements. The results reveal three major findings. (1) The proposed framework effectively links physical spatial features with local perceptual structures, enabling the identification of key elements constituting rural space gene. (2) Three categories of representative space gene and seven core morphological and functional factors are extracted through the coupled analysis of nature–settlement systems. (3) Three adaptive transmission mechanisms—element replication and reinforcement, recombination of disrupted elements, and controlled adjustment of characteristic elements—are identified to support spatial renewal while maintaining local distinctiveness. This research contributes a structured, scalable, and replicable workflow for rural space gene analysis and enhances the application of cognitive principles in geospatial modeling. The findings provide methodological and practical support for rural revitalization, cultural landscape conservation, and vernacular settlement planning in inland agrarian regions undergoing rapid transformation. Full article

Ganoderma sichuanense is a widely studied medicinal mushroom, but the production of its antioxidant proteins has been scarcely evaluated. We assess the influence of different concentrations of culture media components under submerged fermentation, with and without agitation, on production of proteins with antioxidant activity from the mycelial biomass of G. sichuanense. Protein extracts were characterized by scanning electron microscopy, X-ray diffraction, and attenuated total reflectance Fourier-transform infrared spectroscopy. They were also analyzed for total protein and phenolic contents, antioxidant activities (ABTS^•+, DPPH^•, chelating ability, and reducing power), and electrophoretic profiles by SDS-PAGE. The most active extract was tested for cytoprotective potential under H₂O₂-induced oxidative stress in Saccharomyces cerevisiae. Growth kinetics of the best fermentation condition were also analyzed. Microstructural differences ranged from fibrillar to aggregated forms, depending on cultivation. Crystallinity was unaffected, but chemical differences and secondary structure organization were confirmed by infrared spectroscopy. The extract from the static culture with 10 g·L⁻¹ glucose, 5 g·L⁻¹ yeast extract, and 2.5 g·L⁻¹ soy peptone (referred as CM1S) showed the highest protein and phenolic contents and the strongest antioxidant activity (IC₅₀ = 4.8 and 24.0 µg of protein·mL⁻¹ for ABTS^•+ and DPPH^•, respectively). SDS-PAGE revealed higher protein band intensities in static cultures. CM1S showed potential to protect yeast cells from oxidative stress. The Gompertz model estimated a specific growth rate of 0.0068 h⁻¹ in CM1S. The findings highlight a cultivation strategy that modulates fungal metabolism and improves the recovery of antioxidant proteins from G. sichuanense biomass. Full article