Search Results (60)

Colorectal cancer (CRC) exhibits a highly heterogeneous tumor immune microenvironment (TME), ranging from “immune-inflamed” to “immune-desert” or “immune-excluded” phenotypes. Understanding how immune cell composition, cytolytic activity (CYT) and genomic alternations shape tumor-immune interactions is critical for improving immunotherapy outcomes. We analyzed TCGA-COAD and TCGA-READ datasets to evaluate immune competency, CYT, immune subtypes, microsatellite instability (MSI), and genomic instability, including somatic mutations, copy number aberrations (CNAs), and chromothriptic events. Immune cell infiltration was correlated with CYT levels, immune checkpoint expression, and immune-related gene signatures. Immune-competent (IC) tumors were predominantly CYT-high, enriched in stromal and immune scores, and exhibited distinct TME characteristics compared with immune-deficient (ID) tumors. IC/CYT-high tumors expressed higher levels of immune checkpoints (PD-1, PD-L1, CTLA-4, IDO1/2, LAG-3) and cytokines/chemokines (C1QA/B/C, CXCL9/10/11, CXCL13). Differences in immune infiltration were observed across tumors with significant mutations and copy number alterations. No prognostic difference was observed between CYT-high and CYT-low patients, indicating that CYT reflects immune activation rather than clinical outcome. Functionally, stimulated CD8⁺ T cells exhibited cytotoxicity activity against MSI-high (HCT-116) and microsatellite-stable (HT-29) CRC cells, with MSI-H cells showing higher sensitivity. Dynamic 3D co-culture demonstrated tumor-guided T cell infiltration and retention of CD8 expression, and co-culture was associated with moderate upregulation of cytotoxicity-related genes GZMA and PRF1 within the system. Cytotoxic activity decreased at lower effector-to-target ratios, highlighting the importance of effector dose. Overall, these findings link CYT, immune competency, MSI status, and genomic instability to T cell cytotoxic responses, providing insights into tumor-immune interactions, and suggest potential associations relevant for immunotherapy research in CRC. Full article

Background: Sensorineural hearing loss (SNHL) is increasingly recognized as a disorder involving not only hair-cell damage but also selective degeneration of spiral ganglion neurons (SGNs). Recent single-cell, molecular, and functional studies have refined the classical type I/type II classification of SGNs by identifying distinct Ia, Ib, and Ic subtypes within type I neurons. This review aims to synthesize current evidence on how SGN vulnerability is shaped by the interaction between subtype identity, life stage, and injury context. Methods: We conducted a critical narrative review of recent studies on SGN heterogeneity and subtype-specific vulnerability across development, maturity, and aging, with particular attention to molecular profiling, functional studies, and emerging therapeutic strategies. Results: SGN degeneration in SNHL is not uniform. During development, the available evidence mainly supports the vulnerability of subtype specification, synaptogenesis, and activity-dependent maturation, rather than direct selective degeneration of mature Ia/Ib/Ic identities. In the mature cochlea, subtype-specific differences in synaptic architecture, ion-channel composition, and metabolic demand appear to shape responses to noise, ototoxic drugs, and ischemic stress, with Ic-related populations often showing greater vulnerability. During aging, cumulative mitochondrial dysfunction, oxidative stress, chronic inflammation, and declining neurotrophic support may progressively unmask differences in subtype resilience and contribute to age-related auditory decline. Conclusions: A lifespan-oriented and subtype-informed framework may improve the current understanding of selective SGN degeneration and support the development of more precise neuroprotective and reparative strategies for SNHL. Full article

Critical infrastructure restoration (CIR) is a disaster-management and sustainability challenge because prolonged disruption of energy, water, transport, communications, healthcare, and public-administration services can amplify social, economic, and environmental losses. This PRISMA 2020-reported systematic review synthesizes post-2016 scientific literature and official policy, legal, standards, and technical documents on CIR and AI decision support. The review identified 55 records, removed 1 duplicate, excluded 1 ineligible record, and retained 53 core sources for qualitative synthesis, including 31 scholarly publications and 22 official documents. Manual screening was used; no automated screening or AI-assisted exclusion tools were applied. The results are organized around four research questions covering regulatory frameworks, recovery practices, supporting systems, and AI model families. The synthesis shows that CIR is shaped by layered governance through NIS2, the CER Directive, the AI Act, and national measures; by operational recovery practices such as continuity planning, cyber crisis coordination, interdependency mapping, and model-supported restoration; by digital platforms including SCADA/ICS, IoT sensing, GIS/common operating pictures, decision-support systems, simulation environments, and digital twins; and by AI methods ranging from classical machine learning and computer vision to reinforcement learning and generative assistants. However, evidence maturity remains uneven, with many AI applications still simulation-based, sector-specific, or weakly validated in real restoration settings. The review contributes an integrated CIR-oriented framework showing that AI creates practical value when embedded in interoperable, human-supervised, regulation-aware, and empirically validated restoration architectures that support sustainable service continuity rather than isolated automation. Full article

Gondolas are a useful mode of transportation in the mountainous regions. In regions located at high altitudes, atmospheric icing is a significant safety hazard to gondola infrastructure. In this study, multiphase numerical simulations of ice accretion on the monopole gondola tower were performed and validated against experimental and analytical model results. An analytical model has limitations for calculating ice loads on large cylinder diameters, and conducting experiments on large cylinders is also challenging due to practical constraints. Ansys FENSAP-ICE 2025 R2, as the primary numerical simulation tool, appears to be an attractive alternative for better estimation of ice loads on structures with larger diameters. The numerical analysis demonstrates that the ice accretion on the access ladder of the gondola tower is more critical than its main structure. This is because the ice growth on the smaller components is higher than on the larger components. A solution based on passive structural design is suggested, in which a semi-circle-shaped wind shield is introduced along the windward side of the tower which successfully diverts the flow by creating a protective droplet shadow on the trailing components, significantly reducing the accreted ice loads. It can also serve as a safety barrier for maintenance personnel. The study also showed that increasing the shield diameter ultimately reduced overall ice accretion, due to the dominant droplet drag forces over inertial forces. Full article

Background: Edwardsiella piscicida is a significant intracellular pathogen of channel catfish (Ictalurus punctatus) and a major threat to U.S. aquaculture. A recently developed recombinant attenuated vaccine strain (χ16016) uses arabinose-regulated murA expression to trigger delayed cell wall lysis in vivo, ensuring biological containment while conferring strong protection against virulent challenge. Although its efficacy has been demonstrated, the host immune programs underlying protection remain incompletely defined. Methods: We used RNA sequencing to characterize tissue-specific transcriptomic responses in the intestines and kidneys of channel catfish at 7 days post-vaccination. Fish were vaccinated with χ16016 by either bath immersion or intracoelomic (IC) injection, and differentially expressed genes and enriched immune pathways were analyzed to determine how the vaccine delivery route shapes systemic and mucosal immune responses. Results: Across comparisons, 19,101 differentially expressed genes revealed pronounced route- and tissue-dependent immune remodeling. As aquaculture vaccination strategies increasingly prioritize scalability and practical deployment, understanding how the delivery route shapes immune outcomes is critical. Here, IC vaccination induced broader systemic transcriptional changes, particularly in the intestine, whereas bath immunization elicited a more focused yet coordinated mucosal response. Overall, intestinal tissue exhibited greater transcriptional responsiveness than kidney tissue, underscoring its central role in early vaccine-induced immunity. Functional enrichment analyses identified the activation of innate recognition pathways, MAPK and calcium signaling cascades, complement components, antigen processing machinery, and cell adhesion networks. Notably, bath immunization enriched the intestinal immune network for IgA production pathway, which represents an orthology-based mapping of conserved mucosal immune components, alongside the upregulation of IL-6, CXCL12–CXCR4, integrins (α4β7), MHC class II, complement C3, and polymeric immunoglobulin receptor (pIgR). Given that catfish rely primarily on IgM in mucosal immunity, these findings indicate the induction of IgM-mediated mucosal defense rather than classical mammalian IgA responses. Concurrent complement and scavenger receptor signatures suggest a transition toward efficient opsonophagocytic clearance with controlled inflammation at this subacute stage. Conclusions: This study provides the first systems-level view of host transcriptomic responses to a regulated-lysis E. piscicida vaccine in channel catfish. The findings demonstrate that immersion vaccination, although transcriptionally less expansive than injection, effectively activates coordinated mucosal innate and adaptive immune programs, supporting its practical use as a scalable vaccination strategy for aquaculture. Full article

In the complex flow fields of channels affected by sluice gates and bridge piers, winter ice transport, accumulation characteristics upstream of the gate, and the determination of entrainment thresholds are crucial for the safe operation of hydraulic projects. In this study, ice transport experiments were conducted with and without bridge piers upstream of the gate to analyze the key factors governing the transport process and accumulation morphology of floating ice. Four machine learning models were evaluated and compared to identify the optimal model for predicting the motion state of floating ice. Based on this optimal model, the discriminant conditions for ice entrainment under both pier configurations were proposed. The results indicate that, driven by incoming hydraulic parameters, gate boundary conditions, and ice discharge, the upstream floating ice undergoes a progressive evolution: “flat accumulation $\to$ “$\nabla$”-shaped accumulation $\to$ wedge-shaped accumulation $\to$ passing through the gate (entrainment)”. Compared to the GBDT, RF, and SVM models, the LR model achieves higher and more stable accuracy, precision, recall, and F1 scores under configurations without and with bridge piers. With AUC values reaching 0.993 and 0.997, respectively, this model demonstrates optimal comprehensive performance in classifying whether floating ice passes through the gate. Furthermore, based on the LR model, explicit algebraic formulas for the critical entrainment thresholds were constructed. Under the experimental conditions, the critical threshold intervals for the relative gate opening (e/H) are [0.170, 0.182] without piers and [0.142, 0.155] with piers. This study provides a solid theoretical foundation and technical support for ice-prevention operations and gate dispatching in cold-region hydraulic engineering under submerged outflow conditions. Full article

Droplet impact dynamics is a critical subject in interfacial fluid mechanics, with applications in aerospace, energy transport, microfluidics, and chemical engineering. This study investigates the impact behavior of double droplets on cylindrical surfaces, focusing on the interaction dynamics and the effects of parameters such as Weber number, droplet spacing, and surface curvature. Using numerical simulations, the study identifies three distinct rebound modes—twin-wing rebound, vertical rebound, and arc-shaped rebound—regulated by the Weber number and droplet spacing. Results show that increasing the Weber number enhances spreading and reduces contact time, with the arc-shaped rebound mode resulting in the shortest contact times. Droplet spacing further influences the dynamics, with wider spacing increasing contact time due to additional retraction phases. The findings provide valuable insights into the complex multi-field interactions governing droplet behavior on curved surfaces, offering new perspectives for the design of anti-icing coatings and curved microfluidic devices. Full article

In the dynamic and service-intensive context of the tourism and hospitality industry, organizational innovation performance (OIP) is a critical determinant of competitiveness. This study investigates the systemic role of knowledge management capability (KMC) in driving OIP, with a focus on the mediating effects of intellectual capital (IC) and knowledge utilization (KU). Drawing on Dynamic Capabilities Theory and the Knowledge-Based View, KMC is conceptualized as a higher-order capability that facilitates the accumulation, coordination, and application of knowledge resources, thereby shaping both organizational knowledge assets and their practical enactment. Data were collected from senior managers across five-star hotels in Greater Cairo, Egypt, and analyzed using Partial Least Squares Structural Equation Modeling (PLS-SEM). Results indicate that KMC positively influences OIP directly and indirectly through the development of IC and the effective utilization of knowledge. Both IC and KU are found to mediate the relationship between KMC and innovation performance, highlighting the importance of transforming knowledge resources into actionable and value-creating organizational capabilities. The study advances theoretical understanding by elucidating the systemic mechanisms linking knowledge management, intellectual capital, and knowledge utilization to innovation outcomes, and provides practical insights for hospitality managers seeking to leverage knowledge-driven strategies to enhance competitiveness and service excellence. Full article

We present a fully controlled thermodynamic study of the two-dimensional dipolar Q-state clock model on small square lattices with free boundaries, combining exhaustive state enumeration with noise-free evaluation of canonical observables. We resolve the complete energy spectra and degeneracies $\{E_n,c_n\}$ for the Ising case ($Q=2$) on lattices of size $L=3,4,5$, and for clock symmetries $Q=4,6,8$ on a $3\times 3$ lattice, tracking how the competition between exchange and long-range dipolar interactions reorganizes the low-energy manifold as the ratio $\alpha =D/J$ is varied. Beyond a finite-size characterization, we identify several qualitatively new thermodynamic signatures induced solely by dipolar anisotropy. First, we demonstrate that ground-state level crossings generated by long-range interactions appear as exact zeros of the specific heat in the limit $C(T\to 0,\alpha )$, establishing an unambiguous correspondence between microscopic spectral rearrangements and macroscopic caloric response. Second, we show that the shape of the associated Schottky-like anomalies encodes detailed information about the degeneracy structure of the competing low-energy states: odd lattices ($L=3,5$) display strongly asymmetric peaks due to unbalanced multiplicities, whereas the even lattice ($L=4$) exhibits three critical values of $\alpha$ accompanied by nearly symmetric anomalies, reflecting paired degeneracies and revealing lattice parity as a key organizing principle. Third, we uncover a symmetry-driven crossover with increasing Q: while the $Q=2$ and $Q=4$ models retain sharp dipolar-induced critical points and pronounced low-temperature structure, for $Q\ge 6$, the energy landscape becomes sufficiently smooth to suppress ground-state crossings altogether, yielding purely thermal specific-heat maxima. Altogether, our results provide a unified, size- and symmetry-resolved picture of how long-range anisotropy, lattice parity, and discrete rotational symmetry shape the thermodynamics of mesoscopic magnetic systems. We show that dipolar interactions alone are sufficient to generate nontrivial critical-like caloric behavior in clusters as small as $3\times 3$, establishing exact finite-size benchmarks directly relevant for van der Waals nanomagnets, artificial spin-ice arrays, and dipolar-coupled nanomagnetic structures. Full article

Fish is highly prone to spoilage due to a combination of intrinsic biochemical processes and microbial proliferation, which together drive rapid quality deterioration during post-harvest handling and storage. These processes are further accelerated by factors such as elevated temperatures, mechanical damage, and suboptimal handling. In Mediterranean aquaculture, ice slurry is the standard harvesting method. This study aimed to characterize the initial post-harvest enzymatic activity of key proteolytic enzymes, calpain, collagenase, cathepsin B (CTSB), and cathepsin L (CTSL), in the white muscle of three commercially important species (Sparus aurata, Dicentrarchus labrax, and Pagrus major) harvested under standard practices across three seawater harvest temperatures (low, medium, and high). Muscle samples were collected over a 13-day chilled storage period post-harvest, and enzymatic activity was assessed using standardized fluorometric assays. Our findings establish the basal post-mortem proteolytic profiles for each species and reveal marked species-specific differences in enzyme activity patterns. Calpain and collagenase exhibited early and parallel activation, while CTSB and CTSL showed a coordinated increase during storage. Harvest temperature emerged as a critical factor, with the highest enzymatic activities consistently observed during the moderate temperature period. These results underscore the importance of species-specific physiology and seasonal conditions in shaping post-harvest filet degradation, offering a basis for refining harvest strategies to enhance quality management in Mediterranean aquaculture. Full article

Background/Objectives: Maternal immune activation (MIA) increases the risk of Autism Spectrum Disorders (ASD). Experimental models demonstrate that maternal exposure to bacterial endotoxin or the viral mimic polyinosinic:polycytidylic acid [poly (I:C)] reliably recapitulates ASD-like behavioral abnormalities in offspring, yet the underlying neurobiological mechanisms linking MIA to altered neurodevelopment remain incompletely understood. Increasing evidence highlights the placenta as a critical mediator in shaping fetal brain development through immunological and hormonal regulation. Likewise, disruption of placental regulatory functions upon MIA may therefore represent a mechanistic pathway. Here, we investigated how alterations in placental cytokine profiles, innate immune cell composition, and endocrine outputs relate to neuroinflammation and neurogenesis in the offspring. Methods: Pregnant mice at gestational day 12.5 received a single intraperitoneal injection of poly (I:C). Placental macrophages, neutrophils, inflammatory cytokines, and nerve growth factor (NGF) expression were examined 72 h later. Neurodevelopmental outcomes, including microglial activity and neurogenic markers, were evaluated in mouse offspring at postnatal day (P) 1 and 6. Results: MIA induced a significant accumulation of monocytes and neutrophils in the placenta, which was associated with elevated levels of a broad spectrum of inflammatory mediators, including Th17-biased proinflammatory cytokines, chemokines, and adhesion proteins, in the placenta and amniotic fluid. In contrast, the placenta-derived NGF levels were significantly reduced. MIA induced strong and sustained microglial activation in the fetal and neonatal brain. This inflammatory milieu was accompanied by disrupted cortical neurogenesis, characterized by a marked increase in Ki67+ neuronal progenitor cells (NPCs) in the subventricular zone (SVZ), overproduction of early-born Tbr1+ neurons at P1, later-born Satb2+ neurons at P6. Conclusions: Collectively, these findings suggest that heightened Th17 inflammatory signaling, coupled with impaired placental endocrine function, contributes to dysregulated cortical neurogenesis in the offspring. Full article

Transistor-level Integrated Circuit (IC) design is fundamental to modern electronics, yet it remains one of the most expertise-intensive and time-consuming stages of chip development. As circuit complexity continues to rise, the need to automate this low-level design process has become critical to sustaining innovation and productivity across the semiconductor industry. This study presents a fully automated methodology for transistor-level IC design using a novel framework that integrates Grammatical Evolution (GE) with Cadence SKILL code. Beyond automation, the framework explicitly examines how symmetry and asymmetry shape the evolutionary search space and resulting circuit structures. To address the time-consuming and expertise-intensive nature of conventional integrated circuit design, the framework automates the synthesis of both digital and analogue circuits without requiring prior domain knowledge. A specialised attribute grammar (AG) evolves circuit topology and sizing, with performance assessed by a multi-objective fitness function. Symmetry is analysed at three levels: (i) domain-level structural dualities (e.g., NAND/NOR mirror topologies and PMOS/NMOS exchanges), (ii) objective-level symmetries created by logic threshold settings, and (iii) representational symmetries managed through grammatical constraints that preserve valid connectivity while avoiding redundant isomorphs. Validation was carried out on universal logic gates (NAND and NOR) at multiple logic thresholds, as well as on a temperature sensor. Under stricter thresholds, the evolved logic gates display emergent duality, converging to mirror-image transistor configurations; relaxed thresholds increase symmetric plateaus and slow convergence. The evolved logic gates achieve superior performance over conventional Complementary Metal–Oxide–Semiconductor (CMOS), Transmission Gate Logic (TGL), and Gate Diffusion Input (GDI) implementations, demonstrating lower power consumption, a reduced Power–Delay Product (PDP), and fewer transistors. Similarly, the evolved temperature sensor exhibits improved sensitivity, reduced power, and Integral Nonlinearity (INL), and a smaller area compared to the conventional Proportional to Absolute Temperature (PTAT) or “gold” circuit, without requiring resistors. The analogue design further demonstrates beneficial asymmetry in device roles, breaking canonical structures to achieve higher performance. Across all case studies, the evolved designs matched or outperformed their manually designed counterparts, demonstrating that this GE-based approach provides a scalable and effective path toward fully automated, symmetry-aware integrated circuit synthesis. Full article

This paper addresses the challenges of ice ball shape prediction and layout optimization in multi-probe cryoablation treatment through a comprehensive study integrating both simulation and experimental approaches. A three-dimensional numerical model of multi-probe cryoablation, coupled with phase change heat transfer, was developed using the Pennes bioheat equation. The model’s accuracy in predicting core physical phenomena, such as phase change processes and multi-probe thermal field superposition, was initially validated. The simulated and experimentally measured temperature profiles, along with the macroscopic ice ball shapes, were observed to be in excellent agreement (with an average error of 3.75% in the major and minor axes of the ice ball). Additionally, it was determined that a nine-probe layout with 1 cm probe spacing was optimal for generating a uniform low-temperature field. However, histological analysis of porcine liver tissue revealed inconsistencies between the model’s predicted damage boundaries and the actual observed diffuse biological damage transition zone, indicating the limitations of steady-state models relying solely on fixed critical damage threshold temperatures for accurately predicting the cell death region. This study not only provides a rigorously validated thermal-physical prediction tool for preoperative planning but also underscores the importance of incorporating time-temperature thermal dose effects into future models to bridge the gap from physical simulation to biological damage prediction, thus laying a crucial foundation for the development of precise cryoablation technologies. Full article

A coupled CFD-DEM model was adopted to investigate the floating ice accumulation mechanism and its disturbance to the flow field in the pump house of coastal nuclear power plants in cold regions. Based on numerical simulations, the motion, accumulation, and flow interaction characteristics of floating ice under various release positions and heights were analyzed. The results indicate that the release height significantly governs the accumulation morphology and hydraulic response. The release height critically determines ice accumulation patterns and hydraulic responses. For inlet scenarios, lower heights induce a dense, wedge-shaped accumulation at the coarse trash rack, increasing thickness by 57.69% and shifting the accumulation 38.16% inlet-ward compared to higher releases. Conversely, higher releases enhance dispersion, expanding disturbances to the central pump house and intensifying flow heterogeneity. In bottom release cases, lower heights form wall-adhering accumulations, while higher releases cause ice to rise into mid-upper layers, thereby markedly intensifying local vortices (peak intensity 79.68, approximately 300% higher). Spatial release locations induce 2.7–4.8-fold variations in flow disturbance intensity across monitoring points. These findings clarify the combined impact of the release height and location on the ice accumulation and flow field dynamics, offering critical insights for the anti-ice design and flow safety assessment of pump houses. Full article

Understanding global precipitation trends is critical for managing water resources, anticipating extreme events, and assessing the impacts of climate change. This study analyzes spatial and temporal patterns of precipitation from 1998 to 2024 using NASA’s Global Precipitation Measurement Mission (GPM) Integrated Multi-satellite Retrievals for (IMERG) Version 7, which merges satellite observations with rain-gauge data at 0.1° resolution. A total of 324 monthly datasets were aggregated into annual and seasonal composites to evaluate annual and seasonal trends in global precipitation. The non-parametric Mann–Kendall test was applied at the pixel scale to detect statistically significant monotonic trends, and Sen’s slope estimator method was used to quantify the magnitude of change in mean annual and seasonal global precipitation. Results reveal robust and geographically consistent patterns: significant wetting trends are evident in high-latitude regions, with the Arctic and Southern Oceans showing the strongest increases across multiple seasons, including +0.04 mm/day in December–January–February for the Arctic Ocean and +0.04 mm/day in June–July–August for the Southern Ocean. Northern China also demonstrates persistent increases, aligned with recent intensification of extreme late-season precipitation. In contrast, significant drying trends are detected in the tropical East Pacific (up to −0.02 mm/day), northern South America, and some areas in central-southern Africa, highlighting regions at risk of sustained hydroclimatic stress. The North Atlantic south of Greenland emerges as a summer drying hotspot, consistent with Greenland Ice Sheet melt enhancing stratification and reducing precipitation. Collectively, the findings underscore a dual pattern of wetting at high latitudes and drying in tropical belts, emphasizing the role of polar amplification, ocean–atmosphere interactions, and climate variability in shaping Earth’s precipitation dynamics. Full article