Search Results (1,914)

Immunogenic cell death (ICD) links tumor cell demise to the activation of anti-tumor immunity, but its adoption has also generated inconsistent definitions and frequent overinterpretation of surrogate biomarkers. Here, we synthesize mechanistic and methodological evidence showing that danger-associated molecular patterns (DAMPs), cytokine release, and endoplasmic reticulum stress report immunogenic potential rather than ICD itself. We propose that ICD should be defined by its functional immunological endpoint, namely efficient antigen presentation and antigen-specific adaptive immunity, ideally culminating in protective immunological memory. To operationalize this principle, we introduce a hierarchy of experimental validation ranging from correlative hallmarks (Level 0) to innate immune integration (Level 1), antigen-specific T-cell priming (Level 2), definitive vaccination-rechallenge protection with immune-dependence testing (Level 3), and translational relevance supported by convergent human data (Level 4). We also discuss common pitfalls, equating inflammation, necrosis-associated DAMP release, or therapeutic benefit with ICD, and outline minimal immune-context controls (e.g., MHC-I, CD8⁺ T cells, Batf3-dependent dendritic cells, and innate sensing pathways) required to support robust claims. Finally, we highlight why ICD remains strongly context-dependent, shaped by dendritic-cell competence, innate licensing, purinergic metabolism, and microenvironmental constraints. Evidence-graded standards should improve reproducibility, strengthen peer review, and accelerate clinically meaningful ICD-based strategies. Full article

The progressive decline in functional β-cell mass in Type 2 Diabetes (T2D) is increasingly recognized not as a simple apoptotic loss, but as a complex erosion of cellular identity termed “dedifferentiation.” Central to this phenotypic shift is the metabolo-epigenetic axis, where mitochondria act as the primary sensing hub, transducing nutrient flux into biochemical signals that govern the chromatin landscape. This review synthesizes current evidence on how mitochondrial metabolites—including Acetyl-CoA, α-ketoglutarate, and NAD+—serve as obligatory co-factors for the epigenetic machinery. We explore how chronic metabolic stress triggers a “Systemic epigenetic destabilization,” leading to the loss of lineage-specific markers and the formation of persistent “metabolic scars.” Furthermore, we discuss the clinical implications of these changes, specifically regarding the phenomenon of metabolic memory and the molecular limits of β-cell reversibility. By integrating foundational transcriptional studies with emerging epigenomic data, we propose that targeting the mitochondrial–epigenetic axis offers a strategic window for re-differentiating failing β-cells and restoring glycemic homeostasis. Full article

The behavior of shape memory alloy (SMA) materials is more complex than linear isotropic metals because of their nonlinear thermomechanical coupling. When an SMA material is mechanically stressed or joule-heated, phase transformation happens in the material, and accordingly some material properties dramatically change. In any loading or unloading scenario, the initial state of the material should be known because it significantly affects its behavior. Stress and strain alone are not enough to describe such materials. Temperature and martensitic fraction are also required to simulate SMA materials accurately. This paper presents a MATLAB application, called “SMA Simulator,” that was developed to simulate the nonlinear behavior of SMA wires under mechanical or thermal loads. This tool is very effective in helping users understand the shape memory and pseudoelastic effects in such smart materials, as it allows for plotting the loading path in the 3D stress–strain–temperature space while monitoring the evolution of the martensitic fraction. Any load–unload scenario can be studied, including multiple consecutive partial loading cycles. Since the application is not based on any numerical method that would require extensive meshing, the computational time is minimal, allowing users to perform more simulations and acquire results instantaneously. Full article

A large number of existing studies show that fiber-reinforced concrete (FRC) and ultra-high-performance concrete (UHPC) have improved crack resistance relative to conventional concrete, but there is limited research on further advancing the structural performance of FRC and UHPC through prestressing and self-healing. This study addresses this knowledge gap by introducing shape memory alloy (SMA) bars as reinforcement. Existing studies on using SMA bars for prestressing or healing are focused on conventional concrete. Thus, this study experimentally evaluates SMA bars in FRC and UHPC. Small-scale flexural specimens are fabricated for this purpose. Three mix designs are considered, corresponding to mortar, FRC, and UHPC. The prestrained and embedded SMA bars are employed in two different ways. The first method is to activate the SMA to prestress the concrete, thereby delaying cracking. The second is to activate the SMA after cracks develop, thereby closing and “healing” the cracks. Additionally, different heating methods are considered. Heating with electricity is compared to heating by electromagnetic induction to study their efficiency and safety. The experimental results validate the use of SMA for prestressing the different types of concrete. The concept of healing is also validated for all three types of concrete. Reductions in crack width as high as 80%, 90%, and 84% are measured in the mortar, FRC, and UHPC specimens, respectively. Full article

Systemic inflammation leading to neuroinflammation is a matter of concern in recent years because of its implication with neurological disorders. Selective peroxisome proliferator-activated receptor gamma (PPAR-γ) agonists have shown promising anti-inflammatory effects in various neurodegenerative diseases. With pioglitazone being one such PPAR-γ agonist, our study was aimed at investigating the role of pioglitazone on oxidative stress and cognitive changes against LPS-induced neuroinflammation in rats. In-house-bred male Wistar rats, about six weeks old, were utilized for the present study. They were categorized as A (preventive) and B (curative) groups, each with five subgroups: control (1A and 1B), neuro-inflammatory (2A and 2B), and three different dosages of pioglitazone treatment (3A, 3B, 4A, 4B, and 5A, 5B). After the experimental period, cognitive changes were examined by behavioral tests. Brain homogenate was used for biochemical parameters. Deteriorated memory, superoxide dismutase activity and increase in lipid peroxidation in the brain tissue induced by LPS exposure were substantially alleviated (p < 0.001) by pioglitazone treatment. These results suggest that pioglitazone may be neuroprotective against LPS-induced neuroinflammation. Full article

Black Modernist architecture offers a powerful yet underexamined pathway for advancing restorative capacity in American cities. This paper argues that Black Modernism functions as a restorative design methodology, addressing social, economic, and ecological harm imposed on Black communities through slavery, racial capitalism, urban renewal, and infrastructural violence. Grounded in the restorative economics framework pioneered by O’Hara, the paper explores the role Black Modernism plays in sustaining sink capacities defined as the social, ecological, and emotional processes that absorb stress, pollution, waste, and trauma. Conventional economic models ignore these capacities, despite their necessity for economic productivity. Black communities, like all marginalized communities, have historically been forced to provide them without compensation. Situating Black Modernist architecture within this framework, the paper demonstrates how Black architects have designed buildings and landscapes that restore dignity, memory, health, and cultural identity, thereby expanding community sink capacities. Drawing on the works of various scholars, the paper examines case studies from Washington, DC, Atlanta, and Chicago, which reveal how Black communities have borne the burden of unremunerated restorative labor while shaping the American built environment. The paper positions Black Modernism as both a design language and a political–economic intervention, challenging architectural value systems that privilege monumental production over community restoration. It concludes by proposing a Restorative Design Framework that integrates Black Modernist principles with restorative economics, offering policy and planning pathways that recognize cultural labor, emotional restoration, and community well-being as essential components of sustainable urban development. Full article

Heterogeneous multi-core systems (HMCSs) typically face a dilemma: heuristics (e.g., Linux CFS) are fast but blind to global constraints, while meta-heuristics (e.g., GAs) are globally optimal but too slow for real-time OS interaction. To bridge this gap without relying on “black-box” neural networks, we introduce the Tissue P System-Inspired Task Allocator (TPSTA). By mapping HMCS and parallel task scheduling to Tissue P System models and vectorized linear algebra problems, TPSTA achieves a computational complexity of $\mathrm{O}\left(\mathrm{M}/\mathrm{W}\right)$, effectively compressing the decision space. Our rigorous evaluation across four dimensions reveals a system strictly bound by physical constraints rather than algorithmic heuristics. (1) Under sufficient resource provisioning (four chips), TPSTA achieves a 0.00% Deadline Miss Ratio (DMR). Crucially, stress tests on constrained hardware (two chips) show graceful degradation to a 12.88% DMR, matching the optimal theoretical bound of EDF, whereas standard heuristics collapse to failure rates > 68%. On a massive 4096-core cluster, TPSTA outperforms the Linux GTS scalar baseline by 14.4×, maintaining low latency where traditional algorithms fail (>8 s). (3) Adaptability: The system demonstrates adaptive routing in handling hardware heterogeneity; without explicit rule-coding, it autonomously prioritizes data locality during NUMA transfers and migrates compute-bound tasks during thermal throttling events. (4) Physical Limits: Finally, our roofline analysis confirms that while the algorithmic speedup is theoretically linear, practical performance saturates at ~375× due to the Memory Wall, validating the isomorphism between synaptic bandwidth and hardware memory channels. Full article

The proliferation of Internet of Things (IoT) devices has intensified the need for efficient real-time anomaly and intrusion detection, making the selection of an appropriate Complex Event Processing (CEP) engine a critical architectural decision for security-aware data pipelines. Python-based CEP frameworks offer compelling advantages through the seamless integration with data science and machine learning ecosystems; however, rigorous comparative evaluations of such frameworks under realistic IoT security workloads remain absent from the literature. This study presents the first systematic comparative evaluation of Faust and Streamz—two Python-native CEP engines representing fundamentally different architectural philosophies—specifically in the context of IoT network intrusion detection. Faust was selected for its actor-based stateful processing model with native Kafka integration and distributed table support, while Streamz was selected for its reactive, lightweight pipeline design targeting high-throughput stateless processing, making them representative of the two dominant paradigms in Python stream processing. Although both engines target different application niches, their performance characteristics under realistic CEP workloads have never been rigorously compared, leaving practitioners without empirical guidance. The primary evaluation employs an IoT network intrusion dataset comprising 583,485 events from 83 heterogeneous devices. To assess whether the observed performance characteristics are specific to this single dataset or generalize across different workload profiles, a secondary IoT-adjacent benchmark is included: the PaySim financial transaction dataset (6.4 million records), selected because its event schema, fraud-pattern temporal structure, and volume differ substantially from the intrusion dataset, providing a stress test for cross-workload robustness rather than a claim of domain equivalence. We acknowledge the reviewer’s valid point that a second IoT-specific intrusion dataset (such as TON_IoT or Bot-IoT) would constitute a more directly comparable validation; this is identified as a priority for future work. The load levels used in scalability experiments (up to 5000 events per second) intentionally exceed the dataset’s natural rate to stress-test each engine’s architectural ceiling and identify saturation thresholds relevant to large-scale or multi-sensor IoT deployments. We conducted controlled experiments with comprehensive statistical analysis. Our results demonstrate that Streamz achieves superior throughput at 4450 events per second with 89% efficiency and minimal resource consumption (40 MB memory, 12 ms median latency), while Faust provides robust intrusion pattern detection with 93–98% accuracy and stable, predictable resource utilization (1.4% CPU standard deviation). A multi-framework comparison including Apache Kafka Streams and offline scikit-learn baselines confirms that Faust achieves detection quality competitive with JVM-based alternatives (Faust: 96.2%; Kafka Streams: 96.8%; absolute difference of 0.6 percentage points, not statistically significant at $p=0.318$) while retaining the Python ecosystem advantages. Statistical analysis confirms significant performance differences across all metrics ($p<0.001$, Cohen’s $d>0.8$). Critical scalability thresholds are identified: Streamz maintains efficiency above 95% up to 3500 events per second, while Faust degrades beyond 2500 events per second. These findings provide IoT security engineers and system architects with actionable, empirically grounded guidance for CEP engine selection, establish reproducible benchmarking methodology applicable to future Python-based stream processing evaluations, and advance theoretical understanding of the accuracy–throughput trade-off in stateful versus stateless Python CEP architectures. Full article

Gelatin hydrolysate (GH), a bioactive compound derived from collagen, has demonstrated potential therapeutic benefits in various medical conditions. However, its effects on chronic cerebral hypoperfusion-induced vascular dementia remain underexplored. This study aimed to investigate the anti-oxidative stress effects of GH in alleviating brain damage and cognitive impairment in CCH-induced rats. Male Wistar rats underwent bilateral common carotid artery occlusion to induce CCH and were randomly divided into five groups: (1) sham, (2) 2-vessel occlusion (2VO), (3) 2VO + 250 mg/kg GH, (4) 2VO + 500 mg/kg GH, and (5) 2VO + piracetam. Treatments were administered for 35 days of post-operation. GH treatment significantly mitigated oxidative stress, as evidenced by reduced levels of reactive oxygen species (ROS), nitric oxide (NO), and the expression of 4-hydroxynonenal (4-HNE) and NADPH oxidase 4 (NOX4). Furthermore, GH exhibited antioxidant activity by upregulating superoxide dismutase (SOD) levels via nuclear factor E2-related factor 2 (Nrf-2) activation. This, in turn, reduced neuronal apoptosis by decreasing Bax and cleaved-caspase 3 levels and increasing Bcl-2 expression. Additionally, GH treatment ameliorated Tau protein hyperphosphorylation and improved synaptic function. Overall, GH exerted neuroprotective effects against oxidative stress-related neuronal damage and enhanced neuroplasticity, learning, and memory in rats with CCH-induced cognitive impairment. Full article

Background/Objectives: The global incidence of diabetes in childhood is increasing, raising concern about its long-term effects on the developing brain. Although paediatric diabetes research has traditionally focused on microvascular and macrovascular complications, accumulating evidence indicates that the brain is also a vulnerable target. Methods: This narrative review synthesizes current knowledge on the impact of diabetes on brain health in children and adolescents, with emphasis on epidemiology, neuroimaging and cognitive outcomes, underlying mechanisms, risk and protective factors, and clinical implications. Results: In type 1 diabetes (T1D), studies consistently demonstrate subtle but measurable alterations in brain structure, including reduced growth of total, grey, and white matter volumes, alongside functional and microstructural changes. These neurobiological differences are associated with mild deficits in cognition, particularly in attention, executive function, memory, and processing speed. While clinically significant impairment affects a minority, subclinical alterations are common and may accumulate over time. Key risk factors include chronic hyperglycaemia, glycaemic variability, severe hypoglycaemia, diabetic ketoacidosis, and younger age at onset, whereas good glycaemic stability, diabetes technologies, supportive psychosocial environments, and adequate sleep appear protective. Proposed mechanisms involve oxidative stress, neuroinflammation, disrupted insulin signalling, altered cerebral metabolism, and vulnerability of the immature brain during critical developmental windows. Type 2 diabetes (T2D), increasingly diagnosed in youth, is also associated with adverse brain outcomes. Emerging data link early-onset T2D to alterations in brain structure and connectivity, poorer cognitive performance, and increased mental health burden, mediated by hyperglycaemia, insulin resistance, inflammation, and psychosocial stressors. Conclusions: Overall, childhood diabetes—both T1D and T2D—is associated with meaningful effects on brain development and function. Longitudinal and interventional studies are needed to establish causality and determine whether optimizing glycaemic control and psychosocial support can mitigate neurocognitive risk. Recognizing brain health as a potential complication of paediatric diabetes has important implications for monitoring, prevention, and clinical care. Full article

Background/Objectives: This study aimed to investigate the protective effects and underlying molecular mechanisms of cyanidin-3-O-glucoside (C3G) against cognitive impairment in aging mice induced by D-galactose (D-gal). Methods: Spatial learning and memory, hippocampal histopathology, oxidative stress and inflammatory markers, as well as underlying regulatory pathways, were assessed in C3G-treated D-galactose-induced aging mice via Morris water maze, H&E staining, biochemical assays, qRT-PCR and Western blot. Results: Results showed C3G improved cognitive function by reducing escape latency and increasing target quadrant time along with platform crossings, while also alleviating hippocampal damage. It dose-dependently enhanced total antioxidant capacity and activities of key antioxidant enzymes (GSH-Px and SOD), reduced malondialdehyde, and inhibited pro-inflammatory cytokines (TNF-α, IL-1β and IL-6). At the molecular level, C3G treatment was associated with changes in the Nrf2 and NF-κB pathways at mRNA and protein levels. It enhanced Nrf2 expression and reduced Keap1 expression, accompanied by upregulated mRNA levels of Nqo1 and Hmox1. Meanwhile, C3G decreased IKKβ and p65 protein expression and downregulated mRNA levels of Ikbkb, Nfkb1, and RelA. The combined contribution of these pathways in reducing ROS and inflammation may constitute the molecular basis underlying the neuroprotective effects of C3G. Conclusions: C3G alleviates cognitive dysfunction and brain damage in D-gal-induced aging mice, with effects associated with modulation of Nrf2 and NF-κB pathways. These findings offer preliminary insights for its dietary application in brain aging intervention. Full article

Elastocaloric cooling, which leverages stress-induced phase transformation in shape memory materials, represents a sustainable and energy-efficient alternative to conventional vapor-compression cooling systems. Central to optimizing these materials is understanding how thermal processing history dictates phase formation, microstructure, and thermal properties. In this study, we investigated the (Ni₅₀Mn_31.5Ti₁₈)_99.8B_0.2 compound synthesized via vacuum induction melting and arc melting, followed by water quenching. Induction melting results in needle-like, boron-rich precipitates within the martensite lattice. In contrast, vacuum arc melting promoted precipitate growth at the grain boundaries. The vacuum arc melting sample exhibits ~82% martensite phase fraction, a near-ambient transformation temperature of ~277 K, a large transition entropy change of ~75 J·kg⁻¹·K⁻¹, and moderate thermal hysteresis of ~24 K. These results underscore the pivotal role of thermal history in tailoring phase stability and transformation thermodynamics, providing essential design guidelines for subsequent mechanical performance optimization in elastocaloric shape memory alloys for energy-efficient and sustainable thermal management applications. Full article

Individual differences in circadian preference have been shown to influence cognitive functioning, yet their relationship with subjective memory complaints remains unclear. The present study examined the association between chronotype and everyday memory complaints in a sample of Portuguese adults, exploring the sequential mediating roles of sleep quality and psychological distress. A total of 382 participants completed self-report measures of chronotype, sleep quality, psychological distress (anxiety, depression, and stress), and subjective memory complaints. In a cross-sectional self-report design, a path analysis approach was used to test a theoretically driven serial mediation model. Results indicated that greater morningness predicted better perceived sleep quality, which in turn was associated with lower levels of psychological distress. No significant direct effects of chronotype or sleep quality on subjective memory complaints were observed; however, a significant indirect effect was identified through the sequential pathway linking chronotype, sleep quality, and psychological distress. These findings suggest that circadian preferences are associated with self-perceived memory functioning primarily through sleep-related and emotional mechanisms; however, the sequential mediation identified reflects associational rather than causal relationships. The model highlights the central role of sleep quality and emotional state in shaping subjective memory complaints and supports integrative approaches that consider both circadian and emotional factors. Full article

This paper proposes a novel prefabricated beam-to-column joint to increase the seismic performance and post-earthquake recoverability of steel frames, which use the shape memory alloy (SMA) bolts and replaceable steel ring dampers. The comparative analysis of the seismic behavior was conducted for three beam-to-column connection types using finite element models. The three connection types include those installed using internal SMA bolts, external SMA bolts, and external SMA bolts with novel ring dampers. In addition, the novel ring damper was analyzed separately. These analysis results indicate that the connection type installed using external SMA bolts is superior to that by internal SMA bolts for the seismic performance of beam-to-column joints. The beam-to-column joints have the best seismic performance among the three joints when equipped with the additional steel ring damper, which can be easily replaced. This ring damper can increase the energy dissipation by approximately 11% and effectively reduce the stress of SMA bolts, which can delay their failure. The increasing preload of SMA bolts and high-strength bolts has a certain positive effect on the improvement of the seismic performance. All of the three joints exhibit excellent self-centering characteristics, with residual displacements nearly at zero. The gap of replaceable ring dampers can keep the re-centering capacity and improve the energy dissipation of joints. However, the changes in the steel strength of dampers have little impact on the seismic performance. This study verifies the improvement of the replaceable ring dampers on the seismic performance and post-earthquake recoverability, providing a reference for the seismic design of resilient structures. Full article

Type 1 diabetes (T1D) constitutes a chronic metabolic disorder attributed to the autoimmune destruction of insulin-producing pancreatic β cells, which most frequently occurs in childhood. Long-term complications of T1D are expected to occur mainly in adult life, whereas cognitive dysfunction can also occur in children and adolescents with T1D. Most studies demonstrate mild cognitive impairment, especially in the domains of memory, attention and executive functions, all of which affect academic performance, which may also negatively influence adherence to appropriate glucose monitoring and insulin treatment in children and adolescents with T1D. As a result, mild cognitive dysfunction can be an obstacle to both optimal glycemic control during childhood and adolescence and academic achievements for young individuals with T1D. The major metabolic changes occurring around the onset of diabetes, such as severe hyperglycemia and diabetic ketoacidosis, may have a negative impact on brain plasticity during this vulnerable period of neurodevelopment, especially in children diagnosed at a younger age. The pathophysiological mechanisms involved are closely related to increased oxidative stress and the accumulation of advanced glycation end products in the brain, thus leading to neuron cell damage and apoptosis. On the other hand, hypoglycemic episodes and glucose fluctuations may also impair neuronal integrity. The aim of the current narrative review is therefore to present the existing literature data on the clinical aspects, risk factors and molecular mechanisms associated with cognitive dysfunction in children and adolescents with T1D. Full article