Search Results (2,683)

Dengue virus (DENV) and chikungunya virus (CHIKV) co-circulate in many regions and present with overlapping clinical features, which complicate accurate diagnosis and disease management. This study develops an integrative transcriptomic framework to identify robust host gene signatures that distinguish between dengue, chikungunya, and healthy states. Publicly available RNA sequencing (RNA-seq) datasets derived from human blood samples were analyzed using a cross-validation design to ensure robustness and prevent information leakage. Differential expression analysis was performed independently within each dataset using the Generalized Linear Models with Quasi-Likelihood F-tests and Magnitude–Altitude Scoring (GLMQL-MAS) framework, followed by Cross-Magnitude–Altitude Scoring (Cross-MAS) integration to identify shared and virus-specific gene signatures. A strict consensus approach across folds was applied to derive reproducible gene sets. These signatures were used for dimensionality reduction and multinomial logistic regression to evaluate classification performance. A small subset of selected genes showed strong discriminative performance within the cross-validation framework, with test balanced accuracy reaching 0.97, which improved upon models using all genes. Biologically, both infections exhibited a shared antiviral response characterized by interferon signaling and innate immune activation. However, distinct virus-specific patterns were identified. Dengue infection was associated with cell-cycle and DNA replication pathways, while chikungunya infection showed stronger enrichment of inflammatory and immune signaling pathways, including NF-kappaB and Toll-like receptor signaling. Overall, this study provides a cross-validation-based framework for integrative transcriptomic analysis and identifies compact, reproducible host-response signatures with strong discriminative signals in the analyzed cohorts. These signatures require validation in larger independent cohorts before any clinical or diagnostic application. Full article

South Asians appear to be particularly susceptible to diabetes. India hosts 18 percent of the world’s population but more than 25 percent of the world’s diabetics, and individuals of South Asian descent carry this presumed increased risk for diabetes when they emigrate to other parts of the world. One conundrum is that the epidemic of diabetes began around Calcutta (modern day Kolkata) in east India well before it appeared in the United States and Europe, and this emergence occurred despite the frequent occurrence of famines and starvation in India. Here we review the history of diabetes in India and the possible significance of high carbohydrate in low-protein diet contexts. We suggest that the circumstantial relationship between diet and a spectrum that includes diabetes associated with obesity at one end, and impaired glucose tolerance and protein malnutrition (kwashiorkor) at the other, could be significant. If the cause of type 2 diabetes in South Asians is primarily nutritional, and, as suggested by others, aggravated by starvation and famine that increased the risk for low birth weight as an additional risk factor for diabetes, these insights may together help explain an enhanced susceptibility of South Asians to diabetes. Full article

Background/Objectives: Exercise is increasingly recognized as a modulator of host–microbiome interactions, yet its role in irritable bowel syndrome (IBS) remains poorly characterized. Methods: In this prospective, single-arm, before-and-after interventional study, we used an integrated multi-omics approach based on metataxonomics and metabolomics to assess the effects of a structured 12-week moderate aerobic exercise program in 80 patients with mild-to-moderate IBS, stratified by Global Physical Capacity Score (GPCS). Biochemical and inflammatory markers have been gathered. Results: Exercise did not alter overall microbial diversity but selectively enriched short-chain fatty acid (SCFA)-producing taxa and remodeled the volatile organic compound (VOC) profile toward a more efficient metabolic state. Notably, conventional biochemical and inflammatory markers failed to distinguish response subgroups, whereas GPCS stratification revealed distinct microbial and metabolomic trajectories. Individuals with higher baseline physical capacity had higher acetate levels and lower levels of VOCs associated with dysbiosis and oxidative stress. Conclusions: Our results suggest that baseline physical capacity is a primary determinant of the microbiome’s responsiveness to exercise, challenging the reliance on static biochemical profiling. Despite the lack of a control group and the exploratory nature of some metabolomic signals, this study provides a framework for precision exercise interventions in IBS. Our work identifies GPCS as a clinically relevant stratification tool. The full trial protocol is registered on ClinicalTrials.gov under the identifier NCT05453084. Full article

The Yezo virus (YEZV) is a recently discovered tick-borne orthonairovirus with pathogenic potential, causing acute febrile illness in humans. Viral nucleoproteins (N) play a key role in genome packaging, replication, and modulation of host immune responses, making their structural characterization essential for understanding viral pathogenesis and developing targeted countermeasures. However, the absence of structural data for YEZV proteins significantly hinders these efforts. This study presents the first solution structure of the YEZV N domain 1 (D1). A highly purified, soluble, tag-free recombinant YEZV N D1 was produced from the native sequence of the clinical YEZV isolate. The native-state conformation was resolved through an integrated approach combining size-exclusion chromatography coupled with small-angle X-ray scattering (SEC-SAXS), AlphaFold 3 structure prediction, and all-atom molecular dynamics simulations. The YEZV N D1 structure adopts a stable, predominantly α-helical globular fold that remains monomeric under near-physiological conditions. SEC-SAXS data show excellent agreement with computational models, revealing moderate conformational flexibility. The characterized recombinant YEZV N D1 and its first solution structure reported here providing essential insights into understanding of YEZV molecular architecture. These findings lay a foundation for rational serological assay development and structure-guided therapeutic design against this and other emerging orthonairoviruses. Full article

Titanium-bearing blast furnace slag is rich in high-melting-point titanium-containing minerals including perovskite, melilite and spinel, which result in the loss of titanium resources and hinder the comprehensive utilization of such slag. On this basis, combined with process mineralogy theories, this study adopted multiple characterization methods, including a polarized light microscope with transmitted and reflected light, XRD and EPMA. These simulations reveal that the bulk SiO₂ content dictates titanium distribution among the mineral phases, thereby laying a solid foundation for the subsequent experiments. Meanwhile, quantitative analyses were performed on the microstructure, mineral composition and perovskite grain size of the slag. The occurrence state and migration law of titanium in the slag were systematically investigated. The results show that the microstructure of titanium-bearing blast furnace slag presents a porphyritic structure at different SiO₂ levels. Its main mineral phases include perovskite, pyroxene, spinel and glass. Titanium is predominantly hosted in perovskite, with small amounts distributed in the pyroxene, spinel and glass phases. Reducing the SiO₂ content facilitates the formation and grain coarsening of perovskite and promotes the migration of titanium from pyroxene and glass into perovskite. When the SiO₂ content is 20%, the perovskite content reaches 44.3%. Among them, the proportion of grains larger than 40 μm is 59.94%, and the distribution ratio of titanium in perovskite is 86.78%. Under the experimental conditions of this study, 20% SiO₂ is the optimal level. These findings can provide a theoretical reference for the efficient separation and recovery of titanium from titanium-bearing blast furnace slag. Full article

High-Frequency Trading (HFT) dashboards require rapid reception, aggregation, and visualization of order book and trade update streams that may arrive at multi-million message rates. Conventional CPU-based and CPU-GPU hybrid visualization pipelines can suffer from significant delays during periods of burst due to CPU-mediated rendering, synchronization, kernel launch overhead, and copies on the host. This paper presents a visualization pipeline that is entirely resident on the graphics processor with zero-copy access to NIC accessible pinned buffers, persistent CUDA processing, fused stage execution of the parse-aggregate pipeline, and persistent CUDA OpenGL buffer interoperation. The goal is not to reach production status but rather to see whether host-to-host data movement can be decreased and whether the stages of GPU processing can be consolidated to improve latency, throughput and frame cadence in controlled HFT-style workloads. The evaluated workstation achieved a mean ingest-to-pixel latency of 6.3 ms using the proposed design compared to 29.4 ms for the current design, with sustained throughput of 10.2 million messages per second, which is 20 times greater than the current design, and a steady-state range of 185 to 192 frames per second with a burst floor of 178 frames per second for the proposed design. The improvement observed can be attributed to both the zero-copy ingestion and fused persistent kernel execution. Based on the obtained results, the proposed method of use of this technique in the implementation of real-time financial visualization under the proposed conditions is possible. More general testing is still required on other NICs, other generations of GPUs and PCIe configurations, workload traces, and actual exchange feeds. Full article

The Iberian Peninsula hosts one of the world’s most endemic fish faunas. Its extensive evolutionary, palaeogeographic, and geological history has produced a distinctive freshwater fish fauna. Many of these species have very limited distributions, making them especially vulnerable to habitat disturbance. Past monitoring of this biodiversity has revealed alarming results, indicating that most native Spanish species are at risk. The causes of this serious situation are varied and reflect the ongoing deterioration of freshwater ecosystems. The main pressures faced by populations include pollution, loss of river connectivity caused by hydraulic infrastructure, regulation of watercourses, water extraction, fishing, and the presence of invasive species. Additionally, the effects of climate change worsen the risk of extinction for these populations, particularly through the increased frequency and intensity of droughts and heatwaves. It is evident that current planning models and investments are inadequate to conserve freshwater fish. To prevent the extinction of many populations in Spain, especially Iberian endemics, it is crucial to change the management of aquatic ecosystems and adopt integrated solutions that halt population declines and promote the sustainable use of aquatic resources. The IUCN Red Lists of Threatened Species are vital indicators of biodiversity health and are widely used to guide and structure conservation efforts. These lists, published in the Red Books, result from a thorough evaluation process that employs specific categories and criteria to assess the extinction risk of species, both globally and regionally. This report presents preliminary findings from a monitoring study on the current state of freshwater fish in Spain. The monitoring results reveal that, based on IUCN assessment criteria, two species are classified as extinct (EX), four as critically endangered (CR), eighteen as endangered (EN), and twenty-one as vulnerable (VU). Of fifty-seven species documented, 79% are considered threatened. The project’s final outcome is the development of the Atlas and Red Book of Freshwater Fish of Spain. This resource includes the main native and invasive freshwater and diadromous fish species, offers detailed information on their biological and ecological traits, and provides an up-to-date inventory of records along with an assessment of their conservation status. Full article

Interferons (IFNs) are antiviral cytokines that serve as key mediators of the innate immune response, and their production is induced in the majority of cells within hours of pathogen entry. IFNs are predominantly produced by pathogen-infected cells; however, their antiviral effects extend to surrounding cells through autocrine and paracrine signaling mechanisms, inducing the transcription of hundreds of antiviral genes. Numerous gene products either interfere directly with viral replication or play regulatory roles that influence the progression and strength of the ensuing immune response. Viruses, on the other hand, have devised techniques to circumvent the host antiviral immune response and establish infection. This review focuses on the current state of evidence demonstrating how certain viral proteins block antiviral responses via immunomodulatory strategies and discusses how to overcome these immune evasion tactics. Full article

Biofilms are structured communities of microorganisms embedded in a self-produced extracellular polymeric substance (EPS) matrix, whose development significantly enhances microbial resistance to antibiotics, disinfectants, and host immune defenses, posing major challenges in clinical, industrial, and environmental settings. Compared with planktonic cells, biofilm-associated microorganisms can exhibit up to 10- to 1000-fold increased tolerance to antimicrobial agents, contributing to the persistence of biofilm-associated infections (BAIs). These infections remain difficult to eradicate due to reduced penetration, altered metabolic states, and the presence of dormant or persister cells. Anti-biofilm strategies can be broadly classified into physical approaches (e.g., ultrasound, mechanical stress, and light-based approaches) that target biofilm structure; chemical and enzymatic methods (e.g., EPS-degrading enzymes) that destabilize the matrix; and biological and molecular strategies (e.g., quorum-sensing (QS) inhibitors, anti-virulence agents, bacteriophages, phage-derived antimicrobial molecules, antimicrobial peptides, and natural bioactive compounds) that modulate biofilm development and integrity by targeting regulatory pathways and matrix stability through distinct mechanisms of action. Natural compounds, including lactoferrin, lactoferrin-derived peptides, and probiotic and postbiotic fractions of lactic acid bacteria (LAB), as well as plant-derived metabolites, have shown promising anti-biofilm effects, with efficacy often enhanced through complementary or potentially synergistic interactions. However, despite these advancements, clinical translation remains limited. For example, BAIs account for approximately 80% of chronic infections, with high recurrence rates and therapeutic failure reported in device-associated infections and chronic wounds. These limitations highlight the need for clinically translatable, multimodal approaches that integrate structural biofilm disruption, antimicrobial targeting, and host response modulation to design more effective and sustainable anti-biofilm strategies. Full article

Yersinia pestis is the causative agent of bubonic plague, a zoonotic disease that is primarily transmitted by infectious fleas. Plague is endemic in regions around the world, including the United States, where optimal climate conditions support a stable, enzootic sylvatic transmission cycle. Epizootic outbreaks periodically occur with rapid spread of disease that increases the risk of human exposure. As fleas are ectotherms that are responsive to environmental conditions, it is likely that transmission efficiency varies under different ecological conditions, with optimal conditions capable of supporting rapid spread of disease while sub-optimal conditions may promote lower levels of transmission. To test this, we experimentally infected Xenopsylla cheopis with Y. pestis using a membrane feeder in order to define the impact of varying temperature, humidity and mammalian blood sources on infection and transmission. We show that environmental factors and host blood source are key factors influencing colonization, bacterial aggregation, and transmission rates, with variation in the responses seen depending on the experimental conditions. The combined data illustrate the impact of ecological factors on Y. pestis flea infection and suggests that optimal conditions involving the vector–host–pathogen interface are needed for enhanced transmission rates and the rapid spread of infection that occurs during epizootic outbreaks. Full article

An administrator-assisted CLP-SEIRS-T⁺ framework is developed to model malware propagation and urban cyber-resilience in clustered temporal communication networks. The model extends CLP-SEIRS-T by integrating community structure, predicted links, asynchronous node activation, and an endogenous defense layer in which administrator nodes remain infectable, recover faster than ordinary nodes, and trigger local patch diffusion when community-level prevalence exceeds a risk threshold. Unlike formulations that treat defense as an external or perfectly reliable safeguard, the proposed framework embeds administrator intervention directly within the epidemic state space and couples propagation dynamics with resilience-oriented performance measures, including safe functionality, absorptive capacity, spillover attenuation, recovery time, and service continuity. To keep experimental evidence scale-explicit, the validation is organized as a tiered protocol: a 48-node isolated virtual-machine cyber-range verifies safe mechanism realization; emulation-calibrated logical traces and pilot repeated comparisons examine trajectory behavior, pathway composition, and defense-component effects; and expanded numerical sweeps assess scalability, threshold sensitivity, alternative link-prediction scores, and adaptive-stress assumptions. The results show that direct links dominate local amplification, whereas predicted links contribute disproportionately to cross-community spillover. In the pilot comparison, the full CLP-SEIRS-T⁺ configuration achieves the best observed balance, reducing mean peak burden by 56.9%, shortening mean recovery time by 86.7%, increasing absorptive capacity by 37.1%, and improving service continuity by 12.0% relative to the no-intervention baseline. Larger-network sweeps over $N=48,100,150,200,$ and 500 logical hosts preserve the same qualitative mechanism ordering while keeping functionality error below 0.02. Threshold analysis indicates that intermediate trigger values provide a better burden–cost balance than either overly aggressive or delayed patching. Link-score comparisons show that local-neighborhood predictors yield consistent spillover interpretations, whereas degree-driven prediction can increase bridge exposure. Parameterized adaptive-stress tests further indicate that the mechanism remains beneficial under moderate stress but degrades under severe patch suppression, false telemetry, or intensified bridge seeking. These findings suggest that urban cyber-resilience depends jointly on network modularity, temporal availability, structurally likely bridge formation, state-dependent local defense, and the integrity of administrative response. Full article

The galactose/N-acetyl-D-galactosamine (Gal/GalNAc)-inhibitable lectin of Entamoeba histolytica plays essential roles in host cell adhesion and cytotoxicity. The intermediate subunit lectin-1 (Igl1) contributes to these functions, but its molecular state under different environmental conditions remains unclear. In this study, we found that Igl1 is present as multiple fragments in the culture supernatant of trophozoites, whereas a single major species corresponding to intact Igl1 was detected in cell lysates. Notably, the molecular sizes of both intact Igl1 and its extracellular fragments differed depending on culture conditions, with larger apparent sizes observed under co-culture with Caco-2 cells. These differences were not explained by changes in transcript levels, protein folding, or N-terminal truncation. Fragmentation of Igl1 was suppressed by a cysteine protease inhibitor, indicating extracellular generation. These findings demonstrate that host-cell-associated conditions alter the molecular size of Igl1 and that extracellular protease-dependent processing generates multiple Igl1 fragments, providing new insights into the regulation of this key virulence factor. The presence of extracellular fragments further suggests a potential contribution to host tissue damage during amoebiasis. Full article

Dandruff (DF) is a prevalent, recurrent inflammatory scalp disorder increasingly recognized as a complex state of functional dysbiosis rather than a simple Malassezia overcolonization. The scalp microbiome is predominantly shaped by Malassezia species (M. restricta and M. globosa), Cutibacterium, and Staphylococcus species. Recent multi-omics evidence indicates that DF pathogenesis is driven by the destabilization of microbial interaction networks and strain-level functional heterogeneity, characterized by the disruption of the C. acnes/S. epidermidis balance and the opportunistic expansion of Staphylococcus aureus. Mechanistically, Malassezia utilizes its lipolytic repertoire to hydrolyze host sebum into irritant free fatty acids and peroxides. Concurrently, oxidative metabolites like squalene peroxide (SQOOH) penetrate the stratum corneum to activate the NF-κB and aryl hydrocarbon receptor (AhR) pathways, triggering a pro-inflammatory cascade that overexpresses keratins (K6/16/17) and downregulates filaggrin. This molecular cascade drives abnormal keratinocyte turnover and lipidomic remodeling, establishing a self-perpetuating “metabolism–inflammation–barrier disruption” pathological cycle. This review systematically elucidates the molecular etiology of DF as an ecological disorder driven by a tripartite imbalance among the microbiome, host physiology, and the environmental niche. We propose that next-generation therapeutic paradigms must transcend traditional antifungal eradication, focusing instead on targeted molecular intervention and microecological restoration to recalibrate overall scalp homeostasis. Full article

Dengue is the most prevalent arthropod-borne viral disease, caused by infection with the dengue virus (DENV). Severe dengue is characterized by significant vasculopathy involving a proinflammatory and procoagulant state associated with increased vascular permeability. However, the host–virus interactions driving this process remain incompletely elucidated. Monocytes (Mø) are primary target cells during DENV infection and actively release extracellular vesicles, like microparticles (MPs), mediating intercellular communication, contributing to dengue pathogenesis. Here, we evaluated whether MPs released by DENV-infected monocytes represent a previously underappreciated mechanism contributing to dengue-associated vascular dysfunction. The vascular endothelium plays a determining role in the response to injury because it functions as a regulatory interface during hemostasis (coagulation–fibrinolysis–inflammation) and by preserving the endothelial barrier. We found that these vesicles transport viral proteins (E and NS1), exhibit a procoagulant profile that promotes thrombin generation, and enhance endothelial vascular cell (EVC) activation. DENV-infected THP-1 Mø MPs interaction induces a shift toward a procoagulant, proinflammatory, and proadherent phenotype, characterized by increased expression of PAR-1, TF, ICAM-1, and VCAM-1, reflecting the establishment of a sustained HMEC-1 EVC activation that compromises vascular barrier integrity. This leads to increased permeability, a hallmark of DENV-associated vasculopathy and a central event in the progression to severe dengue. Full article

Roman theatres were designed to host spoken drama and musical performances, relying on typical semicircular architectural form and stone materials to achieve favourable acoustic conditions. This study investigates the acoustic behaviour of the Roman theatres of Herculaneum and Cales, two sites characterized by markedly different states of preservation and historical reconstruction challenges. The theatre of Herculaneum remains largely buried beneath volcanic deposits, requiring a hypothetical reconstruction based on archaeological documentation and historical sources, while the theatre of Cales is partially preserved and directly accessible for geometric surveys. Virtual acoustic models of both theatres were developed to analyses their sound field characteristics under unoccupied and occupied conditions. Key acoustic parameters relevant to music, including reverberation time, clarity, strength, and ITDG, were evaluated through numerical simulations. Particular attention was given to the influence of original surface materials, such as stone and wood, on sound propagation and spatial distribution. The comparative analysis highlights how differences in architectural layout, scale, and reconstruction assumptions affect the resulting acoustic performance. Despite these differences, both theatres exhibit acoustic conditions consistent with their intended use, demonstrating the effectiveness of Roman design principles. The results contribute to a better understanding of ancient performance spaces and provide insights into the acoustic restitution of Roman theatres. Full article