Search Results (92)

The concurrent circulation of influenza A virus (IAV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has unveiled complex host–pathogen interactions governed by temporal dynamics of innate immune activation. This narrative review synthesizes evidence from human air–liquid interface (ALI) epithelial models, animal studies (hamster, ferret), clinical cohorts, and randomized controlled trials (2015–2026) to delineate the molecular mechanisms underlying viral interference between these two major respiratory pathogens. Prior IAV infection induces a robust type I/III interferon (IFN) response and broad interferon-stimulated gene (ISG) upregulation that restricts subsequent SARS-CoV-2 replication within a critical 24–72 h temporal window. Conversely, SARS-CoV-2 employs a multi-layered immune evasion strategy that blunts IFN induction, providing minimal heterologous protection. Simultaneous co-infection tends to exacerbate disease severity. Host genetic determinants, including OAS1 and TLR7 variants, modulate interference capacity. Therapeutically, early pegylated IFN-λ shows clinical benefit, while experimental evidence from in vitro and animal models suggests oseltamivir may paradoxically reduce IAV-induced interference. These findings underscore the need for multi-pathogen diagnostics, temporally informed clinical decision-making, and IFN-based therapeutic strategies during co-circulation periods. Full article

Burkitt lymphoma (BL) is an aggressive B-cell lymphoma endemic in children in regions of sub-Saharan Africa, where its incidence geographically overlaps holoendemic Plasmodium falciparum malaria and poorly controlled childhood Epstein–Barr virus (EBV) infection. Despite decades of research, the precise mechanistic synergy between these two pathogens remains incompletely defined. This review synthesizes current epidemiological, immunological, and molecular evidence to propose an integrated model for the etiology of endemic BL. We outline a paradoxical, dual-edged relationship wherein EBV infection during infancy may provide a short-term child survival advantage against severe malaria while simultaneously increasing the long-term oncogenic risk in B-cells infected by EBV. P. falciparum infection triggers polyclonal B-cell activation, increasing the probability of an activation-induced cytidine deaminase (AID)-mediated c-MYC translocation in proportion to the recurrent parasite burden. Concurrently, EBV expands within this B-cell pool and modulates the host immune response, potentially through viral interleukin-10 (vIL-10), to prevent lethal malarial inflammation. At the cellular level, EBV provides a critical “second hit” when it establishes latency I infection that rescues c-MYC-translocated B-cells from apoptosis. This framework explains why BL manifests as a “tumor of malaria survivors,” peaking in incidence years after the highest-risk period for malaria mortality. Ultimately, this model underscores that malaria control is a critical form of cancer control and highlights key future directions for validating these pathways in prospective clinical studies. Full article

Background/Objectives. The intestinal microbiota is a key contributor to postoperative complications, yet direct interventions targeting dysbiosis—antibiotics, probiotics, and synbiotics—have produced inconsistent results. This paradox indicates a fundamental gap in understanding host–microbiota interactions under surgical stress. We aimed to re-examine the causal role of dysbiosis in postoperative pathogenesis and propose a revised therapeutic paradigm centered on host barrier protection. Methods. A narrative literature review was conducted, searching PubMed/MEDLINE, Scopus, and Web of Science for articles published between 2009 and 2025. Reference lists of included publications were additionally screened. Studies in English and Russian were eligible; 107 references were included. Results. We hypothesize that dysbiosis in surgical patients may, at least in part, represent a predictable ecological response to systemic hypoperfusion, pharmacological burden, and ischemia–reperfusion injury, rather than acting solely as an independent pathogenic agent. Microbial shifts, characterized by the depletion of short-chain fatty acid-producing commensals and the expansion of pathobionts, frequently accompany epithelial injury; however, available human data are predominantly observational and do not permit definitive determination of the temporal sequence. This hypothesis provides the conceptual foundation for the proposed therapeutic reorientation. Conclusions. The present findings support the rationale for transitioning from microbiome manipulation to a “host-first” strategy, which prioritizes the restoration of intestinal barrier integrity through the administration of cytoprotective agents and targeted metabolic substrates (glutamine and butyrate). We propose the Gut Resilience Index (GRI) as a theoretical construct to identify patients approaching a critical threshold necessitating rescue therapy. It must be emphasized that both the “host-first” strategy and the GRI remain hypothetical frameworks requiring prospective validation. The most critical next steps include the development and validation of the GRI in prospective cohort studies, as well as randomized controlled trials directly comparing barrier-oriented strategies with standard care. Full article

Marine algal viruses exhibit a high level of diversity, and closely related viruses targeting the same algal host species can stably coexist. Here we report an example of a single virus–host system concealing hidden complexity. We discovered two double stranded (ds) DNA viruses infecting the Arctic picophytoplankter Micromonas polaris coexisting in culture for over a decade. Genomic sequencing of the lysate originally characterized as MpoV-44T revealed that it comprises two distinct prasinoviruses with ~203–204 kb genomes (MpoV-44T.A and MpoV-44T.B), of which conserved regions only accounted for 36% (the nucleotide level). The viruses were subsequently separated and compared at both genomic and phenotypic levels. In dual infection studies using a single host strain under nutrient-replete conditions, MpoV-44T.A outcompeted MpoV-44T.B. Yet MpoV-44T.B-like viruses were more abundant than MpoV-44T.A-like ones in natural Arctic metagenomes. This apparent paradox may be explained by differences in host strain specificity and/or possible resilience to nutrient stress by MpoV-44T.B, which we hypothesize based on genomic data. This work unveils hidden virus diversity, illustrating that the dynamics of viral coexistence are not always easily predictable, and underscores the importance of studying the underlying mechanisms at play. Full article

Host microRNAs (miRNAs) are widely proposed as innate antiviral effectors against SARS-CoV-2, yet whether they actually restrict infection in lung epithelial cells remains unresolved. Two of the most-cited candidates, miR-29a-3p and miR-15b-5p, are predicted to bind both the viral genome and key entry/trafficking factors such as Furin and ATG9A, but functional evidence is fragmented and often contradictory. Here, we put both miRNAs to the test in human Calu-3 cells infected with the SARS-CoV-2 Beta and Omicron BA.1 variants, using parallel gain- and loss-of-function strategies coupled to RT-qPCR of viral and cellular transcripts and back-titration of infectious progeny on VeroE6/TMPRSS2 cells. Both miRNAs transiently suppressed viral gene expression at 6 hpi, but this early dampening was followed by a marked transcript rebound at 24 hpi, especially for Omicron, with virtually no impact on total extracellular viral RNA. More strikingly, miR-15b modulation enhanced infectious virus output during Beta infection, and miR-29a overexpression boosted Omicron BA.1 infectivity, while Furin, ATG9A, AKT3, and TFEB showed only modest, condition-dependent shifts. Rather than acting as clean antiviral effectors, miR-29a and miR-15b emerge as context-dependent modulators that can paradoxically favor SARS-CoV-2 replication—a cautionary signal for miRNA-based antiviral strategies. Full article

Neospora caninum is a major cause of reproductive failure in cattle, responsible for epidemic abortion outbreaks that inflict annual billion-dollar losses on the global livestock industry. In water buffaloes (Bubalus bubalis), however, a phylogenetically close relative often raised in the same environments, the same parasite typically establishes a subclinical persistent infection with markedly lower rates of clinical abortion. This review inverts the traditional narrative by arguing that the key to next-generation control strategies lies in understanding the tolerant host (buffalo) rather than solely the susceptible host (cattle). By dissecting this “Neospora paradox”, we explore the molecular and immunological crosstalk that dictates pregnancy outcomes. We examine the parasite’s invasion proteins, revealed by CRISPR-Cas9 screens, and the maternal–fetal interface, where the balance between immune tolerance and parasite control determines the fate of pregnancy. We also compare N. caninum with the related zoonotic parasite Toxoplasma gondii to highlight how differential host immune recognition shapes infection outcomes. Finally, we propose that deciphering the buffalo’s successful equilibrium with N. caninum can illuminate novel pathways for vaccines and immunotherapeutic strategies, transforming the management of neosporosis worldwide. Full article

Beginning in the mid-sixteenth century, Europeans entered East Asia and introduced Catholicism as new maritime routes were opened and global interconnections deepened. Through practice, missionaries gradually developed a strategy of cultural accommodation, seeking converts by integrating into East Asian cultures. Although the cultural traditions of China, Japan, and Korea were broadly similar, there were differences among them, and the process of Catholic accommodation in each country reflected both shared commonalities and distinct particularities. The accommodation strategy initially led to considerable success; however, Catholic activities later posed a challenge to the traditional cultural and social orders of the three countries, and their rulers eventually adopted policies of religious prohibition to varying degrees. By the early nineteenth century, Catholicism had been banned across all three polities. Therefore, the cultural encounter between East and West on the eve of the modern era ended in intense conflict—yet Catholicism never disappeared from East Asia. Rather, it found a foothold in popular society by merging with the “little tradition.” In identifying this accommodation paradox, the article offers the wider study of religion a model of how a foreign faith interacts with an entrenched host tradition, demonstrating that the effectiveness of accommodation may itself generate the conditions of its subsequent prohibition. Full article

The rise of capture-the-flag (CTF) competitions and offensive security training requires the deployment of systems that are, by design, flawed. This creates a unique architectural paradox: how does one host a system intended to be compromised without compromising the host itself? This paper classifies the security principles of “range engineering”—the discipline of engineering the environment. This research study synthesizes evidence across the cyber-range, honeypot, ICS/OT testbed, and cloud-isolation literature to derive a containment-focused classification of threat planes, security invariants, boundary mechanisms and properties, and operational controls for intentionally vulnerable environments used in education, training, and research. Five security invariants are derived under the assumption of expected compromise and mapped to boundary families and measurable operational objectives. The analysis further identifies under-evidenced areas, particularly control-plane isolation, corrective controls for cross-tenant failures, and systematic validation of externalization defenses. Full article

Hantaviruses are emerging zoonotic pathogens responsible for two severe clinical syndromes: (i) haemorrhagic fever with renal syndrome (HFRS) and (ii) hantavirus cardiopulmonary syndrome (HCPS), collectively causing more than 200,000 human cases annually worldwide. Despite their public-health importance, the molecular mechanisms governing the host response and the population-level dynamics of rodent-to-human spillover remain incompletely characterised. The timeliness of this framework is underscored by the April–May 2026 outbreak of Andes orthohantavirus aboard the MV Hondius cruise ship, the first such cluster in a maritime setting, with three deaths reported across multiple countries. This event revealed critical gaps in existing models that treat humans solely as dead-end spillover hosts. Our coupled Susceptible-Exposed-Infectious-Recovered-Dead (SEIRD) model assumes no human-to-human transmission and is therefore designed for hantavirus strains where spillover does not lead to secondary human cases, specifically Hantaan virus (HTNV), Puumala virus (PUUV), Sin Nombre virus (SNV), and Dobrava-Belgrade virus (DOBV). The Andes virus (ANDV) outbreak aboard the MV Hondius is used as a real-world case study to assess the boundaries of our model and to motivate future extensions, not as a direct validation target for its quantitative predictions. Here, we present an integrated computational study combining three complementary analyses. First, we performed a preliminary phylogenetic analysis of the viral sequence, identifying Orthohantavirus andesense as the likely etiological agent responsible for the vessel-associated outbreak. Second, we carried out a downstream transcriptomic analysis of Hantaan virus (HTNV)-infected human umbilical vein endothelial cells (HUVECs), using publicly available RNA-seq data (GEO accession GSE133751, $n=3$ per group). This analysis identified 184 upregulated and 19 downregulated genes, highlighting a transcriptional response dominated by interferon-stimulated genes (ISGs), including CXCL10, CXCL11, MX2, DDX58, IRF7, STAT1, OASL, and CMPK2. We then constructed a protein–protein interaction (PPI) network using STRING, comprising 176 nodes and 3210 edges, and applied a composite network centrality score to rank putative regulatory hubs. This analysis identified ISG15, IRF1, CXCL10, STAT1, and DDX58 as the most central nodes. Pathway enrichment analysis confirmed a strong activation of interferon signalling (Reactome, $p=1.3\times {10}^{-63}$), antiviral defence mechanisms (Gene Ontology, $p=3.8\times {10}^{-58}$), and NF-$\kappa$B-related pathways, together with a concurrent suppression of ribosomal translation. Finally, we developed a coupled SEIRD epidemiological model that explicitly represents rodent-to-rodent and rodent-to-human transmission with logistic rodent population growth. Preliminary simulation analysis demonstrates that reducing human exposure to rodent excreta is substantially more effective than rodent population control alone for reducing human disease burden, and that rodent control in isolation can paradoxically increase human cases through a dilution-like effect. The integrated framework provides molecular and epidemiological insights relevant to hantavirus surveillance, therapeutic target identification, and public-health intervention design. Full article

Neutrophils are the most abundant circulating leukocytes and are characterized by a proteome in which granule-associated proteins synthesized during granulopoiesis constitute a major fraction of total cellular protein, reflecting their preloaded effector nature in innate immune defense. A striking feature of neutrophil biology is the unusual abundance of the calcium-binding proteins S100A8 and S100A9, which together form the heterodimeric complex known as calprotectin. Early biochemical studies estimated that S100A8/A9 constitutes a substantial fraction of the soluble cytosolic proteome in neutrophils, with later studies often describing it as one of the most abundant protein complexes in these cells. Despite extensive studies on the antimicrobial and inflammatory activities of calprotectin, the biological rationale for this unusual abundance remains incompletely understood. In this review, we examine the structural, biochemical, and regulatory features of S100A8/A9 and explore the potential explanations for its high abundance in the neutrophil cytosol. We first discuss the unique organization of the neutrophil proteome and the transcriptional programs governing granulopoiesis that lead to large-scale production of neutrophil effector proteins. We then review the structural and biochemical properties of S100A8/A9, including its calcium-dependent conformational dynamics and high-affinity transition metal binding, which contribute to antimicrobial defense through nutritional immunity. Several functional hypotheses are considered to explain calprotectin abundance, including roles as an antimicrobial reservoir, a metal-sequestering molecule, a regulator of oxidative stress, and a source of damage-associated molecular patterns. Finally, we discuss the evolutionary logic of neutrophil protein preloading and the implications of calprotectin biology in inflammatory diseases and the tumor microenvironment. Resolving the abundance paradox of S100A8/A9 may reveal fundamental principles governing the organization of innate immune cell proteomes and provide new insights into the strategies used by neutrophils to achieve rapid and effective host defense. Full article

This study examines how digitalization and institutional quality jointly influence the size and dynamics of the shadow economy across EU member states. It adopts an integrated framework in which digital capacity is treated as an operational extension of state capacity that can either complement strong institutions or compensate for institutional weaknesses. The empirical analysis is based on a two-dataset panel covering 27 EU countries over the periods 2013–2022 and 2017–2022. Institutional quality is measured using the Worldwide Governance Indicators, while digitalization is captured through detailed indicators from the Digital Economy and Society Index. Fixed-Effects models with Driscoll–Kraay standard errors are employed, alongside interaction and nonlinear specifications. Results show that institutional quality is consistently associated with lower levels of the shadow economy, but its effect exhibits diminishing returns at higher levels of governance, indicating institutional saturation. Digitalization effects are domain-specific. In isolation, both citizen- and business-oriented digital services show a positive association with the shadow economy, a finding termed the Digitalization Paradox, reflecting a phase where technological facilitation of informal activity outpaces regulatory adaptation. However, their interaction with institutional quality reveals divergent mechanisms. Citizen-oriented services tend to substitute for weaker governance, while business-oriented services complement strong institutional frameworks. The findings indicate that digitalization serves as an institutional amplifier whose final impact on the shadow economy, whether formalizing or facilitating, is dictated by the maturity of the host institution. Full article

Background/Objectives: The prognostic significance of body mass index (BMI) in hepatocellular carcinoma (HCC) remains controversial, and whether the obesity paradox may reflect tumor biology or host-related factors is unclear. This study evaluated the association between BMI and survival after curative hepatic resection using continuous and interaction-based analyses. Methods: We retrospectively analyzed 1349 patients who underwent curative hepatic resection for HCC between 2004 and 2021. BMI was assessed both categorically (low (<18.5 kg/m²), normal (18.5–24.9 kg/m²), and high (≥25 kg/m²)) and as a continuous variable. Overall survival (OS) and recurrence-free survival (RFS) were analyzed using Kaplan–Meier methods and multivariable Cox proportional hazards models. Interaction terms were incorporated to examine whether the prognostic effect of BMI varied across clinically relevant subgroups defined by tumor differentiation, tumor size, tumor number, and alpha-fetoprotein level. Results: OS differed significantly across BMI categories (log-rank p < 0.001), whereas differences in RFS were modest. At 3 years, estimated OS rates were 88%, 82%, and 62% in the high, normal, and low BMI groups, respectively. In multivariable analysis, higher BMI as a continuous variable was independently associated with improved OS (hazard ratio per 1-unit increase, 0.87; 95% confidence interval, 0.79–0.95; p = 0.005), but not with RFS. Subgroup analyses demonstrated a consistent protective association between BMI and OS without significant interactions across tumor-related factors. Conclusions: Higher BMI is independently associated with improved overall survival after hepatic resection for HCC, irrespective of tumor biology. These findings support a host-related explanation for the obesity paradox in surgically treated HCC. Full article

Environmental sustainability (ES) has increasingly become a core focus of the International Olympic Committee (IOC) due to institutional pressures as well as the threat of climate change. Since the IOC continues to urge candidature cities to underscore ES in the bidding and planning process by asking more elaborate questions in the Candidature Questionnaire, it remains unclear how winning cities have adapted their bids to demonstrate their accountability to win the rights to host an ES Games. One approach to better understanding the discourse candidature cities use in their ES plans is to study how bid committees employ Aristotle’s rhetorical appeals—ethos (credibility), pathos (emotion), and logos (logic). To do so, this qualitative case study analyzed winning candidature files of the Summer and Winter Olympic Games (N = 16) from 1992 to present day. The results revealed one distinct rhetorical appeal, ethos, emerged more than the others that underscored the value of highlighting credibility in ES contexts. One of the most interesting findings of the study is that ethos-based arguments depend greatly on existing governance infrastructures, policies, certifications, and previous experience, external to the IOC governance process. This is a significant finding because it shows the paradox of embedded agency, while also highlighting how establishing credibility is more important to cities than merely promising results. Full article

Global warming and international trade are accelerating biological invasions, making the Mediterranean basin a hotspot for alien arthropods. Two invasive species, the drosophilid Zaprionus tuberculatus and the wax scale Ceroplastes ceriferus, were recently detected in central-southern Italy. Surveys conducted between 2023 and 2024 detected Z. tuberculatus across several sites in Campania and Lazio, and C. ceriferus in Campania. Zaprionus tuberculatus was reared from ten host plants, including three new records, and reached its highest abundance on persimmon. Laboratory assays showed that Z. tuberculatus adults reproduced only on intact fig fruits and blueberry, indicating a limited risk for most crops. Ceroplastes ceriferus was found on four hosts, confirming its polyphagy and establishment in southern Italy. Molecular analyses revealed two COI haplotypes in the Italian populations of both species, while three haplotypes were detected globally in Z. tuberculatus and seven in C. ceriferus. Sequence divergences were moderate, indicating limited but appreciable mitochondrial differentiation among geographic populations. In Z. tuberculatus, the COII haplotype detected in Italy did not match available African sequences, underscoring gaps in reference data and complicating the reconstruction of invasion routes. Despite contrasting ecological traits and dispersal strategies, both species achieved successful establishment in Italy, showing that ecological plasticity and human-mediated transport can offset reduced genetic diversity. These records expand the known European range of both species and highlight the need for coordinated surveillance, genetic monitoring, and preventive measures to limit further introductions in the Mediterranean region. Full article

Cutibacterium acnes, a major skin commensal bacterium, induces inflammatory cytokine production in keratinocytes through Toll-like receptor 2 (TLR2) signaling and contributes to acne vulgaris pathogenesis. Although glucocorticoids, e.g., dexamethasone (Dex), exert anti-inflammatory effects in related treatments, prolonged glucocorticoid exposure paradoxically induces acneiform eruptions, a phenomenon referred to as steroid-induced acne. Moreover, how commensal fungi influence bacterial-driven inflammatory signaling under glucocorticoid treatment remains unclear. In this study, we investigated how the lipophilic skin yeast Malassezia restricta affects C. acnes-induced TLR2 expression under Dex treatment using normal human epidermal keratinocytes. We discovered that M. restricta selectively suppressed Dex-enhanced C. acnes-induced TLR2 expression both at the transcriptional level and cell surface. Mechanistically, M. restricta enhanced p38 MAPK phosphorylation and inhibited NF-κB p65 nuclear translocation, indicating context-dependent glucocorticoid-primed TLR2 signaling modulation rather than simple inhibition. These results demonstrate that M. restricta modulates bacterial-induced inflammatory responsiveness in keratinocytes under glucocorticoid exposure and highlight the importance of fungal–bacterial interactions in shaping host immune signaling in steroid-treated skin. Our study provides new insight into the mechanistic basis of steroid-induced acne and the polymicrobial regulation of cutaneous innate immunity. Full article