Search Results (9,668)

Arthropod-borne orthoflaviviruses, including dengue, Zika, Japanese encephalitis, yellow fever and West Nile viruses, pose a significant global public health threat, causing hundreds of millions of infections annually with severe clinical symptoms. However, the lack of effective vaccines and antiviral drugs, coupled with the biosafety risks associated with handling live highly pathogenic strains, hinders progress in antiviral research. Pseudovirus technology, which uses single-round infectious viral particles lacking replication competence, has thus gained prominence as a safe and versatile tool for antiviral research. This review systematically summarizes the construction, optimization, and applications of orthoflavivirus pseudoviruses in antiviral research. The primary construction strategies of orthoflavivirus pseudoviruses rely on multi-plasmid co-transfection of viral replicons and structural protein expression vectors, leveraging the host cell secretory pathway to mimic natural viral assembly and maturation. The core applications of pseudovirus technology are highlighted, including high-throughput screening and detection of neutralizing antibodies, identification of antiviral drugs targeting viral entry or replication, and evaluation of vaccine immunogenicity. Despite these strengths, the approach still faces limitations, such as incomplete simulation of native viral structures and batch-to-batch titer variability, which may affect the physiological relevance of findings. In summary, orthoflavivirus pseudovirus technology has become an essential platform in both basic virology research and translational medicine, providing critical insights and tools in the ongoing fight against arthropod-borne orthoflaviviruses diseases. Full article

Clostridial neurotoxins, botulinum neurotoxins (BoNTs), and tetanus neurotoxin (TeNT) are potent toxins responsible for severe diseases, botulism and tetanus, respectively. BoNTs associate with non-toxic proteins (non-toxic non-hemagglutinin, hemagglutinins, and OrfXs), which protect BoNTs against acidic pH and protease degradation and facilitate BoNT passage through the intestinal barrier. TeNT enters motor neurons and undergoes a retrograde axonal transport until the target inhibitory interneurons in the central nervous system. BoNTs and TeNT recognize specific cell surface receptors which consist of complex sets of protein(s)-glycan-gangliosides and determine specific cell entry pathways. Recent data on structural and functional investigations of BoNT and TeNT receptors bring a better understanding of toxin trafficking in the host and entry into target neuronal cells, which is useful for the development of updated strategies of prevention and treatment of the corresponding diseases. Since clostridial neurotoxins, notably BoNTs, are important therapeutic tools, detailed knowledge of their activity opens the way of the development of engineered molecules for specific clinical applications. Full article

Symbiotic copepods have a wide host group, including not only invertebrates but also vertebrates, with variable symbiotic sites and morphological characteristics. Even though symbiotic copepods exhibit remarkable diversity, our knowledge of them is still very limited, causing significant lacunae in our understanding of their taxonomic characteristics, host associations, and geographical distributions. To fill these knowledge gaps, we have compiled a comprehensive list of symbiotic copepods and their molluscan hosts in the global oceans based on an extensive literature review. The inventory provides a comprehensive synthesis of the diversity, hosts, and geographical distributions of the symbiotic copepods. This review summarizes information on copepods symbiotic with mollusks from 1863 to 2025. Our compilation records a total of 342 symbiotic copepod species associated with more than 435 species of mollusks. This total includes some copepod species for which no specific host has been identified. For each copepod species, we provide details on its hosts, geographical distributions and the original references. Full article

Living systems can be understood as organized entities that capture, transform, and reproduce information. Classical gene-centered models explain adaptation through frequency changes driven by differential fitness, yet they often overlook the higher-order organization and causal closure that characterize living systems. Here we revisit several evolutionary frameworks, from the replicator equation to group selection and holobiont dynamics, and show that evolutionary change in population frequencies can be expressed as a Jeffreys divergence. Building on this foundation, we introduce a categorical model of Information Handlers (IHs), entities capable of self-maintenance, mutation, and combination. This abstract architecture illustrates the usefulness of category theory for framing evolutionary processes that range from very simple to highly complex. The same categorical scheme can represent basic allele-frequency change as well as more elaborate scenarios involving reproductive interactions, symbiosis, and other organizational layers. A key feature of the framework is that different levels of evolutionary change can be summarized through a measure that quantifies the information generated, thereby distinguishing diverse types of evolutionary transformation, such as individual and sexual selection, mate choice, or even holobiont selection. Finally, we show that the informational partition associated with host–microbiome pairings in holobionts generalizes the information-theoretic structure previously developed for non-random mating, revealing a common underlying architecture across biological scales. Full article

Tomato leafminer (Tuta absoluta) significantly affects tomato (Solanum lycopersicum) and eggplant (Solanum melongena) crops worldwide, with its feeding patterns being closely associated with its gut microbiota. We aimed to compare the cultivable gut bacteria of T. absoluta larvae fed on tomato and eggplant to investigate their role in host adaptation. Gut bacteria were cultivated on Luria–Bertani broth, nutrient agar, and Brain Heart Infusion media under different temperature conditions, followed by morphology- and 16S rRNA-based identification. Notably, both feeding groups revealed distinct gut bacterial community structures. Tomato-fed larvae harbored bacteria spanning eight species, five genera, four families, and two phyla. In contrast, eggplant-fed larvae exhibited greater microbial diversity, encompassing 15 species, 10 genera, 9 families, and 3 phyla, including unique genera such as Pseudomonas and Pectobacterium, which was attributed to the host plant contribution. Enterococcus mundtii was the most dominant bacterium, and species such as Bacillus wiedmannii and Micrococcus luteus were most thermotolerant. Overall, these findings highlight the importance of multi-condition culture approaches for thoroughly characterizing insect gut microbiota and underscore the role of host plants in pest adaptability by modulating gut microbial communities, providing new insights for developing sustainable control strategies utilizing “plant–insect–microorganism” interactions. Full article

Phosphatidylserine (PS) externalization is a conserved membrane stress signal that becomes chronically dysregulated in cancer cells and tumor-associated endothelium. In vivo, PS does not exist as a free lipid signal but is presented in specific membrane-associated forms, including apoptotic or stressed cell surfaces, PS-rich extracellular vesicles, and circulating lipid particles. Unlike apoptosis-associated transient PS exposure, malignant PS externalization arises from metabolic rewiring, oxidative stress, epigenetic silencing of flippases, and microenvironmental cues, creating an immunosuppressive interface across the tumor–host boundary. This review synthesizes mechanistic, immunological, and clinical evidence on PS biology, including its roles in tumor immune evasion, extracellular vesicle-mediated systemic suppression, and vascular remodeling. We further summarize the development and evaluation of PS-targeted therapeutic platforms—such as bavituximab, SapC-DOPS/BXQ-350, and PS-directed imaging agents—and highlight their translational potential in combination with radiotherapy, chemotherapy, and checkpoint inhibitors. Chronic PS externalization, as manifested through distinct cellular and vesicular carriers, represents a unifying biomarker of tumor stress, immune suppression, and therapeutic vulnerability, offering a next-generation axis for theragnostic cancer management. Full article

Agroathelia (syn. Sclerotium) is a global soil-borne pathogen with a broad host range, causing significant agricultural losses in diverse crops. However, genomic and population genetic resources of this genus remain limited. To develop genome-based molecular tools, we newly sequenced two Korean isolates (A. rolfsii KACC 93004P and A. delphinii KACC 93031P) and compared them with the reference genome of A. rolfsii GP3. Comparative genome analysis identified 723 polymorphic simple sequence repeat (SSR) loci, from which 14 were selected and validated across 34 Korean isolates representing multiple host plants. Genetic diversity was assessed using the number of alleles (NA), observed heterozygosity (Ho), unbiased expected heterozygosity (He), and polymorphic information content (PIC). Most SSRs were moderately to highly informative (PIC = 0.341 to 0.541 in A. rolfsii; 0.367 to 0.612 when including A. delphinii). Unweighted pair group method with arithmetic mean (UPGMA) clustering based on SSR allele profiles clearly separated the two species and revealed a distinct intraspecific structure within A. rolfsii. Principal coordinates analysis (PCoA) also revealed clear species-level separation, while A. rolfsii isolates were partitioned into two intraspecific clusters with one divergent isolate, indicating structured genetic variation without a host-associated population structure. The developed SSR markers provide useful tools for studying genetic diversity, population structure, and epidemiology of Agroathelia species and isolates. Full article

Exosomes are important mediators of host–parasite communication and contain diverse molecules that may support the survival of Clonorchis sinensis in the biliary tract. To explore their biochemical properties, exosomes isolated from excretory–secretory products of Korean C. sinensis isolates were characterized through integrated morphological, proteomic, and gene ontology analyses. The vesicles exhibited typical exosomal size ranges and marker profiles, and their protein components were enriched for cytoskeletal, metabolic, and vesicle-trafficking components relevant to epithelial signaling and immune modulation. Among these proteins, sphingomyelin phosphodiesterase acid-like 3A (SMPDL3A) was examined in detail to obtain molecular evidence suggesting its role in sphingolipid metabolism in the parasite. The C. sinensis SMPDL3A (Cs_SMPDL3A) shared the overall structure and core catalytic residues with mammalian homologs, SMPDL3A and sphingomyelin phosphodiesterase 1 (SMPD1), a finding consistent with the possibility that Cs_SMPDL3A may retain authentic sphingomyelinase activity. Although lacking the saponin B domain of SMPD1, Cs_SMPDL3A carries a C-terminal transmembrane segment that may facilitate sphingomyelin access by positioning the enzyme on lipid bilayers. Collectively, these findings suggest that Cs_SMPDL3A participates in host sphingomyelin turnover, potentially generating ceramide for uptake by SMPD1-lacking C. sinensis or contributing to ceramide-associated immune responses in the biliary tract, offering new insight into lipid-centered host–parasite interactions during clonorchiasis. Full article

Influenza D virus (IDV), an emerging orthomyxovirus with zoonotic potential, infects diverse hosts, causes respiratory disease, and remains poorly characterized in China despite its global expansion. From October 2023 to January 2025, we collected 563 nasal swabs from cattle across 28 farms in Jilin Province, Northeast China, and identified seven IDV-positive samples (1.2%), recovering two viable isolates (JL/YB2024 and JL/CC2024). Full-genome sequencing revealed complete, stable seven-segment genomes with high nucleotide identity (up to 99.9%) to contemporary Chinese D/Yamagata/2019 strains and no evidence of reassortment. Maximum-likelihood and time-resolved Bayesian phylogenies of 231 global hemagglutinin-esterase-fusion (HEF) sequences placed the Jilin isolates within the East Asian D/Yamagata/2019 clade and traced their most recent common ancestor to approximately 2017 (95% highest posterior density: 2016–2018), suggesting a cross-border introduction likely associated with regional cattle movement. No IDV was detected in parallel surveillance of swine, underscoring cattle as the principal reservoir and amplifying host. Bayesian skyline analysis demonstrated a marked decline in global IDV genetic diversity during 2020–2022, coinciding with livestock-movement restrictions imposed during the COVID-19 pandemic. Collectively, these findings indicate that IDV circulation in China is sporadic and geographically localized, dominated by the D/Yamagata/2019 lineage, and shaped by multiple independent incursions rather than a single emergence. Both the incorporation of IDV diagnostics into routine bovine respiratory disease surveillance and cattle-import quarantine programs, and the adoption of a One Health framework to monitor potential human spillover and future viral evolution, were recommend. Full article

Tan sheep are a characteristic and economically important local breed in the Ningxia Hui Autonomous Region of China, where respiratory diseases continue to pose challenges to animal health and production. In this study, a Pasteurella multocida strain (P6) was isolated from the lung tissue of a single Tan sheep presenting with severe and fatal respiratory disease, and subjected to case-based genomic and pathogenic characterization. The isolate was identified as capsular serotype A based on biochemical profiling, 16S rRNA gene sequencing, kmt-1 PCR, and capsular typing. To provide supportive evidence of virulence potential, a murine infection model was employed, in which P6 induced acute clinical signs and severe pulmonary lesions, including congestion, edema, hemorrhage, and fibrinous inflammatory exudation. Whole-genome sequencing revealed that strain P6 possesses a 2,289,251 bp genome with a GC content of 40.2%, encoding 2155 predicted genes and multiple mobile genetic elements, including genomic islands, prophages, transposons, and a CRISPR locus. Phylogenetic analysis based on seven housekeeping genes placed P6 in close relationship with strains 166CV and 103220, distinct from several rodent- and avian-derived isolates. Functional genomic analyses identified numerous genes associated with carbohydrate metabolism, secondary metabolite biosynthesis, host–pathogen interaction, virulence-related functions, and antimicrobial resistance. Comparative genomic analysis with the reference strain PM70 indicated a largely conserved functional framework, accompanied by a significant enrichment of mobilome-associated genes, suggesting enhanced genomic plasticity. Overall, this study provides a descriptive genomic overview of a P. multocida isolate associated with respiratory disease in Tan sheep and highlights its genetic features and potential adaptive capacity, while acknowledging the limitations inherent to a single-case investigation. Full article

The liver stage of Plasmodium infection represents a critical bottleneck in malaria pathogenesis and a unique interface between parasite development and hepatocyte-intrinsic immunity. Recent evidence suggests that hepatocytes do not eliminate liver-stage parasites through canonical xenophagy, as previously assumed, but instead employ a noncanonical autophagy response known as the conjugation of ATG8 to single membranes (CASM). CASM drives rapid lipidation of LC3 onto the parasitophorous vacuole membrane (PVM) via a V-ATPase-ATG16L1-dependent mechanism, thereby activating the Plasmodium-associated autophagy-related (PAAR) response. This process represents a major hepatocyte-intrinsic mechanism that limits early liver-stage parasite development. Plasmodium liver-stage parasites have evolved specialized strategies to counteract this host defense. The PVM proteins UIS3 and UIS4 enable parasite evasion by sequestering LC3 and remodeling perivacuolar actin, thereby preventing endolysosomal fusion and inhibiting PAAR execution. In parallel, parasites selectively exploit host autophagy components—particularly GABARAP paralogs—to activate TFEB, promoting lysosomal biogenesis and improving access to host-derived nutrients. These interactions highlight autophagy as both a protective and parasite-supportive pathway, depending on the molecular context. Understanding how CASM, PAAR, and parasite evasion mechanisms intersect is crucial for designing pathway-selective interventions that amplify hepatocyte-intrinsic clearance while avoiding the inadvertent enhancement of parasite-supportive autophagy programs. Selective modulation of noncanonical autophagy offers a promising avenue for host-directed therapies that restrict liver-stage development while limiting the emergence of antimalarial resistance. This review synthesizes recent advances in the mechanistic interplay between Plasmodium liver stages and hepatocyte autophagy, identifies major knowledge gaps, and outlines future directions for translating these discoveries into therapeutic innovation. Full article

Enterococcus spp. are opportunistic pathogens and commensals in humans and animals and are widely used as indicators of bacterial exchange, providing insights into antimicrobial resistance (AMR) and virulence dissemination within the One Health continuum. Enterococcus from healthy companion animals and their tutors were characterized to compare AMR profiles and virulence traits between hosts and within households in Lisbon, Portugal. Fecal samples (n = 45) were collected from 17 animals and 11 tutors. Enterococci were recovered from selective media, subjected to random amplified polymorphic DNA PCR (RAPD-PCR) and species identification, tested for antimicrobial susceptibility, and screened for virulence traits. Among animal isolates, 61% were Enterococcus faecalis, 29% E. faecium, and 10% E. hirae, whereas human enterococci comprised 52% E. faecalis, 35% E. faecium, 8% E. hirae, and 4% other species. Erythromycin resistance was identical in both groups (29%; Chi-squared test, p = 0.99). Ampicillin resistance was detected in all animal samples but was absent in human samples, whereas tetracycline and rifampicin resistance showed moderate host-specific patterns. Hemolytic activity was detected in 16% of animal and 31% of human isolates, all cylA-positive. Significant associations were observed between host origin and resistance to ampicillin and rifampicin, and between species and resistance to erythromycin and tetracycline. These findings suggest that companion animals can harbor, and potentially disseminate, AMR and virulence traits, reinforcing the need for One Health surveillance. Full article

The vaginal microbiome plays a crucial role in maintaining host health by preserving a balanced microenvironment. Nevertheless, the definition of a “normal” vaginal microbiome remains controversial, as its composition varies depending on factors such as ethnicity and geographical origin. In most cases, members of the genus Lactobacillus predominate in healthy vaginal microbiomes, protecting against potential pathogens through specific mechanisms such as the secretion of lactic acid and bacteriocins, among others. A reduction in Lactobacillus abundance, accompanied by an increase in anaerobic organisms, predisposes the host to the development of various pathologies. Among these pathologies is infection with human papillomavirus (HPV) and the subsequent development of cervical cancer. A progressive decline in Lactobacillus has been observed as the lesion advances in different populations worldwide. In the case of the Mexican population, several Lactobacillus have been reported in healthy microbiomes: L. gasseri, L. fermentum, L. rhamnosus, L. jensenii, L. crispatus, L. delbrueckii, L. acidophilus, and L. brevis. In contrast, genera reported in dysbiosis include Sneathia, while Brevibacterium aureum and Brachybacterium conglomeratum have been associated with HPV16 infection and/or SIL. The mere presence of some bacteria is not sufficient to modulate the cellular activity of host cells; therefore, the expression, production and activity of different proteins could be affected by the vaginal microbiome. The impact of the microbiome on host cell function is the result of different metabolites produced by the bacteria, which suppress or activate different signaling and metabolic pathways. The molecular interactions between the host and microbiome, as well as their role in cervical carcinogenesis, are still unknown. In this review, we focus on the vaginal microbiome, HPV, and the impact that the interaction of the microbiome with HPV has in cervical cancer development. Full article

Influenza A virus (IAV) continues to present a threat to public health, highlighting the need for safe and multi-target antivirals. In this study, anti-influenza activity, airborne transmission blocking capacity, and immunomodulatory effects of Cnidium monnieri polysaccharides (CMP) were evaluated. Cytotoxicity in A549 cells was assessed by CCK-8 (CC₅₀ = 8.49 mg/mL), antiviral efficacy against A/California/04/2009 (CA04) by dose–response (EC₅₀ = 1.63 mg/mL), and the stage of action by time-of-addition assays (pre-, co-, post-treatment). A guinea pig model infected with CA04 was used for testing the effect of pre-exposure CMP on transmission, with readouts including nasal-wash titers, seroconversion, lung index, and tissue titers (EID₅₀). RT-qPCR was employed to quantify the mRNA expression levels of proinflammatory cytokines, including TNF-α, IL-1β, and IL-6, in lung tissue, while Western blot analysis was performed to assess the expression and phosphorylation status of key proteins involved in the NF-κB signaling pathway. CMP suppressed viral replication in vitro within non-cytotoxic ranges, and pre-treatment—rather than co- or post-treatment—significantly reduced titers and cytopathic effect, consistent with effects at pre-entry steps and/or host priming. In vivo, pre-exposure CMP lowered nasal shedding, reduced aerosol transmission (3/6 seroconverted vs. 6/6 controls), decreased lung indices, and diminished tissue viral loads; IAV was undetectable in trachea at 7 days post-infection in pre-exposed animals, and nasal-turbinate titers declined relative to infection controls. Moreover, during in vivo treatment in mice, CMP significantly suppressed the levels of inflammatory cytokines (TNF-α, IL-1β, and IL-6) in lung tissue. This effect was mechanistically associated with CMP-mediated regulation of the NF-κB signaling pathway, leading to attenuation of inflammatory responses. These data indicate that CMP combines a favorable in vitro safety and efficacy profile with inhibition of airborne spread in vivo, supporting further mechanistic, pharmacokinetic, and fractionation studies toward translational development. Full article

Root-knot nematodes (RKN), especially Meloidogyne incognita, threaten global alfalfa crops because of their broad host range and pathogenic nature. Despite its significance, research on resistance is limited. In this study, 24 varieties from China, the US, Canada, Australia, and France were assessed for resistance using the Disease Index (DI) and Egg Mass Index (EMI). Results identified 19 varieties with varying resistance levels and 5 that were susceptible. Chinese Gannong No. 9 was highly resistant (DI: 10) and achieved the highest composite score (91). The US varieties Dryland and Moste were classified as resistant (DI: 14.3% and 12.5%, respectively) and also ranked highly by composite score (65 and 62.5). A moderate correlation between DI and EMI (r = 0.68) led to some inconsistent classifications, including for 2295, Instict, and WL168HQ, highlighting the importance of using multiple complementary metrics for accurate resistance evaluation. Egg mass production was strongly correlated with galling severity (r = 0.70), while root biomass showed no correlation with galling (r = 0.09), indicating root weight is not a reliable resistance indicator. Preliminary infection dynamics showed similar nematode penetration rates at 2 days post-infection across resistant and susceptible varieties. At 7 days post-infection, both resistant and susceptible varieties retained predominantly J2 larvae (78–89%), with no statistically significant differences in developmental stage distributions. These preliminary observations suggest that resistance-associated effects on nematode development, if present, are not strongly expressed at early stages of infection. The mechanistic basis of resistance in alfalfa remains unresolved and warrants further investigation using additional timepoints, histological analyses of feeding-site development, and molecular characterization. Geographically, American varieties displayed broad performance variation, Chinese varieties showed a bimodal distribution, and Canadian varieties exhibited moderate, consistent resistance. These results offer valuable germplasm for breeding and highlight the importance of multiple resistance metrics. Resistant varieties such as Gannong No. 9 provide important genetic resources for developing durable nematode resistance in alfalfa and can guide variety selection in nematode-infested regions. Full article