Search Results (960)

Global aquaculture faces increasing threats from declining oxygen levels, with several key aquaculture regions now classified as hypoxic. The gills, responsible for oxygen uptake, pathogen-sensing, and immune responses, are the primary interface for this stress. However, the comparative effects of different hypoxic regimes on the gill resilience of Atlantic salmon (Salmo salar) remain poorly understood. In this study, Atlantic salmon were exposed during a 7-day trial to two different moderate hypoxic stress models, chronic hypoxia and cyclic hypoxia. A whole-genome oligo-microarray revealed that both hypoxic stress regimes cause transcriptomic shifts, driven in the chronic hypoxia group by upregulation of PRRs and other immune components and downregulation of DNA repair and cell cycle maintenance. On the other hand, the cyclic hypoxic group focused on physiological plasticity and rapid cellular adjustments. Additionally, RT-qPCR was used to evaluate key gene expression of hypoxia and immune response. The chronic hypoxia group was characterized by downregulation of hif2a, gshpx, and gr-anx1 signaling, with a continuous upregulation state of tnfa2, suggesting an unresolved inflammatory state, often associated with apoptosis and gill damage. In contrast, the cyclic hypoxia group displayed an increased epo expression and recovery of antioxidant enzymes (e.g., gsphx), accompanied by normalized levels of tnfa2 at the end of the 7-day trial. Therefore, chronic hypoxic stress imposes a significantly higher burden on the gills of Atlantic salmon than cyclic hypoxic stress, compromising their ability to respond to secondary stressors and impairing immune homeostasis. Full article

Virus infection requires coordinated activation of pathogen-sensing, innate immune, and cellular stress response pathways to mount an effective antiviral defense. Recognition of nucleic acid pathogen-associated molecular patterns (PAMPs) by pattern recognition receptors (PRRs) initiates signaling cascades that drive the production of type I interferons (IFNs) and proinflammatory cytokines. These responses are often accompanied by the activation of integrated stress response pathways that help optimize host defense. Cytosolic double-stranded dsDNA, generated during viral infection or released from damaged mitochondria, is sensed by cyclic GMP-AMP synthase (cGAS), which generates 2′3′-cGAMP to activate stimulator of interferon genes (STING). Activated STING translocates from the endoplasmic reticulum to the Golgi, where it drives TBK1-dependent IFN and cytokine production. Previous reports show that cGAS activity is enhanced by Ras-GAP SH3 domain binding protein 1 (G3BP1), a key nucleator of stress granules (SGs), independent of its role in SG assembly. Here, we identify a non-canonical role of G3BP1 as a regulator of DNA sensing responses at multiple levels, including STING intracellular trafficking, in addition to potentiating cGAS activity. Loss of G3BP1 impaired STING-dependent IFN and cytokine responses to HSV-1 infection and viral DNA. G3BP1-deficient cells showed reduced cGAMP-induced STING translocation to the Golgi, induction of type I IFN and proinflammatory cytokines, and activation of the ER stress kinase PERK and stress granule formation. Together, these findings demonstrate G3BP1-STING as a node linking DNA sensing, innate immunity, and stress signaling with broad implications for antiviral defense and diseases characterized by aberrant DNA sensing and stress responses, including neurodegeneration, fibrosis, and autoimmunity. Full article

Glioblastoma (GBM) remains the most lethal primary brain tumor in adults, with a median overall survival of approximately 15–20 months despite multimodal treatment including surgery, chemoradiation, and Tumor Treating Fields (TTFields). While the survival benefit of TTFields was established by the EF-14 phase III trial, their biological effects extend well beyond the canonical anti-mitotic mechanism and encompass extensive interactions with the GBM tumor microenvironment (TME). This review provides an integrated mechanistic analysis of TTFields–TME interactions in GBM, with a distinctive focus on their convergence with radiotherapy. We examine how TTFields activate innate immune sensing through cGAS/STING and AIM2 inflammasome pathways, drive immunogenic cell death, reprogram tumor-associated macrophages, and prime adaptive T cell responses. We further address TTFields effects on glioma stem cells, blood–brain barrier permeability, and intracellular signaling governing invasion, angiogenesis, and autophagy. Critically, we develop the mechanistic and clinical case for TTFields-radiotherapy combinations, highlighting convergent mechanisms of DNA repair impairment, mitotic catastrophe, and innate immune activation. Practical considerations for concurrent clinical implementation are discussed alongside a research agenda centered on optimal timing, hypofractionation, and predictive biomarkers. Available evidence—largely preclinical—suggests that TTFields may act as a TME-remodeling platform whose potential is most likely to be realized through mechanistically informed combinations. Full article

Porcine circovirus type 5 (PCV5) is a recently reported porcine-associated CRESS DNA virus, but information regarding its occurrence, genomic characteristics, and evolutionary relationship remains limited. In this study, a total of 100 diagnostic samples collected from clinically diseased pigs from 27 commercial swine farms in 16 cities across seven provinces of China during 2025 were screened for PCV5 using quantitative PCR. PCV5 was detected in 22% (22/100) of the tested samples, with positive samples identified in Henan and Fujian provinces among the sampled regions. PCV5-positive samples were mainly fecal samples and were obtained from pigs showing diarrhea, respiratory signs, wasting, or systemic disease. Co-detection analysis showed that most PCV5-positive samples were also positive for other swine viral pathogens, particularly PCV3, PCV2, and PEDV, indicating that the clinical significance of PCV5 should be interpreted cautiously. Complete genome amplification and sequencing yielded two identical PCV5 genomes from Henan and Fujian provinces. A representative strain, designated PCV5-Henan2025-ZJQ01, was further characterized and deposited in GenBank under accession number PZ496079. The complete genome was 2903 nt in length and contained a positive-sense ORF encoding Cap and a negative-sense ORF encoding Rep, showing a distinct genomic organization compared with classical porcine circoviruses. Phylogenetic analysis based on Rep and Cap amino acid sequences showed that PCV5-Henan2025-ZJQ01 was closely related to previously reported PCV5-related sequences but distinct from classical PCV1–PCV4. These findings provide additional molecular and genomic evidence for PCV5 in Chinese swine diagnostic samples and support the need for continued surveillance and further studies on its epidemiological and pathogenic significance. Full article

Vegetated coastal wetlands, especially mangroves, seagrass beds, and salt marshes, are biodiversity-rich ecosystems whose blue carbon outcomes depend on living communities, sediment dynamics, hydrological connectivity, and landscape context. Biodiversity conservation and blue carbon management are often assessed through separate scientific, monitoring, and policy frameworks. This review uses a staged literature search and thematic synthesis to examine biodiversity–blue carbon linkages across the three major vegetated coastal wetland types. It considers how taxonomic, genetic, functional, and habitat diversity influence productivity, sediment stabilization, trophic exchange, carbon stocks, carbon burial, and carbon retention. It also evaluates how climate change, habitat fragmentation, hydrological alteration, pollution, and anthropogenic disturbance weaken these linkages. The synthesis compares representative carbon-stock and burial-rate baselines, examines conservation and restoration synergies and trade-offs, and expands the discussion of seagrass regime shifts. Field surveys, remote sensing, unmanned aerial vehicles, environmental DNA, and AI-enabled data integration are placed within a tiered monitoring framework. The review further develops an operational decision pathway for biodiversity-centered blue carbon management. Persistent blue carbon benefits arise where conservation and restoration maintain native communities, hydrological exchange, sediment stability, habitat complexity, migration space, and long-term stewardship capacity. Full article

Dairy cows are economically significant ruminants in China, and the dairy industry is closely linked to food safety and the agricultural economy. However, various factors such as pathogenic microorganisms often lead to frequent diseases in dairy cows. Furthermore, as potential hosts for diverse viruses, dairy cows can harbor zoonotic pathogens, which pose a threat to public health. The Shaanxi–Gansu–Ningxia region boasts abundant natural resources and extensive pastures. It is a major animal husbandry base in Northwest China, and dairy farming plays a significant role in the local economy. However, research on dairy cow virus diversity in this region remains limited; epidemic prevention and control capabilities are constrained, and the risk of disease outbreaks is elevated. In this study, 790 dairy cow samples were collected from 13 large-scale farms and free-range households in the Shaanxi–Gansu–Ningxia region from 2021 to 2023. Sample types consisted of nasal and anal swabs. Six viral metagenomic libraries were constructed and analyzed using high-throughput sequencing and bioinformatics methods, leading to the identification of 51 viral families. These comprised 16 positive-sense single-stranded RNA virus families, one Retroviridae family, four double-stranded RNA virus families, 21 double-stranded DNA virus families, and nine single-stranded DNA virus families. Among these, RNA viruses were represented by families such as Astroviridae, Coronaviridae, Caliciviridae, Picornaviridae, and Picobirnaviridae; DNA viruses were primarily detected in Circoviridae, Papillomaviridae, Genomoviridae, and Smacoviridae. Alpha diversity analysis revealed no significant differences in viral diversity and abundance among the three regions (p > 0.05); however, significant differences were observed in the read counts and proportions of RNA and DNA viruses across the provinces. Phylogenetic analysis further indicated that viruses carried by dairy cows exhibit considerable genetic diversity and pose potential cross-species transmission risks. This study established a reference database for the dairy cow virome in the Shaanxi–Gansu–Ningxia region, elucidated the phylogenetic relationships of key viruses, and provided a scientific basis for future monitoring and prevention of dairy cow viruses. Full article

In recent years, wars have gradually increased the risk of marine oil spill accidents. Marine oil spill monitoring becomes more and more important for preventing marine oil pollution. The Chinese Zhuhai-1 satellite can capture abundant spectral reflectance signals. It is a significant way of detecting marine oil spills. Most of the traditional oil spill detection methods only used a small amount of spectral information. It made it difficult identify oil spills accurately from the inhomogeneous marine environment. In order to mine the key differential spectral information of oil slicks, inspired by the encoding method of spectral DNA, an advanced spectral DNA encoding (ASDE) strategy was proposed to describe the spectral details in Zhuhai-1 images. On this basis, two kinds of key spectral information extraction methods were proposed to mine the spectral genes of oil slicks. Finally, the extracted spectral genes were used to detect the marine oil spills. Three Zhuhai-1 satellite images were used to validate the performance of the proposed method based on ASDE strategy. The experimental results indicated that the proposed method could precisely describe the spectral differences in oil slicks and seawater in Zhuhai-1 images. In addition, the extracted spectral genes could detect marine oil spills correctly. Full article

Background/Objectives: Bitter taste receptors (T2Rs), specifically T2R38, are present in the respiratory epithelium and react with bacterial quorum-sensing molecules to induce an innate immunity response. Although TAS2R38 polymorphisms have been correlated with susceptibility to chronic rhinosinusitis (CRS), they have not yet been explored in odontogenic rhinosinusitis (ORS), a distinct form of CRS with particular microbial and inflammatory features. We aim to establish a proof-of-concept methodology for investigating TAS2R38 genetic variants in ORS using direct maxillary sinus tissue analysis and demonstrate the feasibility of this translational approach. Methods: We conducted a prospective pilot case–control study of 36 ORS patients and 37 controls undergoing septoplasty without sinonasal disease. Maxillary sinus mucosal biopsies were obtained intraoperatively with informed consent. Genomic DNA was extracted using the PureLink Genomic DNA Mini Kit and quantified via NanoDrop spectrophotometry. TAS2R38 haplotypes were determined and classified as taster (PAV/PAV), non-taster (AVI/AVI), or intermediate (PAV/AVI) phenotype. Results: Among fully classifiable canonical TAS2R38 phenotypes (32 ORS patients, 28 controls), distributions were: tasters 12.5% vs. 25.0%, non-tasters 31.3% vs. 25.0%, and intermediate 56.3% vs. 50.0%. AVI/AVI non-taster status was not significantly associated with ORS susceptibility (OR = 1.36, 95% CI: 0.44–4.25; Fisher’s exact p = 0.775). Conclusions: This proof-of-concept study demonstrates that genotyping-grade genomic DNA can be recovered from acutely inflamed maxillary sinus mucosa, validating this substrate for future tissue-based expression, functional, and microbiome analyses not obtainable from peripheral samples; germline genotyping itself does not require sinus tissue. The observed difference in non-taster prevalence (31.3% vs. 25.0%) did not reach statistical significance and is reported descriptively. This directional trend is hypothesis-generating only and, given the limited statistical power, does not constitute evidence for an association. The demonstrated feasibility, together with the established biological rationale, supports an adequately powered confirmatory study and lays the foundation for future investigation of taste receptor genetics in ORS pathogenesis, and potentially personalized therapeutic strategies. Full article

Introduction: Species Distribution Models (SDMs) are widely used to infer environmental drivers of freshwater fish distributions and to project biodiversity responses to climate and land-use change. However, freshwater ecosystems present specific conceptual and methodological challenges, including dendritic network structure, strong spatial autocorrelation, dispersal constraints, and scale mismatches between biological processes and environmental predictors that remain insufficiently addressed. At the same time, emerging data sources such as environmental DNA (eDNA) and high-resolution remote sensing offer new opportunities to improve data coverage and ecological realism in SDMs. Methodology: Focusing on Iberian systems as illustrative case studies, here, we synthesize the following recent advances and challenges in SDM applications to freshwater fishes: (i) the implications of using presence–absence versus abundance data; (ii) the integration of hydrological and connectivity metrics as predictors; (iii) approaches to explicitly account for spatial structure and biotic interactions; and (iv) the contribution of novel datasets, including eDNA and remote sensing. Furthermore, we examine the performance and transferability of correlative models under analogue and non-analogue climate conditions. Results: Our synthesis highlights the importance of incorporating network topology, seasonality, dispersal constraints, and novel data sources to improve ecological realism and predictive performance. The integration of emerging biodiversity and environmental data can substantially reduce data gaps and improve model calibration and validation, particularly in poorly sampled systems. Nonetheless, model transferability remains a challenge, particularly for endemic and range-restricted species. Advancing freshwater SDMs through the integration of hydrologically explicit frameworks and novel data sources will strengthen their capacity to support evidence-based management of freshwater fish assemblages facing accelerating environmental changes. Full article

Biosensing performance in graphene-derived field-effect transistors (BioFETs) is widely attributed to surface chemistry, yet the role of the underlying charge transport mechanism remains poorly understood. This work establishes a direct correlation between disorder-driven transport and biosensing transduction in vertical graphene (VG) and nanocrystalline graphite (NCG) FET devices. Temperature-dependent electrical characterization (15–500 K) reveals a hybrid transport regime: three-dimensional Mott variable-range hopping below 240 K, transitioning to thermally activated Arrhenius-type conduction above 240 K. The extracted VRH parameters characteristic temperature T₀, localization length ξ, and density of states N(E_F) quantify fundamentally distinct disorder landscapes: VG operates in a strongly localized, edge-dominated regime, while NCG forms a continuous percolative network with greater transport stability. Surface functionalization via PASE and amine-terminated ssDNA probes, followed by DNA hybridization across four nucleobase systems, demonstrates that the sequence-dependent electrical response is mechanistically interpretable within the VRH–transconductance framework. NCG transduces biomolecular binding through direct charge transfer and hopping pathway perturbation, whereas VG responds through interfacial electrostatic reorganization. These results introduce a unified VRH–transconductance–sensing framework, providing a rational physical basis for next-generation graphene BioFET design. Full article

Fatty liver disease represents a major metabolic disorder affecting domestic animals worldwide, with significant implications for animal health, welfare, and agricultural productivity. Disrupted communication between mitochondria and other organelles—particularly the endoplasmic reticulum, lipid droplets, and lysosomes—plays a critical role in disease pathogenesis. This review synthesizes knowledge on inter-organellar communication across domestic animals, with emphasis on species-specific adaptations. We address the “Dairy Cow Paradox”—periparturient dairy cows develop severe hepatic steatosis (>30% liver fat), yet under sterile conditions, they have a higher threshold for progressing to sterile steatohepatitis compared to rodents and humans. However, it is critical to note that severe fatty liver in dairy cows is indeed associated with impaired autophagy, inflammation, and liver damage, particularly when accompanied by ketosis or concurrent infections, and 39% of transition cows exhibit moderate to severe lymphocytic hepatitis. We propose that the tolerance to severe steatosis in dairy cows arises from three adaptations: (1) attenuated innate immune sensing via the cGAS-STING pathway; (2) enhanced lipid buffering from perilipin 5 (PLIN5) with a hypothesized ruminant-specific Val152 substitution that may stabilize lipid droplet–mitochondria contacts; and (3) dampened calcium signaling due to ER–mitochondria membrane lipid raft rigidity, elevated inositol 1,4,5-trisphosphate receptor 2 (IP₃R2) expression, and reduced mitochondrial calcium uniporter (MCU) conductance. We contrast this with the inflammatory steatohepatitis common in rodent models driven by calcium overload and mitochondrial DNA (mtDNA) release, and glucocorticoid-mediated mitofusin 1 (MFN1) suppression, causing mitochondrial fragmentation in poultry. We identify critical knowledge gaps, including the need to define bovine and avian mitochondria-associated endoplasmic reticulum membrane (MAM) proteomes and spatially resolve hepatic zonal communication patterns. Targeting organellar communication hubs with nutraceuticals or pharmacological agents offers promising therapeutic strategies. Full article

Reliable quality control of adeno-associated virus (AAV) vectors remains a major bottleneck in gene therapy manufacturing, particularly for resolving subtle differences in genome loading and conformation at the single-particle level. Existing approaches often struggle to distinguish AAV populations with similar mass and charge, such as capsids carrying self-complementary versus single-stranded DNA. Here, we introduce an AC plasmonic nanopore sensing framework for AAV9 characterization. Individual AAV capsids were optically trapped within a plasmonic double-nanohole nanopore and interrogated using multi-frequency AC pulse trains spanning 500 Hz to 100 kHz. To enhance sensitivity to localized particle–field interactions, a nanofabricated Ag/AgCl ring electrode was integrated concentrically with the plasmonic nanopore. Relative to a conventional wire electrode, the ring electrode produced broader and more robust analyte-dependent differences across multiple frequency-dependent parameters, enabling reliable discrimination of empty capsids (AAV_empty) and genome-loaded capsids carrying either self-complementary (AAV_scDNA) or single-stranded DNA (AAV_ssDNA), despite their near-identical genome mass. Concentration titration experiments further demonstrated that the extracted multivariate AC features remained largely concentration-independent over the tested range. Together, these results demonstrate that ring-electrode-enabled AC plasmonic nanopore sensing provides a multidimensional framework for resolving closely related AAV populations and advances plasmonic nanopores toward practical single-particle quality control of gene therapy vectors. Full article

Background: Osteosarcoma remains a biologically complex and clinically challenging malignancy, with survival gains plateauing despite decades of multimodal therapy incorporating surgery and cytotoxic chemotherapy. Unlike cancers in which mutation-centric precision oncology has yielded transformative advances, osteosarcoma is characterized by profound structural variation, copy number alteration dominance, and dynamic clonal evolution, limiting the effectiveness of single-target approaches. These realities motivate alternative strategy-level frameworks that better align treatment selection with evolving disease behavior. Methods: This narrative educational review synthesizes contemporary evidence from osteosarcoma biology, radiobiology, and translational oncology to propose a state-based framework for integrating radiotherapy—particularly stereotactic body radiotherapy (SBRT/SABR) and spatially fractionated radiotherapy (SFRT)—into osteosarcoma management and clinical trial design. Rather than relying solely on static anatomic stage, this framework emphasizes clinically actionable, time-varying state variables, including disease burden patterns (localized, oligometastatic, polymetastatic), tempo of progression, prior systemic response, and feasibility of complete local control. Results: Within this context, radiotherapy is presented not only as a local control modality but also as a hypothesis-generating biologic intervention, capable of perturbing tumor vasculature, inflammatory signaling, innate DNA-sensing pathways, and immune/myeloid programs in a dose-, fractionation-, and spatial-distribution-dependent manner. The review critically examines both the potential opportunities (e.g., local eradication, immune modulation) and limitations (e.g., rarity of abscopal responses, risk of unintended systemic signaling) of radiobiotherapy combinations, emphasizing the need for cautious interpretation and prospective validation. Conclusions: Finally, the article outlines practical implications for state-stratified, biomarker-embedded clinical trials, highlighting endpoints beyond conventional response criteria, including circulating tumor DNA dynamics, immune and myeloid signatures, and long-term patterns of disease progression. Overall, this review frames radiobiotherapy as an educational and investigational paradigm intended to support rational hypothesis generation, multidisciplinary decision-making, and learning-oriented trial designs in osteosarcoma, rather than as definitive clinical guidance. Full article

Infertility and ovarian ageing are increasingly acknowledged as illnesses affected not just by endocrine decline but also by chronic inflammatory stress and mitochondrial dysfunction in the reproductive milieu. The cGAS-STING signalling pathway has emerged as a significant possibility linking these activities. The cGAS-STING pathway, originally defined as a cytosolic DNA-sensing mechanism essential for innate immune defence, is now recognised as a broader modulator of sterile inflammation, cellular senescence, and tissue failure. Experimental reproductive models suggest that the activation of this system may operate as a crucial link between mitochondrial dysfunction, cytosolic DNA accumulation, inflammatory cytokine production, and the progressive decline of ovarian and endometrial function. The activation of cGAS-STING in granulosa cells has been associated with inflammatory signalling and impaired steroidogenic activity. Full article

Amaranth (Amaranthus spp.) is a multifaceted genus of C4 plants with significant nutritional and agronomic potential, yet it remains underutilized in mainstream agriculture. Despite growing interest in Amaranth, most germplasm studies have used either phenotypic or molecular approaches alone, lacking integration. Multivariate methods have not been systematically applied to identify promising genotypes, and species-specific selection indices for grain Amaranth remain unexplored. To address these gaps, this study comprehensively characterized 84 Amaranth genotypes representing multiple species (A. caudatus, A. cruentus, A. hypochondriacus, A. hybridus, A. spinosus, A. powellii, A. tricolor, and 38 accessions of unknown taxonomic status) using field experiments in a randomized complete block design with three replications and DNA barcoding with chloroplast (psbA-trnH) and nuclear (ITS) markers. Analysis of variance revealed highly significant differences (p < 0.01) among genotypes for all six agronomic traits evaluated, confirming substantial genetic variability with grain yield exhibiting the widest variation (CV = 28.55%), ranging from 0.25 to 125.56 g/plant. High broad-sense heritability estimates (0.79–0.99) coupled with high genetic advance, particularly for grain yield (117.54%), indicated that these traits would respond favorably to selection. Path analysis and stepwise regression identified early flowering, long inflorescences, and heavy seeds as the primary determinants of grain yield, collectively explaining 27% of yield variation. Mahalanobis D² analysis identified nine multivariate outliers with distinct phenotypic profiles, among which G39 emerged as the most promising breeding candidate, combining exceptional yield (90.50 g/plant) with desirable architecture, long inflorescence, and large seeds. Principal component analysis further resolved trait complexes, identifying 11 PC1-selected promising genotypes as donors for plant architecture and three PC2-selected promising genotypes as donors for seed size characteristics. Molecular analysis revealed distinct genetic relationships. A. caudatus (kiwicha) exhibited limited haplotype diversity indicating a narrow genetic base, while A. cruentus and A. hypochondriacus showed broader diversity, with the nuclear ITS network providing clearer resolution than chloroplast markers due to biparental inheritance. Outlier genotypes, including G82, G83, G13, G10, and G39, occupied unique haplotype positions, confirming that their phenotypic distinctiveness corresponds to genuine genetic differentiation. The novelty of this study lies in integrating multivariate biostatistical techniques (heritability, path analysis, Mahalanobis D², PCA, and stepwise regression) with two complementary DNA barcode systems (chloroplast and nuclear) within a single germplasm collection. This integrated approach provides breeders with well-characterized germplasm, validated selection criteria, and prioritized parental materials for Amaranth improvement. Further multi-location and multi-season evaluations are recommended to ensure the stability and adaptability of these promising germplasm accessions. Full article