Search Results (10,072)

Background/Objectives: Intramuscular immunization elicits systemic IgG and is the primary route of vaccine administration in humans. However, there is growing interest in utilizing other routes of administration to tailor antibody profiles, increase immunity at primary sites of infection, simplify administration, and eliminate needle waste. Here, we investigated the antibody profiles elicited by immunization with bacteriophage virus-like particle vaccine platforms at various routes of administration. Methods: We chose two model bacteriophage vaccines for investigation: bacteriophage MS2 virus-like particles (VLPs) recombinantly displaying a short, conserved peptide from Chlamydia trachomatis major outer membrane protein (MS2) and bacteriophage Qβ VLPs displaying oxycodone through chemical conjugation (Qβ). We comprehensively characterized the antibodies elicited systemically and at various mucosal sites when the vaccines were administered intramuscularly, intranasally or periocularly with or without an intramuscular prime using various prime/boost schemes. Results: Intranasal and periocular immunization elicited robust mucosal and systemic IgA responses for both MS2 and Qβ. The intramuscular prime followed by intranasal or periocular boosts elicited broad antibody responses, and increased antibodies titers at certain anatomical sites. Conclusions: These findings demonstrate the tractability of bacteriophage VLP-based vaccines in generating specific antibody profiles based on the prime–boost regimen and route of administration. Full article

Bone-related defects present a key challenge in orthopaedics. The current gold standard, autografts, poses significant limitations, such as donor site morbidity, limited supply, and poor morphological adaptability. This study investigates the potential of scaffold geometry to induce osteogenic differentiation of human adipose-derived stem cells (hADSCs) through mechanotransduction, without the use of chemical inducers. Four distinct poly-(L)-lactic acid (PLA) scaffold architectures—Traditional Cross (Tc), Triangle (T), Diamond (D), and Gyroid (G)—were fabricated using fused filament fabrication (FFF) 3D printing. hADSCs were cultured on these scaffolds, and their response was evaluated utilising an alkaline phosphatase (ALP) assay, immunofluorescence, and extensive proteomic analyses. The results showed the D scaffold to have the highest ALP activity, followed by Tc. Proteomics results showed that more than 1200 proteins were identified in each scaffold with unique proteins expressed in each scaffold, respectively Tc—204, T—194, D—244, and G—216. Bioinformatics analysis revealed structures with complex curvature to have an increased expression of proteins involved in mid- to late-stage osteogenesis signalling and differentiation pathways, while the Tc scaffold induced an increased expression of signalling and differentiation pathways pertaining to angiogenesis and early osteogenesis. Full article

Forest fires are commonly regarded as negative for ecosystems; however, they also represent a major ecological force shaping the biodiversity of invertebrates and many other organisms. The aim of this study was to better understand how multiple groups of invertebrates respond to wildfire across different forest types in Central Europe. The research was conducted following a large forest fire (ca. 1200 ha) that occurred in 2022. Data were collected over two years (2023 and 2024), from April to September. The research was conducted in coniferous forests and included six pairwise study types: burnt and unburnt dead spruce (bark beetle affected), burnt and unburnt clear-cuts, and burnt and unburnt healthy stands. In total, 96 traps were deployed each year. Across both years, 220,348 invertebrates were recorded (1.Y: 128,323; 2.Y: 92,025), representing 24 taxonomic groups. A general negative trend in abundance following forest fire was observed in the groups Acari, Auchenorhyncha, Blattodea, Dermaptera, Formicidae, Chilopoda, Isopoda, Opiliones, and Pseudoscorionida. Groups showing a neutral response included Araneae, Coleoptera, Collembola, Diplopoda, Heteroptera, Psocoptera, Raphidioptera, Thysanoptera, and Trichoptera. Positive responses, indicated by an increase in abundance, were recorded in Hymenoptera, Orthoptera, Lepidoptera, and Diptera. However, considerable differences among management types (clear-cut, dead spruce, and healthy) were evident, as their distinct characteristics largely influenced invertebrate abundance in both unburnt and burnt variants of the types across all groups studied. Forest fire primarily creates favorable conditions for heliophilous, open-landscape, and floricolous invertebrate groups, while less mobile epigeic groups are strongly negatively affected. In the second year post-fire, the total invertebrate abundance in burnt sites decreased to 59% of the first year’s levels. Conclusion: Forest fire generates a highly heterogeneous landscape from a regional perspective, creating unique ecological niches that persist more than two years after fire. For many invertebrates, successional return toward pre-fire conditions is delayed or incomplete. Full article

The barbel chub (Squaliobarbus curriculus) exhibits remarkable resistance to grass carp reovirus (GCRV), a devastating pathogen in aquaculture. To reveal the molecular basis of this resistance, we investigated complement factor D (DF)—a rate-limiting serine protease governing alternative complement pathway activation. Molecular cloning revealed that the barbel chub DF (ScDF) gene encodes a 1251-bp cDNA sequence translating into a 250-amino acid protein. Crucially, bioinformatic characterization identified a unique N-glycosylation site at Asn¹³⁹ in ScDF, representing a structural divergence absent in grass carp (Ctenopharyngodon idella) DF (CiDF). While retaining a conserved Tryp_SPc domain harboring the catalytic triad (His⁶¹, Asp¹⁰⁹, and Ser²⁰⁴) and substrate-binding residues (Asp¹⁹⁸, Ser²¹⁹, and Gly²²¹), sequence and phylogenetic analyses confirmed ScDF’s evolutionary conservation, displaying 94.4% amino acid identity with CiDF and clustering within the Cyprinidae. Expression profiling revealed constitutive ScDF dominance in the liver, and secondary prominence was observed in the heart. Upon GCRV challenge in S. curriculus kidney (SCK) cells, ScDF transcription surged to a 438-fold increase versus uninfected controls at 6 h post-infection (hpi; p < 0.001)—significantly preceding the 168-hpi response peak documented for CiDF in grass carp. Functional validation showed that ScDF overexpression suppressed key viral capsid genes (VP2, VP5, and VP7) and upregulated the interferon regulator IRF9. Moreover, recombinant ScDF protein incubation induced interferon pathway genes and complement C3 expression. Collectively, ScDF’s rapid early induction (peaking at 6 hpi) and multi-pathway coordination may contribute to barbel chub’s GCRV resistance. These findings may provide molecular insights into the barbel chub’s high GCRV resistance compared to grass carp and novel perspectives for anti-GCRV breeding strategies in fish. Full article

Because artificially cemented granular (ACG) materials employ diverse combinations of aggregates and binders—including cemented soil, low-cement-content cemented sand and gravel (LCSG), and concrete—their stress–strain responses vary widely. In LCSG, the binder dosage is typically limited to 40–80 kg/m³ and the sand–gravel skeleton is often obtained directly from on-site or nearby excavation spoil, endowing the material with a markedly lower embodied carbon footprint and strong alignment with current low-carbon, green-construction objectives. Yet, such heterogeneity makes a single material-specific constitutive model inadequate for predicting the mechanical behavior of other ACG variants, thereby constraining broader applications in dam construction and foundation reinforcement. This study systematically summarizes and analyzes the stress–strain and volumetric strain–axial strain characteristics of ACG materials under conventional triaxial conditions. Generalized hyperbolic and parabolic equations are employed to describe these two families of curves, and closed-form expressions are proposed for key mechanical indices—peak strength, elastic modulus, and shear dilation behavior. Building on generalized plasticity theory, we derive the plastic flow direction vector, loading direction vector, and plastic modulus, and develop a concise, transferable elastoplastic model suitable for the full spectrum of ACG materials. Validation against triaxial data for rock-fill materials, LCSG, and cemented coal–gangue backfill shows that the model reproduces the stress and deformation paths of each material class with high accuracy. Quantitative evaluation of the peak values indicates that the proposed constitutive model predicts peak deviatoric stress with an error of 1.36% and peak volumetric strain with an error of 3.78%. The corresponding coefficients of determination R² between the predicted and measured values are 0.997 for peak stress and 0.987 for peak volumetric strain, demonstrating the excellent engineering accuracy of the proposed model. The results provide a unified theoretical basis for deploying ACG—particularly its low-cement, locally sourced variants—in low-carbon dam construction, foundation rehabilitation, and other sustainable civil engineering projects. Full article

Effective earthquake early warning (EEW) is essential for disaster prevention in the built environment, enabling a rapid structural response, system shutdown, and occupant evacuation to mitigate damage and casualties. However, most current EEW systems lack rigorous reliability analyses of their predictive outcomes, limiting their effectiveness in real-world scenarios—especially for on-site warnings, where data are limited and time is critical. To address these challenges, we propose a Bayesian neural network (BNN) framework based on Stein variational gradient descent (SVGD). By performing Bayesian inference, we estimate the posterior distribution of the parameters, thus outputting a reliability analysis of the prediction results. In addition, we incorporate a continual learning mechanism based on elastic weight consolidation, allowing the system to adapt quickly without full retraining. Our experiments demonstrate that our SVGD-BNN model significantly outperforms traditional peak displacement (Pd)-based approaches. In a 3 s time window, the Pearson correlation coefficient R increases by 9.2% and the residual standard deviation $SD$ decreases by 24.4% compared to a variational inference (VI)-based BNN. Furthermore, the prediction variance generated by the model can effectively reflect the uncertainty of the prediction results. The continual learning strategy reduces the training time by 133–194 s, enhancing the system’s responsiveness. These features make the proposed framework a promising tool for real-time, reliable, and adaptive EEW—supporting disaster-resilient building design and operation. Full article

The rabies virus (RABV) phosphoprotein (P protein) has multiple functions, including acting as the essential non-catalytic cofactor of the viral polymerase (L protein) for genome replication and transcription; the principal viral antagonist of the interferon (IFN)-mediated innate immune response; and the chaperone for the viral nucleoprotein (N protein). Although P protein is known to undergo phosphorylation by cellular kinases, the location and functions of the phosphorylation sites remains poorly defined. Here, we report the identification by mass-spectrometry (MS) of residues of P protein that are modified by phosphorylation in mammalian cells, including several novel sites. Analysis of P protein with phospho-mimetic and phospho-inhibitory mutations of three novel residues/clusters that were commonly identified by MS (Ser48, Ser183/187, Ser217/219/220) indicate that phosphorylation at each of these sites does not have a major influence on nuclear trafficking or antagonistic functions toward IFN signalling pathways. However, phosphorylation of Ser48 in the N-terminus of P protein impaired function in transcription/replication and in the formation of replication structures that contain complexes of P and N proteins, suggestive of altered interactions of these proteins. The crystal structure of P protein containing the S48E phospho-mimetic mutation indicates that Ser48 phosphorylation facilitates the binding of residues 41–52 of P protein into the RNA-binding groove of non-RNA-bound N protein (N⁰), primarily through the formation of a salt bridge with Arg434 of N protein. These data indicate that Ser48 modification regulates the cycling of P-N⁰ chaperone complexes that deliver N protein to RNA to enable transcription/replication, such that enhanced interaction due to S48E phospho-mimetic mutation reduces N protein delivery to the RNA, inhibiting subsequent transcription/replication processes. These data are, to our knowledge, the first to implicate phosphorylation of RABV P protein in conserved replication functions of the P gene. Full article

Since carbohydrate antigen 19-9 (CA 19-9) is a significant biomarker for the clinical diagnosis and treatment of pancreatic cancer, a sensitive sandwich-type immunosensor was proposed with an epoxy functionalized covalent organic framework (EP-COF_TTA-DHTA) as the antibody carrier and an electroactive COF_{TTA-2,6-NA(OH)2} as the signal amplification probe for the sensitive detection of CA 19-9. The flexible covalent linkage between the epoxy-functionalized EP-COF_TTA-DHTA and the antibodies was employed to improve the dynamics of the antigen–antibody interaction significantly. Meanwhile, AuNPs@COF_{TTA-2,6-NA(OH)2} with abundant electroactive sites enhanced the current response of the immunoreaction significantly. After optimizing the incubation time and concentration of the antibody, CA 19-9 was quantitatively detected by differential pulse voltammetry (DPV) based on the sensitive sandwich-type immunosensor with a low detection limit of 0.0003 U/mL and a wide linear range of 0.0009–100 U/mL. The electrochemical immunosensor exhibits high specificity, stability and repeatability, and it provides a feasible and efficient method for the pathologic analysis and treatment of tumor markers. Full article

Urban coral reefs in Jakarta Bay and the Thousand Islands, Indonesia, are chronically exposed to land-based pollution and increasing thermal stress. These reefs—including the site of Indonesia’s first recorded coral bleaching event in 1983—remain highly vulnerable to climate-induced disturbances. During the fourth global coral bleaching event (GCBE), we recorded selective bleaching in the region, associated with a Degree Heating Weeks (DHW) value of 4.8 °C-weeks. Surveys conducted in January 2024 across a shelf gradient at four representative islands revealed patchy bleaching, affecting various taxa at depths ranging from 3 to 13 m. A follow-up survey in May 2024, which tracked the fate of 42 tagged bleached colonies, found that 36% had fully recovered, 26% showed partial recovery, and 38% had died. Bleaching responses varied across taxa, depths, and microhabitats, often occurring in close proximity to unaffected colonies. While some corals demonstrated resilience, the overall findings underscore the continued vulnerability of urban reefs to escalating thermal stress. This highlights the urgent need for a comprehensive and coordinated national strategy—not only to monitor bleaching and assess reef responses, but also to strengthen protection measures and implement best-practice restoration. Such efforts are increasingly critical in the face of more frequent and severe bleaching events projected under future climate scenarios. Full article

Background/Objectives: Mucosal vaccines, delivered intranasally or via inhalation, are being studied for respiratory infectious diseases like COVID-19 and influenza. These vaccines aim to provide non-invasive administration and strong immune responses at infection sites, making them a promising area of research. This systematic review and meta-analysis assessed their immunogenicity, safety, and protective efficacy. Methods: The study design was a systematic review and meta-analysis, searching PubMed and Cochrane databases up to 30 May 2025. Inclusion criteria followed the PICOS framework, focusing on mucosal vaccines for COVID-19, influenza, RSV, pertussis, and tuberculosis. Results: A total of 65 studies with 229,614 participants were included in the final analysis. Mucosal COVID-19 vaccines elicited higher neutralizing antibodies compared to intramuscular vaccines (SMD = 2.48, 95% CI: 2.17–2.78 for wild-type; SMD = 1.95, 95% CI: 1.32–2.58 for Omicron), with varying efficacy by route (inhaled VE = 47%, 95% CI: 22–74%; intranasal vaccine VE = 17%, 95% CI: 0–31%). Mucosal influenza vaccines protected children well (VE = 62%, 95% CI: 30–46%, I² = 17.1%), but seroconversion rates were lower than those of intramuscular vaccines. RSV and pertussis vaccines had high seroconversion rates (73% and 52%, respectively). Tuberculosis vaccines were reviewed systemically, exhibiting robust cellular immunogenicity. Safety was comparable to intramuscular vaccines or placebo, with no publication bias detected. Conclusions: Current evidence suggests mucosal vaccines are immunogenic, safe, and protective, particularly for respiratory diseases. This review provides insights for future research and vaccination strategies, though limitations include varying efficacy by route and study heterogeneity. Full article

The midgut of Antheraea pernyi plays a critical role in antiviral defense. However, its transcriptional complexity remains poorly understood. Here, a full-length (FL) transcriptome atlas of A. pernyi midgut was developed by integrating PacBio Iso-Seq and RNA-seq techniques. The transcriptome sequences included 1850 novel protein-coding genes, 17,736 novel alternative isoforms, 1664 novel long non-coding RNAs (lncRNAs), and 858 transcription factors (TFs). In addition, 2471 alternative splicing (AS) events and 3070 alternative polyadenylation (APA) sites were identified. Moreover, 3426 and 4796 differentially expressed genes (DEGs) and isoforms were identified after ApNPV infection, respectively, besides the differentially expressed lncRNAs (164), TFs (171), and novel isoforms of ApRelish (1) and ApSOCS2 (4). Enrichment analyses showed that KEGG pathways related to metabolism were suppressed, whereas GO terms related to DNA synthesis and replication were induced. Furthermore, the autophagy and apoptosis pathways were significantly enriched among the upregulated genes. Protein–protein interaction network (PPI) analysis revealed the coordinated downregulation of genes involved in mitochondrial ribosomes, V-type and F-type ATPases, and oxidative phosphorylation, indicating the disruption of host energy metabolism and organelle acidification. Moreover, coordinated upregulation of genes associated with cytoplasmic ribosomes was observed, suggesting that the infection by ApNPV interferes with host translational machinery. These results show that ApNPV infection reprograms energy metabolism, biosynthetic processes, and immune response in A. pernyi midgut. Our study provides a foundation for elucidating the mechanisms of A. pernyi–virus interactions, particularly how the viruses affect host defense strategies. Full article

As sustainable cultural heritage tourism increasingly demonstrates its unique value and appeal, effectively stimulating tourists’ emotional experiences and value co-creation behaviors has become a focal issue. This study investigates how multiple tourist motivations (self-enhancement, escapism, and social interaction) shape value co-creation through emotional mediators—namely aesthetic, nostalgic, and flow experiences. Data were collected from 470 valid responses from visitors to the UNESCO-listed Suzhou Classical Gardens in China and analyzed using partial least squares structural equation modeling (PLS-SEM). The results show that these emotional experiences significantly drive value co-creation behavior: self-enhancement motivation enhances all three experiences, escapism mainly promotes nostalgic and flow experiences, and social interaction primarily affects aesthetic experience. These findings clarify the psychological mechanisms through which tourists’ motivations and emotional experiences influence value co-creation behavior in cultural heritage tourism. This research advances our understanding of the motivation–experience–behavior framework and emphasizes that enhancing emotional engagement is key to fostering sustainable cultural heritage tourism practices. The study provides practical implications for designing experiences and strategies that balance visitor satisfaction with the long-term vitality of cultural heritage sites and local communities, thereby contributing to broader sustainable development goals. Full article

The multiscale interactive system composed of wind, leaves, and droplets serves as a critical dynamic unit in precision orchard spraying. Its coupling mechanisms fundamentally influence pesticide transport pathways, deposition patterns, and drift behavior within crop canopies, forming the foundational basis for achieving intelligent and site-specific spraying operations. This review systematically examines the synergistic dynamics across three hierarchical scales: Droplet–leaf surface wetting and adhesion at the microscale; leaf cluster motion responses at the mesoscale; and the modulation of airflow and spray plume diffusion by canopy architecture at the macroscale. Key variables affecting spray performance—such as wind speed and turbulence structure, leaf biomechanical properties, droplet size and electrostatic characteristics, and spatial canopy heterogeneity—are identified and analyzed. Furthermore, current advances in multiscale modeling approaches and their corresponding experimental validation techniques are critically evaluated, along with their practical boundaries of applicability. Results indicate that while substantial progress has been made at individual scales, significant bottlenecks remain in the integration of cross-scale models, real-time acquisition of critical parameters, and the establishment of high-fidelity experimental platforms. Future research should prioritize the development of unified coupling frameworks, the integration of physics-based and data-driven modeling strategies, and the deployment of multimodal sensing technologies for real-time intelligent spray decision-making. These efforts are expected to provide both theoretical foundations and technological support for advancing precision and intelligent orchard spraying systems. Full article

Background/Objectives: The prolonged M1-like pro-inflammatory polarization of macrophages is a key factor in the delayed healing of diabetic ulcers (DU). SIRT3, a primary mitochondrial deacetylase, has been identified as a regulator of inflammation and represents a promising new therapeutic target for DU treatment. Nonetheless, the efficacy of existing SIRT3 agonists remains suboptimal. Methods: Here, we introduce a novel compound, SZC-6, demonstrating promising activity levels. Results: SZC-6 treatment down-regulated the expression of inflammatory factors in LPS-treated RAW264.7 cells and reduced the proportion of M1 macrophages. Mitosox, IF, and JC-1 staining revealed that SZC-6 preserved cellular mitochondrial homeostasis and reduced the accumulation of reactive oxygen species. In vivo experiments demonstrated that SZC-6 treatment accelerated wound healing in diabetic mice. Furthermore, HE and Masson staining revealed increased neovascularization at the wound site with SZC-6 treatment. Tissue immunofluorescence results indicated that SZC-6 effectively decreased the proportion of M1-like cells and increased the proportion of M2-like cells at the wound site. We also found that SZC-6 significantly reduced MyD88, p-IκBα, and NF-χB p65 protein levels and inhibited the nuclear translocation of P65 in LPS-treated cells. Conclusions: The study concluded that SZC-6 inhibited the activation of the NF-χB pathway, thereby reducing the inflammatory response and promoting skin healing in diabetic ulcers. SZC-6 shows promise as a small-molecule compound for promoting diabetic wound healing. Full article

Multivalent lectin–glycan interactions (MLGIs) are vital for viral infection, cell-cell communication and regulation of immune responses. Their structural and biophysical data are thus important, not only for providing insights into their underlying mechanisms but also for designing potent glycoconjugate therapeutics against target MLGIs. However, such information remains to be limited for some important MLGIs, significantly restricting the research progress. We have recently demonstrated that functional nanoparticles, including ∼4 nm quantum dots and varying sized gold nanoparticles (GNPs), densely glycosylated with various natural mono- and oligo- saccharides, are powerful biophysical probes for MLGIs. Using two important viral receptors, DC-SIGN and DC-SIGNR (together denoted as DC-SIGN/R hereafter), as model multimeric lectins, we have shown that α-mannose and α-manno-α-1,2-biose (abbreviated as Man and DiMan, respectively) coated GNPs not only can provide sensitive measurement of MLGI affinities but also reveal critical structural information (e.g., binding site orientation and mode) which are important for MLGI targeting. In this study, we produced mannuronic acid (ManA) coated GNPs (GNP-ManA) of two different sizes to probe the effect of glycan modification on their MLGI affinity and antiviral property. Using our recently developed GNP fluorescence quenching assay, we find that GNP-ManA binds effectively to both DC-SIGN/R and increasing the size of GNP significantly enhances their MLGI affinity. Consistent with this, increasing the GNP size also significantly enhances their ability to block DC-SIGN/R-augmented virus entry into host cells. Particularly, ManA coated 13 nm GNP potently block Ebola virus glycoprotein-driven entry into DC-SIGN/R-expressing cells with sub-nM levels of EC₅₀. Our findings suggest that GNP-ManA probes can act as a useful tool to quantify the characteristics of MLGIs, where increasing the GNP scaffold size substantially enhances their MLGI affinity and antiviral potency. Full article