Search Results (2,534)

Heterogeneous cross-domain networks are plagued by fragmented trust, data silos, and privacy risks, while conventional single-chain architectures fail to reconcile cross-chain interoperability, regulatory compliance, and commercial privacy. To address these limitations, we present an Entity–Data–Asset triple-verification architecture that integrates three key components: Decentralized Identifiers (DIDs) for identity, Verifiable Credentials (VCs) for credentials, and Oracles for cross-chain coordination. Specifically, this architecture enables trustworthy collaboration through three core mechanisms: (1) a cross-chain identity binding mechanism based on DIDs that replaces traditional address binding to construct an “identity-as-access” trust model; (2) a collaborative verification paradigm leveraging VCs and Verifiable Presentations (VPs) to cryptographically link off-chain verification with on-chain execution; and (3) an event-driven Oracle coordination matrix designed for complex business semantics, supporting automated and privacy-preserving state synchronization across asymmetric domains. Experimental evaluation of a prototype integrating Hyperledger Indy and Besu demonstrates a peak Verifiable Presentation batch verification throughput of 0.96 batches/s at $C=20$, though throughput degrades noticeably under high concurrency due to middleware contention, and an average cross-chain transfer latency of 13.31 s under single-process conditions (mean over 10 iterations). Furthermore, by leveraging this asymmetric design, our architectural optimization strategy—anchoring only cryptographic hashes rather than full credential payloads—reduces the regulatory chain’s storage and gas overhead by approximately 85% compared to traditional full-payload schemes. These results validate the architecture’s feasibility, security, and cost-efficiency for facilitating trustworthy collaboration in complex, heterogeneous ecosystems. Full article

Live-attenuated rotavirus (RV) vaccines are the most effective interventions for preventing RV gastroenteritis (RVGE) in young children. However, the molecular basis of attenuation remains not well understood. Here, we describe a compact but comprehensive strategy to identify RV virulence determinants by combining low-passage bidirectional selection, sequence analysis, and segment-level phenotype testing via a reverse genetics infectious system. Using the virulent murine RV strain EW, virulence was quantified by diarrhea severity/duration and body-weight gain. Serial passaging in cell culture selected an attenuated population, which regained virulence after passaging in suckling mice. Sequence comparison of the virulent and attenuated EW populations revealed only seven amino acid differences. We summarized literature describing attenuation/virulence-associated mutations in various RV group A (RVA) strains and found previous findings identical or similar to four of the seven mutations: NSP4-T45M, VP4-S470L, VP4-T612A, and VP7-T75P. Virulent- and attenuated-type EW variants of VP2, VP4, VP7, and NSP4 were introduced individually, or as NSP4/VP7 or VP4/VP7 pairs, into a simian SA11-L2 backbone using an 11-plasmid reverse genetics system. Phenotyping of rescued viruses consistently linked cell-culture–adapted VP4 to enhanced replication in vitro and reduced virulence in suckling mice. In vivo passaging strongly favored VP4 residue S470 over cell-culture-selected L470. More generally, our findings (i) underscore VP4 and VP7 as key determinants of EW virulence, (ii) provide a practical framework for identifying driver mutations underlying RVA attenuation, and (iii) highlight attenuation-associated substitutions shared across diverse RVAs. Full article

Infectious bursal disease virus (IBDV) is a pathogen that causes Gumboro disease in young chickens. Vaccine strains and field IBDV genotypes are disseminated in chickens from commercial poultry farms worldwide. This study aimed to detect the field IBDV genotypic diversity in poultry farms in Latin America, mainly in Brazil. Bursal samples from 69 broiler flocks in eleven Latin American countries were obtained between 2015 and 2025. All 69 samples tested were positive for IBDV; the VP2 (segment A) and VP1 (segment B) genes were sequenced. Phylogenetic and amino acid substitution analyses were performed with large genetic datasets, including previously identified IBDV genotypes worldwide. The results revealed four A (A1, A2, A3, and A4) and three B (B1, B2, and the candidate B6) genogroups in Latin America. Furthermore, genotypes A1B1 (1.4%), A2B1 (59.4%), A3B2 (20.3%), A3B6 (2.9%), and A4B1 (15.9%) were identified. A2B1 could be subdivided into A2aB1a (24.4%), A2bB1a (29.3%), A2dB1b (19.5%), and A2eB1a (26.8%). In Brazil, the field genotypes A3B2, A4B1, and A3B6 were demonstrated. These findings highlight an important IBDV genotypic diversity in Latin American countries and reinforce the need for continuous molecular surveillance to support control and vaccination programs. Full article

Two chikungunya (CHIKV) vaccines have now been licensed, but the human clinical evidence base remains fragmented across vaccine platforms, populations, follow-up periods, and safety settings, complicating product-specific interpretation of durability and benefit–risk. We conducted a PRISMA-ScR–guided scoping review of human CHIKV vaccine evidence indexed in PubMed, Embase, and Web of Science from January 2000 to June 2026. After screening 890 records, we included 77 sources of evidence and mapped them at both the record level and the candidate/product level. The included evidence clustered around a limited number of vaccine programs, including TSI-GSD-218, VRC-CHKVLP059-00-VP/PXVX0317/Vimkunya, MV-CHIK/V184, VLA1553/IXCHIQ, ChAdOx1 Chik, and mRNA-1388/VAL-181388. Late-stage and post-authorization evidence was concentrated mainly in VLA1553/IXCHIQ and PXVX0317/Vimkunya, whereas viral-vector and mRNA candidates remained largely restricted to early-phase adult studies. Evidence has expanded to adolescents and adults aged ≥65 years for selected products but remains limited or product-specific for children, pregnant individuals, immunocompromised populations, and medically complex older adults. Short-term trial safety data were characterized primarily by mild or moderate local and systemic reactogenicity, while post-authorization safety evidence remains recent and concentrated in licensed products. This scoping review provides a structured evidence map for CHIKV vaccine development and highlights priorities for standardized immunogenicity assessment, longer-term durability data, broader population representation, endemic-region effectiveness studies, and continued post-marketing surveillance. Full article

Background/Objectives: Metal artifacts from dental implants degrade CBCT image quality and may impair detection of peri-implant bone defects. Zirconia implants produce stronger artifacts than titanium due to its higher atomic number. This study evaluated the impact of a native MAR algorithm (SMARF) on CBCT detection of buccal fenestration and dehiscence of varying sizes adjacent to zirconia versus titanium implants. Methods: In this ex vivo pilot study, two 4 mm × 12 mm implants (one titanium and one zirconia) were implanted in a dry human mandible. Artificial fenestration and dehiscence defects were created at the buccal surface of right and left premolar regions, in three sizes (small 2 mm × 2 mm× 1 mm; medium 2 mm × 4 mm× 1 mm; large 2 mm × 6 mm× 1 mm). Scans were acquired with a Papaya 3D (Genoray) CBCT using a single-tooth FOV (4 cm× 4 cm × 5 cm), 83 kVp, 10 mA, 0.1 mm voxel; each condition was imaged with MAR on and off (six repeats each). Two trained observers scored defect presence on a five-point Likert scale. Sensitivity, specificity, inter- and intraobserver agreement (Cohen’s kappa), and comparisons across conditions were calculated. Results: Interobserver κ = 0.65 (substantial); intraobserver κ = 0.87–1.00 (excellent). For titanium implants, sensitivity and specificity were 100% across all defect types, sizes, and MAR settings. For zirconia implants, fenestration sensitivity with MAR off increased with size (small 50%, medium 75%, large 100%); MAR on raised sensitivity to 100% for all sizes, with a significant improvement for small fenestrations (p = 0.005). Dehiscence sensitivity for zirconia was 100% across sizes and MAR conditions. Specificity for zirconia defects was 83.3% with MAR off and decreased to 66.6% with MAR on (p = 0.07). Conclusions: With the Papaya 3D system used in this pilot study, MAR was unnecessary for defect detection adjacent to titanium implants but affected performance for zirconia implants: MAR increased sensitivity for small fenestrations while reducing specificity (although not statistically significant). Clinicians should weigh the sensitivity–specificity trade off when applying MAR around zirconia implants. Full article

The plastics industry sector is a massive contributor to greenhouse gas emissions. In this context, it is important to find alternatives to valorise plastic polymer waste, since 63.0% of the plastics produced between 1950 and 2015 were incinerated or disposed of in landfills. This study aims to evaluate the environmental and economic performance of a polymeric control panel for a domestic boiler. The environmental assessment was conducted using the Life Cycle Assessment (LCA) methodology from a cradle-to-grave perspective, allowing the identification of the hotspots of the panel under analysis in two scenarios: virgin panel (VP) and recycled panel (RP). The economic evaluation was performed through a techno-economic analysis (TEA) considering both operating expenditures (OpEx) and annualised capital expenditures (CapEx) allocated to the functional unit. The VP scenario used 100.0% virgin polymer, while the RP scenario used 70.0% virgin polymer and 30.0% internal recycled polymer. The analysis shows a clear synergy: substituting a portion of virgin polymer with recycled PC/ABS reduces both environmental impacts and production costs, while also increasing the sustainability. The results support internal recycling as a practical circularity strategy that can improve environmental performance. The RP scenario is both the environmentally preferable and the economically better option. Additionally, the consistency of results across both LCA and TEA indicates that the identified hotspots represent leverage points for future interventions to amplify benefits to further improve sustainability. For instance, further decarbonization of the Portuguese electricity grid or increased reliance on on-site PV electricity would strengthen the environmental profile of both scenarios. At the same time, continued optimisation of recycling processes could enhance cost savings. Full article

Idiopathic normal pressure hydrocephalus (iNPH) is a potentially reversible neurological disorder characterized by gait disturbance, cognitive impairment, and urinary incontinence; however, its diagnosis and prediction of shunt responsiveness remain challenging. This systematic review aimed to synthesize current evidence on cerebrospinal fluid (CSF) proteomic biomarkers in iNPH and to identify molecular patterns with diagnostic and prognostic relevance. A PRISMA-guided search of PubMed, Web of Science, and Google Scholar identified 14 eligible studies comprising 1171 iNPH patients. Proteomic analyses revealed substantial heterogeneity in study design and detected proteins; however, consistent patterns emerged. iNPH is associated with upregulation of inflammatory and extracellular matrix-related proteins and relative downregulation of synaptic and neuronal markers. Neurodegenerative proteins, including amyloid-β, tau, and neurofilament light chain, demonstrated value in differentiating iNPH from comorbid neurodegenerative diseases and in predicting response to ventriculoperitoneal shunting (VPS). These findings support a multifactorial model of iNPH involving impaired glymphatic clearance, neuroinflammation, blood–brain barrier dysfunction, and mechanical axonal stress. Multidimensional biomarker profiles, rather than single proteins, appear to provide the greatest clinical utility, highlighting the need for standardized proteomic panels and integrative predictive models. However, given the substantial heterogeneity of the included studies and the predominantly exploratory nature of current proteomic evidence, the identified proteins should be interpreted as candidate biomarkers rather than clinically validated diagnostic or prognostic tools. Multidimensional biomarker profiles appear biologically plausible and may offer greater explanatory value than single proteins, but their clinical utility requires validation in standardized prospective cohorts. The authors therefore propose a conceptual iNPH proteomic “Vulnerability Model” integrating CSF biomarkers to reflect the balance between reversible and irreversible pathology; this is currently a hypothetical model that requires rigorous statistical and clinical validation through large-scale prospective cohort studies before it can fulfill its potential for improving patient stratification and prediction of postoperative outcomes. Full article

Ebola virus disease (EVD) is characterized by immune dysregulation and damaging hyperinflammation. We aimed to characterize the signaling pathways and regulatory mechanisms dysregulated during EVD. To avoid hyperinflammation, innate immune signaling is regulated by post-translational modifications (PTMs), including protein phosphorylation. Here, we show that the protein tyrosine phosphatase nonreceptor type 13 (PTPN13) negatively regulates Interferon (IFN)-β while also positively regulating the neutrophil chemoattractant CXCL1. Using vectors encoding IRF3 with mutations on phosphorylation sites, we identified Y292 on IRF3 as a PTPN13 target of dephosphorylation. Knockout of PTPN13 increased IRF3 phosphorylation and expression of IFNβ and IFN-stimulated genes (ISGs) following poly(I:C) stimulation. Intriguingly, depletion of PTPN13 during Ebola virus (EBOV) infection resulted in decreased IFNβ and ISG induction at later time points post-infection, which correlated with increased viral titers. We identified PTPN13-mediated dephosphorylation of the viral protein VP35 as one potential mechanism inhibiting virus replication. Additionally, the induction of inflammatory chemokines, including CXCL1, decreased in PTPN13 knockout cells late during EBOV infection. These effects could be explained by increased phosphorylation of the regulatory p85 subunit of PI3K. Dephosphorylation of p85 promotes its degradation, subsequently enhancing PI3K kinase activity and downstream signaling via AKT. Together, our study suggests that PTPN13 is involved in immune regulation and efficient antiviral responses by dephosphorylation of IRF3, EBOV-VP35 and PI3K-p85. Full article

Canine parvovirus type 2 (CPV-2) remains an important cause of morbidity and mortality in young dogs worldwide. Although the enteric form of the disease is well characterized, myocardial involvement associated with CPV-2 infection remains incompletely understood. The present retrospective study aimed to investigate myocardial lesions in young dogs and to evaluate their association with CPV-2 DNA detection using histopathological examination and PCR-based molecular analysis of formalin-fixed paraffin-embedded (FFPE) cardiac tissue. A total of 27 dogs aged between 3 and 11 months, submitted for diagnostic necropsy between 2019 and 2021, were included in the study. Histopathological evaluation was performed on myocardial tissue sections stained with hematoxylin and eosin, while conventional PCR targeting the VP1/VP2 region was used for the detection of CPV-2 DNA. Associations between PCR positivity and histopathological findings were assessed using Fisher’s exact test. Myocardial abnormalities were identified in all examined cases (27/27, 100%), with myocarditis consistently observed throughout the study population. Cardiomyocyte necrosis and myocardial fibrosis were identified in 9/27 (33.3%) and 14/27 (51.9%) cases, respectively. CPV-2 DNA was detected in 9/27 myocardial tissue samples (33.3%). Cardiomyocyte necrosis was significantly more frequent in CPV-2-positive dogs than in PCR-negative animals (77.8% vs. 11.1%; p ≈ 0.001). Similarly, myocardial fibrosis was identified more frequently in CPV-2-positive cases (100.0% vs. 27.8%; p ≈ 0.001). Myocarditis was present in all examined animals and therefore could not be evaluated statistically according to PCR status. The detection of CPV-2 DNA in myocardial tissues exhibiting histopathological lesions supports a possible association between CPV-2 infection and myocardial injury in young dogs. However, the retrospective design, limited sample size, and the use of conventional PCR do not allow conclusions regarding causality or direct viral involvement in lesion development. Further studies incorporating larger case series and complementary diagnostic techniques are needed to clarify the pathogenesis and clinical significance of CPV-2-associated myocardial lesions. Full article

Vacuolar Protein Sorting 29 (VPS29) is a highly conserved subunit of the retromer complex, which mediates retrograde transport from endosomes to the Golgi apparatus and plays a critical role in membrane trafficking, protein recycling, and organelle biogenesis. In Plasmodium falciparum, the retromer has been implicated in the formation of apical organelles essential for parasite invasion and replication. In this study, we investigated naturally acquired antibody responses to P. falciparum VPS29 (PfVPS29) and the genetic diversity of the vps29 gene in isolates from three malaria-endemic areas of the Brazilian Amazon. Naturally acquired responses to PfVPS29 were evaluated by ELISA in 533 individuals, and genetic diversity was assessed in 62 P. falciparum isolates. Only 17% of participants displayed IgG reactivity, whereas 73.5% showed IgM responses, indicating limited IgG acquisition but a predominant IgM profile associated with recent or ongoing exposure. IgG subclass analysis revealed a predominance of cytophilic IgG1 and IgG3 among responders. IgM responses were significantly boosted during P. falciparum infection. Sequence analysis revealed no polymorphisms among Brazilian isolates, and comparison with global datasets confirmed the high conservation of the PfVPS29 coding sequence. Together, these findings show that PfVPS29 is a highly conserved intracellular protein that elicits an atypical humoral response dominated by IgM, with limited class switching to IgG, like other conserved or repetitive malaria antigens. These results highlight PfVPS29 as an example of a conserved intracellular antigen that induces non-classical humoral responses in naturally exposed populations. Full article

Porcine group A rotavirus (PoRVA) is a significant cause of viral diarrhea in piglets, necessitating urgent global implementation of effective control strategies. This review assesses advancements in PoRVA in vitro cultivation and amplification, crucial for PoRVA vaccine development. Traditional PoRVA cultivation commonly employs primary porcine kidney cells or finite cell lines like MA-104, posing well-documented challenges in scalability, production cost, and their ability to recapitulate the natural intestinal microenvironment. Consequently, research has increasingly focused on adapting PoRVA to alternative systems, particularly immortalized porcine cell lines or physiologically relevant porcine intestinal organoids. This adaptation process, involving serial passaging, can induce genomic alterations and virulence attenuation in piglets, essential for generating live attenuated vaccine (LAV) candidates. Modern biotechnological tools, such as reverse genetics and synthetic genomics, have expedited the creation of recombinant PoRVA strains with defined antigenic profiles and enhanced in vitro growth characteristics. However, a significant concern regarding LAV candidates derived from cell culture adaptation is the risk of virulence reversion upon pig back-passage, necessitating thorough safety and genetic stability evaluations. Nevertheless, utilizing stable cell lines or organoid platforms presents a feasible and cost-effective approach for large-scale PoRVA vaccine production. Future research should focus on identifying vaccine candidates that provide broad protection and exceptional safety, with an emphasis on cross-protection against divergent epidemic genotypes, while ensuring the economic feasibility of innovative manufacturing approaches. Full article

Porcine rotavirus (PoRV) has emerged as a primary pathogen causing viral diarrhea in pigs, resulting in significant economic losses. This study was conducted to systematically characterize the epidemiology and genotypic characteristics of PoRV in Guangxi, China. A total of 870 diarrheic pig samples were collected from Guangxi during 2020–2025. The qRT-PCR results indicated an overall PoRV-positive rate of 41.38% (360/870), and the annual positivity rate showed an overall upward trend. The genetic evolutionary analysis of the VP4, VP6, and VP7 genes indicated that PoRV predominantly belonged to the A group and the predominant P genotype observed was P[13] (76.83%), while the G genotypes were G5 (36.56%) and G9 (33.33%). The most prevalent genotype combinations were G9P[13]I5 and G5P[13]I5. CH-GXGL-PoRV-3151-2021, a PoRV strain isolated from positive samples, was identified via RT-PCR, qRT-PCR, whole-genome sequencing, and IFA. This strain was assigned the 11-segment genotype constellation G9-P[23]-I5-R1-C1-M1-A8-N1-T1-E1-H1 based on whole-genome sequencing. NSP1 and NSP2 showed high similarity to human rotavirus strains, whereas VP1–VP4, VP6, VP7, and NSP3–NSP5 showed high similarity to porcine rotavirus strains. This study indicates the widespread circulation of PoRV in Guangxi, with multiple G genotypes, including G9, G5, G4, G3, G2, and G26, being detected. The isolated G9P[23]I5 strain exhibits the same genotype as the strains that have become increasingly prevalent in recent years. This strain may represent a possible reassortant between porcine and human rotaviruses. This study offers significant insights into the epidemiology of PoRV and the prevalent genotypes in Guangxi, thereby supporting the development of targeted prevention strategies and novel vaccines. Full article

Improvement of the engineering properties of soils by reinforcing them with fibers, at an appropriate percentage of the weight of dry soil, is frequently selected to ensure the safe construction and operation of many structures. However, the published information regarding the investigation of the dynamic properties of fiber-reinforced soils at very small strains is very limited. Toward this end, the dynamic behavior of fiber-reinforced soils is investigated experimentally by conducting Bender Element tests under different confining pressures. The effect of polypropylene fiber reinforcement on the shear wave velocity (V_s), the velocity of the primary wave (V_p), the initial Young’s modulus (E₀) and the initial shear modulus (G₀) of sand and sand–clay mixtures with varying compositions is examined in this study. The soils were reinforced with five different types of polypropylene fibers having lengths from 9 mm to 50 mm, at fiber contents from 0.5% to 2% by weight of dry soil. The results indicate that the dynamic and the small-strain stiffness parameters of fiber-reinforced soils increase with increasing confining pressure, while also being affected by the soil type, the fiber type, and content. Although fiber inclusion resulted generally in a reduction of the dynamic properties of soils, increases ranging from 5% to 55% were observed in certain soil–fiber combinations in comparison with the unreinforced soils. Full article

Neonatal diarrhea remains a significant threat to piglet health, resulting in substantial economic losses worldwide. Among the viral pathogens associated with this condition, rotavirus (RV) has been extensively reported in Brazil; however, lineage-level classification of circulating strains remains limited. This study aimed to characterize G and P genotypes of porcine RV field strains associated with diarrhea in piglets in Southern Brazil. A total of 10 fecal samples were collected by field veterinarian from diarrheic suckling piglets aged 1 to 14 days and analyzed by RT-PCR for the detection of RV species A, B, C, and H. RV species A (RVA) was detected in 90% (9/10) of the samples, while no other RV species were identified. Genotyping based on the VP7 and VP4 genes revealed a single G3P[6] genotype combination in all RVA-positive samples. Nucleotide (nt) and deduced amino acid (aa) sequence analysis revealed high genetic similarity among strains, with values of up to 99.3% for nt and 98.0% for aa of the VP7 gene and 100% for the VP4 gene (nt and aa). Phylogenetic analysis indicated that the VP7 sequences clustered with Brazilian G3 strains, forming a distinct group consistent with a novel lineage (putative G3-XII), whereas VP4 sequences supported a new sublineage (putative P[6]-Ig). These findings demonstrate low genetic variability of RVA field strains in this neonatal diarrhea outbreak, suggesting the circulation of a single viral population. They also emphasize the importance of continuous molecular surveillance to gain a deeper understanding of viral evolution and transmission dynamics in swine populations. Full article

Psoriasis is a chronic inflammatory autoimmune skin disease for which no standardised and reliable molecular biomarkers of disease course or activity are currently available. Here, we aimed to identify serum biomarkers of psoriasis. Serum samples from 40 patients with psoriasis and 40 healthy volunteers were analysed using ELISA and Proximity Extension Assay proteomics. ELISA revealed significantly increased serum levels of AGO2 and APOA1 in psoriatic patients versus controls, with a strong association between APOA1 and psoriasis (OR = 20.72, 95% CI of 4.57–93.87, p = 0.000137). Targeted serum proteomics additionally identified 35 differentially expressed proteins, including well-known psoriasis drivers (e.g., top upregulated IL17A and SERPINB4). The most downregulated was adrenomedullin (ADM, FC = −10.12). For 14 altered proteins, no previous direct associations with psoriasis were reported. Among them, DEFB103A_DEFB103B and DSG3 showed the best discrimination between psoriasis and control samples, while SERPINB4 correlated with psoriasis severity. APOA1, DEFB103A_DEFB103B, and DSG3 emerge as novel candidate circulating psoriasis biomarkers, and SERPINB4 as a biomarker of psoriasis severity. The functional role of DSG3 and other newly identified proteins (ACRV1, HAO1, ADH4, GPD1, GFER, PTGES2, DSG3, AFAP1L1, GALNT3, RASGRP2, MAP2K6, LXN, NBEAL2, and VPS54) in psoriasis requires further studies. Full article