Search Results (729)

Vaccination is highly effective in preventing human papillomavirus (HPV) infection, but traditional pseudovirion-based neutralization assays (PBNA) are technically demanding, labor-intensive, and costly, limiting their use in multivalent vaccine studies. We developed and validated an automated, high-throughput PBNA in a 384-well format that quantifies neutralizing antibodies against 15 HPV types using triple-color pseudotyped viruses. Non-interfering type triplets were defined from cross-neutralization assays of serum against pseudotyped viruses, enabling simultaneous detection of three fluorescence signals per well. The workflow integrates a cap-decapper, semi-automatic sample addition and dilution, and a microplate stacker with automated imaging to reduce hands-on time. The 384-well method showed strong concordance with the conventional 96-well PBNA while increasing daily sample throughput by approximately 6.7-fold, reducing assay duration (including ~4-fold faster imaging), and lowering reaction volume by ~5-fold. Analytical validation demonstrated acceptable specificity, accuracy, repeatability, linearity and robustness for high-throughput use. Serostatus cutoff values were established in an age-appropriate female population to support classification of positive versus negative sera. This platform provides a scalable tool for evaluating neutralizing antibodies after natural infections or vaccination and is well suited for large clinical trials and the development of next-generation and multivalent HPV vaccines. Full article

Biomolecular condensates (BCs), formed through liquid–liquid phase separation (LLPS), are membraneless compartments that dynamically regulate key cellular processes. Beyond their canonical roles in energy metabolism and apoptosis, Mitochondria harbor distinct BCs, including mitochondrial RNA granules (MRGs), nucleoids, and degradasomes, that coordinate RNA processing, genome maintenance, and protein homeostasis. These structures rely heavily on proteins with intrinsically disordered regions (IDRs), which facilitate the transient and multivalent interactions necessary for LLPS. In this review, we explore the composition and function of mitochondrial BCs and their emerging involvement in neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, Amyotrophic lateral sclerosis, and Huntington’s disease. We provide computational evidence identifying IDR-containing proteins within the mitochondrial proteome and demonstrate their enrichment in BC-related functions. Many of these proteins are also implicated in mitochondrial stress responses, apoptosis, and pathways associated with neurodegeneration. Moreover, the evolutionary conservation of phase-separating proteins from bacteria to mitochondria underscores the ancient origin of LLPS-mediated compartmentalization. Comparative analysis reveals functional parallels between mitochondrial and prokaryotic IDPs, supporting the use of bacterial models to study mitochondrial condensates. Overall, this review underscores the critical role of mitochondrial BCs in health and disease and highlights the potential of targeting LLPS mechanisms in the development of therapeutic strategies. Full article

Human metapneumovirus (HMPV) is a major cause of acute respiratory tract infections, particularly in infants, young children, older adults, and immunocompromised individuals. Since its discovery in 2001, the virus has been recognized for its significant clinical and socioeconomic impact. Despite extensive research, no licensed vaccines or antiviral therapies are currently available for HMPV. This review aims to synthesize current knowledge on HMPV prevention and treatment, and to highlight promising avenues for future interventions. Several monoclonal antibodies (mAbs) targeting conserved epitopes of the HMPV fusion (F) protein have shown strong neutralizing activity in vitro and in animal models, although none have reached clinical trials. Vaccine development, including subunit, live attenuated, vector-based, and mRNA platforms, is progressing, with some candidates showing promise in adult populations. However, data in children, especially seronegative infants, remain limited. Antiviral research has explored repurposed drugs such as ribavirin and probenecid, along with novel agents like fusion inhibitors and T-cell-based immunotherapies, though none are yet approved. The development of safe, effective interventions—especially multivalent approaches targeting multiple respiratory viruses—remains a high priority. Continued research is essential to bridge the gap between preclinical promise and clinical application and to reduce the burden of HMPV infection worldwide. Full article

Tungsten disulfide (WS₂), a two-dimensional layered material with favorable electronic properties, has been explored as a promising negative electrode material for calcium-ion batteries (CIBs). Despite its use in monovalent systems, its performance in divalent Ca²⁺ intercalation remains poorly understood. Herein, a combined theoretical and experimental framework is used to elucidate the electronic mechanisms underlying Ca²⁺ intercalation. Theoretical insights were obtained through density functional theory calculations, incorporating periodic simulations using the Vienna Ab initio Simulation Package, and localized orbital-level analysis using the discrete variational Xα method. These approaches reveal that Ca²⁺ insertion induces significant interlayer expansion, lowers diffusion barriers, and narrows the bandgap compared to Li⁺. Orbital analysis revealed strengthened W–S bonding and diminished antibonding interactions, which may contribute to the improved structural resilience. Electrochemical tests validated these predictions; the CaWS₂ electrode delivered an initial discharge capacity of 208 mAh·g⁻¹ at 0.1C, with 61% retention after 50 cycles at 1C. The voltage profile exhibits a distinct plateau near 0.7 V, consistent with a two-phase-like intercalation mechanism, contrasting with the gradual slope observed for Li⁺. These findings suggest that Ca²⁺ intercalation facilitates both rapid ion transport and enhanced structural robustness. This study offers mechanistic insights into multivalent-ion storage and supports the design of high-performance CIB electrodes. Full article

Hemopexin (HPX) is a heme-binding glycoprotein involved in detoxification, oxidative stress regulation, and immune defense. In teleosts, gene duplication gave rise to Wap65-1 and Wap65-2, but the structure and function of ancestral HPX in basal actinopterygians remain poorly understood. Here, we characterized HPX from the Siberian sturgeon (Acipenser baerii), a slow-evolving chondrostean species that diverged prior to the teleost-specific duplication. Structural modeling and superimposed 3D alignment revealed high similarity between sturgeon HPX, human HPX, and Wap65-2, but not Wap65-1. Phylogenetic analysis placed sturgeon HPX in a distinct basal clade within the Actinopterygian lineage, positioned below the divergence of Wap65 paralogs. Tissue expression was liver-dominant but also evident in skin and kidney, and HPX transcripts increased during larval development. Under Aeromonas hydrophila challenge, HPX was strongly upregulated in immune-relevant tissues. Thermal challenge also induced modest, tissue-specific changes, particularly in peripheral tissues. These results indicate that ancestral HPX possessed multivalent stress responsiveness—primarily immune-related—with supplementary thermal sensitivity. The observed functional flexibility is consistent with the hypothesis that ancestral HPX functions were partitioned following Wap65 gene duplication in teleosts, with Wap65-1 evolving toward a specialized thermal response role. Full article

Background/Objectives: To design the pDNA delivery carrier for delivery into skeletal muscle, a total of twelve terminal-alkylated PEGs (Cx-I-PEGy) with four alkyl groups of different carbon numbers (Cx: x = 4, 8, 12, 16) modified via an imine spacer at the ends of three methoxy PEGs of different molecular weights (PEGy: y = 500, 2k, 5k) have been synthesized. Methods: Among them, four Cx-I-PEG5k formed an imine-mediated complex formation with pDNA, as assessed by agarose gel electrophoresis, defined as an iminium mono-ion complex (I-MIC) without multivalent electrostatic interaction by minimizing potential toxic cations. Results: Most resulting I-MICs maintained the flexible structure of pDNA and promoted the binding to pDNA. The expression of pDNA by intramuscular injection with the resulting I-MICs was the highest by using I-MICs with C4-I-PEG5k and was observed extensively by the in vivo imaging system (IVIS). Conclusions: These results suggest that the I-MICs with C4-I-PEG5k are promising for pDNA transfection into skeletal muscle, offering the alkyl iminium for the pDNA binding group to demonstrate the factor of pDNA’s flexible structure as one of the key parameters for in vivo local pDNA transfection. Full article

This review aims to advance quartz processing technology by examining the surface properties, flotation behavior, and selective flotation mechanisms of quartz mineral. Characterized by a strong negative charge over a wide pH range and an isoelectric point around pH 2, quartz surfaces allow physical adsorption of cationic collectors, particularly amines, which render the quartz surface hydrophobic and enhance bubble–particle interactions. In contrast, flotation with anionic collectors requires prior surface activation via multivalent metal cations such as Ca²⁺. The pH value of the medium plays a critical role in both collector adsorption and flotation selectivity. Both direct and reverse flotation strategies can be used, depending on whether quartz is targeted as a valuable mineral or a gangue mineral. In direct flotation, depressants like carboxymethyl cellulose and starch are used to depress gangue minerals, while in reverse flotation, quartz is depressed using chemicals such as fluoride ions and cationic polymers. To improve the efficiency and selectivity of quartz flotation, further research is needed on surface chemistry, collector adsorption mechanisms, and the transition from laboratory-scale experiments to industrial applications. Full article

Avian influenza A viruses (IAVs) pose a persistent threat to the poultry industry, causing substantial economic losses. Although traditional vaccines have helped reduce the disease burden, they typically rely on multivalent antigens, emphasize humoral immunity, and require intensive production. This study aimed to establish a genetically matched host–cell system to evaluate antigen-specific immune responses and identify conserved CD8+ T cell epitopes in avian influenza viruses. To this end, we developed an MHC class I genotype (B21)-matched host (Lohmann VALO SPF chicken) and cell vector (DF-1 cell line) model. DF-1 cells were engineered to express the hemagglutinin (HA) gene of clade 2.3.4.4b H5N1 either transiently or stably, and to stably express the matrix 1 (M1) and nucleoprotein (NP) genes of A/chicken/South Korea/SL20/2020 (H9N2, Y280-lineage). Following prime-boost immunization with HA-expressing DF-1 cells, only live cells induced strong hemagglutination inhibition (HI) and virus-neutralizing (VN) antibody titers in haplotype-matched chickens. Importantly, immunization with DF-1 cells transiently expressing NP induced stronger IFN-γ production than those expressing M1, demonstrating the platform’s potential for differentiating antigen-specific cellular responses. CD8+ T cell epitope mapping by mass spectrometry identified one distinct MHC class I-bound peptide from each of the HA-, M1-, and NP-expressing DF-1 cell lines. Notably, the identified HA epitope was conserved in 97.6% of H5-subtype IAVs, and the NP epitope in 98.5% of pan-subtype IAVs. These findings highlight the platform’s utility for antigen dissection and rational vaccine design. While limited by MHC compatibility, this approach enables identification of naturally presented epitopes and provides insight into conserved, functionally constrained viral targets. Full article

Nanofiltration (NF) is considered a competitive purification method for acidic stream treatments. However, conventional thin-film composite NF membranes degrade under acid exposures, limiting their applications in industrial acid treatment. For example, wet-process phosphoric acid contains impurities of multivalent metal ions, but NF membrane technologies for impurity removal under harsh conditions are still immature. In this work, we develop a novel strategy of acid-resistant nanofiltration membranes based on interfacial polymerization (IP) of polyethyleneimine (PEI) and cyanuric chloride (CC) with the s-triazine ring. The IP process was optimized by orthogonal experiments to obtain positively charged PEI-CC membranes with a molecular weight cut-off (MWCO) of 337 Da. We further applied it to the approximate industrial phosphoric acid purification condition. In the tests using a mixed solution containing 20 wt% P₂O₅, 2 g/L Fe³⁺, 2 g/L Al³⁺, and 2 g/L Mg²⁺ at 0.7 MPa and 25 °C, the NF membrane achieved 56% rejection of Fe, Al, and Mg and over 97% permeation of phosphorus. In addition, the PEI-CC membrane exhibited excellent acid resistance in the 48 h dynamic acid permeation experiment. The simple fabrication procedure of PEI-CC membrane has excellent acid resistance and great potential for industrial applications. 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

Energy storage technology is crucial for addressing the intermittency of renewable energy sources and plays a key role in power systems and electronic devices. In the field of energy storage systems, multivalent vanadium-based oxides have attracted widespread attention. Among these, vanadium dioxide (VO₂) is distinguished by its key advantages, including high theoretical capacity, low cost, and strong structural designability. The diverse crystalline structures and plentiful natural reserves of VO₂ offer a favorable foundation for facilitating charge transfer and regulating storage behavior during energy storage processes. This mini review provides an overview of the latest progress in VO₂-based materials for energy storage applications, specifically highlighting their roles in lithium-ion batteries, zinc-ion batteries, photoassisted batteries, and supercapacitors. Particular attention is given to their electrochemical properties, structural integrity, and prospects for development. Additionally, it explores future development directions to offer theoretical insights and strategic guidance for ongoing research and industrial application of VO₂. Full article

In the present study, for the first time, a biodegradable and non-toxic polyphosphoramidate glycohydrogel (PPAGHGel) was prepared by crosslinking a polyphosphoramidate glycoconjugate (PPAG) with hexamethylene diisocyanate (HMDI) under mild conditions. Poly(oxyethylene H-phosphonate) (POEHP) was used as a precursor and was converted into PPAG via the Staudinger reaction with glucose-containing azide (2-p-azidobenzamide-2-deoxy-1,3,4,6-tetra-O-trimethylsilyl-α-D-glucopyranose). Then, crosslinking of PPAG was performed to yield PPAGHGel, which was thoroughly characterized. The gel showed a gel fraction of 83%, a swelling degree of 1426 ± 98%, and G″ = 1560 ± 65 Pa. The gel was fully degraded by alkaline phosphatase (400 U/L, pH 9) in 19 days, while hydrolytically, up to 52% degradation was observed under similar conditions. Multivalent studies of the obtained hydrogel with lectin–Concanavalin A were performed. PPAGHGel binds 92% of Concanavalin A within 24 h and the complex remains stable until the amount of glucose reaches 0.3 mM. PPAGHGel acts as a stabilizer for silver nanoparticles (12 nm). SEM shows pores measuring 10 µm (surface) and 0.1 mm (interior) with capillary channels, confirming the gel’s suitability for biosensors, drug delivery, or wound dressings. The cytotoxic (IC50) and cell-adhesive properties of the obtained hydrogel were investigated on human cell lines (HeLa). Antibacterial activity tests were also performed with gel containing silver nanoparticles against skin-associated pathogenic bacteria. The results show that PPAGHGel possesses excellent biocompatibility, non-adhesive properties and antibacterial activity. Full article

Background: Vaccines that stimulate systemic and mucosal immunity to a level required to prevent SARS-CoV-2 infection and transmission are an unmet need. Highly protective hepatitis B and human papillomavirus nanoparticle vaccines highlight the potential of multivalent nanoparticle vaccine platforms to provide enhanced immunity. Here, we report the construction and characterization of self-assembling 60-subunit icosahedral nanoparticle SARS-CoV-2 vaccines using the bacterial enzyme lumazine synthase (LuS). Methods and Results: Nanoparticles displaying prefusion-stabilized SARS-CoV-2 spike ectodomains fused to the surface-exposed amino terminus of LuS were designed using structure-guided approaches. Negative stain-electron microscopy studies of purified nanoparticles were consistent with self assembly into 60-mer nanoparticles displaying 20 spike trimers. After two intramuscular doses, these purified spike-LuS nanoparticles elicited significantly higher SARS-CoV-2 neutralizing activity than spike trimers in vaccinated mice. Furthermore, intramuscular DNA priming and intranasal boosting with a SARS-CoV-2 LuS nanoparticle vaccine stimulated mucosal IgA responses. Conclusion: These data identify LuS nanoparticles as highly immunogenic SARS-CoV-2 vaccine candidates and support the further development of this platform against SARS-CoV-2 and its emerging variants. Full article

Egg yolk immunoglobulin Y (IgY) possesses advantages such as low cost, easy availability, simple preparation, high antigen specificity, absence of drug residues, and compliance with animal welfare standards, making it an environmentally friendly and safe alternative to antibiotics. This research utilizes IgY antibody technology to develop a multivalent passive immune vaccine for major pathogenic bacteria in aquaculture. In this study, IgY antibodies against live Shewanella xiamenensis (LSX-IgY) and inactivated S. xiamenensis (ISX-IgY) were prepared by immunizing laying hens, and passive immunization protection experiments were conducted in Carassius auratus infected with S. xiamenensis and Aeromonas hydrophila. The passive immunization protection rates of LSX-IgY and ISX-IgY against S. xiamenensis were 63.64% and 72.73%, respectively, and the passive cross-protection rates against A. hydrophila were 50% and 71.43%, respectively. Further, C. auratus sera could specifically bind to S. xiamenensis or A. hydrophila in vitro, and the phagocytic activity of leukocytes was increased. LSX-IgY and ISX-IgY could reduce the bacterial load in the C. auratus kidneys. Meanwhile, they could significantly reduce the levels of antioxidant factors in serum and inhibit the mRNA expression of inflammation-related factors in the kidneys and spleens. Additionally, histopathology and immunofluorescence analysis showed that both IgY preparations preserved tissue integrity and reduced the expression of apoptosis factor (p53) and DNA damage factor (γH2A.X) of visceral organs, respectively. In summary, LSX-IgY and ISX-IgY can combat various bacterial infections, with no significant difference between the two. Additionally, inactivated bacterial immunization is more aligned with animal welfare standards for laying hens. Therefore, ISX-IgY is expected to serve as a multivalent vaccine against major aquaculture pathogens. Full article

A function that is holomorphic in a set E, in the complex plane, is called p-valent in E if, for every complex number, w, the equation f (z) = w has, at most, p roots in E. In this paper, we established some sufficient conditions for holomorphic functions in the unit disk |z| < 1 to be at most p-valent in the unit disk or p-valent or p-valent starlike in the unit disk. Full article