Development of a DC-targeting Salmonella- amplifying RNA vector platform co-delivering dual antigens and adjuvants for enhanced protection against H9N2 avian influenza.

Development of a recombinant chimeric Newcastle disease virus-vectored vaccine conferring single-dose, triple protection against genotype VII NDV, IBDV, and H9N2 AIV.

Kyasanur Forest Disease (KFD) is a tick-borne viral haemorrhagic fever endemic to forested regions of South India, with case fatality rates ranging from 3% to 10% and seasonal outbreaks causing recurrent illness among at-risk populations such as forest workers and villagers. The historically used formalin-inactivated KFD vaccine showed limited effectiveness in field studies, providing only about 62% protection. This moderate level of protection highlights the need for improved vaccines that offer higher efficacy and longer-lasting immunity for populations living in endemic areas. A major challenge in vaccine development is the limited understanding of immune responses that protect against KFD, along with the lack of preclinical models that fully reflect the disease as it occurs in humans. Existing animal models-including murine systems and limited non-human primate studies -have contributed to understanding viral replication, lethality, viraemia kinetics, and basic immunological responses. However, murine models often fail to reproduce the full spectrum of human immunopathology, particularly haemorrhagic manifestations and complex host immune responses, while non-human primate models remain limited by cost, accessibility, and incomplete characterisation. Furthermore, variability in experimental endpoints and the absence of standardized immunogenicity and neutralisation assays restrict cross-study comparability and hinder identification of immune correlates of protection. This review critically synthesises current knowledge on KFD animal models and host immune responses, identifying key gaps in translational relevance. We propose a prioritised roadmap that includes: (i) development and validation of advanced preclinical models that better mimic human disease progression and immune dysregulation; (ii) systematicidentification of serological and cellular correlates of protection; and (iii) standardisation of virological, serological, and immunological assays to support regulatory evaluation and vaccine benchmarking. Addressing these challenges through coordinated interdisciplinary efforts will accelerate the development of next-generation KFD vaccines and therapeutics tailored to endemic populations.

AI-based monitoring of broiler vocal repertoire dynamics reveals robust developmental and diurnal patterns but limited disease sensitivity.

The increasing complexity of in situ high-energy diffraction microscopy (HEDM) experiments demands a quantitative understanding of the data analysis pipeline to ensure reproducible science. However, the influence of key analysis parameters on the accuracy and precision of microstructural reconstructions is often not well quantified, creating a barrier to progress. This paper addresses this critical gap by presenting a rigorous, systematic validation of the HEDM data reduction methodology as implemented in the MIDAS software suite. Using a new, dedicated Ti-7 Al dataset, we investigate both far-field (FF) and near-field (NF) HEDM. Our results reveal critical sensitivities, demonstrating that grain position accuracy in FF-HEDM is highly dependent on the diversity of sampled diffraction vectors, while orientation precision in NF-HEDM improves dramatically with increased detector separation. We demonstrate the methodology's robustness against common experimental challenges, such as severe diffraction peak overlap, which is effectively filtered by requiring crystallographic consistency. Based on these quantitative findings, we establish a framework of best practices for HEDM data acquisition and analysis to guide the community towards more accurate and reliable results.

Scientific confidence relies on the integrity and verifiability of primary observations, yet increasing experimental scales and computational complexities challenge traditional mechanisms of trust. In proteomics, community standards emphasize the public deposition of raw mass spectrometry (MS) data to enable reanalysis and reproducibility. However, recent advances in software capable of simulating MS data raise the possibility that datasets may be altered or generated entirely in silico and presented as experimentally acquired data. Here, we argue that current standards rarely distinguish between raw data formats in terms of their provenance guarantees or susceptibility to modification. To address this emerging vulnerability, we propose a hierarchy of evidence for MS-based reporting, analogous to established evidence hierarchies in medicine, in which confidence in reported findings increases with the traceability and verifiable provenance of raw data files. With this framework, we aim to support reviewers and readers in assessing the robustness of published claims and to stimulate discussion on strengthening data integrity safeguards in proteomics.

We investigate effects of the density of states of condensed matter on the electronic excitations triggered by penetrating keV ions, in a systematic study of energy deposition along multiple well-defined channeling trajectories. We measure the specific energy deposition of ions with keV energies transmitted through Si-a band gap material-in the form of single-crystalline, self-supporting membranes. Energy transfers observed for Ne ions along the 〈100〉, 〈211〉, and 〈111〉 channeling orientations agree well in magnitude with predictions from density functional theory for the expected unperturbed electron densities in an electron gas. This agreement indicates that, along channeling trajectories, the interaction is dominated by conduction and valence electrons, with atomic (core-electron) processes largely suppressed. In contrast, for H and He ions, the predicted values are found systematically higher than the measured values. Non-linearities in the energy dependence of the specific energy deposition of Ne ions are found along all studied low-index orientations, with an inverted behavior observable for random in comparison to channeling orientation. In this context, we discuss the experimental challenges of limiting selected trajectories for the lowest velocities studied, which can mask effects of electronic excitation thresholds in the target electronic system. The new insights shed also light on earlier studies reporting a complex scaling of energy deposition with excitation thresholds, or even their apparent absence.

Optimized intracellular flow cytometry panel enables CD4 and CD8 T cell cytokine profiling in Syrian hamsters.

Dopamine signaling is essential for regulating movement, learning, and reward processing, and its dysregulation has been implicated in neuropsychiatric conditions such as ADHD and substance use disorder. ADGRL3, an adhesion G protein-coupled receptor enriched in the brain, has been genetically linked to these disorders, and Adgrl3 knockout in animals alters expression of dopaminergic markers and impacts dopamine-related behaviors. However, how ADGRL3 influences dopamine dynamics remains poorly understood. Here, we characterized striatal dopamine release in Adgrl3 knockout mice using complementary ex vivo and in vivo approaches. Fast-scan cyclic voltammetry in acute brain slices revealed increased electrically evoked dopamine release in both dorsal and ventral striatum of Adgrl3 knockout mice. In contrast, in vivo fiber photometry using the dopamine sensor dLight1.2 showed reduced cue-induced dopamine signals in the ventral striatum during an operant fixed interval task. This reduction was accompanied by longer latencies to lever press and retrieve rewards, consistent with altered cue-guided behavioral responses reminiscent of task-switching difficulties in individuals with ADHD. Amphetamine challenge experiments indicated that phasic release capacity was similar between genotypes, suggesting that dopamine stores are intact in Adgrl3 KO mice. Together, these findings reveal that ADGRL3 regulates striatal dopamine release and motivate mechanistic studies of how its loss may alter the spatial organization of dopaminergic terminals.

Nanoscale heat transport plays an important role in energy conversion and thermal management. Therefore, understanding how nanoscale heat transport can be tuned is critical for developing novel technologies, including cooling strategies for microelectronics and nanostructured materials and devices for high-efficiency energy conversion. To probe nanoscale thermal transport phenomena, many calorimetric tools and approaches have been developed. Specifically, suspended microcalorimeters featuring picowatt resolution have been extensively employed for measuring thermal transport in low-dimensional materials, radiative heat transfer in nanoscale gaps, and between subwavelength structures. Further, scanning calorimetric probes, combined with atomic force microscopy and scanning tunneling microscopy, have been utilized for probing atomic-scale thermal transport and near-field thermal radiation. Here, we discuss these advances in calorimetric tools and their use for studying nanoscale thermal transport. We conclude by discussing open experimental challenges and highlighting the importance of future developments in subpicowatt resolution calorimetric tools for accessing unexplored nanoscale thermal transport phenomena.

Measuring the mechanical response of liquid interfaces without direct contact remains a major experimental challenge, particularly in liquid-liquid systems where no solid reference exists. Here, we develop a frequency-modulation atomic force microscopy (FM-AFM) method to probe liquid interfaces through the hydrodynamic confinement of a viscous liquid film between an oscillating probe and the interface. This approach provides simultaneous access to the in-phase and dissipative components of the effective mechanical response under confinement. Initially, the method is validated on a liquid-solid interface, where the measured confinement thickness and the evolution of the mechanical impedance are consistent with elastohydrodynamic theory over nearly one decade in elastic modulus. It is then applied to a liquid-liquid interface, which exhibits a predominantly viscous response with a finite in-phase contribution and a confinement thickness in the micrometric range. These results show that hydrodynamic confinement provides a sensitive, noncontact approach to compare the mechanical responses of soft and liquid interfaces, and opens perspectives for investigating complex and highly deformable systems such as polymer films, biological membranes, and rafts of nanoparticles.

IntroductionA bird’s production, physiological, immunological, and environmental adaptations can be evaluated through the hematological and biochemical profiles they possess. This study examined the adaptive characteristics of Ethiopian indigenous and Sasso chickens reared in rural farming systems based on hematological and hormonal parameters.MethodsTwo hundred sixty‐two apparently healthy adult chickens, above one year, 122 indigenous and 140 Sasso breeds, sampled from three agroecologies, were examined for adaptive characteristics. The studied chickens were managed under farmer husbandry conditions without offering special care or treatment.ResultsMost of the hematological profiles did not significantly (p > 0.05) differ due to breed effects; however, season and agroecology showed significant (p < 0.05) variations. The indigenous chickens had higher mean hematological values at all agroecologies and seasons; however, Sasso chickens had higher hematological profiles at highland and midland during wet seasons. Likewise, season and agroecology effects showed significant differences for triiodothyronine (T3) and thyroxine (T4) hormone levels. Sasso chickens exhibited higher mean T3 and T4 levels than indigenous chickens. The highland chickens, followed by the midlands, had higher T3 and T4 levels, and T3 levels were higher during the wet season, whereas T4 levels were higher during the dry season.ConclusionThe study provided useful insights, implying that season and agroecology had a significant effect on hematological and hormonal profiles and must be considered when distributing less‐adaptive commercial breeds to small‐scale farming systems. Further research involving molecular tools together with controlled thermal challenge experiments is suggested to ascertain the genetic potential for climatic resilience of the studied chickens.

We present a comprehensive theoretical investigation of Ra(II) solvation in water and ammonia micro-solvation environments using hybrid density functional theory Born-Oppenheimer molecular dynamics simulations. While other alkaline earth dications (Mg2+-Ba2+) have been extensively studied, Ra2+ remains poorly characterized due to experimental challenges. Our simulations reveal that Ra2+ exhibits exceptional aqueous solvation dynamics, with a broad first hydration shell (2.7-3.8Å) showing large temporal coordination number (CN) fluctuations between 9 and 12 and short-lived coordination states. The calculated average Ra-O distance (2.92Å) and CN (10.9) are in good agreement with EXAFS experimental data. In the ammonia environment, Ra2+ displays a similar but better-defined solvation structure, with a dominant tenfold coordination, longer coordination lifetimes, and rapid NH3 exchange. Comparative analysis across group IIA cations shows systematic trends: increasing cation size (M2+) correlates with longer M2+-L distances and more extended solvation shells, while structural flexibility at 300K increases dramatically from Mg2+ to Ra2+, with Ba2+ and Ra2+ showing the closest structural analogy, consistent with their similar crystal ionic radii. This work provides fundamental reference data for radium solution chemistry and presents possible implications of the observed solvation differences between water and ammonia for radiochemical separation strategies, as well as the ability of Ra2+ to mimic the coordination properties of Ca2+ in biochemical environments.

A chimeric L1-L2 virus-like particle (VLP) vaccine targeting common cutaneous human papillomavirus type 1 (HPV1).

Oral immunization with attenuated Salmonella enterica serovar Enteritidis expressing dual-toxin antigen induces protective immunity against avian necrotic enteritis.

TLR7 ligand-cyclodextrin conjugate is a promising adjuvant for intranasal influenza vaccine.

ABSTRACT Infectious bursal disease (IBD), caused by infectious bursal disease virus (IBDV), poses a major threat to the global poultry industry. In this study, we identified and characterized a novel field IBDV strain NN040124, which exhibits both reassortment and recombination features. Genotyping identified this field strain as A3B1a, with segment A derived from a very virulent IBDV (vvIBDV) strain (A3) and segment B from a classical-like attenuated vaccine (attIBDV) strains (vv-A/att-B IBDV)). Crucially, recombination analysis revealed that segment B is a backbone originated from vaccine strain B87, with the N-terminal part replaced by the homologous region from a vvIBDV strain (Harbin-1). This replacement is implicated in the restored virulence of the strain, as demonstrated by a challenge experiment in 4-week-old commercial Three-Yellow chickens, which resulted in 40% mortality, typical clinical signs, and severe bursal lesions. These findings confirm the emergence of a novel dually reassortant and recombinant IBDV in Southern China, identify the N-terminal region of segment B as a potential virulence determinant in a naturally occurring field strain, and highlight the potential risks of live vaccine use. Our findings underscore the importance of continuous genetic and pathogenic surveillance of IBDV to inform effective prevention and control strategies.

The continuous evolution and co-circulation of H5 and H7 subtype highly pathogenic avian influenza viruses (HPAIVs) have caused substantial economic losses to the global poultry industry and pose a persistent threat to public health. This study aimed to develop a bivalent nucleoside-modified messenger (mRNA) vaccine encoding the hemagglutinin (HA) antigens of circulating H5N1 and H7N9 strains and to evaluate its immunogenicity and protective efficacy in an SPF chicken model. The bivalent vaccine elicited robust humoral immunity in SPF chickens in a dose-dependent manner following immunization. The immune sera exhibited potent neutralizing activity against the homologous viruses and cross-reactivity with heterologous strains. Challenge experiments demonstrated that chickens immunized with high doses (50μg and 80μg) of the bivalent mRNA vaccine were 100% protected against lethal challenge with homologous and heterologous H5N1, as well as heterologous H7N9 viruses. Furthermore, the vaccine effectively suppressed viral replication in the lungs and significantly reduced or blocked viral shedding. Importantly, splenic transcriptome sequencing revealed that vaccination elicited extensive immune reprogramming, with marked upregulation of key genes associated with Th1-type immune responses, antigen presentation, and cytokine production. The bivalent mRNA-lipid nanoparticle (LNP) vaccine developed in this study exhibited excellent immunogenicity and broad-spectrum protective potential in SPF chickens. Transcriptomic analysis further elucidated the molecular mechanisms underlying the vaccine-induced protective immunity. This study provides a promising vaccine candidate for the control of the co-circulation of H5 and H7 subtype HPAIVs.

The Manila clam (Ruditapes philippinarum) is one of the most valuable bivalves in global aquaculture, but its production is increasingly threatened by Perkinsus olseni, a protozoan parasite responsible for severe mortality events on shellfish beds. Understanding the genetic basis of resistance to this pathogen is essential for developing sustainable breeding strategies and reducing economic losses. We conducted a genome-wide association study (GWAS) on 606 Manila clam offspring from 32 full-sib families to investigate the heritability and genomic architecture of resistance to P. olseni. Following quality control and exclusion of the 42 smallest individuals potentially affected by size-related exposure bias, 564 offspring were retained for the final GWAS analyses. Genomic screening was performed with a newly developed multispecies SNP array comprising 49,392 SNPs for R. philippinarum. Experimental challenges were carried out in two tanks (challenged and control), each containing 1,500 offspring, and parasite load was quantified by qPCR using control Ct values as a non-infected reference. A substantial proportion of phenotypic variation in parasite load was explained by additive genetic effects, with heritability estimated at h² = 0.45 ± 0.09 using the full dataset and increasing to h² = 0.53 ± 0.08 after filtering. Several genome-wide significant quantitative trait loci (QTL) were identified across seven chromosomes, supporting a polygenic basis for resistance. Notably, one QTL on chromosome 18 also showed a highly significant association within one of the largest families. Patterns of linkage disequilibrium (LD) revealed rapid decay across most chromosomes, typical of marine bivalves, except for three chromosomes showing extended LD patterns compatible with putative structural polymorphisms, including possible inversions. These results demonstrate a substantial additive genetic component underlying resistance to P. olseni in Manila clam and highlight chromosome 18 as an important genomic region associated with parasite burden. Overall, our findings support the future integration of genomic tools into selective breeding programmes aimed at improving disease resilience and promoting the long-term sustainability of Manila clam aquaculture under increasing environmental and pathogen pressures.

Chiral spin textures, such as spin spirals and skyrmions, are key to advancing spintronics by enabling ultrathin, energy-efficient memory, and high-density data storage and processing. However, their realization remains hindered by the scarcity of suitable host materials and the formidable experimental challenges associated with the characterization of these intricate chiral magnetic states. Here, we report the observation of tunable chiral magnetic textures in van der Waals magnet CrPS4 with nonlinear optics. These tunable textures exhibit strong chiral third-order nonlinear optical responses, driven by interlayer and intralayer spin couplings under varying magnetic fields and temperatures. These pronounced chiral nonlinear optical responses highlight the potency and high sensitivity of the nonlinear optical readout for probing non-collinear magnetic orders. Moreover, our findings position van der Waals magnets and their heterostructures as an exceptional platform for reconfigurable spin-photonics and spintronics, unifying optical, electrical, and magnetic properties through unique intralayer and interlayer spin coupling properties and effective spin interaction between photons and electrons.