Experimental Challenge Research Articles

Enhancement of protective efficacy of recombinant attenuated Salmonella typhimurium delivering H9N2 avian influenza virus hemagglutinins(HA) antigen vaccine candidate strains by C-C motif chemokine ligand 5 in chickens(chCCL5)

The H9N2 inactivated avian influenza vaccine cannot induce cellular and mucosal immune responses, while the attenuated Salmonella vector as an intracellular bacterium can induce dominant cellular and mucosal immune responses. However, it provides low protection against the virus when delivering viral antigens and needs further optimization. Chicken C-C motif chemokine ligand 5 (chCCL5) is an important CC chemokine associated with immune cell chemotaxis, migration, and viral infection. This study connected the sequence of chCCL5 (CCL5) with the hemagglutinin sequence of the H9N2 avian influenza virus (yH9HA), utilizing the attenuated Salmonella typhimurium vector containing the delayed lysis system MazE/F regulated by arabinose as a carrier. A vaccine strain of recombinant attenuated Salmonella typhimurium and H9N2 avian influenza virus HA, rSC0130 (pS0017-yH9HA-CCL5), was successfully constructed. The experimental results indicate that yH9HA-CCL5 can be expressed in 293 T cells; compared to the strain without CCL5, rSC0130 (pS0017-yH9HA-CCL5) can induce significantly increased cellular immune responses and provide better protective effects in H9N2 virus challenge experiments. The above results indicate that chCCL5 can significantly enhance the protective effect of Salmonella delivering H9N2 avian influenza virus HA protein vaccine against H9N2 avian influenza virus infection, providing valuable theoretical support for further improving the protective efficiency of recombinant attenuated Salmonella vectors for delivering viral antigens.

Regulators of placental antibody transfer through a modeling lens.

Infants are vulnerable to infections owing to a limited ability to mount a humoral immune response and their tolerogenic immune phenotype, which has impeded the success of newborn vaccination. Transplacental transfer of IgG from mother to fetus provides crucial protection in the first weeks of life, and maternal immunization has recently been implemented as a public health strategy to protect newborns against serious infections. Despite their early success, current maternal vaccines do not provide comparable protection across pregnancies with varying gestational lengths and placental and maternal immune features, and they do not account for the dynamic interplay between the maternal immune response and placental transfer. Moreover, progress toward the rational design of maternal vaccines has been hindered by inadequacies of existing experimental models and safety challenges of investigating longitudinal dynamics of IgG transfer in pregnant humans. Alternatively, in silico mechanistic models are a logical framework to disentangle the processes regulating placental antibody transfer. This Review synthesizes current literature through a mechanistic modeling lens to identify placental and maternal regulators of antibody transfer, their clinical covariates, and knowledge gaps to guide future research. We also describe opportunities to use integrated modeling and experimental approaches toward the rational design of vaccines against existing and emerging neonatal pathogen threats.

A chimeric strain of porcine reproductive and respiratory syndrome virus 2 derived from HP-PRRSV and NADC30-like PRRSV confers cross-protection against both strains

Porcine reproductive and respiratory syndrome (PRRS) is one of the most significant swine viral infectious diseases worldwide. Vaccination is a key strategy for the control and prevention of PRRS. At present, the NADC30-like PRRSV strain has become the predominant epidemic strain in China, superseding the HP-PRRSV strain. The existing commercial vaccines offer substantial protection against HP-PRRSV, but their efficacy against NADC30-like PRRSV is limited. The development of a novel vaccine that can provide valuable cross-protection against both NADC30-like PRRSV and HP-PRRSV is highly important. In this study, an infectious clone of a commercial MLV vaccine strain, GD (HP-PRRSV), was first generated (named rGD). A recombinant chimeric PRRSV strain, rGD-SX-5U2, was subsequently constructed by using rGD as a backbone and embedding several dominant immune genes, including the NSP2, ORF5, ORF6, and ORF7 genes, from an NADC30-like PRRSV isolate. In vitro experiments demonstrated that chimeric PRRSV rGD-SX-5U2 exhibited high tropism for MARC-145 cells, which is of paramount importance in the production of PRRSV vaccines. Moreover, subsequent in vivo inoculation and challenge experiments demonstrated that rGD-SX-5U2 confers cross-protection against both HP-PRRSV and NADC30-like PRRSV, including an improvement in ADG levels and a reduction in viremia and lung tissue lesions. In conclusion, our research demonstrated that the chimeric PRRSV strain rGD-SX-5U2 is a novel approach that can provide broad-spectrum protection against both HP-PRRSV and NADC30-like PRRSV. This may be a significant improvement over previous MLV vaccinations.

Refrigeration capacity modeling of europium titanate based magnetocaloric compounds using computational single hidden layer intelligent and random forest regression methods

Europium titanate (EuTiO3) is a quantum para-electric magnetocaloric compound with potential application in green magnetic cooling technology. Super-exchange and indirect interactions existing between the magnetic moments of this compound are responsible for the observed magnetic properties such as the refrigeration capacity which falls among the key factors that characterize the usefulness of magnetic system of cooling in addressing energy crisis. Crystallographic substitutions and ionic replacement potentially shift magnetic ordering between anti-ferromagnetism to ferromagnetism and ultimately alters the refrigeration (magnetic) capacity of EuTiO3 compound. This work proposes extreme learning machine (ELM) and random forest regression (RFR) computational approaches to model refrigeration capacity of europium titanate magnetic refrigerant with the aid of applied magnetic field, ionic concentrations and ionic radii predictors. Sigmoid activation based extreme learning machine algorithm(SGA-ELM) demonstrates superior performance over sine function activation based extreme learning machine algorithm(SIA-ELM) with improvement of 0.03 %, 16.04 % and 35.03 % on the basis of Pearson correlation coefficient (CC), root mean square error (RMSE) and mean absolute error (MAE) performance yardsticks, respectively on testing set of EuTiO3 based magnetocaloric compounds. SGA-ELM performs better than SIA-ELM and RFR model with improvement of 35.03 % and 66.84 %, respectively while SIA-ELM model performs better than RFR model with improvement of 59.97 %. SGA-ELM model developed in this work outperforms the existing swarm based support vector regression (SW-SVR) models with performance improvement of 15.38 % (for SW-SVR-Gas with Gaussian function) and 42. 71 % % (for SW-SVR-Pol with polynomial function) using mean absolute deviation (MAD) performance yardstick. Significance of magnetic field and dopants concentrations on refrigeration capacity of different EuTiO3 perovskite was investigated with SGA-ELM model. The accuracy of developed models in determining refrigeration capacity of EuTiO3 compounds would ultimately circumvents experimental challenges and explores future potentials of these classes of compound for addressing present and future energy crisis in cooling industries.

A high-resolution acoustic goniometer for characterizing sound diffuser reflections

Noise control engineering and architectural acoustics practice have widely applied diffusing elements and devices to create surface scattering and diffuse reflections. An acoustical goniometer in the form of a circular microphone array has been used to characterize scattered responses for various types of diffusing elements/devices. This research is also intended for experimental validation of diffraction simulations of diffusing devices based on the physical theory of diffraction (PTD). To cope with experimental challenges, particularly for the research in the physical theory of diffraction, an acoustic goniometer must achieve a high enough angular resolution in addition to fulfilling far-field requirements. This paper discusses practical implementations and experimental results of portable goniometers with a radius of up to five meters and an angular resolution of 1.25 degrees. The practical implementation is intended to be easily deployable in empty, indoor spaces of sufficiently large dimensions for scattered reflection characterization. This paper discusses an effort of increasing experimental efficiency of characterization procedures for oblique incidences.

Structural evolution of liquid silicates under conditions in Super-Earth interiors

Molten silicates at depth are crucial for planetary evolution, yet their local structure and physical properties under extreme conditions remain elusive due to experimental challenges. In this study, we utilize in situ X-ray diffraction (XRD) at the Matter in Extreme Conditions (MEC) end-station of the Linear Coherent Linac Source (LCLS) at SLAC National Accelerator Laboratory to investigate liquid silicates. Using an ultrabright X-ray source and a high-power optical laser, we probed the local atomic arrangement of shock-compressed liquid (Mg,Fe)SiO3 with varying Fe content, at pressures from 81(9) to 385(40) GPa. We compared these findings to ab initio molecular dynamics simulations under similar conditions. Results indicate continuous densification of the O-O and Mg-Si networks beyond Earth’s interior pressure range, potentially altering melt properties at extreme conditions. This could have significant implications for early planetary evolution, leading to notable differences in differentiation processes between smaller rocky planets, such as Earth and Venus, and super-Earths, which are exoplanets with masses nearly three times that of Earth.

Challenging boundaries: is cross-protection evaluation necessary for African swine fever vaccine development? A case of oral vaccination in wild boar.

African swine fever (ASF) poses a significant threat to domestic pigs and wild boar (Sus scrofa) populations, with the current epidemiological situation more critical than ever. The disease has spread across five continents, causing devastating losses in the swine industry. Although extensive research efforts are ongoing to develop an effective and safe vaccine, this goal remains difficult to achieve. Among the potential vaccine candidates, live attenuated viruses (LAVs) have emerged as the most promising option due to their ability to provide strong protection against experimental challenges. However, ASF virus (ASFV) is highly diverse, with genetic and phenotypic variations across different isolates, which differ in virulence. This study highlights the limitations of a natural LAV strain (Lv17/WB/Rie1), which showed partial efficacy against a highly virulent and partially heterologous isolate (Arm07; genotype II). However, the LAV's effectiveness was incomplete when tested against a more phylogenetically distant virus (Ken06.Bus; genotype IX). These findings raise concerns about the feasibility of developing a universal vaccine for ASFV in the near future, emphasizing the urgent need to assess the protective scope of LAV candidates across different ASFV isolates to better define their limitations.

2-Aminobenzothiazole based adjuvant of polymyxin E against Gram-negative bacteria

Antibiotic resistance has emerged as a pressing global health issue. Polymyxin E, commonly regarded as a clinically important antibiotic, faces limitations due to its dose-dependent toxicity. A crucial strategy to combat this is the development of an antibiotic adjuvant to enhance efficacy while reducing dosage. Screening from our extensive in-house compound library, KJ1071 emerged as a promising adjuvant candidate for polymyxin E. Subsequent structure–activity relationship studies led to the discovery of compound A35, which demonstrated superior synergistic activity. However, its limited aqueous solubility posed challenges for biological experiments. To address this, we carried out a structural derivatization aimed at enhancing its solubility. The amino acid derivative A59 notably improved aqueous solubility to 3.237 mg/mL, a substantial 3237-fold increase compared to compound A35. Moreover, A59 amplified the efficacy of polymyxin E in eradicating a variety of Gram-negative bacteria, including certain clinical strains that are resistant to polymyxin E. The mechanism studies indicated that A59 might target the bacterial membrane. These findings suggest that the discovery of this innovative scaffold could provide critical insights for new adjuvant therapies.

Research progress on single-cell expression quantitative trait loci.

Expression quantitative trait loci (eQTL) represent genetic variants that regulate gene expression levels. eQTL analysis has become a crucial method for identifying the functional roles of disease-associated genetic variants in the post-genome-wide association study (GWAS) era, yielding numerous significant discoveries. Traditional eQTL analysis relies on whole-genome sequencing combined with bulk RNA-seq, which obscures gene expression differences between cells and thus fails to identify cell type- or state-dependent eQTL. This limitation makes it challenging to elucidate the roles of disease-associated genetic variants under specific conditions. In recent years, with the development and widespread application of single-cell RNA sequencing (scRNA-seq) technology, scRNA-seq-based eQTL (sc-eQTL) research has emerged as a focal point. The advantage of this approach lies in its ability to leverage the resolution and granularity of single-cell sequencing to uncover eQTL that are dependent on cell type, cell state, and cellular dynamics. This significantly enhances our ability to analyze genetic variants associated with gene expression. Consequently, it holds substantial significance for advancing our understanding of the formation of complex organs and the mechanisms underlying disease onset, progression, intervention, and treatment. This review comprehensively examines the recent advancements in sc-eQTL studies, focusing on their development, experimental design strategies, modeling approaches, and current challenges. The aim is to offer researchers novel perspectives for identifying disease-associated loci and elucidating gene regulatory mechanisms.

Effects of a potential host gut-derived probiotic, Bacillus amyloliquefaciens AV5, on the growth, biochemical and metabolic responses, and disease resistance of Nile tilapia (Oreochromis niloticus)

The influence of the dietary probiotic Bacillus amyloliquefaciens AV5 on the growth, biochemical and metabolic responses, and disease resistance of Nile tilapia (Oreochromis niloticus) was evaluated. The commercial diet (GC), a diet containing 106 and 108 CFU/g of B. amyloliquefaciens AV5, denoted as G1 and G2, respectively, was fed for 30 days. Fish were allocated to 9 plastic tanks, and each diet was randomly assigned to triplicate groups of 40 fish (22.4 ± 1.3 g).After 30 days of the feeding trial, the specific growth rate, weight gain rate, and final weight increased significantly in G2 compared to those in GC and G1. Feed conversion ratio was significantly higher in the fish-fed GC group than in the G2 group. However, the survival rate of the fish ranged from 99.13 % to 97.17 %, with no significant difference. Glucose levels did not differ significantly (P < 0.05). Total antioxidant capacity (T-AOC), (superoxide dismutase (SOD), and catalase (CAT), as well as digestive enzymes (trypsin, lipase, and protease), were significantly increased in the G2 group relative to the GC and G1 groups.Significantly lower ALT, AST, CHO, TG, and MDA activities were observed in the G2 group than in the GC group. To evaluate the metabolomic response, PCA, OPLS-DA, and volcano plots revealed a distinct difference between the G2 and GC diets, suggesting that the G2 diet impacted the hepatopancreas of fish. Furthermore, challenge experiments revealed that fish fed B. amyloliquefaciens AV5 exhibited substantially increased resistance (P < 0.05) to S. agalactiae at a concentration of 1x108CFU/g. Therefore, dietary supplementation with B. amyloliquefaciens AV5 enhanced the growth performance, metabolic activity, and disease resistance of O. niloticus.

Radiochemistry and Complex Formation of the Cyclen-Derived Chelator DOTI-Me with Mn2+, Cu2+, Zn2+, Ga3+, In3+, Tb3+, and Lu3.

In this work, we describe the complex formation and radiochemistry of the cyclen-based chelator DOTI-Me bearing four methylimidazole arms. Radiolabeling properties were evaluated for 52gMn, 64Cu, 68Ga, 111In, 161Tb, and 177Lu, and DOTI-Me showed distinct differences to the structurally related H4DOTA. While radiochemical conversions (RCCs) for 52gMn and 111In were comparable to those of H4DOTA, DOTI-Me was not suited for 68Ga. Conversely, quantitative RCCs were achieved for 64Cu at ambient temperature, while elevated temperatures were required for complexation with H4DOTA. For 161Tb and 177Lu, good but not quantitative RCCs were obtained with DOTI-Me. With the exemption of 68Ga3+, radiolabeled complexes showed high stability in ligand challenge experiments and in human serum. X-ray analysis of the nonradioactive complexes revealed the formation of 8-coordinate Mn2+ and In3+ DOTI-Me complexes. Cu2+ adopted a unique distorted square-pyramidal 2 + 3 with the neutral DOTI-Me ligand and a Jahn-Teller distorted 4 + 2 coordination geometry for the diprotonated H2DOTI-Me2+ cation, respectively. For Zn2+, the complex with HDOTI-Me+ showed a distorted 4 + 3 pentagonal bipyramidal geometry. Summarizing, the ligand DOTI-Me may be an interesting alternative to H4DOTA for 52gMn, 64Cu, 111In, 161Tb, and 177Lu, covering diagnostic as well as therapeutic radionuclides. Further studies of targeted radiopharmaceuticals based on the DOTI-Me scaffold in combination with the set of radiometals presented herein are thus warranted.

Dietary Chitosan Nanoparticles Enhance Growth, Antioxidant Defenses, Immunity, and Aeromonas veronii biovar sobria Resistance in Nile tilapia Oreochromis niloticus

While chitosan is widely used in aquaculture feed, chitosan nanoparticles (CNPs) offer potential advantages due to their enhanced absorption. This study investigated the safe use of CNP levels in Nile tilapia feed, evaluating its impact on growth, immunity, and disease resistance. Five experimental diets were formulated and supplemented with zero chitosan (served as a control group), 1g/kg of chitosan (CS), and 1, 3, and 5 g/kg of CNPs. Each diet was randomly assigned to three replicate groups of 45 fish per group (15 fish/tank) with an average weight of (42.10 ± 0.05g, mean ± S.E.) twice daily (09:00 a.m. and 4:00 p.m.) to apparent satiation for two months. At the end of the feeding trial, fish fed 5 g/ kg of CNPs had the highest growth performance. However, no significant variations (p &gt; 0.05) in somatic index were seen between the experimental groups. All chitosan and CNP-enriched groups exhibited improved intestinal morphology compared to the control group, characterized by increased villus length and width, reduced necrosis of intestinal tips, and better overall tissue integrity, with the CNP 3g and 5g groups demonstrating the most favorable intestinal structure. The CNP-treated groups (3, 5 g/kg) had significantly higher blood indices and serum globulin. Malondialdehyde (MDA) levels were lower in the CNP-treated groups compared to the chitosan macromolecule group. There was a substantial rise in glutathione (GSH), total antioxidant capacity (TAC), phagocytic index, and respiratory burst activity in the 5 g/kg CNP-treated group. The dietary addition of 5 g/kg of CNPs raised mRNA expression for TLR-2, MUC-2, and IGF-1, but there was no significant difference in HSP70 expression across treatments. After the experimental challenge with Aeromonas veronii biovar sobria, the groups that received 3 and 5 g/kg of CNPs exhibited the lowest mortality rates. Overall, the results suggest that including 5g/kg of CNPs in fish food is safe and effective for enhancing their health and growth, making it a promising addition to aquaculture feed.

Evaluation of Tembusu virus single-round infectious particle as vaccine vector in chickens

Orthoflaviviruses are single-stranded RNA viruses characterized by highly efficient self-amplification of RNA in host cells, which makes them attractive vehicles for vaccines. Numerous preclinical and clinical studies have demonstrated the efficacy and safety of orthoflavivirus replicon vectors for vaccine development. In this study, we constructed Tembusu virus (TMUV) replicon-based single-round infectious particles (SRIPs) as vaccine development platform. To evaluate the potential of TMUV SRIPs as vaccines, we generated SRIPs that express the heterologous Fowl adenovirus 4 (FAdV-4) fiber2 protein and fiber2 head domain, named TMUVRP-fiber2 and TMUVRP-fiber2H, respectively. To assess the immunogenicity of the TMUV SRIPs, SPF chicks were intramuscularly inoculated twice. Our results showed that the TMUVRP-fiber2 vaccines elicited high levels of neutralizing antibodies. Challenge experiments showed that TMUVRP-fiber2 provided full protection against virulent FAdV-4 and significantly reduced viral shedding. Moreover, the immunogenicity of TMUVRP-fiber2H was significantly lower than that of TMUVRP-fiber2, which was reflected in the neutralizing antibody titer, survival rate, and virus shedding after challenge. Therefore, our results suggested that TMUV SRIPs are a promising novel platform for the development of vaccines for existing and emerging poultry diseases.

A New Licensed Quadrivalent Antileptospiral Canine Vaccine Prevents Mortality, Clinical Signs, Infection, Bacterial Excretion, Renal Carriage and Renal Lesions Caused by Leptospira Australis Experimental Challenge.

L. Australis is one of the most prevalent Leptospira strains infecting dogs, leading, in natural conditions, to severe life-threatening cases. The objective was to evaluate the onset and duration of immunity (OOI and DOI) induced by a new licensed quadrivalent antileptospiral vaccine (EURICAN® L4) including four Leptospira components (Canicola, Icterohaemorrhagiae, Grippotyphosa and Australis) against L. Australis. To this end, a severe L. Australis challenge model was developed, using a canine strain recently isolated from the field. Seven- to ten-week-old puppies received two doses of the vaccine four weeks apart and were challenged with an L. Australis isolate two weeks (OOI) and 12 months (DOI) later. Mortality, clinical signs, leptospiremia, leptospiruria, renal carriage, and renal lesions were assessed after challenge. The challenge induced multiple severe clinical signs in controls, leading to the death or euthanasia of 83% of puppies and 57% of adults. In controls, leptospiremia was detected in all dogs, leptospiruria in 67% of puppies and 86% of adults, kidneys tested positive for Leptospira in 83% of puppies and 71% of adults, and kidney lesions were observed in 100% of puppies and 86% of adults. In addition, thrombocytopenia associated with increased concentrations of urea, creatinine, and aspartate aminotransferase was recorded in controls displaying severe clinical signs. In both OOI and DOI studies, none of the vaccinates had clinical signs, no Leptospira was detected in blood, urine, and kidney samples, and no kidney lesions were observed in vaccinates. No significant changes in hematological and biochemical parameters in vaccinates were recorded. EURICAN® L4 was shown to induce quick and long-lasting protection against a severe L. Australis infectious challenge, preventing mortality, clinical signs, infection, bacterial excretion, renal lesions, and renal carriage.

Double-Higgs Production

A major focus in particle physics has been on understanding the interactions of the Higgs boson. Tremendous progress has been made in determining the strength of the couplings of the Higgs boson to fermions and vector bosons, but its self-interaction has yet to be established. Understanding the Higgs self-coupling and the form of the potential function of the Higgs field will illuminate the process by which the Higgs boson acquires a vacuum expectation value and could provide insight into the early Universe and, perhaps, its eventual fate. The most natural way to probe the Higgs self-interaction is via searches for Higgs boson pair (HH) production. Since the Standard Model makes a definite prediction for the Higgs self-coupling, enhanced rates and modified kinematic properties of HH production are a smoking-gun signature for new physics. This article reviews the current experimental status of HH searches, discusses the experimental challenges and limitations, and provides an outlook for the future of the field.

Direct Detection of the Magnetic Force and Field Coupling of Electronic Spins Using Photoinduced Magnetic Force Microscopy.

The intrinsic spin of the electron and its associated magnetic moment can provide insights into spintronics. However, the interaction is extremely weak, as is the case with the coupling between an electron's spin and a magnetic field, and it poses significant experimental challenges. Here we demonstrate the direct measurement of polarized single NV- centers and their spin-spin coupling behaviors in diamond. By using photoinduced magnetic force microscopy, we obtain the extremely weak magnetic force coupling originating from the electron spin. The polarized spin state of NV- centers, transitioning from |0⟩ to |±1⟩, and their corresponding Zeeman effect can be characterized through their interaction with a magnetic tip. The result presents an advancement in achieving electron spin measurements by magnetic force, avoiding the need for manufacturing conductive substrates. This facilitates a better understanding and control of electron spin to novel electronic states for future quantum technologies.

Detecting expressed genes in cell populations at the single-cell level with scGeneXpress.

Determining whether genes are expressed or not remains a challenge in single-cell RNAseq experiments due to their different expression spectra, which are influenced by genetics, the microenvironment and gene length. Current approaches for addressing this issue fail to provide a comprehensive landscape of expressed genes, since they neglect the inherent differences in the expression ranges and distributions of genes. Here, we present scGeneXpress, a method for detecting expressed genes in cell populations of single-cell RNAseq samples based on gene-specific reference distributions. We demonstrate that scGeneXpress accurately detects expressed cell markers and identity genes in 34 human and mouse tissues and can be employed to improve differential expression analysis of single-cell RNAseq data.

Low Energy Dark Matter Searches

This paper summarizes the motivations and challenges for direct detection experiments aimed at dark matter particles with masses below the GeV scale. Two such experiments with large Canadian contributions, currently operating or under construction at SNOLAB, are discussed in detail: SuperCDMS, which employs cryogenic semiconductor crystals, and NEWS-G, which employs noble gas spherical detectors. Finally, we highlight recent efforts to investigate sharply-rising event rates below a few hundred eV, in excess of expectations from existing background models, that have been observed in multiple direct detection experiments.

Multi-omics analysis reveals regime shifts in the gastrointestinal ecosystem in chickens following anticoccidial vaccination and Eimeria tenella challenge.

Coccidiosis, caused by Eimeria parasites, significantly impacts poultry farm economics and animal welfare. Beyond its direct impact on health, Eimeria infection disrupts enteric microbial populations leading to dysbiosis and increases vulnerability to secondary diseases such as necrotic enteritis, caused by Clostridium perfringens. The impact of Eimeria infection or anticoccidial vaccination on host gastrointestinal phenotypes and enteric microbiota remains understudied. In this study, the metabolomic profiles and microbiota composition of chicken caecal tissue and contents were evaluated concurrently during a controlled experimental vaccination and challenge trial. Cobb500 broilers were vaccinated with a Saccharomyces cerevisiae-vectored anticoccidial vaccine and challenged with 15,000 Eimeria tenella oocysts. Assessment of caecal pathology and quantification of parasite load revealed correlations with alterations to caecal microbiota and caecal metabolome linked to infection and vaccination status. Infection heightened microbiota richness with increases in potentially pathogenic species, while vaccination elevated beneficial Bifidobacterium. Using a multi-omics factor analysis, data on caecal microbiota and metabolome were integrated and distinct profiles for healthy, infected, and recovering chickens were identified. Healthy and recovering chickens exhibited higher vitamin B metabolism linked to short-chain fatty acid-producing bacteria, whereas essential amino acid and cell membrane lipid metabolisms were prominent in infected and vaccinated chickens. Notably, vaccinated chickens showed distinct metabolites related to the enrichment of sphingolipids, important components of nerve cells and cell membranes. Our integrated multi-omics model revealed latent biomarkers indicative of vaccination and infection status, offering potential tools for diagnosing infection, monitoring vaccination efficacy, and guiding the development of novel treatments or controls.IMPORTANCEAdvances in anticoccidial vaccines have garnered significant attention in poultry health management. However, the intricacies of vaccine-induced alterations in the chicken gut microbiome and its subsequent impact on host metabolism remain inadequately explored. This study delves into the metabolic and microbiotic shifts in chickens post-vaccination, employing a multi-omics integration analysis. Our findings highlight a notable synergy between the microbiome composition and host-microbe interacted metabolic pathways in vaccinated chickens, differentiating them from infected or non-vaccinated cohorts. These insights pave the way for more targeted and efficient approaches in poultry disease control, enhancing both the efficacy of vaccines and the overall health of poultry populations.

A Helicene‐Based Single‐Molecule Inductor and Capacitor with Frequency‐Dependent Charge‐Transport Pathways

Despite extensive studies has been explored on single‐molecule switches and rectifiers, the design of single‐molecule inductors has not been explored due to the experimental challenges in the investigation of frequency‐dependent charge transport at the single‐molecule scale. In this study, we synthesized a helicene‐based helical molecular wire and carried out meticulous single‐molecule conductance measurements, combined with current‐voltage (IV) studies with varying frequencies using the scanning tunneling microscope break junction (STM‐BJ) technique. Our results reveal the formation of a single‐molecule junction and highlight the unique behavior of the molecular wire in response to different alternating current (AC) varying frequencies. The transport of charges occurs selectively either through the coiled backbone of the conjugated helical structure or vertically via π‐π stacking, depending on the frequency of the applied AC. Notably, our investigation demonstrates the functionality of the wire as an inductor at low frequencies, and a capacitor at high frequencies. This work lays the foundation for a systematic approach to designing, fabricating, and implementing single‐molecule logic devices such as inductors and wave filters.