Pan-genome wide association study of Glaesserella parasuis highlights genes associated with virulence and biofilm formation.

Glaesserella parasuis is a gram-negative bacterium that causes fibrotic polyserositis and arthritis in pig, significantly affecting the pig industry. The pan-genome of G. parasuis is open. As the number of genes increases, the core and accessory genomes may show more pronounced differences. The genes associated with virulence and biofilm formation are also still unclear due to the diversity of G. parasuis. Therefore, we have applied a pan-genome-wide association study (Pan-GWAS) to 121 strains G. parasuis. Our analysis revealed that the core genome consists of 1,133 genes associated with the cytoskeleton, virulence, and basic biological processes. The accessory genome is highly variable and is a major cause of genetic diversity in G. parasuis. Furthermore, two biologically important traits (virulence, biofilm formation) of G. parasuis were studied via pan-GWAS to search for genes associated with the traits. A total of 142 genes were associated with strong virulence traits. By affecting metabolic pathways and capturing the host nutrients, these genes are involved in signal pathways and virulence factors, which are beneficial for bacterial survival and biofilm formation. This research lays the foundation for further studies on virulence and biofilm formation and provides potential new drug and vaccine targets against G. parasuis.

I2-Promoted gem-Diarylethene Involved Aza-Diels-Alder Reaction and Wagner-Meerwein Rearrangement: Construction of 2,3,4-Trisubstituted Pyrimido[1,2-b]indazole Skeletons.

A [3 + 1 + 2] cyclization-rearrangement reaction scheme was developed to synthesize pyrimido[1,2-b]indazoles from aryl methyl ketones, 3-aminoindazoles, and gem-diarylethenes. This metal-free process proceeds via a sequential aza-Diels-Alder reaction and Wagner-Meerwein rearrangement, and a possible reaction mechanism was demonstrated based on control experiments. This method exhibits good substrate compatibility and allows simple reaction conditions. Moreover, the products display significant aggregation-induced emission characteristics after simple modifications.

Corrigendum: Prevalence and outcomes of pancreatic enzymes elevation in patients with COVID-19: a meta-analysis and systematic review.

[This corrects the article DOI: 10.3389/fpubh.2022.865855.].

RNA stability controlled by m6A methylation contributes to X-to-autosome dosage compensation in mammals.

In mammals, X-chromosomal genes are expressed from a single copy since males (XY) possess a single X chromosome, while females (XX) undergo X inactivation. To compensate for this reduction in dosage compared with two active copies of autosomes, it has been proposed that genes from the active X chromosome exhibit dosage compensation. However, the existence and mechanisms of X-to-autosome dosage compensation are still under debate. Here we show that X-chromosomal transcripts have fewer m6A modifications and are more stable than their autosomal counterparts. Acute depletion of m6A selectively stabilizes autosomal transcripts, resulting in perturbed dosage compensation in mouse embryonic stem cells. We propose that higher stability of X-chromosomal transcripts is directed by lower levels of m6A, indicating that mammalian dosage compensation is partly regulated by epitranscriptomic RNA modifications.

Concepts and methods for transcriptome-wide prediction of chemical messenger RNA modifications with machine learning.

The expanding field of epitranscriptomics might rival the epigenome in the diversity of biological processes impacted. In recent years, the development of new high-throughput experimental and computational techniques has been a key driving force in discovering the properties of RNA modifications. Machine learning applications, such as for classification, clustering or de novo identification, have been critical in these advances. Nonetheless, various challenges remain before the full potential of machine learning for epitranscriptomics can be leveraged. In this review, we provide a comprehensive survey of machine learning methods to detect RNA modifications using diverse input data sources. We describe strategies to train and test machine learning methods and to encode and interpret features that are relevant for epitranscriptomics. Finally, we identify some of the current challenges and open questions about RNA modification analysis, including the ambiguity in predicting RNA modifications in transcript isoforms or in single nucleotides, or the lack of complete ground truth sets to test RNA modifications. We believe this review will inspire and benefit the rapidly developing field of epitranscriptomics in addressing the current limitations through the effective use of machine learning.

Exploring the chondroprotective effect of Chaenomeles speciosa on Glucose-6-Phosphate Isomerase model mice using an integrated approach of network pharmacology and experimental validation.

ETHNOPHARMACOLOGICAL RELEVANCE: Traditional Chinese medicine (TCM) has been used in China for a long time and is gradually gaining more and more recognition worldwide. Chaenomeles speciosa (CSP) (Chinese Pinyin: mugua) is a medicinal and food herb that has long been used as a folk medicine for rheumatic diseases, yet its bioactive components and therapeutic mechanisms are not clear. AIM OF THE STUDY: Exploring anti-inflammatory and chondroprotective effects of CSP on rheumatoid arthritis (RA) and its possible targets of action. MATERIALS AND METHODS: In this study, we performed an integrated approach of network pharmacology, molecular docking and experimental studies to explore the potential mechanism of action of CSP in the treatment of cartilage damage in RA. RESULTS: Studies have shown that Quercetin, ent-Epicatechin and Mairin may be the main active compounds of CSP in the treatment of RA, while AKT1, VEGFA, IL-1ß, IL-6, MMP9 etc. are considered as core target proteins to which the main active compounds in CSP bind, as further confirmed by molecular docking. In addition, the potential molecular mechanism of CSP for the treatment of cartilage damage in RA predicted by network pharmacology analysis was validated by in vivo experiments. CSP was found to downregulate the expression of AKT1, VEGFA, IL-1ß, IL-6, MMP9, ICAM1, VCAM1, MMP3, MMP13 and TNF-α and increase the expression of COL-2 in the joint tissue of Glucose-6-Phosphate Isomerase (G6PI) model mice. Thus CSP contributes to the treatment of rheumatoid arthritis cartilage destruction. CONCLUSION: This study showed that CSP has multi-component, multi-target and multi-pathway characteristics in treating cartilage damage in RA, which can achieve the effect of treating RA by inhibiting the expression of inflammatory factors, reducing neovascularization and alleviating the damage to cartilage caused by the diffusion of synovial vascular opacities, and reducing the degradation of cartilage by MMPs to play a protective role in RA cartilage damage. In conclusion, this study indicates that CSP is a candidate Chinese medicine for further research in treating cartilage damage in RA.

ADCY9 functions as a novel cancer suppressor gene in lung adenocarcinoma.

Background: The process of lucubrating into lung adenocarcinoma (LUAD) is of profound clinical and practical significance in improving the prognosis of LUAD patients. Multiple biomarkers are reportedly involved in the proliferation or metastasis of adenocarcinoma. However, whether the ADCY9 gene influences the development of LUAD remains unknown. Therefore, we aimed to elucidate the relationship between the expression of ADCY9 and the proliferation and migration of LUAD. Methods: The ADCY9 gene was filtered via a survival analysis of LUAD acquired from the Gene Expression Omnibus (GEO). Then, we conducted a validation analysis and ADCY9-microRNA, microRNA-lncRNA, and ADCY9-lncRNA targeting relationship analysis through the data obtained from The Cancer Genome Atlas (TCGA) dataset. The survival curve, correlation, and prognostic analysis were implemented through bioinformatics methods. Both protein and mRNA expression levels of LUAD cell lines and LUAD patient samples (80 pairs) were detected using western blot assays and quantitative real-time polymerase chain reaction (qRT-PCR). An immunohistochemistry assay was performed to display the correlation between the expression level of the ADCY9 gene and prognosis in LUAD patients (2012-2013; n=115). Overexpression of cell lines SPCA1 and A549 were used for a series of cell function assays. Results: Compared with the expression level in adjacent normal tissues, ADCY9 expression was downregulated in LUAD tissues. Based on the result of the survival curve analysis, high expression of ADCY9 may lead to a better prognosis and may be seen as an independent predictor for LUAD patients. High expression of ADCY9-related microRNA hsa-miR-7-5p may lead to a worse prognosis, and high expression of hsa-miR-7-5p-related lncRNAs may lead to the opposite effects. Overexpression of ADCY9 restrained the proliferation, invasion, and migration abilities of SPCA1, A549 cells. Conclusions: Results indicate that the ADCY9 gene acts as a tumor suppressor to restrain the proliferation, migration, and invasion in LUAD and can lead to a better survival or prognosis in LUAD patients.

Joint association of hyperuricemia and chronic kidney disease with mortality in patients with chronic heart failure.

Background: The joint association of hyperuricemia and chronic kidney disease (CKD) with mortality in patients with chronic heart failure (CHF) is not conclusive. Methods: This retrospective cohort study was conducted in Chinese People's Liberation Army General Hospital, Beijing, China. We included 9,367 patients with CHF, who were hospitalized between January 2011 and June 2019. The definitions of hyperuricemia and CKD were based on laboratory test, medication use, and medical record. We categorized patients with CHF into 4 groups according to the absence (-) or presence (+) of hyperuricemia and CKD. The primary outcomes included in-hospital mortality and long-term mortality. We used multivariate logistic regression and Cox proportional hazards regression to estimate the mortality risk according to the hyperuricemia/CKD groups. Results: We identified 275 cases of in-hospital mortality and 2,883 cases of long-term mortality in a mean follow-up of 4.81 years. After adjusting for potential confounders, we found that compared with the hyperuricemia-/CKD- group, the risks of in-hospital mortality were higher in the hyperuricemia+/CKD- group (odds ratio [OR], 95% confidence interval [CI]: 1.58 [1.01-2.46]), hyperuricemia-/CKD+ group (OR, 95% CI: 1.67 [1.10-2.55]), and hyperuricemia+/CKD+ group (OR, 95% CI: 2.12 [1.46-3.08]). Similar results were also found in long-term mortality analysis. Compared with the hyperuricemia-/CKD- group, the adjusted hazard ratios and 95% CI for long-term mortality were 1.25 (1.11-1.41) for hyperuricemia+/CKD- group, 1.37 (1.22-1.53) for hyperuricemia-/CKD+ group, and 1.59 (1.43-1.76) for hyperuricemia+/CKD+ group. The results remained robust in the sensitivity analysis. Conclusions: Hyperuricemia and CKD, both individually and cumulatively, are associated with increased mortality risk in patients with CHF. These results highlighted the importance of the combined control of hyperuricemia and CKD in the management of heart failure.

Automatic detection of early osteonecrosis of the femoral head from various hip pathologies using deep convolutional neural network: a multi-centre study.

PURPOSE: The aim of this study was to develop a deep convolutional neural network (DCNN) for detecting early osteonecrosis of the femoral head (ONFH) from various hip pathologies and evaluate the feasibility of its application. METHODS: We retrospectively reviewed and annotated hip magnetic resonance imaging (MRI) of ONFH patients from four participated institutions and constructed a multi-centre dataset to develop the DCNN system. The diagnostic performance of the DCNN in the internal and external test datasets was calculated, including area under the receiver operating characteristic curve (AUROC), accuracy, precision, recall, and F1 score, and gradient-weighted class activation mapping (Grad-CAM) technique was used to visualize its decision-making process. In addition, a human-machine comparison trial was performed. RESULTS: Overall, 11,730 hip MRI segments from 794 participants were used to develop and optimize the DCNN system. The AUROC, accuracy, and precision of the DCNN in internal test dataset were 0.97 (95% CI, 0.93-1.00), 96.6% (95% CI: 93.0-100%), and 97.6% (95% CI: 94.6-100%), and in external test dataset, they were 0.95 (95% CI, 0.91- 0.99), 95.2% (95% CI, 91.1-99.4%), and 95.7% (95% CI, 91.7-99.7%). Compared with attending orthopaedic surgeons, the DCNN showed superior diagnostic performance. The Grad-CAM demonstrated that the DCNN placed focus on the necrotic region. CONCLUSION: Compared with clinician-led diagnoses, the developed DCNN system is more accurate in diagnosing early ONFH, avoiding empirical dependence and inter-reader variability. Our findings support the integration of deep learning systems into real clinical settings to assist orthopaedic surgeons in diagnosing early ONFH.

Development of a Real-Time TaqMan RT-PCR Assay for the Detection of NADC34-like Porcine Reproductive and Respiratory Syndrome Virus.

NADC34-like porcine reproductive and respiratory syndrome virus first appeared in 2017 in a herd of pigs in Liaoning Province, China. The virus was subsequently found in other provinces. Given the potential for this virus to cause an epidemic, rapid, sensitive, and specific detection of NADC34-like PRRSV is required. The virus' ORF5 gene was artificially synthesized based on a Chinese reference strain, and specific primers/probes for the ORF5 gene were designed. Then, the amplified target fragment was cloned into the pMD19-T vector, and a series of diluted recombinant plasmids were used to generate a standard curve. An optimized real-time TaqMan RT-PCR method was established. The method was highly specific for NADC34-like PRRSV, without cross-reactions with other non-targeted pig viruses. The detection limit of this assay was 101 copies/µL. The method had an efficiency of 98.8%, a squared regression value (R2) of 0.999, and showed a linear range of 103-108 copies/µL of DNA per reaction. This method was shown to be analytically specific and sensitive with a low intra- and inter-assay coefficient of variation (<1.40%). A total of 321 clinical samples were tested using the established method, and four were shown to be positive (1.24%). This study confirmed the existence of NADC34-like PRRSV and HP-PRRSV co-infection in Sichuan and provided a promising alternative tool for the rapid detection of NADC34-like PRRSV.

Lightweight, highly tough and durable YBa2Cu3O7 -x superconductor.

The inherent brittleness and low sustainability of YBa2Cu3O7 -x (YBCO) bulk superconductor seriously impede its wide applications. It is a great challenge to achieve toughening of this material and maintain its invariable superconductivity at the same time. Here, we fabricate bulk YBCO composite superconductor with a density of 2.15 g cm-3, which consists of interlocking dual network construction and shows high toughness and durability. The results show that its unit normalized fracture energy at 77 K reaches 638.6 kN m-2, which is ∼14.8 times that of YBCO bulk prepared by the top-seeded melt textured growth (TSMTG) method. Its critical current shows no degradation during the toughening process. Moreover, after 10 000 cycles, the sample does not fracture with the decay of critical current at 4 K of 14.6% whereas the TSMTG sample fractures only after 25 cycles.

Review of progress and challenges of key mechanical issues in high-field superconducting magnets.

The development of modern science and technology requires high magnetic fields exceeding 25T. Second-generation high-temperature superconducting wires, i.e. REBCO (REBa2Cu3O7-x, RE refers to Y, Gd, Dy, Eu and other rare-earth elements) coated conductors (CCs), have become the first choice for high-field magnet construction because of their high irreversible magnetic field. The mechanical stresses caused by manufacturing, thermal mismatch and Lorenz forces closely influence electromagnetic performance during operation for REBCO CCs. In addition, the recently studied screen currents have effects on the mechanical characteristics of high-field REBCO magnets. In this review, the experimental and main theoretical works on critical current degradation, delamination and fatigue, and shear investigations on REBCO CCs, are reviewed at first. Then, research progress on the screening-current effect in the development of high-field superconducting magnets is introduced. Finally, the key mechanical problems facing the future development of high-field magnets based on REBCO CCs are prospected.

M2 Macrophage Membrane-Mediated Biomimetic-Nanoparticle Carrying COX-siRNA Targeted Delivery for Prevention of Tendon Adhesions by Inhibiting Inflammation.

Tendon adhesion is the most common outcome of tendon or tendon-to-bone healing after injury. Our group developed a hydrogel-nanoparticle sustained-release system previously to inhibit cyclooxygenases (COXs) expression and consequently prevent tendon adhesion and achieved satisfactory results. However, effective treatment of multiple tendon adhesions is always a challenge in research on the prevention of tendon adhesion. In the present study, an M2M@PLGA/COX-siRNA delivery system is successfully constructed using the cell membranes of M2 macrophages and poly (lactic-co-glycolic acid) (PLGA) nanoparticles. Targeting properties and therapeutic effects are observed in mice or rat models of flexor digitorum longus (FDL) tendon injury combined with rotator cuff injury. The results showed that the M2M@PLGA/COX-siRNA delivery system has low toxicity and remarkable targeting properties to the injured areas. Treatment with the M2M@PLGA/COX-siRNA delivery system reduced the inflammatory reaction and significantly improved tendon adhesion in both the FDL tendon and rotator cuff tissues. These findings indicate that the M2M@PLGA delivery system can provide an effective biological strategy for preventing multiple tendon adhesions.

Bartonella Neuroretinitis: There Is More to Cat Scratch Disease than Meets the Eye.

BACKGROUND Cat scratch disease (CSD) is a self-limited infection caused by Bartonella henselae that causes lymphadenitis, fevers, skin changes at the inoculation site, headache, nausea, and ocular symptoms. Bartonella neuroretinitis is a form of CSD that presents with ocular symptoms, such as a central scotoma, rather than the typical lymphadenopathy of CSD. Bartonella neuroretinitis is the most common cause of infectious neuroretinitis leading to painless vision loss. Symptoms can mimic the more common optic neuritis, which can lead to under-diagnosis. Early diagnosis of Bartonella neuroretinitis and initiation of appropriate treatment is crucial to prevent vision loss and shorten recovery time. CASE REPORT A 47-year-old man presented to the Emergency Department with nonspecific symptoms of headache, fevers, and visual changes. He was noted to have adopted a cat 2 months prior to presentation. A dilated fundus examination revealed grade 3 optic disc edema with small disc hemorrhages bilaterally without lymphadenopathy, and Bartonella henselae serologies returned positive for the disease. The patient was treated with doxycycline and rifampin at discharge. At his follow-up outpatient ophthalmology visit, the patient had symptomatically improved vision, with dilated fundus examination supporting reduced optic disc edema in the right eye. CONCLUSIONS Early recognition and treatment of Bartonella neuroretinitis is essential to prevent vision loss and shorten recovery time. The current standard of treatment is doxycycline and rifampin for 4 to 6 weeks, and a growing body of literature indicates the supplementation of corticosteroids with these antibiotics.

Notopterol improves cognitive dysfunction and depression-like behavior via inhibiting STAT3/NF-ĸB pathway mediated inflammation in glioma-bearing mice.

Over the past few decades, clinicians and experts applied kinds of therapies for patients with malignant gliomas such as chemotherapy, radiation or surgical extraction. However, they used to ignore the real seriousness of neuropsychiatric symptoms after glioma, including cognitive dysfunction, anxiety, and depression, which severely impeded patients' recovery and prognosis. Interestingly, one of our previous clinical studies have found some behavioral symptoms in glioma patients were associated with systemic inflammation. Notopterol is one of the principal extracts of the traditional Chinese medicinal herb Notopterygium incisum having anti-tumour and anti-inflammatory activity. However, whether notopterol is beneficial to the treatment of glioma has not been reported. In this study, we found that notopterol inhibited growth and increased apoptosis of glioma via inhibiting STAT3 activity. In addition, notopterol treatment improved cognitive impairment and depression-like behavior in GL261 cell-based glioma mice via preventing the loss of dendritic spines and the reduction of synapse related proteins (PSD95 and Synapsin-1) in hippocampal neurons. Notopterol significantly reduced the levels of cytokines (iNOS, TNF-α, IL-6, and IL-ß) and the activity of STAT3/NF-kB signalling pathway in peritumoural brain tissues and GL261 conditioned medium (GCM) treated microglial cell line (BV2 cells). These results demonstrated that notopterol not only exerted anti-glioma effects via inhibiting STAT3 activity, but improved neuropsychiatric symptoms via inhibiting tumour associated inflammation through modulation of the STAT3/NF-kB pathway in glioma-bearing mice.

Solid-State Luminescence Turn-On Sensing Using MOF-Confined Reporter-Spacer-Receptor Architectures Facilitated by Quencher Displacement.

The reporter-spacer-receptor (RSR) approach is prevalent to develop molecular turn-on sensors. However, the fluorescent RSR sensors barely operate in solid state, which hinders their fabrication into devices for practical applications. Herein, we present a novel strategy to achieve solid-state luminescence turn-on sensing by assembling RSR architectures within MOF frameworks. Unlike the regular RSR systems, the framework-confined fluorophore and receptor are well arranged and separated even in the solid state. This concept is illustrated by a multicomponent MOF (Fc@NU-1000), which contains organic linkers with a highly luminescent pyrene core as the reporter, Zr6 nodes with unsaturated sites as the receptor, and the incorporated Fc molecules as the quencher. The separate incorporation of pyrene core and Fc in the multicomponent MOF favors an efficient pseudointramolecular photoinduced electron transfer (PET) process, resulting in significant luminescence quenching. Interestingly, such PET process can be blocked via the quencher displacement initiated by the phosphate analyte, therefore recovering the solid-state luminescence of MOF microcrystals. We found that Fc@NU-1000 is shown as a sensitive solid-state luminescence turn-on probe for phosphate with the naked-eye response at a low content. What's more, this study is the first example of confining a quencher displacement-based RSR system in the MOF framework for solid-state luminescence turn-on sensing, thus also providing new opportunities for MOF materials to develop luminescence turn-on sensors.

Differences in Trainee Evaluations of Faculty by Rater and Ratee Gender.

PURPOSE: To examine whether gender differences exist in medical trainees' (residents' and fellows') evaluations of faculty at a number of clinical departments. METHOD: The authors conducted a single institution (University of Minnesota Medical School) retrospective cohort analysis of 5,071 trainee evaluations of 447 faculty (for which trainee and faculty gender information was available) completed between July 1, 2019, and June 30, 2022. The authors developed and employed a 17-item measure of clinical teaching effectiveness, with 4 dimensions: overall teaching effectiveness, role modeling, facilitating knowledge acquisition, and teaching procedures. Using both between- and within-subject samples, they conducted analyses to examine gender differences among the trainees making ratings (rater effects), the faculty receiving ratings (ratee effects), and whether faculty ratings differed by trainee gender (interaction effects). RESULTS: There was a statistically significant rater effect for the overall teaching effectiveness and facilitating knowledge acquisition dimensions (B = -0.28 and -0.14, 95% CI: [-0.35, -0.21] and [-0.20, -0.09], respectively, P < .001, medium corrected effect sizes between -0.34 and -0.54); female trainees rated male and female faculty lower than male trainees on both dimensions. There also was a statistically significant ratee effect for the overall teaching effectiveness and role modeling dimensions (B = -0.09 and -0.08, 95% CI: [-0.16, -0.02] and [-0.13, -0.04], P = .01 and < .001, respectively, small to medium corrected effect sizes between -0.16 and -0.44); female faculty were rated lower than male faculty on both dimensions. There was not a statistically significant interaction effect. CONCLUSIONS: Female trainees rated faculty lower than male trainees and female faculty were rated lower than male faculty on 2 teaching dimensions each. The authors encourage researchers to continue to examine the reasons for the evaluation differences observed and how implicit bias interventions might help to address them.

L-carnitine alleviates cardiac microvascular dysfunction in diabetic cardiomyopathy by enhancing PINK1-Parkin-dependent mitophagy through the CPT1a-PHB2-PARL pathways.

AIM: To explore the beneficial effects of L-carnitine on cardiac microvascular dysfunction in diabetic cardiomyopathy from the perspectives of mitophagy and mitochondrial integrity. METHODS: Male db/db and db/m mice were randomly assigned to groups and were treated with L-carnitine or a solvent for 24 weeks. Endothelium-specific PARL overexpression was attained via adeno-associated virus serotype 9 (AAV9) transfection. Adenovirus (ADV) vectors overexpressing wild-type CPT1a, mutant CPT1a, or PARL were transfected into endothelial cells exposed to high glucose and free fatty acid (HG/FFA) injury. Cardiac microvascular function, mitophagy, and mitochondrial function were analyzed by immunofluorescence and transmission electron microscopy. Protein expression and interactions were assessed by western blotting and immunoprecipitation. RESULTS: L-carnitine treatment enhanced microvascular perfusion, reinforced endothelial barrier function, repressed the endothelial inflammatory response, and maintained the microvascular structure in db/db mice. Further results demonstrated that PINK1-Parkin-dependent mitophagy was suppressed in endothelial cells suffering from diabetic injury, and these effects were largely alleviated by L-carnitine through the inhibition of PARL detachment from PHB2. Moreover, CPT1a modulated the PHB2-PARL interaction by directly binding to PHB2. The increase in CPT1a activity induced by L-carnitine or amino acid mutation (M593S) enhanced the PHB2-PARL interaction, thereby improving mitophagy and mitochondrial function. In contrast, PARL overexpression inhibited mitophagy and abolished all the beneficial effects of L-carnitine on mitochondrial integrity and cardiac microvascular function. CONCLUSION: L-carnitine treatment enhanced PINK1-Parkin-dependent mitophagy by maintaining the PHB2-PARL interaction via CPT1a, thereby reversing mitochondrial dysfunction and cardiac microvascular injury in diabetic cardiomyopathy.

A Ferritin Nanoparticle-Based Zika Virus Vaccine Candidate Induces Robust Humoral and Cellular Immune Responses and Protects Mice from Lethal Virus Challenge.

The severe consequences of the Zika virus (ZIKV) infections resulting in congenital Zika syndrome in infants and the autoimmune Guillain-Barre syndrome in adults warrant the development of safe and efficacious vaccines and therapeutics. Currently, there are no approved treatment options for ZIKV infection. Herein, we describe the development of a bacterial ferritin-based nanoparticle vaccine candidate for ZIKV. The viral envelope (E) protein domain III (DIII) was fused in-frame at the amino-terminus of ferritin. The resulting nanoparticle displaying the DIII was examined for its ability to induce immune responses and protect vaccinated animals upon lethal virus challenge. Our results show that immunization of mice with a single dose of the nanoparticle vaccine candidate (zDIII-F) resulted in the robust induction of neutralizing antibody responses that protected the animals from the lethal ZIKV challenge. The antibodies neutralized infectivity of other ZIKV lineages indicating that the zDIII-F can confer heterologous protection. The vaccine candidate also induced a significantly higher frequency of interferon (IFN)-γ positive CD4 T cells and CD8 T cells suggesting that both humoral and cell-mediated immune responses were induced by the vaccine candidate. Although our studies showed that a soluble DIII vaccine candidate could also induce humoral and cell-mediated immunity and protect from lethal ZIKV challenge, the immune responses and protection conferred by the nanoparticle vaccine candidate were superior. Further, passive transfer of neutralizing antibodies from the vaccinated animals to naïve animals protected against lethal ZIKV challenge. Since previous studies have shown that antibodies directed at the DIII region of the E protein do not to induce antibody-dependent enhancement (ADE) of ZIKV or other related flavivirus infections, our studies support the use of the zDIII-F nanoparticle vaccine candidate for safe and enhanced immunological responses against ZIKV.