Ov-rich γ-MnO2 enhanced electrocatalytic three-electron oxygen reduction to hydroxyl radicals for sterilization in neutral media.

Marine biofouling severely limits the development of the marine economy, and reactive oxygen species (ROS) produced by electrocatalytic antifouling techniques could inactivate marine microorganisms and inhibit the formation of marine biofouling. Compared with an electro-Fenton reaction, a three-electron oxygen reduction reaction (3e- ORR) could generate a hydroxyl radical (˙OH) in situ without the limitation of pH and iron mud pollutants. Herein, Ov-rich γ-MnO2 is designed to enhance the 3e- ORR performance in neutral media and exhibits excellent sterilization performance for typical marine bacteria. DFT calculation reveals that Ov is beneficial to the "end-on" adsorption and activation of O2, and the Mn site could accept the electrons from *OOH and promote its further reduction to form ˙OH; Ov and Mn sites together guarantee the high 3e- ORR efficiency. In addition, liquid chromatography-tandem mass spectrometry (LC-MS/MS) proves the vast formation of ˙OH in the primary reaction stage, which is the key to sterilization. This work explores the reaction mechanism of the 3e- ORR in neutral media and provides the possibility for the application of electrocatalysis technology in the treatment of marine biofouling pollution.

Progress of Nanomaterials Based on Manganese Dioxide in the Field of Tumor Diagnosis and Therapy.

As a pivotal transition metal oxide, manganese dioxide (MnO2) has garnered significant attention owing to its abundant reserves, diverse crystal structures and exceptional performance. Nanosizing MnO2 results in smaller particle sizes, larger specific surface areas, optimized material characteristics, and expanded application possibilities. With the burgeoning research efforts in this field, MnO2 has emerged as a promising nanomaterial for tumor diagnosis and therapy. The distinctive properties of MnO2 in regulating the tumor microenvironment (TME) have attracted considerable interest, leading to a rapid growth in research on MnO2-based nanomaterials for tumor diagnosis and treatment. Additionally, MnO2 nanomaterials are also gradually showing up in the regulation of chronic inflammatory diseases. In this review, we mainly summarized the recent advancements in various MnO2 nanomaterials for tumor diagnosis and therapy. Furthermore, we discuss the current challenges and future directions in the development of MnO2 nanomaterials, while also envisaging their potential for clinical translation.

Understanding the Adsorption and Diffusion Behaviors of PBUT in Biocompatible MOFs.

With the increasing incidence of chronic kidney disease, the effective control of protein-bound uremic toxins (PBUTs), which are difficult to remove through dialysis, has become a priority. In this study, the adsorption and diffusion behaviors of several metal-organic frameworks (MOFs) for PBUTs (indoxyl sulfate and p-cresyl sulfate) were studied by molecular dynamics (MD) simulations and umbrella sampling. For the NU series of MOFs, good correlations between the Gibbs free energy (ΔG) and the experimental clearance rates of PBUTs are found. For the adsorption behaviors, in terms of ΔG, DAJWET exhibits the best adsorption effect for indoxyl sulfate (IS), whereas NU-1000 shows the best effect for p-cresyl sulfate (pCS). Similar trends observed in the radial distribution function and mean square displacement results suggest that the π-π stacking interactions play a crucial role in the adsorption and diffusion of PBUTs by MOFs. Furthermore, it can be concluded that MOFs with highly conjugated groups (porphyrin rings and pyrene groups) tend to generate more PBUT attraction, and provide design principles for potential MOF candidates in the removal of PBUTs.

Stimulus-Responsive Drug Delivery Nanoplatforms for Inflammatory Bowel Disease Therapy.

Inflammatory bowel disease (IBD) manifests as inflammation in the colon, rectum, and ileum, presenting a global health concern with increasing prevalence. Therefore, effective anti-inflammatory therapy stands as a promising strategy for the prevention and management of IBD. However, conventional nano drug delivery systems (NDDSs) for IBD face many challenges in targeting the intestine, such as physiological and pathological barriers, genetic variants, disease severity, and nutritional status, which often result in nonspecific tissue distribution and uncontrolled drug release. To address these limitations, stimulus-responsive NDDSs have received considerable attention in recent years due to their advantages in providing controlled release and enhanced targeting. This review provides an overview of the pathophysiological mechanisms underlying IBD and summarizes recent advancements in microenvironmental stimulus-responsive nanocarriers for IBD therapy. These carriers utilize physicochemical stimuli such as pH, reactive oxygen species, enzymes, and redox substances to deliver drugs for IBD treatment. Additionally, pivotal challenges in the future development and clinical translation of stimulus-responsive NDDSs are emphasized. By offering insights into the development and optimization of stimulus-responsive drug delivery nanoplatforms, this review aims to facilitate their application in treating IBD. STATEMENT OF SIGNIFICANCE: This review highlights recent advancements in stimulus-responsive nano drug delivery systems (NDDSs) for the treatment of inflammatory bowel disease (IBD). These innovative nanoplatforms respond to specific environmental triggers, such as pH reactive oxygen species, enzymes, and redox substances, to release drugs directly at the inflammation site. By summarizing the latest research, our work underscores the potential of these technologies to improve drug targeting and efficacy, offering new directions for IBD therapy. This review is significant as it provides a comprehensive overview for researchers and clinicians, facilitating the development of more effective treatments for IBD and other chronic inflammatory diseases.

Sphingolipid metabolism and regulated cell death in malignant melanoma.

Malignant melanoma (MM) is a highly invasive and therapeutically resistant skin malignancy, posing a significant clinical challenge in its treatment. Programmed cell death plays a crucial role in the occurrence and progression of MM. Sphingolipids (SP), as a class of bioactive lipids, may be associated with many kinds of diseases. SPs regulate various forms of programmed cell death in tumors, including apoptosis, necroptosis, ferroptosis, and more. This review will delve into the mechanisms by which different types of SPs modulate various forms of programmed cell death in MM, such as their regulation of cell membrane permeability and signaling pathways, and how they influence the survival and death fate of MM cells. An in-depth exploration of the role of SPs in programmed cell death in MM aids in unraveling the molecular mechanisms of melanoma development and holds significant importance in developing novel therapeutic strategies.

A chimeric vaccine derived from Australian genotype IV Japanese encephalitis virus protects mice from lethal challenge.

In 2022, a genotype IV (GIV) strain of Japanese encephalitis virus (JEV) caused an unprecedented and widespread outbreak of disease in pigs and humans in Australia. As no veterinary vaccines against JEV are approved in Australia and all current approved human and veterinary vaccines are derived from genotype (G) III JEV strains, we used the recently described insect-specific Binjari virus (BinJV) chimeric flavivirus vaccine technology to produce a JEV GIV vaccine candidate. Herein we describe the production of a chimeric virus displaying the structural prM and E proteins of a JEV GIV isolate obtained from a stillborn piglet (JEVNSW/22) in the genomic backbone of BinJV (BinJ/JEVNSW/22-prME). BinJ/JEVNSW/22-prME was shown to be antigenically indistinguishable from the JEVNSW/22 parental virus by KD analysis and a panel of JEV-reactive monoclonal antibodies in ELISA. BinJ/JEVNSW/22-prME replicated efficiently in C6/36 cells, reaching titres of >107 infectious units/mL - an important attribute for vaccine manufacture. As expected, BinJ/JEVNSW/22-prME failed to replicate in a variety of vertebrate cells lines. When used to immunise mice, the vaccine induced a potent virus neutralising response against JEVNSW/22 and to GII and GIII JEV strains. The BinJ/JEVNSW/22-prME vaccine provided complete protection against lethal challenge with JEVNSW/22, whilst also providing partial protection against viraemia and disease for the related Murray Valley encephalitis virus. Our results demonstrate that BinJ/JEVNSW/22-prME is a promising vaccine candidate against JEV.

A getah virus-like-particle vaccine provides complete protection from viremia and arthritis in wild-type mice.

Getah virus (GETV) is an emerging mosquito-borne virus with economic impact on the livestock industry in East Asia. In this study, we successfully produced GETV virus-like particles (VLPs) in insect cells using the baculovirus expression vector system. We show that the GETV envelope glycoproteins were successfully expressed at the surface of the insect cell and were glycosylated. VLPs were isolated from the culture fluid as enveloped particles of 60-80 nm in diameter. Two 1 µg vaccinations with this GETV VLP vaccine, without adjuvant, generated neutralizing antibody responses and protected wild-type C57/BL6 mice against GETV viremia and arthritic disease. The GETV VLP vaccine may find application as a horse and/or pig vaccine in the future.

Safety concern of recombination between self-amplifying mRNA vaccines and viruses is mitigated in vivo.

Self-amplifying mRNA (SAM) vaccines can be rapidly deployed in the event of disease outbreaks. A legitimate safety concern is the potential for recombination between alphavirus-based SAM vaccines and circulating viruses. This theoretical risk needs to be assessed in the regulatory process for SAM vaccine approval. Herein, we undertake extensive in vitro and in vivo assessments to explore recombination between SAM vaccine and a wide selection of alphaviruses and a coronavirus. SAM vaccines were found to effectively limit alphavirus co-infection through superinfection exclusion, although some co-replication was still possible. Using sensitive cell-based assays, replication-competent alphavirus chimeras were generated in vitro as a result of rare, but reproducible, RNA recombination events. The chimeras displayed no increased fitness in cell culture. Viable alphavirus chimeras were not detected in vivo in C57BL/6J, Rag1-/- and Ifnar-/- mice, in which high levels of SAM vaccine and alphavirus co-replicated in the same tissue. Furthermore, recombination between a SAM-spike vaccine and a swine coronavirus was not observed. In conclusion we state that although the ability of SAM vaccines to recombine with alphaviruses might be viewed as an environmental safety concern, several key factors substantially mitigate against in vivo emergence of chimeric viruses from SAM vaccine recipients.

Selective lignin arylation for biomass fractionation and benign bisphenols.

Lignocellulose is mainly composed of hydrophobic lignin and hydrophilic polysaccharide polymers, contributing to an indispensable carbon resource for green biorefineries1,2. When chemically treated, lignin is compromised owing to detrimental intra- and intermolecular crosslinking that hampers downstream process3,4. The current valorization paradigms aim to avoid the formation of new C-C bonds, referred to as condensation, by blocking or stabilizing the vulnerable moieties of lignin5-7. Although there have been efforts to enhance biomass utilization through the incorporation of phenolic additives8,9, exploiting lignin's proclivity towards condensation remains unproven for valorizing both lignin and carbohydrates to high-value products. Here we leverage the proclivity by directing the C-C bond formation in a catalytic arylation pathway using lignin-derived phenols with high nucleophilicity. The selectively condensed lignin, isolated in near-quantitative yields while preserving its prominent cleavable ß-ether units, can be unlocked in a tandem catalytic process involving aryl migration and transfer hydrogenation. Lignin in wood is thereby converted to benign bisphenols (34-48 wt%) that represent performance-advantaged replacements for their fossil-based counterparts. Delignified pulp from cellulose and xylose from xylan are co-produced for textile fibres and renewable chemicals. This condensation-driven strategy represents a key advancement complementary to other promising monophenol-oriented approaches targeting valuable platform chemicals and materials, thereby contributing to holistic biomass valorization.

Microplastics dysregulate innate immunity in the SARS-CoV-2 infected lung.

Introduction: Global microplastic (MP) pollution is now well recognized, with humans and animals consuming and inhaling MPs on a daily basis, with a growing body of concern surrounding the potential impacts on human health. Methods: Using a mouse model of mild COVID-19, we describe herein the effects of azide-free 1 µm polystyrene MP beads, co-delivered into lungs with a SARS-CoV-2 omicron BA.5 inoculum. The effect of MPs on the host response to SARS-CoV-2 infection was analysed using histopathology and RNA-Seq at 2 and 6 days post-infection (dpi). Results: Although infection reduced clearance of MPs from the lung, virus titres and viral RNA levels were not significantly affected by MPs, and overt MP-associated clinical or histopathological changes were not observed. However, RNA-Seq of infected lungs revealed that MP exposure suppressed innate immune responses at 2 dpi and increased pro-inflammatory signatures at 6 dpi. The cytokine profile at 6 dpi showed a significant correlation with the 'cytokine release syndrome' signature observed in some COVID-19 patients. Discussion: The findings are consistent with the recent finding that MPs can inhibit phagocytosis of apoptotic cells via binding of Tim4. They also add to a growing body of literature suggesting that MPs can dysregulate inflammatory processes in specific disease settings.

Integrated network toxicology, molecular docking, and in vivo experiments to elucidate molecular mechanism of aflatoxin B1 hepatotoxicity.

Due to the rise in temperature and sea level caused by climate change, the detection rate of aflatoxin B1 (AFB1) in food crops has increased dramatically, and the frequency and severity of aflatoxicosis in humans and animals are also increasing. AFB1 has strong hepatotoxicity, causing severe liver damage and even cancer. However, the mechanism of AFB1 hepatotoxicity remains unclear. By integrating network toxicology, molecular docking and in vivo experiments, this research was designed to explore the potential hepatotoxicity mechanisms of AFB1. Thirty-three intersection targets for AFB1-induced liver damage were identified using online databases. PI3K/AKT1, MAPK, FOXO1 signaling pathways, and apoptosis were significantly enriched. In addition, the proteins of ALB, AKT1, PIK3CG, MAPK8, HSP90AA1, PPARA, MAPK1, EGFR, FOXO1, and IGF1 exhibited good affinity with AFB1. In vivo experiments, significant pathological changes occurred in the liver of mice. AFB1 induction increased the expression levels of EGFR, ERK, and FOXO1, and decreased the expression levsls of PI3K and AKT1. Moreover, AFB1 treatment caused an increase in Caspase3 expression, and a decrease in Bcl2/Bax ratio. By combining network toxicology with in vivo experiments, this study confirms for the first time that AFB1 promotes the FOXO1 signaling pathway by inactivating PI3K/AKT1 and activating EGFR/ERK signaling pathways, hence aggravating hepatocyte apoptosis. This research provides new strategies for studying the toxicity of environmental pollutants and new possible targets for the development of hepatoprotective drugs.

Epitaxial Growth of Two-Dimensional MWW Zeolite.

Two-dimensional (2D) zeolite, with a high aspect ratio, has more open skeletons and accessible active sites than its three-dimensional (3D) counterpart. However, traditional methods of obtaining 2D zeolites often cause structural damage and widespread skeleton defects, hindering efficient selectivity in molecular separation. In this study, we present, for the first time, a direct epitaxial synthesis of 2D zeolite (Epi-MWW) guided by hexagonal boron nitride (h-BN) with a coincidence matching of site lattices to MWW zeolite. The as-grown Epi-MWW zeolite possesses a high crystallinity and intact hexagonal 2D morphology, with an average thickness of 10 nm and an aspect ratio of over 50. Thanks to its excellent molecular accessibility, the diffusion time constants of o-xylene (OX) and p-xylene (PX) are as 12 and 133 times higher than those of conventional MCM-22, respectively; the PX/OX selectivity of Epi-MWW is 7.4 times better than MCM-22 as calculated by the ideal adsorbed solution theory.

SARS-CoV-2 omicron BA.5 and XBB variants have increased neurotropic potential over BA.1 in K18-hACE2 mice and human brain organoids.

The reduced pathogenicity of the omicron BA.1 sub-lineage compared to earlier variants is well described, although whether such attenuation is retained for later variants like BA.5 and XBB remains controversial. We show that BA.5 and XBB isolates were significantly more pathogenic in K18-hACE2 mice than a BA.1 isolate, showing increased neurotropic potential, resulting in fulminant brain infection and mortality, similar to that seen for original ancestral isolates. BA.5 also infected human cortical brain organoids to a greater extent than the BA.1 and original ancestral isolates. In the brains of mice, neurons were the main target of infection, and in human organoids neuronal progenitor cells and immature neurons were infected. The results herein suggest that evolving omicron variants may have increasing neurotropic potential.

Rapid inactivation and sample preparation for SARS-CoV-2 PCR-based diagnostics using TNA-Cifer Reagent E.

RT-qPCR remains a key diagnostic methodology for COVID-19/SARS-CoV-2. Typically, nasal or saliva swabs from patients are placed in virus transport media (VTM), RNA is extracted at the pathology laboratory, and viral RNA is measured using RT-qPCR. In this study, we describe the use of TNA-Cifer Reagent E in a pre-clinical evaluation study to inactivate SARS-CoV-2 as well as prepare samples for RT-qPCR. Adding 1 part TNA-Cifer Reagent E to 5 parts medium containing SARS-CoV-2 for 10 min at room temperature inactivated the virus and permitted RT-qPCR detection. TNA-Cifer Reagent E was compared with established column-based RNA extraction and purification methodology using a panel of human clinical nasal swab samples (n = 61), with TNA-Cifer Reagent E showing high specificity (100%) and sensitivity (97.37%). Mixtures of SARS-CoV-2 virus and TNA-Cifer Reagent E could be stored for 3 days at room temperature or for 2 weeks at 4°C without the loss of RT-qPCR detection sensitivity. The detection sensitivity was preserved when TNA-Cifer Reagent E was used in conjunction with a range of VTM for saliva samples but only PBS (Gibco) and Amies Orange for nasal samples. Thus, TNA-Cifer Reagent E improves safety by rapidly inactivating the virus during sample processing, potentially providing a safe means for molecular SARS-CoV-2 testing outside traditional laboratory settings. The reagent also eliminates the need for column-based and/or automated viral RNA extraction/purification processes, thereby providing cost savings for equipment and reagents, as well as reducing processing and handling times.

A novel metallothionein gene HcMT from halophyte shrub Halostachys caspica respond to cadmium and sodium stress.

Cadmium (Cd) and sodium (Na) are two of the most phytotoxic metallic elements causing environmental and agricultural problems. Metallothioneins (MTs) play an important role in the adaptation to abiotic stress. We previously isolated a novel type 2 MT gene from Halostachys caspica (H. caspica), named HcMT, which responded to metal and salt stress. To understand the regulatory mechanisms controlling HcMT expression, we cloned the HcMT promoter and characterized its tissue-specific and spatiotemporal expression patterns. ß-Glucuronidase (GUS) activity analysis showed that the HcMT promoter was responsive to CdCl2, CuSO4, ZnSO4 and NaCl stress. Therefore, we further investigated the function of HcMT under abiotic stress in yeast and Arabidopsis thaliana (Arabidopsis). In CdCl2, CuSO4 or ZnSO4 stress, HcMT significantly enhanced the metal ions tolerance and accumulation in yeast through function as a metal chelator. Moreover, the HcMT protein also protected yeast cells from NaCl, PEG and hydrogen peroxide (H2O2) toxicity with less effectiveness. However, transgenic Arabidopsis carrying HcMT gene only displayed tolerance to CdCl2 and NaCl, accompanying by higher content of Cd2+ or Na+ and lower H2O2, compared to wild-type (WT) plants. Next, we demonstrated that the recombinant HcMT protein has the ability to bind Cd2+ and the potential of scavenging ROS (reactive oxygen species) in vitro. This result further confirmed that the role of HcMT to influence plants to CdCl2 and NaCl stress may bind metal ions and scavenge ROS. Overall, we described the biological functions of HcMT and developed a metal- and salt-inducible promoter system for using in genetic engineering.

Computer-aided shape features extraction and regression models for predicting the ascending aortic aneurysm growth rate.

OBJECTIVE: ascending aortic aneurysm growth prediction is still challenging in clinics. In this study, we evaluate and compare the ability of local and global shape features to predict the ascending aortic aneurysm growth. MATERIAL AND METHODS: 70 patients with aneurysm, for which two 3D acquisitions were available, are included. Following segmentation, three local shape features are computed: (1) the ratio between maximum diameter and length of the ascending aorta centerline, (2) the ratio between the length of external and internal lines on the ascending aorta and (3) the tortuosity of the ascending tract. By exploiting longitudinal data, the aneurysm growth rate is derived. Using radial basis function mesh morphing, iso-topological surface meshes are created. Statistical shape analysis is performed through unsupervised principal component analysis (PCA) and supervised partial least squares (PLS). Two types of global shape features are identified: three PCA-derived and three PLS-based shape modes. Three regression models are set for growth prediction: two based on gaussian support vector machine using local and PCA-derived global shape features; the third is a PLS linear regression model based on the related global shape features. The prediction results are assessed and the aortic shapes most prone to growth are identified. RESULTS: the prediction root mean square error from leave-one-out cross-validation is: 0.112 mm/month, 0.083 mm/month and 0.066 mm/month for local, PCA-based and PLS-derived shape features, respectively. Aneurysms close to the root with a large initial diameter report faster growth. CONCLUSION: global shape features might provide an important contribution for predicting the aneurysm growth.

Protection of taraxasterol against acetaminophen-induced liver injury elucidated through network pharmacology and in vitro and in vivo experiments.

BACKGROUND: Drug-induced liver injury (DILI) is primarily caused by drugs or their metabolites. Acetaminophen (APAP) is an over-the-counter antipyretic analgesic that exhibits high hepatotoxicity when used for long-term or in overdoses. Taraxasterol is a five-ring triterpenoid compound extracted from traditional Chinese medicinal herb Taraxacum officinale. Our previous studies have demonstrated that taraxasterol exerts protective effects on alcoholic and immune liver injuries. However, the effect of taraxasterol on DILI remains unclear. HYPOTHESIS/PURPOSE: This study aimed to elucidate the effects and mechanisms of action of taraxasterol on APAP-induced liver injury using network pharmacology and in vitro and in vivo experiments. METHODS: Online databases of drug and disease targets were used to screen the targets of taraxasterol and DILI, and a protein-protein interaction network (PPI) was constructed. Core target genes were identified using the tool of Analyze of Cytoscape, gene ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) enrichment analyses were performed. Oxidation, inflammation and apoptosis were evaluated to determine the effect of taraxasterol on APAP-stimulated liver damage in AML12 cells and mice. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blotting were used to explore the potential mechanisms of taraxasterol against DILI. RESULTS: Twenty-four intersection targets for taraxasterol and DILI were identified. Among them, 9 core targets were identified. GO and KEGG analysis showed that core targets are closely related to oxidative stress, apoptosis, and inflammatory response. The in vitro findings showed that taraxasterol alleviated mitochondrial damage in AML12 cells treated with APAP. The in vivo results revealed that taraxasterol alleviated pathological changes in the livers of mice treated with APAP and inhibited the activity of serum transaminases. Taraxasterol increased the activity of antioxidants, inhibited the production of peroxides, and reduced inflammatory response and apoptosis in vitro and in vivo. Taraxasterol promoted Nrf2 and HO-1 expression, suppressed JNK phosphorylation, and decreased the Bax/Bcl-2 ratio and caspase-3 expression in AML12 cells and mice. CONCLUSION: By integrating network pharmacology with in vitro and in vivo experiments, this study indicated that taraxasterol inhibits APAP-stimulated oxidative stress, inflammatory response and apoptosis in AML12 cells and mice by regulating the Nrf2/HO-1 pathway, JNK phosphorylation, and apoptosis-related protein expression. This study provides a new evidence for the use of taraxasterol as a hepatoprotective drug.

Comparative Efficacy of Mayaro Virus-Like Particle Vaccines Produced in Insect or Mammalian Cells.

Mayaro virus (MAYV) is a mosquito-transmitted alphavirus that causes often debilitating rheumatic disease in tropical Central and South America. There are currently no licensed vaccines or antiviral drugs available for MAYV disease. Here, we generated Mayaro virus-like particles (VLPs) using the scalable baculovirus-insect cell expression system. High-level secretion of MAYV VLPs in the culture fluid of Sf9 insect cells was achieved, and particles with a diameter of 64 to 70 nm were obtained after purification. We characterize a C57BL/6J adult wild-type mouse model of MAYV infection and disease and used this model to compare the immunogenicity of VLPs from insect cells with that of VLPs produced in mammalian cells. Mice received two intramuscular immunizations with 1 µg of nonadjuvanted MAYV VLPs. Potent neutralizing antibody responses were generated against the vaccine strain, BeH407, with comparable activity seen against a contemporary 2018 isolate from Brazil (BR-18), whereas neutralizing activity against chikungunya virus was marginal. Sequencing of BR-18 illustrated that this virus segregates with genotype D isolates, whereas MAYV BeH407 belongs to genotype L. The mammalian cell-derived VLPs induced higher mean neutralizing antibody titers than those produced in insect cells. Both VLP vaccines completely protected adult wild-type mice against viremia, myositis, tendonitis, and joint inflammation after MAYV challenge. IMPORTANCE Mayaro virus (MAYV) is associated with acute rheumatic disease that can be debilitating and can evolve into months of chronic arthralgia. MAYV is believed to have the potential to emerge as a tropical public health threat, especially if it develops the ability to be efficiently transmitted by urban mosquito vectors, such as Aedes aegypti and/or Aedes albopictus. Here, we describe a scalable virus-like particle vaccine against MAYV that induced neutralizing antibodies against a historical and a contemporary isolate of MAYV and protected mice against infection and disease, providing a potential new intervention for MAYV epidemic preparedness.

Assessment of shape-based features ability to predict the ascending aortic aneurysm growth.

The current guidelines for the ascending aortic aneurysm (AsAA) treatment recommend surgery mainly according to the maximum diameter assessment. This criterion has already proven to be often inefficient in identifying patients at high risk of aneurysm growth and rupture. In this study, we propose a method to compute a set of local shape features that, in addition to the maximum diameter D, are intended to improve the classification performances for the ascending aortic aneurysm growth risk assessment. Apart from D, these are the ratio DCR between D and the length of the ascending aorta centerline, the ratio EILR between the length of the external and the internal lines and the tortuosity T. 50 patients with two 3D acquisitions at least 6 months apart were segmented and the growth rate (GR) with the shape features related to the first exam computed. The correlation between them has been investigated. After, the dataset was divided into two classes according to the growth rate value. We used six different classifiers with input data exclusively from the first exam to predict the class to which each patient belonged. A first classification was performed using only D and a second with all the shape features together. The performances have been evaluated by computing accuracy, sensitivity, specificity, area under the receiver operating characteristic curve (AUROC) and positive (negative) likelihood ratio LHR+ (LHR-). A positive correlation was observed between growth rate and DCR (r = 0.511, p = 1.3e-4) and between GR and EILR (r = 0.472, p = 2.7e-4). Overall, the classifiers based on the four metrics outperformed the same ones based only on D. Among the diameter-based classifiers, k-nearest neighbours (KNN) reported the best accuracy (86%), sensitivity (55.6%), AUROC (0.74), LHR+ (7.62) and LHR- (0.48). Concerning the classifiers based on the four shape features, we obtained the best accuracy (94%), sensitivity (66.7%), specificity (100%), AUROC (0.94), LHR+ (+∞) and LHR- (0.33) with support vector machine (SVM). This demonstrates how automatic shape features detection combined with risk classification criteria could be crucial in planning the follow-up of patients with ascending aortic aneurysm and in predicting the possible dangerous progression of the disease.