RESUMEN
BACKGROUND: Japanese encephalitis virus (JEV) remains a predominant cause of Japanese encephalitis (JE) globally. Its infection is usually accompanied by disrupted bloodâbrain barrier (BBB) integrity and central nervous system (CNS) inflammation in a poorly understood pathogenesis. Productive JEV infection in brain microvascular endothelial cells (BMECs) is considered the initial event of the virus in penetrating the BBB. Type I/III IFN and related factors have been described as negative regulators in CNS inflammation, whereas their role in JE remains ambiguous. METHODS: RNA-sequencing profiling (RNA-seq), real-time quantitative PCR, enzyme-linked immunosorbent assay, and Western blotting analysis were performed to analyze the gene and protein expression changes between mock- and JEV-infected hBMECs. Bioinformatic tools were used to cluster altered signaling pathway members during JEV infection. The shRNA-mediated immune factor-knockdown hBMECs and the in vitro transwell BBB model were utilized to explore the interrelation between immune factors, as well as between immune factors and BBB endothelial integrity. RESULTS: RNA-Seq data of JEV-infected hBMECs identified 417, 1256, and 2748 differentially expressed genes (DEGs) at 12, 36, and 72 h post-infection (hpi), respectively. The altered genes clustered into distinct pathways in gene ontology (GO) terms and KEGG pathway enrichment analysis, including host antiviral immune defense and endothelial cell leakage. Further investigation revealed that pattern-recognition receptors (PRRs, including TLR3, RIG-I, and MDA5) sensed JEV and initiated IRF/IFN signaling. IFNs triggered the expression of interferon-induced proteins with tetratricopeptide repeats (IFITs) via the JAK/STAT pathway. Distinct PRRs exert different functions in barrier homeostasis, while treatment with IFN (IFN-ß and IFN-λ1) in hBMECs stabilizes the endothelial barrier by alleviating exogenous destruction. Despite the complex interrelationship, IFITs are considered nonessential in the IFN-mediated maintenance of hBMEC barrier integrity. CONCLUSIONS: This research provided the first comprehensive description of the molecular mechanisms of hostâpathogen interplay in hBMECs responding to JEV invasion, in which type I/III IFN and related factors strongly correlated with regulating the hBMEC barrier and restricting JEV infection. This might help with developing an attractive therapeutic strategy in JE.
Asunto(s)
Virus de la Encefalitis Japonesa (Especie) , Virus de la Encefalitis Japonesa (Subgrupo) , Encefalitis Japonesa , Interferón Tipo I , Humanos , Encefalitis Japonesa/genética , Barrera Hematoencefálica , Interferón lambda , Células Endoteliales , Quinasas Janus , Factores de Transcripción STAT , Transducción de Señal , InflamaciónRESUMEN
Duck Tembusu virus (DTMUV) is an infectious disease that emerged in China in 2010. It has caused serious economic losses to the poultry industry and may pose a threat to public health. We aimed to develop a new Bacillus subtilis (B. subtilis)-based oral vaccine to control DTMUV transmission among poultry; to this end, we constructed a B. subtilis strain that can secrete DTMUV E protein. Ducklings were orally immunized, and serum antibodies, mucosal antibodies, and splenic cytokines were detected. The results showed that, in addition to high levels of specific IgG, there were also high levels of specific secretory immunoglobulin A (sIgA) in ducklings orally treated with recombinant B. subtilis. In addition, the levels of IFN-γ, IL-2, IL-4, and IL-10 in spleens were significantly boosted by recombinant B. subtilis. Recombinant B. subtilis could effectively enhance ducklings resistance to DTMUV and significantly reduce viral load (p<0.01), along with pathological damage in the brain, heart, and spleen. This is the first study to apply a B. subtilis live-vector vaccine platform for DTMUV disease prevention and control, and our results suggest that B. subtilis expressing DTMUV E protein may be a candidate vaccine against DTMUV.
Asunto(s)
Bacillus , Infecciones por Flavivirus , Enfermedades de las Aves de Corral , Vacunas , Animales , Bacillus subtilis , Infecciones por Flavivirus/prevención & control , Infecciones por Flavivirus/veterinaria , Patos , Anticuerpos Antivirales , Factores de TranscripciónRESUMEN
The crystal structure of 2,4,6,8,10,12-hexanitro-2,4,6,8,10,12-hexaazaiso-wurtzitane (CL-20) p-xylene solvate, and the solvent effects on the crystal faces of CL-20 were studied through a combined experimental and theoretical method. The properties were analyzed by thermogravimetry-differential scanning calorimetry (TG-DSC), Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD).The growth morphology of CL-20p-xylene solvate crystal was predicted with a modified attachment energy model. The crystal structure of CL-20p-xylene solvate belonged to the Pbca space group with the unit cell parameters, a=8.0704(12) Å, b=13.4095(20) Å, c=33.0817(49) Å, and Z=4, which indicated that the p-xylene solvent molecules could enter the crystal lattice of CL-20 and thus the CL-20 p-xylene solvate is formed. According to the solvent-effected attachment energy calculations, (002) and (11-1) faces should not be visible at all, while the percentage area of the (011) face could be increased from 7.81% in vacuum to 12.51% in p-xylene solution. The predicted results from the modified attachment energy model agreed very well with the observed morphology of crystals grown from p-xylene solution.
Asunto(s)
Compuestos Aza/química , Compuestos Heterocíclicos/química , Modelos Moleculares , Xilenos/química , Cristalografía por Rayos X , Espectroscopía Infrarroja por Transformada de FourierRESUMEN
Artificial moiré superlattices created by stacking 2D crystals have emerged as a powerful platform with unprecedented material-engineering capabilities. While moiré superlattices are reported to host a number of novel quantum states, their potential for spintronic applications remains largely unexplored. Here, the effective manipulation of spin-orbit torque (SOT) is demonstrated using moiré superlattices in ferromagnetic devices comprised of twisted WS2/WS2 homobilayer (t-WS2) and CoFe/Pt thin films by altering twisting angle (θ) and gate voltage. Notably, a substantial enhancement of up to 44.5% is observed in SOT conductivity at θ ≈ 8.3°. Furthermore, compared to the WS2 monolayer and untwisted WS2/WS2 bilayers, the moiré superlattices in t-WS2 enable a greater gate-voltage tunability of SOT conductivity. These results are related to the generation of the interfacial moiré magnetic field by the real-space Berry phase in moiré superlattices, which modulates the absorption of the spin-Hall current arising from Pt through the magnetic proximity effect. This study highlights the moiré physics as a new building block for designing enhanced spintronic devices.
RESUMEN
The S. Enteritidis causes serious economic losses to the poultry industry every year. Vaccines that induce a mucosal immune response may be successful against an S. Enteritidis infection because mucosa plays an important role in preventing S. Enteritidis from entering the body. In order to develop novel and potent oral vaccines based on Bacillus subtilis (B. subtilis) to control the spread of S. Enteritidis in the poultry industry, we constructed a B. subtilis that can secrete a multi-epitope protein (OmpC-FliC-SopF-SseB-IL-18). Oral immunization of chickens was performed, and serum antibodies, mucosal antibodies, specific cellular immunity and serum cytokines were detected. Immunizing chicks with S. Enteritidis was evaluated. The results showed high levels of specific IgG in addition to high levels of specific secretory immunoglobulin A (sIgA) in chickens who received oral administrations of recombinant B. subtilis. Additionally, recombinant B. subtilis may significantly increase the levels of IL-2 and T cell-mediated immunity. Recombinant B. subtilis effectively protected chickens against S. Enteritidis and reduced pathological damage to the spleen and jejunum. Our study's outcomes indicate that the expression of the multi-epitope protein OmpC-FliC-SopF-SseB-IL-18 by B. subtilis could generate a mucosal vaccine candidate for animals to defend against S. Enteritidis in the future.
Asunto(s)
Enfermedades de las Aves de Corral , Salmonelosis Animal , Vacunas contra la Salmonella , Animales , Salmonella enteritidis , Bacillus subtilis , Interleucina-18 , Epítopos , Pollos , Administración Oral , Inmunidad Mucosa , Salmonelosis Animal/prevención & control , Enfermedades de las Aves de Corral/prevención & controlRESUMEN
Salmonellosis causes massive economic losses globally every year. Especially in poultry, numerous drug-resistant bacteria have emerged; thus, it is imperative to find alternatives to antibiotics. As a probiotic, Clostridium butyricum (C. butyricum) provides the latest strategy for inhibiting the proliferation of Salmonella. This study aimed to evaluate the effects of C. butyricum on intestinal environment and gut microbiome under Salmonella infection. In this study, we modeled the infection of Salmonella using specific pathogen-free (SPF) chicks and found that the use of C. butyricum directly reduced the number of Salmonella colonizations in the spleen and liver. It also alleviated the histopathological changes of the liver, spleen, and cecum caused by Salmonella Enteritidis (S. Enteritidis). In addition, S. Enteritidis increased the expression of pro-inflammatory IL-6 in the cecum on day 6 postinfection. Interestingly, we found that C. butyricum changed PPAR-γ transcript levels in the cecum on day 6 postinfection. Analysis of the chick gastrointestinal microbiome showed that Salmonella infection increased the relative abundance of Subdoligranulum variabile. Further analysis found that Salmonella challenge significantly reduced the relative abundance of Faecalibacterium prausnitzii and C. butyricum increased the relative abundance of anaerobic bacteria in the gut on day 6 postinfection. Moreover, early supplementation of C. butyricum restored the epithelial hypoxia in S. Enteritidis infection in chicks. The results suggest that C. butyricum restores epithelial hypoxia caused by S. Enteritidis, improves the stability of intestinal flora, and inhibits the proliferation of Salmonella.
Asunto(s)
Clostridium butyricum , Microbioma Gastrointestinal , Enfermedades de las Aves de Corral , Salmonelosis Animal , Animales , Salmonelosis Animal/microbiología , Pollos , Enfermedades de las Aves de Corral/microbiología , Salmonella enteritidis , Ciego/microbiología , Hipoxia/veterinariaRESUMEN
Proteus mirabilis, an opportunistic pathogen, is found to be an emerging threat to both animals and humans for a variety of infections. However, the characteristics of P. mirabilis infections from foxes, raccoons and minks remain unclear. In this context, we identified the antibiotic resistance genes and virulence genes of P. mirabilis isolates from foxes, raccoons and minks in China. Most isolates showed resistance to florfenicol (90.57%), trimethoprim-sulfamethoxazole (73.58%), and imipenem (71.70%). A total of 73.58% of isolates were resistant to antibiotics from at least three or more classes, and were categorized as multi-drug resistant. A total of 33.33% of the isolates were resistant to antibiotics from seven classes. The most prevalent resistant were sul1 (94.34%), followed by floR, blaTEM, aac(6')Ib-cr and blaOXA-1 with the detection rate of 88.68%, 83.02%, 71.70% and 60.38%, respectively. Among the 51 P. mirabilis isolates that were resistant to beta-lactam antibiotics, all isolates carried at least one beta-lactam gene. In addition, blaNDM and blaOXA-24 genes were firstly reported in carbapenem-resistant P. mirabilis isolates from foxes, raccoons and minks. All isolates exhibited the virulence genes ureC, zapA, pmfA, atfA and mrpA. P. mirabilis isolates carrying all detected 10 virulence genes from different animal species showed different lethal abilities in a G. mellonella larvae model. More importantly, the profiles of antibiotic resistance genes of isolates from fur animals and the environment were generally similar, and phylogenetic analysis showed that the P. mirabilis isolates from farm environment samples may have close relatedness with that from animals.
RESUMEN
Nanodoping is an effective way to improve the dielectric properties and the aging resistance of polyethylene. Nano-zeolite has a nano-level porous structure and larger specific surface area than ordinary nano-inorganic oxide, which can be used to improve dielectric properties of low-density polyethylene (LDPE) nanocomposite. The zeolite/LDPE nanocomposites were prepared and subjected to thermal aging treatment to obtain samples with different aging time. Using scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR) and the differential scanning calorimetry (DSC) test to study the microscopic and structure characteristics, it was found that nano-zeolite doping can effectively reduce the thermal aging damage to the internal structure of the nanocomposite; carbonyl and hydroxyl decreased significantly during the thermal aging time, and the crystallinity effectively improved. Nano-zeolite doping significantly improved the morphology and strengthened the aging resistance of the nanocomposite. In the dielectric strength test, it was found that nanodoping can effectively improve the direct current (DC) and alternating current (AC) breakdown field strength and the stability after the thermal aging. The dielectric constant of nanocomposite can be reduced, and the dielectric loss had no obvious change during the aging process. Moreover, the zeolite/LDPE nanocomposite with the doping concentration of 1 wt % had the best performance, for the nano-zeolite was better dispersed.
RESUMEN
Bacillus subtilis is widely used as a probiotic in various fields as it regulates intestinal flora, improves animal growth performance, enhances body immunity, has short fermentation cycle, and is economic. With the rapid development of DNA recombination technology, B. subtilis has been used as a potential vaccine expression vector for the treatment and prevention of various diseases caused by bacteria, viruses, and parasites as it can effectively trigger an immune response in the body. In this review, we refer to previous literature and provide a comprehensive analysis and overview of the feasibility of using B. subtilis as a vaccine expression vector, with an aim to provide a valuable reference for the establishment of efficient vaccines.
Asunto(s)
Microbioma Gastrointestinal , Probióticos , Animales , Bacillus subtilis/genética , Fermentación , Vacunas AtenuadasRESUMEN
The interface area of nano-dielectric is generally considered to play an important role in improving dielectric properties, especially in suppressing space charge. In order to study the role of interface area on a microscopic scale, the natural charge and injected charge movement and diffusion on the surface of pure LDPE and SiO2/LDPE nanocomposite were observed and studied by gradual discharge under electrostatic force microscope (EFM). It was detected that the charge in SiO2/LDPE nanocomposite moved towards the interface area and was captured, which indicates that the charge was trapped in the interface area and formed a barrier to the further injection of charge and improving the dielectric performance as a result. Moreover, pulsed electro-acoustic (PEA) short-circuited test after charge injection was carried out, and the change of total charge was calculated. The trend of charge decay in the EFM test is also generally consistent with that in PEA short-circuit test and can be used to verify one another. The results revealed the law of charge movement and verified the interface area can inhibit space charge injection in nano-dielectric at the microscale, which provides an experimental reference for relevant theoretical research.