RESUMO
Porcine deltacoronavirus (PDCoV), a novel enteropathogenic coronavirus, causes diarrhea mainly in suckling piglets and has the potential to infect humans. Whereas, there is no commercially available vaccine which can effectively prevent this disease. In this study, to ascertain the duration of immune protection of inactivated PDCoV vaccine, suckling piglets were injected subcutaneously with inactivated PDCoV vaccine using a prime/boost strategy at 3 and 17-day-old. Neutralizing antibody assay showed that the level of the inactivated PDCoV group was still ≥1:64 at three months after prime vaccination. The three-month-old pigs were orally challenged with PDCoV strain CZ2020. Two pigs in challenge control group showed mild to severe diarrhea at 10-11 day-post-challenge (DPC), while the inactivated PDCoV group had no diarrhea. High levels of viral shedding, substantial intestinal villus atrophy, and positive straining of viral antigens in ileum were detected in challenge control group, while the pigs in inactivated PDCoV group exhibited significantly reduced viral load, minor intestinal villi damage and negative straining of viral antigens. These results demonstrated that PDCoV was pathogenic against three-month-old pigs and inactivated PDCoV vaccine can provide effective protection in pigs lasting for three months.
Assuntos
Anticorpos Neutralizantes , Anticorpos Antivirais , Infecções por Coronavirus , Diarreia , Doenças dos Suínos , Vacinas de Produtos Inativados , Vacinas Virais , Eliminação de Partículas Virais , Animais , Anticorpos Neutralizantes/sangue , Anticorpos Neutralizantes/imunologia , Vacinas de Produtos Inativados/imunologia , Vacinas de Produtos Inativados/administração & dosagem , Suínos , Doenças dos Suínos/prevenção & controle , Doenças dos Suínos/imunologia , Doenças dos Suínos/virologia , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Vacinas Virais/imunologia , Vacinas Virais/administração & dosagem , Infecções por Coronavirus/prevenção & controle , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/veterinária , Diarreia/prevenção & controle , Diarreia/imunologia , Diarreia/virologia , Vacinação , Coronavirus/imunologia , Carga Viral , Antígenos Virais/imunologiaRESUMO
Porcine deltacoronavirus (PDCoV) is an emergent enteric coronavirus, primarily inducing diarrhea in swine, particularly in nursing piglets, with the additional potential for zoonotic transmission to humans. Despite the significant impact of PDCoV on swine populations, its pathogenic mechanisms remain incompletely understood. Complement component 3 (C3) plays a pivotal role in the prevention of viral infections, however, there are no reports concerning the influence of C3 on the proliferation of PDCoV. In this study, we initially demonstrated that PDCoV is capable of activating the C3 and eliciting inflammatory responses. The overexpression of C3 significantly suppressed PDCoV replication, while inhibition of C3 expression facilitated PDCoV replication. We discovered that nonstructural proteins Nsp7, Nsp14, and M, considerably stimulated C3 expression, particularly Nsp14, through activation of the p38-MAPK-C/EBP-ß pathway. The N7-MTase constitutes a significant functional domain of the non-structural protein Nsp14, which is more obvious to upregulate C3. Furthermore, functional mutants of the N7-MTase domain suggested that the D44 and T135 of N7-Mtase constituted a pivotal amino acid site to promote C3 expression. This provides fresh insights into comprehending how the virus manipulates the host immune response and suggests potential antiviral strategies against PDCoV.
Assuntos
Complemento C3 , Deltacoronavirus , Proteínas não Estruturais Virais , Replicação Viral , Proteínas Quinases p38 Ativadas por Mitógeno , Animais , Complemento C3/genética , Complemento C3/metabolismo , Complemento C3/imunologia , Proteínas não Estruturais Virais/metabolismo , Proteínas não Estruturais Virais/genética , Suínos , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/genética , Deltacoronavirus/genética , Doenças dos Suínos/virologia , Doenças dos Suínos/genética , Infecções por Coronavirus/virologia , Infecções por Coronavirus/veterinária , Infecções por Coronavirus/imunologia , Sistema de Sinalização das MAP Quinases , Humanos , Proteína beta Intensificadora de Ligação a CCAAT/metabolismo , Proteína beta Intensificadora de Ligação a CCAAT/genéticaRESUMO
Stress granules (SGs), the main component is GTPase-activating protein-binding protein 1 (G3BP1), which are assembled during viral infection and function to sequester host and viral mRNAs and proteins, are part of the antiviral responses. In this study, we found that porcine deltacoronavirus (PDCoV) infection induced stable formation of robust SGs in cells through a PERK (protein kinase R-like endoplasmic reticulum kinase)-dependent mechanism. Overexpression of SGs marker proteins G3BP1 significantly reduced PDCoV replication in vitro, while inhibition of endogenous G3BP1 enhanced PDCoV replication. Moreover, PDCoV infected LLC-PK1 cells raise the phosphorylation level of G3BP1. By overexpression of the G3BP1 phosphorylated protein or the G3BP1 dephosphorylated protein, we found that phosphorylation of G3BP1 is involved in the regulation of PDCoV-induced inflammatory response. Taken together, our study presents a vital aspect of the host innate response to invading pathogens and reveals attractive host targets for antiviral target.
Assuntos
DNA Helicases , Inflamação , Proteínas de Ligação a Poli-ADP-Ribose , RNA Helicases , Proteínas com Motivo de Reconhecimento de RNA , Animais , Suínos , Proteínas com Motivo de Reconhecimento de RNA/genética , Proteínas com Motivo de Reconhecimento de RNA/metabolismo , Fosforilação , Proteínas de Ligação a Poli-ADP-Ribose/metabolismo , Proteínas de Ligação a Poli-ADP-Ribose/genética , RNA Helicases/metabolismo , RNA Helicases/genética , DNA Helicases/metabolismo , DNA Helicases/genética , Replicação Viral , Coronavirus/imunologia , Coronavirus/fisiologia , Linhagem Celular , Doenças dos Suínos/virologia , Doenças dos Suínos/imunologia , Doenças dos Suínos/genética , Imunidade InataRESUMO
Tissue-engineered ear cartilage scaffold based on three-dimensional (3D) bioprinting technology presents a new strategy for ear reconstruction in individuals with microtia. Natural hydrogel is a promising material due to its excellent biocompatibility and low immunogenicity. However, insufficient mechanical property required for cartilage is one of the major issues pending to be solved. In this study, the gelatin methacryloyl (GelMA) hydrogel reinforced with bacterial nanocellulose (BNC) was developed to enhance the biomechanical properties and printability of the hydrogel. The results revealed that the addition of 0.375% BNC significantly increased the mechanical properties of the hydrogel and promoted cell migration in the BNC-reinforced hydrogel. Constructs bioprinted with chondrocyte-laden BNC/GelMA hydrogel bio-ink formed mature cartilage in nude mice with higher Young's modulus and glycosaminoglycan content. Finally, an auricle equivalent with a precise shape, high mechanics, and abundant cartilage-specific matrix was developed in vivo. In this study, we developed a potentially useful hydrogel for the manufacture of auricular cartilage grafts for microtia patients.
RESUMO
The growing application domain of energy storage devices (ESDs) is leading research to temperature tolerant supercapacitors. To realize reliable and safe devices, high modulus solid electrolytes are favored by most researchers. However, the inferior infiltrating ability of such electrolytes usually results in poor electrochemical performances of the ESDs. Herein, we adopted a hierarchical optimization strategy to address the aforementioned interfacial issues. Continuous ionic percolation throughout the hierarchical pores of the 3D electrode was formed by in-situ introducing an ionogel buffer layer. Benefiting from this, the rate of ions diffusing within electrodes was increased by 5 times. Furthermore, the kinetics of ions entering into nanopores was improved via introducing small size ions into ionic liquids (ILs) and adjusting the solvated structures. Both the capacity and rate performance of the electrochemical double layer capacitors (EDLCs) were improved. Additionally, the buffer layer exhibited sufficient thermostability to cooperate with poly(ether ether ketone) (PEEK)-based solid electrolyte. Consequently, the EDLCs exhibited excellent cycling stability (79% capacitance retention after 5000 cycles) at 120 °C and delivered a maximum energy density of 46.9 Wh kg-1 with a power density of 926.9 W kg-1. Our strategy is believed to be effective to cooperate with various solid electrolyte systems and offer a general design principle for durable and high performance EDLCs.
RESUMO
Inter-annual dynamics of grassland yield of the Three Rivers Headwaters Region of Qinghai-Tibet Plateau of China in 1988-2005 was analyzed using the GLO-PEM model, and the herbage supply function was evaluated. The results indicate that while grassland yield in the region showed marked inter-annual fluctuation there was a trend of increased yield over the 18 years of the study. This increase was especially marked for Alpine Desert and Alpine Steppe and in the west of the region. The inter-annual coefficient of variation of productivity increased from the east to the west of the region and from Marsh, Alpine Meadow, Alpine Steppe, Temperate Steppe to Alpine Desert grasslands. Climate change, particularly increased temperatures in the region during the study period, is suggested to be the main cause of increased grassland yield. However, reduced grazing pressure and changes to the seasonal pattern of grazing could also have influenced the grassland yield trend. These findings indicate the importance of understanding the function of the grassland ecosystems in the region and the effect of climate change on them especially in regard to their use to supply forage for animal production. Reduction of grazing pressure, especially during winter, is indicated to be critical for the restoration and sustainable use of grassland ecosystems in the region.
Assuntos
Mudança Climática , Poaceae/crescimento & desenvolvimento , China , Ecossistema , Monitoramento Ambiental , Modelos Teóricos , RiosRESUMO
Increasing heatwave and drought events can potentially alter the carbon cycle. Few studies have investigated the impacts of hundred-year return heatwaves and droughts, as those events are rare. In the summer of 2013, southern China experienced its strongest drought and heatwave on record for the past 113 years. We show that the record-breaking heatwave and drought lasted two months (from July to August), significantly reduced the satellite-based vegetation index and gross primary production, substantially altered the regional carbon cycle, and produced the largest negative crop yield anomaly since 1960. The event resulted in a net reduction of 101.54 Tg C in carbon sequestration in the region during these two months, which was 39-53% of the annual net carbon sink of China's terrestrial ecosystems (190-260 Tg C yr(-1)). Moreover, model experiments showed that heatwaves and droughts consistently decreased ecosystem vegetation primary production but had opposite impacts on ecosystem respiration (TER), with increased TER by 6.78 ± 2.15% and decreased TER by 15.34 ± 3.57% assuming only changed temperature and precipitation, respectively. In light of increasing frequency and severity of future heatwaves and droughts, our study highlights the importance of accounting for the impacts of heatwaves and droughts in assessing the carbon sequestration in terrestrial ecosystems.