In this paper, a new mathematical model based on partial differential equations is proposed to study the spatial spread of infectious diseases. The model incorporates fluid dynamics theory and ...represents the epidemic spread as a fluid motion generated through the interaction between the susceptible and infected hosts. At the macroscopic level, the spread of the infection is modeled as an inviscid flow described by the Euler equation. Nontrivial numerical methods from computational fluid dynamics (CFD) are applied to investigate the model. In particular, a fifth-order weighted essentially non-oscillatory (WENO) scheme is employed for the spatial discretization. As an application, this mathematical and computational framework is used in a simulation study for the COVID-19 outbreak in Wuhan, China. The simulation results match the reported data for the cumulative cases with high accuracy and generate new insight into the complex spatial dynamics of COVID-19.
We propose a new mathematical and computational modeling framework that incorporates fluid dynamics to study the spatial spread of infectious diseases. We model the susceptible and infected ...populations as two inviscid fluids which interact with each other. Their motion at the macroscopic level characterizes the progression and spread of the epidemic. To implement the two-phase flow model, we employ high-order numerical methods from computational fluid dynamics. We apply this model to simulate the COVID-19 outbreaks in the city of Wuhan in China and the state of Tennessee in the US. Our modeling and simulation framework allows us to conduct a detailed investigation into the complex spatiotemporal dynamics related to the transmission and spread of COVID-19.
In this study we observed that mice pretreated with tumor exosomes had a significant acceleration of tumor metastasis in the lung. Tumor metastasis correlated significantly with an increase in ...recruitment of more Myeloid-derived suppressor cells (MDSCs) in the lung of C57BL/6j (B6) mice pretreated with tumor exosomes. These effects were blunted when MyD88 knockout (KO) mice were pretreated with tumor exosomes. MDSCs induced by tumor exosomes and isolated from wild-type B6 mice also more potently inhibited T cell activation and induction of interleukin-6 and tumor necrosis factor-α than MDSCs isolated from the lung of MyD88 KO mice. In vitro , addition of tumor exosomes to bone marrow-derived CD11b+ Gr-1+ cells isolated from wild-type B6 mice resulted in more cytokine production, including tumor necrosis factor-α, interleukin-6, and the chemokine CCL2, than CD11b+ Gr-1+ cells isolated from MyD88 KO mice. Moreover, lower levels of CCL2 were observed in the lungs in MyD88 KO mice pretreated with tumor exosomes than that in wild-type mice. Together these data demonstrate a pivotal role for MyD88 in tumor exosome-mediated expansion of MDSCs and tumor metastasis.
Abstract
Congenital avian leukosis virus subgroup J (ALV-J) infection can induce persistent immunotolerance in chicken, however, the underlying mechanism remains unclear. Here, we demonstrate that ...congenital ALV-J infection induces the production of high-frequency and activated CD4
+
CD25
+
Tregs that maintain persistent immunotolerance. A model of congenital infection by ALV-J was established in fertilized eggs, and hatched chicks showed persistent immunotolerance characterized by persistent viremia, immune organ dysplasia, severe imbalance of the ratio of CD4
+
/CD8
+
T cells in blood and immune organs, and significant decrease in CD3
+
T cells and Bu-1
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B cells in the spleen. Concurrently, the mRNA levels of IL-2, IL-10, and IFN-γ showed significant fluctuations in immune organs. Moreover, the frequency of CD4
+
CD25
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Tregs in blood and immune organs significantly increased, and the frequency of CD4
+
CD25
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Tregs was positively correlated with changes in ALV-J load in immune organs. Interestingly, CD4
+
CD25
+
Tregs increased in the marginal zone of splenic nodules in ALV-J-infected chickens and dispersed to the germinal center. In addition, the proliferation and activation of B cells in splenic nodules was inhibited, and the number of IgM
+
and IgG
+
cells in the marginal zone significantly decreased. We further found that the mRNA levels of TGF- β and CTLA-4 in CD4
+
CD25
+
Tregs of ALV-J-infected chickens significantly increased. Together, high-frequency and activated CD4
+
CD25
+
Tregs inhibited B cells functions by expressing the inhibitory cytokine TGF-β and inhibitory surface receptor CTLA-4, thereby maintaining persistent immunotolerance in congenital ALV-J-infected chickens.
A novel sandwich-type electrochemical immunosensor was fabricated for ultrasensitive detection of subgroup J of avian leukosis virus (ALVs-J) by employing β-cyclodextrin-ferrocene (CD-Fc) host–guest ...complex multifunctional Fe3O4 nanospheres as labels and β-cyclodextrin functional graphene sheets (CD-GS) nanocomposite as sensor platform. The sensitivity was greatly improved based on the triple amplification strategy. Firstly, the CD-GS improved the electron transfer rate as well as increasing the surface area to capture a large amount of primary antibodies (Ab1). Secondly, the CD on the Fe3O4 surface with strong recognition capability could form stable CD-Fc host–guest inclusion complex and provided larger free room for the conjugation of secondary antibodies (Ab2) and glucose oxidase (GOD). Finally, the conjugated GOD exhibited extraordinary electrochemical biocatalysis towards the reduction reaction of Fc+ by glucose. Under the optimized conditions, the electrochemical immunosensor exhibited a wide working range from 102.27–103.50 TCID50/mL (TCID50: 50% tissue culture infective dose) with a low detection limit of 102.19 TCID50/mL (S/N=3). The selectivity, reproducibility, and stability are acceptable. The assay was evaluated for real avian serum sample, receiving satisfactory results. This new type of triple amplification strategy may provide potential applications for the clinic application.
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► Subgroup J of avian leukosis virus were detected by ultrasensitive electrochemical immunnoassay technology. ► β-cyclodextrin-ferrocene host–guest complex multifunctional Fe3O4 nanospheres were used as labels. ► β-cyclodextrin functional graphene sheets nanocomposite was used for the immunosensor platform. ► The extreme enhancement of the sensitivity was greatly improved based on the triple amplification strategy.
Co-infection of Marek's disease virus (MDV) and reticuloendotheliosis virus (REV) synergistically drives disease progression, yet little is known about the mechanism of the synergism. Here, we found ...that co-infection of REV and MDV increased their replication via the RIOK3-Akt pathway. Initially, we noticed that the viral titres of MDV and REV significantly increased in REV and MDV co-infected cells compared with single-infected cells. Furthermore, tandem mass tag peptide labelling coupled with LC/MS analysis showed that Akt was upregulated in REV and MDV co-infected cells. Overexpression of Akt promoted synergistic replication of MDV and REV. Conversely, inhibition of Akt suppressed synergistic replication of MDV and REV. However, PI3K inhibition did not affect synergistic replication of MDV and REV, suggesting that the PI3K/Akt pathway is not involved in the synergism of MDV and REV. In addition, we revealed that RIOK3 was recruited to regulate Akt in REV and MDV co-infected cells. Moreover, wild-type RIOK3, but not kinase-dead RIOK3, mediated Akt phosphorylation and promoted synergistic replication of MDV and REV. Our results illustrate that MDV and REV activated a novel RIOK3-Akt signalling pathway to facilitate their synergistic replication.
The past few years have witnessed a rapid increase in cases of viral arthritis caused by avian reovirus (ARV) in chicken farms in China, attributed to the emergence of variant strains that render ...traditional vaccines ineffective, leading to substantial economic losses. In this study, we successfully isolated a novel ARV strain, designated as 2023ARV-GS-SDAU-1, from chickens in a broiler flock vaccinated with an ARV vaccine in Gansu province. We performed whole-genome sequencing and assessed its pathogenicity through 2 infection routes: oral administration and intraperitoneal injection. Our analysis revealed significant variations in the σA gene, associated with the inhibition of interferon secretion, compared to known ARV strains. The highest nucleotide identity observed was below 80%. Additionally, the σC gene exhibited notable variations compared to its homologous strains within the same group. Multiple alignment of the amino acid sequences classified the 2023ARV-GS-SDAU-1 strain under genotype I. Furthermore, our pathogenicity experiments indicated that the isolated strain exhibited more severe pathogenicity when administered via intraperitoneal injection in SPF chickens. In summary, our data suggest that the 2023ARV-GS-SDAU-1 strain represents a novel variant circulating in broiler flocks in China. These findings enrich currently available genetic information on ARV strains and provide a new complete genome sequence.
Fowl adenovirus (FAdV) has posed a grave threat to the health of poultry, and the sudden outbreak highlights the importance of the new rapid diagnostic method for the control and prevention of ...transmission. Hence, in the present study, a novel recombinase polymerase amplification (RPA) assay, which was suitable for all 12 serotypes (FAdV-1 to 8a and 8b to 11) had been successfully launched to detect FAdV. Also, the entire amplification process could be completed in the isothermal condition when temperature ranged from 26 to 42°C within no more than 14 min, which was remarkably superior to endpoint polymerase chain reaction (98 min) with the same detecting sensitivity (as low as 0.1 fg viral DNA), avoiding sophisticated thermal cyclers with simple operation. Additionally, the same primers did not produce positive reactions with other viruses tested, demonstrating that the specificity of the RPA assay was acceptable. Moreover, this developed method could be efficiently used in the diagnosis of FAdV references and epidemic strains from different avian origins, thus making it a rapid, reliable, and point-of-care FAdV diagnostics tool, as well as an alternative to endpoint PCR.
In this paper, we combine the dielectric metasurface with monolayer graphene to realize a high quality(Q)-factor quasi-BIC-based optical modulator, and the corresponding modulation performances are ...investigated by using the finite-difference time-domain (FDTD) method, which can be well fitting by the Fano formula based on the temporal couple-mode theory. The results demonstrate that bound states in the continuum (BIC) will turn into the quasi-BIC with high Q-factor by breaking the symmetry of every unit of the metasurface. Meanwhile, the amplitude and bandwidth of transmission based on the quasi-BIC mode can be efficiently adjusted by changing the Fermi energy (EF) of monolayer graphene, and the maximum difference in transmission up to 0.92 is achieved. Moreover, we also discuss the influence of the asymmetry degree to further investigate the modulation effect of graphene on the quasi-BIC mode.
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