ABSTRACT
Coronavirus disease 2019 is a global pandemic caused by SARS-CoV-2. The emergence of its variant strains has posed a considerable challenge to clinical treatment. Therefore, drugs capable of inhibiting SARS-CoV-2 infection, regardless of virus variations, are in urgently need. Our results showed that the endosomal acidification inhibitor, Bafilomycin A1 (Baf-A1), had an inhibitory effect on the viral RNA synthesis of SARS-CoV-2, and its Beta and Delta variants at the concentration of 500 nM. Moreover, the human lung xenograft mouse model was used to investigate the anti-SARS-CoV-2 effect of Baf-A1. It was found that Baf-A1 significantly inhibited SARS-CoV-2 replication in the human lung xenografts by in situ hybridization and RT-PCR assays. Histopathological examination showed that Baf-A1 alleviated SARS-CoV-2-induced diffuse inflammatory infiltration of granulocytes and macrophages and alveolar endothelial cell death in human lung xenografts. In addition, immunohistochemistry analysis indicated that Baf-A1 decreased inflammatory exudation and infiltration in SARS-CoV-2-infected human lung xenografts. Therefore, Baf-A1 may be a candidate drug for SARS-CoV-2 treatment.
Subject(s)
COVID-19 , Humans , Animals , Mice , Heterografts , SARS-CoV-2 , Alveolar Epithelial Cells , Disease Models, AnimalABSTRACT
Quantum dots functionalization has been proven to be a simple modification strategy for improving the electroanalytical performance of two-dimensional electrode materials by increasing the specific surface area and active reaction sites. Herein, a new electrochemical sensing platform was fabricated by SnO2 quantum dot-functionalized Ti3C2 MXene (Ti3C2-SnO2QDs) for the highly sensitive detection of Sudan I in food. Ti3C2-SnO2QDs were prepared via in situ synthesis, which can control the nucleation and growth of SnO2QDs, resulting in the well-dispersed SnO2QDs with 2-3 nm size on the intersheet surface of MXene. Moreover, the formation of Ti3C2-SnO2QDs can effectively restrict the aggregation of Ti3C2 and improve the stability of SnO2QDs in aquatic environment. The prepared nanocomposite can be used as an improved modified material to further increase the electrocatalytic performance and electrochemical signal of Sudan I on the surface of a glassy carbon electrode. Under optimized conditions, the proposed analytical method displayed a linear dependence for Sudan I concentration ranging from 0.008 to 10 µM with a detection limit of 0.27 nM (S/N = 3) by electrochemical cyclic voltammetry. This sensor with excellent selectivity, reproducibility and accuracy was quantitatively validated in commercial ketchup and chili powder. This Ti3C2-SnO2QDs-based Sudan I sensor is expected to expand the application of MXene nanocomposites in electrochemical analysis and is envisioned as a promising candidate for monitoring illegal food additives in real food samples.
Subject(s)
Quantum Dots , Titanium , Reproducibility of Results , Naphthols , Electrochemical Techniques/methodsABSTRACT
MicroRNAs (miRNAs) play an important role in the virus-host interaction. Our previous work has indicated that the expression level of miR-10a increased in porcine alveolar macrophages (PAMs) during porcine reproductive and respiratory syndrome virus (PRRSV) infection and further inhibited viral replication through downregulates the expression of host molecule signal-recognition particle 14 (SRP14) protein. However, the molecular mechanism of miR-10a increased after PRRSV infection remains unknown. In the present study, transcription factor interferon regulatory factor 8 (IRF8) was identified as a negative regulator of miR-10a. PRRSV infection decreases the expression level of IRF8 in PAMs, leading to upregulating miR-10a expression to play an anti-PRRSV role. Meanwhile, this work first proved that IRF8 promoted PRRSV replication in an miR-10a-dependent manner. Further, we explained that SRP14, the target gene of miR-10a, promotes the synthesis of the PRRSV genome by interacting with the viral components Nsp2, thus facilitating PRRSV replication. In conclusion, we identified a novel IRF8-miR-10a-SRP14 regulatory pathway against PRRSV infection, which provides new insights into virus-host interactions and suggests potential new antiviral strategies to control PRRSV. IMPORTANCE Porcine reproductive and respiratory syndrome virus (PRRSV) has rapidly spread to the global pig industry and caused incalculable economic damage since first discovered in the 1980s. However, conventional vaccines do not provide satisfactory protection. Understanding the molecular mechanisms of host resistance to PRRSV infection is necessary to develop safe and effective strategies to control PRRSV. During viral infection, miRNAs play vital roles in regulating the expression of viral or host genes at the posttranscriptional level. The significance of our study is that we revealed the transcriptional regulation mechanism of the antiviral molecule miR-10a after PRRSV infection. Moreover, our research also explained the mechanism of host molecule SRP14, the target gene of miR-10a regulating PRRSV replication. Thus, we report a novel regulatory pathway of IRF8-miR-10a-SRP14 against PRRSV infection, which provides new insights into virus-host interactions and suggests potential new control measures for future PRRSV outbreaks.