Rapid and early diagnosis of respiratory viruses is key to preventing infections from spreading and guiding treatments. Here, we developed a sensitive and quantitative surface-enhanced Raman scattering-based lateral flow immunoassay (SERS-based LFIA) strip for simultaneous detection of influenza A H1N1 virus and human adenovirus (HAdV) by using Fe3O4@Ag nanoparticles as magnetic SERS nanotags. The new type of Fe3O4@Ag magnetic tags, which were conjugated with dual-layer Raman dye molecules and target virus-capture antibodies, performs the following functions: specific recognition and magnetic enrichment of target viruses in the solution and SERS detection of the viruses on the strip. Based on this strategy, the magnetic SERS strip can directly be used for real biological samples without any sample pretreatment steps. The limits of detection for H1N1 and HAdV were 50 and 10 pfu/mL, respectively, which were 2000 times more sensitive than those from the standard colloidal gold strip method. Moreover, the proposed strip is easy to operate, rapid, stable, and can achieve high throughput and is thus a potential tool for early detection of virus infection.
No abstract
The p21-activated kinase 1 (PAK1), a serine/threonine kinase that orchestrates cytoskeletal remodeling and cell motility, has been shown to function as downstream node for various oncogenic signaling pathways to promote cell proliferation, regulate apoptosis and accelerate mitotic abnormalities, resulting in tumor formation and invasiveness. Although alterations in PAK1 expression and activity have been detected in various human malignancies, its potential biological and clinical significance in renal cell carcinoma (RCC) remains obscure. In this study, we found increased PAK1 and phosphorylated PAK1 levels in tumor tissues according to TNM stage progression. Elevated phosphorylated PAK1 levels associated with progressive features and indicated unfavorable overall survival (OS) as an independent adverse prognosticator for patients with RCC. Moreover, PAK1 kinase activation with constitutive active PAK1 mutant T423E promoted growth, colony formation, migration, invasion and stem-like phenotype of RCC cells, and vice versa, in PAK1 inhibition by PAK1 kinase inactivation with specific PAK1 shRNA, dead kinase PAK1 mutant K299R or allosteric inhibitor IPA3. Stem-like phenotype due to sunitinib administration via increased PAK1 kinase activation could be ameliorated by PAK1 shRNA, PAK1 mutant K299R and IPA3. Furthermore, nuclear factor-κB (NF-κB)/interleukin-6 (IL-6) activation was found to be responsible for PAK1-mediated stem-like phenotype following sunitinib treatment. Both IL-6 neutralizing antibody and IPA3 administration enhanced tumor growth inhibition effect of sunitinib treatment on RCC cells in vitro and in vivo. Our results unraveled that oncogenic activation of PAK1 defines an important mechanism for maintaining stem-like phenotype and sunitinib resistance through NF-κB/IL-6 activation in RCC, lending PAK1-mediated NF-κB/IL-6 activation considerable appeal as novel pharmacological therapeutic targets against sunitinib resistance.
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