ABSTRACT
Whispering-gallery-mode (WGM) microcavities have shown significant applications in nanoparticle sensing for environmental monitoring and biological analysis. However, the enhancement of detection resolution often calls for active cavities or elaborate structural designs, leading to an increase of fabrication complexity and cost. Herein, heterodyne amplification is implemented in WGM microsensors based on backscattering detection mechanism. By interfering with an exotic reference laser, the reflecting light backscattered by perturbation targets can be strongly enlarged, yielding an easy-to-resolve and consequently sensitive microsensor. The dependence of detection laser frequency has also been characterized with the assistance of optothermal dynamics. We show that exploiting heterodyne interferometry boosts the detection of weak signals in microresonator systems and provides a fertile ground for optical microsensor development.
Subject(s)
NanoparticlesABSTRACT
Azvudine is a novel nucleoside reverse transcriptase inhibitor with antiviral activity on human immunodeficiency virus, hepatitis B virus and hepatitis C virus. Here we reported the in vitro activity of azvudine against HIV-1 and HIV-2 when used alone or in combination with other antiretroviral drugs and its drug resistance features. Azvudine exerted highly potent inhibition on HIV-1 (EC(50)s ranging from 0.03 to 6.92 nM) and HIV-2 (EC(50)s ranging from 0.018 to 0.025 nM). It also showed synergism in combination with six approved anti-HIV drugs on both C8166 and PBMC. In combination assay, the concentrations of azvudine used were 1000 or 500 fold lower than other drugs. Azvudine also showed potent inhibition on NRTI-resistant strains (L74V and T69N). Although M184V caused 250 fold reduction in susceptibility, azvudine remained active at nanomolar range. In in vitro induced resistant assay, the frequency of M184I mutation increased with induction time which suggests M184I as the key mutation in azvudine treatment. As control, lamivudine treatment resulted in a higher frequency of M184I/V given the same induction time and higher occurrence of M184V was found. Molecular modeling analysis suggests that steric hindrance is more pronounced in mutant M184I than M184V due to the azido group of azvudine. The present data demonstrates the potential of azvudine as a complementary drug to current anti-HIV drugs. M184I should be the key mutation, however, azvudine still remains active on HIV-1LAI-M184V at nanomolar range.
