Highly pathogenic H5N1 influenza viruses (HPAIV) cause rapid systemic illness and death in susceptible animals, leading to a disease with high morbidity and mortality rates. Although vaccines and drugs are the best solution to prevent this threat, a more effective treatment for H5 strains of influenza has yet to be developed. Therefore, the development of therapeutics/drugs that combat H5N1 influenza virus infection is becoming increasingly important. Lycorine, the major component of Amaryllidaceae alkaloids, exhibits better protective effects against A/CK/GD/178/04 (H5N1) (GD178) viruses than the commercial neuraminidase (NA) inhibitor oseltamivir in our prior study. Lycorine demonstrates outstanding antiviral activity because of its inhibitory activity against the export of viral ribonucleoprotein complexes (vRNPs) from the nucleus. However, how lycorine affects the proteome of AIV infected cells is unknown. Therefore, we performed a comparative proteomic analysis to identify changes in protein expression in AIV-infected Madin-Darby Canine Kidney cells treated with lycorine. Three groups were designed: mock infection group (M), virus infection group (V), and virus infection and lycorine-treated after virus infection group (L). The multiplexed tandem mass tag (TMT) approach was employed to analyze protein level in this study. In total, 5,786 proteins were identified from the three groups of cells by using TMT proteomic analysis. In the V/M group, 1,101 proteins were identified, of which 340 differentially expressed proteins (DEPs) were determined during HPAIV infection; among the 1,059 proteins identified from the lycorine-treated group, 258 proteins presented significant change. Here, 71 proteins showed significant upregulation or downregulation of expression in the virus-infected/mock and virus-infected/lycorine-treated comparisons, and the proteins in each fraction were functionally classified further. Interestingly, lycorine treatment decreased the levels of the nuclear pore complex protein 93 (Nup93, E2RSV7), which is associated with nuclear–cytoplasmic transport. In addition, Western blot experiments confirmed that the expression of Nup93 was significantly downregulated in lycorine treatment but induced after viral infection. Our results may provide new insights into how lycorine may trap vRNPs in the nucleus and suggest new potential therapeutic targets for influenza virus.

We have performed extensive transport experiments on a 4 nm thick aluminum (Al) superconducting film grown on a GaAs substrate by molecular beam epitaxy (MBE). Nonlinear current-voltage (I-V ) measurements on such a MBE-grown superconducting nanofilm show that V∼I 3 , which is evidence for the Berezinskii-Kosterlitz-Thouless (BKT) transition, both in the low-voltage (T BKT ≈1.97 K) and high-voltage regions (T BKT ≈2.17 K). In order to further study the two regions where the I-V curves are BKT-like, our experimental data are fitted to the temperature-induced vortices/antivortices unbinding model as well as the dynamical scaling theory. It is found that the transition temperature obtained in the high-voltage region is the correct T BKT as confirmed by fitting the data to the aforementioned models. Our experimental results unequivocally show that I-V measurements alone may not allow one to determine T BKT for superconducting transition. Therefore, one should try to fit one's results to the temperatureinduced vortices/antivortices unbinding model and the dynamical scaling theory to accurately determine T BKT in a two-dimensional superconductor.

We have performed detailed transport measurements on a 3 nm thick (as-grown) Al film on GaAs prepared by molecular beam epitaxy (MBE). Such an epitaxial film grown on a GaAs substrate shows the Berezinskii-Kosterlitz-Thouless (BKT) transition, a topological transition in two dimensions. Our experimental data shows that the MBE-grown Al nanofilm is an ideal system for probing interesting physical phenomena such as the BKT transition and superconductivity. The increased superconductor transition temperature (~2.4 K) compared to that of bulk Al (1.2 K), together with the ultrathin film quality, may be advantageous for future superconductor-based quantum devices and quantum information technology.

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