Wavefront distortion correction in scanning tunneling microscope image.

We report an algorithm to identify and correct distorted wavefronts in atomic resolution scanning tunneling microscope images. This algorithm can be used to correct nonlinear in-plane distortions without prior knowledge of the physical scanning parameters, the characteristics of the piezoelectric actuator, or individual atom positions. The 2D image is first defined as a sum of sinusoidal plane waves, where a nonlinear distortion renders a curve for an otherwise ideal linear wavefront. Using the Fourier transforms of local areas of the image, the algorithm generates a wavefront vector field. The identified wavefronts are subsequently linearized for each plane wave without changing lattice orders, giving rise to distortion corrections. Our algorithm is complementary to conventional post-processing algorithms that require prior detection of real space features, which can also be used to correct nonlinear distortions in 2D images acquired by other microscopy techniques.

Disruption of type I interferon pathway and reduced production of IFN-α by parabens in virus-infected dendritic cells.

BACKGROUND: Parabens are widely used preservatives commonly found in foods, cosmetics, and industrial products. Several studies have examined the effects of parabens on human health owing to widespread and continuous exposure to them in daily life. However, little is known about their immune-regulatory effects. OBJECTIVE: Here, we aimed to investigate whether methylparaben, ethylparaben, and propylparaben affect the function of dendritic cells (DCs) as the most potent antigen-presenting cells that play a critical role in the initiation of adaptive immune responses. METHODS: Bone-marrow derived DCs (BMDCs) were treated with three types of parabens (methylparaben, ethylparaben, and propylparaben) for 12 h. Subsequently, the transcriptomic profile was analyzed using RNA sequencing with further gene set enrichment analysis based on commonly regulated differentially expressed genes (DEGs). To test whether parabens suppress the production of type-I interferons (IFN-I) in BMDCs during viral infection, BMDCs or paraben-treated BMDCs were infected with Lymphocytic Choriomeningitis Virus (LCMV) at 10 multiplicity of infection (MOI) and measured the production of IFN-α1. RESULTS: Transcriptomic analyses revealed that all three types of parabens reduced the transcription levels of genes in virus infection-associated pathways, such as IFN-I responses in BMDCs. Furthermore, parabens considerably reduced IFN-α1 production in the virus-infected BMDCs. CONCLUSION: Our study is the first to show that parabens may modulate anti-viral immune responses by regulating DCs.

Monolayer Superconductivity and Tunable Topological Electronic Structure at the Fe(Te,Se)/Bi2 Te3 Interface.

The interface between 2D topological Dirac states and an s-wave superconductor is expected to support Majorana-bound states (MBS) that can be used for quantum computing applications. Realizing these novel states of matter and their applications requires control over superconductivity and spin-orbit coupling to achieve spin-momentum-locked topological interface states (TIS) which are simultaneously superconducting. While signatures of MBS have been observed in the magnetic vortex cores of bulk FeTe0.55 Se0.45 , inhomogeneity and disorder from doping make these signatures unclear and inconsistent between vortices. Here superconductivity is reported in monolayer (ML) FeTe1-y Sey (Fe(Te,Se)) grown on Bi2 Te3 by molecular beam epitaxy (MBE). Spin and angle-resolved photoemission spectroscopy (SARPES) directly resolve the interfacial spin and electronic structure of Fe(Te,Se)/Bi2 Te3 heterostructures. For y = 0.25, the Fe(Te,Se) electronic structure is found to overlap with the Bi2 Te3 TIS and the desired spin-momentum locking is not observed. In contrast, for y = 0.1, reduced inhomogeneity measured by scanning tunneling microscopy (STM) and a smaller Fe(Te,Se) Fermi surface with clear spin-momentum locking in the topological states are found. Hence, it is demonstrated that the Fe(Te,Se)/Bi2 Te3 system is a highly tunable platform for realizing MBS where reduced doping can improve characteristics important for Majorana interrogation and potential applications.

Galectin-4 increases the ability of M2 macrophages to enhance antiviral CD4+ T-cell responses.

Galectin-4 (Gal-4) is a ß-galactoside-binding protein belonging to the galectin family. Although Gal-4 is known to be involved in several physiologic processes of the gastrointestinal tract, its immunomodulatory roles remain unclear. In this study, we investigated whether Gal-4 influences the function of M1 and M2 macrophages. Gal-4 treatment drove more robust changes in the gene expression of M2 macrophages compared to M1 macrophages. Antiviral immune response-related genes were significantly upregulated in Gal-4-treated M2 macrophages. Gal-4 significantly enhanced the immunostimulatory activity of M2 macrophages upon Toll-like receptor 7 stimulation or infection with lymphocytic choriomeningitis virus (LCMV). Moreover, the antibody production against LCMV infection and the antiviral CD4+ T-cell responses, but not the antiviral CD8+ T-cell responses, were greatly increased by Gal-4-treated M2 macrophages in vivo. The present results indicate that Gal-4 enhances the ability of M2 macrophages to promote antiviral CD4+ T-cell responses. Thus, Gal-4 could be used to boost antiviral immune responses.

Inhibition of KIF20A suppresses the replication of influenza A virus by inhibiting viral entry.

The influenza A virus (IAV) has caused several pandemics, and therefore there are many ongoing efforts to identify novel antiviral therapeutic strategies including vaccines and antiviral drugs. However, influenza viruses continuously undergo antigenic drift and shift, resulting in the emergence of mutated viruses. In turn, this decreases the efficiency of existing vaccines and antiviral drugs to control IAV infection. Therefore, this study sought to identify alternative therapeutic strategies targeting host cell factors rather than viruses to avoid infection by mutated viruses. Particularly, we investigated the role of KIF20A that is one of kinesin superfamily proteins in the replication of IAV. The KIF20A increased viral protein levels in IAV-infected cells by regulating the initial entry stage during viral infection. Furthermore, the KIF20A inhibitor significantly suppressed viral replication, which protected mice from morbidity and mortality. Therefore, our findings demonstrated that KIF20A is highly involved in the viral replication process and viral propagation both in vitro and in vivo, and could thus be used as a target for the development of novel antiviral drugs.

Anti-influenza A virus activity by Agrimonia pilosa and Galla rhois extract mixture.

Influenza A virus (IAV) continues to threaten human health. To date, two classes of antiviral drugs have been approved to treat IAV infection, but the continuous emergence of the drug-resistant IAV mutant reinforces the need to develop new antiviral drugs. In this study, we aimed to investigate the anti-IAV activity of an aqueous mixture of Agrimonia pilosa and Galla rhois extracts (APRG64). We demonstrated that APRG64 significantly reduced the IAV-induced cytopathic effect, the transcription/expression of viral proteins, and the production of infectious viral particles. Among nine major components of APRG64, apigenin was identified as the main ingredient responsible for the anti-IAV activity. Interestingly, APRG64 and apigenin inhibited the cell attachment and entry of virus and polymerase activity. Importantly, intranasal administration of APRG64 or apigenin strongly reduced viral loads in the lungs of IAV-infected mice. Furthermore, oral administration of APRG64 significantly reduced the level of viral RNAs and the expression level of pro-inflammatory cytokines in the lungs, which protected mice from IAV-induced mortality. In conclusion, APRG64 could be an attractive antiviral drug to treat IAV infection.

Potent antiviral activity of the extract of Elaeocarpus sylvestris against influenza A virus in vitro and in vivo.

BACKGROUND: Elaeocarpus sylvestris (Lour.) Poir. (Elaeocarpaceae) belongs to a genus of tropical and semitropical evergreen trees, which has known biological activities such as antiviral and immunomodulatory activities. However, its antiviral potential against influenza virus infection remains unknown. PURPOSE: In this study, we investigated the antiviral activity of the 50% aqueous ethanolic extract of E. sylvestris (ESE) against influenza A virus (IAV) infection, which could lead to the development of novel phytomedicine to treat influenza virus infection. METHODS: To investigate the in vitro antiviral activity of ESE and its main ingredients, 1,​2,​3,​4,​6-​penta-​O-​galloyl-ß-d-glucose (PGG) and geraniin (GE), the levels of viral RNAs, proteins, and infectious viral particles in IAV-infected MDCK cells were analyzed. Molecular docking analysis was performed to determine the binding energy of PGG and GE for IAV proteins. To investigate in vivo antiviral activity, IAV-infected mice were treated intranasally or intragastrically with ESE, PGG, or GE. RESULTS: ESE and its gallate main ingredients (PGG and GE) strongly inhibited the production of viral RNAs, viral proteins, and infectious viral particles in vitro. Also through the viral attachment on cells, polymerase activity, signaling pathway, we revealed the ESE, PGG, and GE inhibit multiple steps of IAV replication. Molecular docking analysis revealed that PGG and GE could interact with 12 key viral proteins (M1, NP, NS1 effector domain (ED), NS1 RNA-binding domain (RBD), HA pocket A, HA receptor-binding domain (RBD), NA, PA, PB1, PB2 C-terminal domain, PB2 middle domain, and PB2 cap-binding domain) of IAV proteins with stable binding energy. Furthermore, intranasal administration of ESE, PGG, or GE protected mice from IAV-induced mortality and morbidity. Importantly, oral administration of ESE suppressed IAV replication and the expression of inflammatory cytokines such as IFN-γ, TNF-α, and IL-6 in the lungs to a large extent. CONCLUSION: ESE and its major components (PGG and PE) exhibited strong antiviral activity in multiple steps against IAV infection in silico, in vivo, and in vitro. Therefore, ESE could be used as a novel natural product derived therapeutic agent to treat influenza virus infection.

Note: Development of a wideband amplifier for cryogenic scanning tunneling microscopy.

A wideband cryogenic amplifier has been developed for low temperature scanning tunneling microscopy. The amplifier consisting of a wideband complementary metal oxide semiconductor field effect transistors operational amplifier together with a feedback resistor of 100 kΩ and a capacitor is mounted within a 4 K Dewar. This amplifier has a wide bandwidth and is successfully applied to scanning tunneling microscopy applications at low temperatures down to ∼7 K. The quality of the designed amplifier is validated by high resolution imaging. More importantly, the amplifier has also proved to be capable of performing scanning tunneling spectroscopy measurements, showing the detection of the Shockley surface state of the Au(111) surface and the superconducting gap of Nb(110).