ATAD1 inhibits hepatitis C virus infection by removing the viral TA-protein NS5B from mitochondria.

ATPase family AAA domain-containing protein 1 (ATAD1) maintains mitochondrial homeostasis by removing mislocalized tail-anchored (TA) proteins from the mitochondrial outer membrane (MOM). Hepatitis C virus (HCV) infection induces mitochondrial fragmentation, and viral NS5B protein is a TA protein. Here, we investigate whether ATAD1 plays a role in regulating HCV infection. We find that HCV infection has no effect on ATAD1 expression, but knockout of ATAD1 significantly enhances HCV infection; this enhancement is suppressed by ATAD1 complementation. NS5B partially localizes to mitochondria, dependent on its transmembrane domain (TMD), and induces mitochondrial fragmentation, which is further enhanced by ATAD1 knockout. ATAD1 interacts with NS5B, dependent on its three internal domains (TMD, pore-loop 1, and pore-loop 2), and induces the proteasomal degradation of NS5B. In addition, we provide evidence that ATAD1 augments the antiviral function of MAVS upon HCV infection. Taken together, we show that the mitochondrial quality control exerted by ATAD1 can be extended to a novel antiviral function through the extraction of the viral TA-protein NS5B from the mitochondrial outer membrane.

Using Fuzzy C-Means Clustering to Determine First Arrival of Microseismic Recordings.

Accurate and automatic first-arrival picking is one of the most crucial steps in microseismic monitoring. We propose a method based on fuzzy c-means clustering (FCC) to accurately divide microseismic data into useful waveform and noise sections. The microseismic recordings' polarization linearity, variance, and energy are employed as inputs for the fuzzy clustering algorithm. The FCC produces a membership degree matrix that calculates the membership degree of each feature belonging to each cluster. The data section with the higher membership degree is identified as the useful waveform section, whose first point is determined as the first arrival. The extracted polarization linearity improves the classification performance of the fuzzy clustering algorithm, thereby enhancing the accuracy of first-arrival picking. Comparison tests using synthetic data with different signal-to-noise ratios (SNRs) demonstrate that the proposed method ensures that 94.3% of the first arrivals picked have an error within 2 ms when SNR = -5 dB, surpassing the residual U-Net, Akaike information criterion, and short/long time average ratio approaches. In addition, the proposed method achieves a picking accuracy of over 95% in the real dataset tests without requiring labelled data.

CO2 Reduction Mechanism on the Cu2 O(110) Surface: A First-Principles Study.

Cu2 O is an attractive catalyst for the selective reduction of CO2 to methanol. However, the mechanism of the reaction and the role of the Cu species in different oxidation states are not well understood yet. In this work, by first-principles calculations, we investigate the mechanism of the reaction on the Cu2 O(110) surface, which is the most selective for methanol, in different degrees of reduction: ideal surface, slightly reduced surface (SRS), and partially reduced surface (PRS). The most favorable reaction pathways on the three surfaces were identified. We found that Cu(I) on the ideal surface is not capable of chemisorbing CO2 , but surface oxygen serves as the active site which selectively converts CO2 to CH3 OH with a limiting potential of -0.77 V. The Cu(0) on the SRS and PRS promotes the adsorption and reduction of CO2 , while the removal of the residue O* becomes potential/rate limiting with a more negative limiting potential than the ideal surface. The SRS is selective to methanol while the PRS becomes selective to methane. The result suggests that the key to high methanol selectivity is to avoid the reduction of Cu(I), which provides a new strategy for the design of more efficient catalysts for selective CO2 reduction to methanol.

PPP2R5D promotes hepatitis C virus infection by binding to viral NS5B and enhancing viral RNA replication.

BACKGROUND: Hepatitis C virus (HCV) infection increased the risk of hepatocellular carcinoma. Identification of host factors required for HCV infection will help to unveil the HCV pathogenesis. Adaptive mutations that enable the replication of HCV infectious clones could provide hints that the mutation-carrying viral protein may specifically interact with some cellular factors essential for the HCV life cycle. Previously, we identified D559G mutation in HCV NS5B (RNA dependent RNA polymerase) important for replication of different genotype clones. Here, we searched for the factors that potentially interacted with NS5B and investigated its roles in HCV infection. METHODS: Wild-type-NS5B and D559G-NS5B of HCV genotype 2a clone, J6cc, were ectopically expressed in hepatoma Huh7.5 cells, and NS5B-binding proteins were pulled down and identified by mass spectrometry. The necessity and mode of action of the selected cellular protein for HCV infection were explored by experiments including gene knockout or knockdown, complementation, co-immunoprecipitation (Co-IP), colocalization, virus infection and replication, and enzymatic activity, etc. RESULTS: Mass spectrometry identified a number of cellular proteins, of which protein phosphatase 2 regulatory subunit B'delta (PPP2R5D, the PP2A regulatory B subunit) was one of D559G-NS5B-pulled down proteins and selected for further investigation. Co-IP confirmed that PPP2R5D specifically interacted with HCV NS5B but not HCV Core and NS3 proteins, and D559G slightly enhanced the interaction. NS5B also colocalized with PPP2R5D in the endoplasmic reticulum. Knockdown and knockout of PPP2R5D decreased and abrogated HCV infection in Huh7.5 cells, respectively, while transient and stable expression of PPP2R5D in PPP2R5D-knockout cells restored HCV infection to a level close to that in wild-type Huh7.5 cells. Replicon assay revealed that PPP2R5D promoted HCV replication, but the phosphatase activity and catalytic subunit of PP2A were not affected by NS5B. CONCLUSIONS: PPP2R5D interactes with HCV NS5B and is required for HCV infection in cultured hepatoma cells through facilitating HCV replication.

Understanding the role of Cl doping in the oxygen evolution reaction on cuprous oxide by DFT.

Designing highly active and earth-abundant oxygen evolution reaction (OER) electrocatalysts for electrochemical water splitting remains a challenge. Recently, Cl-doped Cu2O has emerged as a very promising non-noble-metal electrocatalyst candidate for the OER. However, the mechanism of the OER catalyzed by Cl-doped Cu2O has not been explored systematically. Herein, a comprehensive density functional theory (DFT) study is employed to study the role of Cl doping via comparing the OER on pure and Cl-doped Cu2O surfaces with/without Cu vacancies. Our results reveal that Cl doping increases the adsorption ability of Cu2O(111) by providing an excess electron, while a Cu vacancy decreases its adsorption ability by changing the geometric structure of the adsorption sites and the electronic structures. Cl-Cu2O(111) (η = 0.58 V) and VCu-Cl-Cu2O(111) (η = 0.46 V) have comparable or even better OER activity than those of widely used OER electrocatalysts such as the IrO2 catalyst (η = 0.56 V). It is facile to have a Cu vacancy when Cu2O(111) is doped with Cl because of a large strain introduced by Cl doping. Thus, VCu-Cl-Cu2O(111) should be the most feasible catalyst for the OER catalyzed by Cl-doped Cu2O material. The dual role of Cl doping is that it not only increases the OER activity but also helps to form a Cu vacancy. The results show that Cu2O(111) activity can be greatly enhanced via electronic and geometric structure modulation, which is helpful for the design of more efficient Cu2O-based catalysis.

Hepatitis C virus hypervariable region 1 antibodies interrupt E2-SR-B1 interaction to suppress viral infection.

Whether hypervariable region 1 (HVR1)-targeting antibodies elicited during natural hepatitis C virus (HCV) infection contribute to virus clearance and what is the mechanism underlying remain unclear. Here, we demonstrated that treatment of HCV-infected hepatoma Huh7.5 cells with the IgGs purified from 2 of 28 (7.1%) chronic hepatitis C (CHC) patients efficiently controlled the infection, for which genotype 1b HVR1 (1bHVR1)-binding antibody was critical. Moreover, we found that 1bHVR1 peptide was superior to 2aHVR1 in rabbit immunization to elicit antibodies neutralizing genotypes 1a, 2a, 3a, and 4a. The neutralization effect of 1bHVR1 IgG could be augmented by HH-1, an antibody constructed from CHC memory B cells but without binding to HVR1 peptide. Mechanistic studies showed that 1bHVR1 antisera and IgGs disrupted the interaction of E2-SR-B1 receptor. This study highlights the neutralizing activity of HVR1 antibody elicited by CHC patients and generated by HVR1-immunization against the established infections of multiple HCV genotypes.

Multifunctional Peroxidase-Encapsulated Nanoliposomes: Bioetching-Induced Photoelectrometric and Colorimetric Immunoassay for Broad-Spectrum Detection of Ochratoxins.

In this study, a versatile dual-modal readout immunoassay platform was achieved for sensitive and broad-spectrum detection of ochratoxins based on the photocurrent response of flexible CdS/ZnO nanorod arrays/reduced graphene oxide and the localized surface plasmon resonance (LSPR) peak shift of Au nanobipyramids (Au NBPs). By using nanoliposomes as the vehicle to carry the secondary antibody and encapsulate horseradish peroxidase (HRP), the photocurrent change and the peak shift can be greatly amplified. The reaction mechanism was investigated in detail, indicating that HRP can trigger enzymatic bioetching in the presence of H2O2. In the photoelectrochemical detection, the oxidized HRP can etch CdS on the photoelectrode, resulting in the photocurrent change, while in the colorimetric detection, HRP can oxidize H2O2 to produce hydroxyl radicals that can etch Au NBPs to form multiple color changes and LSPR shifts. Compared with the common single-modal immunoassay for ochratoxins, such dual-modal immunoassay is more precise and reliable, owing to the completely independent signal conversion and transmission mechanism. Therefore, we hope that this accurate, simple, and visualized strategy may create a new avenue and provide innovative inspiration for food analysis.

Different recycle behavior of Cu2+ and Fe3+ ions for phenol photodegradation over TiO2 and WO3.

Photocatalytic degradation of organic pollutants on TiO2 and WO3 have been widely studied, but the effects of Cu(2+) and Fe(3+) ions still remain unclear. In this work, we have found that the recycle behavior of Cu(2+) and Fe(3+) are greatly dependent on the photocatalytic activity of metal oxide used. With TiO2 (P25, anatase, and rutile), all the time profiles of phenol degradation in water under UV light well fitted to the apparent first-order rate equation. On the addition of Cu(2+), phenol degradation on anatase, rutile and WO3 also followed the first-order kinetics. On the addition of Fe(3+), the initial rate of phenol degradation on each oxide was increased, but only the reactions on three TiO2 became to follow the first order kinetics after half an hour. The relevant rate constants for phenol degradation in the presence of Cu(2+) or Fe(3+) were larger than those in the absence of metal ions. Under visible light, phenol degradation on WO3 was also accelerated on the addition of Fe(3+) or Cu(2+). Moreover, several influencing factors were examined, including the metal ion photolysis in solution. It becomes clear that as electron scavengers of TiO2 and WO3, Fe(3+) is better than Cu(2+), while they are better than O2. We propose that Fe(3+) recycle occurs through H2O2, photogenerated from TiO2, not from WO3, while Cu(2+) regeneration on a moderate photocatalyst is through the dissolved O2 in water.