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Hepatitis B virus (HBV) infection is a major public health problem. The high levels of HBV DNA and HBsAg are positively associated with the development of secondary liver diseases, including hepatocellular carcinoma (HCC). Current treatment with nucleos(t)ide analogues mainly reduces viral DNA, but has minimal, if any, inhibitory effect on the viral antigen. Although IFN reduces both HBV DNA and HBsAg, the serious associated side effects limit its use in clinic. Thus, there is an urgent demanding for novel anti‐HBV therapy. In our study, viral parameters were determined in the supernatant of HepG2.2.15 cells, HBV‐expressing Huh7 and HepG2 cells which transfected with HBV plasmids and in the serum of HBV mouse models with hydrodynamic injection of pAAV‐HBV1.2 plasmid. RT‐qPCR and Southern blot were performed to detect 35kb mRNA and cccDNA. RT‐qPCR, Luciferase assay and Western blot were used to determine anti‐HBV effects of MLN4924 and the underlying mechanisms. We found that treatment with MLN4924, the first‐in‐class neddylation inhibitor currently in several phase II clinical trials for anti‐cancer application, effectively suppressed production of HBV DNA, HBsAg, 3.5kb HBV RNA as well as cccDNA. Mechanistically, MLN4924 blocks cullin neddylation and activates ERK to suppress the expression of several transcription factors required for HBV replication, including HNF1α, C/EBPα and HNF4α, leading to an effective blockage in the production of cccDNA and HBV antigen. Our study revealed that neddylation inhibitor MLN4924 has impressive anti‐HBV activity by inhibiting HBV replication, thus providing sound rationale for future MLN4924 clinical trial as a novel anti‐HBV therapy.

Supplemental Material, sj-pdf-1-ccx-10.1177_10732748211051548 for Trends in Incidence and Prognostic Factors of Two Subtypes of Primary Liver Cancers: A Surveillance, Epidemiology, and End Results-Based Population Study by Jiping Yao, Xue Liang, Yanning Liu and Shuangshuang Li, Min Zheng in Cancer Control

Hepatocellular Carcinoma (HCC) lacks effective anti-metastasis drugs. Traditional Chinese Medicine (TCM) monomers have shown anti-proliferation activity in HCC, but few of them are specifically anti-metastasis. Therefore, further clarifying the indicators of HCC metastasis and screening TCM monomers based on the indicators, will effectively guide the development of novel anti-HCC drugs. The perinucleolar compartment (PNC), existing in the nuclear of tumor cells, is closely correlated with metastasis of several tumors. In this study, we found positive correlation between higher PNC prevalence and metastasis in HCC tissue of patients. The PNC prevalence was also positively correlated with the malignancy of HCC cell lines. On this premise, we established a PNC-based screening system for anti-metastasis TCM monomers and obtained Camptothecin (CPT), Evodiamine and Isoglycyrrhizin, the three most effective TCM monomers from a TCM monomer library to reduce the PNC prevalence in Huh7 cells. The anti-metastasis effect of these TCM monomers was positively correlated with their PNC inhibitor effect. Our data further revealed that CPT reduced metastasis of Huh7 cells possibly by inhibiting Epithelial-Mesenchymal Transition by upregulating the expression of ZO-1, E-cadherin and Claudin-1. The PNC-based screening system is effective and it may provide an effective technical platform for the development of anti-metastasis drugs.

In this paper, Bi

A reconstruction method based on convex hull was developed to reconstruct the overlapped citrus in natural scenes in order to improve the success rate of citrus harvesting robot. Due to the circular shape of citrus fruit, two reconstruction parameters were determined: the center point and the radius. Firstly, the K-means clustering method and threshold segmentation method were applied to detect the citrus targets in HSV color space. After that, the center points of each citrus fruit targets were extracted respectively by combing with the convex hull and the minimum external affine transformation rectangle. Finally, the reconstruction radiuses of the overlapped citrus targets were determined by searching the gray scale gradient extremum along the connecting line of each center point of citrus and the occlusion order is given. Experiments verified the validity of the method proposed. It provides a basis for the design of end-effector and the path planning of the harvesting robot.

In this paper, Bi2Te3 nanowires were prepared in anodized aluminum oxide template by electrochemical deposition. The morphological microstructural and electrical resistance characteristics of the nanowires were discussed to reveal the effect of deposition potential and electroactive substance (HTeO2 +) concentration. According to the electrode dynamics formula, it is found that the increase of electrode potential leads to the decrease of deposition current, so that deposition rate of nanowires decreases. At the same time, the deposition current controlled by diffusion in the mass transport process will have a maximum value with the increasing of deposition time. The deposition potential determines the favorable crystal plane for nanowires growth by the selection of proper surface energy. The temperature dependence of resistances in Bi2Te3 nanowires fabricated under different concentration of HTeO2 + reveals the transformation of the carriers' main scattering mechanism. This study could provide a better understanding of the deposition process of Bi2Te3 nanowires.