Establishment of a Novel Mouse Hepatocellular Carcinoma Model for Dynamic Monitoring of Tumor Development by Bioluminescence Imaging.

In this study, a novel mouse model of hepatocellular carcinoma (HCC) was established by simultaneously knocking out Pten and p53 suppressor genes and overexpressing c-Met and △90-ß-catenin proto-oncogenes in the livers of mice via hydrodynamic injection (HDI). The mutations were introduced using the CRISPR/Cas9 and Sleeping Beauty transposon systems. In this way, a primary liver cancer model was established within six weeks. In addition, macrophages expressing arginase-1(Arg1) promoter coupled with firefly luciferase were engineered for bioluminescence imaging (BLI) of the tumor microenvironment. This novel, rapidly-generated model of primary hepatocellular carcinoma can be monitored noninvasively, which can facilitate not only applications of the model, but also the development of new drugs and treatment strategies of HCC.

Scavenger receptor class B type I is more conducive for genotype 1b hepatitis C virus internalization than low-density lipoprotein receptor.

The current limited understanding of HCV entry mechanisms hinders the development of specific antiviral drug screening techniques and vaccine assessment. HCV subtypes and cellular surface proteins both can affect virus tropism. Human factors such as low-density lipoprotein receptor (hLDLR), CD81 (hCD81), scavenger receptor class B type I (hSR-BI), claudin 1 (hCLDN1), and occludin (hOCLN) assist HCV entry into hepatocytes. Here, we studied the importance of five human proteins in the process of cell culture-derived (HCVcc) and serum-derived (HCV-sd) HCV entry using constructed humanized mouse hepatocytes and mouse models. We determined that unlike hLDLR, hSR-BI was an indispensable factor for 1b genotype HCV adsorption. Furthermore, this attachment can be completely prevented by treatment with a monoclonal antibody targeting hSR-BI. Our data support the idea that SR-BI is an essential factor in HCV infection, particularly during the initial HCV particle-binding step. This novel finding will facilitate the development of antiviral drugs and vaccines. Keywords: hepatitis C virus; virus internalization; model construction; hSR-BI.

A PET imaging study of the brain changes of glucose metabolism in patients with temporal lobe epilepsy and depressive disorder.

BACKGROUND: This study aims to compare the difference of the brain changes of glucose metabolism between temporal lobe epilepsy patients (TLE) with major depressive disorder and temporal TLE without major depressive disorder. METHODS: A total of 24 TLE patients, who met the inclusion criteria of our hospital, were enrolled in this study. They were divided into a TLE with depression group (n = 11) and a TLE without depression group (n = 13), according to the results of the HAMD-24 Scale. Two groups patients were examined using 18F-FDG PET brain imaging. RESULTS: The low metabolic regions of the TLE with depression group were mainly found in the left frontal lobe, temporal lobe and fusiform gyrus, while the high metabolic regions of the TLE with depression group were mainly located in the right frontal lobe, visual joint cortex and superior posterior cingulate cortex. Both of the TLE groups had high metabolic compensation in the non-epileptic area during the interictal period. CONCLUSIONS: There is an uptake difference of 18F-FDG between TLE patients with depression and TLE patients without depression in multiple encephalic regions.

Temporal and spectral dynamics underlying cognitive control modulated by task-irrelevant stimulus-response learning.

Behavioral and recent neuroimaging findings have shown reversal of interference effects due to manipulating proportion congruency (PC), which suggests that task-irrelevant stimulus-response (S-R) associations are strengthened and applied to predict responses. However, it is unclear how the strengthened S-R associations are represented and applied in the brain. We investigated with a between-subjects PC paradigm of the Hedge and Marsh task using electroencephalography (EEG). The behavioral results showed the reversal of the conflict effects, suggesting that task-irrelevant S-R associations were strengthened and used to prepare responses. The EEG results revealed the PC-related reversal of the conflict effects in the frontocentral N2 and parietal P3b amplitudes. Time-frequency analyses showed more pronounced PC-related reversal of the conflict effects in theta band (4-8 Hz) activity in frontocentral sites. These results suggest that the strengthened S-R associations due to PC manipulation modulated cognitive control. Importantly, the amplitude of lateralized readiness potential was higher in the high-PC condition than in the low-PC condition, suggesting that the strengthened short-term-memory spatial S-R associations that modulated cognitive control were applied similarly to long-term-memory spatial S-R associations.