A simplified qPCR method revealing tRNAome remodeling upon infection by genotype 3 hepatitis E virus

The landscape of tRNA–viral codons regulates viral adaption at the translational level, presumably through adapting to host codon usage or modulating the host tRNAome. We found that the major zoonotic genotype of hepatitis E virus (HEV) has not adapted to host codon usage, prompting exploration of the effects of HEV infection on the host tRNAome. However, tRNAome quantification is largely impeded by the extremely short sequences of tRNAs and redundancy of tRNA genes. Here, we present a length-extension and stepwise simplified qPCR method that utilizes a universal DNA/RNA hybrid tRNA adaptor and degenerate primers. Using this novel methodology, we observe that HEV infection dramatically reprograms the hepatic tRNAome, which is likely to facilitate translation of viral RNAs. This tRNAome quantification method bears broad implications for future tRNA research and possibly tRNA-based diagnostics

Combination of oncolytic adenovirus and luteolin exerts synergistic antitumor effects in colorectal cancer cells and a mouse model

In recent years, oncolytic viruses have attracted increasing interest due to their potent antitumor effects. Luteolin, a natural product, has additionally been observed to exhibit various pharmacological antitumor activities. Previously, a novel dual-targeting oncolytic adenovirus, complement decay-accelerating factor (CD55)-tumor necrosis factor ligand superfamily member 10 (TRAIL), was constructed, which exhibited significant growth inhibitory effects in various types of tumor cell. The present study investigated whether the combination of luteolin and CD55-TRAIL was able to exert a synergistic antitumor effect in colorectal carcinoma (CRC) cells. The cytotoxicity and tumor cell apoptosis mediated by combination treatment in CRC cells were detected via an MTT assay, Hoechst staining and western blotting, respectively. Tumor growth in vivo was examined in a CRC mouse xenograft model following various treatments. The results demonstrated that the addition of luteolin enhanced oncolytic adenovirus-mediated enhanced green fluorescent protein, early region 1A and TRAIL expression. The combination of CD55-TRAIL with luteolin synergistically inhibited tumor growth and promoted CRC cellular apoptosis in vitro and in vivo. Additionally, the combination of CD55-TRAIL with luteoli n significa ntly decrea sed cy totoxicit y in lung/bronchial normal epithelial cells, compared with single treatment

Direct-acting antiviral agents for liver transplant recipients with recurrent genotype 1 hepatitis C virus infection: Systematic review and meta-analysis

Background: Comprehensive evaluation of safety and efficacy of different combina‐ tions of direct‐acting antivirals (DAAs) in liver transplant recipients with genotype 1 (GT1) hepatitis C virus (HCV) recurrence remains limited. Therefore, we performed this systematic review and meta‐analysis in order to evaluate the clinical outcome of DAA treatment in liver transplant patients with HCV GT1 recurrence. Methods: Studies were included if they contained information of 12 weeks sustained virologic response (SVR12) after DAA treatment completion as well as treatment re‐ lated complications for liver transplant recipients with GT1 HCV recurrence. Results: We identified 16 studies comprising 885 patients. The overall pooled esti‐ mate proportion of SVR12 was 93% (95% confidence interval (CI): 0.89, 0.96), with moderate heterogeneity observed (τ 2 = 0.01, P < 0.01, I 2 =75%). High tolerability was observed in liver transplant recipients reflected by serious adverse events (sAEs) with pooled estimate proportion of 4% (95% CI: 0.01, 0.07; τ2 = 0.02, P < 0.01, I 2 = 81%). For subgroup analysis, a total of five different DAA regimens were applied for treating these patients. Sofosbuvir/Ledipasvir (SOF/LDV) led the highest pooled estimate SVR12 proportion, followed by Paritaprevir/Ritonavir/Ombitasivir/Dasabuvir (PrOD), Daclatasvir (DCV)/Simeprevir (SMV) ± Ribavirin (RBV), and SOF/SMV ± RBV, Asunaprevir (ASV)/DCV. There was a tendency for favoring a higher pooled SVR12 proportion in patients with METAVIR Stage F0‐F2 of 97% (95% CI: 0.93, 0.99) com‐ pared to 85% (95% CI: 0.79, 0.90) for stage F3‐F4 (P < 0.01). There was no significant difference between LT recipients treated with or without RBV (P = 0.23). Conclusions: Direct‐acting antiviral treatment is highly effective and well‐tolerated in liver transplant recipients with recurrent GT1 HCV infection

Dichotomal functions of phosphorylated and unphosphorylated STAT1 in hepatocellular carcinoma

Abstract: Interferons (IFNs) with antiviral and immune-stimulatory functions have been widely used in prevention and treatment of hepatocellular carcinoma (HCC). Signal transducer and activator of transcription 1 (STAT1) is a key element of the IFN signaling, and the function of STAT1 is critically determined by its phosphorylation state. This study aims to understand the functions of phosphorylated (p-) and unphosphorylated (u-) STAT1 in HCC. We found that u-STAT1 is significantly elevated in patient HCC tumor tissues and predominantly expressed in cytoplasm; while p-STAT1 is absent. Loss of u-STAT1 potently arrested cell cycle and inhibited cell growth in HCC cells. Induction of p-STAT1 by IFN-α treatment effectively triggers the expression of interferon-stimulated genes (ISGs), but has moderate effect on HCC cell growth. Interestingly, both u-STAT1 and p-STAT1 are induced by IFN-α, through with distinct time-dependent process. Furthermore, the ISG induction patterns mediated by p-STAT1 and u-STAT1 are also distinct. Importantly, artificial blocking of the induction of u-STAT1, but not p-STAT1, sensitizes HCC cells to treatment of IFNs. Therefore, p-STAT1 and u-STAT1 exert dichotomal functions and coordinately regulate the responsiveness to IFN treatment in HCC. Key Messages: STAT1 is upregulated and predominantly presented as u-STAT1 in HCC, while p-STAT1 is absent.U-STAT1 sustains but p-STAT1 inhibits HCC growth.The dynamic change of phosphorylation state of STAT1 control the responsiveness to IFN treatment

Investigation of Tensile Creep Behavior for High-Density Polyethylene (HDPE) via Experiments and Mathematical Model

Temperatures of −25 °C, +5 °C, and +35 °C were selected to study the creep behavior of high-density polyethylene (HDPE). The ultimate tensile strength of HDPE materials was obtained through uniaxial tensile experiments and the time–strain curves were obtained through creep experiments. When the loaded stress levels were lower than 60% of the ultimate strength, the specimens could maintain a longer time in the stable creep stage and were not prone to necking. In contrast, the specimens necked in a short time. Then, the time hardening form model was applied to simulate the time–strain curve and the parameter values were solved. The parameter values changed exponentially with the stresses, thereby expanding and transforming the time hardening model. The expanded model can easily and accurately predict creep behaviors of the initial and stable creep stages as well as the long-term deformations of HDPE materials. This study would provide a theoretical basis and reference value for engineering applications of HDPE

Research on Human Gait Phase Recognition Algorithm Based on Multi-Source Information Fusion

Gait phase detection is of great significance in the field of motion analysis and exoskeleton-assisted walking, and can realize the accurate control of exoskeleton robots. Therefore, in order to obtain accurate gait information and ensure good gait phase detection accuracy, a gait recognition framework based on the New Hidden Markov Model (NHMM) is proposed to improve the accuracy of gait phase detection. A multi-sensor gait data acquisition system was developed and used to collect the training data of eight healthy subjects to measure the acceleration and plantar pressure of the human body. Accuracy of the recognition framework, filtering algorithm and window selection, and the missing validation of the generalization performance of the method were evaluated. The experimental results show that the overall accuracy of NHMM is 94.7%, which is better than all other algorithms. The generalization of the performance is 84.3%. The results of this study provide a theoretical basis for the design and control of the exoskeleton

Effects of Oblique Incidence of SV Waves on Nonlinear Seismic Response of a Lined Arched Tunnel

The incident direction of earthquake motion is an important factor affecting the seismic response of underground structures. In this study, a three-dimensional (3D) oblique incidence method of SV waves is proposed and the effects of incident angles of SV waves on the seismic response of a lined arched tunnel are evaluated. Based on wave field decomposition principle and equivalent node force method and together with viscous-spring artificial boundary, the oblique incidence method of SV waves is implemented by transforming seismic wave field into the equivalent nodal forces acting on the artificial boundaries. By deriving the distance of the incident waves and the reflected wave on free surface to artificial boundaries, this method can comprehensively consider the phase difference of the seismic wave propagation and the influence of the damping effect of the rock medium on the seismic wave propagation. The method is programed into a dynamic finite element program and its effectiveness is examined by a numerical example. Consequently, the oblique incidence method is applied to evaluate the seismic behaviors of the tunnel. The numerical results reveal that (1) the oblique incidence of the seismic wave results in a larger seismic response; (2) the response amplitudes of the stress and displacement increase with the increase of incident angles and reaching the maximum in the case of 30° incident angle; (3) the damage extent increases with an increase in the incident angles, and the oblique incidence of the seismic wave is believed to increase the spatial difference of damage distribution