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Abstract Background Avian leukosis virus (ALV) is a major infectious disease that impacts the poultry industry worldwide. Despite intensive efforts, no effective vaccine has been developed against ALV because of mutations that lead to resistant forms. Therefore, there is a dire need to develop antiviral agents for the treatment of ALV infections and RNA interference (RNAi) is considered an effective antiviral strategy. Results In this study, the avian leukosis virus subgroup J (ALV-J) proviral genome, including the gag genes, were treated as targets for RNAi. Four pairs of miRNA sequences were designed and synthesized that targeted different regions of the gag gene. The screened target (i.e., the gag genes) was shown to effectively suppress the replication of ALV-J by 19.0-77.3%. To avoid the generation of escape variants during virus infection, expression vectors of multi-target miRNAs were constructed using the multi-target serial strategy (against different regions of the gag, pol, and env genes). Multi-target miRNAs were shown to play a synergistic role in the inhibition of ALV-J replication, with an inhibition efficiency of viral replication ranging from 85.0-91.2%. Conclusion The strategy of multi-target miRNAs might be an effective method for inhibiting ALV replication and the acquisition of resistant mutations.

With the rapid development of mobile crowdsourcing,crowdsourcing programs in the market have sprung up.They distribute tasks and use the power of the crowd to perform the tasks for collecting data and an effective incentive mechanism in mobile crowdsourcing becomes very important.However,the existing incentive mechanisms nowadays partially consider the reputation value,location and execution time of workers,which makes it difficult for crowdsourcing platform to select high-quality workers and assign multiple tasks on limited budgets or other constraints.To solve the above problems,this paper proposes an incentive mechanism on the basis of the multi-constrained worker selection (MSIM),which relies on two related algorithms.One is the algorithm of worker selection based on improved reverse auction model,which comprehensively considers many important limitations to select great workers to perform the tasks,such as worker reputation,geographical location,task completion degree and result quality.The other is the algorithm of reward and punishment by evaluation,which contains the evaluation of task-perceiving results and workers' reputation.The experimental results showed that not only can MSIM select excellent workers,but also it improved the credibility of the task results and the reputation of workers.It is proved within this paper that the MSIM is an effective incentive mechanism.

Background: Adipose stem cell‐derived exosomes (ADSC‐EXO) and botulinum toxin type A (BTX‐A) individually showed a therapeutic effect on skin wound repair. Aims: This study investigated their synergistic effect on promoting skin wound healing in vitro and in vivo and the underlying molecular events. Methods: ADSCs were isolated from Sprague–Dawley (SD) rats to obtain ADSC‐EXO by ultrafiltration and ultracentrifugation and were confirmed using nanoparticle tracking analysis and transmission electron microscopy. Human skin fibroblasts (HSF) were cultured and treated with or without ADSC‐EXO, BTX‐A, or their combination. Changes in cell phenotypes and protein expression were analyzed using different in vitro assays, and a rat skin wound model was used to assess their in vivo effects. Results: The isolated ADSC‐EXO from primarily cultured ADSCs had a circular vesicle shape with a 30–180 nm diameter. Treatment of HSF with ADSC‐EXO and/or BTX‐A significantly accelerated HSF migration in vitro and skin wound healing in a rat model. Moreover, ADSC‐EXO plus BTX‐A treatment dramatically induced VEGFA expression but reduced COL III and COL I levels in vivo. ADSC‐EXO and/or BTX‐A treatment significantly upregulated TGF‐β3 expression on Day 16 after surgery but downregulated TGF‐β1 expression, suggesting that ADSC‐EXO plus BTX‐A promoted skin wound healing and reduced inflammatory cell infiltration. Conclusions: The ADSC‐EXO plus BTX‐A treatment demonstrated a synergistic effect on skin wound healing through upregulation of VEGF expression and the TGF‐β3/TGF‐β1 and COL III/COL I ratio. [ABSTRACT FROM AUTHOR]

Ferroptosis is regulated by genes and participates in the physiological and pathological processes of ischemia-reperfusion injury, stroke, tumor and other diseases. The pathogenic mechanism is not yet clear. It is known that regulating p53 gene can induce ferroptosis of endothelial cells and tumor cells. Inhibiting ferroptosis enables GPX4 to function normally, blocking lipid oxidation on cell membranes, reducing the accumulation of reactive oxygen species (ROS), and protecting normal cells. In view of the polyreactivity of ferroptosis, it may help kill cancer cells and may damage normal cells. Therefore, genes related to regulatory ferroptosis sensitivity and the trigger mechanism need to be elucidated urgently. This article mainly reviews the known functional mechanisms of regulatory ferroptosis sensitive genes such as GPX4, FSP1, SLC7A11, P53, et al, in order to provide a reference for the in-depth analysis of ferroptosis research and the selection of drugs for major diseases. [ABSTRACT FROM AUTHOR]

Madecassoside is one of increasingly used constituent of Centella asiatica, a frequently prescribed crude drug in South eastern Asia and China for wound healing. In the present experiment, it exposes the neuroprotective nature of Madecassoside in GT1-7 cell lines, further, which the antioxidant activities are performed. The cellular toxicity was assessed using 3-(4,5-Dimethylthiazol-2-Yl)-2,5-Diphenyltetrazolium Bromide (MTT) assay with increased cell viability with IC 50 2.5µg/ml. the regulation of antioxidant levels showed changes in madecassoside treated cell lysate viz., SOD assay. Also, the antioxidative assays confirmed the negligible cellular damage caused to the GT1-7 cell lines. Hence, the results advocate that the current antioxidant and antitumor activity be justified by the high concentration of phenolic constituents, primarily the triterpene present in the C. asiatica.

Objective: To investigate the abnormal expression of microRNAs (miR-216, miR-222, miR-181) in the serum of patients with hepatocellular carcinoma (HCC) and its clinical significance., Methods: Serum miRNAs expression was investigated in 49 patients with HCC and 25 healthy normal controls by using real-time PCR technique, and then correlations between miRNAs expression and the clinicopathological features and prognosis of HCC patients were evaluated., Results: No differences were observed between the HCC patients and healthy controls with respect to the expressions of serum miR-181 and miR-216 (P > 0.05), while miR-222 was found to be significantly overexpressed in HCC serum samples (6.1 ± 6.6 vs 1.2 ± 0.6, P < 0.01). According to the median fold change of miR-222 (3-fold) in all HCC serum samples, we divided the 49 patients into two groups:a low expression group (25 patients) and a high expression group (24 patients).High level of miR-222 expression was correlated with cirrhosis (P < 0.01), tumor number (P = 0.013), portal vein tumor thrombosis (P = 0.002) and TNM stage (P = 0.020), while not correlated with serum alpha-fetoprotein level, tumor size and HbsAg. Kaplan-Meier survival analysis showed that the median overall survival in the high miR-222 expression group was significantly shorter than that in the low expression group (8.7 months vs 16.5 months, P = 0.036). In multivariate Cox analysis, TNM stage and serum miR-222 expression were two independent prognostic factors., Conclusion: Serum miR-222, upregulated in HCC, maybe helpful in prognosis of HCC patients.

Objective: To explore the prognostic significance of serum vascular endothelial growth factor receptor-2 (VEGFR-2) in patients with hepatocellular carcinoma (HCC) after transcatheter arterial chemoembolization (TACE)., Methods: A total of 69 HCC patients undergoing TACE from October 2008 to April 2012 were recruited and examined. Their serum level of VEGFR-2 level was measured by enzyme-linked immunosorbent assay (ELISA). The relationship between VEGFR-2 and their clinicopathologic features were observed. Prognostic significance of VEGFR-2 was assessed for their survival., Results: Significant differences existed when the serum level of VEGFR-2 was categorized by tumor number and liver cirrhosis (P = 0.021, P = 0.049). The post-treatment serum level of VEGFR-2 was significant higher than that at pre-treatment (P = 0.045). When the mean pre-treatment serum level of VEGFR-2 (8709 ng/L) was used as a cut-off point, the patients with a low serum level of VEGFR-2 had better overall and progression-free survival than those with a high serum level of VEGF (17 vs. 28 months, P = 0.001 and 10 vs. 15 months P = 0.031 respectively). As revealed by multivariate Cox analysis, the pre-treatment serum level of VEGFR-2 was an independent and significant prognostic factor of survival for HCC patients at post-TACE., Conclusion: The pre-treatment serum level of VEGFR-2 may predict the post-TACE prognosis in HCC patients.

To screen small animals susceptible to SARS-CoV, five species of animals, including guinea pig, hamster, albino hamster, chicken and rat, were experimentally infected with SARS-CoV strain BJ-01 by different routes. On the basis of this, further cynomolgus and rhesus macaques were selected and experimentally inoculated SARS-CoV, the quality they serve as animal model for SARS was evaluated. The results showed that, all five species of small animals chosed were not susceptible to SARS-CoV, no characterized changes in clinical sign and histopathology were observed after infection, but from the lung samples of large rat and pig guinea, the genomic RNA of SARS-CoV could be detected by RT-PCR at day 14 post infection, this suggested that SARS-CoV could replicate in these animals. After inoculated with SARS-CoV, all inoculated cynomolgus and rhesus macaques had developed interstitial pneumonia of differing severity. These changes on histopathology were similar to that seen in SARS patients, but the pathological lesions were less severe than that of human. Except interstitial pneumonia, no other characterized pathological changes were observed. This suggested cynomolgus and rhesus macaques were not the ideal animal model for SARS in fact, but they could serve as animal model for SARS when a more ideal animal model is absent.