The Sleeping Beauty (SB) transposon system, derived from teleost fish sequences, is extremely effective at delivering DNA to vertebrate genomes, including those of humans. We have examined several parameters of the SB system to improve it as a potential, nonviral vector for gene therapy. Our investigation centered on three features: the carrying capacity of the transposon for efficient integration into chromosomes of HeLa cells, the effects of overexpression of the SB transposase gene on transposition rates, and improvements in the activity of SB transposase to increase insertion rates of transgenes into cellular chromosomes. We found that SB transposons of about 6 kb retained 50% of the maximal efficiency of transposition, which is sufficient to deliver 70-80% of identified human cDNAs with appropriate transcriptional regulatory sequences. Overexpression inhibition studies revealed that there are optimal ratios of SB transposase to transposon for maximal rates of transposition, suggesting that conditions of delivery of the two-part transposon system are important for the best gene-transfer efficiencies. We further refined the SB transposase to incorporate several amino acid substitutions, the result of which led to an improved transposase called SB11. With SB11 we are able to achieve transposition rates that are about 100-fold above those achieved with plasmids that insert into chromosomes by random recombination. With the recently described improvements to the transposon itself, the SB system appears to be a potential gene-transfer tool for human gene therapy.

This study examines the trends and determinants of child marriage among women aged 20-49 in Bangladesh. Data were extracted from the last six nationally representative Demographic and Health Surveys conducted during 1993-2011. Simple cross-tabulation and multivariate binary logistic regression analyses were adopted. According to the survey conducted in 2011, more than 75% of marriages can be categorized as child marriages. This is a decline of 10 percentage points in the prevalence of child marriage compared with the survey conducted in 1993-1994. Despite some improvements in education and other socioeconomic indicators, Bangladeshi society still faces the relentless practice of early marriage. The mean age at first marriage has increased by only 1.4 years over the last one and half decades, from 14.3 years in 1993-1994 to 15.7 years in 2011. Although the situation on risk of child marriage has improved over time, the pace is sluggish. Both the year-of-birth and year-of-marriage cohorts of women suggest that the likelihood of marrying as a child has decreased significantly in recent years. The risk of child marriage was significantly higher when husbands had no formal education or little education, and when the wives were unemployed or unskilled workers. Muslim women living in rural areas have a greater risk of child marriage. Women's education level was the single most significant negative determinant of child marriage. Thus, the variables identified as important determinants of child marriage are: education of women and their husbands, and women's occupation, place of residence and religion. Programmes to help and motivate girls to stay in school will not only reduce early marriage but will also support overall societal development. The rigid enforcement of the legal minimum age at first marriage could be critical in decreasing child marriage.

To identify hepatocellular carcinoma (HCC)‐implicated long noncoding RNAs (lncRNAs), we performed an integrative omics analysis by integrating mRNA and lncRNA expression profiles in HCC tissues. We identified a collection of candidate HCC‐implicated lncRNAs. Among them, we demonstrated that an lncRNA, which is named as p53‐stabilizing and activating RNA (PSTAR), inhibits HCC cell proliferation and tumorigenicity through inducing p53‐mediated cell cycle arrest. We further revealed that PSTAR can bind to heterogeneous nuclear ribonucleoprotein K (hnRNP K) and enhance its SUMOylation and thereby strengthen the interaction between hnRNP K and p53, which ultimately leads to the accumulation and transactivation of p53. PSTAR is down‐regulated in HCC tissues, and the low PSTAR expression predicts poor prognosis in patients with HCC, especially those with wild‐type p53. Conclusion: This study sheds light on the tumor suppressor role of lncRNA PSTAR, a modulator of the p53 pathway, in HCC.

Decreased levels of ALDH2 may indicate a poor prognosis in HCC patients, while forcing the expression of ALDH2 in HCC cells inhibited their aggressive behavior in vitro and in mice largely by modulating the activity of the ALDH2-acetaldehyde-redox-AMPK axis. Therefore, identifying ALDH2 expression levels in HCC might be a useful strategy for classifying HCC patients and for developing potential therapeutic strategies that specifically target metastatic HCC. (Hepatology 2017;65:1628-1644).

This study aimed to examine the macrophage phenotype and its relationship to renal function and histological changes in human DN and the effect of TREM-1 on high-glucose-induced macrophage activation. We observed that in renal tissue biopsies, the expression of CD68 and M1 was apparent in the glomeruli and interstitium, while accumulation of M2 and TREM-1 was primarily observed in the interstitium. The numbers of CD68, M1, and M2 macrophages infiltrating in the DN group were increased in a process-dependent manner compared with the control group, and the intensities of the infiltrates were proportional to the rate of subsequent decline in renal function. M1 macrophages were recruited into the kidney at an early stage (I+IIa) of DN. The M1-to-M2 macrophage ratio peaked at this time, whereas M2 macrophages predominated at later time points (III) when the percentage of M1/M2 macrophages was at its lowest level. In an in vitro study, we showed that under high glucose conditions, macrophages began to up-regulate their expression of TREM-1, M1, and marker iNOS and decreased the M2 marker MR. However, the above effects of high-glucose were abolished when TREM-1 expression was inhibited by TREM-1 siRNA. In conclusion, our study demonstrated that there was a positive correlation between the M1/M2 activation state and the progress of DN, and TREM-1 played an important role in high-glucose-induced macrophage phenotype transformation.