Small RNAs Targeting Transcription Start Site Induce Heparanase Silencing through Interference with Transcription Initiation in Human Cancer Cells

Heparanase (HPA), an endo-h-D-glucuronidase that cleaves the heparan sulfate chain of heparan sulfate proteoglycans, is overexpressed in majority of human cancers. Recent evidence suggests that small interfering RNA (siRNA) induces transcriptional gene silencing (TGS) in human cells. In this study, transfection of siRNA against −9/+10 bp (siH3), but not −174/−155 bp (siH1) or −134/−115 bp (siH2) region relative to transcription start site (TSS) locating at 101 bp upstream of the translation start site, resulted in TGS of heparanase in human prostate cancer, bladder cancer, and gastric cancer cells in a sequence-specific manner. Methylation-specific PCR and bisulfite sequencing revealed no DNA methylation of CpG islands within heparanase promoter in siH3-transfected cells. The TGS of heparanase did not involve changes of epigenetic markers histone H3 lysine 9 dimethylation (H3K9me2), histone H3 lysine 27 trimethylation (H3K27me3) or active chromatin marker acetylated histone H3 (AcH3). The regulation of alternative splicing was not involved in siH3-mediated TGS. Instead, siH3 interfered with transcription initiation via decreasing the binding of both RNA polymerase II and transcription factor II B (TFIIB), but not the binding of transcription factors Sp1 or early growth response 1, on the heparanase promoter. Moreover, Argonaute 1 and Argonaute 2 facilitated the decreased binding of RNA polymerase II and TFIIB on heparanase promoter, and were necessary in siH3-induced TGS of heparanase. Stable transfection of the short hairpin RNA construct targeting heparanase TSS (−9/+10 bp) into cancer cells, resulted in decreased proliferation, invasion, metastasis and angiogenesis of cancer cells in vitro and in athymic mice models. These results suggest that small RNAs targeting TSS can induce TGS of heparanase via interference with transcription initiation, and significantly suppress the tumor growth, invasion, metastasis and angiogenesis of cancer cells

Evaluating the Forecast Performance of the Meiyu Front Rainbelt Position: A Case Study of the 30 June to 4 July 2016 Extreme Rainfall Event

An impactful and poorly forecasted heavy rainfall event was observed in association with the Meiyu front over the Yangtze River valley of China from 30 June–4 July 2016. Operational global numerical weather prediction models for almost all forecast lead times beyond 24 h incorrectly forecasted the location and intensity of the precipitation associated with this event. This study presents the first examination of this poleward bias in the operational models for the Meiyu front, which has been frequently noted by meteorologists at the Chinese Meteorological Administration, and explores areas of forecast error and uncertainty in the prediction of the position of the primary frontal rainbelt that is crucial to the placement and intensity of the heavy rainfall. A new zonal mean maximum accumulated precipitation index is introduced and utilized to identify members in the European Centre for Medium-Range Forecasts (ECMWF) Ensemble Prediction System (EPS) that either perform well or perform poorly in forecasting the location of the Meiyu front. Using this new precipitation metric, five-member subgroups representing the EPS members that were most accurate and those that incorrectly displace the Meiyu front the furthest north were identified. An analysis of composite mean fields for the EPS subgroups and the correlation between the rain band placement and the 500 hPa heights was performed for several EPS model runs. We showed that a successful prediction of the location of the Meiyu front rainbelt position by the EPS is most sensitive to the intensity of the 500 hPa trough located over eastern China for the event. The ensemble members that had the largest northward error in the location of the rain band were found to have a more intense 500 hPa trough than the members that more accurately predicted the rainbelt. The more intense upper level trough was found to have enhanced the lower tropospheric southerly flow equatorward of the front and led to a less zonal-oriented Meiyu front, resulting in a northward displacement of both the rainbelt and the regions of more intense precipitation rates. Finally, an examination of the evolution of the differences between the subgroups shows that the primary differences in 500 hPa intensity propagate in-phase with the 500 hPa trough. We show that it is the intensity of the trough, rather than the rate of propagation, that is the most important source of forecast dissimilarities between the successful and failed forecasts

An Improved SPEA2 Algorithm with Adaptive Selection of Evolutionary Operators Scheme for Multiobjective Optimization Problems

A fixed evolutionary mechanism is usually adopted in the multiobjective evolutionary algorithms and their operators are static during the evolutionary process, which causes the algorithm not to fully exploit the search space and is easy to trap in local optima. In this paper, a SPEA2 algorithm which is based on adaptive selection evolution operators (AOSPEA) is proposed. The proposed algorithm can adaptively select simulated binary crossover, polynomial mutation, and differential evolution operator during the evolutionary process according to their contribution to the external archive. Meanwhile, the convergence performance of the proposed algorithm is analyzed with Markov chain. Simulation results on the standard benchmark functions reveal that the performance of the proposed algorithm outperforms the other classical multiobjective evolutionary algorithms

A hybrid self-adaptive invasive weed algorithm with differential evolution

The invasive weed algorithm (IWO) is a meta-heuristic algorithm, which is an effective and promising optimiser to address the optimisation problems. In this study, a hybrid algorithm based on the self-adaptive invasive weed algorithm (IWO) and differential evolution algorithm (DE), named SIWODE, is proposed to address the continuous optimisation problems. In the proposed SIWODE, first, the two parameters are adaptively proposed to improve the convergence speed of the algorithm. Second, the crossover and mutation operations are introduced in SIWODE to improve the population diversity and increase the exploration capability during the iterative process. Furthermore, a local perturbation strategy is presented to improve exploitation ability during the late process. The exploration and exploitation ability of the algorithm is effectively balanced by cooperative mechanisms. The experiment results of SIWODE show that the SIWODE has the superior searching quality and stability than other mentioned approaches

Promotion and Application of Innovative Technology in the Construction of Yunmao Expressway Green Road

With Yunfu Luoding city to Maoming Xinyi city highway as the support, builders focus on introducing innovative technology in the process of creating green road demonstration project, promoting energy conservation and emission reduction, reducing common quality problems, improving the technical level and management level of green road construction, and playing a reference role for the scientific application of innovative technology in common national and provincial highways

An improved water wave optimisation algorithm enhanced by CMA-ES and opposition-based learning

Water Wave Optimisation algorithm (WWO) is a new swarm-based metaheuristic inspired by shallow wave models for global optimisation. In this paper, an enhanced WWO, which combines with multiple assistant strategies (EWWO), is proposed. First, the random opposition-based learning (ROBL) mechanism is introduced to generate the initial population with high quality. Second, a new modified operation is designed and embedded into propagation operation to balance the global exploration and the local exploitation. Third, the covariance matrix self-adaptation evolution strategy (CMA-ES) is employed by the refraction operation to further strengthen the local exploitation. Furthermore, the diversity of the population is maintained in the evolution process by using a crossover operator. The experiment results based on CEC 2017 benchmarks indicate that the EWWO outperforms the state-of-the-art variant algorithms of the WWO and the standard WWO

Bacteriocins: Potential for Human Health

Due to the challenges of antibiotic resistance to global health, bacteriocins as antimicrobial compounds have received more and more attention. Bacteriocins are biosynthesized by various microbes and are predominantly used as food preservatives to control foodborne pathogens. Now, increasing researches have focused on bacteriocins as potential clinical antimicrobials or immune-modulating agents to fight against the global threat to human health. Given the broad- or narrow-spectrum antimicrobial activity, bacteriocins have been reported to inhibit a wide range of clinically pathogenic and multidrug-resistant bacteria, thus preventing the infections caused by these bacteria in the human body. Otherwise, some bacteriocins also show anticancer, anti-inflammatory, and immune-modulatory activities. Because of the safety and being not easy to cause drug resistance, some bacteriocins appear to have better efficacy and application prospects than existing therapeutic agents do. In this review, we highlight the potential therapeutic activities of bacteriocins and suggest opportunities for their application