RNA Nanotechnology for Next Generation Targeted Drug Delivery

The emerging field of RNA nanotechnology is developing into a promising platform for therapeutically application. Utilizing the state-of-art RNA nanotechnology, RNA nanoparticles can be designed and constructed with controllable shape, size for both RNA therapeutics and chemical drug delivery. The high homogeneity in particle size and ease for RNA therapeutic module conjugation, made it feasible to explore versatile RNA nanoparticle designs for preclinical studies. One vital module for therapeutic RNA nanoparticle design is RNA aptamer, which can enable the RNA nanoparticles find its specific target for targeted drug delivery. A system of screening divalent RNA aptamers for cancer cell targeting was developed. The system utilized a highly stable three way junction (3WJ) derived from phi29 bacteriophage packing RNA (pRNA). Instead of using one random loop for aptamer SELEX as traditionally, the divalent RNA nanoparticle library contains two variable loops for substrate binding, similar to protein antibodies. The presence of two binding sites on one aptamer greatly enhanced its affinity, and the thermodynamically stability of pRNA-3WJ motif enables controllable RNA folding of each loop. The selected RNA antibody against epithelial adhesion molecule (EpCAM) A9-8 can deliver therapeutic anti-miR21 to EpCAM positive cancer cells in vitro. The feasibility of using RNA aptamer for targeted chemical drug delivery is explored. A phosphorothioate bond modified DNA (thio-DNA) aptamer targeting annexin A2 was utilized as ligand to build nucleic acid nanoparticles for ovarian cancer targeted drug delivery. A DNA/RNA hybrid nanoparticle was generated by conjugating the thio-DNA aptamer to pRNA-3WJ motif. The DNA/RNA hybrid nanoparticles showed favorable property for delivering doxorubicin to ovarian cancer cells in vitro, also targeted to ovarian cancer xenograft in bio-distribution study in vivo. Utilizing the spatial orientation of pRNA-3WJ, cholesterol modification on the arrow tail of pRNA-3WJ can display RNA nanoparticle on the surface of exosomes/extracellular vesicles (EV) for active targeting. Taking the advantage of RNA ligand for specific targeting; and exosome for efficient membrane fusion, cytosol homing and functional siRNA delivery; the RNA ligand decorated exosomes were constructed for specific delivery of siRNA to cancer cells. PSMA aptamer-displaying exosomes and encapsulated survivin siRNA (PSMAapt/EV/siSurvivin) showed efficient gene silencing both in cell culture and animal trials. After systemically injection of PSMAapt/EV/siSurvivin to prostate cancer xenograft mice, cancer growth was almost completely blocked. These results suggest the advance of RNA nanotechnology can further drive its way towards clinical application as a novel next generation drug delivery system

Simulation Methods Comparison and Parameter Estimation for a Fractional Stochastic Volatility Model with Application in Stock Price Analysis

This paper studies continuous-time stock pricing models with stochastic volatility driven by fractional Brownian motion. We compare two ways for simulating the paths of stochastic volatility and stock price when the Hurst parameter of fractional Brown motion is between 0.5 and 1. The first approach, is to use truncated fractional Brownian motion to approximate the fractional Brownian motion and estimate the volatility by Monte Carlo integral and symbolic integral. In the second one, Euler method is employed in simulation, without truncating the fractional Brownian process. Simulating the fractional Brownian motion in the second approach, we use spectral representation. Simulation results show that the latter is more efficient than using the symbolic integral and Monte Carlo integral is the worst. The application of the stochastic model is illustrated through real financial data

Research Progress of Abnormal Expression of LKB1/STK111 in Non-Small Cell Lung Cancer

Non small cell lung cancer (NSCLC) is a kind of malignant tumor originated from bronchial mucosa, bronchial glands and alveolar epithelium. It has become the main cause of death of malignant tumors in our population. STK11 is a common tumor suppressor gene, its encoded protein liver kinase B1 (LKB1) is an essential serine / threonine protein kinase. LKB1/STK111 inhibits the occurrence and development of tumors through a variety of mechanisms and plays a key regulatory role in malignant tumors. The increased risk of cancer development is also associated with the absence of STK11. More and more studies have found that the abnormal expression of LKB1/STK111 will affect the occurrence and development of lung cancer, especially in NSCLC. This paper reviews the tumor suppressive mechanism of LKB1/STK111 in the occurrence and development of NSCLC, its relationship with NSCLC, and the prognosis and treatment

Cluster Correspondence Analysis and Reduced K-Means: A Two-Step Approach to Cluster Low Back Pain Patients

For the IFCS 2017 data challenge on low back pain (LBP) patients clustering, we used a two-step approach. Two of the challenging characteristics of the data set are the presence of missing values and mixed type variables. After a specific pretreatment, in the first step, we performed domain clustering using cluster correspondence analysis (clusCA). Upon the output variables from each domain, we did the second step, reduced K-means clustering, to get the final clusters of patients. The conclusion section shows the final clustering results and a profile plot of the clusters. Every cluster is highly interpretable and evaluated well with some descriptive variables which are used for measuring the clustering results

Aroma Compounds in Wine

Volatile aroma compounds are very important to grape wine quality. In order to understand the flavor of wine, a multitude of scientific investigations was carried out and a number of appropriate analytical tools for flavor study were developed in the past few decades. This chapter deals with major achievements reported in wine aroma and flavor. Firstly, we illustrate the existing knowledge on aroma compounds contributing to wine flavor, as well as the types of wine aroma compounds. Furthermore, the main factors affecting flavor quality in wine are discussed. Finally, the genomics and biotechnology of wine flavor are also summarized. This chapter broadens the discussion of wine aroma compounds to include more modern concepts of biotechnology and also provides relevant background and offers directions for future study

Equity evaluation of urban park system: a case study of Xiamen, China

Urban parks play a distinctive and important role in satisfying residents’ demands on leisure and recreation, and thus have become the focus of research in the field of urban planning and sustainable development. This paper used equity as indicator to combine both the supply and demand sides of urban park service. Taking Xiamen as the study case, the relationship between spatial distribution of population and park services was analyzed. The results show that while population density has a significant spatial relationship with urban park service level at the city scale, Xiamen has the problem of neglecting the equity of urban park service between people and regions within the city. The proposed approach builds up the linkage between urban park service and urban population in order to evaluate the performance of urban park. Although the mechanism remains to be discussed, this study provides a useful auxiliary tool for constructing a guideline for urban green space planning, since urban park is increasingly seen as a kind of restricted public resource and ensuring its equity should be an important task for city mangers

Study on the Rough-set-based Clustering Algorithm for Sensor Networks

The traditional clustering algorithm is a very typical level routing algorithm in wireless sensor networks (WSN). On the basis of the classical LEACH (Low Energy Adaptive Clustering Hierarchy) algorithm, this paper proposes an energy efficient clustering algorithm in WSN. Through the introduction of rough set, the new algorithm mainly introduces how to confirm an optimized strategy to choose the cluster head effectively by the simplified decision table. That is to say, by discrete normalized data preprocessing of attribute value, getting discretization decision table. Finally, the results from simulated experiments show that the clustering algorithm based on rough set theory can optimize the clustering algorithm in network data. That is to say, the rough-set-based clustering algorithm can effectively choose the cluster head, balance the energy of the nodes in the cluster and prolong the lifetime of sensor networks

Protective Effects of Salvia miltiorrhizae on Multiple Organs of Rats with Obstructive Jaundice

Purpose. we aim to explore the protective effects of Salvia miltiorrhizae injection on multiple organs of obstructive jaundice (OJ) rats through observing the impact of this injection on the pathological alterations in these organs and the contents of endotoxin, PLA2, and TNF-α in the blood. Methods. A total of 90 mice were randomly divided into sham-operated group, model-control group, and Salvia miltiorrhizae-treated group (n = 30). According to the duration of postoperative administration, each group was further divided into two subgroups, namely, 21 d subgroup (consecutive administration for 21 d, n = 15) and 28 d subgroup (consecutive administration for 28 d, n = 15). After administration, the pathological alterations in multiple organs were observed and the contents of endotoxin, PLA2, and TNF-α in the blood were determined. Results. Compared to model control group, the number of dead rats in treated group decreased though there was no statistical difference between the two groups. The pathological alterations in the liver, kidney, and spleen in treated group showed varying degrees of mitigation. At all time points, the contents of plasma endotoxin declined significantly. On day 28, plasma PLA2 content in treated group was significantly lower than that in model-control group. Conclusion. Salvia miltiorrhizae injection is able to obviously reduce the contents of inflammatory mediators in the blood of OJ rats and exert some protective effects on multiple organs of these rats