Overexpression of long non-coding RNA NORAD promotes invasion and migration in malignant melanoma via regulating the MIR-205-EGLN2 pathway.

Growing evidence suggests that long non-coding RNAs NORAD and miR-205 play a significant role in regulating cancer progression and metastasis. In this study, high expression of NORAD was firstly observed in melanoma tissues and human malignant melanoma cell lines, our aim was to study the interaction of them in the process of invasion and migration of malignant melanoma cells. NORAD, miR-205, and EGLN2 mRNA level in MM cells was detected by qRT-PCR. In situ hybridization (ISH) was performed to detect NORAD expression in MM tissues specimens. Effects of NORAD and miR-205 on Prolyl hydroxylase 2 (EGLN2) expression was explored by western blot in MM cells line. Dual-luciferase reporter assay was performed to verify the interaction relationship between NORAD and miR-205, as well as, miR-205 and EGLN2. Transwell assay was conducted to explore the effects of NORAD and miR-205 in vitro. Xenografts in nude mice experiment were used to confirm the role of NORAD and miR-205 in vivo. In vitro, NORAD knockdown significantly inhibited migration and invasion of malignant melanoma cells and elevated the expression of miR-205, there was an interaction between miR-205 and NORAD in the RNA-induced silencing complex. Upregulation of miR-205 induced significant inhibition of migratory and invasive ability compared with the scrambled control. However, downregulating NORAD largely reversed this effect. Furthermore, the regulatory effects of miR-205 on EGLN2 levels and the induction of endoplasmic reticulum stress were reversed by NORAD. In vivo, deletion of miR-205 induced tumor growth in nude mice. NORAD may play critical roles in tumorigenesis and progression of malignant melanoma by regulating of the miR-205-EGLN2 pathway, and may serve as a new therapeutic target

Conceptual Design of Non-ideal Mixtures Separation with Light Entrainers

A method is proposed to study the separation of minimum-, maximum-boiling azeotropic, and low volatility mixtures with a light entrainer, to investigate feasible regions of the key operating parameters reboil ratio (S) and entrainer - feed flowrate ratio (FE/F) for continuous processes. The thermodynamic topological predictions are carried out for 1.0–2, 1.0–1a, and 0.0–1 Serafimov’s class diagrams. It relies upon the knowledge of residue curve maps, along with the univolatility line, and it enables the prediction of possible products at the bottom of the column and limiting values of FE/F. The profiles of the stripping, extractive, and rectifying sections are calculated by equations considering S and FE/F, and they bring information about the location of singular points and possible composition profile separatrices that could impair process feasibility. Providing specified product composition and recovery, the approximate calculations are compared with rigorous simulations of extractive distillation processes. Separating non-ideal mixtures using a light entrainer provides more opportunities for the case when it is not easy to find an appropriate heavy or intermediate entraine

Cytotoxic Peptide Conjugates: Anticancer Therapeutic Strategies

ABSTRACT Traditional chemotherapeutic agents exhibit potent anticancer efficacy. However, in clinical applications, they also exhibit severely toxic side effects, and result in multidrug resistance (MDR) of cancer cells. So, receptor-targeted therapy is catching more attention of scientists from both academic and industry and recently is coming to the central stage of drug development. Certain peptides, due to their advantages like, easy synthesis and low cost, less or no immunogenicity, stability and high affinity, have been used as drug delivery vehicles. For example, cell-targeting peptides and cell-penetrating peptides (CPPs) in conjugation with cytotoxic agents have elicited remarkable effects. Luteinizing hormone-releasing hormone, somatostatin, and bombesin/gastrinreleasing peptide are the cell-targeting peptides that interact with their cognate surface receptors aberrantly expressed in many cancer cells, so these hormone peptides can be incorporated into cytotoxic agents for cell-specific targeting in cancer chemotherapy. Due to their cell-penetrating ability, CPPs also serve as cytotoxic drug delivery vehicles to carry drugs across the plasma membrane and overcome MDR of cancer cells. Cytotoxic agents linked to cell-targeting peptides and CPPs have been considered as an effective and reliable method in cancer chemotherapy. In this review, we address the applications of these peptides as drug delivery vehicles in targeted anticancer drug development

A Wideband Receiver with Adaptive Strong Interference Suppression

In this paper, a wideband receiver with high dynamic range is proposed. At the front end of the proposed receiver, a sensing waveform is used to sense the input signal. And by adjusting the sensing waveform so as to project the interference to zero, the receiver can eliminate the strong interference signal adaptively before sampling. Both the theoretic analysis and simulation show that this method can suppress the interference signal effectively and improve the sampling accuracy of the weak desired signal when the instantaneous dynamic range of the input signal is larger than the dynamic range of the ADC's quantizer

Novel Procedure for Assessment of Feasible Design Parameters of Dividing-Wall Columns: Application to Non-azeotropic Mixtures

Dividing wall columns (DWCs), as a subset of fully thermally coupled distillation systems (FTCDS), is considered as one of most appealing distillation technologies to the chemical industry, because it can bring about substantial reduction in the capital investment, as well as savings in the operating costs. This study targets on how to improve the energy efficiency of DWCs by achieving their well-designed feasible parameters. Two methods are applied to study the effect of liquid and vapor split ratios including a shortcut method and a method of systematic calculations by using differential equation profiles. In the latter approach, differential composition profiles in each column section are obtained by considering feasible key design parameters. The finding of pinch points for each section profiles allowed determining the limiting values of the operating parameters. The intersections of these profiles are used to get well-designed feasible parameters of the liquid and vapor split ratios in an attempt to obtain the desired purities of the top, bottom, and side-stream products. The obtained parameters are validated by rigorous simulations. Three types of case studies involve the separation of hydrocarbons (n-pentane, n-hexane, n-heptane), aromatics (benzene, toluene, p-xylene), and alcohols (ethanol, propanol, butanol)

High Altitude Frogs (Rana kukonoris) Adopt a Diversified Bet-hedging Strategy in the Face of Environmental Unpredictability

Environmental unpredictability can influence strategies of maternal investment among eggs within a clutch. Models predict that breeding females should adopt a diversified bet-hedging strategy in unpredictable environments, but empirical field evidence from Asia is scarce. Here we tested this hypothesis by exploring spatial patterns in egg size along an altitudinal gradient in a frog species (Rana kukunoris) inhabiting the Tibetan Plateau. Within-clutch variability in egg size increased as the environment became variable (e.g., lower mean monthly temperature and mean monthly rainfall at higher altitudes), and populations in environments with more unpredictable rainfall produced eggs that were smaller and more variable in size. We provide support for a diversified bet-hedging strategy in high-altitude environments, which experience dynamic weather patterns and therefore are of unpredictable environmental quality. This strategy may be an adaptive response to lower environmental quality and higher unpredictable environmental variance. Such a strategy should increase the likelihood of breeding success and maximize maternal lifetime fitness by producing offspring that are adapted to current environmental conditions. We speculate that in high-altitude environments prone to physical disturbance, breeding females are unable to consistently produce the optimal egg size due to physiological constraints imposed by environmental conditions (e.g., duration of the active season, food availability). Species and populations whose breeding strategies are adapted to cope with uncertain environmental conditions by adjusting offspring size and therefore quality show a remarkable degree of ability to cope with future climatic changes