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Tools for intuitive visualization of dynamic datasets are highly demanded for capturing information and revealing potential patterns, especially in understanding the trend of data changes. We propose a novel resolution-independent heuristic algorithm, termed Orthogonal Stable Treemap (OST), to implicitly display dynamic hierarchical data value changes. OST adopts a site-based method as the Voronoi treemap (VT), to preserve the layout stability for diversified data values. Meanwhile, OST partitions the whole canvas with horizontal or vertical lines, instead of the lines with arbitrary orientations in VT. Technical innovations are made in three parts: Initialization of site state to speed up the algorithm and preserve the layout; efficient computation of orthogonal rectangular diagram to partition the empty canvas; self-adaption of site state to quickly reach an equilibrium. The performance of OST is quantitatively evaluated in terms of computation complexity, computation time, convergence rate, visibility, and stability. Moreover, qualitative evaluations (use case and user study) are demonstrated on the dynamic work-in-process dataset in the wafer fab. Evaluation results show that OST combines the advantages of layout stability and tidiness, contributing to easier and faster plot understanding. [ABSTRACT FROM AUTHOR]

Prostate cancer (PCa) is a common cancer worldwide, which mostly occurs in males over the age of 50. Accumulating evidence have determined that long non‐coding RNA/microRNA (lncRNA/miRNA) axis plays a critical role in cell progression of cancers, including PCa. However, the pathogenesis of PCa has not been fully indicated. In this study, quantitative real‐time polymerase chain reaction was used to detect the expression of HCG11 and miR‐543. Western blot was applied to measure the protein expression of proliferating cell nuclear antigen, cleavage‐caspase 3 (cle‐caspase 3), N‐cadherin, E‐cadherin, GAPDH, P‐AKT, AKT, p‐mTOR, and mTOR. 3‐(4,5‐Dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT), transwell invasion, and transwell migration assay were used to detect cell proliferation, invasion, and migration, respectively. The function and mechanism of lncRNA HCG11 were confirmed in PCa cell and xenograft mice models. Luciferase assay indicated that miR‐543 was a target miRNA of HCG11. Further investigation revealed that overexpression of HCG11 inhibited cell proliferation, invasion, and migration, whereas induced cell apoptosis by regulating miR‐543 expression in vitro and in vivo. More than that, lncRNA HCG11 inhibited phosphoinositide‐3 kinase/protein kinaseB (PI3K/AKT) signaling pathway to suppress PCa progression. Our data showed the overexpression of HGC11‐inhibited PI3K/AKT signaling pathway by downregulating miR‐543 expression, resulting in the suppression of cell growth in PCa. This finding proved a new regulatory network in PCa and provided a novel therapeutic target of PCa. [ABSTRACT FROM AUTHOR]

Visual analytics tools are of paramount importance in handling high-dimensional datasets such as those in our turbine performance assessment. Conventional tools such as RadViz have been used in 2D exploratory data analysis. However, with the increase in dataset size and dimensionality, the clumping of projected data points toward the origin in RadViz causes low space utilization, which largely degenerates the visibility of the feature characteristics. In this study, to better evaluate the hidden patterns in the center region, we propose a new focus + context distortion approach, termed PolarViz, to manipulate the radial distribution of data points. We derive radial equalization to automatically spread out the frequency, and radial specification to shape the distribution based on user's requirement. Computational experiments have been conducted on two datasets including a benchmark dataset and a turbine performance simulation data. The performance of the proposed algorithm as well as other methods for solving the clumping problem in both data space and image space are illustrated and compared, and the pros and cons are analyzed. Moreover, a user study was conducted to assess the performance of the proposed method. [ABSTRACT FROM AUTHOR]

In this study, the marine ecological cycle is divided into subsystems of science and technology ( T ), the environment ( E ), resources ( R ), and the economy ( E ). A TERE model is constructed to measure the marine bearing capacity by taking the energy output of oceans as the impetus for the entire marine system. We construct a system dynamics model of the marine bearing capacity in Qingdao, China and establish the TERE model to simulate the status of 30 variables when the system reaches a steady state. Accordingly, five schemes—population control, pollution control, fishery control, economic growth, and no change—are proposed to predict the trends in economic growth, population growth, and environmental development in Qingdao City over a five-year period and to determine the optimal scheme. Generally, the pollution control scheme is optimal, regardless of economic development or reductions in energy-consumption and emissions. Therefore, Qingdao City should enhance its environmental protection measures to ensure that the economy and environment develop in harmony. [ABSTRACT FROM AUTHOR]

Bridging tensor is fundamental to the Bridging Model for prediction of thermomechanical and strength behaviors of a fiber reinforced composite based on constituent fiber and matrix properties. This paper focuses on derivation of the bridging tensors with an imperfect fiber–matrix interface. Using a three-phase coaxial cylinder assemblage (CCA) model, the stress fields in all of the three materials in the assemblage when subjected to six kinds of loading conditions are obtained by means of rigorous elasticity theory. The stresses are then averaged with respect to the corresponding phase volumes. By imposing that the averaged stress components in each phase be correlated with those in an adjacent phase through a bridging tensor and solving the resulting simultaneous linear algebraic equations, the bridging tensor elements are determined. Comparison of the thus obtained effective off-axis moduli with experiments for a SCS-6/Ti unidirectional (UD) composite is made to show the efficiency of the three-phase bridging tensors. Effect of interphases on the effective elastic properties and stress ratios of the composite with different coatings is investigated. [ABSTRACT FROM AUTHOR]

Interleukin 6 (IL-6) is a pro-inflammatory cytokine that is well established as a vital factor in determining the risk of coronary heart disease and pathogenesis of atherosclerosis. Moreover, accumulating evidences have shown that oxidized low-density lipoprotein (ox-LDL) can promote IL-6 expression in macrophages. Nevertheless, the underlying mechanism of how ox-LDL upregulates IL-6 expression remains largely unexplained. We found that the expression of insulin-like growth factor 2 (IGF2), nuclear factor kappa B (NF-κB), and IL-6 was upregulated at both the messenger RNA (mRNA) and protein levels in a dose-dependent manner when treated with 0, 25, 50, or 100 μg/mL of ox-LDL for 48 h in THP-1 macrophages. Moreover, overexpression of IGF2 significantly upregulated NF-κB and IL-6 expressions in THP-1 macrophages. However, the upregulation of NF-κB and IL-6 expressions induced by ox-LDL were significantly abolished by IGF2 small interfering RNA (siRNA) in THP-1 macrophages. Further studies indicated the upregulation of IL-6 induced by ox-LDL could be abolished when treated with NF-κB siRNA in THP-1 macrophages. Ox-LDL might upregulate IL-6 in the cell and its secretion via enhancing NF-κB in an IGF2-dependent manner in THP-1 macrophages. [ABSTRACT FROM AUTHOR]

Bridging Model is an efficient micromechanical theory which can be used to predict the effective thermomechanical as well as strength properties of a fiber reinforced composite. The key to the Bridging Model is a bridging tensor, which was obtained on Eshelby's inclusion method [Huang and Zhou, Strength of Fibrous Composites, Vol. 53, Zhejiang University Press, Springer, Hangzhou, (2011)]. A different approach to the closed-form expressions for the elements of a bridging tensor is presented in this work. The method is based on averaging the stress fields of a single-fiber inclusion embedded within an infinite matrix subjected to various load conditions. By solving the bridging equations between the averaged stress components in the fiber and those in the matrix, the exact expressions for the bridging tensor elements are obtained. The Bridging Model can be established by neglecting some small quantities in the bridging tensor elements. Effective elastic moduli of a unidirectional (UD) composite are expressed as functions of a bridging tensor. Comparisons of predicted elastic properties of a total number of 18 UD composites on simplified and the exact bridging tensors are made. POLYM. COMPOS., 36:1417-1431, 2015. © 2014 Society of Plastics Engineers [ABSTRACT FROM AUTHOR]

Prestack seismic inversion methods adopt approximations of the Zoeppritz equations to describe the relation between reflection coefficients and P-wave velocity, S-wave velocity, and density. However, the error in these approximations increases with increasing angle of incidence and variation of the elastic parameters, which increases the number of inversion solutions and minimizes the inversion accuracy. In this study, we explore a method for solving the reflection coefficients by using the Zoeppritz equations. To increase the accuracy of prestack inversion, the simultaneous inversion of P-wave velocity, S-wave velocity, and density by using prestack large-angle seismic data is proposed based on generalized linear inversion theory. Moreover, we reduce the ill posedness and increase the convergence of prestack inversion by using the regularization constraint damping factor and the conjugate gradient algorithm. The proposed prestack inversion method uses prestack large-angle seismic data to obtain accurate seismic elastic parameters that conform to prestack seismic data and are consistent with logging data from wells. [ABSTRACT FROM AUTHOR]

Abstract: A series of experiments using technologies of gene mutation and silencing as well as chemical biology have demonstrated that spinal d-amino acid oxidase (DAAO) contributes to the development of central sensitization-mediated chronic pain and might be a potential molecular target for the treatment of chronic pain. DAAO inhibitors are now under clinical investigations for the management of chronic neuropathic pain. This study examined the interactions between morphine and the DAAO inhibitor CBIO (5-chloro-benzo[d]isoxazol-3-ol) in pain and analgesia tolerance mainly in the formalin test. Given subcutaneously CBIO acutely interacted with morphine in analgesia in an additive manner both in the acute nociception settings (the formalin acute phase nociception, hot-plate test and tail immersion test) and in formalin-induced tonic pain. Bi-daily exposure of CBIO given subcutaneously for 7 days did not produce self-tolerance to analgesia or cross-tolerance to morphine whereas 7-day subcutaneous morphine induced self-tolerance to analgesia but not cross-tolerance to CBIO. More importantly, subcutaneous co-administrations or even single dose of CBIO completely prevented or reversed morphine tolerance to analgesia (exhibited by a single dose or a dose–response curve of morphine) in both formalin-induced acute phase nociception and tonic phase pain. These results, for the first time, identified DAAO as an efficacious molecule mediating morphine tolerance, in addition to clarifying the complex interactions between morphine and DAAO inhibitors probed by CBIO, and provided a pharmacological basis for DAAO inhibitors in combination with morphine to clinically manage pain. [Copyright &y& Elsevier]

To explore the anti-inflammatory effect of apolipoprotein M (apoM) on regulation of tumor necrosis factor-α (TNF-α)-induced expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) and further investigate the molecular mechanism of apoM in this process. We found that TNF-α could decrease expression of apoM and inhibitor of NF-κB-α (IκBα) in HepG2 cells. Overexpression of apoM caused a significant decrease of ICAM-1 and VCAM-1 expression, while it caused a significant increase of IκBα expression in HepG2 cells. Furthermore, the treatment with TNF-α could increase ICAM-1 and VCAM-1 expression, decrease IκBα protein expression, and increase nuclear factor-κB (NF-κB) activity, and these effects were markedly enhanced by small interfering RNA (siRNA)-mediated silencing of apoM in HepG2 cells. Our findings demonstrated that apoM suppressed TNF-α-induced expression of ICAM-1 and VCAM-1 through inhibiting the activity of NF-κB. [ABSTRACT FROM AUTHOR]

The oscillations of solar coronal filaments have received significant interest, and the restoring force and damping mechanism are the focus of discussion. We study the basic physical principles of the multi-factor, coupled, longitudinal oscillations of a filament, including its dominant restoring force and the damping mechanism. Using the Smoothed Particle Hydrodynamics (SPH) method we have performed for the first time a one-dimensional (1D) hydrodynamic numerical simulation of the longitudinal oscillation of the prominence. We modeled the process of mass uplift, that is the chromosphere mass enters the corona directly with the uplifted magnetic-flux tube. We studied multiple parameters, including the mass density, the initial perturbation velocity, and the geometry of the magnetic depression. We found that a sudden velocity disturbance can result in the oscillation of the prominence mass along the magnetic dip. Our numerical simulation analysis and theoretical study show that the oscillation period can be expressed as D − 0.616 w 0.978 v 0 0.261 (where D is the dip depth of the magnetic tube, w is half the length of the prominence magnetic dip, and v 0 is the initial velocity disturbance), which is slightly different from the previous linear pendulum theory. The particle-collision viscosity also affects the longitudinal-oscillation period. In a non-adiabatic process, the oscillation decays with time. Radiant cooling is the primary factor that causes damping. Plasma particles' collisional viscosity is also a cause of damping, which primarily occurs once the prominence moves to the farthest point from the equilibrium state. The proportional law of the attenuation time scale is deduced, that is τ ∼ l 1.194 ρ 0.615 D 0.732 ω − 1.099 v 0 − 0.412 (where l is the prominence length, and ρ is the prominence density). Compared to previous simulations, v 0 plays a more important role. The greater the amplitude, the greater the oscillation damping. The advantage of the SPH method used in this article is that it can avoid the accuracy loss caused by mesh distortion in extremely large deformations, and it can avoid the interface problem of the Euler mesh in the Euler method. Therefore, it is especially suitable for solving dynamic large deformation problems such as prominence oscillation and explosion. [ABSTRACT FROM AUTHOR]

Improvement of the treatment for Glioblastoma multiforme (GBM) especially the development of in situ controllable drug release is still a major concern. In this study, we developed waterborne biodegradable polyurethane (WBPU) scaffolds incorporated with redox-sensitive and RGD-decorated paclitaxel (PTX) polymer-drug conjugates (PDCs) for targeted GBM therapy in situ. The drug scaffolds could be implanted at residual GBM site post-operation. Dual-targeting PTX-PDCs were obtained through step-by-step conjugation of disulfide linked PTX, poly(ethylene glycol) (PEG), and arginine-glycine-aspartic acid (RGD). The RGD-modified PTX-PDCs were spherical nanoparticles (NPs) that would be released from scaffolds and identified GBM cells actively. Internalized redox-sensitive PTX-PDCs would be decomposed and release PTX inside GBM cells under the circumstances of glutathione (GSH). The release profiles of PTX from the scaffolds with/without GSH were investigated. In vitro cytotoxicity assay revealed that the dual-targeting PTX-PDCs from scaffolds could specifically kill GBM cells and protect normal cells, suggesting that dual-targeting PTX-PDC-loaded scaffolds may have the potential to repair tumor-induced brain injury. In vivo anti-recurrence assay indicated that the PTX-PDC-scaffolds could deliver PTX-PDCs to the GBM cells followed by inhibiting tumor growth and inducing apoptosis. In general, the PTX prodrug-loaded devices exhibited significant anti-GBM effects and normal tissue protection simultaneously, indicating that the WBPU scaffolds incorporated with dual-targeting PTX-PDCs may be a promising strategy for local therapy of GBM. [ABSTRACT FROM AUTHOR]

Highlights: [•] This paper reports an improved solid-state method which leads to a uniform coating. The influence of Li3PO4 and carbon coating on the electrochemical performance of LiFePO4 was studied. [•] LiFePO4 coating with Li3PO4 and carbon shows a higher capacity than pure carbon coating sample. [•] Results indicate that the surface structure has an important influence on the electrochemical performance of LiFePO4. The addition of Li3PO4 can decrease the interfacial resistance of Li FePO4. [Copyright &y& Elsevier]

At present, low-pass whole-genome sequencing (WGS) is frequently used in clinical research and in the screening of copy number variations (CNVs). However, there are still some challenges in the detection of triploids. Restriction site-associated DNA sequencing (RAD-Seq) technology is a reduced-representation genome sequencing technology developed based on next-generation sequencing. Here, we verified whether RAD-Seq could be employed to detect CNVs and triploids. In this study, genomic DNA of 11 samples was extracted employing a routine method and used to build libraries. Five cell lines of known karyotypes and 6 triploid abortion tissue samples were included for RAD-Seq testing. The triploid samples were confirmed by STR analysis and also tested by low-pass WGS. The accuracy and efficiency of detecting CNVs and triploids by RAD-Seq were then assessed, compared with low-pass WGS. In our results, RAD-Seq detected 11 out of 11 (100%) chromosomal abnormalities, including 4 deletions and 1 aneuploidy in the purchased cell lines and all triploid samples. By contrast, these triploids were missed by low-pass WGS. Furthermore, RAD-Seq showed a higher resolution and more accurate allele frequency in the detection of triploids than low-pass WGS. Our study shows that, compared with low-pass WGS, RAD-Seq has relatively higher accuracy in CNV detection at a similar cost and is capable of identifying triploids. Therefore, the application of this technique in medical genetics has a significant potential value. [ABSTRACT FROM AUTHOR]

BACKGROUND AND PURPOSE Spinal reactive oxygen species (ROS) are critically involved in chronic pain. d-Amino acid oxidase (DAAO) oxidizes d-amino acids such as d-serine to form the byproduct hydrogen peroxide without producing other ROS. DAAO inhibitors are specifically analgesic in tonic pain, neuropathic pain and cancer pain. This study examined the role of spinal hydrogen peroxide in pain and the mechanism of the analgesic effects of DAAO inhibitors. EXPERIMENTAL APPROACH Formalin-induced pain behaviours and spinal hydrogen peroxide levels were measured in rodents. KEY RESULTS Formalin injected into the paw increased spinal hydrogen peroxide synchronously with enhanced tonic pain; both were effectively prevented by i.t. fluorocitrate, a selective astrocyte metabolic inhibitor. Given systemically, the potent DAAO inhibitor CBIO (5-chloro-benzo[ d]isoxazol-3-ol) blocked spinal DAAO enzymatic activity and specifically prevented formalin-induced tonic pain in a dose-dependent manner. Although CBIO maximally inhibited tonic pain by 62%, it completely prevented the increase in spinal hydrogen peroxide. I.t. catalase, an enzyme specific for decomposition of hydrogen peroxide, completely depleted spinal hydrogen peroxide and prevented formalin-induced tonic pain by 65%. Given systemically, the ROS scavenger PBN (phenyl- N- tert-butylnitrone) also inhibited formalin-induced tonic pain and increase in spinal hydrogen peroxide. Formalin-induced tonic pain was potentiated by i.t. exogenous hydrogen peroxide. CBIO did not increase spinal d-serine level, and i.t. d-serine did not alter either formalin-induced tonic pain or CBIO's analgesic effect. CONCLUSIONS AND IMPLICATIONS Spinal hydrogen peroxide is specifically and largely responsible for formalin-induced pain, and DAAO inhibitors produce analgesia by blocking spinal hydrogen peroxide production rather than interacting with spinal d-serine. [ABSTRACT FROM AUTHOR]

Objective: Malignancy following renal transplantation remains inconsistent with the reported safety of kidney donation during the long-term follow-up.Methods: We conducted searches of the published literature which included healthy participants, recipients, living kidney donors (LKDs), and the availability of outcome data for malignancy. Eight from 938 potentially relevant studies were analyzed by means of fixed-effects model or random-effects model, as appropriately.Results: In 48,950 participants, the follow-up range was 18 months to 20 years, and the mean age of the subjects was approximately 41 years. The incidence rate with 95% confidence interval (CI) for malignancy after kidney transplantation was 0.03 (0.01–0.05) in recipients and 0.03 (0.1–0.07) in LKDs, giving a pooled incidence rate of 0.03 (95% CI 0.02–0.04). LKDs contrasted nondonors by the overall odds ratio and 95% CI for total cancer of 2.80 (2.69–2.92).Conclusions: Kidney transplantation was associated with an increased risk of cancer during a long-term follow-up. Long-term risk for cancer in LKDs and kidney recipients should be monitored. [ABSTRACT FROM AUTHOR]

Background Atherosclerosis is a chronic inflammatory disease and represents the leading cause of morbidity and mortality throughout the world. Accumulating evidences have showed that Dihydrocapsaicin (DHC) has been found to exert multiple pharmacological and physiological effects. Nevertheless, the effects and possible mechanism of DHC on proinflammatory response remain largely unexplained. Methods and results We found that DHC markedly upregulated NFIA and suppressed NF-κB expression in THP-1 macrophages. Up-regulation of proinflammatory cytokines induced by LPS including TNF-α, IL-1β and IL-6 were markedly suppressed by DHC treatment. We also observed that protein level of NFIA was significantly increased while NF-κB and proinflammatory cytokines were decreased by DHC treatment in apoE −/− mice. Lentivirus-mediated overexpression of NFIA suppressed NF-κB and proinflammatory cytokines expression both in THP-1 macrophages and plaque tissues of apoE−/− mice. Moreover, treatment with lentivirus-mediated overexpression of NFIA made the down-regulation of DHC on NF-κB and proinflammatory cytokines expression notably accentuated in THP-1 macrophages and apoE −/− mice. In addition, treatment with siRNA targeting NF-κB accentuated the suppression of proinflammatory cytokines by lentivirus-mediated overexpression of NFIA. Conclusion These observations demonstrated that DHC can significantly decrease proinflammatory cytokines through enhancing NFIA and inhibiting NF-κB expression and thus DHC may be a promising candidate as an anti-inflammatory drug for atherosclerosis as well as other disorders. [ABSTRACT FROM AUTHOR]

A series of 5-azaquinoxaline-2,3-dione derivatives were synthesized and evaluated on d -amino acid oxidase (DAAO) inhibition as potential α-hydroxylactam-based inhibitors. The potent inhibitory activities in vitro suggested that 5-nitrogen could significantly enhance the binding affinity by strengthening relevant hydrogen bond interactions. The analgesic effects of intrathecal and systemic injection of 8-chloro-1,4-dihydropyrido[2,3- b ]pyrazine-2,3-dione, a representative molecule of 5-azaquinoxaline-2,3-dione, were investigated in rodents. This research not only confirmed the analgesic effect of the DAAO inhibitors but provided a new class of chemical entities with oral application potential for the treatment of chronic pain and morphine analgesic tolerance. [ABSTRACT FROM AUTHOR]

C-reactive protein (CRP) is an acute-phase reactant protein that not only plays a predictive role in determining atherogenesis risk but also represents an active participant in atherogenesis onset and progression. Moreover, an increasing number of studies have reported that oxidized low-density lipoprotein (Ox-LDL) plays a significant role in the initiation and progression of atherosclerosis. However, the effect and underlying mechanism of Ox-LDL on CRP expression remains unclear. THP-1 macrophages were treated with 0, 25, 50, or 100 μg/mL of Ox-LDL for 48 h, or 50 μg/mL of Ox-LDL for 0, 12, 24, and 48 h, respectively. Messenger RNA (mRNA) and protein levels were measured by real-time quantitative PCR and Western blot analysis, respectively. We found that Ox-LDL markedly increased insulin-like growth factor 2 (IGF2) and CRP mRNA and protein levels in a dose- and time-dependent manner in THP-1 macrophages. Treatment with Ox-LDL increased CRP protein expression, and this effect was completely abolished by siRNA-mediated silencing of IGF2 in THP-1 macrophages. Moreover, treatment with pcDNA3.1-IGF2 significantly enhanced CRP protein expression in Ox-LDL-stimulated THP-1 macrophages. CRP expression is upregulated by Ox-LDL through the IGF2 pathway in THP-1 macrophages. [ABSTRACT FROM AUTHOR]

This work firstly established a one-to-one correspondence between a matrix and a natural number with Godel coding, by which it could judge two matrixes equality. Secondly, the work presented a secure protocol for computing matrix eigenvalues. Lastly, it proved the two protocols to be secure by simulation paradigm. Besides in the field of data outsourcing services, they have practical value with lower computational complexity and communication complexity. [ABSTRACT FROM AUTHOR]

Abstract: Two series of more available novel 1,2,3-triazole-Jaspine B hybrids were efficiently synthesized employing click chemistry approach and evaluated for their cytotoxic activities against three human cancer cell lines (EC-9706, MGC-803 and MCF-7). Among them, compound 14h showed excellent inhibition against MCF-7 (IC50 = 1.93 μM) and was more potent than 5-Fu and Jaspine B against all three cancer cell lines. Further investigation of apoptosis assay and cell cycle analysis demonstrated that compound 14h caused cellular early and late apoptosis and arrested the cell cycle at G2/M phase in a concentration- and time-independent manner. This was the first report about the synthesis and in vitro cytotoxic evaluation of 1,2,3-triazole-Jaspine B hybrids. [Copyright &y& Elsevier]

Aims: ATP-binding cassette transporter A1 (ABCA1) mediates the efflux of cholesterol and phospholipids to lipid-poor apolipoproteins, which then form nascent HDL, a key step in the mechanism of reverse cholesterol transport (RCT). While a series of microRNAs (miRNAs) have been identified as potent post-transcriptional regulators of lipid metabolism, their effects on ABCA1 function and associated mechanisms remain unclear. Methods and Results: ABCA1 was identified as a potential target of miR-144-3p, based on the results of bioinformatic analysis and the luciferase reporter assay, and downregulated after transfection of cells with miR-144-3p mimics, as observed with real-time PCR and western blot. Moreover, miR-144-3p mimics (agomir) enhanced the expression of inflammatory factors, including IL-1β, IL-6 and TNF-α, in vivo and in vitro, inhibited cholesterol efflux in THP-1 macrophage-derived foam cells, decreased HDL-C circulation and impaired RCT in vivo, resulting in accelerated pathological progression of atherosclerosis in apoE−/− mice. Clinical studies additionally revealed a positive correlation of circulating miR-144-3p with serum CK, CK-MB, LDH and AST in subjects with AMI. Conclusions: Our findings clearly indicate that miR-144-3p is essential for the regulation of cholesterol homeostasis and inflammatory reactions, supporting its utility as a potential therapeutic target of atherosclerosis and a promising diagnostic biomarker of AMI. [ABSTRACT FROM AUTHOR]

Rationale: It is clear that lipid disorder and inflammation are associated with cardiovascular diseases and underlying atherosclerosis. Nur77 has been shown to be involved in inflammatory response and lipid metabolism. Objective: Here, we explored the role of Nur77 in atherosclerotic plaque progression in apoE−/− mice fed a high-fat/high cholesterol diet. Methods and Results: The Nur77 gene, a nuclear hormone receptor, was highly induced by treatment with Cytosporone B (Csn-B, specific Nur77 agonist), recombinant plasmid over-expressing Nur77 (pcDNA-Nur77), while inhibited by treatment with siRNAs against Nur77 (si-Nur77) in THP-1 macrophage-derived foam cells, HepG2 cells and Caco-2 cells, respectively. In addition, the expression of Nur77 was highly induced by Nur77 agonist Csn-B, lentivirus encoding Nur77 (LV-Nur77), while silenced by lentivirus encoding siRNA against Nur77 (si-Nur77) in apoE−/− mice fed a high-fat/high cholesterol diet, respectively. We found that increased expression of Nur77 reduced macrophage-derived foam cells formation and hepatic lipid deposition, downregulated gene levels of inflammatory molecules, adhesion molecules and intestinal lipid absorption, and decreases atherosclerotic plaque formation. Conclusion: These observations provide direct evidence that Nur77 is an important nuclear hormone receptor in regulation of atherosclerotic plaque formation and thus represents a promising target for the treatment of atherosclerosis. [ABSTRACT FROM AUTHOR]

Abstract: A series of inhibitors of d-amino acid oxidase (DAAO) are specific in blocking chronic pain, including formalin-induced tonic pain, neuropathic pain and bone cancer pain. This study used RNA interference technology to further validate the notion that spinal DAAO mediates formalin-induced pain. To target DAAO, a siRNA/DAAO formulated in polyetherimide (PEI) complexation and a shRNA/DAAO (shDAAO, with the same sequence as siRNA/DAAO after intracellular processing) expressed in recombinant adenoviral vectors were designed. The siRNA/DAAO was effective in blocking DAAO expression in NRK-52E rat kidney tubule epithelial cells, compared to the nonspecific oligonucleotides. Furthermore, multiple-daily intrathecal injections of both siRNA/DAAO and Ad-shDAAO for 7days significantly inhibited spinal DAAO expression by 50–80% as measured by real-time quantitative PCR and Western blot, and blocked spinal DAAO enzymatic activity by approximately 60%. Meanwhile, both siRNA/DAAO and Ad-shDAAO prevented formalin-induced tonic phase pain by approximately 60%. Multiple-daily intrathecal injections of siRNA/DAAO and Ad-shDAAO also blocked more than 30% spinal expression of GFAP, a biomarker for the activation of astrocytes. These results further suggest that down-regulation of spinal DAAO expression and enzymatic activity leads to analgesia with its mechanism potentially related to activation of astrocytes in the spinal cord. [Copyright &y& Elsevier]

Abstract: Background: Sleep deprivation as well as peripheral neuropathy and cutaneous neurogenic inflammation has a facilitatory effect on pain perception. Here we studied whether oxidative stress-related mechanisms in the spinal cord that have been shown to contribute to pain facilitation in peripheral neuropathy and cutaneous neurogenic inflammation play a role in sleep deprivation-induced pain hypersensitivity. Methods: Flower pot method was used to induce rapid eye movement sleep deprivation (REMSD) of 48h duration in the rat that had a chronic intrathecal (i.t.) catheter for spinal administration of drugs. Pain behavior was assessed by determining the monofilament-induced limb withdrawal response. Results: REMSD of 48h produced mechanical hypersensitivity that was attenuated in a dose-related fashion by i.t. administration of two different antioxidants, phenyl-N-tert-butylnitrone (PBN) or 4-hydroxy-2,2,6,6-tetramethylpiperidine-1 oxyl (TEMPOL). While both antioxidants attenuated mechanical pain behavior also in control animals, their effects were significantly stronger after REMSD than in control conditions. Conversely, i.t. administration of a reactive oxygen species (ROS) donor, tert-butyl-hydroperoxide (t-BOOH), in control animals produced pain hypersensitivity that was prevented by i.t. pretreatment with an antioxidant, TEMPOL. I.t. treatment with PBN or TEMPOL at the currently used doses failed to influence motor behavior in the Rotarod test. Conclusions: The results indicate that among common mechanisms contributing to mechanical pain hypersensitivity following sleep deprivation as well as nerve injury or neurogenic inflammation is oxidative stress in the spinal cord. Implications: Compounds with antioxidant properties might prove useful in suppressing the vicious pronociceptive interaction between chronic pain and sleep-deprivation. [Copyright &y& Elsevier]

The concrete filled narrow rectangular steel tube (CFNRST) member is being increasingly used in the apartment buildings in China. Experimental study is conducted on the behavior of CFNRST members subjected to combined compression and uniaxial bending about the weak axis. Eleven specimens were fabricated considering the variation of key parameters including the slenderness, the width/height ratio of cross-section and eccentricity of compression. Comparisons are made between the predictions of representative solutions of design codes and the test results to examine their capacity for predicting the ultimate load of CFNRST members. New solutions with modifications on two existing solutions are proposed for the ultimate load of CFNRST members subjected to combined compression and uniaxial bending. Good agreements are achieved between the predictions of the proposed solutions and test results. • CFNRST members (wider side/shorter side = 2.0-3.5) subjected to combined compression and uniaxial bending were tested. • Representative solutions of design codes for the concrete filled rectangular steel tube are examined. • New solutions are proposed for the concrete filled narrow rectangular steel tube member. [ABSTRACT FROM AUTHOR]

Modularized circuit designs for chaotic systems are introduced in this paper. Especially, a typical improved modularized design strategy is proposed and applied to a new hyper-chaotic system circuit implementation. In this paper, the detailed design procedures are described. Multisim simulations and physical experiments are conducted, and the simulation results are compared with Matlab simulation results for different system parameter pairs. These results are consistent with each other and they verify the existence of the hyper-chaotic attractor for this new hyper-chaotic system. [ABSTRACT FROM AUTHOR]