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A new bergamotane sesquiterpenoid, fumigatanol (1), along with nine known compounds (2-10) were isolated from the Aconitum-derived fungus Aspergillus fumigatus M1. Their structures were established on the basis of extensive spectroscopic analyses, ECD experiment and NMR computational method. Antibacterial and cytotoxic activities of compound 1 were evaluated and no obvious antibacterial and cytotoxic activities were observed at concentrations of 256 μg/mL and 40.00 μM, respectively.

Background: Increasing evidence has identified circular RNAs (circRNAs) as ideal molecular biomarkers for cancer diagnosis, therapy, and prognosis. However, the overall diagnostic efficiency of circRNAs remains unclear. Thus, this meta-analysis aimed to comprehensively evaluate the diagnostic accuracy of circRNA expression profiles for cancer. Methods: A literature search of online databases was conducted to identify all eligible studies. The quality of the studies was assessed using the Quality Assessment of Diagnostic Accuracy Studies 2 tool. All statistical analyses were executed using STATA 14.0, Meta-DiSc 1.4, and Review Manager 5.2 software. Results: A total of 32 studies, involving 2,400 cases and 2,295 controls, were included in the diagnostic meta-analysis. The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, and area under the curve were 0.79 (95% CI: 0.73-0.84), 0.73 (95% CI: 0.67-0.79), 2.9 (95% CI: 2.5-3.5), 0.29 (95% CI: 0.24-0.36), 10 (95% CI: 8-13), and 0.83 (95% CI: 0.79-0.86), respectively. The overall analysis suggested that circRNAs are useful diagnostic biomarkers for cancer. Subgroup analysis indicated that plasma samples had a better diagnostic performance than cancer tissue samples for cancer detection. Studies involving ≥100 cases or gastric cancer showed higher sensitivities than those including

Thiol-disulfide glutaredoxin systems of bacterial cytoplasm favor reducing conditions for the correct disulfide bonding of functional proteins, and therefore were employed by bacteria to defend against oxidative stress. Listeria monocytogenes has been shown to encode a putative glutaredoxin, Grx (encoded by lmo2344), while the underlying roles remain unknown. Here we suggest an unexpected role of L. monocytogenes Grx in oxidative tolerance and intracellular infection. The recombinant Grx was able to efficiently catalyze the thiol-disulfide oxidoreduction of insulin in the presence of DTT as an election donor. Unexpectedly, the deletion of grx resulted in a remarkably increased tolerance and survival ability of this bacteria when exposed to various oxidizing agents, including diamide, and copper and cadmium ions. Furthermore, loss of grx significantly promoted bacterial invasion and proliferation in human epithelial Caco-2 cells and murine macrophages, as well as a notably increasing invasion but not cell-to-cell spread in the murine fibroblasts L929 cells. More importantly, L. monocytogenes lacking the glutaredoxin exhibited more efficient proliferation and recovery in the spleens and livers of the infected mice, and hence became more virulent by upregulating the virulence factors, InlA and InlB. In summary, we here for the first time demonstrated that L. monocytogenes glutaredoxin plays a counterintuitive role in bacterial oxidative resistance and intracellular infection, which is the first report to provide valuable evidence for the role of glutaredoxins in bacterial infection, and more importantly suggests a favorable model to illustrate the functional diversity of bacterial Grx systems during environmental adaption and host infection.

In this article, we estimate structural labor supply with piecewise-linear budgets and nonseparable endogenous unobserved heterogeneity. We propose a two-stage method to address the endogeneity issue that comes from the correlation between the covariates and unobserved heterogeneity. In the first stage, Evdokimov’s nonparametric de-convolution method serves to identify the conditional distribution of unobserved heterogeneity from the quasi-reduced model that uses panel data. In the second stage, the conditional distribution is plugged into the original structural model to estimate labor supply. We apply this methodology to estimate the labor supply of U.S. married men in 2004 and 2005. Our empirical work demonstrates that ignoring the correlation between the covariates and unobserved heterogeneity will bias the estimates of wage elasticities upward. The labor elasticity estimated from a fixed effects model is less than half of that obtained from a random effects model.

This paper proposes a new model to identify if and how much the educational attainment gap between blacks and whites is due to the difference in their neighborhoods. In this model, individuals belong to two unobserved types: the endogenous type, which may move in response to the neighborhood effect on their education; or the exogenous type, which may move for reasons unrelated to education. The Heckman sample selection model becomes a special case of the current model in which the probability of one type of individuals is zero. Although we cannot find any significant neighborhood effect in the usual Heckman sample selection model, we do find heterogeneous effects in our two-type model. In particular, there is a substantial neighborhood effect for the movers who belong to the endogenous type. No significant effects exist for other groups. We also find that the endogenous type has more education and moves more often than the exogenous type. On average, we find that the neighborhood variable, the percentage ...

In chronic thromboembolic pulmonary hypertension (CTEPH), central thrombi are the most likely disease initiators, and progressive pulmonary vascular remodeling, which is characterized by marked proliferation of pulmonary artery smooth muscle cells (PASMCs), may also contribute to the long-term progression of CTEPH. This study was designed to investigate the cellular characteristics of PASMCs isolated from the organized thrombotic tissues of CTEPH. In the present study, analysis of PASMCs isolated from five CTEPH patients and three control subjects showed that cells from CTEPH patients had certain characteristics that distinguished them from control cells, including inferior or no cell–cell contact inhibition growth, increased sensitivity to hypoxia-induced proliferation, resistance to serum starvation-induced apoptosis, and mitochondrial metabolism disorder. These differences in the PASMCs in endarterectomized tissue of CTEPH patients may prove useful in understanding the pathobiology of CTEPH.

Spinal NR2B-containing N-methyl-D-aspartate receptors (NR2B) play a critical role in the formation of central sensitization and persistent pain. Previous studies show that gene silencing of the spinal NR2B subunit by small interfering RNA (siRNA) could alleviate nociception in animals. The siRNA is a 19- to 23-nt RNA duplex, which can be synthesized in vitro or derived from short hairpin RNAs (shRNAs). In the present study, we investigated whether intrathecal injection of shRNAs targeting NR2B (GRIN2B shRNA) could affect nociception on formalin-induced pain in mice. Our results showed that intrathecal injection of GRIN2B shRNA could decrease NR2B mRNA and protein expression levels and hence effectively relieve formalin-induced nociception in mice, suggesting that intrathecal delivery of GRIN2B shRNA can be an efficient way to silence the target gene and provide new insights into the treatment of chronic pain.

Tubulin-binding agents have received considerable interest as potential anti-cancer drugs. These compounds interfere with tubulin dynamics and microtubule organization and thereby induce cell growth arrest at G(2)/M phase, and eventually lead to apoptotic cell death. Herein, we report that sulfated oligosaccharide JG3 was effective at inhibiting viability of cancer cells, and suppressing tumor growth in vivo. Our studies showed that JG3 significantly arrested cell cycle at G(2)/M phase and led cancer cells to apoptotic death. Consistent with this, tubulin was identified as a binding protein of JG3 using affinity chromatography and liquid chromatography-tandem mass spectrometry (LC-MS/MS). The interaction between JG3 and tubulin was characterized by surface plasmon resonance (SPR) analysis. Furthermore, it was demonstrated both at cellular level and in cell free system that JG3 potently prevented tubulin polymerization, thereby demolished microtubule organization in cancer cells. The underlying mechanism lies in its binding to tubulin on a unique site distinct from other conventional binding sites. All these suggest that JG3 is a novel antimitotic reagent, and this might shed new light on the understanding of anti-cancer activities and mechanisms of novel antimitotic reagents, and help develop new antimitotic agents in cancer therapy.

The aim of this work was to optimize time-dependent tablets using artificial neural network (ANN). The time-dependent tablet consisted of a tablet core, which contained sustained release pellets (70% isosorbide-5-mononitrate [5-ISMN]), immediate release granules (30% 5-ISMN), superdisintegrating agent (sodium carboxymethylstarch, CMS-Na), and other excipients, surrounded by a coating layer composed of a water-insoluble ethylcellulose and a water-soluble channeling agent. The chosen independent variables, i.e., X(1) coating level of tablets, X(2) coating level of pellets, and X(3) CMS-Na level, were optimized with a three-factor, three-level Box-Behnken design. Data were analyzed for modeling and optimizing the release profile using ANN. Response surface plots were used to relate the dependent and the independent variables. The optimized values for the factors X(1)-X(3) were 4.1, 14.1, and 29.8%, respectively. Optimized formulations were prepared according to the factor combinations dictated by ANN. In each case, the observed drug release data of the optimized formulations were close to the predicted release pattern. An in vitro model for predicting the effect of food on release behavior of optimized products was used in this study. It was concluded that neural network technique could be particularly suitable in the pharmaceutical technology of time-dependent dosage forms where systems were complex and nonlinear relationships often existed between the independent and the dependent variables.

The displacement behavior of hydrogen-deuterium at the high flow rate has been studied. The results show that displacement efficiency of deuterium decreases as displacement time decreases. Compared with the effects at low flow rate, high displacement efficiency still can be attained at high flow rate because higher displacement pressure that increases the collision frequency partly compensates the loss of exchange caused by an increase in flow rate.

We give simple necessary and sufficient conditions for consistency and asymptotic optimality of a root to the likelihood equation. Based on the results, a large-sample test is proposed for detecting whether a given root is consistent and asymptotically efficient, a property often possessed by the global maximizer of the likelihood function. A number of examples, and the connection between the proposed test and the test of White for model misspecification, are discussed. Monte Carlo studies show that the test performs quite well when the sample size is large but may suffer the problem of overrejection with relatively small samples.

A dual beam single-staggered Millitron TWT has been investigated, which was made up of a new type of structure: the ‘Bonded Multiple-Channel’ slow–wave system. A method was suggested to improve the gain and bandwidth of this device by controlling the coupling between the two chains of cavities. The dispersion characteristic and the interaction impedance have been analysed. The linear theory of the beam–wave interaction has been established. As a kind of TWT applying the concept ‘active power combining’, this tube will provide highly increasing output power by summation of the output power of each circuit.

A series of bichromophor compounds N — Hn — A( $ n = 2,4,6,8,10) has been synthesized by ourselves for the investigation of Energy Transfer. Bichromophore compound with γ — CD or β — CD aqueous solution are made up at the molar ratio of 1:1. It has been discovered that the efficiency of the energy transfer of the compound (n=10) in the γ—CD is obviously higher than that in the β — CD. This means that the cavity of the γ — CD is

(2014). Economic and Financial Challenges and Issues in the Asia-Pacific Countries: Guest Editors' Introduction. Emerging Markets Finance and Trade: Vol. 50, No. 1, pp. 118-119.