Recruitment of bone marrow-derived myelomonocytic cells plays a fundamental role in tumor angiogenesis and metastasis. Placental growth factor (PlGF) is a potent cytokine that can attract myelomonocytic cells to the tumor. However, the underlying mechanism remains obscure. In this study, we demonstrate that tumor-derived PlGF activates NFAT1 via vascular endothelial growth factor receptor 1 in both murine and human myelomonocytic cells. Activation of NFAT1 is crucial for PlGF-induced myelomonocytic cell recruitment as shown by the in vitro transwell migration assay, transendothelial migration assay, and PlGF-overexpressing tumor models in mice, respectively. TNF-alpha is upregulated by PlGF in myelomonocytic cells in an NFAT1-dependent manner, which in turn contributes to PlGF-induced myelomonocytic cell recruitment. Blockade of TNF-alpha expression by RNA interference or neutralization of secreted TNF-alpha with its Ab attenuates PlGF-induced myelomonocytic cell migration and transendothelial migration. Furthermore, the inhibitory effect of NFAT1 RNA interference on PlGF function is rescued by exogenously added TNF-alpha. Taken together, we demonstrate that NFAT1 mediates PlGF-induced myelomonocytic cell recruitment via the induction of TNF-alpha. Our present studies discover a novel role of the NFAT1-TNF-alpha pathway in tumor inflammation, which may provide potential targets to diversify current cancer therapy.

PURPOSE: Notch signaling was recently found to be associated with prognosis of some cancers. The aim of the study is to investigate significance of the expression of HES1/HES5 protein, downstream effectors of Notch, in prognosis of the patients with advanced ovarian epithelial cancers. METHODS: Formalin-fixed, paraffin embedded tissues and clinic-pathological parameters from 61 patients with FIGO stage IIIc-IV ovarian serous adenocarcinoma were collected, the expression of HES1 and HES5 protein were immunohistochemically detected, and the association of HES1 and HES5 expression with survival of the patients were analyzed. RESULTS: The expressions of both HES1 and HES5 in adenocarcinoma were significantly higher than those in adenoma and normal control (chi (2)= 32.915, P = 0.000 and chi (2)= 46.863, P = 0.000 respectively). Overall survival and disease-free period were longer in HES1 low-expression patients (median 43.0 and 22.0 months) than those in high-expression patients (median 24.0 and 14.5 months). Of those, Overall survival period of patients with HES1 low-expression was significantly longer than that of those with high-expression (chi (2)= 4.049, P = 0.044). Univariate analysis and multivariate Cox regression model did not show that HES1 or HES5 expression was a factor associated with survival of advanced ovarian serous adenocarcinoma patients. CONCLUSIONS: The expressions of bHLH gene HES1 and HES5 are increased in advanced ovarian serous adenocarcinomas, and HES1 high-expression probably is a potential poor prognostic factor for the patients.

OBJECTIVE: To investigate the genetic characterizations and genotypes of measles viruses that was prevalent in Ningbo city. METHODS: Measles viruses were isolated from throat swab specimens of suspected measles cases from 2004 to 2008 and 456 bp fragments of C terminus of nucleprotein (N) gene were amplified by RT-PCR. Sequence analysis was conducted of all 22 virus strains while compared with other measles virus strain which published in GenBank. RESULTS: All of the 22 measles isolates belonged to genotype H1. The homogeneities of 456 bp fragments of C terminus of nucleprotein (N) gene were as high as 97.1%-98.5%,98.2%-99.6% and 98.5%-98.9% respectively. The nucleotide (amino acids) variability was 8.0%-9.5%(9.8%-14.5%) compared to S191. CONCLUSION: Genotype H1 measles virus circulated in Ningbo, China from 2004 to 2008. H1a was the predominant epidemic strain, H1b strain was existed as well.

Quantitative nucleophilicity scales are fundamental to organic chemistry and are usually constructed on the basis of Mayr's equation [log k=s(N+E)] by using benzhydrylium ions as reference electrophiles. Here an ab initio protocol was developed for the first time to predict the nucleophilicity parameters N of various pi nucleophiles in CH(2)Cl(2) through transition-state calculations. The optimized theoretical model (BH&HLYP/6-311++G(3df,2p)//B3LYP/6-311+G(d,p)/PCM/UAHF) could predict the N values of structurally unrelated pi nucleophiles within a precision of ca. 1.14 units and therefore may find applications for the prediction of nucleophilicity of compounds that are not readily amenable to experimental characterization. The success in predicting N parameters from first principles also allowed us to analyze in depth the electrostatic, steric, and solvation energies involved in electrophile-nucleophile reactions. We found that solvation does not play an important role in the validity of Mayr's equation. On the other hand, the correlations of the E, N, and log k values with the energies of the frontier molecular orbitals indicated that electrostatic/charge-transfer interactions play vital roles in Mayr's equation. Surprising correlations observed between the electrophile-nucleophile C--C distances in the transition state, the activation energy barriers, and the E and N parameters indicate the importance of steric interactions in Mayr's equation. A method is then proposed to separate the attraction and repulsion energies in the nucleophile-electrophile interaction. It was found that the attraction energy correlated with N+E, whereas the repulsion energy correlated to the s parameter.

Summary Growing evidence supports the importance of the chloroplast as a battlefield in plant-pathogen interaction. The Arabidopsis SIB1 gene encoding the chloroplast-localized SIGMA FACTOR-BINDING PROTEIN 1 is rapidly induced by infection with the bacterial pathogen Pseudomonas syringae, suggesting its possible role in connecting defense signaling with chloroplast function. Our study indicates that SIB1 might be involved in disease resistance by modulating the salicylate- and jasmonate-mediated defense responses.

Transition-metal-catalyzed decarboxylative coupling presents a new and important direction in synthetic chemistry. Mechanistic studies on decarboxylative coupling not only improve the understanding of the newly discovered transformations, but also may have valuable implications for the development of more effective catalyst systems. In this work, a comprehensive theoretical study was conducted on the mechanism of Myers' Pd-catalyzed decarboxylative Heck reaction. The catalytic cycle was found to comprise four steps: decarboxylation, olefin insertion, beta-hydride elimination, and catalyst regeneration. Decarboxylation was the rate-limiting step, and it proceeded through a dissociative pathway in which Pd(II) mediated the extrusion of CO(2) from an aromatic carboxylic acid to form a Pd(II)-aryl intermediate. Further analysis was conducted on the factors that might control the efficiency of Myers' decarboxylative Heck reaction. These factors included Pd salts, ligands, acid substrates, and metals.(1) Regarding Pd salts, PdCl(2) and PdBr(2) were worse catalysts than Pd(TFA)(2), because the exchange of Cl or Br by a carboxylate from Pd was thermodynamically unfavorable.(2) Regarding ligands, DMSO provided the best compromise between carboxyl exchange and decarboxylation. Phosphines and N-heterocarbenes disfavored decarboxylation because of their electron richness, whereas pyridine ligands disfavored carboxyl exchange.(3) Regarding acid substrates, a good correlation was observed between the energy barrier of R-COOH decarboxylation and the R-H acidity. Substituted benzoic acids showed deviation from the correlation because of the involvement of pi(substituent)-sigma(C(ipso)-Pd) interaction.(4) Regarding metals, Ni and Pt were worse catalysts than Pd because of the less favorable carboxyl exchange and/or DMSO removal steps in Ni and Pt catalysis.

The graph construction procedure essentially determines the potentials of those graph-oriented learning algorithms for image analysis. In this work, we propose a process to build the so-called directed ;1-graph, in which the vertices involve all the samples and the ingoing edge weights to each vertex describe its ;1-norm driven reconstruction from the remaining samples and the noise. Then, a series of new algorithms for various machine learning tasks, e.g., data clustering, subspace learning, and semi-supervised learning, are derived upon the ;1-graphs. Compared with the conventional k-nearest-neighbor graph and (2)-ball graph, the ;1-graph possesses the advantages: 1) greater robustness to data noise, 2) automatic sparsity, and 3) adaptive neighborhood for individual datum. Extensive experiments on three real-world datasets show the consistent superiority of ;1-graph over those classic graphs in data clustering, subspace learning, and semi-supervised learning tasks.

OBJECTIVE: To test the effects of VEGF-siRNA-transfected corneal epithelium on corneal neovascularization (CNV). METHODS: It was an experimental study. Cultured rat corneal epithelial cells and keratocytes were transfected with synthesize VEGF siRNA by lipofectamine 2000. The level of VEGF mRNA was analyzed by real time PCR, and the protein levels were determined by enzyme-linked immunosorbnent assay (ELISA). CNV was induced by cauterization with 1 mol/L sodium hydroxide in rat corneas. The VEGF-siRNA-transfected-corneal epithelium cells were transplanted to the CNV lesions. Immediately after transplantation, the VEGF-siRNA combined with lipofectamine 2000 were directly transfected rat cornea through injecting into the anterior chamber. After surgery, the surface areas occupied by new vessels were measured, and VEGF protein was localized by immunohistochemistry. RESULTS: The levels of VEGF expression at both mRNA and protein in the VEGF-siRNA transfected corneal epithelial cells and keratocytes were significantly lower than those of control cells. VEGF siRNA could inhibit the expression of VEGF mRNA in corneal epithelial cells and keratocytes to 57%- 85% and 59%- 78%, respectively. The VEGF-siRNA-transfected-corneal epithelium transplantation significantly decreased the surface areas occupied by new vessels. VEGF expression level in interference groups was lower than that in the control group. CONCLUSIONS: The development of CNV is markedly suppressed by VEGF-siRNA transfection in vivo.

Although nitrogen-containing group-directed cyclopalladation reactions have been well-known, Pd(II) insertion into C-H bonds promoted by coordination of an oxygen-only group to the palladium remains rather rare. In the present study, the first cyclopalladation complex formed from a simple phenol ester was characterized by X-ray crystallography. A promising protocol for the ortho C-H activation/aryl-aryl coupling of phenol esters that was not sensitive to moisture or air was then established. The utility of the reaction was demonstrated for the synthesis of useful phenol derivatives.

Dual-sensitive probe of 1-imidazole-2-(5-benzoacridine)-ethanone (IBAE) for the determination of free amines with fluorescence detection and online highly sensitive atmospheric chemical ionization-mass spectrometry identification (APCI-MS) has been developed. 2-(Benzoacridine)-5-acetic acid (BAAA) reacts with coupling agent N,N'-carbonyldiimidazole (CDI) to form a highly activated amide intermediate 1-imidazole-2-(5-benzoacridine)-ethanone (IBAE), which is dual-sensitive probe. The amide intermediate (IBAE) reacts preferably with amines in dimethylformamide (DMF) solvent to give the high yields of derivatives. IBAE-amine derivatives are not only sensitive to fluorescence but also to MS ionizable efficiency. The percent ionization delta values change from 0 to 57.32% in aqueous acetonitrile and from 0 to 62.14% in aqueous methanol. The relative standard deviations of the peak areas with fluorescence detection for each amine are <1.24%(40ng/ml, n=6). The fluorescence detection limits (at a signal-to-noise ratio of 3) are in the range of 0.15-0.50ng/ml. The online APCI-MS detection limits are in the range of 2.07-8.51ng/ml (at a signal-to-noise ratio of 3). Therefore, the facile IBAE intermediate derivatization allowed the development of a highly sensitive and specific method for the quantitative analysis of trace levels of amines in environmental water.