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Sludge drying gases (SDG), evolving from drying and mild thermal decomposition (<300°C) of raw sewage sludge contain NH3 and SO2 as well as other N- and S-compounds. All of these are potential PCDD/Fs suppressants. It is indeed observed that these SDG suppress 2,3,7,8-substitued PCDD/Fs formation on Model Fly Ash (MFA) with an efficiency up to 97.6% in wt. units and 96% in I-TEQ, respectively. This suppression is strong for (the bulk of) PCDD/Fs, adsorbed on the model fly ash; conversely, sludge drying gases enhance PCDD/Fs desorption from MFA. Moreover, TCDD/Fs are suppressed least, possibly following stepwise dechlorination of higher chlorinated PCDD/Fs. Characteristics, such as the type, origins and amount of sludge, its moisture-, nitrogen- and sulfur content and the nature of the thermal treatment applied are all expected to influence upon the suppression capabilities. In this study three types of dry sludge are tested and applied as suppressant in four different amounts or modes. The quality of the sludge drying gases is continuously monitored: the Gasmet results reveal that NH3 and SO2 are the most important components of SDG. The MFA reaction residue is scrutinized by Scanning Electron Microscope (SEM) and Energy Dispersive Spectrometer (EDS) analysis. A large number of particles attaching to the surface of model fly ash are observed by SEM. Moreover, EDS analysis reveals that part of the chlorine in MFA is carried away with the SDG and replaced by sulfur, so that eliminating chlorine may be part of the inhibition mechanism. However, further research is still needed to establish the optimum operating modes and to confirm the role of both inorganic and organic nitrogen and sulfur compounds in the suppression of PCDD/Fs formation on model fly ash. [ABSTRACT FROM AUTHOR]

Drug-induced ototoxicity, as a toxic side effect, is an important issue needed to be considered in drug discovery. Nevertheless, current experimental methods used to evaluate drug-induced ototoxicity are often time-consuming and expensive, indicating that they are not suitable for a large-scale evaluation of drug-induced ototoxicity in the early stage of drug discovery. We thus, in this investigation, established an effective computational prediction model of drug-induced ototoxicity using an optimal support vector machine (SVM) method, GA-CG-SVM. Three GA-CG-SVM models were developed based on three training sets containing agents bearing different risk levels of drug-induced ototoxicity. For comparison, models based on naïve Bayesian (NB) and recursive partitioning (RP) methods were also used on the same training sets. Among all the prediction models, the GA-CG-SVM model II showed the best performance, which offered prediction accuracies of 85.33% and 83.05% for two independent test sets, respectively. Overall, the good performance of the GA-CG-SVM model II indicates that it could be used for the prediction of drug-induced ototoxicity in the early stage of drug discovery. [ABSTRACT FROM AUTHOR]

The omasal epithelial barrier plays important roles in maintaining nutrient absorption and immune homeostasis in ruminants. However, little information is currently available about the changes in omasal epithelial barrier function at the structural and molecular levels during feeding of a high-grain (HG) diet. Ten male goats were randomly assigned to two groups, fed either a hay diet (0% grain; n = 5) or HG diet (65% grain; n = 5). Changes in omasal epithelial structure and expression of tight junction (TJ) proteins were determined via electron microscopy and Western blot analysis. After 7 weeks on each diet, omasal contents in the HG group showed significantly lower pH (P< 0.001) and significantly higher concentrations of free lipopolysaccharides (LPS; P= 0.001) than the hay group. The goats fed a HG diet showed profound alterations in omasal epithelial structure and TJ proteins, corresponding to depression of thickness of total epithelia, stratum granulosum, and the sum of the stratum spinosum and stratum basale, marked epithelial cellular damage, erosion of intercellular junctions and down-regulation in expression of the TJ proteins, claudin-4 and occludin. The study demonstrates that feeding a HG diet is associated with omasal epithelial cellular damage and changes in expression of TJ proteins. These research findings provide an insight into the possible significance of diet on the omasal epithelial barrier in ruminants. [ABSTRACT FROM AUTHOR]

Highlights: [•] High-level concentrations of PCDD/Fs are hard to destroy catalytically. [•] A mixture of catalyst and activated carbon can enhance the destruction and removal efficiency. [•] Such a mixture performs well, even at low temperature (180, 160°C). [•] The AC characteristics may influence upon the adsorption and degradation ability of this mixture. [ABSTRACT FROM AUTHOR]

Abstract: Current treatment for hepatitis C is barely satisfactory, there is an urgent need to develop novel agents for combating hepatitis C virus infection. This study discovered a new class of thieno[2,3-b]pyridine derivatives as HCV inhibitors. First, a hit compound characterized by a thienopyridine core was identified in a cell-based screening of our privileged small molecule library. And then, structure activity relationship study of the hit compound led to the discovery of several potent compounds without obvious cytotoxicity in vitro (12c, EC50 =3.3μM, SI >30.3, 12b, EC50 =3.5μM, SI >28.6, 10l, EC50 =3.9μM, SI >25.6, 12o, EC50 =4.5μM, SI >22.2, respectively). Although the mechanism of them had not been clearly elucidated, our preliminary optimization of this class of compounds had provided us a start point to develop new anti-HCV agents. [Copyright &y& Elsevier]

The average path length of a network is an important index reflecting the network transmission efficiency. In this paper, we propose a new method of decreasing the average path length by adding edges. A new indicator is presented, incorporating traffic flow demand, to assess the decrease in the average path length when a new edge is added during the optimization process. With the help of the indicator, edges are selected and added into the network one by one. The new method has a relatively small time computational complexity in comparison with some traditional methods. In numerical simulations, the new method is applied to some synthetic spatially embedded networks. The result shows that the method can perform competitively in decreasing the average path length. Then, as an example of an application of this new method, it is applied to the road network of Hangzhou, China. [ABSTRACT FROM AUTHOR]

Background: Laparoscopic transcystic common bile duct exploration has become a safe and ideal treatment of common bile duct stones. This study was designed to explore the clinical value of modified laparoscopic transcystic common bile duct exploration as a first line of treatment for patients with common bile duct stones. Patients and Methods: A retrospective, case-control study of clinically comparable groups of patients who underwent the laparoscopic transcystic approach with micro-incision of the cystic duct and its confluence part in common bile duct exploration (LTM-CBD) (n = 110) and laparoscopic common bile duct exploration (LCBD) (n = 100) under the care of one surgeon was performed. All clinical data were analyzed retrospectively. Results: There was no significant difference in terms of operation time between the two groups (P > .05). Postoperative hospital stay and abdominal drainage time were shorter in the LTM-CBD group than in the LCBD group (P < .05). Postoperative bile leakage was seen in 1 case (1 of 110) in the LTM-CBD group and 10 cases (10 of 100) in the LCBD group (P < .05). Twenty patients underwent T-tube drainage in the LCBD group, and primary closure was performed in the other patients; however, all cases in the LTM-CBD group underwent primary closure. The median follow-up was 12 months; 2 patients in the LCBD group who suffered from bile leakage presented with obstructive jaundice due to bile duct stenosis 6 months postoperatively. Conclusions: LTM-CBD, which can avoid postoperative T-tube drainage, decrease complications, shorten hospitalization time, and enhance the existing quality, is a minimally invasive, safe, and effective treatment. [ABSTRACT FROM AUTHOR]

The article discusses a study which investigates organic synthesis of chiral phosphorus acids through chiral catalyst Binapthol (BINOL). It says that chiral BINOL-derived phosphorus acids are utilized as Brøsted acid catalysts for ennatioselective reactions. It adds that chromatographic purification is required for the synthesis of enantiopure chiral phosphorus acids.

Abstract: In order to improve the ductility of the core wall in super high-rise buildings subjected to high axial compressive force and seismic effect, a new detailed concrete filled double-steel-plate (CFDSP) composite wall using high-strength concrete is proposed. This CFDSP composite wall is composed of concrete filled steel tubular columns at the two boundaries and concrete filled double-steel-plate wall body which is divided into several compartments by vertical stiffeners transversely connected by distributed batten plates. In order to intensively investigate the structural mechanism of this new type of CFDSP composite walls, twelve specimens are tested under large axial compressive force and reversed cyclic lateral load. No evident buckling of surface steel plates can be observed due to reasonable width-to-thickness ratios of steel plates and properly arranged batten plates, so that the surface steel plates and infill high-strength concrete can work compatibly in the whole loading process. All the specimens exhibited good energy dissipation ability and deformation capacity with full hysteretic curves and large ultimate drift ratios, thereby indicating that high-strength concrete can be used in seismic-resistant structures when the proposed new detailed walls are adopted. Based on the test results, the stiffness and strength degradations are analyzed, and the deformation characteristics of all the specimens are discussed in detail. Finally, a strength prediction approach based on the section analysis method is presented, and some detailing requirements for routine design practice are recommended. [Copyright &y& Elsevier]

Abstract: Preferential attachment is considered one of the key factors in the formation of scale-free networks. However, complete random attachment without a preferential mechanism can also generate scale-free networks in nature, such as protein interaction networks in cells. This article presents a new scale-free network model that applies the following general mechanisms: (i) networks expand continuously by the addition of new vertices, and (ii) new vertices attach to random neighbors of random vertices that are already well connected. The proposed model does not require global-based preferential strategies and utilizes only the random attachment method. Theoretical analysis and numerical simulation results denote that the proposed model has steady scale-free network characteristics, and random attachment without a preferential mechanism may generate scale-free networks. [Copyright &y& Elsevier]

Abstract: Coating technology is commonly utilized for the air leakage prevention in the roadway of coal mines in China because of low work load and high efficiency. However, traditional coating materials (e.g. concrete) and chemical materials (e.g. polyurethane foam) utilized for air leakage prevention and underground fire, are impracticable to be broadly utilized because of their difficult appliance, high transportation cost and high prices. In terms of the characteristics of underground coating technology, specific requirements for coating air-sealing materials were put forward. The optimized mixing ratio for clay composite slurry (CCS) based on clay, cement, additives (sodium silicate) and glass fibers was determined. The incombustibility of the material was verified using a self-made box test system. The micropore structure of the materials was determined with a micropore structure analyzer. The CCS coating material produced has excellent air sealing performance and very good fire resistance, air tightness, low dehydration, and crack prevention after coagulation in addition to the low cost. Moreover, it has very good application prospects for coating along gob-side roadways, sealed-wall and permanent maintenance roadway, etc. [Copyright &y& Elsevier]

Background: Melanoma is considered as one of the most aggressive and deadliest cancers and current targeted therapies of melanoma often suffer limited efficacy or drug resistance. Discovery of novel multikinase inhibitors as anti-melanoma drug candidates is still needed. Methods: In this investigation, we assessed the in vitro and in vivo anti-melanoma activities of SC-535, which is a novel small molecule multikinase inhibitor discovered by us recently. We analyzed inhibitory effects of SC-535 on various melanoma cell lines and human umbilical vascular endothelial cells (HUVEC) in vitro. Tumor xenografts in athymic mice were used to examine the in vivo activity of SC-535. Results: SC-535 could efficiently inhibit vascular endothelial growth factor receptor (VEGFR) 1/2/3, B-RAF, and C-RAF kinases. It showed significant antiangiogenic potencies both in vitro and in vivo and considerable anti-proliferative ability against several melanoma cell lines. Oral administration of SC-535 resulted in dose-dependent suppression of tumor growth in WM2664 and C32 xenograft mouse models. Studies of mechanisms of action indicated that SC-535 suppressed the tumor angiogenesis and induced G2/M phase cell cycle arrest in human melanoma cells. SC-535 possesses favorable pharmacokinetic properties. Conclusion: All of these results support SC-535 as a potential candidate for clinical studies in patients with melanoma. Copyright © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

To evaluate lactation performance and changes in plasma and fecal lipopolysaccharide (LPS) concentrations in response to the supplementation of Saccharomyces cerevisiae fermentation product (SC), two dairy farms were selected. On each farm, 32 cows in early to mid lactation (21 to 140 DIM) were blocked by parity and days in milk (DIM), and randomly assigned to one of the two treatments within block (Control or 56 g SC/cow/d). Effect of SC on lactation performance (daily) and changes in blood and fecal LPS level were examined on d 0 and 28 of supplementation. The results showed that SC supplementation increased lactation performance of dairy cows on both farms. On Farm 1, milk production, 3.5% fat corrected milk (FCM), and yield of milk fat and protein were greater (p<0.01) for cows supplemented with SC. Supplementation of SC increased percentage milk fat (p = 0.029) from 81 to 110 DIM. There was no significant effect (p>0.05) of SC supplementation on percentage of milk protein, dry matter intake and feed efficiency. On Farm 2, cows supplemented with SC had a greater (p<0.05) milk yield, percentage of milk fat and milk protein, yield of milk fat and protein, 3.5% FCM and feed efficiency. Supplemental SC had no effect on LPS concentrations in feces (p>0.05) while it trended to reduce (p = 0.07 or 0.207) the concentration in plasma. The results indicate that supplemental SC can increase lactation performance of dairy cattle and has potential for reducing plasma LPS concentration. [ABSTRACT FROM AUTHOR]

Alterations in rumen epithelial tight junctions (TJs) at the tissue and molecular levels during high-grain (HG) diet feeding are unknown. Here, 10 male goats were randomly assigned to either a hay diet (0% grain; n = 5) or HG diet group (65% grain; n = 5) to characterize the changes in ruminal epithelial structure and TJ protein expression and localization using scanning and transmission electron microscopy, quantitative real-time PCR, Western blot analysis, and immunofluorescence. After 7 wk of feeding, ruminal free LPS in HG group increased significantly (P < 0.001) compared with the hay group, and free LPS in the peripheral blood was detectable with concentrations of 0.8 ± 0.20 EU/ml, while not detectable in the control, suggesting a leakage of LPS into the blood in the HG group. Correspondingly, the HG-fed goats showed profound alterations in ruminal epithelial structure and TJ proteins, depicted by marked epithelial cellular damage and intercellular junction erosion, down-regulation of TJ proteins claudin-4, occludin, and zonula occludens-1 mRNA and protein expression, as well as redistribution of claudin-1, claudin-4, and occludin. Furthermore, these changes in TJ proteins in the HG group were coupled with the upregulation of mRNA levels for the cytokines TNF-α and IFN-γ in the ruminal epithelia. These results demonstrated for the first time that the HG diet feeding caused disruption of ruminal epithelial TJs that was associated with a local inflammatory response in the rumen epithelium. These findings may provide new insights into understanding the role of TJ proteins in the ruminal epithelial immune homeostasis of ruminants. [ABSTRACT FROM AUTHOR]

Using different phaseCO 2 -brine, the effect of stress corrosion on the micro-fabric, topology of the minerals and the elemental composition of saline rock was evaluated, to understand how this affect transport properties of rocks. Image analysis was used to evaluate changes in micro-fabric, topology of mineral and elemental composition from SEM images. The micro-fabric of all the CO 2 bearing samples changed significantly according to the different phaseCO 2 -brine. Grain roundness, grain smoothness, and pore smoothness increased after compression while the roundness of pores reduced. There was a significant change in the weight percentage of silicon, carbon and oxygen in the CO 2 -bearing samples compared to the brine sample. Change in the shape, solidity and roundness of the pores led to a change in permeability of rocks by altering the tortuosity of the pores. This study provides an understanding of changes in micro-fabric and elemental changes occurring in saline CO 2 storage sites under different possible phaseCO 2 -brine and highlights their implication for storage and properties of the rock. • Change in the composition of the rock is linked to change in micro-fabric and strength of the rocks. • The micro-fabric of CO 2 bearing samples changed according to the different phaseCO 2 -brine. • Tortuosity of pores had a greater effect on the permeability than the porosity. • Stress accelerates the change in micro-fabric especially for gCO 2 -br reservoir. [ABSTRACT FROM AUTHOR]

The nitrofuran/nitroimidazole/sulfonamide antibiotics are significant chemotherapeutic agents for the prevention and treatment of infections by bacteria. However, the misuse of antibiotics can trigger antimicrobial resistance or even result in environmental pollution by antibiotic residues. In this regard, sensitive recognition of antibiotics associated with a quantitative platform is desirable. Herein, the antibiotic pollutants can be quantitatively detected by a new luminescent sensor derived from a stable europium(III) metal-organic framework, namely {[Eu 2 (FDA) 3 (H 2 O) 3 (DMF)·DMF·2H 2 O]} n (Eu-MOF , H 2 FDA ​= ​furan-2,5-dicarboxylic acid). The Eu-MOF features a 6,6-connected pcu alpha-Po primitive cubic topology with 1D channels occupied by lattice N , N -dimethylformamide and water molecules. More importantly, the Eu-MOF represents superior luminescent properties, which can be quenched by trace amounts of the nitrofuran/nitroimidazole/sulfonamide antibiotics at μM levels in water. The results indicate that Eu-MOF is qualified as a promisingly favorable sensor for the sensitive detection of the antibiotics in water, being potentially beneficial for monitoring water quality. The antibiotic pollutants can be quantitatively detected by a Eu-MOF luminescent chemosensor with trace amounts of the antibiotics in water at μM levels. [Display omitted] • The antibiotic pollutants can be quantitatively detected by a Eu-MOF luminescent chemosensor. • The Luminescence of Eu-MOF can be efficiently quenched by trace amounts of the antibiotics in water at μM levels. • The selective quehching phenomenon on the antibiotics has been discussed. [ABSTRACT FROM AUTHOR]

DBU-catalyzed Michael additions of bulky glycine imines to α,β-unsaturated isoxazoles and pyrazolamides have been realized in THF with 1.0 eq. LiBr as an additive at room temperature to provide Michael adducts in excellent yields (up to 97%) and diastereoselectivities (> 20:1). [Display omitted] [ABSTRACT FROM AUTHOR]

Highlights: [•] A target database termed TargetDB was compiled. [•] Docking- and pharmacophore-based target prediction protocols were established. [•] A combined target prediction strategy was developed. [•] A probabilistic fusion method was presented for target ranking. [Copyright &y& Elsevier]

Abstract: In this study, carbon nanosheets and nanohoneycombs were synthesized on Si (100) substrates using a hot filament physical vapor deposition technique under methane ambient and vacuum, respectively. The four-point Au electrodes are then sputtered on the surface of the nanostructured carbon (n-C) films to form prototypical humidity sensors. The sensing properties of prototypical sensors at different temperature, humidity, direct current (DC), and alternative current (AC) voltage were characterized. Linear sensing response of sensors to relative humidity ranging from 11% to 95% is observed at room temperature. Experimental data indicate that the carbon nanosheets based sensors exhibit an excellent reversible behavior and long-term stability. It also has higher response than that of the humidity sensor with carbon nanohoneycombs materials. [Copyright &y& Elsevier]

Wedescribe the structural optimization of a hit compound, 1-(4-(1H-pyrazolo[3,4-d]pyrimidin-4-ylamino)phenyl)-3-(3-methoxyphenyl)urea(1), which exhibits inhibitory activity but low potencyagainst FLT3 and VEGFR2. A series of pyrazolo[3,4-d]pyrimidine derivatives were synthesized, and structure–activityrelationship analysis using cell- and transgenic-zebrafish-based assaysled to the discovery of a number of compounds that exhibited bothhigh potency against FLT3-driven human acute myeloid leukemia (AML)MV4-11 cells and a considerable antiangiogenic effect in transgenic-zebrafish-basedassays. The compound 1-(4-(1H-pyrazolo[3,4-d]pyrimidin −4-yloxy)phenyl)-3-(4-chloro-3-(trifluoromethyl)phenyl)urea(33), which exhibited the highest activity in preliminaryin vivo anti-AML assays, was chosen for further anti-AML studies.The results demonstrated that compound 33is a multikinaseinhibitor that potently inhibits FLT3 and VEGFR2. In an MV4-11 xenograftmouse model, a once-daily dose of compound 33at 10 mg/kgfor 18 days led to complete tumor regression without obvious toxicity.Western blot and immunohistochemical analyses were performed to determinethe mechanism of action of compound 33. [ABSTRACT FROM AUTHOR]

In this investigation, a common feature pharmacophore model of anaplastic lymphoma kinase inhibitors was developed based on several known anaplastic lymphoma kinase inhibitors that were co-crystallized with anaplastic lymphoma kinase. The established pharmacophore model Hypo1 was carefully validated and then adopted to screen two in silico chemical databases, Specs (202 408 compounds) and Enamine (1 105 894 compounds), for retrieving novel anaplastic lymphoma kinase inhibitors. The hit compounds were further filtered using a fast bumping-check tool and molecular docking. Finally, 25 compounds were selected and purchased from market. The bioactivity of these compounds was firstly measured at the cellular level against a typical anaplastic lymphoma kinase mutant-driven cancer cell line, Karpas299. And six of them showed a good anti-viability activity. The kinase inhibitory potency against the recombinant human anaplastic lymphoma kinase kinase was tested to the most active compound at the cellular level, T0508-5181 (from Specs), which gave a half maximal inhibitory concentration (IC50) of 5.3 μ m. [ABSTRACT FROM AUTHOR]

This paper describe the structural optimization of ahit compound, N2-(4-(4-methylpiperazin-1-yl)phenyl)-N8-phenyl-9H-purine-2,8-diamine(1), which is a reversible kinase inhibitor targetingboth EGFR-activating and drug-resistance (T790M) mutations but haspoor binding affinity. Structure–activity relationship studiesled to the identification of 9-cyclopentyl-N2-(4-(4-methylpiperazin-1-yl)phenyl)-N8-phenyl-9H-purine-2,8-diamine (9e) that exhibits significant in vitro antitumor potency against thenon-small-cell lung cancer (NSCLC) cell lines HCC827 and H1975, whichharbor EGFR-activating and drug-resistance mutations, respectively.Compound 9ewas further assessed for potency and selectivityin enzymatic assays and in vivo anti-NSCLC studies. The results indicatedthat compound 9eis a highly potent kinase inhibitoragainst both EGFR-activating and resistance mutations and has goodkinase spectrum selectivity across the kinome. In vivo, oral administrationof compound 9eat a dose of 5 mg/kg caused rapid andcomplete tumor regression in a HCC827 xenograft model, and an oraldose of 50 mg/kg initiated a considerable antitumor effect in an H1975xenograft model. [ABSTRACT FROM AUTHOR]

Abstract: Aberrant activation of casein kinase 1 (CK1) has been demonstrated to be implicated in the pathogenesis of cancer and various central nervous system disorders. Discovery of CK1 inhibitors has thus attracted much attention in recent years. In this account, we describe the discovery of N6-phenyl-1H-pyrazolo[3,4-d]pyrimidine-3,6-diamine derivatives as novel CK1 inhibitors. An optimal common-feature pharmacophore hypothesis, termed Hypo2, was firstly generated, followed by virtual screening using Hypo2 against several chemical databases. One of the best hit compounds, N6-(4-chlorophenyl)-1H-pyrazolo[3,4-d]pyrimidine-3,6-diamine, was chosen for the subsequent hit-to-lead optimization under the guide of Hypo2, which led to the discovery of a new lead compound (1-(3-(3-amino-1H-pyrazolo[3,4-d]pyrimidin-6-ylamino)phenyl)-3-(3-chloro-4-fluorophenyl)urea) that potently inhibits CK1 with an IC50 value of 78 nM. [Copyright &y& Elsevier]

Polychlorinated dibenzo- p-dioxins and dibenzofurans (PCDD/Fs) are formed jointly with numerous products of incomplete combustion during waste incineration. Chlorobenzenes (CBz) are often cited as surrogates or precursors of PCDD/Fs. Experiments were conducted to investigate the effect of some key parameters on CBz formation, including moisture (H2O), chlorine gas (Cl2), cupric chloride (CuCl2), urea [(NH2)2CO], ammonia (NH3), and ammonium sulfate [(NH4)2SO4]. Cl2 and CuCl2 promoted CBz formation from fly ash, increasing the chlorination degree. In addition, Cl in cupric compound was more active than chlorine atom of Cl2, and chlorine type significantly affected the chlorination process. Less CBz yield was detected after S- and N-containing compounds [(NH2)2CO, NH3, and (NH4)2SO4] were added into reactive ash. High content of moisture in gas prevented CBz synthesis and reduced chlorination. These experimental results are useful to optimize CBz emission control and realize the mechanism of the correlation between CBz and PCDD/Fs. [ABSTRACT FROM AUTHOR]

Bruton's tyrosine kinase has emerged as a potential target for the treatment for B-cell malignancies and autoimmune diseases. Discovery of Bruton's tyrosine kinase inhibitors has thus attracted much attention recently. In this investigation, we introduced a hybrid protocol of virtual screening methods including support vector machine model-based virtual screening, pharmacophore model-based virtual screening and docking-based virtual screening for retrieving new Bruton's tyrosine kinase inhibitors from commercially available chemical databases. Performances of the hybrid virtual screening approach were evaluated against a test set, which results showed that the hybrid virtual screening approach significantly shortened the overall screening time, and considerably increased the hit rate and enrichment factor compared with the individual method (SB-VS, PB-VS and DB-VS) or their combinations by twos. This hybrid virtual screening approach was then applied to screen several chemical databases including Specs (202 408 compounds) and Enamine (980 000 compounds) databases. Thirty-nine compounds were selected from the final hits and have been shifted to experimental studies. [ABSTRACT FROM AUTHOR]

AbstractIt has been shown that Caspy2, a zebrafish active caspase, can efficiently suppress the growth of malignant tumor. The present study was designed to test whether combined gene therapy with IP-10, a potent antitumor chemokine, and Caspy2 would improve therapy efficacy. Recombinant plasmid expressing both Caspy2 and IP-10 genes was mixed with DOTAP–cholesterol nanoparticles. Immunocompetent mice bearing CT26 colon carcinoma, B16-F10 melanoma, and 4T1 breast carcinoma were treated with the complex. We found that the combined gene therapy more efficiently inhibited tumor growth, while efficiently prolonging the survival of tumor-bearing animals, compared with monotherapy. Moreover, a significant reduction in spontaneous lung metastasis could be observed in the 4T1 breast carcinoma model. Infiltration of CD8+T lymphocytes was also observed. In addition, apoptotic cells were widely detected by TUNEL assay and caspase-3 immunostaining in coadministered tumor tissues. The combination treatment also successfully inhibited angiogenesis and tumor cell proliferation as assessed by CD31 and Ki-67 immunostaining, respectively. Furthermore, depletion of CD8+T lymphocytes could significantly abrogate the antitumor activity, whereas the depletion of CD4+cells or natural killer cells showed partial abrogation. Rechallenged CT26 tumors were rejected in all of the surviving mice treated by combination therapy. Our results suggest that combined therapy with Caspy2 and IP-10 can significantly enhance antitumor activity by acting as an immune response initiator, apoptosis inducer, and angiogenesis inhibitor, which may be important for further applications in clinical cancer therapy. [ABSTRACT FROM AUTHOR]

Game theory (GT) is a mathematical method that describes the phenomenon of conflict and cooperation between intelligent rational decision-makers. In particular, the theory has been proven very useful in the design of wireless sensor networks (WSNs). This article surveys the recent developments and findings of GT, its applications in WSNs, and provides the community a general view of this vibrant research area. We first introduce the typical formulation of GT in the WSN application domain. The roles of GT are described that include routing protocol design, topology control, power control and energy saving, packet forwarding, data collection, spectrum allocation, bandwidth allocation, quality of service control, coverage optimization, WSN security, and other sensor management tasks. Then, three variations of game theory are described, namely, the cooperative, non-cooperative, and repeated schemes. Finally, existing problems and future trends are identified for researchers and engineers in the field. [ABSTRACT FROM AUTHOR]

Abstract: Protein kinase casein kinase 2 (CK2), a member of the serine/threonine kinase family, has been established as one of the most attractive targets for molecularly targeted cancer therapy. The discovery of CK2 inhibitors has thus attracted much attention in recent years. In this investigation, a hybrid virtual screening approach based on Bayesian classification model, pharmacophore hypothesis and molecular docking was proposed and employed to identify CK2 inhibitors. We first established a naïve Bayes classification model of CK2 inhibitors/non-inhibitors and pharmacophore hypotheses of CK2 inhibitors. The docking parameters and scoring functions were also optimized in advance. The three virtual screening methods were sequentially used to screen two large chemical libraries, Specs and Enamine, for retrieving new CK2 inhibitors. Finally 30 compounds were selected from the final hits for in vitro CK2 kinase inhibitory assays. Five compounds with completely novel scaffolds showed a good inhibitory potency against CK2, which have good potentials for a future hit-to-lead optimization. [Copyright &y& Elsevier]

The well-defined unnatural dipeptides based on cis-2,5-disubstituted pyrrolidine backbone were synthesized from commercially available starting materials meso-diethyl-2,5-dibromoadipate, ( S)-(−)-1-phenylethylamine, and phenylalanine. The configurations of all the chiral centers in these unnatural dipeptides are confirmed by X-ray crystal diffraction analysis. [ABSTRACT FROM AUTHOR]

An improved synthesis of 6-aryl-3-cyanopyridine-2-(1H)-thiones utilizing enaminones as starting materials catalyzed by 1,4-diazabicyclo[2.2.2]octane (DABCO) was described. Moreover, a convenient one-pot conversion of aryl ketones to 6-aryl-3-cyanopyridine-2-(1H)-thiones was also developed in moderate to good yields (up to 80%). [ABSTRACT FROM AUTHOR]

Structure–activity relationship (SAR) studiesof 2-(quinazolin-4-ylthio)thiazolederivatives, which are for optimizing the in vitroand in vivoantiacute myeloid leukemia (AML) activityof a previously identified FLT3 inhibitor 2-(6,7-dimethoxyquinazolin-4-ylthio)thiazole(1), are described. SAR studies centering around thehead (thiazole) and tails (6- and 7-positions) of the quinazolinemoiety of 1led to the discovery of a series of compoundsthat exhibited significantly increased potency against FLT3-drivenAML MV4-11 cells. Preliminary in vivoassays werecarried out on three highly active compounds, whose results showedthat 1-{5-[7-(3-morpholinopropoxy)quinazolin-4-ylthio]-[1,3,4]thiadiazol-2-yl}-3-p-tolylurea (20c) had the highest invivoactivity. Further in vitroand in vivoanti-AML studies were then performed on 20c; in an MV4-11 xenograft mouse model, a once-daily dose of 20cat 100 mg/kg for 18 days led to complete tumor regressionwithout obvious toxicity. Western blot and immunohistochemical analysiswere carried out to illustrate the mechanism of action of 20c. [ABSTRACT FROM AUTHOR]

Abstract: A numerical simulation has been conducted to study the solid–fluid multi-phase flow problem in concrete pumping process. The kinematics and trajectory of the discrete particles as well as the particle–particle interaction were predicted by DEM while the motion of the continuous fluid phase was evaluated by a Navier–Stokes solver, and a pressure gradient force model was adopted to calculate the solid–fluid interaction force. A case of pneumatic conveying was utilized to demonstrate the capability of the coupling model. The concrete pumping process was then simulated, where several flow features were observed such as roping, particle segregation and particle concentration. The frequency of the particles impacting on the bended pipe was monitored, a new time average collision intensity model based on impact force has been proposed to investigate the wear mechanism of the elbow. The location of maximum erosive wear damage in the elbow was predicted. Statistical results were in good agreement with that observed in actual pumping process. It is found that the present multi-phase coupling model can predict the wear behavior of the bended pipe accurately, and consequently provide an effective guidance for the design of concrete pumping pipe. [Copyright &y& Elsevier]

Abstract: A numerical simulation of fluid transportation process was carried out focused on the investigation into predicting the location of the puncture point location in elbow. The kinematics and trajectory of the discrete particles as well as the particle–particle interaction were described by discrete element method (DEM) while the hydrodynamic model of the fluid phase was based on the volume-averaged Navier–Stokes equations, and a fluid density-based buoyancy model was adopted to calculate the solid–fluid interaction force. In this paper, the spatial distribution of particle–wall interaction force was calculated and corresponded to the wear pattern in the elbow, the puncture point locations have been observed. In particular, the influences of slurry velocity, bend orientation and angle of elbow on the puncture point location were discussed. [Copyright &y& Elsevier]

This paper gives a novel traffic feature for identifying abnormal variation of traffic under DDOS flood attacks. It is the histogram of the maxima of the bounded traffic rate on an interval-by-interval basis. We use it to experiment on the traffic data provided by MIT Lincoln Laboratory under Defense Advanced Research Projects Agency (DARPA) in 1999. The experimental results profitably enhance the evidences that traffic rate under DDOS attacks is statistically higher than that of normal traffic considerably. They show that the pattern of the histogram of the maxima of bounded rate of attack-contained traffic greatly differs from that of attack-free traffic. Besides, the present traffic feature is simple in mathematics and easy to use in practice. [ABSTRACT FROM AUTHOR]

Abstract: Inducing apoptosis is a promising therapeutic approach to overcome cancer. Here we described that a novel synthesized compound, 3-amino-N-(4-chlorobenzyl)-6-(3-methoxyphenyl)thieno[2,3-b]pyridine-2-carboxamide (SKLB703), exhibits antitumor activity via inducing apoptosis both in vitro and in vivo. Our results showed that SKLB703 inhibited the proliferation of a panel of human cancer cell lines, and human hepatocellular carcinoma cell line HepG2 was the most sensitive. The proliferation inhibitory effect of SKLB703 was associated with its apoptosis-inducing effect by activating caspase-3 and caspase-9 rather than caspase 8. Exposure of HepG2 to SKLB703 also resulted in Bax upregulation, Bcl-2 downregulation, cytochrome c release and mitochondrial transmembrane potential change in mitochondrial apoptotic pathway. Moreover, the decrease of phosphorylated p 44/42 mitogen-activated protein kinase and phosphorylated Akt was observed. SKLB703 suppressed the growth of established tumors in xenograft models in mice, whereas no toxicity was exhibited. TUNAL analysis showed that SKLB703 induced HepG2 tumor apoptosis. Taken together, the present study demonstrates that SKLB730 exhibits its antitumor activity through inducing apoptosis via mitochondrial apoptotic pathway. Its potential to be a candidate of anticancer agent is worth being further investigated. [Copyright &y& Elsevier]

In a cell-based screen of novel anticancer agents, the hit compound 1a which bears a pyrazolo[3,4-d]pyrimidine scaffold exhibited high inhibitory activity against a panel of four different types of tumor cell lines. In particular, the IC50 for A549 cells was 2.24 μM, compared with an IC50 of 9.20 μM for doxorubicin, the positive control. Four synthetic routes of the key intermediate 3 of 1a were explored and 1a was prepared via route D on the gram scale for further research. Two analogs of 1a were synthesized and their preliminary structure-activity relationships were studied. Flow cytometric analysis revealed that compound 1a could significantly induce apoptosis in A549 cells in vitro at low micromolar concentrations. These results suggest that the target compound 1a and its analogs with the pyrazolo[3,4-d]pyrimidine scaffold might potentially constitute a novel class of anticancer agents, which requires further studies. [ABSTRACT FROM AUTHOR]

Abstract: Drug-induced seizures are a serious adverse effect and assessment of seizure risk usually takes place at the late stage of drug discovery process, which does not allow sufficient time to reduce the risk by chemical modification. Thus early identification of chemicals with seizure liability using rapid and cheaper approaches would be preferable. In this study, an optimal support vector machine (SVM) modeling method has been employed to develop a prediction model of seizure liability of chemicals. A set of 680 compounds were used to train the SVM model. The established SVM model was then validated by an independent test set comprising 175 compounds, which gave a prediction accuracy of 86.9%. Further, the SVM-based prediction model of seizure liability was compared with various preclinical seizure assays, including in vitro rat hippocampal brain slice, in vivo zebrafish larvae assay, mouse spontaneous seizure model, and mouse EEG model. In terms of predictability, the SVM model was ranked just behind the mouse EEG model, but better than the rat brain slice and zebrafish models. Nevertheless, the SVM model has considerable advantages compared with the preclinical seizure assays in speed and cost. In summary, the SVM-based prediction model of seizure liability established here offers potential as a cheaper, rapid and accurate assessment of seizure liability of drugs, which could be used in the seizure risk assessment at the early stage of drug discovery. The prediction model is freely available online at http://www.sklb.scu.edu.cn/lab/yangsy/download/ADMET/seizure_pred.tar. [Copyright &y& Elsevier]

Despite many evidences supporting the concept of ''oncogene addiction'' and many hypotheses rationalizing it, there is still a lack of detailed understanding to the precise molecular mechanism underlying oncogene addiction. In this account, we developed a mathematic model of epidermal growth factor receptor (EGFR) associated signaling network, which involves EGFR-driving proliferation/pro-survival signaling pathways Ras/extracellular-signal-regulated kinase (ERK) and phosphoinositol- 3 kinase (PI3K)/AKT, and pro-apoptotic signaling pathway apoptosis signal-regulating kinase 1 (ASK1)/p38. In the setting of sustained EGFR activation, the simulation results show a persistent high level of proliferation/pro-survival effectors phospho-ERK and phospho-AKT, and a basal level of pro-apoptotic effector phospho-p38. The potential of p38 activation (apoptotic potential) due to the elevated level of reactive oxygen species (ROS) is largely suppressed by the negative crosstalk between PI3K/AKT and ASK1/p38 pathways. Upon acute EGFR inactivation, the survival signals decay rapidly, followed by a fast increase of the apoptotic signal due to the release of apoptotic potential. Overall, our systems biology modeling together with experimental validations reveals that inhibition of survival signals and concomitant release of apoptotic potential jointly contribute to the tumor cell death following the inhibition of addicted oncogene in EGFR addicted cancers. [ABSTRACT FROM AUTHOR]

Abstract: Breast cancer resistance protein (BCRP) is one of the key multi-drug resistance proteins, which significantly influences the therapeutic effects of many drugs, particularly anti-cancer drugs. Thus, distinguishing between substrates and non-substrates of BCRP is important not only for clinical use but also for drug discovery and development. In this study, a prediction model of the substrates and non-substrates of BCRP was developed using a modified support vector machine (SVM) method, namely GA–CG–SVM. The overall prediction accuracy of the established GA–CG–SVM model is 91.3% for the training set and 85.0% for an independent validation set. For comparison, two other machine learning methods, namely, C4.5 DT and k-NN, were also adopted to build prediction models. The results show that the GA–CG–SVM model is significantly superior to C4.5 DT and k-NN models in terms of the prediction accuracy. To sum up, the prediction model of BCRP substrates and non-substrates generated by the GA–CG–SVM method is sufficiently good and could be used as a screening tool for identifying the substrates and non-substrates of BCRP. [Copyright &y& Elsevier]

Abstract: We propose an ideal -depth clique network model. In this model, the original network is composed of cliques (maximal complete subgraphs) that overlap with each other. The network expands continuously by the addition of new cliques. The final diameter of the network can be set in advance, namely, it is controllable. Assuming that the diameter of the network is , the network exhibits a logistic structure with layers. In this structure, the 0th layer represents the original network and each node of the th layer corresponds to a clique in the th layer. In the growth process of the network, we ensure that any th layer network is composed of overlapping cliques. Any node in an th layer network corresponds to an -depth community in the original network, and the diameter of an -depth community is . Therefore, the th layer network will contain only one clique, the th layer network will contain only one node, and the diameter of the corresponding original network is . Then an ideal -depth clique network will be obtained. Based on the ideal -depth clique network model, we construct a bus transport network model with an ideal -depth clique network topology (ICNBTN). Moreover, our study compares this model with the real bus transport network (RealBTN) of three major cities in China and a recently introduced bus transport network model (BTN) whose network properties correspond well with those of real BTNs. The network properties of the ICNBTN are much closer to those of the RealBTN than those of the BTN are. At the same time, the ICNBTN has higher clustering extent of bus routes, smaller network diameter, which corresponds to shorter maximum transfer times in a bus network, and lower average shortest path time coefficient than the BTN and the RealBTN. Therefore, the ICNBTN can achieve higher transfer efficiency for a bus transport system. [Copyright &y& Elsevier]

Abstract: Aberrant c-Met activation has been demonstrated to be implicated in tumorigenesis and anti-cancer drug resistance. Discovery of c-Met inhibitors has attracted much attention in recent years. In this study, a support vector machine (SVM) classification model that discriminates c-Met inhibitors and non-inhibitors was first developed. Evaluation through screening a test set indicates that combined SVM-based and docking-based virtual screening (SB/DB-VS) considerably increases hit rate and enrichment factor compared with the individual methods. Thus the combined SB/DB-VS approach was adopted to screen PubChem, Specs, and Enamine for c-Met inhibitors. 75 compounds were selected for in vitro assays. Eight compounds display a good inhibitory potency against c-Met. Five of them are found to have novel scaffolds, implying a good potential for further chemical modification. [Copyright &y& Elsevier]

FAK (focal adhesion kinase), which plays a pivotal role in mediating cell proliferation, survival and migration, is frequently overexpressed in human malignant glioma. The expression of FAK increases with the advance of tumour grade and stage. Based on these observations, we hypothesized that attenuation of FAK expression may have inhibitory effects on the growth of malignant glioma. In the present study, human glioma cell line U251 was transfected with plasmids containing U6 promoter-driven shRNAs (small-hairpin RNAs) against human FAK using cationic liposome. The effects of FAK knockdown in U251 cells in vitro were analysed by using flow cytometry and PI (propidium iodide)-staining assays. Based on the encouraging in vitro results with FAK silencing, plasmids encoding FAK-targeted shRNA were encapsulated by DOTAP (dioleoyltrimethylammonium propane): Chol (cholesterol) cationic liposome and injected via tail vein to evaluate its therapeutic efficiency on suppressing tumour growth in a human glioma xenograft model. PCNA (proliferating-cell nuclear antigen), CD34 immunostaining and TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling) assay were used to assess the changes in tumour angiogenesis, apoptosis and proliferation respectively. The results indicated that DOTAP:Chol cationic liposome could deliver therapeutic plasmids systemically to tumour xenografts, resulting in suppression of tumour growth. Treatment with plasmid encoding FAK-targeted shRNA reduced mean tumour volume by approx. 70% compared with control groups ( P<0.05), accompanied with angiogenesis inhibition ( P<0.05), tumour cell proliferation suppression ( P<0.05) and apoptosis induction ( P<0.05). Taken together, our results demonstrated that shRNA-mediated silencing of FAK might be a potential therapeutic approach against human malignant glioma. [ABSTRACT FROM AUTHOR]

Abstract: Pre-stressing scratching tests have been preformed on polished surfaces of Al2O3 ceramic under a Rockwell diamond indenter which moved with uniform speed and constant normal load to investigate how the pre-stress contributes to the material removal mechanism. With the measurement of acoustic emission signals as well as indenter tangential forces, surface damages and cross-section of grooves of Al2O3 ceramic were evaluated under the action of different values of pre-stress. It was found that the scratched groove width was increased with the increasing of pre-stress when same normal loads were applied. The existence of pre-stress tends to restrain the crack propagation along the direction of pre-stress, and obvious plastic deformation at the bottom of scratched groove has been observed. Moreover, the fluctuation of tangential force was obviously enhanced, and the magnitude of tangential force in the test of pre-stress was higher than that of without pre-stress. The acoustic emission signals showed that fewer damages were produced in the process of scratching with an appropriate pre-stress. However, the continuing increase of pre-stress would aggravate the machining process. [Copyright &y& Elsevier]

Antagonizing angiogenesis-related receptor tyrosine kinase is a promising therapeutic strategy in oncology. In present study, we designed and synthesized a novel vascular endothelial growth factor receptor (VEGFR) inhibitor N-methyl-4-(4-(3-(trifluoromethyl) benzamido) phenoxy) picolinamide SKLB610 that potently suppresses human tumor angiogenesis. SKLB610 inhibited angiogenesis-related tyrosine kinase VEGFR2, fibroblast growth factor receptor 2 (FGFR2) and platelet-derived growth factor receptor (PDGFR) at rate of 97%, 65% and 55%, respectively, at concentration of 10μM in biochemical kinase assays. In vitro, SKLB610 showed more selective inhibition of VEGF-stimulated human umbilical vein endothelial cells (HUVECs) proliferation, and this proliferation inhibitory effect was associated with decreased phosphorylation of VEGFR2 and p42/44 mitogen-activated protein kinase (p42/44 MAPK). Antiangiogenic evaluation showed that SKLB610 inhibited the HUVECs capillary-tube formation on Matrigel in vitro and the sub-intestinal vein formation of zebrafish in vivo. Moreover, SKLB610 inhibited a panel of human cancer cells proliferation in a concentration-dependent manner and human non-small cell lung cancer cell line A549 and human colorectal cancer cell line HCT116 were most sensitive to SKLB610 treatment. In vivo, chronic intraperitoneally administration of SKLB610 at dose of 50mg/kg/d resulted in significant inhibition in the growth of established human A549 and HCT116 tumor xenografts in nude mice without exhibit toxicity. Histological analysis showed significant reductions in intratumoral microvessel density (CD31 staining) of 43-55% relative to controls depending on the specific tumor xenografts. In conclusion, the present study demonstrated that SKLB610 exhibited its antitumor activity as a multi-targeted inhibitor with more potent inhibition of VEGFR2 activity. Its potential to be a candidate of anticancer agent is worth being further investigated. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Abstract: Development of glutamate non-competitive antagonists of mGluR1 (Metabotropic glutamate receptor subtype 1) has increasingly attracted much attention in recent years due to their potential therapeutic application for various nervous disorders. Since there is no crystal structure reported for mGluR1, ligand-based virtual screening (VS) methods, typically pharmacophore-based VS (PB-VS), are often used for the discovery of mGluR1 antagonists. Nevertheless, PB-VS usually suffers a lower hit rate and enrichment factor. In this investigation, we established a multistep ligand-based VS approach that is based on a support vector machine (SVM) classification model and a pharmacophore model. Performance evaluation of these methods in virtual screening against a large independent test set, M-MDDR, show that the multistep VS approach significantly increases the hit rate and enrichment factor compared with the individual SB-VS and PB-VS methods. The multistep VS approach was then used to screen several large chemical libraries including PubChem, Specs, and Enamine. Finally a total of 20 compounds were selected from the top ranking compounds, and shifted to the subsequent in vitro and in vivo studies, which results will be reported in the near future. [Copyright &y& Elsevier]

Abstract: A series of novel benzothiazole-2-thiol derivatives were synthesized, and their anti-proliferative activities on HepG2 and MCF-7 cells were investigated. Most compounds had inhibitory effects on cell growth, and some of them were more effective than cisplatin. Compounds 6m and 6t displayed good inhibitory activities against a panel of different types of human cancer cell lines, with IC50 values in the low micromolar range. Further biological evaluation indicated that 6m induced apoptosis in HepG2 cancer cells. Structure–activity relationships were also proposed. [Copyright &y& Elsevier]

Abstract: Discrete element method (DEM) was used to model progressive delamination of fiber reinforced composite laminates. The anisotropic composite plies were constructed through a hexagonal packing of particle elements. Contacts between the particles were represented by parallel bonds with the verified normal and shear elastic properties. The ply interface was characterized by a contact softening model with a bilinear elastic behavior which is similar to the cohesive zone model in the continuum mechanics. DCB, ELS and FRMM tests were simulated by the DEM model to assess its capability of modeling mode I, mode II and mix mode fracture of delamination, respectively. Good agreements were observed between the DEM and existing numerical and experimental results of loading curves, which confirmed that the DEM model can be used to simulate initiation and propagation of composite delamination, with more insights into microscopic material behavior, such as damage extension and plastic zone. [ABSTRACT FROM AUTHOR]

Abstract: Novel thienopyridine derivatives 1b–1r were synthesized, based on a hit compound 1a that was found in a previous cell-based screening of anticancer drugs. Compounds 1a–1r have the following features: (1) their anticancer activity in vitro was first reported by our group. (2) The most potent analog 1g possesses hepatocellular carcinoma (HCC)-specific anticancer activity. It can specifically inhibit the proliferation of the human hepatoma HepG2 cells with an IC50 value of 0.016μM (compared with doxorubicin as a positive control, whose IC50 was 0.37μM). It is inactive toward a panel of five different types of human cancer cell lines. (3) Compound 1g remarkably induces G0/G1 arrest and apoptosis in HepG2 cells in vitro at low micromolar concentrations. These results, especially the HCC-specific anticancer activity of 1g, suggest their potential in targeted chemotherapy for HCC. [ABSTRACT FROM AUTHOR]

Abstract: Metastatic breast cancers are hard to treat and almost always fatal. Chloroquine diphosphate, a derivative of quinine, has long been used as a potent and commonly used medicine against different human diseases. We therefore investigated the effects of chloroquine diphosphate on a highly metastatic mouse mammary carcinoma cell line. In vitro treatment of 4T1 mouse breast cancer cells with chloroquine diphosphate resulted in significant inhibition of cellular proliferation and viability, and induction of apoptosis in 4T1 cells in a time- and dose-dependent manner. Further analysis indicated that induction of apoptosis was associated with the loss of mitochondrial membrane potential, release of cytochrome c, and activation of caspase-9 and caspase-3, and cleavage of poly(ADP-ribose) polymerase. The effect of chloroquine diphosphate was then examined using a mice model in which 4T1 cells were implanted subcutaneously. Chloroquine diphosphate (25mg/kg and 50mg/kg, respectively) significantly inhibited the growth of the implanted 4T1 tumor cells and induced apoptosis in the tumor microenvironment. Moreover, the metastasis of tumor cells to the lungs was inhibited significantly and the survival of the mice enhanced. These data suggested that chloroquine diphosphate might have chemotherapeutic efficacy against breast cancer including inhibition of metastasis. [ABSTRACT FROM AUTHOR]

Abstract: Utilizing a solid phase extraction column (MCT) containing mixed hydrophilic functional gel and cation exchange sorbent, a sensitive and rapid HPLC–MS/MS method for simultaneously determining the residues of melamine (MEL) and cyanuric acid (CYA) in human foodstuffs was developed. MEL and CYA in egg, pork, liver, kidney and pork, shrimp, sausage casing, honey, soybean milk, soybean powder and dairy product were extracted using acetonitrile/water, defatted with hexane and isolated using MCT solid phase extraction column. The residues were separated upon a hydrophilic interaction liquid chromatography (HILIC) column and analyzed by electrospray ionization under negative–positive switched mode on a triplequadrupole mass spectrometry. The selected reaction monitoring was performed on [M+H]+ of m/z 127.9 to provide the transition of 127>85 and 127>68 (MEL) while the [M−H]− of m/z 127.1 was selected as the precursor ion for CYA resulting in product ions m/z 85 and 42. Isotope labeled internal standard (15N3-MEL and 13C3-CYA) and matrix-matched calibration were both used to observe the recovery to be 70.0–129.6% and 70.0–128.9% with RSD of 1.4–23.3% and 1.5–21.7% for MEL and CYA, respectively (n =6). All the LODs and LOQs of MEL and CYA were less than 39.4 and 99.1μgkg−1, respectively, in 18 matrices, which were sensitive enough for quantitative analysis. This method has been proven effective in simultaneous determination of melamine and cyanuric acid when inspecting unknown and positive samples. [ABSTRACT FROM AUTHOR]