Noble-metal-free Fe3O4/Co3S4 nanosheets with oxygen vacancies as an efficient electrocatalyst for highly sensitive electrochemical detection of As(III).

The electrochemical method for highly sensitive determination of arsenic(III) in real water samples with noble-metal-free nanomaterials is still a difficult but significant task. Here, an electrochemical sensor driven by noble-metal-free layered porous Fe3O4/Co3S4 nanosheets was successfully employed for As(III) analysis, which was prepared via a facile two-step method involves a hydrothermal treatment and a subsequent sulfurization process. As expected, the electrochemical detection of As(III) in 0.1 M HAc-NaAc (pH 6.0) by square wave anodic stripping voltammetry (SWASV) with a considerable sensitivity of 4.359 µA/µg·L-1 was obtained, which is better than the commonly used noble metals modified electrodes. Experimental and characterization results elucidate the enhancement of As(III) electrochemical performance could be attributed to its nano-porous structure, the presence of oxygen vacancies and strong synergetic coupling effects between Fe3O4 and Co3S4 species. Besides, the Fe3O4/Co3S4 modified screen printed carbon electrode (Fe3O4/Co3S4-SPCE) shows remarkable stability and repeatability, valuable anti-interference ability and could be used for detection in real water samples. Consequently, the results confirm that as-prepared porous Fe3O4/Co3S4 nanosheets is identified as a promising modifier to detect As(III) in real sample analysis.

Prediction of outflow parameters for a shower head.

Bathing or showering is one of the main pathways of water consumption. The shower head, as an important part of our bathing facilities, is directly related to water saving and bathing satisfaction. To design a water-saving and comfortable shower, it is extremely important to know its likely outflow parameters .In the resent research, the shower head structure and the water jet characteristics, and the Lagrangian control volume (CV) element integration method is used to establish a theoretical model describing the motion of the jet from the spray-holes of a shower head. The model also includes a method of calculation of the spraying force, considering the velocity distribution over the jet cross-section. The model can be used to predict jet parameters, spraying force, water temperature drop, and sprayed water volume distribution. To validate the predictions,experiments are conducted to measure the spraying force, temperature drop, and sprayed water volume distribution for the shower head. Comparisons between experiments and predictions show that the prediction accuracy of the model is satisfactory and the model can be adopted to evaluate the performance of the shower head. In addition, using the model, the salient jet parameters for the spraying hole are also simulated, and the influences of the flow rate and the size of the spraying hole on the motion of the jet can be assessed. These results guide research and development into water-conservation, energy-conservation, and comfort when showering.

Ammonia borane dehydrogenation and selective hydrogenation of functionalized nitroarene over a porous nickel-cobalt bimetallic catalyst.

The hydrolysis of ammonia borane is a promising strategy for hydrogen energy exploration and exploitation. The in situ produced hydrogen could be directly utilized in hydrogenation reactions. In this work, a bimetallic nickel-cobalt material with porous structure was developed through the pyrolysis of ZIF-67 incorporated with Ni ions. Through the introduction of Ni(NO3)2 as an etching agent, the ZIF-67 polyhedrons were transformed into hollow nanospheres, and further evolved into irregular nanosheets. The bimetallic NiCo phase was formed after pyrolysis in a nitrogen atmosphere at high temperature, with the decomposition and release of organic ligands as gaseous molecules under flowing nitrogen. The obtained bimetallic NiCo porous materials show superior catalytic performance towards hydrolytic dehydrogenation of ammonia borane, thereby nitrobenzene with reducible functional groups can be reduced with high selectivity to the corresponding aniline.

Yb2O3 Doped Zr0.92Y0.08O2-α(8YSZ) and Its Composite Electrolyte for Intermediate Temperature Solid Oxide Fuel Cells.

Yb3+ and Y3+ double doped ZrO2 (8YSZ+4Yb2O3) samples were synthesized by a solid state reaction method. Moreover, 8YSZ+4Yb2O3-NaCl/KCl composites were also successfully produced at different temperatures. The 8YSZ+4Yb2O3, 8YSZ+4Yb2O3-NaCl/KCl (800 °C), and 8YSZ+4Yb2O3-NaCl/KCl (1000 °C) samples were characterized by x⁻ray diffraction (XRD) and scanning electron microscopy (SEM). The results showed that a dense composite electrolyte was formed at a low temperature of 800 °C. The maximum conductivities of 4.7 × 10-2 S·cm-1, 6.1 × 10-1 S·cm-1, and 3.8 × 10-1 S·cm-1 were achieved for the 8YSZ+4Yb2O3, 8YSZ+4Yb2O3-NaCl/KCl (800 °C), and 8YSZ+4Yb2O3-NaCl/KCl (1000 °C) samples at 700 °C, respectively. The logσ~log (pO2) plot result showed that the 8YSZ+4Yb2O3-NaCl/KCl (800 °C) composite electrolyte is a virtually pure ionic conductor. An excellent performance of the 8YSZ+4Yb2O3-NaCl/KCl (800 °C) composite was obtained with a maximum power density of 364 mW·cm-2 at 700 °C.

Discovery of an Orally Bioavailable Dual PI3K/mTOR Inhibitor Based on Sulfonyl-Substituted Morpholinopyrimidines.

The discovery and optimization of a series of 2-morpholino-pyrimidine derivatives containing various sulfonyl side chains at the C4 position led to the identification of compound 26 as a potent dual PI3K/mTOR inhibitor. It exhibited high inhibitory activity against PI3Kα/ß/γ/δ (IC50 = 20/376/204/46 nM) and mTOR (IC50 = 189 nM), potent functional suppression of AKT phosphorylation (IC50 = 196 nM), and excellent antiproliferative effects on a panel of cancer cells. Enzymic data and modeling simulation indicate that a cyclopropyl ring on the C4 sulfone chain and a fluorine on the C6 aminopyridyl moiety are responsible for its maintained PI3K activity and enhanced mTOR potency, respectively. Furthermore, compound 26 exhibited higher efficiency in the HT-29 colorectal carcinoma xenograft model at the daily dose of 3.75 and 7.5 mg/kg relative to BKM120 at the dose of 15 and 30 mg/kg.

Discovery of N-aryl-N'-pyrimidin-4-yl ureas as irreversible L858R/T790M mutant selective epidermal growth factor receptor inhibitors.

A novel series of N-aryl-N'-pyrimidin-4-yl ureas has been optimized to afford potent and selective inhibitors of the EGFR L858R/T790M. The most representative compound 28 showed high activity against EGFR L858R/T790M kinase (IC50 = 4 nM) and 22-fold selectivity against wild type EGFR. Moreover, compound 28 potently inhibited EGFR L858R/T790M phosphorylation (IC50 = 41 nM) and cellular proliferation (IC50 = 37 nM) in the H1975 cell line, while being significantly less toxic to A431 cells. Further, compound 28 exhibited a great selectivity in a mini-panel of kinases.

Accelerated idioventricular rhythm degenerating into bidirectional ventricular tachycardia following acute myocardial infarction.

Bidirectional ventricular tachycardia (BVT) is a rare ventricular tachyarrhythmia. It is usually regular, demonstrating a beat-to-beat alternation in the QRS frontal axis that varies between -20° to -30° and +110°. The tachycardia rate is typically between 140 and 180 beats/min and the QRS is relatively narrow, with a duration of 120 to 150 ms. The etiology of published BVT cases is most commonly digitalis toxicity and, rarely, herbal aconitine poisoning, hypokalemic periodic paralysis, catecholaminergic polymorphic ventricular tachycardia (CPVT), myocarditis, and Andersen-Tawil syndrome. We report a case of accelerated idioventricular rhythm (AIVR) degenerating into BVT following acute myocardial infarction, and briefly discuss the proposed mechanisms underlying BVT.

[The Latest Research Progress of Coupling between BiOX and Semiconductor Photocatalyst].

The heterojunction was formed between two kinds of coupling semiconductors , which improved the charge separation efficiency of system, widened the spectral response range of catalysts and improved photocatalytic propertirs of catalysts. The process of preparation of semiconductors coupling was easily affected by preparation methods and reaction temperature and so on, which would cause the changes in crystal structure and surface properties of coupling semiconductors, thus photocatalytic quantum efficiency of coupling semiconductors was increased. In this article, the following three aspects were mainly discussed. (1) About the coupled system of halogen bismuth oxide and oxide, because generaling BiOX with the semiconductor material compound, the efficient heterojunction structure could be formed, photocatalytic performances of the photocatalytic degradation of pollutants were improved. (2) About the coupled system of AgX and BiOX, compared with the pure AgI or BiOI, composite photocatalytic materials of AgI/BiOI had higher photocatalytic reactivity in visible light. (3) About the coupled system of halogen bismuth oxide and other compounds, after Bi2S3 coupled with BiOX, photoproduction electronic migrated in the two kinds of catalysts, the separation efficiency of electrons and holes was improved, and photocatalytic performances of coupling compound were improved. In addition, in recent years, the latest research progress of the preparation method, the influencing factors of the photocatalytic performance and improving the utilization efficiency of visible light of semiconductors coupling at home and abroad was reviewed in this paper. Finally, the main problems and the future striving direction in semiconductors coupling were presented.

[A Study on Preparation and Photocatalytic Activity of Mn-BiOCl].

Using Bi2O3 and MnC2 x 4H2O as raw materials, with HCl as solvent, photocatalysts of Mn-BiOCl with different molar ratio of Mn and Bi were prepared by a hydrolysis method. The obtained samples were characterized by XRD, HRTEM, TEM, UV-Vis DRS and SPS. The UV light photocatalytic activity of Mn-BiOCl was evaluated by using methyl orange as model compounds of photocatalytic reaction. The active species in the degradation process of methyl orange were studied. The results show that the Mn content of Mn-BiOCl photocatalysts has an important effect on the catalytic activity. When the molar ratio of Mn and Bi is 0.25%, the as-prepared Mn-BiOCl photocatalyst has the highest catalytic activity toward the degradation of methyl orange. Photocatalytic degradation rate of methyl orange can reach 95.1%.

Discovery of fruquintinib, a potent and highly selective small molecule inhibitor of VEGFR 1, 2, 3 tyrosine kinases for cancer therapy.

VEGF/VEGFR signal axis has been proven to be an important target for development of novel cancer therapies. One challenging aspect in small molecular VEGFR inhibitors is to achieve sustained target inhibition at tolerable doses previously seen only with the long-acting biologics. It would require high potency (low effective drug concentrations) and sufficient drug exposures at tolerated doses so that the drug concentration can be maintained above effective drug concentration for target inhibition within the dosing period. Fruquintinib (HMPL-013) is a small molecule inhibitor with strong potency and high selectivity against VEGFR family currently in Phase II clinical studies. Analysis of Phase I pharmacokinetic data revealed that at the maximum tolerated dose of once daily oral administration fruquintinib achieved complete VEGFR2 suppression (drug concentrations were maintained above that required to produce >85% inhibition of VEGFR2 phosphorylation in mouse) for 24 hours/day. In this article, the preclinical data for fruquintinib will be described, including kinase enzyme activity and selectivity, cellular VEGFR inhibition and VEGFR-driven functional activity, in vivo VEGFR phosphorylation inhibition in the lung tissue in mouse and tumor growth inhibition in a panel of tumor xenograft and patient derive xenograft models in mouse. Pharmacokinetic and target inhibition data are also presented to provide a correlation between target inhibition and tumor growth inhibition.

Discovery of (S)-1-(1-(Imidazo[1,2-a]pyridin-6-yl)ethyl)-6-(1-methyl-1H-pyrazol-4-yl)-1H-[1,2,3]triazolo[4,5-b]pyrazine (volitinib) as a highly potent and selective mesenchymal-epithelial transition factor (c-Met) inhibitor in clinical development for treatment of cancer.

HGF/c-Met signaling has been implicated in human cancers. Herein we describe the invention of a series of novel triazolopyrazine c-Met inhibitors. The structure-activity relationship of these compounds was investigated, leading to the identification of compound 28, which demonstrated favorable pharmacokinetic properties in mice and good antitumor activities in the human glioma xenograft model in athymic nude mice.

[Study on synthesis and matching degree of energy level of terbium complexes using o-fluoro-benzoic acid as ligand].

Tb(2-FBA)3 x 2H2O and Tb(2-FBA)3 phen were synthesized using o-fluoro-benzoic acid (2-FBA) as the first ligand, and 1,10-phenanthroline (phen) as the second ligand. Elemental analysis and IR spectra were employed to characterize the molecular composition of the two kinds of lanthanide complexes. The UV absorption spectra with same concentration show that the second ligand phen of Tb(2-FBA)3 phen absorbs the portion of the UV light instead of the first ligand 2-FBA. Liquid fluorescence spectra with same concentration show that the fluorescence intensity of Tb(2-FBA)3 x 2H2O is higher than that of Tb (2-FBA)3 phen. The analytical results show that the energy level of 2-FBA matches the lowest excited state energy level of Tb3+ (5D4) better than that of phen. The O-H oscillation of the crystal water in Tb(2-FBA)3 x 2H2O will greatly consume the absorbed energy by ligands, and cause the fluorescence intensity of Tb(2-FBA)3 x 2H2O significantly decline. The energy level of triplet state of the first ligand 2-FBA corresponding to the absorption peak 273 nm has poor matching degree with the 5D4 energy level of Tb3+. In this case, the emission intensity of Tb(2-FBA)3 x 2H2O is still stronger than that of Tb(2-FBA)3 phen. It illustrates that the energy level of the triplet state of the first ligand 2-FBA corresponding to 252 nm has much better matching degree with the lowest excited state of 5D4 energy level of Tb3+ than that of phen. It is the only way to compensate for energy loss by thermal vibration of water molecules and low energy transfer efficiency for poor matching degree between the energy level of corresponding to 273 nm of the first ligand 2-FBA and 5D4 energy level of Tb3+. By combining UV absorption spectra with fluorescence spectra of lanthanide complexes to qualitatively analyze energy level of ligands, the contribution of different types of ligands to the fluorescence properties can be preliminarily understood.

One-pot synthesis of α-Fe2O3 nanospheres by solvothermal method.

We have successfully prepared α-Fe2O3 nanospheres by solvothermal method using 2-butanone and water mixture solvent for the first time, which were about 100 nm in diameter and composed of very small nanoparticles. The as-prepared samples were characterized using X-ray diffraction, scanning electron microscopy, and transmission electron microscopy. The results showed that the product was α-Fe2O3 nanosphere, and the temperature was an important factor on the formation of α-Fe2O3 nanospheres.

[Study on preparations and fluorescent properties of rare earth complex with property of fluorescence sensor].

Europium chloride, 2-thienylformyltrifluoroacetone and sodium silicate were used to synthesize new-style rare earth complex (Eu-TNS). By adding into dichloromethane solution containing Eu-TNS, the fluorescent intensities were enhanced gradually and regularly. High-resolution mass spectrometry was used to detect the formula of Eu-TNS, which belongs to multi-core rare-earth complex. Polarity of solution increasing by adding absolute ethanol will cause Eu-TNS to dissociate, which enhances the fluoresceot intensities of Eu-TNS solution. This rare earth complex Eu-TNS can be employed as fluorescence sensor to detect the content of ethanol in organic solvent.

[Synthesis of SiO2 coated Eu(TTA)3phen and study on its fluorescent property].

New-style fluorescent material of SiO2/Eu(TTA)3 phen was synthesized by the method of dispersing Eu(TTA)3 phen in isopropanol and hydrolyzing TEOS. Fluorescence spectra showed that the emission intensities of SiO2/Eu(TTA)3 phen were much more stronger than that of Eu(TTA)3 phen by more than two times. At the same time, the peak at 617.4 nm became very sharp, which could not be observed for Eu(TTA)3 phen. This indicated that the structure of Eu(TTA)3 phen became more rigid after coated by SiO2. Thus, the emission intensity was enhanced largely. Life-time of SiOz/Eu(TTA)3 phen decreasing just confirmed the rigidity of SiO2/Eu(TTA)3 phen.

[Synthesis and characterization of new lanthanide complexes using pipemidic acid (PPA) and dioxane as ligands].

Eu(PPA)3 dioxane and Tb(PPA)3 dioxane were synthesized by firstly adopting dioxane as second ligand and using pipemidic acid (PPA) as first ligand. In contrast with two kinds of binary lanthanide complexes Eu(PPA)3 and Tb(PPA)3, the photoluminescent intensities of Eu (PPA)3 dioxane and Tb (PPA)3 dioxane are much stronger, especially for that of Tb(PPA)3 dioxane. The enhancement of photoluminescent intensities of Eu(PPA)3 dioxane and Tb(PPA)3 dioxane is because of the replacement of dioxane for water bonded to Eu3+ and Tb3+, by which the energy loss through heat oscillation will be inhibited. The as-synthesized lanthanide complexes were characterized by FT-IR, photoluminescence spectra and photoluminescence lifetime. The lifetime of Eu(PPA)3 dioxane and Tb(PPA) dioxane remarkably changed compared with those of Eu(PPA)3 and Tb(PPA)3. However, there is much difference for the lifetime change of as-synthesized lanthanide complexes formed by Eu3+ and Tb3+, which shows that there is different energy transfer process for the lanthanide complexes formed by Eu3+ and Tb3+. The synthesis of lanthanide complexes using dioxane as second ligand will provide a new method to detect the existence of dioxane.

Kushen flavonoids induce apoptosis in tumor cells by inhibition of NF-kappaB activation and multiple receptor tyrosine kinase activities.

In this report, the mechanism of the antitumor activities of Kushen flavonoids (KS-Fs) were explored. KS-Fs and kurarinone (Kur), a single flavonoid compound, were able to induce apoptosis of H460 and Eca-109 cells in vitro and H460 cells in vivo. The apoptosis inducing effect was enhanced in the presence of Taxol. In H460 xenograft mice treated with Kur, down-regulation of Bcl-2 and up-regulation of caspase 8 and caspase 3 in tumors were observed by immunohistochemical staining. In addition, KS-Fs and Kur were able to inhibit TNFalpha-induced NF-kappaB activation in 293 cells mediated by the decreased IkappaBalpha phosphorylation. Further the effects of KS-Fs and Kur on multiple receptor tyrosine kinase activities were explored. In cell-based assays, KS-Fs and Kur inhibited the EGF-induced EGF receptor phosphorylation in A431 cells and a constitutively activated Her-2 in MDA-MB-453s cells. In enzymatic assays, KS-Fs and Kur inhibited KDR, but not PDGF BR activities. In A431 xenograft mice treated with Kur, an inhibition of EGF receptor phosphorylation in tumors was observed. These results reveal a novel mechanism by which KS-Fs induces apoptosis in tumors by acting on multiple cellular targets including the inhibition of NF-kappaB activation and multiple receptor tyrosine kinase activities.

Novel antitumor activities of Kushen flavonoids in vitro and in vivo.

Kushen (KS), the dried roots of Sophora flavescens Aiton, has a long history of use in traditional Chinese medicine to treat inflammatory diseases and cancer. Kushen alkaloids (KS-As) and Kushen flavonoids (KS-Fs) are the well characterized components in KS. KS-As have been considered biologically active and developed in China as anticancer drugs. In an effort to screen novel antitumor agents from botanicals, more potent antitumor activities were identified in KS-Fs than in KS-As. KS-Fs were able to inhibit the growth of a panel of tumor cell lines and enhanced the antitumor activities of Taxol in vitro. The antitumor activities of KS-Fs and Kur, a single KS-Fs compound, were demonstrated in murine and xenograft human tumor models. Further, it was shown that KS-Fs and Kur were able to enhance the effect of Taxol to inhibit the growth of H460 and Eca-109 xenograft tumors. In addition, peripheral blood cell counts were not significantly affected in normal mice treated with KS-Fs at 200 mg/kg/day for 2 weeks. These results suggest that KS-Fs may be developed as novel antitumor agents and that the currently marketed KS-As drugs in China may have missed the major antitumor activities in Kushen.

Assembly of TbetaRI:TbetaRII:TGFbeta ternary complex in vitro with receptor extracellular domains is cooperative and isoform-dependent.

Transforming growth factor-beta (TGFbeta) isoforms initiate signaling by assembling a heterotetrameric complex of paired type I (TbetaRI) and type II (TbetaRII) receptors on the cell surface. Because two of the ligand isoforms (TGFbetas 1, 3) must first bind TbetaRII to recruit TbetaRI into the complex, and a third (TGFbeta2) requires a co-receptor, assembly is known to be sequential, cooperative and isoform-dependent. However the source of the cooperativity leading to recruitment of TbetaRI and the universality of the assembly mechanism with respect to isoforms remain unclear. Here, we show that the extracellular domain of TbetaRI (TbetaRI-ED) binds in vitro with high affinity to complexes of the extracellular domain of TbetaRII (TbetaRII-ED) and TGFbetas 1 or 3, but not to either ligand or receptor alone. Thus, recruitment of TbetaRI requires combined interactions with TbetaRII-ED and ligand, but not membrane attachment of the receptors. Cell-based assays show that TbetaRI-ED, like TbetaRII-ED, acts as an antagonist of TGFbeta signaling, indicating that receptor-receptor interaction is sufficient to compete against endogenous, membrane-localized receptors. On the other hand, neither TbetaRII-ED, nor TbetaRII-ED and TbetaRI-ED combined, form a complex with TGFbeta2, showing that receptor-receptor interaction is insufficient to compensate for weak ligand-receptor interaction. However, TbetaRII-ED does bind with high affinity to TGFbeta2-TM, a TGFbeta2 variant substituted at three positions to mimic TGFbetas 1 and 3 at the TbetaRII binding interface. This proves both necessary and sufficient for recruitment of TbetaRI-ED, suggesting that the three different TGFbeta isoforms induce assembly of the heterotetrameric receptor complex in the same general manner.

Epidermal growth factor modulates tyrosine phosphorylation of a novel tensin family member, tensin3.

Here, we report the identification of a new tensin family member, tensin3, and its role in epidermal growth factor (EGF) signaling pathway. Human tensin3 cDNA encodes a 1445 amino acid sequence that shares extensive homology with tensin1, tensin2, and COOH-terminal tensin-like protein. Tensin3 is expressed in various tissues and in different cell types such as endothelia, epithelia, and fibroblasts. The potential role of tensin3 in EGF-induced signaling pathway is explored. EGF induces tyrosine phosphorylation of tensin3 in MDA-MB-468 cells in a time- and dose-dependent manner, but it is independent of an intact actin cytoskeleton or phosphatidylinositol 3-kinase. Activation of EGF receptor is necessary but not sufficient for tyrosine phosphorylation of tensin3. It also requires Src family kinase activities. Furthermore, tensin3 forms a complex with focal adhesion kinase and p130Cas in MDA-MB-468 cells. Addition of EGF to the cells induces dephosphorylation of these two molecules, leads to disassociation of the tensin3-focal adhesion kinase-p130Cas complex, and enhances the interaction between tensin3 and EGF receptor. Our results demonstrate that tensin3 may function as a platform for the disassembly of EGF-related signaling complexes at focal adhesions.