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Two series of novel 4-phenoxypyridine derivatives containing imidazole-4-carboxamide and 4-methyl-5-oxo-4,5-dihydro-1,2,4-triazole-3-carboxamide moieties were synthesized and evaluated for their in vitro inhibitory activities against c-Met kinase and antiproliferative activities against MKN-45, A549 and H460 cancer cell lines. The results indicated that most of the compounds showed moderate to good antitumor activities. The most promising compound T14 (with c-Met IC

On the basis of N-(3-amino-4-methoxyphenyl)acrylamide scaffold, a series of novel compounds containing 3-substitutional-1-methyl-1H-indole, 2-substitutional pyrrole or thiophene moieties were synthesized and their in vitro antiproliferation activities against A549 and H1975 cell lines were evaluated. The results indicated that most of the compounds showed moderate to excellent antitumor activities. Especially, compounds 9a (A549 IC50 = 1.96 μM, H1975 IC50 = 0.095 μM), 17i (A549 IC50 = 4.17 μM, H1975 IC50 = 0.052 μM), 17j (A549 IC50 = 1.67 μM, H1975 IC50 = 0.061 μM) exhibited comparable antitumor activities and selectivity ratios compared to the positive control osimertinib (A549 IC50 = 2.91 μM, H1975 IC50 = 0.064 μM). In vitro inhibitory activities against EGFR kinases containing different mutations were also tested. Compound 17i showed remarkable inhibitory activity (with IC50 value of 1.7 nM) to EGFRL858R/T790M kinase and selectivity (22-folds compared to EGFRWT kinase). Furthermore, acridine orange/ethidium bromide (AO/EB) staining assay, cell apoptosis assay, cell cycle distribution assay and wound-healing assay of the compounds 9a and 17i were performed on H1975 cell line. The results showed dose-dependent activities of the induction of apoptosis, G0/G1-phase arrestation and inhibition of migration, which were similar to the positive control osimertinib. Additionally, molecular docking analysis was performed to seek the possible binding mode between the selected compounds (9a, 17i-17j) and EGFRL858R/T790M kinase. The results demonstrated that compound 17i is a promising candidate and worth further study.

In order to develop novel LpxC inhibitors with good activities and metabolic stability, two series of compounds with hydrophilic terminus have been synthesized and their in vitro antibacterial activities against Escherichial coli and Pseudomonas aeruginosa were evaluated. Especially, compounds 22b and c exhibited comparable antibacterial activities to CHIR-090 and better metabolic stability than CHIR-090 and LPC-011 in liver microsomes (rat and mouse), which indicated the terminal methylsulfone may be a preferred structure in the design of LpxC inhibitors and worthy of further investigations.

In our previous Letter, we reported the discovery of a novel benzoxazinyl-oxazolidinone antibacterial candidate 2. In order to identify a potential backup compound, extensive modifications on the B/C ring and C3 side chain were undertaken. A series of novel [6,6,5] tricyclic analogues were synthesized and their in vitro antibacterial activities were tested against a panel of susceptible and resistant Gram-positive pathogens. Among of them, benzothiazinyl-oxazolidinones with acetamide or thioamide as C3 side chains exhibited moderate to good antibacterial activity, such as compounds 54, 58, 59 and 63. In vitro liver microsomal stability was further evaluated and the results manifested that compounds 54 and 58 were both metabolically stable in rat and human liver microsomes. Additionally, insights gained from this investigation should provide directions for the further research of new oxazolidinone antibiotics.

SummaryDuring the development of vertebrate neuromuscular junction (NMJ), agrin stabilizes, whereas acetylcholine (ACh) destabilizes AChR clusters, leading to the refinement of synaptic connections. The intracellular mechanism underlying this counteractive interaction remains elusive. Here, we show that caspase-3, the effector protease involved in apoptosis, mediates elimination of AChR clusters. We found that caspase-3 was activated by cholinergic stimulation of cultured muscle cells without inducing cell apoptosis and that this activation was prevented by agrin. Interestingly, inhibition of caspase-3 attenuated ACh agonist-induced dispersion of AChR clusters. Furthermore, we identified Dishevelled1 (Dvl1), a Wnt signaling protein involved in AChR clustering, as the substrate of caspase-3. Blocking Dvl1 cleavage prevented induced dispersion of AChR clusters. Finally, inhibition or genetic ablation of caspase-3 or expression of a caspase-3-resistant form of Dvl1 caused stabilization of aneural AChR clusters. Thus, caspase-3 plays an important role in the elimination of postsynaptic structures during the development of NMJs.

β-Sialon/ZrN/ZrON composites were successfully fabricated by an in-situ carbothermal reduction-nitridation process with fly ash, zircon and active carbon as raw materials. The effects of raw materials composition and holding time on synthesis process were investigated, and the formation process of the composites was also discussed. The phase composition and microstructure of the composites were characterized by means of XRD and SEM. It was found that increasing carbon content in a sample and holding time could promote the formation of β-Sialon, ZrN and ZrON. The proper processing parameters to synthesize β-Sialon/ZrN/ZrON composites were mass ratio of zircon to fly ash to active carbon of 49:100:100, synthesis temperature of 1550 °C and holding time of 15 h. The average grain size of β-Sialon and ZrN(ZrON) synthesized at 1550 °C for 15 h reached about 2 and 1 μm, respectively. The fabrication process of β-Sialon/ZrN/ZrON composites included the formation of β-Sialon and ZrO 2 as well as the conversion of ZrO 2 to ZrN and ZrON.

Objective To explore the best clinical treatment for infantile malnutrition. Methods Three hundred and forty-three patients were randomly divided into a pricking at Sifeng ( EX-UE 10) group (priking group, n=105), a Chinese herbs group (n=85) and a pricking and Chinese herbs group (n=153). The improvements of the clinical symptoms of all three groups were evaluated after the treatment. Results The results of these treatments for all the patients were satisfying. The effective rate of the pricking and Chinese herbs group, which was 98.7 % (151/153), was superior to that of 94.3 % (99/105) (P 0.05). Conclusion The pricking at Sifeng ( EX-UE 10) combined with Chinese herbs is the best treatment for infantile malnutrition.

β-Sialon based composites were successfully prepared from fly ash and carbon black under nitrogen atmosphere by carbothermal reduction-nitridation process. Effects of heating temperature and raw materials composition on synthesis process were investigated, and the formation process of the composites was also discussed. The phase composition and microstructure of the composites were characterized by X-ray diffraction and scanning electronic microscopy. The results show that increasing heating temperature or mass ratio of carbon black to fly ash can promote the formation of O ′-Sialon. The β-Sialon based composites can be synthesized at 1723 K for 6 h while heating the sample with mass ratio of carbon black to fly ash of 0.56. The as-received β-Sialon in the composites exists as granular with an average particle size of 2–3 μm. The preparation process of β-Sialon based composites includes the formation of O '-Sialon, X -Sialon and β-Sialon as well as the conversion processes of O ′-Sialon and X -Sialon to β-Sialon.

In this article, we focus on discussing the degree distribution of the DMS model from the perspective of probability. On the basis of the concept and technique of first-passage probability in Markov theory, we provide a rigorous proof for existence of the steady-state degree distribution, mathematically re-deriving the exact formula of the distribution. The approach based on Markov chain theory is universal and performs well in a large class of growing networks.

Three Ni-based catalysts, namely Ni/ZrO 2 /Al 2 O 3 , Ni/La–Ca/Al 2 O 3 and Ni 0.5 Mg 2.5 AlO 9 catalysts were prepared, tested and characterized for steam reforming of methane (SRM), especially at high space velocities. Experimental results demonstrated that Ni 0.5 Mg 2.5 AlO 9 catalysts showed excellent catalytic activity, e.g., the high reaction performance (i.e., activity and stability) at a very short residence time of 20 ms. For the accompanied water gas shift (WGS) reaction with the SRM at the steam to methane ratio of 3:1, the overall hydrogen yield depended on both the CH 4 conversion and the CO 2 selectivity. The results showed that CO 2 selectivity had opposite trend compared with CH 4 conversion in such a short-contact process. Catalyst characterizations by XRD, SEM-EDS, TEM and TGA suggested that the good performance of nickel catalysts was closely related with the good dispersion of the active component. The nano-sized nickel particles in strong interaction with the supports would lead to the good dispersion, thereafter having a slight tendency to sintering, and then to coking.

The growing network model with loops and multiple edges proposed by Bollobas et al. (Random Structures and Algorithms 18(2001)) is restudied from another perspective. Based on the first-passage probability of Markov chains, we prove that the degree distribution of the LCD model is power-law with degree exponent 3 as the network size grows to infinity.

micro-reactor has drawn more and more attention in recent years due to the process intensification on basic transport phenomena in micro-channels, which would often lead to the improved reactor performance. Steam reforming of methane (SRM) in micro-reactor has great potential to realize a low-cost, compact process for hydrogen production via an evident shortening of reaction time from seconds to milliseconds. This work focuses on the detailed modeling and simulation of a micro-reactor design for SRM reaction with the integration of a micro-channel for Rh-catalyzed endothermic reaction, a micro-channel for Pt-catalyzed exothermic reaction and a wall in between with Rh or Pt-catalyst coated layer. The elementary reaction kinetics for SRM process is adopted in the CFD model, while the combustion channel is described by global reaction kinetics. The model predictions were quantitatively validated by the experimental data in the literature. For the extremely fast reactions in both channels, the simulations indicated the significance of the heat conduction ability of the reactor wall as well as the interplay between the exothermic and endothermic reactions (e.g., the flow rate ratio of fuel gas to reforming gas). The characteristic width of 0.5 mm is considered to be a suitable channel size to balance the trade-off between the heat transfer behavior in micro-channels and the easy fabrication of micro-channels.

CFD simulation with detailed chemistry was conducted to understand the catalytic partial oxidation of methane (CPOM) on rhodium-coated foam monolith. For the underlying process occurred extremely fast with large gradients of temperature and species concentrations at the inlet, special attention must be paid to the appropriate treatment on computational geometry and corresponding boundary conditions for the simulation. Discussions were made carefully on this proposed issue in geometry modeling that the reliable predictions can be authentically obtained by adopting the same geometry as the experiments from the viewpoint of physics in order to fully consider the heat conduction/diffusion at the reactor inlet. The right model system was sufficiently validated by both the conceptual analysis and the experimental results. The reactor performance of CPOM process was thereafter studied by numerically revealing the effects of wall heat conduction, the channel diameter and the catalytic surface area on the profiles of temperature and species concentrations. The results showed that the maximum wall temperature, which was crucial for the catalyst stability, could be significantly reduced by increasing the thermal conductivity of the wall, and/or the channel diameter, and/or the catalytic surface area, but accompanied with a slight drop of the methane conversion. This deficiency can be retrieved by decreasing the atom feed ratio of C/O and/or elongating the catalytic bed. These results pointed out the necessity of facilitating the foam material, the channel diameter and the catalytic surface area with the operating conditions in order to achieve the best performance of the CPOM process in the millisecond reactor.

A series of Ag-doped manganese oxide catalyst were synthesized by the reflux method in an acid medium. The surface structure of the catalysts was characterized by N 2 adsorption, XRD and TEM experiments. The catalysts showed excellent catalytic activity for CO oxidation. The adsorption and oxidation of CO on a 1.0% Ag/MnO x catalyst between 393 and 493 K were studied by means of single pulse experiments in a TAP reactor. The adsorption of CO was reversible at these temperatures and CO 2 was formed in an oxidation reaction of CO and lattice oxygen. Curve fitting to the experimental TAP response curves of the reactant and product was used to determine the kinetic parameters for the elementary steps. The activation energies were 83 kJ/mol for CO desorption, 31 kJ/mol for CO 2 desorption, and 116 kJ/mol for the surface CO oxidation by lattice oxygen. In addition, the effect of coadsorbed O 2 on CO adsorption was studied by the TAP technique. Below 353 K, there was a sharp increase, by about one order of magnitude, in the rate constant of CO adsorption promoted by the presence of coadsorbed O 2 .

The changes in the eluted reactant's response curves from a pulse reactor operated in Knudsen flow [e.g. a temporal-analysis-of-products (TAP) reactor] as a function of the pulse size was interpreted as due to varying fractional coverages of the catalyst surface. These were used with the reactor modeling of the response curves to determine the active site concentration on a catalyst powder. The technique uses a transient pulse to bring about significant site coverage, and is an improvement on the present use of gas–surface concentration equilibrium because it is able to selectively determine just the active site concentration and not the entire exposed surface atom concentration.

Intermittent hypoxia has been found to prevent brain injury and to have a protective role in the CNS. To address the possible causes of this phenomenon, we made investigative effort to find out whether intermittent hypoxia affects neurogenesis in the adult rat brain by examining the newly divided cells in the subventricular zone (SVZ) and dentate gyrus (DG). The adult rats were treated with 3000 and 5000 m high altitude 4 h per day for 2 weeks consecutively. 5-Bromo-2-deoxyuridine-5-monophosphate (BrdU) immunocytochemistry demonstrated that the BrdU-labeled cells in the SVZ and DG increased after 3000 and 5000 m intermittent hypoxia. The number of BrdU-labeled cells in the SVZ returned to normal level 4 weeks following intermittent hypoxia. However, the BrdU-labeled cells in the DG had a twofold increase 4 weeks subsequent to intermittent hypoxia. From these data, we conclude that intermittent hypoxia facilitates the proliferation of neural stem cells in situ, and that the newly divided cells in the SVZ and DG react differently to hypoxia. We are convinced by these findings that the proliferation of neural stem cells in SVZ and DG may contribute to adaptive changes following intermittent hypoxia.

The determination of the static and seismic response of curved girder bridges is important and difficult. It is therefore the purpose of this paper to present a direct method for evaluating accurately the mode shapes and the final seismic actions of continuous curved girders supported on high piers, with minimum computation time, using the Rayleigh-Ritz method. Application of the method, compared to the matrix technique, is presented in detail.