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The radioactive aerosols deposited wash-down by condensate on walls in containment is one of the pathways for radioactive migration. Condensate film coverage is critical to the transport properties of aerosol particles during wash-down. In this paper, an experimental study was carried out to visualize the processes of condensation and aerosol wash-down on an aerosol-containing wall. The evolutionary pattern of condensate was observed in the experiment. Variations in condensate coverage on walls with different inclination angles of 0°, 0.4°, 2°, 30°, and 90° were noted. The effect of coverage on aerosol removal efficiency was also analyzed based on the results. Experimental results show that wall coverage on horizontal (0°) or quasi-horizontal walls (0.4°) is close to 100 %. For inclined or vertical walls, under the influence of thermal capillary forces, rivulets are the main forms of condensate coverage, with the maximum area that can be covered by rivulets being about 2/3 of the wall area. The experimental results show that the removal efficiency of aerosol during washing will be higher than the coverage rate of condensate. In the experiments, both condensation rate and aerosol loading tended to promote the spreading of condensate. [ABSTRACT FROM AUTHOR]

The washing behavior of radioactive aerosol caused by condensation on floor is of great significance for evaluating radioactive migration in case of an accident in nuclear power plant. Compared to the inclined or vertical wall, on a nearly horizontal floor the aerosol particles may have a characteristic transport progress, considering the slower speed of the condensate flow and weaker erosion ability to wash-down aerosol due to insufficient shear stress. An experiment in the steam environment is conducted on this study, focusing on condensation and wash-down of deposited insoluble aerosol particles on a 0.4° quasi-horizontal plate. An exponential trend of removed aerosol mass is obtained based on the experimental aerosol transport process on the quasi-horizontal surface. This paper evaluated the effects of particle load and condensation rate on transport process and removed mass. Furthermore, based on the experimental results, a fitting empirical correlation between dimensionless aerosols' removal mass and dimensionless mass of condensate are obtained by modifying the conditions of different condensation rates and aerosol loads. [ABSTRACT FROM AUTHOR]

In order to improve catalytic activity, increase recycling times, reduce use cost for enzyme, superparamagnetic carboxymethyl chitosan/sodium alginate nanosphere (SM/CMC/SA) has been synthesized via an improved hydrothermal method, molecular self-assembly technology, electrostatic interaction and amide linkage. Its mean diameter was 65 nm, zeta potential was −36.9 mV and BET was 53.8 m 2 /g. α-Amylase was selected as a simulation object to manufacture an immobilized enzyme (SM/CMC/CA/α-Amy), and its catalytic activity, release behavior, reusability and stability were researched. Immobilization increased 4.67 times to catalytic activity, slowed down release rate and improved reusable performance. SM/CMC/CA/α-Amy showed higher activity over a wider pH range, especially in strong acidic and alkaline environments. The thermal stability and storage stability were improved remarkably too. All these results indicated that SM/CMC/SA was an ideal carrier for immobilizing enzyme. [ABSTRACT FROM AUTHOR]

Abstract: Recently we reported that middle ear pressure (MEP), middle ear effusion (MEE), and ossicular changes each contribute to the loss of tympanic membrane (TM) mobility in a guinea pig model of acute otitis media (AOM) induced by Streptococcus pneumoniae (Guan and Gan, 2013). However, it is not clear how those factors vary along the course of the disease and whether those effects are reproducible in different species. In this study, a chinchilla AOM model was produced by transbullar injection of Haemophilus influenzae. Mobility of the TM at the umbo was measured by laser vibrometry in two treatment groups: 4 days (4D) and 8 days (8D) post inoculation. These time points represent relatively early and later phases of AOM. In each group, the vibration of the umbo was measured at three experimental stages: unopened, pressure-released, and effusion-removed ears. The effects of MEP and MEE and middle ear structural changes were quantified in each group by comparing the TM mobility at one stage with that of the previous stage. Our findings show that the factors affecting TM mobility do change with the disease time course. The MEP was the dominant contributor to reduction of TM mobility in 4D AOM ears, but showed little effect in 8D ears when MEE filled the tympanic cavity. MEE was the primary factor affecting TM mobility loss in 8D ears, but affected the 4D ears only at high frequencies. After the release of MEP and removal of MEE, residual loss of TM mobility was seen mainly at low frequencies in both 4D and 8D ears, and was associated with middle ear structural changes. Our findings establish that the factors contributing to TM mobility loss in the chinchilla ear were similar to those we reported previously for the guinea pig ears with AOM. Outcomes did not appear to differ between the two major bacterial species causing AOM in these animal models. [Copyright &y& Elsevier]

Abstract: A set of 22 toluene- and ethylbenzene-degrading strains were screened for the enantioselective benzylic hydroxylation of indan and tetralin, and Pseudomonas monteilii TA-5 was discovered as an active and selective biocatalyst for such hydroxylations. Cells of P. monteilii TA-5 can be easily grown to a high density and demonstrated a specific hydroxylation activity of 24U/g cdw (cell dry weight). Conditions for the hydroxylation of indan 1a and tetralin 1b with resting cells of this strain were optimized, to give the corresponding (R)-1-indanol 2a and (R)-1-tetralol 2b in 99% ee and 62–67% yields, respectively. No significant product inhibition was observed, and biohydroxylation with cell-free extracts suggested that the responsible hydroxylase is a soluble enzyme depending on either NADH or NADPH. Preparative biohydroxylation was demonstrated with resting cells as biocatalysts, affording (R)-2a in 99% ee and 65% yield, and (R)-2b in 99% ee and in 63% yield, respectively. [Copyright &y& Elsevier]

Abstract: Forty one microorganisms belonging to different taxonomical groups were used to carry out the enantioselective reduction of methyl benzoylformate to afford the corresponding (R)-methyl mandelate, with moderate to high ee. In contrast, the monooxygenase enzyme in Helminthosporium sp. CIOC3.3316 catalyzed the hydroxylation of methyl 2-phenylacetate to (S)-methyl mandelate. This combination of oxidation and reduction biotransformations thus provides a method for preparing the enantiomers of chiral α-hydroxy acid derivatives. [Copyright &y& Elsevier]

To overcome cancer drug resistance, in present study, a series of podophyllotoxin-indirubin hybrids were designed, synthesized, and evaluated for anticancer efficacy against two human chronic myeloid leukemia cell cultures. Among them, compound Da-1 was the most potent in resistent K562/VCR cells with an IC 50 value of 0.076 ± 0.008 μM. Preliminary mechanism studies showed that Da-1 significantly induced apoptosis and cell cycle arrest at the G2 phase. Decrease in mitochondrial membrane potential, accompanied by activated PARP cleavage, was observed in K562/VCR cells after incubation with Da-1 . Meanwhile, Da-1 caused the accumulation of intracellular ROS, regulated JNK and AKT signaling, and down-regulated the expression levels of P-gp and MRP1 proteins. Importantly, Western blotting revealed that Da-1 could induce K562/VCR cells autophagy, by increasing the levels of Beclin1 and LC3-II. Finally, Da-1 could disrupt microtubule organization, and binding mode to tubulin was investigated by using molecular modeling. Together, Da-1 was a novel hybrid with potent antiproliferative activity and might be a promising agent for the treatment of drug-resistant leukemia cancer. [ABSTRACT FROM AUTHOR]

A scale ration of 1:1 test loop was constructed to investigate the water seal formation phenomenon in front of pressurizer safety valve in nuclear plant. The water seal features were investigated under the condition of pressure ranging from 0.15 to 0.55 MPa. The test was placed in a room with air conditioner to make sure the temperature in the room is keep relative stability thermal conditions, the temperature in the room may fluctuation between 20° and 25°. Water level oscillates in the process of water seal stabilization, the experimental data fit very well with the proposed model in the paper. The water seal formation time reduced significantly with pressure increasing and air concentration decreasing. Refilling of the pipe is much more rapid than the initial one due to a lower content of non-condensable gases remaining in the steam. Finally, the water seal starting point judgment method has been put forward in this paper. [ABSTRACT FROM AUTHOR]

A two-step enantioselective synthetic strategy for the preparation of β -hydroxyl-sulfoxides has been described. With the enzymatic reduction of β -ketosulfides using Pseudomonas monteilii ZMU-T04 followed by the asymmetric sulfoxidation with Ti(O i Pr) 4 /( S )-BINOL complexe, a wide range of corresponding β -hydroxyl-sulfoxide derivatives were smoothly obtained with excellent stereoselectivities (up to 99:1 dr and >99% ee). A plausible chelate structure of titanium complexe in the asymmetric sulfoxidation of β -hydroxyl-sulfides was also proposed on the basis of control experiments. [ABSTRACT FROM AUTHOR]

Currently, multi-drug resistance (MDR) to antineoplastic drugs is a major obstacle to successful treatment of carcinoma. Looking for novel agents with anti-MDR activity is an effectively way to overcome cancer drug resistance. Our previous study showed that podophyllotoxin derivative exhibited potent anti-proliferative effect and down-regulated the expression level of P-gp in K562/ADR cells, which probably was related with the MAPK pathways. However, the relation of P-gp expression and MAPK pathways still remains unclear. In this study, a series of aromatic heterocyclic esters of podophyllotoxin were synthesized and their anticancer effects were evaluated against two human chronic myeloid leukemia cell lines (K562 and K562/ADR), simultaneously, the initial structure-activity relationship was summarized. The most potent compound, Z5 , displayed an IC 50 value of 0.032 ± 0.006 μM against K562/ADR cells, with a lower resistant factor value of 1.280. Treatment of K562/ADR cells with Z5 caused S cell cycle arrest through reductions in cyclinA, cyclinB1, CDK1 and CDK2 levels. Moreover, Z5 treatment resulted in the induction of apoptosis as characterized by DNA staining, flow cytometry analysis and cleavage of procaspases-3, -8, -9 and PARP. Notably, Z5 significantly inhibited P-gp expression in K562/ADR cells. Additionally, Z5 also caused reactive oxygen species (ROS) generation, which was further demonstrated by preincubation with the antioxidant N-acetylcysteine (NAC). Western blotting revealed that Z5 markedly stimulated the MAPK pathways, including ERK1/2, JNK and P38, however, the mechanisms were prevented by NAC. Finally, the employment of NAC and MAPK inhibitors (U0126, SP600125 and SB203580) remarkably blocked the S phase arrest, apoptosis and down-regulation of P-gp induced by Z5 . Taken together, Z5 strongly possessed the potential anti-MDR activity in K562/ADR cells through ROS/MAPK pathways-dependent S phase arrest, apoptosis and down-regulation of P-gp expression. [ABSTRACT FROM AUTHOR]

[Display omitted] • A new function of monoamine oxidase (MAO-5) was found. • Bio-mediated oxidative resolution of racemic 2-substituted indolines was developed. • (R)-2-methyl-indoline and its derivates was obtained with high enantioselectivity by biocatalytic process. Monoamine oxidase strain (MAO-5) from Pseudomonas monteilii ZMU-T01 mediated oxidative resolution of racemic 2-substituted indolines has been successfully described. A series of highly enantioselective 2-substituted indoline derivatives were obtained in up to 50 % conversion and >99 % ee. [ABSTRACT FROM AUTHOR]

Multidrug resistance (MDR) is the main cause for chemotherapeutic failure in cancer treatment. To overcome MDR, a serious of pyridine acid esters of podophyllotoxin was synthesized and their antiproliferation activities were evaluated against two human chronic myeloid leukemia cell lines in vitro. Most of them exhibited potent growth inhibition with IC 50 values in the nanomolar range as well as markedly reduced resistance factors. The most potent compound, Y8 exhibited an IC 50 of 0.046 ± 0.003 μM against resistance K562/ADR cells, showing more significant than that of adriamycin and etoposide, respectively. Furthermore, Y8 efficiently triggered cell cycle arrest at S phase and simultaneously induced apoptosis in K562/ADR cells. Meanwhile, Y8 also regulated the expression levels of cell cycle- and apoptosis-related proteins. Additionally, Y8 stimulated the ERK1/2 signalling and reduced the expression of Pgp protein. Finally, on the basis of results obtained using U0126, an ERK1/2 inhibitor, the ERK1/2 signalling pathway was proposed for the multidrug resistance-reversing effect of Y8 in K562/ADR cells. Together, Y8 could be a novel potential MDR reversal agent for the treatment of drug-resistant leukemia. [ABSTRACT FROM AUTHOR]

An efficient whole cell-mediated bioreduction of 3-methylene-2-oxindoles has been developed, affording a range of 3-monosubstituted oxindoles in moderate to good yields (41–82%) with Pseudomonas monteilii ZMU-T17 as biocatalyst. Additionally, a possible reaction pathway for this bioreduction of C C double bond was proposed. [ABSTRACT FROM AUTHOR]

A novel conjugate of artesunate–podophyllotoxin was prepared and evaluated for its cytotoxicity against diverse normal and multidrug resistance human cancer cell lines by CCK-8 assay. The conjugate exhibited good cytotoxicity on all the cell lines with IC 50 values of 0.453 ± 0.156–3.011 ± 0.272 μM and reduced the resistant factor. The conjugate was further found to disrupt the microtubule network and induce G2/M cell cycle arrest in multidrug resistance K562/ADR cells. Meanwhile, Hoechst staining analysis suggested that conjugate induced cell death by apoptosis. Furthermore, conjugate could downregulate the levels of P-glycoprotein (P-gp) in P-gp overexpressing K562/ADR cells. [ABSTRACT FROM AUTHOR]

Vinyl 2-chloroacetate was used as an efficient acyl donor for enantioselective acylation of racemic 1,2,3,4-tetrahydroquinolin-4-ols and 2,3,4,5-tetrahydro-1 H -benzo[ b ]azepin-5-ols with Novozyme 435 lipase. Two enantiocomplimentary tetrahydroquinolin-4-ol or tetrahydro-1 H -benzo[ b ]azepin-5-ol derivatives could be smoothly obtained in good to excellent yields and ee values at the same time. Noteworthily, large scale preparation experiment was also demonstrated when amplified the reaction system to 10 g scale experiment, and products were obtained with high yields and ee values. [ABSTRACT FROM AUTHOR]

Through the use of MAAP5 code we carried out an analysis of the severe accident scenarios initiated by an unusual small-break loss-of-coolant accident (SBLOCA) located at the reactor pressure vessel (RPV) lower head with the failure of high-pressure injection system (HPIS) in a PWR power plant. The cases of 0.4-inch-break LOCA with and without manual depressurization of the reactor coolant system (RCS), and 1.0-inch-break LOCA were studied. The results showed that without manually depressurizing the RCS, reactor core underwent slow heatup and completely melted and eventually failed the RPV lower head at the primary system pressure of 6.87 MPa for 0.4-inch-break LOCA and 2.71 MPa for 1.0-inch-break LOCA. There was a strong interaction between the discharged melt and collected pool water in the reactor cavity at the time of RPV lower head failure by creep. A 0.472 MPa containment peak pressure was caused by hydrogen combustion for 0.4-inch-break LOCA. For 1.0-inch-break LOCA the pressure peaked twice, the first one (0.396 MPa) by intense steam generation and the second one (0.331 MPa) by hydrogen combustion. These pressure spikes were lower than the containment design pressure of 0.52 MPa. It was not likely to stop the cavity from being eroded by molten corium through continuously pouring water down into the cavity. Thus there were constant reactor cavity ablation and hydrogen generation, leading to dangerous erosion depths and elevated hydrogen volume fraction in the presence of containment spray system. On the other hand, timely manually opening the pressurizer (PZR) safety valves (SVs) was an effective mitigation measure to recover the core coolabilty by cold-leg accumulator injection system (AIS) and low-pressure injection system (LPIS). Besides, reasonably manually opening the steam generators (SGs) SVs while keeping the auxiliary feedwater on also helped to depressurize the RCS and prevent the severe accident. Both of the two mitigation measures successfully prevented the core from complete melt, but the latter one is preferable to the former one provided no steam generator tube rupture takes place. [ABSTRACT FROM AUTHOR]

A novel asymmetric “metal-biocatalytic system”, involving Rh-catalyzed asymmetric transfer hydrogenation and whole cell mediated asymmetric hydroxylation in aqueous buffer, has been achieved. The methodology gives access to 2-subsituted-tetrahydroquinoline-4-ols bearing two stereocenters from 2-subsituted-quinolines in moderate to excellent results (up to 47% yield, 99:1 dr, and >99% ee). [ABSTRACT FROM AUTHOR]

[Display omitted] • Transition-metal-free, direct C H radical trifluoromethylation of nitroimidazoles. • Green and mild reaction conditions. • Late-stage fluoroalkylation of medicinal agents. Trifluoromethyl moiety in bioactive compounds can dramatically change both the physicochemical and physiological properties, which could further improve both the pharmacokinetic and pharmacological profiles. It has therefore become indispensable to develop an efficient and mild synthetic methodology for the incorporation of trifluoromethyl group. In present study, a green, mild and practical method which allows for the transition-metal-free, direct C H radical trifluoromethylation of nitroimidazoles with Togni's regent II as the CF 3 radical precursor is described. Diverse nitroimidazoles and their drug molecules were smoothly transformed into trifluoromethylated compounds in moderate to good yields under mild conditions. This new method provides an alternative approach for the prepare of trifluoromethylated compounds, as well as late-stage modification of bioactive nitroimidazoles. [ABSTRACT FROM AUTHOR]

Abstract: Highly chemo- and regio-selective benzylic hydroxylations of o- and m-substituted toluenes were achieved with the easily available and easy-to-handle resting cells of Cellulosimicrobium cellulans EB-8-4 as biocatalysts, giving the corresponding benzyl alcohols as single product. Benzyl alcohols were obtained in 78–94% yield, demonstrating the first green, clean, and simple method for the preparation of benzyl alcohols via hydroxylations. Biotransformation of 4-methylbenzyl chloride with the same strain gave 4-methylbenzyl alcohol in 67–81% yield, suggesting a novel dehalogenation activity of the cells and providing a novel, green, and efficient method for the preparation of 4-methylbenzyl alcohol as well as the application potential in biodegradation of chlorine-containing aromatics. [ABSTRACT FROM AUTHOR]

Whole cell of Pseudomonas monteilii ZMU-T01 strains mediated oxidative resolution of racemic 2-substituted 1,2,3,4-tetrahydroquinolines has been successfully described. A series of highly enantioselective 2-substituted 1,2,3,4-tetrahydroquinoline derivatives were obtained in up to 50% conversion and >99% ee. [ABSTRACT FROM AUTHOR]

[Display omitted] • Visible-light-promoted fluoroalkylation of nitroimidazoles. • Mild reaction conditions. • Late-stage fluoroalkylation of medicinal drugs. Incorporation of fluoroalkyl groups into bioactive compounds can dramatically change their physicochemical and physiological properties, and further improve their pharmacokinetic as well as pharmacological profiles. Therefore, the fluoroalkylation has been acknowledged as a vital strategy in medicinal chemistry for drug discovery. In this study, an efficient and convenient method for the preparation of fluoroalkylated nitroimidazoles through visible-light-prompted direct radical reaction with commercially available materials is described. The strategy proceeds smoothly under mild conditions to afford the fluoroalkyl nitroimidazoles under mild conditions. In addition, control experiments have been performed, revealing a radical process involved in the reaction mechanism. Preliminary evaluations on some products display enhanced antibacterial activities, which further demonstrates the approach to be a versatile protocol for the late-stage fluoroalkylation of clinical drugs toward a diversity-oriented drug discovery. [ABSTRACT FROM AUTHOR]

Indirubin is the crucial ingredient of Danggui Longhui Wan and Qing-Dai, traditional Chinese medicine herbal formulas used for the therapy of chronic myelocytic leukemia in China for hundreds of years. Although the monomeric indirubin has been used in China for the treatment human chronic myelocytic leukemia. However, due to low water solubility, poor pharmacokinetic properties and low therapeutic effects are the major obstacle, and had significantly limited its clinical application. Consequently, the attractive anticancer profile of indirubin has enthused numerous researchers to discover novel indirubin derivatives with improved pharmacodynamic activity as well as good pharmacokinetic property. In this paper, we comprehensively review the recent progress of anticancer potential of indirubins, structural modification and structure-activity relationship, which may provide useful direction for the further development of novel indirubins with improved pharmacological profiles for the treatment of various types of cancer. This review covers the recent advances of anticancer potential of indirubins, structural modification and structure-activity relationship, which may provide useful direction for the further development of novel indirubins with improved pharmacological profiles. [Display omitted] • Indirubin is an important natural bisindole alkaloid for anticancer drug exploration. • The recent advances of structural modification of indirubin were comprehensively summarized. • The multiple mechanisms underlying the anticancer action were included. • The structure-activity relationship was discussed. • The review will be conducive to the medicinal research of indirubin. [ABSTRACT FROM AUTHOR]