Polyketides comprise a large and highly diverse group of natural products produced by polyketide synthases (PKSs), and many of these compounds display remarkable biological activities. Although PKSs ...share a common mechanism in the assembly of polyketides from short carboxylic acid precursors, different types of PKSs have been classified according to their structures and modes of action. This review discusses a growing group of bacterial PKSs that are structurally type I but act in an iterative manner to produce aromatic polyketides. We summarize the genetic and biochemical features of these enzymes and compare them with other types of PKSs with an emphasis on the evolutionary relationship. We also discuss the different mechanisms for polyketide off-loading and the diverse post-PKS modifications on the resulting aromatic rings. Insights into bacterial iterative type I PKSs for aromatic polyketide formation and the relevant tailoring enzymes may guide rational bioengineering efforts to produce novel natural products.
Background： Survivin is an oncoprotein silenced in normal mature tissues but reactivated in serous ovarian cancer （SOC）. Although transcriptional activation is assumed for its overexpression, the ...long 3＇-untranslated region （3＇-UTR） in survivin gene, which contains many alternate polyadenylation （APA） sites, implies a propensity for posttranscriptional control and therefore was the aim of our study. Methods： The abundance of the coding region, the proximal and the distal region of survivin mRNA 3＇-UTR, was evaluated by real-time polymerase chain reaction （PCR） in SOC samples, cell lines, and normal fallopian tube （NFT） tissues. The APA sites were confirmed by rapid amplification ofcDNA 3＇ ends and DNA sequencing. Real-time PCR were used to screen survivin-targeting microRNAs （miRNAs） that were inversely correlated with survivin. The expression of an inversely correlated miRNA was restored by pre-miRNA transfection or induction with a genotoxic agent to test its inhibitory effect on survivin overexpression. Results： Varying degrees of APA were observed in SOC by comparing the abundance of the proximal and the distal region of survivin 3＇-UTR, and changes of 3＇-UTR correlated significantly with survivin expression （r = 0.708, P 〈 0.01）. The main APA sites are proved at 1197 and 1673 of survivin 3＇-UTR by DNA sequencing. Higher level of 3＇-UTR proximal region than coding region was observed in NFT, as well as in SOC and cell lines. Among the survivin-targeting miRNAs, only a few highly expressed miRNAs were inversely correlated with survivin levels, and they mainly targeted the distal part of the 3＇-UTR. However, in ovarian cancer cells, restoration of an inversely correlated miRNA （miR-34c） showed little effect on survivin expression. Conclusions： In NFT tissues, survivin is not transcriptionally silenced but regulate posttranscriptionally. In SOC, aberrant APA leads to the shortening of survivin 3＇-UTR which enables it to escape the negative regulation of miRNAs and is responsible for survivin up-regulation.
To prepare layer-by-layer（LbL） multilayers in time-efficient manners by the dipping method is highly ap- pealing. However, the fast LbL assembly produces multilayers with high surface roughness. In ...our attempt to smooth the surface morphologies of LbL multilayers obtained by fast assembly（5 s dipping）, we studied the influence of the assembly conditions on the surface morphologies. The study shows that by properly adjusting the assembly condi- tions, such as washing duration, water annealing period, and drying with nitrogen flow, LbL multilayers with en- hanced surface smoothness could be obtained through fast LbL assembly.
In this article, we propose a causal relationship between a region's communist revolutionary legacy before 1949 and the variation in private sector development after 1949. In the case of Zhejiang, ...the pre-1949 revolutionary experience led to the power struggle between two elite groups, the guerrilla cadre group and the southbound cadre group, in the province after 1949. As the weak side, guerrilla cadres were willing to protect local economic interests in exchange for local popular support, which improved their odds of political survival. As a result, in contrast with counties where the guerrilla forces were historically weak, counties with strong guerrilla forces before 1949 saw significantly more robust private sector development throughout much of the Mao and post-Mao periods. In this article we provide preliminary historical and statistical evidence to support this hypothesis.
We present an approach to predict the explosion load for aluminized explosives using a numerical calculation. A code to cal- culate the species of detonation products of high energy ingredients and ...those of the secondary reaction of aluminum and the detonation products, velocity of detonation, pressure, temperature and JWL parameters of aluminized explosives has been de- veloped in this study. Through numerical calculations carried out with this code, the predicted JWL parameters for aluminized explosives have been compared with those measured by the cylinder test. The predicted JWL parameters with this code agree with those measured by the cylinder test. Furthermore, the load of explosion for the aluminized explosive was calculated using the numerical simulation by using the JWL equation of state. The loads of explosion for the aluminized explosive obtained using the predicted JWL parameters have been compared with those using the measured JWL parameters. Both of them are almost the same. The numerical results using the predicted JWL parameters show that the explosion air shock wave is the strongest when the mass fraction of aluminum rmwder in the exnlosive mixtures is ~f）%. This result n~rees with the e~mniricnl darn
Particle suspension characteristics are predicted computationally in a stirred tank driven by a Smith turbine. In order to verify the hydrodynamic model and numerical method, the predicted power ...number and flow pattern are compared with designed values and simulated results from the literature, respectively. The effects of particle density, particle diameter, liquid viscosity and initial solid loading on particle suspension behavior are investigated by using the Eulerian-Eulerian two-fluid model and the standard k-ε turbulence model. The results indicate that solid concentration distribution depends on the flow field in the stirred tank. Higher particle density or larger particle size results in less homogenous distribution of solid particles in the tank. Increasing initial solid loading has an adverse impact on the homogeneous suspension of solid particles in a low-viscosity liquid, whilst more uniform particle distribution is found in a high-viscosity liquid.
Background Polymer coating on coronary stents induces vascular inflammatory response, reduces re-endothelialization, and affects long-term outcome after percutaneous coronary intervention （PCI）. The ...SERY-1 registry aimed to determine whether a novel polymer-free paclitaxel-eluting microporous Yinyi stent could improve 1-year outcome after index procedure in real-world clinical practice. Methods Clinical and angiographic data and follow-up outcome were collected in 1045 patients who underwent PCI with implantation of 〉1 Yinyi stents between June 2008 and August 2009 at 27 medical centers. The primary endpoint was the cumulative rate of composite major adverse cardiac events （MACE） and the secondary endpoint was the incidence of stent thrombosis at 1 year. Results Overall, 1376 lesions were treated successfully with 1713 Yinyi stents, and 1019 （98.7%） patients received dual antiplatelet therapy for at least 12 months. During 1-year follow-up, 8 patients （0.78%） had cardiac death, 6 （0.58%） suffered non-fatal myocardial infarction, and 46 （4.46%） underwent repeat PCI due to recurrence of angina, resulting in 1-year MACE-free survival of 94.09%. Stent thrombosis occurred in 10 （0.97%） patients, and the rate of Academic Research Consortium （ARC） definite or probable stent thrombosis was 0.78%. Conclusions Polymer-free paclitaxel-eluting microporous Yinyi stent is effective and safe for interventional treatment of coronary artery disease in real-world clinical practice, without recourse to carrier polymer. Potential long-term clinical advantages of this stent deserve further investigation.
The ultrasonic time-of-flight-diffraction (TOFD) method is a widely used flaw sizing and locating method. A signal identification technique is used to improve the arrival time resolution of a TOFD ...signal and to size and locate flaws more accurately. The ultrasonic signal is decomposed into several intrinsic mode functions by empirical mode decomposition. Some modes are selected to reconstruct a new signal considering their frequencies and energy. The reconstructed signal has a better signal-tonoise ratio and enhanced flaw information. A Hilbert transform is conducted to get the envelope and exact arrival time of the signal. All vertical flaws can be detected correctly with average sizing and locating accuracy of 0.08 mm in the laboratory. The deeper the flaw is located, the higher the accuracy. The blind area of TOFD is reduced to 2.5 mm under the surface. Material: steel.
The present study was designed to investigate the chemical constituents and bioactivities of the roots of Liriope muscari (Decne.) L.H. Bailey. The compounds were isolated through various ...chromatography techniques, including silica gel, Sephadex LH-20, and semi-preparative HPLC. The structures were elucidated by infrared (IR), mass spectrometric (MS), 1D- and 2D-NMR analyses in comparison with reference data. In addition, the cytotoxicity of these compounds against human breast cancer MDA-MB-435 cells was evaluated by the MTT assay. Two new steroidal glycosides, 25(R, S)-ruscogenin-1-O-β-D-fucopyranosyl (1→2)-β-D-xylopyranosyl(1→3)β-D-glucopyranoside (Liriopem I, 1) and 25(R, S)- ruscogenin-1-O-β-D-fucopyranosyl (1→2)-β-D-xylopyranosyl(1→4)-β-D-fucopyranoside (Liriopem II, 2 and two known compounds LM-S6 (3) and DT-13 (4) were isolated and identified. Liriopem I(1), liriopem II(2) and DT-13 (4) showed remarkable cytotoxicity with IC50 values being (0.58 ± 0.08), (0.05 ± 0.10), and (0.15 ± 0.09) μg·mL−1, respectively. In summary, compounds 1 and 2 identified in the present study exerted cytotoxicity against breast cancer cells, providing a basis for future development of these compounds as novel anticancer agents.
Two novelsteroidal glycosidesextracted from the roots of Liriope muscari (Decne.) L.H. Bailey exerted cytotoxicity against breast cancer cells.
PDF
