Our results suggest a potential role for PSMB5 as a biomarker and therapeutic target for TNBC.

No abstract

β-cyclodextrin complex can be used as an effective formulation strategy for development of BCL-loaded delivery system with better therapeutic outcomes.

A new de-noising method combining Wavelet threshold and empirical mode decomposition (EMD) (WTEMD for short) is proposed to improve the precision of de-noising performance for vibration signal of flood discharge structure in low signal to noise ratio (SNR). White noise is partially filtered out by decomposing the vibration signal with wavelet. Then conducting the further EMD on wavelet reconstructed signal to obtain Intrinsic Mode Function (IMF), through analyzing spectrum diagram of every IMF component, low-frequency waterflow noise and the rest of high-frequency white noise are filtered out, regarding SNR and root mean square error (RMSE) as evaluation index for noise reduction effect. The novelty of this method is that it can reduce the endpoint effect of EMD. By comparing the filtering effect of WTEMD with other methods on simulation signals, study shows that, WTEMD has a higher precision and a better de-noising effect. The dominant vibration information of dam structure is achieved by using WTEMD in Laxiwa arch dam hydro-elastic model and Three Gorges Dam, which can provide the basis for safe operation and on-line monitoring of the dam structure. This method can effectively solve the problem of dominant information extraction for large flood discharge structure.

A fiber-optical intrusion alarm system based on quasi-distributed fiber Bragg grating (FBG) sensors is demonstrated in this papaer. The algorithms of Empirical Mode Decomposition (EMD) and wavelet packet characteristic entropy are adopted to determine the intrusion location. The intrusion alarm software based on the Labview was developed, and it was also proved by the experiments.The results show that such a fiber-optical intrusion alarm system can offer the automatic intrusion alarm in real-time.

As new drugs for the treatment of malignant tumors, transforming growth factor-beta receptor 1 (TGFβR1) antagonists have attracted wide attention. Based on the crystal structure of TGFβR1-BMS22 complex, the pharmacophore model A02 with two hydrogen bond acceptors (HBAs) and four hydrophobic (HYD) properties was constructed. From the common features of active ligands reported in the literature, pharmacophore model B10 was also generated, which has two aromatic ring centers (RAs) and two HYD properties. The two models have high sensitivity and specificity to the training set, and they are highly consistent in spatial structure. Combining the two pharmacophore models, two novel skeleton structures with potential activity were selected by virtual screening from the DruglikeDiverse, MiniMaybridge, and ZINC Drug-Like databases. Four compounds (YXY01–YXY04) with potential anti-TGFβR1 activity were designed based on the new skeleton structures. In combination with Lipinski’s rules; absorption, distribution, metabolism, excretion, and toxicity (ADMET); and, toxicological properties predicted in the study, YXY01-03 with the novel skeleton, good drug-like properties, and potential activity were finally discovered and may have higher safety relative to BMS22, which may be valuable for further research.

Enzymes are biocatalysts. In this study, a novel biocatalyst consisting of magnetic combined cross-linked enzyme aggregates (combi-CLEAs) of 3-quinuclidinone reductase (QNR) and glucose dehydrogenase (GDH) for enantioselective synthesis of (R)-3-quinuclidinolwith regeneration of cofactors in situ was developed. The magnetic combi-CLEAs were fabricated with the use of ammonium sulfate as a precipitant and glutaraldehyde as a cross-linker for direct immobilization of QNR and GDH from E. coli BL(21) cell lysates onto amino-functionalized Fe 3 O 4 nanoparticles. The physicochemical properties of the magnetic combi-CLEAs were characterized by Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD) and magnetic measurements. Field emission scanning electron microscope (FE-SEM) images revealed a spherical structure with numerous pores which facilitate the movement of the substrates and coenzymes. Moreover, the magnetic combi-CLEAs exhibited improved operational and thermal stability, enhanced catalytic performance for transformation of 3-quinuclidinone (33 g/L) into (R)-3-quinuclidinol in 100% conversion yield and 100% enantiomeric excess (ee) after 3 h of reaction. The activity of the biocatalysts was preserved about 80% after 70 days storage and retained more than 40% of its initial activity after ten cycles. These results demonstrated that the magnetic combi-CLEAs, as cost-effective and environmentally friendly biocatalysts, were suitable for application in synthesis of (R)-3-quinuclidinol essential for the production of solifenacin and aclidinium with better performance than those currently available.

Reported here is the exclusive formation of 1,4-diketones by the uncatalyzed reaction of silyl enolates and a-haloketones. Enolates I are inherently more likely to react with a-haloketones II at the carbonyl carbon to produce halohydrin derivatives III or 2-(2-oxoethyl)-oxiranes IV. Thus, a variety of metal-catalyzed coupling reactions have been developed to avoid the undesired reaction when attempting the preparation of 1,4diketones. We found that the oxyallyl zwitterions in situ generated from a-haloketones enabled the addition of silyl enolates to the a-carbonyl position to exclusively form 1,4-diketones in weakly basic conditions. Various types of silyl enolates and a-haloketones were applied to the catalyst-free coupling.Scheme 1 Reaction approaches of enolates with a-haloketones.Scheme 2 Reaction approaches of enolates with oxyallyl zwitterions.Scheme 3 The reaction of oxyallyls with p-nucleophiles.Scheme 4 The reaction of oxyallyl zwitterions with p-nucleophiles using TFE or HFIP as solvent.67902 | RSC Adv., 2015, 5, 67901-67908This journal is