Search

Abstract: A LC–MS/MS method for determining the concentration of the small molecule Hsp90 inhibitor, GM-AMPL, has been developed and validated in rat plasma to support preclinical development. 17-[2-(morpholine-4-yl)ethyl]amino-17-demethoxygeldanamycin (GM-AMPL) and the internal standard 17-allylamino-17-demethoxygeldanamycin (17-AAG) were sufficiently separated on a Venusil MP C18 column that was eluted with 80% methanol in water at 40°C. Quantification studies were performed with a multiple reaction monitoring (MRM) transition of m/z 657.3→614.3 and 584.3→541.3 for GM-AMPL and IS, respectively, in the negative ion mode. The present method exhibited good linearity (R >0.999) over the concentration range of 2–600ng/mL for GM-AMPL in rat plasma with a lower limit of quantification (LLOQ) of 2ng/mL. The intra-batch and inter-batch assay coefficients of variation (CV) were in range of 1.56–6.84% and 1.62–6.98%, respectively. The plasma samples were extracted with methanol to precipitate protein with extraction recovery in range of 84.09–95.25%. The matrix effect was determined as internal substance (IS) normalized matrix factor of 1.09, 1.18 and 1.05 for samples with three concentration levels of 4, 40 and 400ng/mL, respectively. This validated method was further applied to successfully determine the pharmacokinetic parameters and oral availability of GM-AMPL in Sprague-Dawley rats following intravenous injection and oral administration. [Copyright &y& Elsevier]

The MYB-CC family is a subtype within the MYB superfamily. This family contains an MYB domain and a predicted coiled-coil (CC) domain. Several MYB-CC transcription factors are involved in the plant’s adaptability to low phosphate (Pi) stress. We identified 30, 34, and 55 MYB-CC genes in Brassica rapa, Brassica oleracea, and Brassica napus, respectively. The MYB-CC genes were divided into nine groups based on phylogenetic analysis. The analysis of the chromosome distribution and gene structure revealed that most MYB-CC genes retained the same relative position on the chromosomes and had similar gene structures during allotetraploidy. Evolutionary analysis showed that the ancestral whole-genome triplication (WGT) and the recent allopolyploidy are critical for the expansion of the MYB-CC gene family. The expression patterns of MYB-CC genes were found to be diverse in different tissues of the three Brassica species. Furthermore, the gene expression analysis under low Pi stress revealed that MYB-CC genes may be related to low Pi stress responses. These results may increase our understanding of MYB-CC gene family diversification and provide the basis for further analysis of the specific functions of MYB-CC genes in Brassica species.

Monolayer ${\mathrm{MoS}}_2$ is a typical valleytronic material with valley-spin locked valence bands. We numerically investigate the valley-spin polarized current in monolayer ${\mathrm{MoS}}_2$ via adiabatic electron pumping. By introducing an exchange field to break the energy degeneracy of monolayer ${\mathrm{MoS}}_2$ , the top of its valence bands is valley-spin polarized and tunable by the exchange field. A device with spin-up polarized left lead, spin-down polarized right lead, and untuned central region is constructed through applying different exchange fields in the corresponding regions. Then, equal amount of pumped currents with opposite valley-spin polarization are simultaneously generated in the left and right leads when periodically varying two pumping potentials. Numerical results show that the phase difference between the pumping potentials can change the direction and hence polarization of the pumped currents. It is found that the pumped current exhibits resonant behavior in the valley-spin locked energy window, which depends strongly on the system size and is enhanced to resonant current peaks at certain system lengths. More importantly, the pumped current periodically oscillates as a function of the system length, which is closely related to the oscillation of transmission. The effects of other system parameters, such as the pumping amplitude and the static potential, are also thoroughly discussed.

The surface plasmonic resonance, surface wettability, and related mechanical nanohardness and of face-centered-cubic (fcc) chromium nitride (CrN) films have been successfully manipulated via the simple method of tuning nitrogen-containing gas with different nitrogen-to-argon ratios, varying from 3.5 (N35), to 4.0 (N40), to 4.5 (N45), which is directly proportional to argon. All of the obtained CrN films showed that the surface wettability was due to hydrophilicity. All of the characteristics were mainly confirmed and explained by using X-ray diffraction (XRD) patterns, including plan-view and cross-section SEM images, with calculations of the average grain size performed via histograms accompanied by different preferred grain orientations. In the present work, not only the surface plasmonic resonance, but also the surface wettability and the related mechanical nanohardness of CrN films were found to be tunable via a simple method of introducing adjustable nitrogen-reactive-containing gas during the deposition process, while the authors suggest that the crystal orientation transition from the (111) to the (200) crystalline plane changed significantly with the nitrogen-containing gas. So the transition of the preferred orientation of CrN’s cubic close-packed from (111) to (200) varied at this composite, caused and found by the nitrogen-containing gas, which can be tuned by the nitrogen-to-argon ratio. The surface plasmonic resonance and photoluminescence quenching effects were coupled photon and electron oscillations, which could be observed, and which existed at the interface between the CrN and Au metals in the designed heterostructures.

In order to improve the pharmacokinetic and pharmacodynamic properties of recombinant human interleukin-11 mutein (mIL-11) and to reduce the frequency of administration, we examined the feasibility of chemical modification of mIL-11 by methoxy polyethylene glycol succinimidyl carbonate (mPEG-SC). PEG-mIL-11 was prepared by a pH controlled amine specific method. Bioactivity of the protein was determined in a IL-11-dependent in vitro bioassay, its pharmacodynamic and pharmacokinetic properties were investigated by using normal and thrombocytopenic monkey models. N-terminus sequencing and peptide mapping analysis revealed that Lys33 is the PEGylated position for PEG-mIL-11. Bioactivity of PEG-mIL-11 assessed by B9-11 cell proliferation assay was comparable to that of mIL-11. More than 79-fold increase in area-under-the curve (AUC) and 26-fold increase in maximum plasma concentration (C max ) was observed in pharmacokinetic analysis. Single dose administration of the PEG-mIL-11 induced blood platelets number increase and the effect duration were comparable to that of 7 to 10 consecutive daily administration of mIL-11 to the normal and thrombocytopenic monkey models. PEG-mIL-11 is a promising therapeutic for thrombocytopenia. [ABSTRACT FROM AUTHOR]

We numerically study the focusing effect induced by a single p – n junction in three-dimensional topological insulators (3D TIs). It is found that, for either surface states or bulk states of 3D TIs, the corresponding electrons injected from the n / p region can be perfectly focused at the symmetric position in the p / n region. These results suggest that the focusing effect is a general phenomenon in materials which can be described by massless or massive Dirac equations. We also find that the focusing effect is robust against moderate random disorders. In the presence of external magnetic fields, the focusing effect remains good, but the position of the focus point oscillates periodically due to the finite size effect.

Abstract: Bi2Fe4O9 submicron-rods were synthesized by a low-heating temperature solid state precursor method. This process, featured by low cost and simplicity, does not involve the use of metal catalyst or protective gas. The effects of different calcine temperatures on the structure, morphology, magnetic and optical properties of the Bi2Fe4O9 were characterized by X-ray diffraction, scanning electron microscope, energy dispersive X-ray spectroscopy, transmission electron microscopy techniques, vibrating sample magnetometer and ultraviolet visible absorption spectra. The Bi2Fe4O9 submicron-rods attained at 700°C possess a perfect submicron-rod shape with a smaller bandgap (1.76eV). [Copyright &y& Elsevier]

Abstract: Two zinc(II) and cadmium(II) complexes based on a V-shaped ligand 2,6-bis(2-benzimidazolyl)pyridine (bbp) have been synthesized and characterized by elemental analysis, molar conductivities, IR, UV–Vis spectra and X-ray single crystal diffraction. Zn(II) and Cd(II) ions are six-coordinated in the structures of [Zn(bbp)2](pic)2·2DMF (1) and [Cd(bbp)2](pic)2·2DMF (2) (pic=picrate), and forming a distorted octahedron. The DNA-binding properties of the complexes were investigated by spectrophotometric methods and viscosity measurements. The experimental results suggest the complexes bind to DNA in an intercalation mode, and DNA-binding affinity of the Zn(II) complex is stronger than that of the Cd(II) complex owning to the different V-shaped angle (αV). Antioxidant assay in vitro shows that both two complexes possess significant hydroxyl radical scavenging activity, and the Zn(II) complex also reveal potent superoxide radical scavenging activity. [Copyright &y& Elsevier]

This study focused on the design and synthesis of two Cu-based coordination polymers, [Cu 2 (4-dpye)(5-HSIP)(μ 3 -O)(H 2 O) 2 ]·3H 2 O (Cu-CP-1) and [Cu(4-dpye) 0.5 (BCA) 2 ] (Cu-CP-2), where 4-dpye = N , N '-bis(4-pyridinecarboxamide)-1,2-ethane, 5-H 3 SIP = 5-sulfoisophthalic acid, and HBCA = benzoic acid, by using a hydrothermal method. Single-crystal X-ray diffraction (SCXRD) study revealed that by adding various auxiliary ligands, the architectures of the Cu-CPs could be altered, yielding two distinct multinuclear Cu clusters. Moreover, the Cu-CPs can be used as urease inhibitors (UIs). In vitro experiments showed that the Cu-CPs had good urease inhibition effects with IC 50 values of 0.53 ± 0.01 μM for Cu-CP-1 and 1.44 ± 0.01 μM for Cu-CP-2 and 98.48% (Cu-CP-1) and 96.27% (Cu-CP-2) inhibition of urease was achieved at a concentration of 100 μM, respectively. Furthermore, the inhibition effect of the tetranuclear Cu-CP was better than that of the binuclear Cu-CP. To better understand the potential mechanism of inhibition of the two copper complexes, we performed kinetic analysis using Lineweaver-Burk (L-B) plots in the presence of different concentrations of urea and different concentrations of inhibitors, and both Cu-CP-1 and Cu-CP-2 showed a non-competitive mode of inhibition. In addition, molecular docking analysis showed that the Cu-CPs were able to enter well into the urease binding pocket, thus interacting with key amino acid residues of urease to different degrees. Both kinetic and molecular docking studies theoretically explain and demonstrate the inhibition effect of both Cu-CPs on urease activity in vitro , which is expected to provide reasonable guidance and effective strategies for the development of novel, efficient, stable and safe CP-based UIs.

This study aimed to investigate pollutant concentration and nitrogen interception characteristics of a forward osmosis (FO) process for concentrating black odorous water. The membrane cell was operated in active layer facing feed solution (AL-FS) mode with aquaporin (AQP) as the membrane material and NaCl solution as the draw solution (DS). The organic pollutants (COD), TP, NH+4-N, NO-3-N, TN, Fe and Mn in black odorous water were concentrated non-intermittently for 24 h, and their interception characteristics were investigated. The results showed that the average interception rates of COD, TP, NO- 3-N, TN, Fe and Mn were 97.2%, 98.0%, 58.7%, 54.3%, 61.8% and 60.0%, respectively, while the average interception rate of NH + 4 -N was only 1.27%-3.47%. To explore the characteristics of nitrogen interception, a comparison was conducted between AQP membrane and thin film composite (TFC) membrane. Because the surface electronegativity of AQP membrane was stronger than that of TFC, the effect of cation exchange on ammonia nitrogen interception was more serious with AQP membrane. With NaCl solution as DS, the reverse osmosis flux of Na + was (0.53 ± 0.02 mol·m -2 ·h -1 ), which was significantly higher than that of Cl - (0.29 ± 0.03 mol·m -2 ·h -1 ) ( P  < 0.05). The interception effect of AQP membrane on TN was related to the proportion of NH + 4 -N in TN. The pretreatment of black odorous water by aeration could transform part of NH + 4 -N into NO - 3-N, and reduce the negative effect of cation exchange effect on nitrogen interception. The TN interception rate increased from 54.3% to 66.1%.

BACKGROUND Long non-coding RNAs (lncRNAs) participate in all cancer biology processes of cells. Although functions and associated mechanisms of lncRNAs have been proven in colorectal cancer (CRC), the roles of lncRNA X-inactive specific transcript (XIST) have not been clearly investigated in CRC. MATERIAL AND METHODS Expression of XIST was detected by quantitative real-time PCR (qRT-PCR) assay in CRC cell lines and 196 clinical samples. Correlations between XIST expression and CRC clinicopathological features were analyzed. Log-rank test and Kaplan-Meier test were performed to assess and compare the prognoses of patients with higher and lower expression of XIST. The multivariate Cox regression and univariate Cox regression were conducted to evaluate the risk factors for prognosis of CRC. RESULTS lncRNA XIST was upregulated in CRC cells lines and tissues (p<0.05). Statistical analysis found high XIST expression was correlated with larger tumor size, N1, M1, and topography lymph node metastasis (TNM) III+IV stage of CRC. Moreover, higher expression of XIST could predict poor progression-free survival (PFS) and poor overall survival (OS) of CRC patients. The M1 stage and high expression of XIST were proven to be independent risk factors for poor prognosis (p<0.05). CONCLUSIONS XIST is upregulated in CRC and is significantly correlated with CRC clinical progression. lncRNA XIST overexpression predict poor PFS and poor OS for CRC patients. lncRNA XIST can be an independent risk factor for CRC prognosis, and could be a potential therapeutic target and prognostic biomarker for CRC patients.

Objective: To establish HPLC fingerprint of Folium Pyrrosiae for identification., Methods: The HPLC method was developed with Diamonsil C18 column (250 mm x 4.6 mm, 5 microm),and a mixture liquid of acetonitrile-0.8% acetic acid solution as mobile phase in a gradient elution. HPLC fingerprints of44 samples were analyzed by similarity, cluster and principal component analysis., Results: The HPLC fingerprint common pattern of Pyrrosia petiolosa, Pyrrosia lingua and common pattern of Pyrrosia sheareri were set up separately. Samples from different species were classified based on the result of cluster and principal component analysis. Fingerprints of Pyrrosia sheareri and Pyrrosia lingua have high degree of similarity, but were different from Pyrrosia petiolosa, while Pyrrosia calvata and Pyrrosia assimlis were classified as adulterants with their dissimilar fingerprints., Conclusion: The method is stable and reliable with a good reproducibility and provides a reference standard for identifying Folium Pyrrosiae from different habitats and species.

To analyze and identify the constituents in rat plasma after oral administration of the active fraction of Corydalis yanhusuo, a LC-MS/MS method was established. The constituents absorbed into blood, their original crude drugs and their metabolites were identified either by comparing the retention time and mass spectrometry data with that of reference compounds or by mass spectrometry analysis and retrieving the reference literatures. Nine species are the original form in Corydalis yanhusuo, moreover, some metabolites in blood identified as glucuronide were found. The constituents absorbed into blood and the possible metabolites which demonstrate to originate from the active fraction of Corydalis yanhusuo are responsible for the observed efficacy. Its serum pharmacochemistry should be subjected to complete investigation so as to illuminate the pharmacology and active mechanism of the active fraction of Corydalis yanhusuo.