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[en] Mammalian target of rapamycin (mTOR) is a therapeutic target for head and neck squamous cell carcinoma (HNSCC). Here, we evaluated the activity of AZD-2014, a potent mTOR complex 1/2 (mTORC1/2) dual inhibitor, against HNSCC cells. We showed that AZD-2014 blocked mTORC1/2 activation in established and primary human HNSCC cells, where it was anti-proliferative and pro-apoptotic. Yet, AZD-2014 was non-cytotoxic to the human oral epithelial cells with low basal mTORC1/2 activation. In an effect to identify possible AZD-2014 resistance factors, we showed that the anti-apoptosis protein Bcl-2 was upregulated in AZD-2014-resistant SQ20B HNSCC cells. Inhibition of Bcl-2 by ABT-737 (a known Bcl-2 inhibitor) or Bcl-2 shRNA dramatically potentiated AZD-2014 lethality against HNSCC cells. On the other hand, exogenous overexpression of Bcl-2 largely attenuated AZD-2014’s activity against HNSCC cells. For the in vivo studies, we showed that oral gavage of AZD-2014 suppressed SQ20B xenograft growth in severe combined immunodeficient (SCID) mice. It also significantly improved mice survival. Importantly, AZD-2014’s anti-HNSCC activity in vivo was potentiated with co-administration of ABT-737. The preclinical results of this study suggest that AZD-2014 could be further tested as a valuable anti-HNSCC agent, either alone or in combination with Bcl-2 inhibitors. - Highlights: • AZD-2014 blocks mTORC1/2 activation in HNSCC cells. • AZD-2014 suppresses HNSCC cell proliferation. • AZD-2014 activates caspase-3 and apoptosis in HNSCC cells. • Bcl-2 is the key resistance factor of AZD-2014 in HNSCC cells. • ABT-737 sensitizes AZD-2014-induced anti-HNSCC activity in vivo.
[en] A highly selective sample cleanup procedure combined with molecularly imprinted solid-phase extraction (MISPE) was developed for the isolation of gonyautoxins 2,3 (GTX2,3) from Alexandrium tamarense sample. The molecularly imprinted polymer microspheres (MIPMs) were prepared by suspension polymerization using caffeine as the dummy template molecule, methacrylic acid as the functional monomer, ethylene glycol dimethacrylate as the cross-linker and polyvinyl alcohol as the dispersive reagent. The polymer microspheres were used as a selective sorbent for the solid-phase extraction of gonyautoxins 2,3. An off-line MISPE method followed by high-performance liquid chromatography (HPLC) with fluorescence detection for the analysis of gonyautoxins 2,3 was established. Finally, the extract samples from Alexandrium tamarense were analyzed. The results showed the imprinted polymer microspheres exhibited high affinity and selectivity for gonyautoxins 2,3. The interference matrix in the extract were obviously cleaned by MISPE and the extraction efficiency of gonyautoxins 2,3 in the sample ranged from 81.74% to 85.86%. -- Graphical abstract: This is the SEM photograph of molecularly imprinted polymer microspheres (MIPMs). MIPMs were prepared by suspension polymerization and used as selective sorbents for the solid-phase extraction of gonyautoxins 2,3. An off-line MISPE method followed by high-performance liquid chromatography with fluorescence detection for the analysis of gonyautoxins 2,3 was established. The extract samples from Alexandrium tamarense were analyzed by molecularly imprinted solid-phase extraction. Highlights: •The molecularly imprinted polymer microspheres (MIPMs) for GTX2,3 were prepared. •The characteristics and regeneration property of MIPMs were studied. •An off-line method using MIPMs as solid-phase extraction (SPE) sorbents was developed. •GTX2,3 from Alexandrium tamarense extract was successfully isolated by MIPMs-SPE. -- MIPMs for GTX2,3 were prepared and applied as special SPE sorbents. The MISPE process was valid for the isolation and clean-up of GTX2,3 from A. tamarense extract
[en] In this work, the behavior of the three-dimensional (3D) jet coiling based on the viscoelastic Oldroyd-B model is investigated by a corrected particle scheme, which is named the smoothed particle hydrodynamics with corrected symmetric kernel gradient and shifting particle technique (SPH-CS-SP) method. The accuracy and stability of SPH-CS-SP method is first tested by solving Poiseuille flow and Taylor–Green flow. Then the capacity for the SPH-CS-SP method to solve the viscoelastic fluid is verified by the polymer flow through a periodic array of cylinders. Moreover, the convergence of the SPH-CS-SP method is also investigated. Finally, the proposed method is further applied to the 3D viscoelastic jet coiling problem, and the influences of macroscopic parameters on the jet coiling are discussed. The numerical results show that the SPH-CS-SP method has higher accuracy and better stability than the traditional SPH method and other corrected SPH method, and can improve the tensile instability. (paper)
[en] The design of the tube penetration structure which is one of the important structure in the GIS/GDC system was conducted. The detailed design and preliminary results of divertor port extension and cryostat penetration structure, and of upper port extension and torus vacuum closure flange penetration structure were given. (authors)
[en] During inflammation in the glomerulus, the proliferation of myofiroblast-like mesangial cells is commonly associated with the pathological process. Macrophages play an important role in regulating the growth of resident mesangial cells in the glomeruli. Alternatively activated macrophage (M2 macrophage) is a subset of macrophages induced by IL-13/IL-4, which is shown to play a repair role in glomerulonephritis. Prompted by studies of development, we performed bone marrow derived macrophage and rat mesangial cell co-culture study. Conditioned medium from IL-4 primed M2 macrophages induced rat mesangial cell apoptosis. The pro-apoptotic effect of M2 macrophages was demonstrated by condensed nuclei stained with Hoechst 33258, increased apoptosis rates by flow cytometry analysis and enhanced caspase-3 activation by western blot. Fas protein was up-regulated in rat mesangial cells, and its neutralizing antibody ZB4 partly inhibited M2 macrophage-induced apoptosis. The up-regulated arginase-1 expression in M2 macrophage also contributed to this apoptotic effect. These results indicated that the process of apoptosis triggered by conditioned medium from M2 macrophages, at least is partly conducted through Fas in rat mesangial cells. Our findings provide compelling evidence that M2 macrophages control the growth of mesangial cells in renal inflammatory conditions. - Highlights: • Conditioned-medium from M2 macrophages induces rat mesangial cell (MsC) apoptosis. • M2 macrophage conditioned medium exerts its pro-apoptotic effects via Fas ligand. • Arginase-1 activity in M2 macrophages plays a role in inducing apoptosis in rat MsC
[en] The research of TS-TA transfer time delay error in Ling'ao II is introduced in the paper. The problem is solved finally, contributing in CFT stable power supply and later BAS tests. Experience also gathered for CRP1000 new projects. (authors)
[en] Graphical abstract: Two kinds of Ag–NaCMC films for surface-enhanced Raman scattering (SERS) were prepared by conventional heating and microwave assisted in situ reduction methods without any additional capping or reducing agents. A relatively narrow and symmetric surface plasmon resonance band was observed in the absorption spectra of the films fabricated by the microwave assisted in situ reduction method. More uniform silver nanoparticles (NPs) implied by the symmetric absorption spectrum were further confirmed by the scanning electron microscopy images. After the simulation of the E-field intensity distribution around the silver NPs in NaCMC film, the Raman scattering enhancement factors (EFs) of these films were then investigated with 4-mercaptobenzoic acid molecule as a SERS reporter. Improved reproducibility of SERS signal was obtained in the microwave assisted synthesized Ag–NaCMC film, although it maintained an EF as only 1.11 × 10"8. The reproducible SERS signal of the Ag–NaCMC film is particularly attractive and this microwave assisted in situ reduction method is suitable for the production of excellent substrate for biosensor application. - Highlights: • The synthesis of Ag–NaCMC films was successfully fulfilled by a low-cost microwave method. • More uniform silver nanoparticles were observed in Ag–NaCMC film synthesized by microwave. • Improved reproducibility of SERS signal was obtained in microwave synthesized Ag–NaCMC film. - Abstract: Two kinds of Ag–NaCMC films for surface-enhanced Raman scattering (SERS) were prepared by conventional heating and microwave assisted in situ reduction methods without any additional capping or reducing agents. A relatively narrow and symmetric surface plasmon resonance band was observed in the absorption spectra of the films fabricated by the microwave assisted in situ reduction method. More uniform silver nanoparticles (NPs) implied by the symmetric absorption spectrum were further confirmed by the scanning electron microscopy images. After the simulation of the E-field intensity distribution around the silver NPs in NaCMC film, the Raman scattering enhancement factors (EFs) of these films were then investigated with 4-mercaptobenzoic acid molecule as a SERS reporter. Improved reproducibility of SERS signal was obtained in the microwave assisted synthesized Ag–NaCMC film, although it maintained an EF as only 1.11 × 10"8. The reproducible SERS signal of the Ag–NaCMC film is particularly attractive and this microwave assisted in situ reduction method is suitable for the production of excellent substrate for biosensor application
[en] Red emission with high color purity in Y2Ti2O7:Yb3+,Er3+ material is successfully obtained by high-concentration doping of Yb3+ and Er3+ under 980 and 1550 nm excitation based on the special layer structure of pyrochlore crystal. It shows that Yb3+ ion content and excitation wavelength greatly influence the red emission percent of total up-conversion luminescence intensity of Y2Ti2O7:Yb3+,Er3+. Y2Ti2O7:Yb3+,Er3+ shows much better red color purity at 1550 nm excitation than at 980 nm. Furthermore, the co-doping of Yb3+ ions considerably boosts the red emission under 980 or 1550 nm pumping with different luminescence mechanisms compared with Y2Ti2O7:Er3+ sample. The red emission percent of total up-conversion luminescence intensity gradually increases with the increment of Yb3+ concentration at both excitation sources. The red-to-green emission ratio of the sample is 6.97 (980 nm) and 23.26 (1550 nm) when the Yb3+ content is 30 mol%.
[en] 156 samples from Zhutongjian uranium deposits of Xiazhuang ore field were used to study the relation of uranium-radium equilibrium coefficient to uranium content, elevation and lithologic type in northern Guangdong. Relation analysis found that balance of uranium and radium are equilibrium or slightly to uranium. The equilibrium coefficient decreases with the increase of uranium content. If uranium content is less than 0.15%, the coefficient will decreased while uranium content increased; if uranium content is higher than 0.15%, the relationship between uranium content is not obvious. From the surface to the depth, the uranium-radium equilibrium was strongly bias to radium, and then to uranium and relatively balanced. The relationship of equilibrium coefficient with silicification belt, fractured granite, fine and medium grain biotite granite were studied to provide scientific basis for geophysical logging, correct calculation of gamma logging, ore body boundary determination and resources estimation. (authors)
[en] As a part of technical improvements of chromosome aberration analysis on human peripheral lymphocytes for biological radiation dosimetry, we examined the optimal conditions for the use of colcemid in chromosome preparation in order to obtain enough number of cells at metaphase in the first cell division. When treated with colcemid at concentrations below 0.01 μg/ml from the beginning of culture, cultures harvested at 48 hours had low mitotic indices. Colcemid treatment at 0.025 to 0.05 μg/ml during 48 hours resulted in high mitotic indices (8 to 15%) and almost of the mitotic cells remaining in the 1st cell division, suggesting that this range of colcemid concentration was appropriate for continuous treatment with colcemid. We further examined the effect of colcemid concentration on the quantitative consistency of the yields of radiation-induced chromosome aberration. Repeated experiments showed that the yield of dicentrics and centric rings in the culture having colcemid at 0.025 μg/ml concentration were larger than that at 0.05 μg/ml. These data indicate the importance of assuring the accuracy of colcemid concentration in the lymphocyte culture for cytogenetic radiation dosimetry. (author)