The aim of this study was to construct an expression vector carrying the hypoxia/radiation dual-sensitive chimeric hypoxia response element (HRE)/early growth response 1 (Egr-1) promoter in order to ...overexpress the therapeutic second mitochondria-derived activator of caspases (Smac). Using this expression vector, the present study aimed to explore the molecular mechanism underlying radiotherapy-induced A549 human lung adenocarcinoma cell death and apoptosis under hypoxia. The plasmids, pcDNA3.1-Egr1-Smac (pE-Smac) and pcDNA3.1-HRE/Egr-1-Smac (pH/E-Smac), were constructed and transfected into A549 human lung adenocarcinoma cells using the liposome method. CoCl2 was used to chemically simulate hypoxia, followed by the administration of 2 Gy X-ray irradiation. An MTT assay was performed to detect cell proliferation and an Annexin V-fluorescein isothiocyanate apoptosis detection kit was used to detect apoptosis. Quantitative polymerase chain reaction and western blot analyses were used for the detection of mRNA and protein expression, respectively. Infection with the pE-Smac and pH/E-Smac plasmids in combination with radiation and/or hypoxia was observed to enhance the expression of Smac. Furthermore, Smac overexpression was found to enhance the radiation-induced inhibition of cell proliferation and promotion of cycle arrest and apoptosis. The cytochrome c/caspase-9/caspase-3 pathway was identified to be involved in this regulation of apoptosis. Plasmid infection in combination with X-ray irradiation was found to markedly induce cell death under hypoxia. In conclusion, the hypoxia/radiation dual-sensitive chimeric HRE/Egr-1 promoter was observed to enhance the expression of the therapeutic Smac, as well as enhance the radiation-induced inhibition of cell proliferation and promotion of cycle arrest and apoptosis under hypoxia. This apoptosis was found to involve the mitochondrial pathway.
We measured the ratios of electroproduction cross sections from a proton target for three exclusive meson-baryon final states: ΛK(+), pπ(0), and nπ(+), with the CLAS detector at Jefferson Lab. Using ...a simple model of quark hadronization, we extract qq creation probabilities for the first time in exclusive two-body production, in which only a single qq pair is created. We observe a sizable suppression of strange quark-antiquark pairs compared to nonstrange pairs, similar to that seen in high-energy production.
Blend modified polyimide (PI) hollow fiber membranes were used in vapor permeation for gas phase dehydration of ethanol. Dry air sweeping operation was used and the dry air was supplied by a ...dehumidification membrane module of compressed air. An integrated membrane process was composed. The effects of some factors, such as the modification of membrane materials, the humidity and current velocity of sweeping air, the operation temperature, on the efficiency of dehydration were discussed.
Traditionally, fluorescence probes have focused on the detection of a single biomarker for a specific process. In this work, we set out to develop a number of fluorescence probes that enable the ...detection of a chosen analyte in the presence of reactive oxygen/nitrogen species (ROS/RNS). These fluorescence probes when activated result in the formation of the highly fluorescent pink dye, resorufin. Therefore, we have labelled these fluorescent probes as 'Pinkments'. Our first 'Pinkment' was shown to detect biologically relevant concentrations of ONOO- and have an excellent selectivity against other ROS/RNS. Pinkment-OH was developed to provide a core unit which could be easily functionalised to produce a range of 'AND' based fluorescence probes for the detection of ROS/RNS and a second analyte. For proof of concept, we synthesised Pinkment-OTBS and Pinkment-OAc. These 'AND'-based probes were successfully shown to detect ROS/RNS and F- or esterase, respectively.
The evolution of topological magnetic domains microscopically correlates the dynamic behavior of memory units in spintronic application. Nanometric bubbles with variation of spin configurations have ...been directly observed in a centrosymmetric hexagonal magnet (Mn
0.5
Ni
0.5
)
65
(Ga
1−
y
Y
y
)
35
(
y
= 0.01) using Lorentz transmission electron microscopy. Magnetic bubbles instead of biskyrmions are generated due to the enhancement of quality factor Q caused by the substitution of rare-earth element Y. Furthermore, the bubble density and diversified spin configurations are systematically manipulated
via
combining the electric current with perpendicular magnetic fields. The magnetic bubble lattice at zero field is achieved after the optimized manipulation.
The spin configuration evolution due to the Y substitution and electromagnetic manipulation in MnNiGaY.
Dislocation behavior in laminated metallic composites (LMCs) plays a pivotal role in strength and ductility of bulk materials. Here, we studied evolutions of geometrically necessary dislocations ...(GNDs) and statistically stored dislocations (SSDs) as well as their effects on strain hardening in the uniaxially deformed Ti/Nb LMCs fabricated by accumulative roll bonding plus the subsequent annealing. By combining in-situ neutron diffraction and ex-situ electron backscattered diffraction (EBSD) techniques, for the first time, we quantitatively reveal that dislocation evolutions in the laminates are independent of initial layer thickness within the micron scale. As the applied strain reaches the uniform elongation stage, GND density in Ti increases remarkably by an order of magnitude in all laminates, while that in Nb almost remains unchanged. Besides, the total dislocation density in Ti develops rapidly with deformation, whereas the SSD density does not increase monotonically. In Nb, both total dislocation density and SSD density increase significantly below 0.02 true strain, and gradually saturate in the late stage of strain hardening. During the whole plastic deformation, Nb bears more stress and dominates the global hardening because of the significant development of SSDs in this metal. Importantly, the strengthening induced by heterophase interfaces is more significant in the softer Ti in which GNDs are extensively activated, and SSDs only marginally contribute to the heterophase interface strengthening. These findings provide insights into the exploration of deformation mechanisms in materials with laminated and gradient structures, and also guide the development of LMCs with advanced mechanical properties.
In the underdoped regime, the cuprate high-temperature superconductors exhibit a host of unusual collective phenomena, including unconventional spin and charge density modulations, Fermi surface ...reconstructions, and a pseudogap in various physical observables. Conversely, overdoped cuprates are generally regarded as conventional Fermi liquids possessing no collective electronic order. In partial contradiction to this widely held picture, we report resonant X-ray scattering measurements revealing incommensurate charge order reflections for overdoped (Bi,Pb)2.12Sr1.88CuO6+δ (Bi2201), with correlation lengths of 40–60 lattice units, that persist up to temperatures of at least 250 K. The value of the charge order wavevector decreases with doping, in line with the extrapolation of the trend previously observed in underdoped Bi2201. In overdoped materials, however, charge order coexists with a single, unreconstructed Fermi surface without nesting or pseudogap features. The discovery of re-entrant charge order in Bi2201 thus calls for investigations in other cuprate families and for a reconsideration of theories that posit an essential relationship between these phenomena.
Mucin 1 (MUC1) is a tumor-associated antigen that is overexpressed in several adenocarcinomas. However, clinical trials with MUC1 showed that MUC1 is a relatively poor immunogen in humans. In view of ...the low immunogenicity of this protein vaccine, we designed a method based on an immunoadjuvant and immunization strategy to enhance the cellular immune response to this protein vaccine. DDA/MPL has been evaluated as an adjuvant to induce strong immunity for the tuberculosis vaccine. However, its adjuvant role combined with the vaccine targeting MUC1 in malignant carcinomas has not previously been reported. Our previous study showed that adenovirus prime protein boost vaccination could significantly enhance the cellular immunity and antitumor efficacy. In our study, we used MUC1 VNTRs as the target of cancer vaccine and DDA/MPL as the adjuvant to enhancing the cellular immunity of recombinant MUC1 protein vaccine, and an AD-9M adenoviral vector prime-recombinant protein and DDA/MPL boost (designated MUC-1 VPP vaccine) strategy was studied to enhance the antitumor efficacy. The results demonstrated that antigen-specific IFN-γ-secreting T cells were increased by 2-fold, and cytotoxic T lymphocytes (CTLs) were induced effectively when the protein vaccine was combined with the DDA/MPL adjuvant. Moreover, the vaccination induced nearly 60% inhibition of the growth of B16 melanoma in mice and prolonged the survival of tumor-bearing mice. The inhibition was correlated with the specific immune responses induced by the MUC1 VPP vaccine. The data suggested that DDA/MPL-adjuvant MUC-1 VPP vaccine may be developed into effective tumor vaccines for melanomas and possibly for other tumors expressing MUC1 protein.
Superconductivity in FeSe is greatly enhanced in films grown on SrTiO3 substrates, although the mechanism behind remains unclear. Recently, surface potassium (K) doping has also proven able to ...enhance the superconductivity of FeSe. Here, by using scanning tunneling microscopy, we compare the K doping dependence of the superconductivity in FeSe films grown on two substrates: SrTiO3 (001) and graphitized SiC (0001). For thick films (20 unit cells (UC)), the optimized superconducting (SC) gaps are of similar size (∼9 meV) regardless of the substrate. However, when the thickness is reduced to a few UC, the optimized SC gap is increased up to ∼15 meV for films on SrTiO3, whereas it remains unchanged for films on SiC. This clearly indicates that the FeSe/SrTiO3 interface can further enhance the superconductivity, beyond merely doping electrons. Intriguingly, we found that this interface enhancement decays exponentially as the thickness increases, with a decay length of 2.4 UC, which is much shorter than the length scale for relaxation of the lattice strain, pointing to interfacial electron–phonon coupling as the likely origin.
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