RNA‐based therapeutics is a promising approach for curing intractable diseases by manipulating various cellular functions. For eliciting RNA (i.e., mRNA and siRNA) functions successfully, the RNA in the extracellular space must be protected and it must be delivered to the cytoplasm. In this study, the development of a self‐degradable lipid‐like material that functions to accelerate the collapse of lipid nanoparticles (LNPs) and the release of RNA into cytoplasm is reported. The self‐degradability is based on a unique reaction “Hydrolysis accelerated by intra‐Particle Enrichment of Reactant (HyPER).” In this reaction, a disulfide bond and a phenyl ester are essential structural components: concentrated hydrophobic thiols that are produced by the cleavage of the disulfide bonds in the LNPs drive an intraparticle nucleophilic attack to the phenyl ester linker, which results in further degradation. An oleic acid‐scaffold lipid‐like material that mounts all of these units (ssPalmO‐Phe) shows superior transfection efficiency to nondegradable or conventional materials. The insertion of the aromatic ring is unexpectedly revealed to contribute to the enhancement of endosomal escape. Since the intracellular trafficking is a sequential process that includes cellular uptake, endosomal escape, the release of mRNA, and translation, the improvement in each process synergistically enhances the gene expression. 相似文献
Comprehensive functional analyses of E-isoprenyl diphosphate synthases (E-IDSs) from nonpathogenic Mycobacterium vanbaalenii have been performed. Mv0992 and Mv1577 represent a nonaprenyl diphosphate (E-C45) synthase and a geranylgeranyl diphosphate (E-C20) synthase, respectively. Although Mv3536 was identified as an E-C20 synthase using a single enzyme, co-incubation of Mv3536 and Z-IDSs (Mv4662 and Mv3822) strongly suggested it releases an intermediate geranyl diphosphate (E-C10) during a continuous condensation reaction. Mv0992 and Mv3536 functions differed from those of the previously reported pathogenic Mycobacterium tuberculosis homologues Rv0562 and Rv2173, respectively. Re-analysis of Rv0562 and Rv2173 demonstrated that their functions were similar to those of Mv0992 and Mv3536 (Rv0562: E-C45 synthase; Rv2173: E-C10–15 synthase). The newly proposed functions of Rv0562 and Rv2173 would be in the biosynthesis of menaquinone and glycosyl carrier lipids essential for growth. Furthermore, a reduced allylic diphosphate could be used as the Z-IDS of the Mv3822 substrate, thereby introducing a potentially novel pathway of cyclic sesquarterpene biosynthesis. 相似文献
An enantioselective one‐pot synthesis of 3‐azabicyclo[3.1.0]hexanes from allyl carbonates and propargyl amines is reported. An amine catalyst promoted the allylic substitution to form intermediary N‐allyl propargylamines, which underwent enantioselective Pd(II)/Pd(IV)‐mediated oxidative cyclization in situ. The chiral ligand (P,R,R)‐i‐Pr‐SPRIX is crucial to the cyclization, producing the desired bicyclic compounds in up to 92% yield and 90% ee.
Damaged structures in the MgAl2O4 spinel induced by swift heavy ions were investigated using the X-ray absorption near edge structure (XANES) and small angle X-ray scattering (SAXS). Increasing the fluence of 100 MeV Xe ions leads to increased SAXS intensity and XANES spectral changes on both Mg and Al K-edges. The damaged regions of ion tracks were observed by SAXS to be cylindrical in shape with a diameter of 5 nm. The theoretical XANES spectra indicated that the changes in the experimental spectra were due to the cationic disordering between tetrahedral and octahedral sites. This disordering caused an increase in the inversion degree of the cations. Furthermore, the quantitative analysis of the XANES spectra revealed the preferential occupation of cations at the octahedral sites at high fluence. 相似文献
Mn4+-activated phosphors, Mg28Ge10O48-δFδ:Mn4+ (MGFs), can be obtained through an oxygen postannealing process. Analyses of the crystal structure and elemental composition by powder X-ray diffraction (XRD) and electron probe microanalysis (EPMA), respectively, indicated that under an O2 atmosphere, oxygen atoms were substituted with fluorine atoms in the original MGF structure to leach the fluorine atoms with germanium atoms as GeF4 by oxygen postannealing. The MGF phosphor annealed in O2 exhibited ~1.3 times higher quantum efficiency (QE) than that annealed in ambient air. The Raman spectroscopy results suggested that an increase in the content of the [Mn4+O6] octahedron led to an increase in the QE values. Additionally, the relaxation of lattice defects in the lattice interior and on the surface observed by XRD and X-ray photoelectron spectroscopy (XPS) measurements could explain the change in thermal quenching behavior between the different atmospheres, and the decrease in lattice defects increased the QE. The investigation of MGF phosphors prepared by different processes provides insight into the relationships among the surface and local structures, chemical composition, and photoluminescence properties. The optimized synthetic procedure increases the Mn4+ content and decreases the Mn2+ and Mn3+ contents in the phosphor, which drastically increases the luminescence efficiency. 相似文献
A new element based on the concept of Rigid Body Spring Model (RBSM) that inherently incorporates Poisson effect is developed and utilized to simulate the nonlinear behavior of concrete. Initially, the behavior of element in linear state is successfully verified. For the nonlinear applications in simulation of concrete, nonlinear material models are implemented based on mesoscale modeling technique that does not suffer from complexity of macroscopic models based on volumetric and deviatoric stress and strain tensors separation. Beside capability of incorporating the Poisson's ratio of the material, with the new material models implemented, the new element can represent the complex behavior of concrete. The uniaxial compressive and tensile test beside splitting tensile test on concrete specimen were simulated successfully and similar cracking patterns to the experiments were observed in the simulations. 相似文献
AbstractIn this paper, the fracture problem of an axisymmetric crack in a functionally graded thermal barrier coating (FGTBC) bonded to a homogeneous substrate is considered. The problem is solved for the laminate that is suddenly heated from the upper surface of the FGTBC. The bottom surface of the homogeneous substrate is maintained at the initial temperature. The crack faces are supposed to be completely insulated. Material properties are assumed to be exponentially dependent on the distance from the interface. By using both the Laplace and Hankel transforms, the thermo-mechanical fracture problem is reduced to a singular integral equation and a system of singular integral equations which are solved numerically. The stress intensity factors of the crack are computed and presented as functions of the normalized time for various values of the nonhomogeneous and geometric parameters. 相似文献
Biochemical sensors are used for discrimination of biochemical species, concentration measurement, and so on. Because metamaterial responds to slight changes in the ambient refractive index, it is possible to realize ultrasensitive biochemical sensors. We designed and fabricated refractive index sensors using polarization independent metamaterial and examined their application as biochemical sensors. Refractive index sensitivity, concentration measurement, and DNA detection were carried out. 相似文献
Humidity sensors based on QCM (quartz crystal microbalance) have been developed using an anodized alumina thin‐film as a sensing material. An aluminum thin‐film is deposited on a silver‐coated quartz crystal by electron beam deposition and is anodized in an acid solution. The resultant alumina film is porous. The resonant frequency gradually decreases from 5% to 94% relative humidity (RH) and steeply changes near 100% RH. This result shows that the sensor can be used as a dew‐point sensor as well as a humidity sensor. The response times to the humidity changes from 27% to 59% RH and from 59% to 27% RH are less than 5 s. The sensor shows reversible response to some gases such as ethanol, toluene, and acetone vapors in addition to airborne particles such as pollen. 相似文献
Recent increases in the power conversion efficiency of crystalline silicon (c‐Si) heterojunction (SHJ) solar cells are due to implementation of carrier‐selective contacts (CSCs) with high passivation performance and low contact resistivity. These electrical properties of CSCs significantly depend on the nature of the CSCs/c‐Si interface at the atomistic scale, and precise control of the interface with the SiOx interlayer is the key to obtaining superior electrical properties. It is shown that a TiOx/c‐Si structure with an interlayer prepared by nitric acid at room temperature shows the best performance among points with five different interlayer formation methods. The underlying mechanisms are investigated by combining high‐resolution transmission electron microscopy and electron energy loss (EEL) spectroscopy. The EEL spectra reveal that the Si:O ratio of an as‐deposited SiOx interlayer is nonstoichiometric (x < 2), which could contribute to lower contact resistivity. Furthermore, the as‐deposited SiOx leads to formation of a Ti containing SiOx layer with few oxygen vacancies after forming gas annealing, resulting in the significant enhancement of passivation performance. These results show that the control of the interlayer with atomistic scale is of crucial importance to realize higher power conversion efficiency of SHJ solar cells. 相似文献
