Molecularly targeted agents that are designed to target specific lesions have been proven effective as clinical cancer therapies; however, most currently available therapeutic agents are poorly water-soluble and require oral administration, thereby resulting in low bioavailability and a high risk of side effects due to dose intensification. The rational engineering of systemically injectable medicines that encapsulate such therapeutic payloads may revolutionize anticancer therapies and remains an under-explored area of drug development. Here, the injectable delivery of a nanomedicine complexed with an oral multitargeted kinase inhibitor, vandetanib (vanib), was explored using polymeric nanoparticles (NPs) to achieve the selective accumulation of drug payloads within tumor lesions. To demonstrate this concept, we used biodegradable amphiphilic block copolymer poly(ethylene glycol)-block-poly(D, L-lactic acid) (PEG-PLA) to nanoprecipitate this potent agent to form water-soluble NPs that are suitable for intravenous administration. NP-vanib induced cytotoxic activity by inhibiting the angiogenetic events mediated by VEGFR and EGFR kinases in tested cancer cells and inhibited the growth, tube formation and metastasis of HUVECs. The intravenously injection of NP-vanib into mice bearing HCC BEL-7402 xenografts more effectively inhibited the tumor than the oral administration of vanib. In addition, due to the modular design of these NPs, the drug-loaded particles can easily be decorated with iRGD, a tumor-homing and -penetrating peptide motif, which further improved the in vivo performance of these vanib-loaded NPs. Our results demonstrate that reformulating targeted therapeutic agents in NPs permits their systemic administration and thus significantly improves the potency of currently available, orally delivered agents.
The oxidation of Si3N4-SiC materials containing different Si3N4 content at different temperatures was studied.Through analysis of the oxidation weight gain after oxidation,it is found that the higher content of Si3N4 and the higher temperature,the more complete the oxidation occurs,furthermore the oxidation weight gain rate and the oxidation time follow linear-parabolic law.
Reducing parameter correlations to enhance scatterometry measurement accuracy, precision and tool matching is a crucial component of every modeling effort. Parameter sensitivity can largely depend on the orientation of the plane of incidence relative to the grating orientation. Conventional scatterometry is done with the plane if incidence normal to the grating orientation, whereas azimuthal scatterometry allows measurements at an arbitrary angle or set of angles. A second technique examined in this paper is hybrid metrology where inputs from source tools such as CD-SEM and CD-AFM are used to determine values of critical parameters. The first examples shows LER sensitivity gains by measuring narrow resist lines in an orientation parallel with the long axis of the grating. Hybridization of LER results in a CD and SWA FMP improvement of about 60%. We also showcase the benefits of azimuthal scatterometry measuring resist lines with CD larger than the wavelengths of the incident light. A CD and SWA FMP reduction of about 60% and 30% is obtained using azimuthal scatterometry at 0, 45 and 90 degrees azimuth angles. Hybridization of the ARC SWA after RIE results in CD and resist SWA FMP improvements by over 60% and 30%, respectively.
An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.
Mid-oceanic ridge basalts (MORBs) are frequently grouped as depleted (D-MORBs), normal (N-MORBs), or enriched (E-MORBs) based on the abundances of highly incompatible elements. E-MORBs, characterized by enriched in incompatible elements, were first noted near mantle plumes, so that enrichment of highly incompatible elements was initially understood as a result of infiltration of plume-related melts into the MORB plumbing system. But for E-MORBs far from plumes, it is still controversial of the lithology of enriched components of these E-MORBs. Two major explanations are proposed that the enriched components are generated by the melting of entrained recycled crust (pyroxenite) beneath ridges or by the melting of refertilized peridotites from subducted slabs. The reason for this problem is that melting of the ambient refractory peridotite along with the enriched component will dilute the signals recorded in MORB. Therefore, the in-situ analyses of minerals and/or melt inclusions will shed new light on this question. Here high-precision in-situ analyses were conducted on olivine and plagioclase in the studied samples. According to the major and minor element contents of olivine phenocrysts, we found they have similar Ni, Mn and Ni/(Mg/Fe) contents with those from N-MORB at a given Fo, indicating a peridotitic source. Furthermore, in-situ Sr isotope in plagioclase phenocrysts and in-situ Pb isotope of plagioclase-hosted melt inclusions are also reported to constrain origin of parental magma. The isotopic results show that unlike the uniform whole-rock 87Sr/ 86Sr and 206Pb/204Pb ratios, the plagioclase phenocrysts record highly Sr and Pb isotopic heterogeneity. Strontium isotopic heterogeneity is observed between crystals even in a single thin section. Based on the high An contents of plagioclase phenocrysts and chemical disequilibrium between plagioclase phenocrysts and groundmass, we propose they crystallized early in the magma chamber and were most likely formed in different batches of mantle-derived melts. The enrichment of LREE and negative correlations between La/Sm and Pb isotopes melt inclusions, suggest that ancient continent lithosphere materials are likely present in the sub-ridge mantle of the east of the Melville FZ, SWIR. Collectively, we proposed that the continent lithosphere materials were slabbed into the upper mantle under MOR as refertilized peridotites.
Si3N4-SiC material was prepared by the directly silicon nitride sintering method.Furthermore,the impact of the micro-structure on its performance was studied,by means of observing the micro-structure of materials and analyzing the physical and mechanical properties.
As the implementation of clean coal policies in China, the chunk coal has been gradually replaced by briquette coal in domestic energies. In this study the molecular composition of fine particles (PM2.5) from chunk and briquette coal combustion is characterized using the Fourier transform-ion cyclotron resonance mass spectrometry (FT-ICR MS). More than 6,000 molecular formulae were detected in each PM2.5 sample. A remarkable decrease in unsaturation and aromatic compounds was found from chunk coal to briquette derived aerosols. Around 73.6% of the unique CHON compounds in chunk coal are considered to have aromatic structures, while it decreased to 7.3% in briquette. Most of these nitroaromatics detected only in chunk coal are highly carcinogenic and mutagenic with 4-6 rings. Moreover, the aromatic compounds in sulfur-containing compounds also showed a significant decrease. Meanwhile, because of the perforated shape and the additives during the production of briquettes, there are more heteroatoms-containing molecules released from briquette combustion, which are highly functional compounds with high molecular weight, high degree of oxidation, and low volatility. Our results provide molecular level evidence that the transformation from chunk coal to briquette effectively reduces the aromatic compounds, which is beneficial to assessing and reducing the human health impacts.
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