A major goal in cancer research is to develop carriers that can deliver drugs effectively and without side effects. Liposomal and particulate carriers with diameters of ∼100 nm have been widely used to improve the distribution and tumour accumulation of cancer drugs, but so far they have only been effective for treating highly permeable tumours. Here, we compare the accumulation and effectiveness of different sizes of long-circulating, drug-loaded polymeric micelles (with diameters of 30, 50, 70 and 100 nm) in both highly and poorly permeable tumours. All the polymer micelles penetrated highly permeable tumours in mice, but only the 30 nm micelles could penetrate poorly permeable pancreatic tumours to achieve an antitumour effect. We also showed that the penetration and efficacy of the larger micelles could be enhanced by using a transforming growth factor-β inhibitor to increase the permeability of the tumours.
Nicotianamine (NA), a chelator of metals, is ubiquitously present in higher plants. Nicotianamine aminotransferase (NAAT) catalyzes the amino group transfer of NA in the biosynthetic pathway of phytosiderophores and is essential for iron acquisition in graminaceous plants. The gene that encodes NAAT from barley was introduced into the nongraminaceous plant tobacco, which produces NA but not phytosiderophores. Transgenic tobacco plants (naat tobacco) that constitutively expressed the NAAT gene had young leaves with interveinal chlorosis and flowers that were abnormally shaped and sterile. Endogenous NA was consumed as a result of NAAT overproduction in naat tobacco. The resulting NA shortage caused disorders in internal metal transport, leading to these abnormal phenotypes. In addition to its role in long-distance metal transport, NA may be involved in the regulation of metal transfer within the cells. These results suggest that a shortage of NA impaired the functions of metal-requiring proteins, including transcription factors.
Engineered nanoparticles that respond to pathophysiological parameters, such as pH or redox potential, have been developed as contrast agents for the magnetic resonance imaging (MRI) of tumours. However, beyond anatomic assessment, contrast agents that can sense these pathological parameters and rapidly amplify their magnetic resonance signals are desirable because they could potentially be used to monitor the biological processes of tumours and improve cancer diagnosis. Here, we report an MRI contrast agent that rapidly amplifies magnetic resonance signals in response to pH. We confined Mn(2+) within pH-sensitive calcium phosphate (CaP) nanoparticles comprising a poly(ethylene glycol) shell. At a low pH, such as in solid tumours, the CaP disintegrates and releases Mn(2+) ions. Binding to proteins increases the relaxivity of Mn(2+) and enhances the contrast. We show that these nanoparticles could rapidly and selectively brighten solid tumours, identify hypoxic regions within the tumour mass and detect invisible millimetre-sized metastatic tumours in the liver.
Nb 2 O 5 exhibits various crystal systems, such as orthorhombic ͑o͒, tetragonal ͑t͒, and monoclinic ͑m͒, among which Nb 2 O 5 synthesized at 900-1000°C is commercially used as a cathode material of the 2-V lithium ion battery. The battery performances depended on the structure of Nb 2 O 5 , and the t-Nb 2 O 5 synthesized at 1000°C exhibited an excellent cycling performance with a large discharge capacity of 190 mAh ͑g oxide͒ −1 . The structural variations of Nb 2 O 5 during electrochemical reaction were examined. The in situ synchrotron radiation-X-ray diffraction ͑XRD͒ measurement indicated that o-and t-Nb 2 O 5 maintain their original crystal lattices, accompanying a small change in the cell volume even after the Li intercalation. The in situ X-ray absorption fine structure ͑XAFS͒ analysis of o-and t-Nb 2 O 5 revealed that the continuous variation from Nb 5+ to Nb 4+ took place during the intercalation process. A significant rearrangement of the Nb-O octahedra accompanied by the change of Nb-O and Nb-Nb interactions occurred in both structures with Li intercalation. XRD and XAFS data suggests that the two-dimensional layer structure of t-Nb 2 O 5 seems to be more flexible regarding the Li intercalation compared with the three-dimensional structure of o-Nb 2 O 5 . This may account for the better cyclic performance of the former material as the electrode material.
Carbonaceous meteorites are thought to be fragments of C-type (carbonaceous) asteroids. Samples of the C-type asteroid (162173) Ryugu were retrieved by the Hayabusa2 spacecraft. We measure the mineralogy, bulk chemical and isotopic compositions of Ryugu samples. They are mainly composed of materials similar to carbonaceous chondrite meteorites, particularly the CI (Ivuna-type) group. The samples consist predominantly of minerals formed in aqueous fluid on a parent planetesimal. The primary minerals were altered by fluids at a temperature of 37 ± 10°C, 5.2 − 0.8 + 0.7 (Stat.) − 2.1 + 1.6 (Syst.) million years after formation of the first solids in the Solar System. After aqueous alteration, the Ryugu samples were likely never heated above ~100°C. The samples have a chemical composition that more closely resembles the Sun’s photosphere than other natural samples do.
In this study, we investigated local structures of Sb species in synthetic Sb(V)-coprecipitated and -adsorbed ferrihydrite and goethite, which are common iron(III) oxyhydroxides in environment, at various Sb/Fe molar ratios by extended X-ray absorption fine structure (EXAFS) analyses. The EXAFS analyses showed that Sb(V) is adsorbed on ferrihydrite and goethite by the formation of an inner-sphere surface complex at pH 7.5. In the EXAFS spectra of the coprecipitated ferrihydrite and goethite, some features of the spectra significantly differed from those in the adsorbed samples. The EXAFS simulation indicated that the difference is due to the larger coordination number of the Fe atom to the Sb atom in the coprecipitation samples, indicating a structural incorporation (heterovalent substitution) of Sb(V) into ferrihydrite and goethite. The incorporation of Sb(V) into the structure was also confirmed in natural iron(III) oxyhydroxides in contaminated soil near an Sb mine tailing using mu-EXAFS. This study directly provided the first evidence for the structural incorporation of Sb(V) into the iron(III) oxide structure. Our findings are important for understanding the fate of Sb in the aquatic environment because the behavior of the elements incorporated into solids by such a substitution is not greatly influenced by aquatic factors such as the pH and ionic strength because of isolation of the incorporated metal(loid) ions from the aqueous phase.
Phytic acid (inositol hexakisphosphate [InsP 6 ]) is the storage compound of phosphorus in seeds. As phytic acid binds strongly to metallic cations, it also acts as a storage compound of metals. To understand the mechanisms underlying metal accumulation and localization in relation to phytic acid storage, we applied synchrotron-based x-ray microfluorescence imaging analysis to characterize the simultaneous subcellular distribution of some mineral elements (phosphorus, calcium, potassium, iron, zinc, and copper) in immature and mature rice (Oryza sativa) seeds. This fine-imaging method can reveal whether these elements colocalize. We also determined their accumulation patterns and the changes in phosphate and InsP 6 contents during seed development. While the InsP 6 content in the outer parts of seeds rapidly increased during seed development, the phosphate contents of both the outer and inner parts of seeds remained low. Phosphorus, calcium, potassium, and iron were most abundant in the aleurone layer, and they colocalized throughout seed development. Zinc was broadly distributed from the aleurone layer to the inner endosperm. Copper localized outside the aleurone layer and did not colocalize with phosphorus. From these results, we suggest that phosphorus translocated from source organs was immediately converted to InsP 6 and accumulated in aleurone layer cells and that calcium, potassium, and iron accumulated as phytic acid salt (phytate) in the aleurone layer, whereas zinc bound loosely to InsP 6 and accumulated not only in phytate but also in another storage form. Copper accumulated in the endosperm and may exhibit a storage form other than phytate.
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