Ziyu Wu

Arsenic Trioxide Controls the Fate of the PML-RARα Oncoprotein by Directly Binding PML

Arsenic on the Fingers Arsenic, an ancient drug used in traditional Chinese medicine, has attracted wide interest because it has therapeutic activity in patients with acute promyelocytic leukemia (APL). The drug acts by promoting degradation of an oncogenic protein, PML-RARα, a fusion protein containing sequences from the PML zinc finger protein and retinoic acid receptor α, which is found specifically in APL cells and helps drive their growth. Zhang et al. (p. 240; see the Perspective by Kogan) now explain how arsenic initiates the molecular events leading to PML-RARα degradation. Arsenic was found to bind directly to cysteine residues within zinc finger domains of PML. Arsenic binding then induced oligomerization of PML, which in turn enhanced its association with an enzyme that helps catalyze SUMOylation, a posttranslational modification that can target proteins for degradation. Arsenic, a drug used clinically for leukemia, binds directly to an oncogenic protein, thereby promoting its degradation. Arsenic, an ancient drug used in traditional Chinese medicine, has attracted worldwide interest because it shows substantial anticancer activity in patients with acute promyelocytic leukemia (APL). Arsenic trioxide (As2O3) exerts its therapeutic effect by promoting degradation of an oncogenic protein that drives the growth of APL cells, PML-RARα (a fusion protein containing sequences from the PML zinc finger protein and retinoic acid receptor alpha). PML and PML-RARα degradation is triggered by their SUMOylation, but the mechanism by which As2O3 induces this posttranslational modification is unclear. Here we show that arsenic binds directly to cysteine residues in zinc fingers located within the RBCC domain of PML-RARα and PML. Arsenic binding induces PML oligomerization, which increases its interaction with the small ubiquitin-like protein modifier (SUMO)–conjugating enzyme UBC9, resulting in enhanced SUMOylation and degradation. The identification of PML as a direct target of As2O3 provides new insights into the drug’s mechanism of action and its specificity for APL.

Low-cost synthesis of flowerlike α-Fe2O3 nanostructures for heavy metal ion removal: adsorption property and mechanism.

Flowerlike α-Fe(2)O(3) nanostructures were synthesized via a template-free microwave-assisted solvothermal method. All chemicals used were low-cost compounds and environmentally benign. These flowerlike α-Fe(2)O(3) nanostructures had high surface area and abundant hydroxyl on their surface. When tested as an adsorbent for arsenic and chromium removal, the flowerlike α-Fe(2)O(3) nanostructures showed excellent adsorption properties. The adsorption mechanism for As(V) and Cr(VI) onto flowerlike α-Fe(2)O(3) nanostructures was elucidated by X-ray photoelectron spectroscopy and synchrotron-based X-ray absorption near edge structure analysis. The results suggested that ion exchange between surface hydroxyl groups and As(V) or Cr(VI) species was accounted for by the adsorption. With maximum capacities of 51 and 30 mg g(-1) for As(V) and Cr(VI), respectively, these low-cost flowerlike α-Fe(2)O(3) nanostructures are an attractive adsorbent for the removal of As(V) and Cr(VI) from water.

Ultrathin nickel hydroxide and oxide nanosheets: synthesis, characterizations and excellent supercapacitor performances.

High-quality ultrathin two-dimensional nanosheets of α-Ni(OH)2 are synthesized at large scale via microwave-assisted liquid-phase growth under low-temperature atmospheric conditions. After heat treatment, non-layered NiO nanosheets are obtained while maintaining their original frame structure. The well-defined and freestanding nanosheets exhibit a micron-sized planar area and ultrathin thickness (<2 nm), suggesting an ultrahigh surface atom ratio with unique surface and electronic structure. The ultrathin 2D nanostructure can make most atoms exposed outside with high activity thus facilitate the surface-dependent electrochemical reaction processes. The ultrathin α-Ni(OH)2 and NiO nanosheets exhibit enhanced supercapacitor performances. Particularly, the α-Ni(OH)2 nanosheets exhibit a maximum specific capacitance of 4172.5 F g−1 at a current density of 1 A g−1. Even at higher rate of 16 A g−1, the specific capacitance is still maintained at 2680 F g−1 with 98.5% retention after 2000 cycles. Even more important, we develop a facile and scalable method to produce high-quality ultrathin transition metal hydroxide and oxide nanosheets and make a possibility in commercial applications.

Low-dose, simple, and fast grating-based X-ray phase-contrast imaging

Phase sensitive X-ray imaging methods can provide substantially increased contrast over conventional absorption-based imaging and therefore new and otherwise inaccessible information. The use of gratings as optical elements in hard X-ray phase imaging overcomes some of the problems that have impaired the wider use of phase contrast in X-ray radiography and tomography. So far, to separate the phase information from other contributions detected with a grating interferometer, a phase-stepping approach has been considered, which implies the acquisition of multiple radiographic projections. Here we present an innovative, highly sensitive X-ray tomographic phase-contrast imaging approach based on grating interferometry, which extracts the phase-contrast signal without the need of phase stepping. Compared to the existing phase-stepping approach, the main advantages of this new method dubbed “reverse projection” are not only the significantly reduced delivered dose, without the degradation of the image quality, but also the much higher efficiency. The new technique sets the prerequisites for future fast and low-dose phase-contrast imaging methods, fundamental for imaging biological specimens and in vivo studies.

Synthesis and characterization of functionalized silica-coated Fe3O4 superparamagnetic nanocrystals for biological applications

Superparamagnetic Fe3O4 nanocrystals were prepared by a chemical coprecipitation method with a thin thickness-adjustable silica layer coated on the surface by hydrolysis of tetraethyl orthosilicate. The silica-coated Fe3O4 nanocrystals were well dispersed and consisted of a 6-7 nm diameter magnetic core and a silica shell about 2 nm thick, according to transmission electron microscopy observations. Fourier transform infrared spectra revealed that amino (-NH2) groups were successfully covalently bonded to the silica-coated Fe3O4 and then carboxyl (-COOH) groups were functionalized to the surface through the reaction of -NH2 and glutaric anhydride. The synthesized nanocrystals have a cubic spinel structure as characterized by x-ray diffraction, electron diffraction and high-resolution transmission electron microscopy. Their magnetic properties were carefully investigated by a SQUID magnetometer. The results showed that the nanocrystals were superparamagnetic and the blocking temperature TB shifted from 131 K down to 92 K after they were coated with a thin nonmagnetic layer, since this layer can effectively suppress the magnetic dipolar interaction between particles; the chemically inert silica layer can limit the outside environment effect on the Fe3O4 cores quite well due to the excellent magnetic reproducibility of the coated nanocrystals after ageing for 7 months at room temperature. In addition, the dependence of their high-field specific magnetization on temperature has a T-2 relationship. These functionalized silica-coated Fe3O4 superparamagnetic nanocrystals have great potential in biomagnetic applications.

Aligned Fe2TiO5-containing nanotube arrays with low onset potential for visible-light water oxidation

There remains a pressing challenge in the efficient utilization of visible light in the photoelectrochemical applications of water splitting. Here, we design and fabricate pseudobrookite Fe2TiO5 ultrathin layers grown on vertically aligned TiO2 nanotube arrays that can enhance the conduction and utilization of photogenerated charge carriers. Our photoanodes are characterized by low onset potentials of ~0.2 V, high photon-to-current efficiencies of 40-50% under 400-600 nm irradiation and total energy conversion efficiencies of ~2.7%. The high performance of Fe2TiO5 nanotube arrays can be attributed to the anisotropic charge carrier transportation and elongated charge carrier diffusion length (compared with those of conventional TiO2 or Fe2O3 photoanodes) based on electrochemical impedance analysis and first-principles calculations. The Fe2TiO5 nanotube arrays may open up more opportunities in the design of efficient and low-cost photoanodes working in visible light for photoelectrochemical applications.

Nanoscale Morphological and Chemical Changes of High Voltage Lithium–Manganese Rich NMC Composite Cathodes with Cycling

Understanding the evolution of chemical composition and morphology of battery materials during electrochemical cycling is fundamental to extending battery cycle life and ensuring safety. This is particularly true for the much debated high energy density (high voltage) lithium–manganese rich cathode material of composition Li1 + xM1 – xO2 (M = Mn, Co, Ni). In this study we combine full-field transmission X-ray microscopy (TXM) with X-ray absorption near edge structure (XANES) to spatially resolve changes in chemical phase, oxidation state, and morphology within a high voltage cathode having nominal composition Li1.2Mn0.525Ni0.175Co0.1O2. Nanoscale microscopy with chemical/elemental sensitivity provides direct quantitative visualization of the cathode, and insights into failure. Single-pixel (∼30 nm) TXM XANES revealed changes in Mn chemistry with cycling, possibly to a spinel conformation and likely including some Mn(II), starting at the particle surface and proceeding inward. Morphological analysis of the particles revealed, with high resolution and statistical sampling, that the majority of particles adopted nonspherical shapes after 200 cycles. Multiple-energy tomography showed a more homogeneous association of transition metals in the pristine particle, which segregate significantly with cycling. Depletion of transition metals at the cathode surface occurs after just one cycle, likely driven by electrochemical reactions at the surface.

A large iron isotope effect in SmFeAsO1-xFx and Ba1-xKxFe2As2

The recent discovery of superconductivity in oxypnictides with a critical transition temperature (TC) higher than the McMillan limit of 39 K (the theoretical maximum predicted by Bardeen–Cooper–Schrieffer theory) has generated great excitement. Theoretical calculations indicate that the electron–phonon interaction is not strong enough to give rise to such high transition temperatures, but strong ferromagnetic/antiferromagnetic fluctuations have been proposed to be responsible. Superconductivity and magnetism in pnictide superconductors, however, show a strong sensitivity to the crystal lattice, suggesting the possibility of unconventional electron–phonon coupling. Here we report the effect of oxygen and iron isotope substitution on TC and the spin-density wave (SDW) transition temperature (TSDW) in the SmFeAsO1 - xFx and Ba1 - xKxFe2As2 systems. The oxygen isotope effect on TC and TSDW is very small, while the iron isotope exponent αC = -dlnTC/dlnM is about 0.35 (0.5 corresponds to the full isotope effect). Surprisingly, the iron isotope exchange shows the same effect on TSDW as TC. This indicates that electron–phonon interaction plays some role in the superconducting mechanism, but a simple electron–phonon coupling mechanism seems unlikely because a strong magnon–phonon coupling is included.

Hydrogen-Incorporation Stabilization of Metallic VO2(R) Phase to Room Temperature, Displaying Promising Low-Temperature Thermoelectric Effect

Regulation of electron-electron correlation has been found to be a new effective way to selectively control carrier concentration, which is a crucial step toward improving thermoelectric properties. The pure electronic behavior successfully stabilized the nonambient metallic VO(2)(R) to room temperature, giving excellent thermoelectric performance among the simple oxides with wider working temperature ranges.

Bioremediation of Cr(VI) and Immobilization as Cr(III) by Ochrobactrum anthropi

Bioremediation of Cr(VI) through reduction relies on the notion that the produced Cr(III) may be precipitated or efficiently immobilized. However, recent reports suggest that soluble organo-Cr(III) complexes are present in various chromate-reducing bacterial systems. This work was designed to explore the factors that affect the immobilization of Cr(III) in the Ochrobactrum anthropi system. X-ray absorption fine structure analysis on the cell debris clearly verified that coordination of Cr(III) occurs on the surfaces via the chelating coordination with carboxyl- and amido-functional groups. However, competitive coordination experiments of Cr(III) revealed that the small molecules such as amino acids and their derivatives or multicarboxyl compounds hold stronger coordination ability with Cr(III) than with cell debris. We speculate that it is the preferential coordination of Cr(III) to the soluble organic molecules in the bacterial culture medium that inhibits effective immobilization of Cr(III) on the cells. On the basis of this understanding, a strategy with two-step control of the medium was proposed, and this achieved successful immobilization of Cr(VI) as Cr(III) by O. anthropi and Planococcus citreus in 5-50 L pilot-scale experiments.