Fabrication of Wear-Resistant Ti3AlC2/Al3Ti Hybrid Aluminum Composites by Friction Stir Processing

Metallurgical and Materials Transactions A - Hybrid nanocomposites have potential as wear-resistant materials. However, synthesizing these nanocomposites by conventional molten state methods result...     

Assembly of a DNA Origami Chinese Knot by Only 15% of the Staple Strands

As a giant leap in DNA self-assembly, DNA origami has exhibited an unprecedented ability to construct nanostructures with arbitrary shapes and sizes. In typical DNA origami, hundreds of short DNA staple strands fold a long, single-stranded (ss) DNA scaffold cooperatively into designed nanostructures. However, large numbers of DNA strands are expensive and would hinder applications such as pharmaceutical investigations because of the complicated components. Therefore, one challenge is how to reduce the number of staple strands needed to construct DNA origami. For a DNA origami structure, the scale-free folding pattern of the scaffold strand is determined by staple strands at the branching vertexes. Simple duplex regions help to define the size-related features of the origami geometry. In this study, we hypothesized that a scaffold strand can be correctly folded into a designed topology by using only staple strands involved in branching vertexes. After assembly, any remaining, flexible, single-stranded regions of the scaffold could be converted into rigid duplexes by DNA polymerase to achieve the designed geometric structures. To demonstrate the concept, we used only 18 staple strands (covering 15 % of the scaffold strand) to assemble a porous DNA nanostructure, which was visualized by atomic force microscopy (AFM). This study helps understanding of the role of cooperativity in origami folding, and provides a cost-effective approach for small-scale prototyping DNA origami.     

Crossing the Border: From Keto- to Imine Reduction in Short-Chain Dehydrogenases/Reductases

The family of NAD(P)H-dependent short-chain dehydrogenases/reductases (SDRs) comprises numerous biocatalysts capable of C=O or C=C reduction. The highly homologous noroxomaritidine reductase (NR) from Narcissus sp. aff. pseudonarcissus and Zt_SDR from Zephyranthes treatiae, however, are SDRs with an extended imine substrate scope. Comparison with a similar SDR from Asparagus officinalis (Ao_SDR) exhibiting keto-reducing activity, yet negligible imine-reducing capability, and mining the Short-Chain Dehydrogenase/Reductase Engineering Database indicated that NR and Zt_SDR possess a unique active-site composition among SDRs. Adapting the active site of Ao_SDR accordingly improved its imine-reducing capability. By applying the same strategy, an unrelated SDR from Methylobacterium sp. 77 (M77_SDR) with distinct keto-reducing activity was engineered into a promiscuous enzyme with imine-reducing activity, thereby confirming that the ability to reduce imines can be rationally introduced into members of the “classical” SDR enzyme family. Thus, members of the SDR family could be a promising starting point for protein approaches to generate new imine-reducing enzymes.     

Dual Inhibition of Pyruvate Dehydrogenase Complex and Respiratory Chain Complex Induces Apoptosis by a Mitochondria-Targeted Fluorescent Organic Arsenical in vitro and in vivo

Based on the potential therapeutic value in targeting mitochondria and the fluorophore tracing ability, a fluorescent mitochondria-targeted organic arsenical PDT-PAO-F16 was fabricated, which not only visualized the cellular distribution, but also exerted anti-cancer activity in vitro and in vivo via targeting pyruvate dehydrogenase complex (PDHC) and respiratory chain complexes in mitochondria. In details, PDT-PAO-F16 mainly accumulated into mitochondria within hours and suppressed the activity of PDHC resulting in the inhibition of ATP synthesis and thermogenesis disorder. Moreover, the suppression of respiratory chain complex I and IV accelerated the mitochondrial dysfunction leading to caspase family-dependent apoptosis. In vivo, the acute promyelocytic leukemia was greatly alleviated in the PDT-PAO-F16 treated group in APL mice model. Our results demonstrated the organic arsenical precursor with fluorescence imaging and target-anticancer efficacy is a promising anticancer drug.     

Manganese ferrite-polyaniline hybrid materials: Electrical and magnetic properties

Magnetic MnFe₂O₄ nanopowders were synthesized by an original solvothermal method in the absence and in the presence of tetra-n-butylammonium bromide (TBAB) and Tween 80 (TW) as surfactants. Manganese ferrite/polyaniline (PANI) hybrid materials were synthesized by in situ polymerization of aniline on the surface of MnFe₂O₄ using ammonium persulfate as oxidant. The purpose of the study was to investigate the influence of the two surfactants on the properties of the MnFe₂O₄ powders and of their composites with PANI. The specific surface area, the cumulative surface area of pores and the cumulative volume of pores are influenced by the nature of surfactant in case of MnFe₂O₄ powders and are higher by comparison to those of the MnFe₂O₄/PANI hybrid materials. The values of saturation magnetization in case of MnFe₂O₄ powders are higher than those of the hybrid materials and are not influenced by the surfactant nature. These features revealed that MnFe₂O₄ powders can be efficiently used as adsorbents for the purification of wastewaters. The values of the electrical conductivity of the composites exhibit a significant increase in comparison to the MnFe₂O₄ powders and depend on the surfactant nature. The highest value of electrical conductivity was achieved by the composite obtained using Tween 80 as surfactant (σ_DC = 54.5·10^?5S?m^?1) which was close to that of PANI (σ_DC = 61.2·10^?5 S?m^?1). The fact that the magnetic and electric properties of the synthesized MnFe₂O₄/PANI composites can be changed by design, demonstrate the high potential of these materials to be used in magneto-electric applications.     

Deacylation of Calcium-Dependent Antibiotics from Streptomyces violaceoruber in Co-culture with Streptomyces sp. MG7-G1

When Streptomyces violaceoruber grows together with Streptomyces sp. MG7-G1, it reacts with strongly induced droplet production on its aerial mycelium. Initially the metabolite profile of droplets from S. violaceoruber in co-culture with Streptomyces sp. MG7-G1 was compared to samples from S. violaceoruber in single-culture by using high-performance liquid chromatography-mass spectrometry (HPLC-MS). Then, the exudate from agar plates of co-cultures and single cultures (after freezing and thawing) was also analysed. Several compounds were only observed when S. violaceoruber was grown in co-culture. Based on their high-resolution ESI mass spectra and their comparable retention times to the calcium-dependent antibiotics (CDAs) produced by S. violaceoruber, the new compounds were suspected to be deacylated calcium-dependent antibiotics (daCDAs), lacking the 2,3-epoxyhexanoyl residue of CDAs. This was verified by detailed analysis of the MS/MS spectra of the daCDAs in comparison to the CDAs. The major CDA compounds present in calcium ion-supplemented agar medium of co-cultures were daCDAs, thus suggesting that Streptomyces sp. MG7-G1 expresses a deacylase that degrades CDAs.     

Triphenylphosphonium (TPP)-Based Antioxidants: A New Perspective on Antioxidant Design

Mitochondrial oxidative damage and dysfunction contribute to a wide range of human diseases. Considering the limitation of conventional antioxidants and that mitochondria are the main source of reactive oxygen species (ROS) which induce oxidative damage, mitochondria-targeted antioxidants which can selectively block mitochondrial oxidative damage and prevent various types of cell death have been widely developed. As a lipophilic cation, triphenylphosphonium (TPP) has been commonly used in designing mitochondria-targeted antioxidants. Conjugated with the TPP moiety, antioxidants can achieve more than 1000-fold higher mitochondrial concentration depending on cell membrane potentials and mitochondrial membrane potentials. Herein we discuss the deficiencies of conventional antioxidants and the advantages of mitochondrial targeting, and review various types of TPP-based mitochondria-targeted antioxidants. These provide theoretical and background support for the design of new anti-oxidant.     

N-Substituted Nipecotic Acids as (S)-SNAP-5114 Analogues with Modified Lipophilic Domains

Potential mGAT4 inhibitors derived from the lead substance (S)-SNAP-5114 have been synthesized and characterized for their inhibitory potency. Variations from the parent compound included the substitution of one of its aromatic 4-methoxy and 4-methoxyphenyl groups, respectively, with a more polar moiety, including a carboxylic acid, alcohol, nitrile, carboxamide, sulfonamide, aldehyde or ketone function, or amino acid partial structures. Furthermore, it was investigated how the substitution of more than one of the aromatic 4-methoxy groups affects the potency and selectivity of the resulting compounds. Among the synthesized test substances (S)-1-{2-[(4-formylphenyl)bis(4-methoxyphenyl)-methoxy]ethyl}piperidine-3-carboxylic acid, that features a carbaldehyde function in place of one of the aromatic 4-methoxy moieties of (S)-SNAP-5114, was found to have a pIC₅₀ value of 5.89±0.07, hence constituting a slightly more potent mGAT4 inhibitor than the parent substance while showing comparable subtype selectivity.