Detection of small-sized DNA fragments in a glassy nanopore by utilization of CRISPR-Cas12a as a converter system.

The fabrication of nanopores with a matched pore size, and the existence of multiple interferents make the reproducible detection of small-sized molecules by means of solid-state nanopores still challenging. A useful method to solve these problems is based on the detection of large DNA nanostructures related to the existence of small-sized targets. In particular, a DNA tetrahedron with a well-defined 3D nanostructure is the ideal candidate for use as a signal transducer. Here, we demonstrate the detection of an L1-encoding gene of HPV18 as a test DNA target sequence in a reaction buffer solution, where long single-stranded DNA linking DNA tetrahedra onto the surface of the magnetic beads is cleaved by a target DNA-activated CRISPR-cas12 system. The DNA tetrahedra are subsequently released and can be detected by the current pulse in a glassy nanopore. This approach has several advantages: (1) one signal transducer can be used to detect different targets; (2) a glassy nanopore with a pore size much larger than the target DNA fragment can boost the tolerance of the contaminants and interferents which often degrade the performance of a nanopore sensor.

Total synthesis, structural, and biological evaluation of stylissatin A and related analogs.

The natural product cyclic peptide stylissatin A (1a) was reported to inhibit nitric oxide production in LPS-stimulated murine macrophage RAW 264.7 cells. In the current study, solid-phase total synthesis of stylissatin A was performed by using a safety-catch linker and yielded the peptide with a trans-Phe(7) -Pro(6) linkage, whereas the natural product is the cis rotamer at this position as evidenced by a marked difference in NMR chemical shifts. In order to preclude the possibility of 1b being an epimer of the natural product, we repeated the synthesis using d-allo-Ile in place of l-Ile and a different site for macrocyclization. The resulting product (d-allo-Ile(2) )-stylissatin A (1c) was also found to have the trans-Phe(7) -Pro(6) peptide conformations like rotamer 1b. Applying the second route to the synthesis of stylissatin A itself, we obtained stylissatin A natural rotamer 1a accompanied by rotamer 1b as the major product. Rotamers 1a, 1b, and the epimer 1c were separable by HPLC, and 1a was found to match the natural product in structure and biological activity. Six related analogs 2-7 of stylissatin A were synthesized on Wang resin and characterized by spectral analysis. The natural product (1a), the rotamer (1b), and (d-allo-Ile(2) )-stylissatin A (1c) exhibited significant inhibition of NO(.) . Further investigations were focused on 1b, which also inhibited proliferation of T-cells and inflammatory cytokine IL-2 production. The analogs 2-7 weakly inhibited NO(.) production, but strongly inhibited IL-2 cytokine production compared with synthetic peptide 1b. All analogs inhibited the proliferation of T-cells, with analog 7 having the strongest effect. In the analogs, the Pro(6) residue was replaced by Glu/Ala, and the SAR indicates that the nature of this residue plays a role in the biological function of these peptides. Copyright © 2016 European Peptide Society and John Wiley & Sons, Ltd.

Experimental and theoretical study for CO2 activation and chemical fixation with epoxides.

The synthesis of five-membered cyclic carbonates via catalytic cycloaddition reaction of CO2 with epoxides is considered to be an effective technology for alleviation of the energy crisis and global warming. Various commercial organic bases and ionic salts were used as catalysts, while the relationship of catalytic activity and compound structure has been seldom explored. Herein, a facilely obtained binary catalytic system based on triethylamine/NBu4Br was developed for CO2 activation and chemical fixation. The highly efficient catalytic system showed outstanding conversion and above 99% selectivity under metal-free mild reaction conditions (100 °C, 1 atm) in one hour. The detailed process of CO2 activation and chemical fixation was investigated at the molecular level by a series of experiments and theoretical calculation, which provided a mode for the design and synthesis of a highly efficient catalytic system for conversion of CO2 under mild conditions.

Nanohybrid of Carbon Quantum Dots/Molybdenum Phosphide Nanoparticle for Efficient Electrochemical Hydrogen Evolution in Alkaline Medium.

The exploration of highly efficient non-noble metal electrocatalysts for hydrogen evolution reaction (HER) under alkaline conditions is highly imperative but still remains a great challenge. In this work, the nanohybrid of carbon quantum dots and molybdenum phosphide nanoparticle (CQDs/MoP) has been firstly demonstrated as an efficient alkaline HER electrocatalyst. The CQDs/MoP nanohybrid is readily prepared through a charge-directed self-assembly of CQDs with phosphomolybdic acid (H3PMo12O40) at the molecular level, followed by facile phosphatizing at 700 °C. The introduction of CQDs greatly helps to alleviate the agglomeration and surface oxidation of MoP nanoparticles and ensures each MoP nanoparticle to be electronically addressed, thus significantly enhancing the intrinsic catalytic activity of MoP. The optimized CQDs/MoP exhibits high-efficiency synergistic catalysis toward HER in 1 M KOH electrolyte with a low onset potential of -0.08 V and a small Tafel slope of 56 mV dec-1 as well as high durability with negligible current loss for at least 24 h.