DFT Calculations for the HONO Elimination Process of CL-20 Conformers

The HONO elimination process is regarded to be an important initial decomposition process of energetic nitramines. Four CL-20 conformers based on the ε-CL-20 were obtained by the optimization at the m062x/cc-pvtz level in this study, and the Transition State (TS) and Intrinsic Reaction Coordinate (IRC) calculations were carried out at the same level. In addition, the rate coefficients and activation energy of the HONO elimination process were evaluated using conventional transition state theory (TST) and canonical variational transition state theory (CVT) with Eckart and small-curvature tunneling (SCT) methods to correct the transmission coefficients for the quantum tunneling effect. The calculation results have shown that the HONO elimination process concerning the nitro groups located on six numbered rings is the hardest to happen, and it seems that the longer distance between nitro groups and the adjacent hydrogen atom would result in the higher barrier energy; the HONO elimination process is most likely to happen for the axial positioning of nitro groups located on five numbered rings and most unlikely to happen for the ones located on six numbered rings; CL-20 II and CL-20 IV conformers are the most unstable one and most stable one concerning the reaction difficulty of the HONO elimination process.

Design of time-delayed safety switches for CRISPR gene therapy

CRISPR system is a powerful gene editing tool which has already been reported to address a variety of gene relevant diseases in different cell lines. However, off-target effect and immune response caused by Cas9 remain two fundamental problems. Inspired by previously reported Cas9 self-elimination systems, time-delayed safety switches are designed in this work. Firstly, ultrasensitive relationship is constructed between Cas9-sgRNA (enzyme) and Cas9 plasmids (substrate), which generates the artificial time delay. Then intrinsic time delay in biomolecular activities is revealed by data fitting and utilized in constructing safety switches. The time-delayed safety switches function by separating the gene editing process and self-elimination process, and the tunable delay time may ensure a good balance between gene editing efficiency and side effect minimization. By addressing gene therapy efficiency, off-target effect, immune response and drug accumulation, we hope our safety switches may offer inspiration in realizing safe and efficient gene therapy in humans.

Bioaccumulation of Zn and 137Cs in Glauconomya virens (Linnaeus, 176) Upon Exposure to Sigle and Mixture of Zn or 137Cs and Salinity

This study aims to determine the effect of concentrations and salinity of seawater on the bioaccumulation of zinc and cesium in the Glauconomya virens. Salinity conditions and contaminant concentrations in the marine environment can change due to weather and other inputs. A biokinetic experiment was carried out using a single compartment approach that used radiotracer 65Zn and 137Cs. The experiments conducted were biota collection, acclimatization, bioaccumulation, and elimination. Acclimatization aims for the adaptation of biota in an experimental environment. Bioaccumulation was by placing the biota in an aquarium containing seawater media spiked by 65Zn, Zn, and 137Cs radiotracer contaminants. The elimination process was the release of contaminants from the body of the biota by placing them in clean and flowing seawater. The experimental results show that the uptake and elimination of Zn and Cs were influenced by these two parameters (water concentration and salinity). The highest value of Concentration Factor (CF) for Zn was 11.14 ml.g-1 under influences its concentration of 0.7 ppm in water. In the depuration process, Zn maintained by G virens were 39.44; 31.17; 23.62; and 23.92% after these organisms accumulate this element from seawater containing 0.1; 0.3, 0.5, and 0.7 ppm, respectively. The highest of 137Cs under influences its concentration of 3 Bg.ml-1 reached 2.65 mL.g-1. The effect of salinity is directly proportional to the factor value of Zn and 137Cs concentration.

Refinement of the Feline Musculoskeletal Pain Index (FMPI) and development of the short-form FMPI

Objectives The aim of this study was to investigate the reliability and responsiveness of the Feline Musculoskeletal Pain Index (FMPI) using the collective results of multiple clinical studies and iteratively refine the FMPI for future use. Methods Data were compiled from previously conducted studies involving client-owned cats with degenerative joint disease (DJD) and which used the FMPI. The reliability of the FMPI was assessed using the data from the initial visits of those studies. For the assessment of responsiveness of the FMPI, only placebo-controlled studies that used analgesic treatments were included. Treatment groups from each study were combined and categorized as ‘placebo’ group and ‘analgesic’ group. Then, the mean change from baseline in score of each FMPI item and across all items within and between these groups were assessed. Based on the results of the reliability and responsiveness of the FMPI, stepwise elimination was used to remove the items that were least able to distinguish between the placebo and analgesic groups. Finally, after the stepwise elimination, a proposed new FMPI-short form (FMPI-sf) was constructed and its reliability was reassessed using the data sets described above. Individual and combined data sets of the studies were also used to compare the responsiveness of the original FMPI and the FMPI-sf. Results The data from 180 cats from four studies were included. The original FMPI had a reasonable reliability, but low/no responsiveness. The elimination process of FMPI items refined the responsiveness of the instrument while maintaining its reliability. When the responsiveness was compared between the original FMPI (17 items) and the FMPI-sf (nine items), the treatment effect between groups was always greater when the FMPI-sf was used. Conclusions and relevance The proposed FMPI-sf may be able to better distinguish between placebo and analgesic effects in cats with DJD.

The effect of hemoadsorption on rivaroxaban blood plasma concentration in emergency cardiac surgery

Hemoadsorption was used in a 59-year-old patient with an acute type A aortic dissection, who was on rivaroxaban and dual antiplatelet therapy with clopidogrel and acetylsalicylic acid. Our aim was to expeditiously remove rivaroxaban preoperatively. After 8 h of hemoadsorption, the rivaroxaban blood plasma concentration (RBPC) did not decrease below 42.1 μg/l. Intraoperatively, hemoadsorption was repeated during extracorporeal circulation. Sixteen hours after surgery and a total of 13 h of hemoadsorption, the RBPC was 40.1 μg/l. Thereafter, the RBPC spontaneously decreased to 24.7 μg/l within 14 h. In our patient, hemoadsorption may have enhanced rivaroxaban removal at higher RBPC (cutoff value 40–50 μg/l). At lower RBPC, the removal of rivaroxaban may depend solely on the natural drug elimination process. The evolution of the RBPC under hemoadsorption in vivo warrants a thorough investigation. Further clinical studies are required to assess the effectiveness and limitations of hemoadsorption to preclude a fatal bleeding event in patients with rivaroxaban in need of major emergency surgery.

Facile One-Pot Synthesis of Diarylacetylenes from Arylaldehydes via Addition-Double Elimination Process

A practical one-pot protocol has been developed to synthesize diarylacetylenes from arylaldehydes by treatment with 1-(arylmethyl)benzotriazoles and LiN(SiMe3)2. The reaction proceeded smoothly through imine formation, Mannich-type addition and double elimination...