Suppression of E. multilocularis Hydatid Cysts after Ionizing Radiation Exposure

Background

Heavy-ion therapy has an advantage over conventional radiotherapy due to its superb biological effectiveness and dose conformity in cancer therapy. It could be a potential alternate approach for hydatid cyst treatment. However, there is no information currently available on the cellular and molecular basis for heavy-ion irradiation induced cell death in cystic echinococcosis.

Methododology/Principal Findings

LD50 was scored by protoscolex death. Cellular and ultrastructural changes within the parasite were studied by light and electron microscopy, mitochondrial DNA (mtDNA) damage and copy number were measured by QPCR, and apoptosis was determined by caspase 3 expression and caspase 3 activity. Ionizing radiation induced sparse cytoplasm, disorganized and clumped organelles, large vacuoles and devoid of villi. The initial mtDNA damage caused by ionizing radiation increased in a dose-dependent manner. The kinetic of DNA repair was slower after carbon-ion radiation than that after X-rays radiation. High dose carbon-ion radiation caused irreversible mtDNA degradation. Cysts apoptosis was pronounced after radiation. Carbon-ion radiation was more effective to suppress hydatid cysts than X-rays.

Conclusions

These studies provide a framework to the evaluation of attenuation effect of heavy-ion radiation on cystic echinococcosis in vitro. Carbon-ion radiation is more effective to suppress E. multilocularis than X-rays.     

Immobilization of Rhizopus oryzae in a modified polyvinyl alcohol gel for L(+)-lactic acid production

The production of L(+)-lactic acid (LA) by Rhizopus oryzae immobilized in polyvinyl alcohol (PVA) was investigated. To decrease diffusional resistance, we modified the PVA gel through the addition of sodium alginate and phosphate esterification. The production of L(+)-LA improved notably in the immobilized Rhizopus oryzae. Maximum L(+)-LA production (106.27 g/L), with a yield of 73.1 % and rate of 2.95 g/L·h, was obtained at a temperature of 38 °C, 6 % PVA, and 0.8 % sodium alginate. The immobilized R. oryzae was stable in 14 serial-batch cultures using non-growth medium. The immobilized beads also displayed good tolerance to low temperature and long-term storage at 4 °C with the preservation of biochemical properties.     

Pierisformotoxins A – D,Polyesterified Grayanane Diterpenoids from Pieris formosa and Their cAMP‐Decreasing Activities

Four highly acylated diterpenoids, designated as pierisformotoxins A–D ( 1 – 4 , resp.), along with 26 known compounds, were isolated from the flowers of Pieris formosa. Among them, pierisformotoxins A and B ( 1 and 2 , resp.) were new highly acylated grayanane diterpenoids, of which the five‐membered ring A has undergone an oxidative cleavage between C(3) and C(4), followed by lactonization, to give rise to a five‐membered lactone ring between C(3) and C(5), differing from the previously reported grayanane diterpenoids with a 5/7/6/5 ring system. Results of the cAMP‐regulation‐activity assay showed that pierisformotoxin C ( 3 ) at 10 μM (inhibitory ratio (IR): 10.1%) or 2 μM (9.8%), and pierisformotoxin B ( 2 ) at 50 μM (13.9%) significantly decreased the cAMP level in N1E‐115 neuroblastoma cells (p<0.05).     

Molecular dynamics study on the correlation between structure and sensitivity for defective RDX crystals and their PBXs

Molecular dynamics simulation was applied to investigate the sensitivities of perfect and defective RDX (cyclotrimethylene trinitramine) crystals, as well as their PBXs (polymer-bonded explosives) with the polymeric binder F₂₃₁₁, in the NPT (constant number of particles, constant pressure, constant temperature) ensemble using the COMPASS force field. Five kinds of defects—two dislocations, one vacancy, and two types of doping—were considered separately. The bond length distribution and the maximum (L _max) and average (L _ave) bond lengths of the N–NO₂ trigger bonds in RDX were obtained and their relationships to the sensitivities of RDX and PBXs are discussed. L _max was found to be an important structural parameter for judging the relative sensitivity, and defects were observed to have little effect on the sensitivities of PBXs, due to the strong desensitizing effect of the polymer F₂₃₁₁.     

The investigations on HIV-1 gp120 bound with BMS-488043 by using docking and molecular dynamics simulations

BMS-488043, like its predecessor BMS-378806, is a small molecule that can block the interactions between gp120 and CD4, and has shown good clinical efficacy. However, the crystal structure of drug-gp120 complexes or the full-length gp120 free of bound ligand is unpublished until now. Docking combined with molecular dynamics simulation is used to investigate the binding mode between BMS-488043 and gp120. On the basis of the analysis of the simulated results, the plausible binding mode is acquired, such as the changes of binding mode in the trajectory and the calculated binding free energy. Subsequently, a number of residues which make contacts with the small molecule are studied by binding free energy decomposition to understand the mutation experiments, such as Trp427, Ser375, and Thr257 residues with the help of the acquired binding mode above. Especially, the importance of the hydrophobic groove formed by residues Ile371 and Gly472 which bind BMS-488043 is elaborated, which has not been explored much. In addition, theoretical investigations on the dynamics behavior of the gp120 associated with BMS-488043 enhanced binding are performed; the results indicate that the BMS-488043 may be more deeply inserted into the Phe43 cavity compared with the previous binding mode acquired by docking.     

Theoretical investigations on the synthesis mechanism of cyanuric acid from NH3 and CO2

In the synthesis of cyanuric acid from NH₃ and CO₂, urea and isocyanic acid OCNH are two pivotal intermediates. Based on density functional theory (DFT) calculations, the synthesis mechanism of cyanuric acid from NH₃ + CO₂ was investigated systematically. Urea can be synthesized from NH₃ and CO₂, and cyanuric acid can be obtained from urea or NH₃ + CO₂. In the stepwise mechanism of cyanuric acid from urea or NH₃ + CO₂, the energy barriers are relatively high, and the condition of high pressure and temperature does not decrease the energy barriers. Our theoretical model shows that cyanuric acid is actually acquired from OCNH via a one-step cycloaddition reaction.

Theoretical studies on the crystal structure, thermodynamic properties, detonation performance and thermal stability of cage-tetranitrotetraazabicyclooctane as a novel high energy density compound

The B3LYP/6-31G (d) method of density functional theory (DFT) was used to study molecular geometry, electronic structure, infrared spectrum (IR) and thermodynamic properties. The heat of formation (HOF) and calculated density were estimated to evaluate the detonation properties using Kamlet–Jacobs equations. Thermal stability of 3,5,7,10,12,14,15,16-octanitro- 3,5,7,10,12,14,15,16-octaaza-heptacyclo[7.5.1.1^2,8.0^1,11.0^2,6.0^4,13.0^6,11]hexadecane (cage-tetranitrotetraazabicyclooctane) was investigated by calculating the bond dissociation energy (BDE) at unrestricted B3LYP/6-31G (d) level. The calculated results show that the N–NO₂ bond is a trigger bond during thermolysis initiation process. The crystal structure obtained by molecular mechanics (MM) methods belongs to Pna2₁ space group, with cell parameters a?=?12.840 Å, b?=?9.129 Å, c?=?14.346 Å, Z?=?6 and ρ?=?2.292 g·cm^?3. Both the detonation velocity of 9.96 km·s^?1 and the detonation pressure of 47.47 GPa are better than those of CL-20. According to the quantitative standard of energetics and stability, as a high energy density compound (HEDC), cage-tetranitrotetraazabicyclooctane essentially satisfies this requirement.     

Theoretical study of the triangular bonding complex formed by carbon tetrabromide, a halide, and a solvent molecule in the gas phase

MP2(full)/aug-cc-pVDZ(-PP) computations predict that new triangular bonding complexes (where X^? is a halide and H–C refers to a protic solvent molecule) consist of one halogen bond and two hydrogen bonds in the gas phase. Carbon tetrabromide acts as the donor in the halogen bond, while it acts as an acceptor in the hydrogen bond. The halide (which commonly acts as an acceptor) can interact with both carbon tetrabromide and solvent molecule (CH₃CN, CH₂Cl₂, CHCl₃) to form a halogen bond and a hydrogen bond, respectively. The strength of the halogen bond obeys the order CBr₄???Cl^? > CBr₄???Br^? > CBr₄???I^?. For the hydrogen bonds formed between various halides and the same solvent molecule, the strength of the hydrogen bond obeys the order C-H???Cl^? > C-H???Br^? > C-H???I^?. For the hydrogen bonds formed between the same halide and various solvent molecules, the interaction strength is proportional to the acidity of the hydrogen in the solvent molecule. The diminutive effect is present between the hydrogen bonds and the halogen bond in chlorine and bromine triangular bonding complexes. Complexes containing iodide ion show weak cooperative effects.