Evaluation of the PSMA-Binding Ligand 212Pb-NG001 in Multicellular Tumour Spheroid and Mouse Models of Prostate Cancer

Radioligand therapy targeting the prostate-specific membrane antigen (PSMA) is rapidly evolving as a promising treatment for metastatic castration-resistant prostate cancer. The PSMA-targeting ligand p-SCN-Bn-TCMC-PSMA (NG001) labelled with ²¹²Pb efficiently targets PSMA-positive cells in vitro and in vivo. The aim of this preclinical study was to evaluate the therapeutic potential of ²¹²Pb-NG001 in multicellular tumour spheroid and mouse models of prostate cancer. The cytotoxic effect of ²¹²Pb-NG001 was tested in human prostate C4-2 spheroids. Biodistribution at various time points and therapeutic effects of different activities of the radioligand were investigated in male athymic nude mice bearing C4-2 tumours, while long-term toxicity was studied in immunocompetent BALB/c mice. The radioligand induced a selective cytotoxic effect in spheroids at activity concentrations of 3–10 kBq/mL. In mice, the radioligand accumulated rapidly in tumours and was retained over 24 h, while it rapidly cleared from nontargeted tissues. Treatment with 0.25, 0.30 or 0.40 MBq of ²¹²Pb-NG001 significantly inhibited tumour growth and improved median survival with therapeutic indexes of 1.5, 2.3 and 2.7, respectively. In BALB/c mice, no signs of long-term radiation toxicity were observed at activities of 0.05 and 0.33 MBq. The obtained results warrant clinical studies to evaluate the biodistribution, therapeutic efficacy and toxicity of ²¹²Pb-NG001.     

Collective reflection strategy for moderating conformity tendency and promoting reflective judgment performance

Reflective judgement is crucial for medical-related practitioners in dealing with controversial issues. However, the conformity phenomenon is likely to occur and interfere with reflective judgement learning during interactive activities. Effective strategies are required to moderate the conformity behaviour tendency (CBT) and improve reflective judgement performance (RJP). This study demonstrates two significant results: (a) Compared with the guided self-reflection learning strategy, the online collective reflection (OCR) learning strategy effectively weakened the learners' general CBT while dealing with professional controversial issues; and (b) a significantly negative correlation between the RJP achieved and the change of CBT in online environment was detected in the OCR group. The implications and potential applications in higher education were discussed. Further studies are needed to confirm the long-term effects and the extending application to other professional studies.     

Enzymatic polymerization of polythiophene by immobilized glucose oxidase

In this study ‘green’, environmentally friendly enzymatic reaction-based synthesis of conducting polymer polythiophene (PTP) is proposed. Glucose oxidase (GO_x) was shown as an effective catalyst, which, in the presence of glucose, produces hydrogen peroxide suitable for the oxidative polymerization of PTP under ambient conditions at neutral pH. Enzymatically induced formation of the PTP layer over GO_x-modified graphite rod electrode (GRE) was demonstrated and evaluated amperometrically and by attenuated total reflectance – Fourier transform infrared (ATR-FTIR) spectroscopy. Surface morphology of GO_x- and PTP-modified GR electrodes was characterized by atomic force microscopy. It was clearly shown that the apparent kinetic Michaelis constant (K_M(app.)) of GO_x/PTP-modified GRE increased by increasing the duration of polymerization reaction. Therefore, enzymatic polymerization could be applied in adjustment and/or tuning of K_M(app.) and other kinetic parameters of GO_x-based electrodes used in biosensor design.     

Simulation of ion-track ranges in uranium oxide

Direct comparisons between statistically sound simulations of ion-tracks and published experimental measurements of range densities of iodine implants in uranium dioxide have been made with implant energies in the range of 100–800 keV. Our simulations are conducted with REED-MD (Rare Event Enhanced Domain-following Molecular Dynamics) in order to account for the materials structure in both single crystalline and polycrystalline samples. We find excellent agreement between REED-MD results and experiments for polycrystalline target materials.     

Liquid crystalline polyamines containing side dendrons: Toward the building of ion channels based on polyamines

In this article, we modified poly[2-(aziridin-1-yl)ethanol] (PAZE) with the dendron 3,4,5-tris[4-(n-dodecan-1-yloxy)benzyloxy]benzoic acid, to obtain liquid crystalline columnar polyamines. The chemical modification reaction was first tuned on a model compound, N,N-dimethyl-2-hydroxyethylamine. The best results were obtained by the esterification method with N,N'-dicyclohexylcarbodiimide at room temperature, in the presence of 4-dimethylaminopyridine. The obtained copolymers showed higher char yield than starting PAZE. In all cases they exhibited small crystalline portions after annealing and columnar mesophases, as inferred by DSC, XRD and POM. The dimension of the unit cell resulted slightly narrower than in the case of the copolyethers bearing the same dendron. This is probably due to the presence of a longer spacer in PAZE, which allows better accommodating of the side tapered group.     

Evaluation of amperometric glucose biosensors based on glucose oxidase encapsulated within enzymatically synthesized polyaniline and polypyrrole

In this article potential and suitability of enzymatically synthesized conducting polymers polyaniline (PANI) and polypyrrole (PPY) for fabrication of enzymatic amperometric glucose biosensors were evaluated. The polymerisation of these polymers was induced by catalytic activity of glucose oxidase (GOx) from Penicillium vitale cross-linked by glutaraldehyde (GA) on the graphite rod electrode (GOx-electrode) surface. The main precursors for initiation of polymerisation reactions were hydrogen peroxide as an initiator of polymerisation reaction and β-d-gluconic acid as a medium, which reduced the pH towards acidic one is the most suitable for the formation of PANI and PPY. During the polymerisation reactions the immobilized GOx was self-encapsulated within formed PANI or PPY layers in order to form GOx/PANI- and GOx/PPY-modified electrodes (GOx/PANI-electrode and GOx/PPY-electrode, respectively). Kinetic properties of GOx, which is acting as a biocatalyst in GOx/PANI- and GOx/PPY-electrodes, were studied and results were compared with GOx-electrode. The results show that in both GOx/PANI- and GOx/PPY-electrodes self-encapsulated GOx exhibited different parameters of catalysed reaction kinetics due to increasing diffusion limitations if compared with that of the GOx-electrode and it allowed the detection of glucose in a wider concentration interval. Moreover, both GOx/PANI- and GOx/PPY-electrodes exhibited good operational stability and reproducibility of analytical signal. The electrochemical characteristics of formed PANI and PPY in the GOx/PANI- and GOx/PPY-electrodes were also determined. In addition, the influence of temperature, pH and common interfering compounds on the steady-state current response of modified electrodes were investigated and discussed.     

Mechanism and dynamics of shrinking island grains in mazed bicrystal thin films of Au

This work investigates the mechanism and dynamics of grain boundary migration driven by capillary forces via in situ electron microscopy, complemented by molecular-dynamics simulations. Using thin films of Au with the mazed bicrystal geometry, the shrinkage of island grains with 90°〈1 1 0〉 tilt grain boundaries was observed by diffraction contrast and high-resolution imaging. The grains remained cylindrical throughout the shrinkage, and there was no measurable grain rotation even at very small sizes. The rate of shrinkage was found to be erratic and inconsistent with parabolic kinetics, accelerating before complete disappearance. Residual defects were found immediately after complete shrinkage, although the type and magnitude of the defects varied from grain to grain. Measurement of the grain boundary shape anisotropy showed a preference for facets on low-index planes of the crystals, including the mirror-symmetry planes of the bicrystal. These facets were also found directly on individual images extracted from high-resolution video recordings of shrinking grains at ～300 °C. The dynamics of boundary motion were found to be limited by nucleation and propagation of steps on these facets. The cylindrical geometry and size of the experimentally observed island grains allow direct comparison with molecular-dynamics simulations on the same length scale, which reproduced many of the experimentally observed features, including non-parabolic shrinkage, absence of systematic grain rotation, step-controlled migration and dislocation debris after complete grain shrinkage. Differences between model and experiment are discussed in terms of the possible role of impurities, surfaces and interfacial steps.     

Calculation of impurity diffusivities in α-Fe using first-principles methods

Self- and impurity diffusivities in body-centered-cubic (bcc) iron have been calculated within the formalisms of harmonic transition-state theory and the Le Claire nine-frequency model for vacancy-mediated diffusion. The approach combines first-principles calculations of vacancy formation, migration, and solute-binding enthalpies and entropies in the ferromagnetic phase, with an empirical relationship for the effect of magnetic disorder on diffusion activation energies. Calculated Fe self-diffusion and Mo and W impurity-diffusion coefficients are shown to agree within a factor of five with the most recent experimental measurements in both the ferromagnetic and paramagnetic phases. Calculated diffusion coefficients for Mo and W impurities are comparable to or larger than that for Fe self-diffusion at all temperatures below the α–γ phase transition. Calculated activation energies for Ta and Hf impurities suggest that these solutes should also display impurity-diffusion coefficients larger than that for self-diffusion in body-centered cubic Fe.