In Vivo Albumin-Binding of a C-Functionalized Cyclam Platform for 64Cu-PET/CT Imaging in Breast Cancer Model

An improved glucose-chelator-albumin bioconjugate (GluCAB) derivative, GluCAB-2^Mal, has been synthesized and studied for in vivo ⁶⁴Cu-PET/CT imaging in breast cancer mice models together with its first-generation analogue GluCAB-1^Mal. The radioligand works on the principle of tumor targeting through the enhanced permeability and retention (EPR) effect with a supportive role played by glucose metabolism. [⁶⁴Cu]Cu-GluCAB-2^Mal (99 % RCP) exhibited high serum stability with immediate binding to serum proteins. In vivo experiments for comparison between tumor targeting of [⁶⁴Cu]Cu-GluCAB-2^Mal and previous-generation [⁶⁴Cu]Cu-GluCAB-1^Mal encompassed microPET/CT imaging and biodistribution analysis in an allograft E0771 breast cancer mouse model. Tumor uptake of [⁶⁴Cu]Cu-GluCAB-2^Mal was clearly evident with twice as much accumulation as compared to its predecessor and a tumor/muscle ratio of up to 5 after 24 h. Further comparison indicated a decrease in liver accumulation for [⁶⁴Cu]Cu-Glu-CAB-2^Mal.     

Involvement of GPx-3 in the Reciprocal Control of Redox Metabolism in the Leukemic Niche

The bone marrow (BM) microenvironment plays a crucial role in the development and progression of leukemia (AML). Intracellular reactive oxygen species (ROS) are involved in the regulation of the biology of leukemia-initiating cells, where the antioxidant enzyme GPx-3 could be involved as a determinant of cellular self-renewal. Little is known however about the role of the microenvironment in the control of the oxidative metabolism of AML cells. In the present study, a coculture model of BM mesenchymal stromal cells (MSCs) and AML cells (KG1a cell-line and primary BM blasts) was used to explore this metabolic pathway. MSC-contact, rather than culture with MSC-conditioned medium, decreases ROS levels and inhibits the Nrf-2 pathway through overexpression of GPx3 in AML cells. The decrease of ROS levels also inactivates p38MAPK and reduces the proliferation of AML cells. Conversely, contact with AML cells modifies MSCs in that they display an increased oxidative stress and Nrf-2 activation, together with a concomitant lowered expression of GPx-3. Altogether, these experiments suggest that a reciprocal control of oxidative metabolism is initiated by direct cell–cell contact between MSCs and AML cells. GPx-3 expression appears to play a crucial role in this cross-talk and could be involved in the regulation of leukemogenesis.     

Evaluation of small-scale combustion of an insensitive high explosive formulation containing 3-nitro-1,2,4-triazol-5-one (NTO), 2,4-dinitroanisole (DNAN), and 1,3,5-trinitroperhydro-1,3,5-triazine (RDX)

ABSTRACT

Energetic materials are often disposed by open-burning or open-detonation as it is a cost-effective and efficient means of destroying explosive material, and often minimizes the need to transport hazardous explosives to treatment facilities. This practice is often scrutinized for the negative environmental impact of the odorous and unsightly toxic gaseous emissions as well as the resulting deposition residues, which often contain unburned energetic materials. With the increasing use of Insensitive High Explosive compositions in munitions, it is essential that the potential environmental impact of their disposal is assessed before their extensive use to prevent the kind of contamination incidents experienced with legacy explosives. Therefore, the aim of this work was to develop a controlled laboratory experiment to identify the gaseous emissions and the energetic material residues that are generated through the combustion of the IHE components 3-nitro-1,2,4-triazol-5-one (NTO), 2,4-dinitroanisole (DNAN), and 1,3,5-trinitroperhydro-1,3,5-triazine (RDX). A sealed vial containing small (mg) quantities of energetic material was heated until the energetic material combusted. Gas chromatography/mass spectrometry (GCMS) was used to calculate the oxygen consumption and to identify the gases that were generated. The solid residues were analyzed by high-performance liquid chromatography (HPLC) to quantify unburned energetic material. Results showed that DNAN was the most resistant to burning, thus leaving significant quantities of unreacted starting material in the vial. An interesting observation for the IHE formulation was that DNAN also inhibited the combustion of NTO and RDX. The gases emitted during the open burning of IHE components and mixtures included CO, CO₂, and N₂O as expected, but the proportions differed when the components and mixture were compared, reflecting the influence of DNAN on the burning behavior. From our data, we concluded that open-burning DNAN-based formulations is an environmentally unfavorable waste-management practice for the disposal of IHEs mainly due to generation of solid residues as well as unburnt DNAN.     

Induction of Oxidative Stress and Antioxidative Mechanisms in Arabidopsis thaliana after Uranium Exposure at pH 7.5

To evaluate the environmental impact of uranium (U) contamination, it is important to investigate the effects of U at ecologically relevant conditions. Since U speciation, and hence its toxicity, strongly depends on environmental pH, the present study aimed to investigate dose-dependent effects of U at pH 7.5. Arabidopsis thaliana plants (Mouse-ear Cress) were exposed for three days to different U concentrations at pH 7.5. In the roots, the increased capacities of ascorbate peroxidase and glutathione reductase indicate an important role for the ascorbate-glutathione cycle during U-induced stress. However, a significant decrease in the ascorbate redox state was observed after exposure to 75 and 100 µM U, indicating that those roots are severely stressed. In accordance with the roots, the ascorbate-glutathione cycle plays an important role in the antioxidative defence systems in A. thaliana leaves exposed to U at pH 7.5 as the ascorbate and glutathione biosynthesis were upregulated. In addition, small inductions of enzymes of the antioxidative defence system were observed at lower U concentrations to counteract the U-induced stress. However, at higher U concentrations it seems that the antioxidative defence system of the leaves collapses as reductions in enzyme activities and gene expression levels were observed.     

FeO0.7F1.3/C Nanocomposite as a High‐Capacity Cathode Material for Sodium‐Ion Batteries

Searching high capacity cathode materials is one of the most important fields of the research and development of sodium‐ion batteries (SIBs). Here, we report a FeO_0.7F_1.3/C nanocomposite synthesized via a solution process as a new cathode material for SIBs. This material exhibits a high initial discharge capacity of 496 mAh g^?1 in a sodium cell at 50 °C. From the 3^rd to 50^th cycle, the capacity fading is only 0.14% per cycle (from 388 mAh g^?1 at 3^rd the cycle to 360 mAh g^?1 at the 50^th cycle), demonstrating superior cyclability. A high energy density of 650 Wh kg^?1 is obtained at the material level. The reaction mechanism studies of FeO_0.7F_1.3/C with sodium show a hybridized mechanism of both intercalation and conversion reaction.     

Corrosion of hot-dip-galvanised steel and zinc alloy-coated steel in ammonia and ammonium chloride

There are many potential causes of corrosion in animal buildings. Animals exhale large quantities of moisture into the air creating high relative humidity in the building if the moisture is not properly vented. High humidity increases the potential for condensation. In addition, ammonia may be found in large quantities in animal buildings. Ammonia is released from manure and urine. In addition, ammonium chloride is used as a nitrogen source in fertilisers. In this study, the atmospheric corrosion of hot-dip-galvanised steel and zinc alloy-coated steel such as zinc–aluminium and zinc–aluminium–magnesium has been studied in atmospheres containing different levels of ammonia. Investigations have also been conducted at different levels of ammonium chloride. The results are discussed in view of the mechanisms of corrosion of zinc and zinc alloy-coated steel in ammonia and ammonium chloride-containing environments.     

Processing of CaLa2S4 infrared transparent ceramics: A comparative study of HP and FAST/SPS techniques

The densification of CaLa₂S₄ (CLS) powders prepared by combustion method was investigated by the use of Field-Assisted Sintering Technique (FAST) and Hot Pressing (HP). CLS powders were sintered using FAST at 1000°C at different pressures and heating rates and sintered by HP under 120 MPa from 800°C to 1100°C for 6 hours with a heating rate of 10°C/min. Comparison of both techniques was further realized by use of the same conditions of pressure, dwell time, and heating rate. Complementary techniques (XRD, SEM-EDS, density measurements, FTIR spectroscopy) were employed to correlate the sintering processes/parameters to the microstructural/compositional developments and optical transmission of the ceramics. Both sintering techniques produce ceramics with submicrometer grain size and relative density of about 99%. Nevertheless, HP is more suitable to densify CLS ceramics without fragmentation and also reach higher transmission than FAST. Transmission of 40%–45% was measured out of a possible maximum of 69% based on the Fresnel losses in the 8-14 μm window when HP is applied at 1000°C for 6 hours under 120 MPa. In both techniques, ceramics undergo reduction issues that originate from graphitic sintering atmosphere.