Submicron immunoglobulin particles exhibit FcγRII-dependent toxicity linked to autophagy in TNFα-stimulated endothelial cells.

In intravenous immunoglobulins (IVIG), and some other immunoglobulin products, protein particles have been implicated in adverse events. Role and mechanisms of immunoglobulin particles in vascular adverse effects of blood components and manufactured biologics have not been elucidated. We have developed a model of spherical silica microparticles (SiMPs) of distinct sizes 200-2000 nm coated with different IVIG- or albumin (HSA)-coronas and investigated their effects on cultured human umbilical vein endothelial cells (HUVEC). IVIG products (1-20 mg/mL), bare SiMPs or SiMPs with IVIG-corona, did not display significant toxicity to unstimulated HUVEC. In contrast, in TNFα-stimulated HUVEC, IVIG-SiMPs induced decrease of HUVEC viability compared to HSA-SiMPs, while no toxicity of soluble IVIG was observed. 200 nm IVIG-SiMPs after 24 h treatment further increased ICAM1 (intercellular adhesion molecule 1) and tissue factor surface expression, apoptosis, mammalian target of rapamacin (mTOR)-dependent activation of autophagy, and release of extracellular vesicles, positive for mitophagy markers. Toxic effects of IVIG-SiMPs were most prominent for 200 nm SiMPs and decreased with larger SiMP size. Using blocking antibodies, toxicity of IVIG-SiMPs was found dependent on FcγRII receptor expression on HUVEC, which increased after TNFα-stimulation. Similar results were observed with different IVIG products and research grade IgG preparations. In conclusion, submicron particles with immunoglobulin corona induced size-dependent toxicity in TNFα-stimulated HUVEC via FcγRII receptors, associated with apoptosis and mTOR-dependent activation of autophagy. Testing of IVIG toxicity in endothelial cells prestimulated with proinflammatory cytokines is relevant to clinical conditions. Our results warrant further studies on endothelial toxicity of sub-visible immunoglobulin particles.

Tuning the electronic properties of the γ-Al2O3 surface by phosphorus doping.

Tuning the electronic properties of oxide surfaces is of pivotal importance, because they find applicability in a variety of industrial processes, including catalysis. Currently, the industrial protocols for synthesizing oxide surfaces are limited to only partial control of the oxide's properties. This is because the ceramic processes result in complex morphologies and a priori unpredictable behavior of the products. While the bulk doping of alumina surfaces has been demonstrated to enhance their catalytic applications (i.e. hydrodesulphurization (HDS)), the fundamental understanding of this phenomenon and its effect at an atomic level remain unexplored. In our joint experimental and computational study, simulations based on Density Functional Theory (DFT), synthesis, and a variety of surface characterization techniques are exploited for the specific goal of understanding the structure-function relationship of phosphorus-doped γ-Al2O3 surfaces. Our theoretical calculations and experimental results agree in finding that P doping of γ-Al2O3 leads to a significant decrease in its work function. Our computational models show that this decrease is due to the formation of a new surface dipole, providing a clear picture of the effect of P doping at the surface of γ-Al2O3. In this study, we uncover a general paradigm for tuning support-catalyst interactions that involves electrostatic properties of doped γ-Al2O3 surface, specifically the surface dipole. Our findings open a new pathway for engineering the electronic properties of metal oxides' surfaces.

P-Doped Porous Carbon as Metal Free Catalysts for Selective Aerobic Oxidation with an Unexpected Mechanism.

An extremely simple and rapid (seconds) approach is reported to directly synthesize gram quantities of P-doped graphitic porous carbon materials with controlled P bond configuration. For the first time, it is demonstrated that the P-doped carbon materials can be used as a selective metal free catalyst for aerobic oxidation reactions. The work function of P-doped carbon materials, its connectivity to the P bond configuration, and the correlation with its catalytic efficiency are studied and established. In direct contrast to N-doped graphene, the P-doped carbon materials with higher work function show high activity in catalytic aerobic oxidation. The selectivity trend for the electron donating and withdrawing properties of the functional groups attached to the aromatic ring of benzyl alcohols is also different from other metal free carbon based catalysts. A unique catalytic mechanism is demonstrated, which differs from both GO and N-doped graphene obtained by high temperature nitrification. The unique and unexpected catalytic pathway endows the P-doped materials with not only good catalytic efficiency but also recyclability. This, combined with a rapid, energy saving approach that permits fabrication on a large scale, suggests that the P-doped porous materials are promising materials for "green catalysis" due to their higher theoretical surface area, sustainability, environmental friendliness, and low cost.

Microwave Enabled One-Pot, One-Step Fabrication and Nitrogen Doping of Holey Graphene Oxide for Catalytic Applications.

The unique properties of a holey graphene sheet, referred to as a graphene sheet with nanoholes in its basal plane, lead to wide range of applications that cannot be achieved by its nonporous counterpart. However, the large-scale solution-based production requires graphene oxide (GO) or reduced GO (rGO) as the starting materials, which take hours to days for fabrication. Here, an unexpected discovery that GO with or without holes can be controllably, directly, and rapidly (tens of seconds) fabricated from graphite powder via a one-step-one-pot microwave assisted reaction with a production yield of 120 wt% of graphite is reported. Furthermore, a fast and low temperature approach is developed for simultaneous nitrogen (N) doping and reduction of GO sheets. The N-doped holey rGO sheets demonstrate remarkable electrocatalytic capabilities for the electrochemical oxygen reduction reaction. The existence of the nanoholes provides a "short cut" for efficient mass transport and dramatically increases edges and surface area, therefore, creates more catalytic centers. The capability of rapid fabrication and N-doping as well as reduction of holey GO can lead to development of an efficient catalyst that can replace previous coin metals for energy generation and storage, such as fuel cells and metal-air batteries.

[Comparative analysis of the radionuclide composition in fallout after the Chernobyl and the Fukushima accidents].

The nuclear accident occurred at Fukushima Dai-ichi Nuclear Power Plant (NPP) (March 11, 2011) similarly to the accident at the Chernobyl NPP (April 26, 1986) is related to the level 7 of the INES. It is of interest to make an analysis of the radionuclide composition of the fallout following the both accidents. The results of the spectrometric measurements were used in that comparative analysis. Two areas following the Chernobyl accident were considered: (1) the near zone of the fallout - the Belarusian part of the central spot extended up to 60 km around the Chernobyl NPS and (2) the far zone of the fallout--the "Gomel-Mogilev" spot centered 200 km to the north-northeast of the damaged reactor. In the case of Fukushima accident the near zone up to about 60 km considered. The comparative analysis has been done with respect to refractory radionuclides (95Zr, 95Nb, 141Ce, 144Ce), as well as to the intermediate and volatile radionuclides 103Ru, 106Ru, 131I, 134Cs, 137Cs, 140La, 140Ba and the results of such a comparison have been discussed. With respect to exposure to the public the most important radionuclides are 131I and 137Cs. For the both accidents the ratios of 131I/137Cs in the considered soil samples are in the similar ranges: (3-50) for the Chernobyl samples and (5-70) for the Fukushima samples. Similarly to the Chernobyl accident a clear tendency that the ratio of 131I/137Cs in the fallout decreases with the increase of the ground deposition density of 137Cs within the trace related to a radioactive cloud has been identified for the Fukushima accident. It looks like this is a universal tendency for the ratio of 131I/137Cs versus the 137Cs ground deposition density in the fallout along the trace of a radioactive cloud as a result of a heavy accident at the NPP with radionuclides releases into the environment. This tendency is important for an objective reconstruction of 131I fallout based on the results of 137Cs measurements of soil samples carried out at late dates after the Fukushima accident.

The use of gallium-67 scintigraphy to monitor tumor response rates and predict long-term clinical outcome in patients with lymphoma.

The aim of this study was to determine whether gallium (Ga)-67 scintigraphy can monitor the treatment response rates and predict the long-term clinical outcome in patients with lymphoma. Gallium-67 scintigraphy was performed upon admission (baseline Ga) in 33 consecutive, newly diagnosed patients. Twenty-eight patients (Hodgkin's disease, n = 18; non-Hodgkin's lymphoma, n = 13) with Ga avid tumors were included in the study. All the patients were treated with induction chemotherapy. Gallium-67 scintigraphy was performed in all patients after the first cycle of chemotherapy (post-cycle 1 Ga) and repeated after the fourth cycle (post-cycle 4 Ga) or after completion of treatment (end-of-chemotherapy Ga). Nineteen patients had a fast response (68%, negative in post-cycle 1 and end-of-chemotherapy Ga), 4 intermediate response (14%, partial positive post-cycle 1 Ga that progressed to negative post-cycle 4 Ga), 3 slow response (11%, partial positive in both post-cycle 1 and post-cycle 4 Ga) and 2 no response (7%, positive in both post-cycle 1 and end-of-chemotherapy Ga). In patients who had either fast or intermediate response, 22 (96%) were free of disease at a median follow-up period of 30 months (range, 11-45 months). All 5 patients (100%) who had slow or no response had progressive disease or residual disease. In conclusion, the findings indicate that Ga could effectively be used to monitor the treatment response rates and predict the long-term clinical outcome in patients with lymphoma and should be used in treatment modifications aimed at reducing toxicity of effective therapy in patients with fast response and replacing treatments early in patients with slow or no response.