Towards control over redox behaviour and ionic conductivity in LiTi2(PO4)(3) fast lithium-ion conductor

[EN] The location of redox couples in transition metal compounds is among the key factors that determine their applicability. AM2(PO4)3 NASICONs (A ¿ Na, Li; M ¿ Ti, Zr, Hf, Ge, Sn, Fe, ¿) form an intriguing group that feature fast ion diffusion and tunable reduction/oxidation potentials and can therefore find numerous applications. The present study focuses on the LiTi2(PO4)3 member of this family and the possibility of controlling its transport and redox properties. It highlights the close relationship between the modification of the crystal and band structures via substitutions in the Ti sublattice or intercalation with lithium and its redox behaviour as well as transport properties. The correlation between ionic conductivity and the position of the Ti4þ/Ti3þ redox potential is discussed. UV-VIS reflectance spectra revealed a significant impact of the type of dopant as well as the level of intercalation on the position of the fundamental absorption edge, indicating the possibility of modifying the electronic structure. In the case of some of the examined dopants (Nb, Sn, In), more complex interaction was observed, since they introduce their own redox activity, and thus enable the material's behaviour to be modified even further.This work was funded by the National Science Centre of Poland as part of the grant no. 2012/05/D/ST5/00472.Zajac, W.; Tarach, M.; Trenczek-Zajac, A. (2017). Towards control over redox behaviour and ionic conductivity in LiTi2(PO4)(3) fast lithium-ion conductor. Acta Materialia. 140:417-423. https://doi.org/10.1016/j.actamat.2017.08.064S41742314

Determining the Probability of Unproductive Manipulations in Inland Intermodal Terminal Operations

The paper concerns the method of determining the probability of unproductive manipulations during operations, maintenance or repairs on an inland intermodal terminal. The method is mathematically based on the semi-Markov process. The developed method enables revision of unproductive manipulation frequency and duration. It provides an opportunity to analyse and change inland terminal operations so as to increase productivity

Inhibition of protein disulfide isomerase induces differentiation of acute myeloid leukemia cells

Acute myeloid leukemia is a malignant disease of immature myeloid cells. Despite significant therapeutic effects of differentiation-inducing agents in some acute myeloid leukemia subtypes, the disease remains incurable in a large fraction of patients. Here we show that SK053, a thioredoxin inhibitor, induces differentiation and cell death of acute myeloid leukemia cells. Considering that thioredoxin knock-down with short hairpin RNA failed to exert antiproliferative effects in one of the acute myeloid leukemia cell lines, we used a biotin affinity probe-labeling approach to identify potential molecular targets for the effects of SK053. Mass spectrometry of proteins precipitated from acute myeloid leukemia cells incubated with biotinylated SK053 used as a bait revealed protein disulfide isomerase as a potential binding partner for the compound. Biochemical, enzymatic and functional assays using fluorescence lifetime imaging confirmed that SK053 binds to and inhibits the activity of protein disulfide isomerase. Protein disulfide isomerase knockdown with short hairpin RNA was associated with inhibition of cell growth, increased CCAAT enhancer-binding protein α levels, and induction of differentiation of HL-60 cells. Molecular dynamics simulation followed by the covalent docking indicated that SK053 binds to the fourth thioredoxin-like domain of protein disulfide isomerase. Differentiation of myeloid precursor cells requires the activity of CCAAT enhancer-binding protein α, the function of which is impaired in acute myeloid leukemia cells through various mechanisms, including translational block by protein disulfide isomerase. SK053 increased the levels of CCAAT enhancer-binding protein α and upregulated mRNA levels for differentiation-associated genes. Finally, SK053 decreased the survival of blasts and increased the percentage of cells expressing the maturation-associated CD11b marker in primary cells isolated from bone marrow or peripheral blood of patients with acute myeloid leukemia. Collectively, these results provide a proof-of-concept that protein disulfide isomerase inhibition has potential as a therapeutic strategy for the treatment of acute myeloid leukemia and for the development of small-molecule inhibitors of protein disulfide isomerase

GPR54 (KISS1R) Transactivates EGFR to Promote Breast Cancer Cell Invasiveness

Kisspeptins (Kp), peptide products of the Kisspeptin-1 (KISS1) gene are endogenous ligands for a G protein-coupled receptor 54 (GPR54). Previous findings have shown that KISS1 acts as a metastasis suppressor in numerous cancers in humans. However, recent studies have demonstrated that an increase in KISS1 and GPR54 expression in human breast tumors correlates with higher tumor grade and metastatic potential. At present, whether or not Kp signaling promotes breast cancer cell invasiveness, required for metastasis and the underlying mechanisms, is unknown. We have found that kisspeptin-10 (Kp-10), the most potent Kp, stimulates the invasion of human breast cancer MDA-MB-231 and Hs578T cells using Matrigel-coated Transwell chamber assays and induces the formation of invasive stellate structures in three-dimensional invasion assays. Furthermore, Kp-10 stimulated an increase in matrix metalloprotease (MMP)-9 activity. We also found that Kp-10 induced the transactivation of epidermal growth factor receptor (EGFR). Knockdown of the GPCR scaffolding protein, β-arrestin 2, inhibited Kp-10-induced EGFR transactivation as well as Kp-10 induced invasion of breast cancer cells via modulation of MMP-9 secretion and activity. Finally, we found that the two receptors associate with each other under basal conditions, and FRET analysis revealed that GPR54 interacts directly with EGFR. The stability of the receptor complex formation was increased upon treatment of cells by Kp-10. Taken together, our findings suggest a novel mechanism by which Kp signaling via GPR54 stimulates breast cancer cell invasiveness

Chronic Ingestion of Sodium and Potassium Bicarbonate, with Potassium, Magnesium and Calcium Citrate Improves Anaerobic Performance in Elite Soccer Players

Anaerobic power and anaerobic capacity significantly influence performance in many sport disciplines. These include prolonged sprints in athletics, swimming, or cycling, and other high intensity intermittent sports, such as soccer or basketball. Considering the association of exercise-induced acidosis and fatigue, the ingestion of potential buffering agents such as sodium bicarbonate, has been suggested to attenuate metabolic acidosis and improve anaerobic performance. Since elite soccer players cover from 200 to 350 m while sprinting, performing 40⁻60 all out sprints during a game, it seems that repeated sprint ability in soccer players is among the key components of success. In our experiment, we evaluated the effectiveness of chronic supplementation with sodium and potassium bicarbonate, fortified with minerals, on speed and speed endurance in elite soccer players. Twenty-six soccer players participated in the study. The subjects were randomly divided into two groups. The experimental group was supplemented with sodium bi-carbonate and potassium di-carbonate fortified with minerals, while the control group received a placebo. The athletes were tested at baseline and after nine days of supplementation. Anaerobic performance was evaluated by the Repeated Anaerobic Sprint Test (RAST) protocol which involved 6 × 30 m max sprints, separated by 10 s of active recovery. Resting, post ingestion and post exercise concentrations of HCO3− and blood pH were measured as well as lactate concentration. The current investigation demonstrated a significant increase in RAST performance of elite soccer players supplemented with sodium and potassium bicarbonate along with calcium phosphate, potassium citrate, and magnesium citrate ingested twice a day over a nine-day training period. The improvements in anaerobic performance were caused by increased resting blood pH and bicarbonate levels