We comment on phase selection of the scattering amplitude, emphasizing that the elastic overlap function should have a central impact parameter profile at high energies and highlighting the role of ...the reflective scattering mode at the LHC energies. Emerging problems with the use of peripheral impact parameter dependence of the elastic overlap function are explicitly indicated. Their solution is an elimination of the phases connected to peripheral form of the elastic overlap function. Contrary, we adhere to a relative peripheral form of the inelastic overlap function with an additional new feature of a maximum at nonzero value of the impact parameter at the highest energies. Phenomenologically, the dynamics of hadron scattering is motivated by a hadron structure with a hard central core presence.
The recently identified ferroptotic cell death is characterized by excessive accumulation of hydroperoxy-arachidonoyl (C20:4)- or adrenoyl (C22:4)- phosphatidylethanolamine (Hp-PE). The ...selenium-dependent glutathione peroxidase 4 (GPX4) inhibits ferroptosis, converting unstable ferroptotic lipid hydroperoxides to nontoxic lipid alcohols in a tissue-specificmanner. While placental oxidative stress and lipotoxicity are hallmarks of placental dysfunction, the possible role of ferroptosis in placental dysfunction is largely unknown. We found that spontaneous preterm birth is associated with ferroptosis and that inhibition of GPX4 causes ferroptotic injury in primary human trophoblasts and during mouse pregnancy. Importantly, we uncovered a role for the phospholipase PLA2G6 (PNPLA9, iPLA2beta), known to metabolize Hp-PE to lyso-PE and oxidized fatty acid, in mitigating ferroptosis induced by GPX4 inhibition in vitro or by hypoxia/reoxygenation injury in vivo. Together, we identified ferroptosis signaling in the human and mouse placenta, established a role for PLA2G6 in attenuating trophoblastic ferroptosis, and provided mechanistic insights into the ill-defined placental lipotoxicity that may inspire PLA2G6-targeted therapeutic strategies.
Were conducted a series of experiments, the purpose of which had to verify the mathematical model of the radiation environment sensor. Theoretical values of the beta particles count rate from 90Sr - ...90Y source registered by radiation environment sensor was compared with the experimental one. Theoretical (calculated) count rate of beta particles was found with using the developed mathematical model of the radiation environment sensor. Deviation of the calculated values of the beta particle count rate does not exceed 10% from the experimental.
We fabricated neutron detectors based on thin epitaxial CVD diamond films grown on single crystal diamond substrates, with a buried graphitic electrode produced by ion implantation and annealing. The ...spectra of 5.5 MeV alpha particles were measured with ≈3.5% energy resolution, and, based on the features of those spectra, a precise assessment of the film thickness was able achieved. A 10 μm thick detector was tested for 252Cf neutron and γ-radiation source, using 10B and 6Li isotopes as converters. Due to the small film thickness the contribution from the γ-quanta background to the spectra was restricted by energies below 200 keV, and could be easily discriminated from the neutron related signals. The performance of the detectors was tested for 5.5 MeV α-particles at fluences up to 109cm−2, and no detrimental polarization effect was observed for the best sample.
Ferroptosis is a non-apoptotic form of cell death induced by small molecules in specific tumour types, and in engineered cells overexpressing oncogenic RAS. Yet, its relevance in non-transformed ...cells and tissues is unexplored and remains enigmatic. Here, we provide direct genetic evidence that the knockout of glutathione peroxidase 4 (Gpx4) causes cell death in a pathologically relevant form of ferroptosis. Using inducible Gpx4(-/-) mice, we elucidate an essential role for the glutathione/Gpx4 axis in preventing lipid-oxidation-induced acute renal failure and associated death. We furthermore systematically evaluated a library of small molecules for possible ferroptosis inhibitors, leading to the discovery of a potent spiroquinoxalinamine derivative called Liproxstatin-1, which is able to suppress ferroptosis in cells, in Gpx4(-/-) mice, and in a pre-clinical model of ischaemia/reperfusion-induced hepatic damage. In sum, we demonstrate that ferroptosis is a pervasive and dynamic form of cell death, which, when impeded, promises substantial cytoprotection.
Ferroptosis is a programmed iron-dependent cell death associated with peroxidation of lipids particularly, phospholipids. Several studies suggested a possible contribution of mitochondria to ...ferroptosis although the mechanisms underlying mitochondria-mediated ferroptotic pathways remain elusive. Reduced glutathione (GSH) is a central player in ferroptosis that is required for glutathione peroxidase 4 to eliminate oxidized phospholipids. Mitochondria do not produce GSH, and although the transport of GSH to mitochondria is not fully understood, two carrier proteins, the dicarboxylate carrier (DIC, SLC25A10) and the oxoglutarate carrier (OGC, SLC25A11) have been suggested to participate in GSH transport. Here, we elucidated the role of DIC and OGC as well as mitochondrial bioenergetics in ferroptosis in H9c2 cardioblasts. Results showed that mitochondria are highly sensitive to ferroptotic stimuli displaying fragmentation, and lipid peroxidation shortly after the onset of ferroptotic stimulus. Inhibition of electron transport chain complexes and oxidative phosphorylation worsened RSL3-induced ferroptosis. LC-MS/MS analysis revealed a dramatic increase in the levels of pro-ferroptotic oxygenated phosphatidylethanolamine species in mitochondria in response to RSL3 (ferroptosis inducer) and cardiac ischemia-reperfusion. Inhibition of DIC and OGC aggravated ferroptosis and increased mitochondrial ROS, membrane depolarization, and GSH depletion. Dihydrolipoic acid, an essential cofactor for several mitochondrial multienzyme complexes, attenuated ferroptosis and induced direct reduction of pro-ferroptotic peroxidized phospholipids to hydroxy-phospholipids in vitro. In conclusion, we suggest that ferroptotic stimuli diminishes mitochondrial bioenergetics and stimulates GSH depletion and glutathione peroxidase 4 inactivation leading to ferroptosis.
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•Cardiac mitochondria demonstrate an early response to ferroptotic stimulus.•RSL3 induces accumulation of ferroptotic PEox species in cardiac mitochondria.•Inhibition of DIC and OGC aggravates ferroptosis and increases mtROS, ΔΨm loss, and mitochondrial GSH depletion.•DHLA exerts anti-ferroptotic effects and eliminates PEox in vitro.
•Two ligands with antioxidant moieties and six complexes on their base were synthesized.•The antioxidant properties of compounds were studied.•Cytotoxity on cancer cell lines and tumor samples from ...patients was estimated.•Lead compound demonstrated IC50 = 6 nM on MCF-7 cell line.•Plausible cytotoxicity mechanism is related to promotion of tubulin polymerization.
A series of novel imidazole-containing ligands and their organotin complexes were synthesized and characterized by NMR, IR, MALDI and elemental analysis. Redox behavior was studied by cyclic voltammetry (CV). Antioxidant properties were estimated in model reactions of single-electron reduction (CUPRAC-test), scavenging of 2,2-diphenyl-1-picrylhydrazyl (DPPH) and O2−. radical anion, enzymatic oxidation of linoleic acid by lipoxygenase and Fe3+-induced lipid peroxidation of rat liver homogenates. It was found that ligands and complexes both possess radical scavenging activity of prolonged action type. Compounds exhibited notable antioxidant activity in lipid peroxidation. Cytotoxicity was estimated in standard MTT-test on multiple cell lines. Compounds demonstrated high toxicity on colon carcinoma and breast cancer cells and based on obtained data, lead compound was proposed. Additional assays were carried out for the lead compound, including regular MTT-test on cancer cells possessing various resistant mechanisms and modified MTT-test on tumor tissue samples, obtained from patients as well as apoptosis and cell cycle studies. All organotin complexes were also studied for their influence on tubulin polymerization. It was demonstrated that obtained compounds demonstrate unorthodox activity, promoting microtubules assembly rate instead of inhibiting it. Significant influence of compound 5 on G2/M phase of cell cycle is in accordance with influence on tubulin polymerization and lets us to mark synthesized compounds as mitotic poisons. The results open up the scopes for the search of novel antitumor agents for treatment of advanced forms of cancer.
Novel organotin complexes with 2,6-di‑tert-butylphenol moieties were synthesized. Antioxidant activity of prolonged action type was demonstrated. Introduction of cytoprotective group into organotins leads to attenuation of cytotoxicity of resulting pharmacologically active agents. Display omitted
Gadolinium orthoniobate ceramics, GdNbO4, were prepared by a conventional solid state reaction method. The synthesized sample was characterized by means of X-ray diffraction and μ-X-ray fluorescence ...spectrometry methods. The temperature dependence of the heat capacity of GdNbO4 was first measured by relaxation, adiabatic and differential scanning calorimetry in the temperature range of 4–1308 K. The high-temperature enthalpy increments of GdNbO4 were measured by drop calorimetry between 434 and 1745 K. A small step-like change in the Cp,m(T) associated with a fergusonite-to-scheelite phase transition was detected. The temperature of a second order phase transition was determined to be 1078 K. Based on the fitted values of the Cp,m(T), the thermodynamic functions (entropy, enthalpy change and Gibbs energy) were calculated in the range from T→0–1750 K.
•The heat capacity of GdNbO4 was first measured over a temperature range of 4–1308 K.•High-temperature enthalpy increments (434–1745 K) were obtained by drop calorimetry.•The second order phase transition was detected by DSC.•Thermodynamic properties of GdNbO4 were calculated from 0 K to 1750 K.
A preliminary conformational analysis of chemical reactions of functional groups in Polikon K was performed. Five mechanisms for chemical reactions of polyacrylonitrile fibers with amines were ...identified. The level of steric energy was estimated preliminarily as a characteristic of the heterostructure strain. A general scheme for calculating the potential energy of the Polikon K molecular system was based on Allinger force field concepts.
The mercury test is a rapid and widely used method for distinguishing truly homogeneous molecular catalysis from nanoparticle metal catalysis. In the current work, using various M0 and MII complexes ...of palladium and platinum that are often used in homogeneous catalysis as examples, we demonstrated that the mercury test is generally inadequate as a method for distinguishing between homogeneous and cluster/nanoparticle catalysis mechanisms for the following reasons: (i) the general and facile reactivity of both molecular M0 and MII complexes toward metallic mercury and (ii) the very high and often unpredictable dependence of the test results on the operational conditions and the inability to develop universal quantitatively defined operational parameters. Two main types or mercury-induced transformations, the cleavage of M0 complexes and the oxidative–reductive transmetalation of MII complexes, including a reaction of highly popular MII/NHC complexes, were elucidated using NMR, ESI-MS, and EDXRF techniques. A mechanistic picture of the reactions involving metal complexes was revealed with mercury, and representative metal species were isolated and characterized. Even in an attempt to not overstate the results, one must note that the use of the mercury tests often leads to inaccurate conclusions and complicates the mechanistic studies of these catalytic systems. As a general concept, distinguishing reaction mechanisms (homogeneous vs cluster/nanoparticle) by using catalyst poisoning requires careful rethinking in the case of dynamic catalytic systems.
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