Heterogeneous and mechanochemical syntheses of new materials based on titanium, calcium, and magnesium phosphates were developed for the first time. The products demonstrated high efficiency as sorbents for the removal of heavy metal cations and radionuclides from solutions. The joint action of the sorption components ensures high sorption capacity towards various cations over a wide pH range. The optimal conditions providing products with a specified phase composition were identified. The use of a solution of a phosphorus-containing agent and solid precursors taken in a stoichiometric ratio, together with mild hydrothermal conditions make it possible to minimize the amount of liquid waste. In the first step of the synthesis, precipitation of titanium phosphate and formation of the precursor needed for the second step (formation of calcium and magnesium phosphates) take place simultaneously. Thus, the synthesis protocol complies with the green chemistry principles.

Transketolase (TKT) is an essential thiamine diphosphate (ThDP)-dependent enzyme of the non-oxidative branch of the pentose phosphate pathway, with the glucose-6P flux through the pathway regulated in various medically important conditions. Here, we characterize the brain TKT regulation by acylation in rats with perturbed thiamine-dependent metabolism, known to occur in neurodegenerative diseases. The perturbations are modeled by the administration of oxythiamine inhibiting ThDP-dependent enzymes in vivo or by reduced thiamine availability in the presence of metformin and amprolium, inhibiting intracellular thiamine transporters. Compared to control rats, chronic administration of oxythiamine does not significantly change the modification level of the two detected TKT acetylation sites (K6 and K102) but doubles malonylation of TKT K499, concomitantly decreasing 1.7-fold the level of demalonylase sirtuin 5. The inhibitors of thiamine transporters do not change average levels of TKT acylation or sirtuin 5. TKT structures indicate that the acylated residues are distant from the active sites. The acylations-perturbed electrostatic interactions may be involved in conformational shifts and/or the formation of TKT complexes with other proteins or nucleic acids. Acetylation of K102 may affect the active site entrance/exit and subunit interactions. Correlation analysis reveals that the action of oxythiamine is characterized by significant negative correlations of K499 malonylation or K6 acetylation with TKT activity, not observed upon the action of the inhibitors of thiamine transport. However, the transport inhibitors induce significant negative correlations between the TKT activity and K102 acetylation or TKT expression, absent in the oxythiamine group. Thus, perturbations in the ThDP-dependent catalysis or thiamine transport manifest in the insult-specific patterns of the brain TKT malonylation and acetylations.

Recently, there has been increasing evidence in favor of prenatal programming influence on the development of many diseases in adults, including cardiovascular pathologies. However, the mechanisms underlying the programming effect of developing cardiovascular dysfunction remain unclear, which prevents timely diagnosis and identification of potential clinical therapy. The aim of this study was to evaluate the effects of acute hypoxia during early organogenesis on heart rhythm formation and its regulation in early postnatal development in rats. It was shown that acute hypoxia suffered by rat pups on day 10 of intrauterine development did not change the overall dynamics of heart rhythm formation in the first month of the postnatal period. However, the experimental animals showed lower heart rate compared to control in the first weeks of life in addition to higher values of rhythm variability and the RMSSD index (root mean square of successive differences in RR intervals) indicating an expressed tone of parasympathetic department of the ANS. Moreover, in the first week of life, the basic heart rate following pharmacological blockade of sympathetic and parasympathetic cardiotropic nervous influences in rats suffering from prenatal hypoxia turned out to be 15

Risk factors associated with environmental exposure, especially during critical periods of intrauterine development, affect fetal development and increase the risk of certain diseases in adulthood including cardiovascular diseases (CVD). Hypoxia is considered the most common and clinically significant form of intrauterine stress that causes systemic pathological changes, in 78% of cases associated with cardiovascular system disorders. The purpose of this study was to evaluate the effects of acute hypoxia on the 10th day of gestation on heart rate and its regulation in rats' offspring of prepubescent and pubertal age, as well as to analyze the dependence of resulting disorders on gender. By the beginning of puberty the heart rate of rats survived prenatal hypoxia was significantly higher than in control accompanied by significant decrease in heart rate variability (dX) which naturally leads to stress index (SI) increase indicating growing sympathetic activity in heart rhythm regulation. At the same time the base heart rate in animals suffered intrauterine hypoxia turned out to be lower than in control. The fact that matured animals of both sexes, survived intrauterine hypoxia in early organogenesis, also show changes in dX and SI indicates long-term and irreversible disorders in heart rhythm regulation. Thus hypoxia during early organogenesis is of a programming nature potentially increasing the risk of developing CVD in adult animals. Moreover the autonomic system balance shift towards the activation of sympathetic tone was more pronounced in females making them more vulnerable to the risk of developing cardiac pathology in puberty.

Sorbents based on Ti–Ca–Mg phosphates were synthesized, their physicochemical and sorption properties towards Cs(I), Sr(II), Co(II) (in the form of both stable ions and radionuclides 137 Cs, 60 Co, 90 Sr) were investigated. Samples of TiCaMg-1 and TiCaMg-2 were prepared by heterogeneous interaction of acidic and tertiary Ca–Mg phosphates with a solution of titanyl-diammonium sulfate, and a sample of TiCaMg-3 was prepared by heat-treated dolomite with a preliminarily precipitated suspension of titanium hydrogen phosphate. It was shown that the samples have a high affinity for Cs + , Sr 2+ , Co 2+ ions and their radionuclides. The TiCaMg-3 sample has the highest distribution coefficients for 137 Cs, 60 Co, and 90 Sr radionuclides (>10 5 mL/g). It was established that the difference in the properties of composites is due to their phase and chemical composition, as well as textural characteristics (specific surface area, sorption volume, and pore size). The TiCaMg-3 sorbent is characterized by the largest sorption volume (0.410 cm 3 /g) and average pore diameter (10.2 nm), which provides better accessibility of ionogenic groups during exchange reactions.

Epilepsy is characterized by recurrent seizures due to a perturbed balance between glutamate and GABA neurotransmission. Our goal is to reveal the molecular mechanisms of the changes upon repeated challenges of this balance, suggesting knowledge-based neuroprotection. To address this goal, a set of metabolic indicators in the post-seizure rat brain cortex is compared before and after pharmacological kindling with pentylenetetrazole (PTZ). Vitamins B1 and B6 supporting energy and neurotransmitter metabolism are studied as neuroprotectors. PTZ kindling increases the seizure severity (1.3 fold, p < 0.01), elevating post-seizure rearings (1.5 fold, p = 0.03) and steps out of the walls (2 fold, p = 0.01). In the kindled vs. non-kindled rats, the post-seizure p53 level is increased 1.3 fold (p = 0.03), reciprocating a 1.4-fold (p = 0.02) decrease in the activity of 2-oxoglutarate dehydrogenase complex (OGDHC) controlling the glutamate degradation. Further, decreased expression of deacylases SIRT3 (1.4 fold, p = 0.01) and SIRT5 (1.5 fold, p = 0.01) reciprocates increased acetylation of 15 kDa proteins 1.5 fold (p < 0.01). Finally, the kindling abrogates the stress response to multiple saline injections in the control animals, manifested in the increased activities of the pyruvate dehydrogenase complex, malic enzyme, glutamine synthetase and decreased malate dehydrogenase activity. Post-seizure animals demonstrate correlations of p53 expression to the levels of glutamate (r = 0.79, p = 0.05). The correlations of the seizure severity and duration to the levels of GABA (r = 0.59, p = 0.05) and glutamate dehydrogenase activity (r = 0.58, p = 0.02), respectively, are substituted by the correlation of the seizure latency with the OGDHC activity (r = 0.69, p < 0.01) after the vitamins administration, testifying to the vitamins-dependent impact of the kindling on glutamate/GABA metabolism. The vitamins also abrogate the correlations of behavioral parameters with seizure duration (r 0.53–0.59, p < 0.03). Thus, increased seizures and modified post-seizure behavior in rats after PTZ kindling are associated with multiple changes in the vitamin-dependent brain metabolism of amino acids, linked to key metabolic regulators: p53, OGDHC, SIRT3 and SIRT5.

The highly alkaline multicomponent systems TiO2–H2SO4–Na2SiO3–NaOH–H2O and TiO2–H2SO4–(NH4)2SO4–Na2SiO3–NaOH–H2O have been studied under conditions of hydrothermal synthesis, which gives new products with specified technical properties. It has been shown that, by a targeted selection of structure-forming components, in particular, titanium compounds, together with optimal parameters of hydrothermal treatment of the formed precursor, one can obtain compounds with given chemical composition and particle size and morphology. It has been found that the rate of structural transformations in the synthesis depends on the phase composition of titanosilicate precursors. Their hydrothermal treatment involves the alkaline and thermal hydrolysis followed by dehydration of the hydrolyzed phases of titanium(IV) and silicon. This is accompanied by the localization of free bonds ensuring the formation of Ti–O–Si–O bridges and their subsequent transformation into new structured species.

Sorption properties of titanium phosphate ion-exchanger (Li-TiOP) towards Cu2+, Co2+, Mn2+, Ni2+ and Cr3+ ions in saturated LiNO3 solution were investigated. Solid samples were characterized by XRD, SEM, TG, DSC, NGSP and elemental analysis. Concentrations of elements in the solutions were determined by AAS and ICP MS methods. The adsorption isotherms for studied metal ions were calculated using the Langmuir, Freundlich, Temkin and Nikolsky models. Necessity for allowing for the solvated state of the sorbate is shown in studying the sorption of metal ions. Selectivity of Li-TiOP towards studied ions is found to be described in the following order of Cr3+ > Cu2+ > Mn2+ > Co2+ > Ni2+ for all models. The change in the thermodynamic parameters of the sorption process is associated with that in the ionic potential of the sorbent. Titanium phosphate effectively removes trace concentrations of metal ions from multi-component solutions, resulting in achievement of LiNO3 purity level of > 99.999 wt.%.

Синтезированы сорбенты на основе фосфатов Ti-Ca-Mg, изучены их физико-химические и сорбционные свойства по отношению к Cs(I), Sr(II), Co(II) (в виде как стабильных ионов, так и радионуклидов 137 Cs, 60 Co, 90 Sr). Образцы TiCaMg-1 и TiCaMg-2 получали путем гетерогенного взаимодействия кислых и средних фосфатов Ca-Mg с раствором сульфата титанил-диаммония, а образец TiCaMg-3 - термообработанного доломита с предварительно осажденной суспензией кислого фосфата титана. Показано, что полученные образцы обладают высоким сродством к ионам Cs + , Sr 2+ , Co 2+ и их радионуклидам. Образец TiCaMg-3 имеет наиболее высокие значения коэффициента распределения радионуклидов 137 Cs, 60 Co и 90 Sr (>10 5 см 3 /г). Установлено, что различие в свойствах композитов обусловлено их фазовым и химическим составом, а также текстурными характеристиками (удельная поверхность, сорбционный объем и размер пор). Сорбент TiCaMg-3 характеризуется наибольшим сорбционным объемом (0.410 см 3 /г) и средним диаметром пор (10.2 нм), что обеспечивает лучшую доступность ионогенных групп при обменных реакциях.

Разработан новый высокоэффективный метод получения тонкодисперсного порошка LiCoPO 4 с заданной морфологией из аммоний замещенного прекурсора NH 4 CoPO 4 ⋅H 2 O в расплаве нитрата лития. Показано, что морфология полученного продукта определяется морфологией используемого прекурсора и зависит от физико-химических условий его получения. Полученный LiCoPO 4 , а также его прекурсоры охарактеризованы методами РФА, СЭМ, БЭТ. Проведенные электрохимические испытания показали, что полученный порошок является электрохимически активным. Катодный материал на основе полученного LiCoPO 4 показал высокую удельную разрядную емкость 110 мА ч/г при плотности тока, соответствующей скорости заряда/разряда 1С, что обусловлено высокой дисперсностью и пластинчатой морфологией частиц синтезированного порошка. Предложенный метод отличается быстротой получения целевого продукта и не требует применения дорогостоящего оборудования, а также дополнительных стадий высокотемпературной кристаллизации и измельчения и может быть масштабирован до промышленного применения.

The paper presents a new low-temperature method for the synthesis of highly dispersed powders of double phosphates LiCoPO4 and LiNiPO4 using low-waste technology. It has been shown that the morphology and particle size of the obtained materials depend on the type of initial precursors. The obtained compounds are characterized by elemental, XRD, SEM, cyclic volammetry, cyclic chronopotentiometry analyses. A new approach to the synthesis of submicron powders of lithium double phosphates and transition metal (nickel, cobalt) is more effective compared to current methods.

Pilot-plant testing of a laboratory technology for producing alkaline titanosilicate sorbent from the current titanium-containing technogenic waste from the enrichment of the Khibiny apatite–nepheline ore shows that this technology can be modeled on an enlarged (pilot-plant) scale. The parameters of the main technological operations in systems of various salt compositions are checked and optimized. For example, in the ammonium sulfate systems, a two-phase precipitate is formed, which consists of phases similar to the minerals zorite and ivanyukite at their weight ratio of about 1 : 0.8–1.0. A one-phase precipitate in the form of ivanukite crystals is formed in the sulfate system. A study of the technical and sorption properties characterized in the tests of sorbents finds that the absorption of the Cs + cation is due to the substitution for the Na + cation in the interframework space of the crystal. The Sr 2+ cation is also substituted for Na + and is additionally deposited on the sorbent particles due to the alkaline reaction of its surface. The sorption capacities of powder and granules for Sr 2+ are, on average, 170 and 160 mg g –1 , respectively; and for Cs+, 275 and 245 mg g –1 , respectively. Tests will be continued as pilot batches of the sorbent with stable structure and properties are produced for testing in specialized organizations.

The paper presents a new low-temperature method for the synthesis of fine powders of double phosphates LiCoPO 4 and LiNiPO 4 using a low-waste technology. It has been shown that the morphology and particle size distribution of the synthesized materials are determined by the type of precursor used. The resulting compounds are characterized by chemical analysis, X-ray powder diffraction analysis, scanning electron microscopy, cyclic voltammetry, and cyclic chronopotentiometry. The new approach to the synthesis of submicron powders of lithium and transition metal (nickel or cobalt) double phosphates is more efficient than the existing conventional methods.

A new and highly efficient way of obtaining finely dispersed LiCoPO 4 powder is developed with a given morphology from ammonium substituted precursor NH 4 CoPO 4 ⋅H 2 O in a lithium nitrate melt. It is shown that the morphology of the obtained product is determined by the morphology of the used precursor and depends on the physicochemical conditions of its preparation. The obtained LiCoPO 4 and its precursors are characterized by means of XRD, SEM, and BET. Electrochemical tests show the resulting powder is electrochemically active. Cathode material based on the obtained LiCoPO 4 shows a high specific discharge capacity of 110 mA h/g at a current density corresponding to a charge/discharge rate of 1C, due to the high dispersion and lamellar morphology of the particles of the synthesized powder. The proposed procedure is characterized by the speed of obtaining the target product. It does not require the use of expensive equipment or additional stages of high-temperature crystallization and grinding, and can be scaled up to industrial use.

Hypoxia is damaging to the fetus, but the developmental impact may vary, with underlying molecular mechanisms unclear. We demonstrate the dependence of physiological and biochemical effects of acute prenatal hypoxia (APH) on sex and gestational age. Compared to control rats, APH on the 10th day of pregnancy (APH-10) increases locomotion in both the male and female offspring, additionally increasing exploratory activity and decreasing anxiety in the males. Compared to APH-10, APH on the 20th day of pregnancy (APH-20) induces less behavioral perturbations. ECG is changed similarly in all offspring only by APH-10. Sexual dimorphism in the APH outcome on behavior is also observed in the brain acetylation system and 2-oxoglutarate dehydrogenase reaction, essential for neurotransmitter metabolism. In view of the perturbed behavior, more biochemical parameters in the brains are assessed after APH-20. Of the six enzymes, APH-20 significantly decreases the malic enzyme activity in both sexes. Among 24 amino acids and dipeptides, APH-20 increases the levels of only three amino acids (Phe, Thr, and Trp) in male offspring, and of seven amino acids (Glu, Gly, Phe, Trp, Ser, Thr, Asn) and carnosine in the female offspring. Thus, a higher reactivity of the brain metabolism to APH stabilizes the behavior. The behavior and brain biochemistry demonstrate sexually dimorphic responses to APH at both gestational stages, whereas the APH effects on ECG depend on gestational age rather than sex.

Abnormal energy expenditure during seizures and metabolic regulation through post-translational protein acylation suggest acylation as a therapeutic target in epilepsy. Our goal is to characterize an interplay between the brain acylation system components and their changes after seizures. In a rat model of pentylenetetrazole (PTZ)-induced epilepsy, we quantify 43 acylations in 29 cerebral cortex proteins; levels of NAD+; expression of NAD+-dependent deacylases (SIRT2, SIRT3, SIRT5); activities of the acyl-CoA-producing/NAD+-utilizing complexes of 2-oxoacid dehydrogenases. Compared to the control group, acylations of 14 sites in 11 proteins are found to differ significantly after seizures, with six of the proteins involved in glycolysis and energy metabolism. Comparing the single and chronic seizures does not reveal significant differences in the acylations, pyruvate dehydrogenase activity, SIRT2 expression or NAD+. On the contrary, expression of SIRT3, SIRT5 and activity of 2-oxoglutarate dehydrogenase (OGDH) decrease in chronic seizures vs. a single seizure. Negative correlations between the protein succinylation/glutarylation and SIRT5 expression, and positive correlations between the protein acetylation and SIRT2 expression are shown. Our findings unravel involvement of SIRT5 and OGDH in metabolic adaptation to seizures through protein acylation, consistent with the known neuroprotective role of SIRT5 and contribution of OGDH to the Glu/GABA balance perturbed in epilepsy.

The authors investigated the synthesis of composite materials produced by not simply mix-ing the components mechanically. The materials are chemically derived on the basis that the com-bined action of the beneficial properties of such compositions significantly outweighs the action of each component due to synergistic effects. For this purpose, a titanosilicate precursor, TiO2 center dot nSiO2 (TSP), synthesized from an accessible technogenic waste containing the mineral titanite (CaSiTiO5) was used. Researches were carried out in the heterogeneous system TiO2 center dot SiO2-H3PO4-H2O. And the innovative method was developed for obtaining silicon-containing titanophosphate of the com-position TiOHPO4 center dot 2H2O or TiO(H2PO4)2 center dot 2H2O, depending on the structural features of TSP, as well as on the synthesis conditions -phosphoric acid concentration and temperature. The influence of structural characteristics of titanosilicate precipitate on its chemical activity in heterogeneous synthesis of silicon-containing titanophosphate was studied. The synthesised mesaporous material is a powder with a particle size of 5-15 mu m. The correlation between the phase composition of the synthesised compositions and the surface properties of their particles is shown. The sorption ca-pacity of the obtained titanophosphates in the static mode was determined. In particular, the more titanophosphate phase is in the composition of the composition, the higher are the values of Ssp and Vpore particles and therefore their sorption capacity is higher. When comparing the sorption properties of synthesised and conventional sorbents, ion exchange resins and titanium phos-phates, used for purification of liquid effluents from Sr2+, Cs+, Co2+ cations, comparable indica-tors were obtained. The results have shown that the use of silicon-containing titanium phosphate for the treatment of liquid effluents containing non-ferrous metal cations as well as radionuclides may be promising.

— Intrauterine hypoxia is the most common prenatal risk factor presenting a direct danger not only to the life of the fetus but also to the future postnatal life of the organism. The aim of this study is to reveal an association between fetal hypoxia and oxidative stress as well as to estimate the significance of gestational age and gender for the development of oxidative stress. Pregnant rats were exposed to acute hypoxia on the tenth or 20th day of pregnancy, which corresponds to the first and second trimesters of human pregnancy. In newborn rats on the second day of life and in sexually mature offspring of both sexes on the 60th day of life, the state of antioxidant protection was estimated by the content of nonprotein thiols in the blood and liver homogenate, catalase, and superoxide dismutase activity in the liver homogenate, total antioxidant activity, and ceruloplasmin level in blood plasma as well as by the intensity of lipid peroxidation in blood plasma and liver homogenate. Regardless of the gestational age at which the offspring experienced acute hypoxia numerous changes in the indices of the antioxidant protection system were recorded in newborn rats, indicating in favor of the development of oxidative stress; this can be a cause of neurological and cardiological disorders shown already in adult animals.

Pregnancy in mammals is characterized by an increase in basal oxygen consumption. As it develops, there is an increase in oxidative stress, while the oxidative damage enhances in pregnancy complicated by hypoxic stress. The oxidative stress during prenatal development seems to be one of the key factors in the pathogenesis of most pregnancy disorders, including preterm birth and preeclampsia. The growing demand for oxygen increases either the production of reactive oxygen species or the synthesis of antioxidant defense components. To assess the antioxidant defense activity in rats, the content of nonprotein thiols in the blood and liver homogenate, catalase activity in liver homogenate, superoxide dismutase activity in blood plasma and liver homogenate, total antioxidant capacity in blood plasma, and the intensity of lipid peroxidation in blood plasma and liver homogenate were determined. According to obtained data, a decrease in antioxidant defense activity in blood plasma and liver of females is shown in the prenatal period of normal pregnancy and, particularly, in the same period of pregnancy complicated by hypoxic stress. It can be assumed that changes in blood’s antioxidant defense parameters reflect changes not only in the mother’s body but also in the placenta, providing potential danger to the developing fetus.

The disturbed metabolism of vitamins B1 or B6, which are essential for neurotransmitters homeostasis, may cause seizures. Our study aims at revealing therapeutic potential of vitamins B1 and B6 by estimating the short- and long-term effects of their combined administration with the seizure inductor pentylenetetrazole (PTZ). The PTZ dose dependence of a seizure and its parameters according to modified Racine’s scale, along with delayed physiological and biochemical consequences the next day after the seizure are assessed regarding sexual dimorphism in epilepsy. PTZ sensitivity is stronger in the female than the male rats. The next day after a seizure, sex differences in behavior and brain biochemistry arise. The induced sex differences in anxiety and locomotor activity correspond to the disappearance of sex differences in the brain aspartate and alanine, with appearance of those in glutamate and glutamine. PTZ decreases the brain malate dehydrogenase activity and urea in the males and the phenylalanine in the females. The administration of vitamins B1 and B6 24 h before PTZ delays a seizure in female rats only. This desensitization is not observed at short intervals (0.5–2 h) between the administration of the vitamins and PTZ. With the increasing interval, the pyridoxal kinase (PLK) activity in the female brain decreases, suggesting that the PLK downregulation by vitamins contributes to the desensitization. The delayed effects of vitamins and/or PTZ are mostly sex-specific and interacting. Our findings on the sex differences in sensitivity to epileptogenic factors, action of vitamins B1/B6 and associated biochemical events have medical implications.