Nanofluorides

The present review article covers major aspects of inorganic chemistry of nanofluorides, including methods of their synthesis (thermolysis of the precursors, co-precipitation from solutions, reversed micelle technique, hydro- and solvo-thermal techniques, sol–gel method, etc.), nanochemical effects (enhanced chemical activity, self-organization and self-assembly, non-classical mechanism of the single crystal growth, synthesis of non-equilibrium phases), targeted preparation of 1D, 2D, and 3D nanostructures, surface modification of the nanoparticles, fluoride nanocomposites (glass- and nano-ceramics) as well as applications of nanofluorides.     

Phospholipidomic identification of potential plasma biomarkers associated with type 2 diabetes mellitus and diabetic nephropathy

Type 2 diabetes mellitus (T2DM) and its attendant complications, such as diabetic nephropathy (DN), impose a significant societal and economic burden. The investigation of discovering potential biomarkers for T2DM and DN will facilitate the prediction and prevention of diabetes. Phospholipids (PLs) and their metabolisms are closely allied to nosogenesis and aggravation of T2DM and DN. The aim of this study is to characterize the human plasma phospholipids in T2DM and DN to identify potential biomarkers of T2DM and DN. Normal phase liquid chromatography coupled with time of flight mass spectrometry (NPLC-TOF/MS) was applied to the plasma phospholipids metabolic profiling of T2DM and DN. The plasma samples from control (n = 30), T2DM subjects (n = 30), and DN subjects (n = 52) were collected and analyzed. The significant difference in metabolic profiling was observed between healthy control group and DM group as well as between control group and DN group by the help of partial least squares discriminant analysis (PLS-DA). PLS-DA and one-way analysis of variance (ANOVA) were successfully used to screen out potential biomarkers from complex mass spectrometry data. The identification of molecular components of potential biomarkers was performed on Ion trap-MS/MS. An external standard method was applied to quantitative analysis of potential biomarkers. As a result, 18 compounds in 7 PL classes with significant regulation in patients compared with healthy controls were regarded as potential biomarkers for T2DM or DN. Among them, 3 DM-specific biomarkers, 8 DN-specific biomarkers and 7 common biomarkers to DM and DN were identified. Ultimately, 2 novel biomarkers, i.e., PI C18:0/22:6 and SM dC18:0/20:2, can be used to discriminate healthy individuals, T2DM cases and DN cases from each other group.     

Bioanalytical method validation,biopharmaceutical and pharmacokinetic evaluation of GSK-650394, a serum- and glucocorticoid-regulated kinase 1 inhibitor

GSK-650394 is an inhibitor of serum- and glucocorticoid-regulated kinase 1 that displays potency for treating cancer, hypertension, cardiovascular and neuronal diseases, such as Parkinson’s disease. However, the biopharmaceutical properties and pharmacokinetics of GSK-650394 have not been studied extensively. Also, there are currently no bioanalytical assays available for this new drug candidate. In this study, we developed a simple and sensitive liquid chromatography-tandem mass spectrometry method to quantify GSK-650394 in rat plasma and validated its selectivity, linearity, accuracy and precision, sensitivity, matrix effects, extraction recovery, and stability, following the United States Food and Drug Administration guidelines. In vitro studies showed the biopharmaceutical properties of GSK-650394, including its low solubility in water and simulated gastrointestinal fluids, passive transport in Caco-2 cell monolayers, high plasma protein binding, and primary metabolism by glucuronide conjugation in the small intestine and liver of rats. Following intravenous administration (2 mg/kg) to rats, GSK-650394 exhibited low total clearance (11.18 ± 1.28 mL/min/kg) and volume of distribution at steady-state (346.1 ± 120.6 mL/kg). Following oral administration (2, 5, and 10 mg/kg) to rats, GSK-650394 underwent enterohepatic circulation, with low bioavailability (～9%). The insignificant difference in bioavailability among three oral doses suggests that GSK-650394 may follow linear pharmacokinetics up to an oral dose of 10 mg/kg. In addition, the total form of parent drug and glucuronide conjugate in rat plasma from three oral doses showed a much higher value of area under the plasma concentration versus time curve than the parent drug, indicating that the primary metabolism process of GSK-650394 was glucuronidation. Our findings suggest that the low oral bioavailability of GSK-650394 is associated with its low solubility, instability under acidic gastric conditions, and extensive glucuronidation metabolism.     

Secure communication over RIS-aided underlay CR MIMO wiretap channel without Eve’s CSI

This paper investigates a reconfigurable intelligent surface (RIS)-aided underlay cognitive radio (CR) multiple-input multiple-output (MIMO) wiretap channel where the secondary transmitter (ST) communicates with primary user (PU) and secondary user (SU) in the absence of the eavesdropper’s (Eve’s) channel state information (CSI). To enhance the secrecy performance in CR MIMO wiretap channel, the power of useful signal is minimized at ST, and then the residual power is further utilized to design artificial noise (AN) based on statistical CSI at ST. Specifically, we first optimize the transmit covariance matrix at ST and the diagonal phase-shifting matrix at RIS jointly leveraging large-system approximation results. Then the power allocation for SU is optimized to obtain the minimum transmit power of useful information at ST. Besides, we further design AN with the residual power by aligning it into the null space of the SU channel and thus avert the harmful effects of AN to improve the secure communication quality of SU. Finally, through numerical simulations, we illustrate the effectiveness of the proposed algorithm and validate the existence of a trade-off between the quality-of-service (QoS) at SU and secrecy rate.