Crystal Structural Characteristics and Electrical Properties of (Ba0.7Sr0.3-xCax)(Ti0.9Zr0.1)O3 Ceramics Prepared Using the Citrate Gelation Method.

The electrical properties of (Ba0.7Sr0.3-xCax)(Ti0.9Zr0.1)O3 (0 ≤ x ≤ 0.2) (BSCTZ) ceramics prepared using citrate gelation (CG) method were investigated by substituting Ca2+ ions for the Sr2+ sites based on the structural characteristics of the ceramics. BSCTZ was sintered for 3 h at 1300 °C, lower than the temperature (1550 °C) at which the specimens prepared using the solid-state reaction (SSR) method were sintered, which lasted for 6 h. As the amount of substituted Ca2+ ions increased, the unit cell volume of the BSCTZ decreased because of the smaller ionic radius of the Ca2+ ions compared to the Sr2+ ions. The dielectric constant of BaTiO3-based ceramics is imparted by factors such as the tetragonality and B-site bond valence of the ceramics. Although the ceramic tetragonality increased with Ca2+ ion substitution, the x = 0.05 specimens exhibited the highest dielectric constant. The decrease in the dielectric constant of the sintered x > 0.05 specimens was attributed to the increase in the B-site bond valence of the ABO3 perovskite structure. Owing to the large number of grain boundaries, the breakdown voltage (6.6839 kV/mm) of the BSCTZ prepared using the CG method was significantly improved in relation to that (2.0043 kV/mm) of the specimen prepared using the SSR method.

A Risk Scoring System Utilizing Machine Learning Methods for Hepatotoxicity Prediction One Year After the Initiation of Tyrosine Kinase Inhibitors.

Background: There is currently no method to predict tyrosine kinase inhibitor (TKI) -induced hepatotoxicity. The purpose of this study was to propose a risk scoring system for hepatotoxicity induced within one year of TKI administration using machine learning methods. Methods: This retrospective, multi-center study analyzed individual data of patients administered different types of TKIs (crizotinib, erlotinib, gefitinib, imatinib, and lapatinib) selected in five previous studies. The odds ratio and adjusted odds ratio from univariate and multivariate analyses were calculated using a chi-squared test and logistic regression model. Machine learning methods, including five-fold cross-validated multivariate logistic regression, elastic net, and random forest were utilized to predict risk factors for the occurrence of hepatotoxicity. A risk scoring system was developed from the multivariate and machine learning analyses. Results: Data from 703 patients with grade II or higher hepatotoxicity within one year of TKI administration were evaluated. In a multivariable analysis, male and liver metastasis increased the risk of hepatotoxicity by 1.4-fold and 2.1-fold, respectively. The use of anticancer drugs increased the risk of hepatotoxicity by 6.0-fold. Patients administered H2 blockers or PPIs had a 1.5-fold increased risk of hepatotoxicity. The area under the receiver-operating curve (AUROC) values of machine learning methods ranged between 0.73-0.75. Based on multivariate and machine learning analyses, male (1 point), use of H2 blocker or PPI (1 point), presence of liver metastasis (2 points), and use of anticancer drugs (4 points) were integrated into the risk scoring system. From a training set, patients with 0, 1, 2-3, 4-7 point showed approximately 9.8%, 16.6%, 29.0% and 61.5% of risk of hepatotoxicity, respectively. The AUROC of the scoring system was 0.755 (95% CI, 0.706-0.804). Conclusion: Our scoring system may be helpful for patient assessment and clinical decisions when administering TKIs included in this study.

Selective optosensing of iron(III) ions in HeLa cells using NaYF4:Yb3+/Tm3+ upconversion nanoparticles coated with polyepinephrine.

Novel polyepinephrine-modified NaYF4:Yb,Tm upconversion luminescent nanoparticles (UCNP@PEP) were prepared via the self-polymerization of epinephrine on the surfaces of the UCNPs for selective sensing of Fe3+ inside a cell and for intracellular imaging. The proposed UCNP@PEP probe is a strong blue light emitter (λmax = 474 nm) upon exposure to an excitation wavelength of 980 nm. The probe was used for detecting Fe3+ owing to the complexation reaction between UCNP@PEP and Fe3+, resulting in reduced upconversion luminescence (UCL) intensity. The proposed probe has a detection limit of 0.2 µM and a good linear range of 1-10 µM for sensing Fe3+ ions. Moreover, the UCNP@PEP probe displays high cell viability (90%) and is feasible for intracellular imaging. The ability of the probe to sense Fe3+ in a human serum sample was tested and shows promising output for diagnostic purposes. The prepared UCNP@PEP probe was characterized by using UV-visible (UV-Vis) absorption spectrometry, fluorescence (FL) spectrometry, field emission scanning electron microscopy (FE-SEM), X-ray photoelectron spectroscopy (XPS), and Fourier transform infrared spectroscopy (FT-IR).

Preparation and characterization of various chitin-glucan complexes derived from white button mushroom using a deep eutectic solvent-based ecofriendly method.

Deep eutectic solvents (DESs) have gained great interests as ecofriendly and safe solvents in diverse areas. Herein, various chitin-glucan complexes (CGCs) were prepared from white button mushroom (Agaricus bisporus) using DESs. Ultrasonication of mushroom in five DESs yielded two types of CGCs from each DES, one from the DES-insoluble residue (DES_P) and another from the DES-soluble extract (DES_S). The ten resulting CGCs with varying chitin-to-ß-glucan ratios were compared with alkali-insoluble matter (AIM), chemically prepared using NaOH. BU_S and BU_P, prepared using BU comprising betaine and urea, were obtained in the highest yields with reasonably low protein and mineral contents. Despite different acetylation degrees (77.3% and 57.3%, respectively), BU_S and BU_P both degraded at 318 °C and showed remarkably low crystallinity (32.0% and 37.0% for BU_S and BU_P, respectively) compared to AIM, commercial chitin, and the reported CGCs. The surface of BU_S and BU_P was very porous and rough compared with AIM as a result of reduced H-bonds and lowered crystallinity. The DES-based method can potentially enable the preparation of advanced biomaterials from mushrooms under mild and ecofriendly conditions.

Factors affecting high-grade hepatotoxicity of tyrosine kinase inhibitors in cancer patients: a multi-center observational study.

PURPOSE: Although several studies have examined tyrosine kinase inhibitor (TKI)-induced hepatotoxicity, the majority of patients in those studies displayed low-grade (grade I-II) hepatotoxicity. The purpose of this study was to investigate factors affecting high-grade (grade III-IV) hepatotoxicity of TKIs. METHODS: This multi-center, retrospective study used individual patient data from five studies that examined factors affecting hepatotoxicity by TKIs (crizotinib, erlotinib, gefitinib, imatinib, and lapatinib). Odds ratio (OR) and adjusted OR (AOR) were estimated from univariate and multivariate analyses, respectively. RESULTS: Data from 1279 patients treated with TKIs were analyzed. The rate of patients who experienced high-grade hepatotoxicity after TKI administration was 5.5%. In multivariable analysis, H2 blockers and CYP3A4 inducers increased high-grade hepatotoxicity 2.2- (95% CI 1.255-3.944) and 3.3-fold (95% CI 1.260-8.698), respectively. Patients with liver metastasis revealed a 3.4-fold (95% CI 1.561-7.466) higher risk of high-grade hepatotoxicity. Among underlying malignancies, pancreatic cancer and other cancers including acute lymphoblastic leukemia increased the risk of high-grade hepatotoxicity by 2.6- and 24.3-fold, respectively, whereas breast cancer decreased the risk (AOR 0.3, 95% CI 0.106-0.852), compared to non-small cell lung cancer. In patients who administrated TKIs which form reactive metabolites, use of CYP3A4 inducers and liver metastasis increased incidence of high-grade hepatotoxicity by 3.0- and 2.3-fold, respectively. In patients with EGFR mutation, exon 19 deletion and use of proton pump inhibitors were risk factors for high-grade hepatotoxicity in addition to liver metastasis and use of H2 blockers. CONCLUSION: The use of H2 blockers, presence of liver metastasis, and CYP3A4 inducers were associated with high-grade hepatotoxicity of TKIs. In subgroup analyses, presence of exon 19 deletion, and/or proton pump inhibitors, was additional risk factors for high-grade hepatotoxicity in special patients and use of specific TKIs. Close liver function monitoring is recommended, especially in patients with liver metastasis or using H2 blockers or CYP3A4 inducers.

In situ formation of thymol-based hydrophobic deep eutectic solvents: Application to antibiotics analysis in surface water based on liquid-liquid microextraction followed by liquid chromatography.

A simple and ecofriendly sample preparation method was developed for quantifying fluoroquinolone (FQ) antibiotics in surface water. Seventeen combinations of monoterpenes (menthol, thymol, and camphor), fatty acids (heptanoic, octanoic, nonanoic, and decanoic acids), and a benzoate ester (salol) were utilized for the in situ formation of hydrophobic deep eutectic solvents (hDESs) for liquid-liquid microextraction (LLME). The hDES comprising thymol and heptanoic acid (HA) exhibited the highest extraction efficiency for ofloxacin, norfloxacin, ciprofloxacin, and enrofloxacin. Optimization via the one-variable-at-a-time strategy revealed that a 2:1 ratio of thymol to HA yielded the highest efficiency for antibiotic extraction at pH 4-7. Further, response surface methodology-based optimization suggested that the optimal extraction conditions involved the use of appropriate amounts of thymol and HA to generate 100 µL of hDES in 10 mL of aqueous sample with incubation at 52 °C for 5 min, followed by automated shaking for 1 min. The collected hDES phase was diluted and subjected to liquid chromatography-ultraviolet detection analysis. The established method based on in situ formation of hDES coupled with shaker-assisted LLME (in situ hDES-SA-LLME) was validated. The method was specific and showed good linearity in the 15-3000 ng mL-1 concentration range (r2 ≥ 0.9997), with a limit of detection of 3.0 ng mL-1, limit of quantification of 9.0 ng mL-1, accuracy of 84.1-113.65%, and intra-day and inter-day precision of ≤7.78% RSD and ≤7.91% RSD, respectively. The method was successfully applied to three different types of real surface water samples. Without toxic volatile organic solvents, the developed method allows for safe and rapid, yet reliable, analysis of FQ antibiotics.

Fluorescence Optosensing of Triclosan by Upconversion Nanoparticles with Potassium Permanganate.

It is greatly significant to develop a simple and rapid sensing method for triclosan (TCS) because it is a widely used and a chronically toxic compound that adversely affects biological organisms and human health. This paper presents the design and development of a novel simple optosensor that uses carboxylic group-functionalized NaYF4:Yb3+/Er3+ upconversion nanoparticles (UCNPs) coated with potassium permanganate (KMnO4). The sensor enables the rapid, non-autofluorescence, sensitive, and selective detection of TCS based on the "turn off-on fluorescence" technique through fluorescence resonance energy transfer. Under an near-infrared radiation excitation (980 nm), the "turn-off fluorescence" process involves the transfer of fluorescence resonance energy between the UCNPs and KMnO4, whereas the "turn-on fluorescence" process occurs when KMnO4 is reduced in the presence of TCS. TCS was detected by recovering the green emission of UCNPs. Under optimized conditions, the resulting sensor offered an excellent response to TCS with 0.2 µM of a limit of detection. The developed sensor showed higher selectivity to TCS than other phenolic compounds. Moreover, the analytical performance of the proposed probe was practically demonstrated to successfully monitor trace levels of TCS in samples of tap water and personal care products. The developed simple and sensitive method may offer a new approach for determining TCS in environmental applications.

Factors affecting crizotinib-induced hepatotoxicity in non-small cell lung cancer patients.

Crizotinib is an orally available tyrosine kinase inhibitor for patients with anaplastic lymphoma kinase-positive non-small cell lung cancer (NSCLC). Despite that crizotinib-induced hepatotoxicity may cause a dose reduction or interruption that can affect the patient's treatment, there is no study to investigate factors for crizotinib-induced hepatotoxicity. The purpose of this study was to evaluate factors affecting crizotinib-induced hepatotoxicity. From February 2012 to April 2018, a retrospective study was performed on NSCLC patients treated with crizotinib. Various factors were reviewed including sex, age, body weight, height, body surface area, underlying disease, smoking history, genetic mutation, and concomitant drugs. Among 153 patients, incidence of crizotinib-induced hepatotoxicity of grade I or higher was 83% (n = 127). The presence of liver disease or HBV revealed significant effect on hepatotoxicity within 28 days after crizotinib administration in univariate analysis. Patients with liver disease or HBV carriers revealed 2.3 times the hazard of time to hepatotoxicity compared to those without liver disease or HBV. Use of H2-antagonist or H2-antagonist/proton pump inhibitor revealed 1.7 times the hazard of time to hepatotoxicity compared to those that did not use those medications. Thus, close monitoring of liver function is recommended, especially in patients with liver impairment or using anti-acid secreting agents.

One-step synthesis of NaLu80-xGdxF4:Yb183+/Er23+(Tm3+) upconversion nanoparticles for in vitro cell imaging.

Upconversion nanoparticles (UCNPs) possess a unique type of photoluminescence (PL) in which lower-energy excitation is converted into higher-energy emission via multi-photon absorption processes. In this work, we have used a facile one-step hydrothermal method promoted water solubility to synthesis NaLuGdF4:Yb3+/Er3+(Tm3+) UCNPs coated with malonic acid (MA). Scanning electron microscopy images and X-ray diffraction patterns reveal sphere-shaped UCNPs with an average size of ~80nm crystallized in the cubic NaLuF4 structure. The characteristic vibrations of cubic UCNPs have been taken into account by using Fourier-transform infrared spectroscopy. Based on PL studies, we have determined an optimal concentration of Gd3+ doping. The dependence of upconversion PL intensity on Gd3+ concentration is discussed via the results of magnetization measurements, which is related to the coupling/uncoupling of Gd3+ ions. Particularly, our study reveals that carboxyl-functionalized NaLuGdF4:Yb3+/Er3+(Tm3+) UCNPs have a relatively high cell viability with HeLa cells.

Enhanced photodegradation of 2,4-dichlorophenoxyacetic acid using a novel TiO2@MgFe2O4 core@shell structure.

A novel TiO2@MgO-Fe2O3 core-shell structure has been synthesized via a hydrolysis and co-precipitation method followed by calcination at 500 °C and has proven to be an efficient photocatalyst. The obtained TiO2@MgO-Fe2O3 core-shell was characterized by scanning electron microscopy, X-ray diffraction, and UV-Vis diffused reflectance techniques. Its photocatalytic activity toward 2,4-dichlorophenoxyacetic acid (2,4-D) was investigated in aqueous solutions with and without visible light irradiation in the presence and absence of hydrogen peroxide. It was revealed that a strong electronic coupling exists between two components within the TiO2@MgO-Fe2O3 core-shell structure. The present findings clearly highlight that TiO2@MgO-Fe2O3 exhibits excellent photocatalytic activity under visible light irradiation in the presence of H2O2. More than 83% degradation of 2,4-D was observed within 240 min, at an initial concentration of 100 mg L-1 with 0.5 g of catalyst per liter. Moreover, the material showed high chemical stability after four consecutive experiments with no significant difference in the rate of photocatalytic degradation. Therefore, the results reported herein offer a green, low cost and highly efficient photocatalyst for environmental remediation.