Synthesis of Iron Sulfide Nanocrystals Encapsulated in Highly Porous Carbon-Coated CNT Microsphere as Anode Materials for Sodium-Ion Batteries.

Highly porous carbon materials with a rationally designed pore structure can be utilized as reservoirs for metal or nonmetal components. The use of small-sized metal or metal compound nanoparticles, completely encapsulated by carbon materials, has attracted significant attention as an effective approach to enhancing sodium ion storage properties. These materials have the ability to mitigate structural collapse caused by volume expansion during the charging process, enable short ion transport length, and prevent polysulfide elution. In this study, a concept of highly porous carbon-coated carbon nanotube (CNT) porous microspheres, which serve as excellent reservoir materials is suggested and a porous microsphere is developed by encapsulating iron sulfide nanocrystals within the highly porous carbon-coated CNTs using a sulfidation process. Furthermore, various sulfidation processes to determine the optimal method for achieving complete encapsulation are investigated by comparing the morphologies of diverse iron sulfide-carbon composites. The fully encapsulated structure, combined with the porous carbon, provides ample space to accommodate the significant volume changes during cycling. As a result, the porous iron sulfide-carbon-CNT composite microspheres exhibited outstanding cycling stability (293 mA h g-1 over 600 cycles at 1 A g-1 ) and remarkable rate capability (100 mA h g-1 at 5 A g-1 ).

Determination of enantiomeric impurity of tenofovir disoproxil fumarate on a cellulose tris(3,5-dichlorophenyl-carbamate) chiral stationary phase and the characterization of its related substances.

A simple and reliable high-performance liquid chromatography method was developed to determine the enantiomeric impurity of tenofovir disoproxil fumarate, an orally bioavailable prodrug of tenofovir, commonly used for the treatment of human immunodeficiency virus and hepatitis B. Tenofovir disoproxil and its enantiomer, were completely separated on a Chiralpak IC column (3 µm, 100 × 4.6 mm, i.d.). The chiral separation was achieved using a mobile phase containing n-hexane, ethanol, methanol, and triethylamine 65/25/10/0.1 (v/v/v/v) at a flow rate of 0.6 mL/min. Ideally, the reversal of enantiomer elution order was achieved on the Chiralpak IC column, to allow the elution of the minor enantiomeric impurity before the major component. Moreover, the proposed method was able to discriminate the active ingredient from the related substances available in the tenofovir disoproxil fumarate raw materials. These compounds were isolated and structurally elucidated by MS and nuclear magnetic resonance. Based on the spectral data, the structures of related substances were confirmed as tenofovir isoproxil monoester and fumaric acid. The high-performance liquid chromatography method was optimized by the design of experiment approach and successfully validated following the International Conference on Harmonization guideline. Proposed method was effectively applied for the quantification of enantiomeric impurity in tenofovir disoproxil fumarate raw materials.

A capillary electrophoresis method for the determination of the linagliptin enantiomeric impurity.

Linagliptin is a highly specific, long-acting inhibitor that is used as an orally administrable agent for type-2 diabetes treatment. Because only the R-enantiomer is of clinical use, we developed a capillary electrophoresis method for the determination of the enantiomeric impurity of this compound. Carboxymethyl-ß-cyclodextrin was selected as the chiral selector for the separation of linagliptin enantiomers. Design of experiments and desirability functions were used for the analytical optimization, which was focused on understanding and improving the electrophoretic process. The effects of significant parameters (background electrolyte concentration and pH, cyclodextrin concentration, temperature, and voltage) were thoroughly investigated. The complete separation of linagliptin and its enantiomeric impurity with baseline resolution was achieved within 10 min on an uncoated fused-silica capillary (50 µm inner diameter, 365 µm outer diameter, 64.5/56 cm in total/ effective length) maintained at 25°C, under an applied voltage of 28.0 kV. The background electrolyte contained 70 mM sodium acetate and 4.7 mM carboxymethyl-ß-cyclodextrin, and the pH was adjusted to 6.10. The method was validated, and a limit of quantitation of 0.05% for the impurity was estimated.

Mesoporous Si-Cu nanocomposite anode for a lithium ion battery produced by magnesiothermic reduction and electroless deposition.

Copper deposited mesoporous silicon was fabricated by magnesiothermic reduction and electroless deposition and its electrochemical properties as an anode for lithium ion batteries were investigated. The 300-400 nm sized mesoporous Si particles were synthesized by magnesiothermic reduction of SiO2 nanospheres prepared by the Stöber method. The mesopores of Si particles were effectively decorated with Cu using Sn sensitization/Pd activation and subsequent Cu electroless deposition. The homogeneous distribution of Cu inside the mesoporous Si particles was confirmed by high resolution transmission electron microscopy images and energy dispersive spectroscopy mapping on the cross-sectional specimen prepared by a focused ion beam. The mesoporous Si-Cu nanocomposite exhibited high initial Coulombic efficiency, long cycle stability, and high rate capability, delivering a high capacity of 1569 mAh g-1 after 200 cycles at the current density of 1000 mA g-1. The improved electrochemical performance in a mesoporous Si-Cu nanocomposite was attributed to the high electrical conductivity, high Li+ ion mobility, and structural stability to restrict the aggregation and pulverization of active materials.

Pharmacokinetic comparisons between two formulations containing 100 mg of miglitol in healthy male Korean volunteers: a randomized, open-label, single-dose, two-period, two-sequence crossover bioequivalence study.

BACKGROUND: Miglitol is an α-glucosidase inhibitor (AGI) used as an antihyperglycemic agent in the treatment of type 2 diabetes mellitus. The mechanism is that miglitol binds to and inhibits the α-glucosidase reversibly in the proximal intestine. Thus, carbohydrates not digested in the upper small intestine are transported to the lower intestine where they are eventually digested. OBJECTIVE: This study was performed for the subsequent marketing of the test miglitol formulation in Korea. We evaluated the comparative bioavailability and tolerability of the test and reference formulations in healthy male adult volunteers. METHODS: A total of 40 healthy adult subjects were enrolled in this single-dose, randomized, open-label, 2-period, 2-sequence, crossover bioequivalence study. During each period, subjects received 100 mg of miglitol test or reference. Blood samples from the subjects were obtained before dosing at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, 9, and 12 hours after oral drug administration. Plasma concentrations were determined by using liquid chromatography/mass spectrometry/mass spectrometry (LC-MS/MS). The PK parameters including AUCt, AUC∞, Cmax, and tmax were measured and all treatment-emergent adverse events (TEAEs) and their relationships to study these medications were recorded throughout the entire study. RESULTS: A total of 40 healthy adult male Korean subjects were enrolled in the study and randomized into two treatment groups. Ultimately, 33 subjects completed the study. During each treatment period, blood samples were collected at specific time intervals from 0 to 12 hours after administration of a single drug dose. The PK parameters including AUCt, AUC∞, Cmax, and tmax were calculated and the 90% CIs of the ratio (test/reference) of the parameters were obtained by analysis of variance (ANOVA) on logarithmically transformed data. The 90% CIs of the geometric mean ratios for the test to reference formulations were as follows: 1.05 (0.97 - 1.13) for AUCt and 1.05 (0.96 - 1.14) for Cmax. Statistical analysis confirmed that the 90% CIs for these PK parameters were within the commonly accepted bioequivalence range of 0.8 - 1.25. There were no serious or unexpected TEAEs during the study. CONCLUSIONS: In the healthy adult Korean subjects, the test and reference formulations had similar PK parameters and similar plasma concentration-time profiles. The test formulation of miglitol met the Korean regulatory criteria (AUCt and Cmax) for assuming bioequivalence and both formulations were generally well-tolerated. The CRiS identifiers: KCT0000770.

Synthesis of Graphitic Carbon Coated ZnPS3 and its Superior Electrochemical Properties for Lithium and Sodium Ion Storage.

Graphitic carbon-coated ZnPS3 is prepared via direct phosphosulfurization and high energy mechanical milling (HEMM) with multiwall carbon nanotubes (MWCNTs) and first introduced as an anode for lithium-ion batteries (LIBs) and sodium-ion batteries (SIBs). The HEMM process with MWCNTs reduces the particle size of as-synthesized ZnPS3 bulk to 100-500 nm and yields the ≈5 nm thick graphitic carbon coated ZnPS3 nanoparticles, which are the nanocomposites of 5 nm sized nanocrystallites embedded in the amorphous matrix. The ZnPS3 electrode undergoes the combined conversion and alloying reactions with Li and Na ions and exhibits high initial discharge and charge capacities in both LIBs and SIBs. The graphitic carbon-coated ZnPS3 electrode exhibits excellent high-rate capability and long-term cyclability. The superior electrochemical properties can be attributed to high electrical conductivity, high Li ion mobility, and high reversibility and structural stability derived from the graphitic carbon-coated nanoparticles. This study demonstrates that the novel graphitic carbon-coated ZnPS3 is a promising anode material for both LIBs and SIBs and the graphitic carbon coating methodology by HEMM is expected to apply to the various metal oxides, sulfides, and phosphides.

Mast cell stabilizing effect of (-)-Elema-1,3,11(13)-trien-12-ol and thujopsene from Thujopsis dolabrata is mediated by down-regulation of interleukin-4 secretion in antigen-induced RBL-2H3 cells.

Several isolated compounds from the wood part of Thujopsis dolabrata were evaluated for their inhibitory effects against antigen-induced mast cell degranulation and interleukin-4 (IL-4) secretion, as well as IL-4 mRNA and protein expression in immunoglobulin E (IgE)-sensitized RBL-2H3 cells. Among the five isolated compounds, (-)-elema-1,3,11(13)-trien-12-ol (1) and thujopsene (2) exhibited the potent inhibitory activity against mast cell degranulation measured by ß-hexosaminidase release with IC values of 27.4 µM and 25.1 µM, respectively. These compounds also inhibited the release of IL-4 (IC values of 7.0, 6.7 µM, respectively), IL-4 mRNA expression (IC values of 16.5, 7.2 µM, respectively) and IL-4 protein expression (IC values of 17.0, 9.6 µM, respectively) in antigen-induced IgE-sensitized RBL-2H3 cells. These results suggested that (-)-elema-1,3,11(13)-trien-12-ol (1) and thujopsene (2) effectively inhibits mast cell degranulation as well as IL-4 production, suggesting that these compounds from Thujopsis dolabrata can be used as candidates for IgE-mediated allergic disorders.

Confinement Effects of Hollow Structured Pt-Rh Electrocatalysts toward Complete Ethanol Electrooxidation.

In the anodic ethanol oxidation reaction (EOR) for direct ethanol fuel cells, the coverage of hydroxide (OHads) is a major adsorbent competing with C-C bond cleavage, which is necessary for complete ethanol oxidation (C1-pathway) and durability. Beyond utilizing a less-alkaline electrolyte that causes ohmic losses, an alternative strategy to optimize OHads coverage is to intentionally exploit local pH changes near the electrocatalyst surface that are governed by a combination of released H+ during EOR and OH- mass transport from the bulk solution. Here, we manipulate the local pH swing by fine-tuning the electrode porosity with Pt1-xRhx hollow sphere electrocatalysts based on particle size (250 and 350 nm) and mass loading. With the smaller size of 250 nm, Pt0.5Rh0.5 (∼50 µg cm-2) shows a high activity of 1629 A gPtRh-1 (2488 A gPt-1) in a 0.5 M KOH-containing electrolyte, which is ∼50% higher than the most active binary catalysts to date. Moreover, a higher C1-pathway Faradaic efficiency (FE) of 38.3% and 80% longer durability are achieved with a 2-fold increase in mass loading. In the more porous electrodes, a local acidic environment created by hindered OH- mass transport better optimizes OHads coverage, providing more active sites for the desired C1-pathway and a continuous EOR.

Chiral separation and molecular modeling study of decursinol and its derivatives using polysaccharide-based chiral stationary phases.

Plant-based bioactive substances have long been used to treat inflammatory ailments, owing to their low toxicity and cost-effectiveness. To enhance plant treatment by eliminating undesirable isomers, optimizing the chiral separation techniques in pharmaceutical and clinical studies is important. This study reported a simple and effective method for chiral separation of decursinol and its derivatives, which are pyranocoumarin compounds with anti-cancer and anti-inflammatory properties. Baseline separation (Rs >1.5) was achieved using five different polysaccharide-based chiral stationary phases (CSPs) that differed in chiral origin, chiral selector chemistry, and preparation technique. To separate all six enantiomers simultaneously, n-hexane and three alcohol modifiers (ethanol, isopropanol, and n-butanol) were used as mobile phases in the normal-phase mode. The chiral separation ability of each column with various mobile phase compositions was compared and discussed. As a result, amylose-based CSPs with linear alcohol modifiers demonstrated superior resolution. Three cases of elution order reversal caused by modifications of CSPs and alcohol modifiers were observed and thoroughly analyzed. To elucidate the chiral recognition mechanism and enantiomeric elution order (EEO) reversal phenomenon, detailed molecular docking simulations were conducted. The R- and S-enantiomers of decursinol, epoxide, and CGK012 exhibited binding energies of -6.6, -6.3, -6.2, -6.3, -7.3, and -7.5 kcal/mol, respectively. The magnitude of the difference in binding energies was consistent with the elution order and enantioselectivity (α) of the analytes. The molecular simulation results demonstrated that hydrogen bonds, π-π interactions, and hydrophobic interactions have a significant impact on chiral recognition mechanisms. Overall, this study presented a novel and logical approach of optimizing chiral separation techniques in the pharmaceutical and clinical industries. Our findings could be further applied for screening and optimizing enantiomeric separation.

Energy-Efficient Ingestible Drug Delivery System in the Dynamic Gastrointestinal Environment.

Ingestible electronics are promising platforms for on-demand health monitoring and drug delivery. However, these devices and their actuators must operate in the gastrointestinal (GI) environment, which has a pH range of 1 to 8. Drug delivery systems using electrochemical dissolution of metal films are particularly susceptible to pH changes. Optimal operation in this dynamic environment stands to transform our capacity to help patients across a range of conditions. Here we present an energy-efficient ingestible electronic electrochemical drug delivery system to support subjects through operation in this dynamic environment. The proposed system consists of a drug reservoir sealed with an electrochemically dissolvable gold membrane and an electronic subsystem. An electronic subsystem controls the rate of gold dissolution by sensing and adapting to the pH of the GI environment and provides an option for energy-efficient drug delivery, reducing energy consumption by up to 42.8 %. Integrating the electronics with electrochemical drug delivery enables the proposed system to adapt to the dynamic physiological environments which makes it suitable for drug and/or therapeutic delivery at different locations in the GI tract.

Fully Automated Segmentation of Human Eyeball Using Three-Dimensional U-Net in T2 Magnetic Resonance Imaging.

Purpose: To develop and validate a fully automated deep-learning-based tool for segmentation of the human eyeball using a three-dimensional (3D) U-Net, compare its performance to semiautomatic segmentation ground truth and a two-dimensional (2D) U-Net, and analyze age and sex differences in eyeball volume, as well as gaze-dependent volume consistency in normal subjects. Methods: We retrospectively collected 474 magnetic resonance imaging (MRI) scans, including different gazing scans, from 119 patients. A 10-fold cross-validation was applied to separate the dataset into training, test, and validation sets for both the 3D U-Net and 2D U-Net. Performance accuracy was measured using four quantitative metrics compared to the ground truth, and Bland-Altman plot analysis was conducted. Age and sex differences in eyeball volume and variability in eyeball volume differences across gazing directions were analyzed. Results: The 3D U-Net outperformed the 2D U-Net with mean accuracy scores >0.95, showing acceptable agreement in the Bland-Altman plot analysis despite a tendency for slight overestimation (mean difference = -0.172 cm³). Significant sex differences and age effects on eyeball volume were observed for both methods (P < 0.05). No significant volume differences were found between the segmentation methods or within each method for the different gazing directions. Significant differences in performance accuracy were identified among the five gazing directions, with the upward direction showing a notably lower performance. Conclusions: Our study demonstrated the effectiveness of 3D U-Net human eyeball volume segmentation using T2-weighted MRI. The robustness and reliability of 3D U-Net across diverse populations and gaze directions support enhanced ophthalmic diagnosis and treatment strategies. Translational Relevance: Our findings demonstrate the feasibility of using the proposed 3D U-Net model for the automatic segmentation of the human eyeball, with potential applications in various ophthalmic research fields that require the analysis of 3D geometric eye globe shapes or eye movement detection.

Mapping the electrocatalytic water splitting activity of VO2 across its insulator-to-metal phase transition.

The electrocatalytic water splitting activity of V-based oxides has been rarely investigated, even though several polymorphs in VO2 are expected to exhibit different electrocatalytic activities depending on their crystal and electronic structures. The rutile structure of VO2(R), showing metallic character, is a good candidate for a new electrocatalyst since it undergoes insulator-to-metal transition (IMT) from the insulating VO2(M1) at a low temperature of 68 °C, and involves a substantially increased electrical conductivity by three orders of magnitude. The extensive improvements in the electrocatalytic activity for both the oxygen evolution reaction (OER) and the hydrogen evolution reaction (HER) are confirmed when the IMT is induced where the overpotential (η10) is reduced from 1056 mV to 598 mV in the OER and 411 mV to 136 mV in the HER, respectively. This improvement is attributed to the increased electrochemically active surface area (ECSA), reduced charge transfer resistance, and increased electron density, driven by the IMT to the metallic VO2(R) phase.

Neuroprotective effects of 3α-acetoxyeudesma-1,4(15),11(13)-trien-12,6α-olide against dopamine-induced apoptosis in the human neuroblastoma SH-SY5Y cell line.

Dopamine (DA), as a neurotoxin, can elicit severe Parkinson's disease-like syndrome by elevating intracellular reactive oxygen species (ROS) levels and apoptotic activity. We examined the inhibitory effects of 3α-acetoxyeudesma-1,4(15),11(13)-trien-12,6α-olide (AETO), purified from the leaves of Laurus nobilis L., on DA-induced apoptosis and α-synuclein (α-syn) formation in dopaminergic SH-SY5Y cells. AETO decreased the active form of caspase-3 and the levels of p53, which were accompanied by increased levels of Bcl-2 in a dose-dependent manner. Flow cytometric and Western blot analysis showed that AETO significantly inhibited DA-induced apoptosis along with suppression of intracellular tyrosinase activity, ROS generation, quinoprotein, and α-syn formation (P < 0.01). These results indicate that AETO inhibited DA-induced apoptosis, which is closely related to the suppression of intracellular tyrosinase activity and the formation of α-syn, ROS, and quinoprotein in SH-SY5Y cells.

Inhibitory effects of costunolide isolated from Laurus nobilis on IgE-induced degranulation of mast cell-like RBL-2H3 cells and the growth of Y16 pro-B cells.

This study investigated the inhibitory effects of costunolide isolated from the leaves of Laurus nobilis L. (Lauraceae) on basophil-mediated allergic reactions and interleukin (IL)-5-mediated B cell growth. The effects of costunolide on ß-hexosaminidase (a key parameter of degranulation) release and IL-4 expression in rat basophilic leukemia (RBL-2H3) cells were determined by measuring ß-hexosaminidase activity and by semi-quantitative RT-PCR, respectively. The effects of costunolide on Y16 pro-B cell viability and growth were determined by 3-(4,5-dimethylthiazol-2-yl)2,5-diphenyltetrazolium bromide (MTT) assay. Costunolide was found significantly to inhibit ß-hexosaminidase activity (p < 0.01) and IL-4 transcription in RBL-2H3 cells in a dose-dependent manner. Its 50% inhibitory concentration (IC50 ) was 34 µM, while that of the positive control, ketotifen, was 24 µM (IL-4 mRNA transcription). Moreover, costunolide dose-dependently suppressed pro-B cell growth in IL-5-stimulated Y16 cells. These results provide evidence that costunolide stabilizes mast cells by inhibiting IgE-mediated degranulation and inhibits IL-5-stimulated B cell growth.

Amelioration of oxygen and glucose deprivation-induced neuronal death by chloroform fraction of bay leaves (Laurus nobilis).

The purpose of this study was to determine whether the Laurus nobilis chloroform fraction (LNCF) protects against cerebral ischemia neuronal damage. Human neuroblastoma SH-SY5Y cells and brain slices from rats were subjected to oxygen and glucose deprivation (OGD), followed by reoxgenation with and without LNCF. The viabilities of SH-SY5Y cells and brain slices from the rats were 58.5±4.9% and 79.7±5.9% in the group subjected to OGD, and 80.4±0.4% and 97.2±1.9% at 4 µg/ml of LNCF, respectively. LNCF also significantly inhibited death-associated protein kinase (DAPK) dephosphorylation. Pretreatment with LNCF at 4 mg/kg significantly decreased infarct size by 79% of vehicle control in the middle cerebral artery occlusion (MCAO) in vivo model. LNCF is a neuroprotective drug candidate against cerebral ischemia neuronal damage.

A MnV2O6/graphene nanocomposite as an efficient electrocatalyst for the oxygen evolution reaction.

A MnV2O6/graphene nanocomposite was fabricated through hydrothermal synthesis and high energy milling to introduce it as an efficient OER electrocatalyst. The MnV2O6/graphene nanocomposite with 20 wt% graphene exhibited superior electrocatalytic OER performance with a low overpotential and high stability and durability in 1 M KOH aqueous solution, exhibiting even after 1000 CV cycles.

Preparative resolution of etodolac enantiomers by preferential crystallization method.

Pure enantiomers are of large interest for several industries. This study was aimed to establish a method for separation of etodolac enantiomers by preferential crystallization after a conglomerate formation of its derivatives. S-(+)-etodolac and R-(-)-etodolac enantiomers were both prepared by classical resolution via crystallization of diastereoisomeric salt with (-)-brucine and (-)-cinchonidine. Enantiomeric purity of etodolac was determined by HPLC method using Chiralcel OD-H column. The pure diastereomeric salt collected from repeated recrystallization was further fractionated by liquid-liquid extraction to pure enantiomers. Etodolac enantiomers were recovered with overall yield more than 20% and the purities were over 99.9%.

Stable Silicon Anode for Lithium-Ion Batteries through Covalent Bond Formation with a Binder via Esterification.

Silicon (Si) is considered to be one of the most promising anode candidates for next-generation lithium-ion batteries because of its high theoretical specific capacity and low discharge potential. However, its poor cyclability, caused by tremendous volume change during cycling, prevents commercial use of the Si anode. Herein, we demonstrate a high-performance Si anode produced via covalent bond formation between a commercially available Si nanopowder and a linear polymeric binder through an esterification reaction. For efficient ester bonding, polyacrylic acid, composed of -COOH groups, is selected as the binder, Si is treated with piranha solution to produce abundant -OH groups on its surface, and sodium hypophosphite is employed as a catalyst. The as-fabricated electrode exhibits excellent high rate capability and long cycle stability, delivering a high capacity of 1500 mA h g-1 after 500 cycles at a high current density of 1000 mA g-1 by effectively restraining the susceptible sliding of the binder, stabilizing the solid electrolyte interface layer, preventing the electrode delamination, and suppressing the Si aggregation. Furthermore, a full cell is fabricated with as-fabricated Si as an anode and commercially available LiNi0.6Mn0.2Co0.2O2 as a cathode, and its electrochemical properties are investigated for the possibility of practical use.

Solid solution phosphide (Mn1-xFexP) as a tunable conversion/alloying hybrid anode for lithium-ion batteries.

The substitutional solid solution Mn1-xFexP compounds between alloying reaction-type MnP and conversion reaction-type FeP are successfully synthesized via facile high energy mechanical milling and their electrochemical properties as an anode for lithium ion batteries (LIBs) are investigated. A complete solid solution is formed between two end members and the Mn1-xFexP solid solution phosphide electrodes show an enhanced electrochemical performance, delivering a capacity of 360 mA h g-1 after 100 cycles at a high current density of 2 A g-1 when the advantages of the two reaction mechanisms are beneficially combined. These synergistic effects resulted from the in situ generated nanocomposite of the Li-Mn-P alloying element and the Fe nano-network in combination with the surrounding amorphous lithium phosphide, which effectively buffers the accompanying volume variation, hinders the aggregation of the alloying element, and ensures the electron and ion transport.

Superior electrochemical sodium storage of V4P7 nanoparticles as an anode for rechargeable sodium-ion batteries.

V4P7 nanoparticles were synthesized via high-energy mechanical milling and their electrochemical properties as an anode for sodium-ion batteries were studied and compared with those of VO2(B)/Na and V4P7/Li cells, focusing on the electrochemical reaction mechanism and cycle performance. The V4P7 showed excellent cycling behavior even without any conductive material.