Alcohol-Processable All-Polymer n-Type Thermoelectrics.

The general strategy for n-type organic thermoelectric is to blend n-type conjugated polymer hosts with small molecule dopants. In this work, all-polymer n-type thermoelectric is reported by dissolving a novel n-type conjugated polymer and a polymer dopant, poly(ethyleneimine) (PEI), in alcohol solution, followed by spin-coating to give polymer host/polymer dopant blend film. To this end, an alcohol-soluble n-type conjugated polymer is developed by attaching polar and branched oligo (ethylene glycol) (OEG) side chains to a cyano-substituted poly(thiophene-alt-co-thiazole) main chain. The main chain results in the n-type property and the OEG side chain leads to the solubility in hexafluorineisopropanol (HFIP). In the polymer host/polymer dopant blend film, the Coulombic interaction between the dopant counterions and the negatively charged polymer chains is reduced and the ordered stacking of the polymer host is preserved. As a result, the polymer host/polymer dopant blend exhibits the power factor of 36.9 µW m-1 K-1, which is one time higher than that of the control polymer host/small molecule dopant blend. Moreover, the polymer host/polymer dopant blend shows much better thermal stability than the control polymer host/small molecule dopant blend. This research demonstrates the high performance and excellent stability of all-polymer n-type thermoelectric.

Photo-Thermal Mediated Li-ion Transport for Solid-State Lithium Metal Batteries.

The development of lithium-based solid-state batteries (SSBs) has to date been hindered by the limited ionic conductivity of solid polymer electrolytes (SPEs), where nonsolvated Li-ions are difficult to migrate in a polymer framework at room temperature. Despite the improved cationic migration by traditional heating systems, they are far from practical applications of SSBs. Here, an innovative strategy of light-mediated energy conversion is reported to build photothermal-based SPEs (PT-SPEs). The results suggest that the nanostructured photothermal materials acting as a powerful light-to-heat converter enable heating within a submicron space, leading to a decreased Li+ migration barrier and a stronger solid electrolyte interface. Via in situ X-ray diffraction analysis and molecular dynamics simulation, it is shown that the generated heating effectively triggers the structural transition of SPEs from a highly crystalline to an amorphous state, that helps mediate lithium-ion transport. Using the assembled SSBs for exemplification, PT-SPEs function as efficient ion-transport media, providing outstanding capacity retention (96% after 150 cycles) and a stable charge/discharge capacity (140 mA g-1 at 1.0 C). Overall, the work provides a comprehensive picture of the Li-ion transport in solid polymer electrolytes and suggests that free volume may be critical to achieving high-performance solid-state batteries.

Ionic Liquids: An Ideal Solvent for Tuning the UCST Phase Behavior of Polymer Gels.

Liquid-liquid phase separation (LLPS) is a common stimulus-responsive phenomenon widely studied and applied in constructing intelligent systems such as microfluidic valves, smart windows, and biosensors. However, LLPS in an aqueous solution has limited applicability confined to a narrow temperature range within 0-100 °C. In addition, for easy exploitation of thermoresponsive behavior, phase separation must be stable and accurately predictable under varying conditions. This study proposes a gel system exhibiting UCST phase behavior using ionic liquids (ILs) and hydrophilic polymers, whose phase transition temperature can be linearly tuned within a wide range (from subzero to over 100 °C) by varying the mixing ratio of ILs in their blends. Similar to the mixing of ILs with structurally similar cations, mixing ILs containing different anions proved to be an effective ideal random mixing method based on experimental results and molecular dynamics simulations. This mixing mechanism of ILs accounts for the linear regulation of the UCST of the ionogels when the mixing ratio of ILs in their blends varies. Moreover, the unique feature of ILs was further demonstrated using other hydrophilic polymer networks and multiple combinations of ILs, suggesting the generality of this strategy for UCST regulation in the ionogels.

Autonomous underwater adhesion driven by water-induced interfacial rearrangement.

Underwater adhesives receive extensive attention due to their wide applications in marine explorations and various related industries. However, current adhesives still suffer from excessive water absorption and lack of spontaneity. Herein, we report an autonomous underwater adhesive based on poly(2-hydroxyethyl methacrylate-co-benzyl methacrylate) amphiphilic polymeric matrix swollen by hydrophobic imidazolium ionic liquid. The as-prepared adhesive is tough and flexible, showing little to none instantaneous underwater adhesion onto the PET substrate, whereas its adhesion energy on the substrate can grow more than 5 times to 458 J·m-2 after 24 hours. More importantly, this process is entirely spontaneous, without any external pressing force. Our comprehensive studies based on experimental characterizations and molecular dynamic simulations confirm that such autonomous adhesion process is driven by water-induced rearrangement of the functional groups. It is believed that such material can provide insights into the development of next-generation smart adhesives.

Effects of temperature on microstructures of MSA-type electroplating solution: a coarse-grained molecular dynamics simulation.

In this study, we employ coarse-grained molecular dynamics simulations to explore the microstructure of MSA (methanesulfonic acid)-type electroplating solution, containing Sn(MSA)2 as the primary salt, MSA as the stabilizer, amphiphilic alkylphenol ethoxylate (APEO) as surfactants and cinnamaldehyde (CA) as the brightener agents, as well as water as the solvent. Our simulation indicates that temperature variations can significantly affect the structural properties of the electroplating solution and the adsorption behavior of its key components onto the substrate. Specifically, at low temperatures, the primary salt ions aggregate into ionic clusters, and the amphiphilic APEO surfactants and CA molecules form micelles composed of hydrophobic cores and hydrophilic shells, which reduces the uniformity of the solution and hinders the adsorption of ions, CA and surfactants onto the substrate. Appropriately increasing the temperature can weaken the aggregation of these components in bulk solution due to the accelerated molecular movements and arouse their adsorption. However, on further increasing the temperature, the elevated kinetic energy of the components thoroughly overwhelms the adsorption interactions, and therefore, the ions, surfactants, and CA desorb from the substrate and redissolve into the solution. We systematically analyze the complex interactions between these components at different temperatures and clarify the mechanism of the non-monotonic dependence of adsorption strength on the temperature at the molecular level. Our simulations demonstrate that there is low-temperature scope for reprocessing/recycling and intermediate-temperature scope for substrate-adsorptions of the key components. This study confers insights into a fundamental understanding of the microscopic mechanism for electroplating and can provide guidance for the development of precise electroplatings.

Structures of cationic and anionic polyelectrolytes in aqueous solutions: the sign effect.

In this study, we use molecular dynamics simulation to explore the structures of anionic and cationic polyelectrolytes in aqueous solutions. We first confirm the significantly stronger solvation effects of single anions compared to cations in water at the fixed ion radii, due to the reversal orientations of asymmetric dipolar H2O molecules around the ions. Based on this, we demonstrate that the solvation discrepancy of cations/anions and electrostatic correlations of ionic species can synergistically cause the nontrivial structural difference between single anionic and cationic polyelectrolytes. The cationic polyelectrolyte shows an extended structure whereas the anionic polyelectrolyte exhibits a collapsed structure, and their structural differences decline with increasing the counterion size. Furthermore, we corroborate that multiple cationic polyelectrolytes or multiple anionic polyelectrolytes can exhibit largely differential molecular architectures in aqueous solutions. In the solvation dominant regime, the polyelectrolyte solutions exhibit uniform structures; whereas, in the electrostatic correlation dominant regime, the polyelectrolyte solutions exhibit heterogeneous structures, in which the likely charged chains microscopically aggregate through counterion condensations. Increasing the intrinsic chain rigidity causes polyelectrolyte extension and hence moderately weakens the inter-chain clustering. Our work highlights the various, unique structures and molecular architectures of polyelectrolytes in solutions caused by the multi-body correlations between polyelectrolytes, counterions and asymmetric dipolar solvent molecules, which provides insights into the fundamental understanding of ion-containing polymers.

Pharmacokinetic and tissue distribution study of ZCY-15, a novel compound against Alzheimer's disease, in rats by liquid chromatography-tandem mass spectrometry.

ZCY-15, N-(3,5-dimethyladamatan-1-yl)-N-(3-methylphenyl) urea, is a candidate compound synthesized from the memantine structure and has been shown to be remarkably effective in treating Alzheimer's disease. To elucidate the pharmacokinetics and tissue distribution of ZCY-15 in rats after oral and intravenous administration, a rapid and selective LC-MS/MS method was established for the determination of ZCY-15 in rat plasma and tissues. According to the dissolution characteristics, the plasma samples were prepared by acetonitrile protein precipitation and carbamazepine was selected as the internal standard (IS). After separation by gradient elution using Aqela Venusil ASB C8 (2.1 × 50 mm, 3 µm), the pretreated samples were analyzed in MRM mode in positive ESI mode. The effective detection limit of this method was 1.95-1000 ng·mL-1. Tissue samples were collected from the heart, liver, spleen, lung, kidney, fat, muscle, brain, hippocampus, testicles or ovaries, large intestine, small intestine and stomach. The proposed method demonstrated fine precision and accuracy for analyzing ZCY-15 in selected tissues within the concentration range of standard liquid chromatography-tandem mass spectrometry. The whole analysis time was 3.6 min per sample. After oral administration, the blood and tissue concentrations of ZCY-15 in female rats were significantly higher than those in male rats. The clearance rate of ZCY-15 in female rats was lower than that in male rats. The results confirmed that there were gender differences. It has been shown that ZCY-15 could pass through the blood-brain barrier and was highly concentrated in the hippocampus. We established the first bioanalytical method to quantify ZCY-15 in rodent bio-samples for ongoing pharmacokinetic and tissue distribution studies, and the results were expected to lay foundation for the subsequent studies.

Structure and dynamics of ions in dipolar solvents: a coarse-grained simulation study.

We employ the coarse-grained molecular dynamics simulation to investigate the fundamental structural and dynamic properties of the ionic solution with and without the application of an external electric field. Our simulations, in which the solvent molecules are treated as Stockmayer fluids and the ions are modeled as spheres, can effectively account for the multi-body correlations between ion-ion, ion-dipole, and dipole-dipole interactions, which are often ignored by the mean-field theories or coarse-grained simulations based on a dielectric continuum. By focusing on the coupling between effects of ion solvation, electrostatic correlations and applied electric field, we highlight some nontrivial microscopic molecular features of the systems, such as the reorganization of the dipolar solvent, clustering of the ions, and diffusions of ions and dipolar solvent molecules. Particularly, our simulation indicates the nonmonotonic dependence of the ionic clustering and ion diffusion rates on the dipolar nature of the solvent molecules, as well as the amplification of these tendencies caused by the electric field application. This work provides insights into the fundamental understanding of physicochemical properties for ion-containing liquids and contributes to the design and development of ion-containing materials.

Efficacy and safety of urate-lowering treatments in patients with hyperuricemia: A comprehensive network meta-analysis of randomized controlled trials.

WHAT IS KNOWN AND OBJECTIVE: Hyperuricemia (HUA) and gout are considerable public health problems because of their increasing incidence and interactions with other diseases. We aimed to evaluate the efficacy and safety of urate-lowering therapies (ULTs) for patients. METHODS: A systematic literature review was conducted, and a network meta-analysis was performed on the included studies using the Markov Chain Monte Carlo simulation method and a Bayesian statistical framework. We calculated surface under the cumulative ranking curve (SUCRA) values and performed clustered ranking to combine the efficacy and safety results. RESULTS: Twenty-two randomized controlled studies were identified for the efficacy analysis, and 20 studies were identified for the safety analysis. Compared with the placebo, the ULTs were efficient and safe. Febuxostat 120 mg/d and allopurinol 200 mg/d had the highest SUCRA scores for efficacy and safety, respectively. Clustered ranking results showed that febuxostat 120 mg/d was the best in terms of efficacy and safety, topiroxostat 120/160 mg/d was similar to febuxostat 80 mg/d in terms of efficacy but safer, and allopurinol was not inferior to topiroxostat. WHAT IS NEW AND CONCLUSION: Febuxostat had the best efficacy and safety results among the tested agents, and topiroxostat and allopurinol appeared to have fewer adverse events.

Pharmacokinetics, bioavailability and tissue distribution study of JCC-02, a novel N-methyl-d-aspartate (NMDA) receptor inhibitor, in rats by LC-MS/MS.

JCC-02, N-(3,5-dimethyladamantan-1-yl)-N'-(3-chlorophenyl) urea, has been developed as a novel N-methyl-d-aspartate (NMDA) receptor inhibitor for the treatment of Alzheimer's disease (AD). In this study, a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed to determine the concentration of JCC-02 in rat plasma and different tissues to investigate its pharmacokinetic behavior in vivo and distribution character in organs. The matrix samples were prepared by protein precipitation method with acetonitrile using gliclazide as the internal standard (IS). This validated method was successfully applied to JCC-02 pharmacokinetic study in rats after oral administration of low (0.7 mg·kg-1), medium (2 mg·kg-1) and high (6 mg·kg-1) concentration, intravenous administration (2 mg·kg-1) as well as tissue distribution in rats after administration of JCC-02 (2 mg·kg-1) orally. The results indicated that the area under the time curve (AUC0-∞) and peak plasma concentration (Cmax) were directly proportional to dosage and the pharmacokinetic behavior of JCC-02 in rats was a linear process with respect to dosage. JCC-02 could be absorbed into blood circulation rapidly because of its short time to reach peak plasma concentration (tmax). Meanwhile, JCC-02 has a low clearance and a high volume of distribution, which might result in its long half-time. Oral absolute bioavailability (F) of JCC-02 was (14.61 ±â€¯5.81)%, which was turned out to be low relatively. In tissues, the differences of JCC-02 concentration were quite large. After administration, small intestine (22.29 ±â€¯15.86 µg·mL-1), stomach (7.21 ±â€¯2.87 µg·mL-1), large intestine (1.27 ±â€¯0.57 µg·mL-1), liver (0.96 ±â€¯0.52 µg·mL-1) and fat (0.48 ±â€¯0.24 µg·mL-1) were the first five organs with the largest drug concentration. Small intestine could be the main part of drug absorption where most of the drug was distributed after oral administration. More importantly, JCC-02 could cross the blood-brain barrier (BBB), which may probably have a pretty good therapeutic effect on AD.

Inhibition of paclitaxel resistance and apoptosis induction by cucurbitacin B in ovarian carcinoma cells.

Ovarian cancer is the leading cause of mortality among all gynecological malignancies. Drug resistance is a cause of ovarian cancer recurrence and low rate of overall survival. There is a requirement for more effective treatment approaches. Cucurbitacin B (CuB) is an antineoplastic agent derived from traditional Chinese medicinal herbs. Its activity against paclitaxel-resistant human ovarian cancer cells has, however, not yet been established. The purpose of the present study was to investigate the effect and mechanism of CuB on human paclitaxel-resistant ovarian cancer A2780/Taxol cells. Cell viability was evaluated by a cell counting assay, while cell cycle arrest and apoptosis were assessed by microscopy and flow cytometry, and proteins associated with apoptotic pathways and drug resistance were evaluated by western blotting. The present results demonstrated that CuB exerts dose- and time-dependent cytotoxicity against the ovarian cancer A2780 cell line, with half-maximal inhibitory concentration (IC50) values 0.48, 0.25 and 0.21 µM following 24, 48 and 72 h of incubation, respectively. Compared with its sensitive counterpart, A2780, paclitaxel-resistant A2780/Taxol cells had almost identical IC50 values. Cell cycle analysis demonstrated that treatment with CuB may induce cell cycle arrest at the G2/M phase of the cell cycle in the two cell lines. As revealed by Annexin V/propidium iodide-labeled flow cytometry and Hoechst 33258 staining, CuB-induced apoptosis was accompanied by activation of caspase-3 and downregulation of B-cell lymphoma-2. Western blotting demonstrated that CuB may enhance the expression of p53 and p21 in the two cell lines. CuB may also downregulate the expression of P-glycoprotein. These results indicate that CuB may exert a therapeutic effect on paclitaxel-resistant human ovarian cancer.

Growth inhibition and apoptosis induction by alternol in pancreatic carcinoma cells.

AIM: To investigate the effect of alternol on pancreatic cancer cells. METHODS: Pancreatic cancer cells PANC-1 and BxPC3 were treated with various concentrations of alternol for 24, 48 and 72 h. Cell proliferation was measured by cell counting. Cell cycle distribution and mitochondrial membrane potential were determined by flow cytometry. Apoptosis was determined by a TdT-mediated dUTP nick end labeling assay and Hoechst staining. Expression of caspase 3, Bcl-2, p53 and p21 was measured by western blotting. RESULTS: Alternol showed dose- and time-dependent inhibition of the proliferation of PANC-1 and BxPC3 cells in vitro. Alternol induced apoptosis and cell cycle arrest at S phase and decreased mitochondrial membrane potential. Alternol activated caspase 3, upregulated p53 and p21 expression, and downregulated Bcl-2 expression in a dose-dependent manner. CONCLUSION: Our results suggested that alternol is a candidate for treatment of pancreatic cancer.