Duloxetine protected indomethacin-induced gastric mucosal injury by increasing serotonin-dependent RANTES expression and activating PI3K-AKT-VEGF pathway.

Antidepressant duloxetine has been shown protective effect on indomethacin-induced gastric ulcer, which was escorted by inflammation in the gastric mucosa. Cytokines are the principal mediators of inflammation. Thus, by screening the differential expression of cytokines in the gastric mucosa using cytokine array at 3 h after indomethacin exposure, when the gastric ulcer began to format, we found that indomethacin increased cytokines which promoted inflammation responses, whereas duloxetine decreased pro-inflammatory cytokines increased by indomethacin and increased RANTES expression. RANTES was consistently increased by pretreated with both 5 mg/kg and 20 mg/kg duloxetine at 3 h and 6 h after indomethacin exposure in male rats. Selective blockade of RANTES-CCR5 axis by a functional antagonist Met-RANTES or a CCR5 antagonist maraviroc suppressed the protection of duloxetine. Considering the pharmacologic action of duloxetine on reuptake of monoamine neurotransmitters, we examined the serotonin (5-HT), norepinephrine and dopamine contents in the blood and discovered 20 mg/kg duloxetine increased 5-HT levels in platelet-poor plasma, while treatment with 5-HT promoted expression of RANTES in the gastric mucosa and alleviated the indomethacin-induced gastric injury. Furthermore, duloxetine activated PI3K-AKT-VEGF signaling pathway, which was regulated by RANTES-CCR5, and selective inhibitor of VEGF receptor axitinib blocked the prophylactic effect of duloxetine. Furthermore, duloxetine also protected gastric mucosa from indomethacin in female rats, and RANTES was increased by duloxetine after 6 h after indomethacin exposure too. Together, our results identified the role of cytokines, particularly RANTES, and the underlying mechanisms in gastroprotective effect of duloxetine against indomethacin, which advanced our understanding in inflammatory modulation by monoamine-based antidepressants.

Facile Tailoring of Surface Terminations of MXenes by Doping Nb Element: Toward Extraordinary Pseudocapacitance Performance.

MXenes show promising potential in supercapacitors due to their unique two-dimensional (2D) structure and abundant surface functional groups. However, most studies about MXenes have focused on tailoring surface structures by alternating synthesis methods or post-etch treatments, and little is known about the inherent relationship between surface groups and M elements. Herein, we propose a simple and novel strategy to adjust the surface structure of few-layered MXene flakes by adding a small amount of Nb element. Because of the strong affinity between Nb and O elements, the as-received V1.8Nb0.2CTx and Ti2.7Nb0.3C2Tx MXenes have much fewer -F functional groups and a higher O content than V2CTx and Ti3C2Tx MXenes, respectively. Thus, both V1.8Nb0.2CTx and Ti2.7Nb0.3C2Tx MXenes show enhanced pseudocapacitance performance. Especially, V1.8Nb0.2CTx delivers an ultrahigh volumetric capacitance of 1698 F/cm3 at a scan rate of 2 mV/s. Moreover, benefiting from the high activity of MAX precursors obtained through a fast self-propagating high-temperature synthesis, the etching time to produce V-based MXenes is much shorter than that in previous reports. Therefore, the results presented here are applicable to the surface engineering and rational design of 2D MXene materials and develop them into promising, cost-effective electrode materials for supercapacitors or other energy-storage equipment.

Efficient, Color-Stable, and Long-Lived White Organic Light-Emitting Diodes Utilizing Phosphorescent Molecular Aggregates.

Highly efficient and stable single-stack hybrid white organic light-emitting diode (WOLED) devices are developed using two emissive layers: one with amber-colored phosphorescent molecular-aggregate emission from the Pd(II) complex, Pd(II) 7-(3-(pyridine-2-yl-κN)phenoxy-κC)(benzo-κC)([c]benzo[4,5]imidazo-κN)[1,2-a][1,5]naphthyridine, Pd3O8-Py5, and the other with blue fluorescence emission. An optimized device structure achieves high color stability under various current densities, an external quantum efficiency (EQE) of 45.5%, a power efficiency of 97.4 Lm W-1 , and an estimated LT95 (operational time to 95% of the initial luminance) of 50 744 h at an initial luminance of 1000 cd m-2 .

Increasing Aspartoacylase in the Central Amygdala: The Common Mechanism of Gastroprotective Effects of Monoamine-Based Antidepressants Against Stress.

Monoamine-based antidepressants can prophylactically protect against stress-induced gastric ulcers. Although the central nucleus of amygdala (CeA) has been shown to modulate the severity of stress ulcers, little is known about the molecular mechanisms underlying the gastroprotective effect of this kind of drugs. Here, we first used proton magnetic resonance spectroscopy, a non-invasive tool, to explore the change of neurometabolites of the CeA of rats pretreated with the duloxetine of selective serotonin-norepinephrine reuptake inhibitors during 6 h of water-immersion restraint stress (WIRS). Duloxetine decreased N-acetyl-aspartate/creatine ratio (NAA/creatine) in CeA after WIRS, which was paralleled by the amelioration of gastric lesions. Meanwhile, the gastric ulcer index was negatively correlated with reduced NAA/creatine. Furthermore, the intra-CeA infusion of NAA aggravated WIRS-induced gastric mucosa damage, which suggested the crucial role of reduced NAA. Western blotting was performed to identify the specific enzymes responsible for the change of the contents of NAA at 0.5 h/3 h/6 h after WIRS, considering the preventative gastric protection of duloxetine. The NAA-catabolizing enzyme aspartoacylase (ASPA) was the only enzyme downregulated by 0.5 h WIRS and upregulated by duloxetine. Moreover, overexpressing ASPA in CeA alleviated stress ulcers. Additionally, all of the other three monoamine-based antidepressants, the fluoxetine of selective serotonin reuptake inhibitors, the amitriptyline of tricyclic agents, and the moclobemide of MAOs, increased ASPA expression in CeA. Together, these results indicate that increasing ASPA to hydrolyze NAA in CeA is a common mechanism of gastroprotective effects against stress exerted by monoamine-based antidepressants, and ASPA is a shared target more than monoamine regulation for this kind of drugs.

Stable and Efficient Near-Infrared Organic Light-Emitting Diodes Employing a Platinum(II) Porphyrin Complex.

Stable and efficient emitters are highly desired for near-infrared organic light-emitting diodes (NIR OLEDs) due to their extensive applications in biometric authentication, night vision display, and telecommunication. As this technology advances, there is an increasing demand for the development of NIR OLEDs with an emission spectrum beyond 900 nm. This work reports a stable and efficient near-infrared Pt(II) porphyrin complex, i.e., Pt(II) tetra(3,5-difluorophenyl)tetranaphthoporphyrin named PtTPTNP-F8, of which 84% of the total emitted photons are at wavelengths longer than 900 nm. By introducing fluorine atoms on the meta positions of all four phenyl groups, PtTPTNP-F8 can successfully overcome the common thermal instability issue emerging from the heavy Pt(II) porphyrin complexes, demonstrating a sublimation yield of above 90%. By carefully choosing the host materials, a NIR OLED device with PtTPTNP-F8 as an emissive material achieves a high peak device efficiency of 1.9%. Furthermore, devices of PtTPTNP-F8 fabricated in a stable device structure demonstrate extraordinary operational stability with an LT99 lifetime (time to 99% of the initial photocurrent) of more than 1000 h at a constant driving current density of 20 mA cm-2.

Efficient and Stable Molecular-Aggregate-Based Organic Light-Emitting Diodes with Judicious Ligand Design.

Phosphorescent molecular aggregates show promise in realizing efficient and stable organic light-emitting diodes (OLEDs) operating at high brightness level, which is highly desired for future lighting and display applications. Herein, four tetradentate Pd(II) complexes are prepared with judicious ligand design, and their electrochemical and photophysical properties are thoroughly examined. The studies indicate that slight structural changes of ligands can modify the hole and electron transporting capabilities, and alter the horizontal emitting dipole ratios of aggregates in amorphous film, the latter of which are sensitive to the thin-film deposition conditions including the deposition rate and the choice of the templating layer. An optimized OLED device using Pd3O8-Py5 aggregates exhibits a peak external quantum efficiency (EQE) of 37.3% and a reduced efficiency roll-off with high EQEs of 36.0% and 32.5% at 1000 and 10 000 cd m-2 , respectively. Moreover, such an efficient device demonstrates a long measured LT95 (time to 95% of the initial luminance) lifetime of over 500 h with an initial brightness of 17 304 cd m-2 corresponding to an estimated LT95 lifetime of 48 246 h at 1000 cd m-2 .

Multi-mode Organic Light-Emitting Diode to Suppress the Viewing Angle Dependence.

A typical top-emitting organic light-emitting diode (OLED) has a strong microcavity effect because of the two reflective electrodes. The cavity effect causes a serious color shift with the viewing angles and restricts the organic layer thickness. To overcome these drawbacks, we design a multi-mode OLED structure with dual-dielectric spacer layers, which extend the cavity length by more than 10 times. This design completely eliminates the intrinsic cavity effect caused by the top and bottom boundaries and provides freedom for the organic layer thickness. We demonstrate these effects in a white multi-mode OLED using a white emitter, which shows a negligible angular chromaticity shift of Δuv = 0.006 from 0 to 70° and a Lambertian emission profile. The simple design and the perfect angular color profiles make the multi-mode OLED structure promising in large-area displays and solid-state lighting applications.

DUOX2, a common modulator in preventive effects of monoamine-based antidepressants on water immersion restraint stress- and indomethacin- induced gastric mucosal damage.

Multiple kinds of monoamine-based antidepressants have been shown prophylactic effects in experimentally induced gastric ulcer. The loss of redox homeostasis plays a principle role in the development of peptic mucosal damage. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidases are one of the most important sources of reactive oxygen species within the gastrointestinal tract. It is unclear whether there are some common NADPH oxidases modulated by monoamine-based antidepressants in different gastric mucosal damage models. We explored the effects of selective serotonin-norepinephrine reuptake inhibitor (SNRI) duloxetine on the reactive oxygen species production and antioxidant capacity in the gastric mucosa of water immersion restraint (WIRS) or indomethacin treated rats, and examined the role of NADPH oxidases in the protective effects. Pretreated duloxetine prevented the increase of gastric mucosal NADPH oxidase activity and NADPH oxidase inhibitor apocynin dose-dependently protected gastric mucosa from damage by the two factors. Furthermore, dual oxidase 2 (DUOX2) and NADPH oxidase4 (NOX4) are involved in the protective effects of duloxetine in both models. We then examined NADPH oxidases expression modulated by the other monoamine-based antidepressants including selective serotonin reuptake inhibitor (SSRIs) fluoxetine, tricyclic agent (TCAs) amitriptyline and monoamine oxidase inhibitor (MAOs) moclobemide in the two models, and all the three antidepressants reduced the DUOX2 expression in the gastric mucosa. So DUOX2 was a common modulator in the preventive effects of all the monoamine-based antidepressants on WIRS- and indomethacin-induced gastric lesion. Our work provided a peripheral joint molecular target for monoamine modulatory antidepressants, which may be helpful to reveal the mechanisms of this kind of drugs more than monoamine regulation.

A Solution-Processable (Tetraaniline-b-Polyethylene Glycol)3 Star-Shaped Rod-Coil Block Copolymer with Enhanced Electrochromic Properties.

A novel electroactive star-shaped rod-coil copolymer composed of a benzene core and three symmetrically positioned tetraaniline-b-poly(ethylene glycol) arms, (TAni-b-PEG)3 rod-coil block copolymer, is synthesized successfully and characterized using Fourier transform infrared spectroscopy (FTIR), UV-vis, (1)H NMR, and matrix-assisted laser desorption/ionization (MALDI) mass spectrometry. Uniform and high-quality (TAni-b-PEG)3 thin films onto indium tin oxide-coated glass surface are fabricated simply from its DMF solution. Resulting (TAni-b-PEG)3 copolymer thin films possess excellent electrochromic properties with a high optical contrast of 73.3%, superb coloration efficiency of 318.5 cm(2) C(-1) at 750 nm. Very short switching times, that is, 2.11 s and 2.14 s for coloring and bleaching times, respectively, are observed as well. The mechanism of these impressive electrochromic properties of (TAni-b-PEG)3 thin films possessed is proposed based on the atomic force microscopy investigation, star-shaped molecular geometry, synergetic electronic and ionic conductivity and amphiphilic self-assembly feature of (TAni-b-PEG)3 copolymer, which can self-assemble to form cylinder pattern consisting of quick pathways for electronic charges and ionic species, respectively.