PP121, a dual inhibitor of tyrosine and phosphoinositide kinases, relieves airway hyperresponsiveness, mucus hypersecretion and inflammation in a murine asthma model.

BACKGROUND: Tyrosine kinase and phosphoinositide kinase pathways play important roles in asthma formation. As a dual tyrosine and phosphoinositide kinase inhibitor, PP121 has shown anticancer efficacy in multiple tumors. However, the study of PP121 in pulmonary diseases is still limited. Herein, we investigated the therapeutic activities of PP121 in asthma treatment. METHODS: Tension measurements and patch clamp recordings were made to investigate the anticontractile characteristics of PP121 in vitro. Then, an asthma mouse model was established to further explore the therapeutic characteristics of PP121 via measurement of respiratory system resistance, histological analysis and western blotting. RESULTS: We discovered that PP121 could relax precontracted mouse tracheal rings (mTRs) by blocking certain ion channels, including L-type voltage-dependent Ca2+ channels (L-VDCCs), nonselective cation channels (NSCCs), transient receptor potential channels (TRPCs), Na+/Ca2+ exchangers (NCXs) and K+ channels, and accelerating calcium mobilization. Furthermore, PP121 relieved asthmatic pathological features, including airway hyperresponsiveness, systematic inflammation and mucus secretion, via downregulation of inflammatory factors, mucins and the mitogen-activated protein kinase (MAPK)/Akt signaling pathway in asthmatic mice. CONCLUSION: In summary, PP121 exerts dual anti-contractile and anti-inflammatory effects in asthma treatment, which suggests that PP121 might be a promising therapeutic compound and shed new light on asthma therapy.

Duloxetine HCl Alleviates Asthma Symptoms by Regulating PI3K/AKT/mTOR and Nrf2/HO-1 Signaling Pathways.

Asthma is an inflammatory disease characterized by airway hyperresponsiveness, airway remodeling, and airway inflammation. In recent years, the prevalence of asthma has been increasing steadily and the pathogenesis of asthma varies from person to person. Due to poor compliance or resistance, existing drugs cannot achieve the desired therapeutic effect. Therefore, developing or screening asthma therapeutic drugs with high curative effects, low toxicity, and strong specificity is very urgent. Duloxetine HCl (DUX) is a selective serotonin and norepinephrine reuptake inhibitor, and it was mainly used to treat depression, osteoarthritis, and neuropathic pain. It was also reported that DUX has potential anti-infection, anti-inflammation, analgesic, antioxidative, and other pharmacological effects. However, whether DUX has some effects on asthma remains unknown. In order to investigate it, a series of ex vivo and in vivo experiments, including biological tension tests, patch clamp, histopathological analysis, lung function detection, oxidative stress enzyme activity detection, and molecular biology experiments, were designed in this study. We found that DUX can not only relax high potassium or ACh precontracted tracheal smooth muscle by regulating L-type voltage-dependent Ca2+ channel (L-VDCC) and nonselective cation channel (NSCC) ion channels but also alleviate asthma symptoms through anti-inflammatory and antioxidative response regulated by PI3K/AKT/mTOR and Nrf2/HO-1 signaling pathways. Our data suggests that DUX is expected to become a potential new drug for relieving or treating asthma.

Three-Dimensional MoS2/Reduced Graphene Oxide Nanosheets/Graphene Quantum Dots Hybrids for High-Performance Room-Temperature NO2 Gas Sensors.

This study presents three-dimensional (3D) MoS2/reduced graphene oxide (rGO)/graphene quantum dots (GQDs) hybrids with improved gas sensing performance for NO2 sensors. GQDs were introduced to prevent the agglomeration of nanosheets during mixing of rGO and MoS2. The resultant MoS2/rGO/GQDs hybrids exhibit a well-defined 3D nanostructure, with a firm connection among components. The prepared MoS2/rGO/GQDs-based sensor exhibits a response of 23.2% toward 50 ppm NO2 at room temperature. Furthermore, when exposed to NO2 gas with a concentration as low as 5 ppm, the prepared sensor retains a response of 15.2%. Compared with the MoS2/rGO nanocomposites, the addition of GQDs improves the sensitivity to 21.1% and 23.2% when the sensor is exposed to 30 and 50 ppm NO2 gas, respectively. Additionally, the MoS2/rGO/GQDs-based sensor exhibits outstanding repeatability and gas selectivity. When exposed to certain typical interference gases, the MoS2/rGO/GQDs-based sensor has over 10 times higher sensitivity toward NO2 than the other gases. This study indicates that MoS2/rGO/GQDs hybrids are potential candidates for the development of NO2 sensors with excellent gas sensitivity.

High-Hole-Mobility Metal-Organic Framework as Dopant-Free Hole Transport Layer for Perovskite Solar Cells.

A dopant-free hole transport layer with high mobility and a low-temperature process is desired for optoelectronic devices. Here, we study a metal-organic framework material with high hole mobility and strong hole extraction capability as an ideal hole transport layer for perovskite solar cells. By utilizing lifting-up method, the thickness controllable floating film of Ni3(2,3,6,7,10,11-hexaiminotriphenylene)2 at the gas-liquid interface is transferred onto ITO-coated glass substrate. The Ni3(2,3,6,7,10,11-hexaiminotriphenylene)2 film demonstrates high compactness and uniformity. The root-mean-square roughness of the film is 5.5 nm. The ultraviolet photoelectron spectroscopy and the steady-state photoluminescence spectra exhibit the Ni3(HITP)2 film can effectively transfer holes from perovskite film to anode. The perovskite solar cells based on Ni3(HITP)2 as a dopant-free hole transport layer achieve a champion power conversion efficiency of 10.3%. This work broadens the application of metal-organic frameworks in the field of perovskite solar cells.

Enable a Facile Size Re-distribution of MBE-Grown Ga-Droplets via In Situ Pulsed Laser Shooting.

A MBE-prepared Gallium (Ga)-droplet surface on GaAs (001) substrate is in situ irradiated by a single shot of UV pulsed laser. It demonstrates that laser shooting can facilely re-adjust the size of Ga-droplet and a special Ga-droplet of extremely broad size-distribution with width from 16 to 230 nm and height from 1 to 42 nm are successfully obtained. Due to the energetic inhomogeneity across the laser spot, the modification of droplet as a function of irradiation intensity (IRIT) can be straightly investigated on one sample and the correlated mechanisms are clarified. Systematically, the laser resizing can be perceived as: for low irradiation level, laser heating only expands droplets to make mergences among them, so in this stage, the droplet size distribution is solely shifted to the large side; for high irradiation level, laser irradiation not only causes thermal expansion but also thermal evaporation of Ga atom which makes the size-shift move to both sides. All of these size-shifts on Ga-droplets can be strongly controlled by applying different laser IRIT that enables a more designable droplet epitaxy in the future.

Synthesis of Cu2O-Modified Reduced Graphene Oxide for NO2 Sensors.

Nowadays, metal oxide semiconductors (MOS)-reduced graphene oxide (rGO) nanocomposites have attracted significant research attention for gas sensing applications. Herein, a novel composite material is synthesized by combining two p-type semiconductors, i.e., Cu2O and rGO, and a p-p-type gas sensor is assembled for NO2 detection. Briefly, polypyrrole-coated cuprous oxide nanowires (PPy/Cu2O) are prepared via hydrothermal method and combined with graphene oxide (GO). Then, the nanocomposite (rGO/PPy/Cu2O) is obtained by using high-temperature thermal reduction under Ar atmosphere. The results reveal that the as-prepared rGO/PPy/Cu2O nanocomposite exhibits a maximum NO2 response of 42.5% and is capable of detecting NO2 at a low concentration of 200 ppb. Overall, the as-prepared rGO/PPy/Cu2O nanocomposite demonstrates excellent sensitivity, reversibility, repeatability, and selectivity for NO2 sensing applications.

Gas Sensors Based on Chemically Reduced Holey Graphene Oxide Thin Films.

The nanosheet stacking phenomenon in graphene thin films significantly deteriorates their gas-sensing performance. This nanosheet stacking issue should be solved and reduced to enhance the gas detection sensitivity. In this study, we report a novel ammonia (NH3) gas sensor based on holey graphene thin films. The precursors, holey graphene oxide (HGO) nanosheets, were prepared by etching graphene under UV irradiation with Fenton reagent (Fe2+/Fe3+/H2O2). Holey graphene was prepared by the reduction of HGO (rHGO) with pyrrole. Holey graphene thin-film gas sensors were prepared by depositing rHGO suspensions onto the electrodes. The resulting sensing devices show excellent response, sensitivity, and selectivity to NH3. The resistance change is 2.81% when the NH3 level is as low as 1 ppm, whereas the resistance change is 11.32% when the NH3 level is increased to 50 ppm. Furthermore, the rHGO thin-film gas sensor could be quickly restored to their initial states without the stimulation with an IR lamp. In addition, the devices showed excellent repeatability. The resulting rHGO thin-film gas sensor has a great potential for applications in numerous sensing fields because of its low cost, low energy consumption, and outstanding sensing performance.

Polymer Foam-Supported Chemically Reduced Graphene Oxide Conductive Networks for Gas Sensing.

In this work, gas sensors based on chemically reduced graphene oxide (rGO) foams were reported for NH3 detection. Polymer foams were used as scaffolds to support rGO, and the resultant soft sensing devices exhibited a high sensitivity, high selectivity, and rapid recovery for NH3 detection at room temperature. The sensor showed more than 0.90% and 3.67% resistance changes respectively, when it's exposed to 1 ppm and 50 ppm NH3. The graphene foam gas sensors (FGS) also showed excellent repeatability. Furthermore, the response of rGO foam gas sensor to NH3 was more than two times higher than that to methanol vapors diluted to 1% of the saturated vapor concentration. Above all, the unique features, such as simple preparation, low cost and energy consumption, as well as excellent sensing performance, endow the sensor a great potential for NH3 detection.

Ammonia gas sensors based on chemically reduced graphene oxide sheets self-assembled on Au electrodes.

We present a useful ammonia gas sensor based on chemically reduced graphene oxide (rGO) sheets by self-assembly technique to create conductive networks between parallel Au electrodes. Negative graphene oxide (GO) sheets with large sizes (>10 µm) can be easily electrostatically attracted onto positive Au electrodes modified with cysteamine hydrochloride in aqueous solution. The assembled GO sheets on Au electrodes can be directly reduced into rGO sheets by hydrazine or pyrrole vapor and consequently provide the sensing devices based on self-assembled rGO sheets. Preliminary results, which have been presented on the detection of ammonia (NH3) gas using this facile and scalable fabrication method for practical devices, suggest that pyrrole-vapor-reduced rGO exhibits much better (more than 2.7 times with the concentration of NH3 at 50 ppm) response to NH3 than that of rGO reduced from hydrazine vapor. Furthermore, this novel gas sensor based on rGO reduced from pyrrole shows excellent responsive repeatability to NH3. Overall, the facile electrostatic self-assembly technique in aqueous solution facilitates device fabrication, the resultant self-assembled rGO-based sensing devices, with miniature, low-cost portable characteristics and outstanding sensing performances, which can ensure potential application in gas sensing fields.