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Background: Outer membrane protein A (OmpA) is the major virulence factor of Acinetobacter baumannii and plays a wide role in the pathogenesis and antimicrobial resistance of A. baumannii. Dendritic cells (DCs) are the most effective antigen‐presenting cells and play a crucial role in regulating the immune response to multiple antigens and immune sentries. We aimed to study the role and molecular mechanisms of OmpA‐induced mouse bone marrow‐derived dendritic cells (BMDCs) autophagy in the immune response of A. baumannii. Methods: First, purified A. baumannii OmpA was assessed by sodium dodecyl sulfate‐polyacrylamide gel electrophoresis (SDS‐PAGE) and western blot. OmpA effect on BMDCs viability was evaluated by MTT assay. BMDCs were pretreated with autophagy inhibitor chloroquine or transfected with overexpression plasmids (oe‐NC or oe‐PI3K). Then BMDCs apoptosis, inflammatory cytokines, protein kinase B (PI3K)/mammalian target of rapamycin (mTOR) pathway, and autophagy‐related factors levels were evaluated. Results: SDS‐PAGE and western blot verified the successful purification of OmpA. BMDCs viability repressed gradually with the increase of OmpA concentration. OmpA treatment of BMDCs led to apoptosis and inflammation in BMDCs. OmpA caused incomplete autophagy in BMDCs, and light chain 3 (LC3), Beclin1, P62, and LC3II/I levels were significantly elevated with the increase of the time and concentration of OmpA treatment. Chloroquine reversed OmpA effects on autophagy in BMDCs, that was, LC3, Beclin1, and LC3II/I levels were reduced, while P62 level was elevated. Furthermore, chloroquine reversed OmpA effects on apoptosis and inflammation in BMDCs. PI3K/mTOR pathway‐related factor expression was affected by OmpA treatment of BMDCs. After overexpression of PI3K, these effects were reversed. Conclusions: A. baumannii OmpA induced autophagy in BMDCs involving the PI3K/mTOR pathway. Our study may provide a novel therapeutic target and theoretical basis for treating infections caused by A. baumannii. [ABSTRACT FROM AUTHOR]

Psittacosis is a rare zoonotic disease caused by Chlamydia psittaci infection, and tetracyclines are the preferred treatment. Omadacycline is a novel tetracycline that has a strong in vitro antibacterial activity against atypical pathogens, including C. psittaci; however, clinical data for its usage are lacking. We report a patient with severe C. psittaci-induced pneumonia presenting with a high fever, muscle aches, severe hepatic and renal insufficiency, and acute respiratory failure requiring tracheal intubation and mechanical ventilation. The condition was diagnosed using metagenomic next-generation sequencing. The patient was discharged after treatment with omadacycline. The findings of this study suggest that metagenomic next-generation sequencing is valuable for the rapid and accurate diagnosis of psittacosis. With its good safety profile and no requirement for dose adjustment in special populations, omadacycline is a new option for the treatment of severe C. psittaci pneumonia. However, additional case reports are needed to support this conclusion. [ABSTRACT FROM AUTHOR]

Mesoporous Pt-containing nanocomposites with well-organized pores are desirable for fuel cells as well as sensors, electronics, and various chemical reactions. However, it remains challenging to construct three-dimensional (3D) ordered honeycomb-like (OHC) nanostructures with Pt species anchored in the mesopores. Herein, we show for the first time an in situ strategy of developing an N-doped ordered honeycomb (N-OHC) nanopattern with well-dispersed Pt–N2 moieties by using the self-assembly of a block copolymer (BCP). The as-mentioned Pt including Pt single atoms (SAs) and Pt ∼2.5 nm ultrafine nanoparticles (NPs) was hierarchically located on the inner walls and the outer surfaces of the N-OHC mesopores (Pt/N-OHC), forming well-dispersed Pt–N active sites and showing efficient catalytic activity towards the oxygen reduction reaction (ORR). By changing the film thickness of the pristine Pt/BCP template, double-layered Pt/N-OHC could be designed and the ORR activity could be correspondingly improved, for which a current density of 1.60 A cm−2@0.6 V and a peak power density of 1.07 W cm−2 were observed at a very low Pt-loading of 0.04 mg cm−2, better than 1.21 A cm−2@0.6 V and 0.79 W cm−2 of the commercial Pt/C catalyst at a Pt-loading of 0.15 mg cm−2. The electron donating behavior of Pt–N2 and the pathway for O2 reduction were investigated via the density functional theory (DFT) computation. The electron transfer from Pt to N gave rise to the formation of Pt–N covalent bonds, which resulted in a lower d band center and a weaker O adsorption energy and endowed the Pt/N-OHCs with enhanced ORR activity. [ABSTRACT FROM AUTHOR]

Background: Delirium, a disorder of consciousness, often occurs for a period of time during hospitalisation. It is characterised by a disturbance of attention or awareness. Hyperactive delirium may lead to accidental removal of medical equipment, while hypoactive delirium may inhibit patients from participating in nursing interventions, medical treatment, and physical therapy. However, there are limited relevant studies of the strain of care of nurses in China when caring for patients with delirium. This study, thus, aimed to investigate the subjective level of the strain of care experienced by pulmonary and critical care nurses when caring for patients with delirium.Methods: This was a descriptive, cross-sectional study. A survey was conducted with 100 nurses in the Chinese pulmonary and critical care medical (PCCM) department in 2018. The Strain of Care for Delirium Index (SCDI) was used to measure nurses' strain of care. Participants were instructed to rate the degree of perceived difficulty in managing patients who displayed the behaviours listed in the SCDI, on a scale from 1 (quite easy) to 4 (very difficult). The mean ± standard deviation (SD) scores of the ranked difficulty scores were calculated.Results: In our sample, 47 % of the nurses had received delirium-related training previously. The three wards with the highest strain of care scores when caring for patients with delirium were the chronic obstructive pulmonary disease ward (3.29 ± 0.72), interstitial lung disease ward (3.11 ± 1.31), and respiratory intensive care unit (3.02 ± 0.78). The three types of patient behaviours associated with the highest degree of nursing strain of care were being uncooperative and difficult to manage (3.37 ± 0.84), pulling out tubes and tearing out dressings (3.33 ± 0.98), and irritability (3.22 ± 0.95).Conclusions: This study is the first to focus on nurses' subjective strain of care when caring for patients with delirium in PCCM departments in China. The findings suggest the need to pay more attention to the working status of Chinese nurses. Further trials with large samples assessing relevant outcomes of patients with delirium are warranted. [ABSTRACT FROM AUTHOR]

In order to investigate the effects of the substitution position on the photovoltaic performance of donor polymers, two benzothiophene ring substituted benzo(1,2-b:4,5-b′)dithiophene (BDT)-based conjugated polymers (PBDTBTs-BDD and PBDTTBs-BDD) are designed and synthesized. The variation in the substitution position has small influences on the photophysical properties but has a great effect on the intramolecular π–π stack structure, charge transport and photovoltaic properties. PBDTBTs-BDD (with the 6-position of the benzothiophene substituent) exhibited a smaller π–π stacking distance of 3.67 Å compared to 4.11 Å seen for PBDTTBs-BDD (with the 2-position of the benzothiophene substituent). And the charge mobilities of PBDTBTs-BDD-based devices are higher and more balanced than those of PBDTTBs-BDD-based devices, which are highly beneficial for reducing recombination of free carriers and then lead to a higher short-circuit current density (JSC) and fill factor (FF) of devices. With ITIC or Y6 as non-fullerene acceptors, PBDTBTs-BDD-based devices exhibit power conversion efficiencies (PCE) of 7.76% and 12.07%, respectively, which are higher than those of PBDTTBs-BDD-based devices (5.04% and 5.81%). This work demonstrates that the photovoltaic properties of donor polymers can be highly tunable through slight modifications of their side chain structures. [ABSTRACT FROM AUTHOR]

Background and Objective: Inhibition of thrombosis and platelet aggregation through a thromboxane synthetase inhibitor proved to be an effective and promising treatment for cardiovascular and/or cerebrovascular disease (CCVD) patients. This phase I study evaluated the safety, tolerability, and pharmacokinetics of sodium pyragrel, a novel thromboxane A2 synthetase inhibitor, in healthy volunteers. Methods: A total of 84 healthy Chinese volunteers were enrolled in the study and randomized into one of five dosing regimens of intravenous pyragrel, which were single ascending dose (30 to 300 mg), multiple doses (pyragrel 180 mg once daily on Day 1 and Day 6, twice daily from Day 2 to Day 5), 3×3 Latin square crossover (60, 120, 240 mg), and a continuous dose (360 mg in 24 h), respectively. Plasma concentrations were determined using HPLC-MS/MS. Pharmacokinetics parameters were calculated with non-compartment analysis. Results: The maximum plasma concentrations of pyragrel were essentially reached at the end of the 3 h infusion. The pharmacokinetic process of pyragrel and two main metabolites (BBS and BJS) is linear over the 30–300 mg dose range, with no significant accumulation on multiple doses. The urinary excretion of pyragrel accounted for more than 70% of the total drug amount. Preliminary pharmacodynamic results demonstrated that the production of urinary 11-D-HTXB2 was time- and dose-dependently inhibited by single i.v. dose of pyragrel. Conclusions: Pyragrel was well tolerated after single ascending doses up to 300 mg, multiple doses of 180 mg, and continuous administration of 360 mg within 24 h. No drug-related, serious adverse drug reactions occurred during the five-part study. The most common pyragrel-related adverse events (AEs) were total bilirubin (TB)/direct bilirubin (DB) elevations with a relatively low incidence rate and seemed to be dose independent. Given the acceptable safety and appropriate pharmacokinetic properties of sodium pyragrel proven in this study, continued clinical development is warranted. The study was registered at http://www.chictr.org.cn (ChiCTR-IID-16010159). [ABSTRACT FROM AUTHOR]

A series of Ni-modified Mo2C catalysts with La2O3-stabilized ZrO2 supports were synthesized via template method coupled with incipient wetness impregnation and temperature-programmed carbonization. The catalyst was tested in dry reforming of methane (DRM) reaction at the temperature range from 973 to 1173 K in a fixed-bed quartz reactor under atmospheric pressure. XRD, Raman, BET, H2-TPD, SEM, EDS and TEM were conducted to characterize the phase constitution, the pore structure, the morphology and the crystal structure of the catalysts. Ni-Mo2C nanoparticles of ~ 3 nm diameter were obtained for these catalysts, and the La2O3-ZrO2 supports exhibited a cubic lattice structure with a sheet shape, which is believed to contain an abundant of oxygen vacancies. And the synergistic interaction between the oxygen vacancy in La-Zr-O solid solution and the Ni-Mo2C particles could decrease the apparent activation energy of CO2. Both of them are beneficial for accelerating DRM reaction. CH4 conversion of the best specimen catalyst reaches 94% at 1173 K, and the catalyst maintains its stability after 100-h reaction. The superior catalytic activity of NMLZ-7.5 is attributed to the improved BET surface area (33.2 m2/g), smaller crystallites, grain boundaries and oxidation-carbonization cycle of Ni-Mo2C. [ABSTRACT FROM AUTHOR]

Introduction: Nerve growth factor (NGF) plays an important role in asthmatic inflammatory responses. However, the effects of NGF on dendritic cells (DCs) in asthmatic inflammation remain unknown. Therefore, we examined the effects of NGF on co-stimulatory molecules and the release of cytokines after ovalbumin (OVA) and a low dose of LPS (low LPS) stimulation of dendritic cells.Methods: Bone-marrow-derived dendritic cells (BMDCs) were collected from 6- to 8-week-old wide or TLR4−/−mice. BMDCs were treated with OVA and/or low LPS for 12h, and then stimulated with NGF for 24h. ELISA and flow cytometry were performed to measure TSLP, IL-6, IL-10, and IL-12 production and MHCII and CD86 expression on BMDCs. BMDCs were exposed to p75 neurotrophin receptor (p75NTR) inhibitor (TAT-Pep5) or NF-kB inhibitor (QNZ) 30 min prior to NGF 1 h after NGF intervention, the levels of RelA and RelB in cytoplasmic and nuclear were detected by west blot. Co-cultured BMDCs with naïve CD4+T cells, and ELISA was used to detect IL-4 and INF-γ levels.Results: NGF was found to markedly promote OVA and low LPS-induced expression of MHCII, CD86, secretion of TSLP and IL-6, and Th2-response-stimulating capacity of BMDCs. NGF affected BMDCs through LPS-induced p75NTR expression. TAT-Pep5 or QNZ could attenuate the promotive effect of NGF.Conclusions: NGF facilitates OVA with lowLPS-induced maturation of mouse BMDCs through LPS-up-regulated p75 NTR via activation of NF-κB pathways, providing another mechanism for the involvement of NGF in the Th2 response. [ABSTRACT FROM PUBLISHER]

Dimemorfan phosphate has been widely used for 40 years throughout the world for the treatment of coughs. This is the first report on the use of an LC-MS/MS-based assay for the determination of dimemorfan in human plasma using estazolam as an internal standard after one-step protein precipitation with acetonitrile. Chromatographic separation was achieved on a Phenomenex Luna C18 column (3 µm, 50 × 2.0 mm) using a fast gradient method, which involves water and methanol as the mobile phase (both containing 0.1% formic acid). Dimemorfan and estazolam were detected with proton adducts at m/z values of 255.8 → 155.1 and 295.0 → 267.0, respectively, in the selected reaction monitoring positive mode. The linear dynamic range of the assay was 0.04-5.00 ng/mL. The chromatographic run time for each plasma sample was <5 min. The method was proven to be accurate, precise, and repeatable. Finally, the developed method was successfully applied for the determination of dimemorfan in a pharmacokinetic study using healthy Chinese subjects. Copyright © 2014 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

In a proton exchange membrane (PEM) water electrolyser, Pt‐coated porous titanium plate always acts as the current collector both in the anode and cathode. However, the Pt particles on the Ti current collector cannot take part in the electrochemical reactions and thus lead to a lower utilization of the noble metal. In this work, the Pt‐coated Ti current collector is directly used as the cathode in the PEM water electrolyser instead of the conventional Pt/C electrode. To improve the performance, Nafion ionomer is coated on the Pt/Ti electrode to enlarge the electrochemical surface area (ECSA); the ECSA of the Pt/Ti electrode is increased by six times, and the utilization of Pt can be elevated to 45%. The voltage of the electrolyser with the Pt/Ti electrode is only 31 mV higher than the conventional Pt/C catalyst layer at 1 A cm−2. After stability tests, an obvious membrane thinning is observed using Pt/C as the cathode while the membrane of the electrolyser with the ionomer‐coated Pt/Ti cathode does not show a significant change in thickness. The F ion emission rate shows the membrane degradation rate is reduced by 15 times compared with the conventional Pt/C cathode. [ABSTRACT FROM AUTHOR]

Neutrophil extracellular traps (NETs) facilitate the extracellular killing of pathogens. However, excessive NETs formation and poor degradation are associated with exacerbated immune responses and tissue injury. In this study, we investigated the role of NETs in lipopolysaccharide (LPS)-mediated acute lung injury (ALI) and assessed the use of DNase I, for the treatment of ALI. Additionally, we focused on the controversial issue of whether LPS directly induces NETs release in vitro. NETs formation was detected in murine ALI tissue in vivo and was associated with increased NETs markers, citrullinated-histone H3 tissue levels and NET-DNA levels in BALF. Treatment with DNase I significantly degraded NETs and reduced citrullinated-histone H3 levels, which protected against ALI and ameliorated pulmonary oedema and total protein in BALF. In addition, DNase I significantly reduced IL-6 and TNF-α levels in plasma and BALF. In vitro, LPS-activated platelets rather than LPS alone efficiently induced NETs release. In conclusion, NETs formed during LPS-induced ALI, caused organ damage and initiated the inflammatory response. NETs degradation by DNase I promoted NET-protein clearance and protected against ALI in mice; thus, DNase I may be a new potential adjuvant for ALI therapy. Specifically, LPS induced NETs formation in an indirect manner via platelets activation. [ABSTRACT FROM AUTHOR]

Pyragrel is a novel thromboxane A2-synthetase inhibitor for the treatment of cerebral infarction, and it is currently being investigated in phase I clinical trials. This paper reports the first reliable LC–MS/MS method for the simultaneous determination of Pyragrel and its two main metabolites, M1 and M2, in human plasma. All analytes were extracted from human serum using liquid-phase extraction and separated on a Zorbax EcLipse XDB C18 column using isocratic elution with a mobile phase composed of methanol, water and formic acid (65:35:0.1, v/v/v). Determination of the analytes was achieved by tandem-mass spectrometry with positive electrospray ionization. The multiple reaction monitoring transitions under positive electrospray ionization were performed at m / z 329.0 →  m / z 135.9 for Pyragrel, m / z 303.1 →  m / z 135.0 for M1, m / z 331.2 →  m / z 135.0 for M2, and 482.2 →  m / z 258.0 for IS, respectively. The following parameters were validated: specificity, recovery, matrix effects, carry-over, linearity, sample stability under a variety of storage and handling conditions, and stock solution stability. The validated method has been successfully applied to an initial pharmacokinetic study in healthy volunteers following intravenous administrations of 60 mg of Pyragrel, and this method will facilitate further studies involving more comprehensive identification of the metabolic profile of Pyragrel and the appropriate dosage regimen. [ABSTRACT FROM AUTHOR]

To fabricate effective and stable OER electrode in water electrolysis, self-doped TiO 2 nanotube arrays which has a higher electrical conductivity than pristine TiO 2 nanotube arrays was used as the support for loading IrO 2 . The self-doped TNTA was fabricated by a simple electrochemical reduction of TNTA in neutral electrolyte solution, and then IrO 2 nano particles were deposited by pulse electro-deposition method. The cyclic voltammetric behavior, electrical conductivity and micro structure of self-doped TNTA prepared at different reduction potential were characterized to obtain an optimal performance, and self-doped TNTA prepared under −1.9 V (vs. Ag/AgCl) shows the best electrochemical performance. After depositing IrO 2 , the OER activity and stability of new electrodes were also determined. Due to the enhanced electrical conductivity of support, the mass activity of IrO 2 /self-doped TNTA are 50 times higher than IrO 2 /TNTA. The OER stability of new electrode was evaluated under constant current of 5 mA/cm 2 , IrO 2 /TNTA and IrO 2 /Ti were also tested for comparison. A higher stability of IrO 2 /self-doped TNTA electrode is observed than the other two electrodes, and XPS studies indicate a lower oxidation state of Ir in IrO 2 /self-doped TNTA, this shows a possible interactions between IrO 2 and the new support. [ABSTRACT FROM AUTHOR]

Reducing noble metal loading in membrane electrode assembly (MEA) can lower the cost of proton exchange membrane (PEM) water electrolyser, but it always leads to performance decline. In-plane conductivity of catalyst layer is mentioned very critical to the cell performance, and it is necessary to fully understand the role of planar electron transportation of catalyst layer. Herein, a bilayer cathode which consists of catalyst layer and planar electron conductive layer is developed to investigate the role of in-plane electron transportation. The additional planar electron conductive layer can significantly improve the performance of the cathode under low noble metal loading. The ohmic polarization as well as the active overpotential are reduced. The results highlight the benefit of bilayer structure and provide a method for enhancing the performance even though the catalyst layer is less homogeneous. Moreover, it can be also used to guide the design of cost-effective anode. • Additional electron transport layer was added. • Bilayer electrode shows a significant performance enhancement. • Bilayer structure can improve cell performance when catalyst layer is less homogeneous. [ABSTRACT FROM AUTHOR]

Highly efficient non-noble metal hydrogen evolution reaction (HER) catalysts are of particular importance for cost-effective proton exchange membrane water electrolyser (PEMWE). Here, hierarchical WMoC nano arrays (NAs) with superhydrophilic surface and optimal crystal facet is synthesized. Mo plays a crucial role in preferred growth of active crystal facet and the formation of NA. Thanks to the optimal crystal facet and unique structure, WMoC NA exhibits an enhanced HER activity and stability under high current density. PEMWE single cell based on WMoC cathode shows an outstanding performance, which obtains a current density of 1 A cm−2 at voltage of 1.888 V with N117 at 80 °C, making it one of the best PEMWEs using non-noble metal cathode. The single cell also shows a stable operation under 1A cm−2 at 80 °C over 700 h, demonstrating WMoC cathode's great potential for application use. • Superhydrophilic WMoC nanoarray with a pine-like morphology was fabricated. • Mo plays a crucial role in preferred growth of active crystal facet. • PEM electrolyzer achieved 1.888 V at 1 A cm−2 and 700 h stable operation with N117. [ABSTRACT FROM AUTHOR]