Search

New materials for oxygen evolution reaction (OER) electrocatalysts in alkaline conditions have been highly investigated in recent years for the advancement of water splitting. However, questions such as the lack of stability and the use of noble metals as electrocatalysts still need to be addressed. In this study, we report the synthesis and electrocatalytic properties of a series of wolframite tungsten‐based materials (MWO4, M=Fe, Mn, Ni, Co) towards OER in basic conditions. Our results showed that Ni0.5Mn0.5WO4 is a promising electrocatalyst, exhibiting ease of preparation, stability over the course of our experiments, and OER activity comparable to the standard iridium oxide. This study highlights the potential of wolframite tungsten‐based materials as a new class of electrocatalysts for OER in alkaline conditions. [ABSTRACT FROM AUTHOR]

Background. Granuloma annulare (GA) and sarcoidosis are granulomatous inflammatory diseases that share similarities. Objective. To identify the histological and immunohistochemical (IHC) features of GA and sarcoidosis. Methods. A retrospective review of 36 patients with GA and 26 with sarcoidosis was performed. Results from hematoxylin and eosin (H&E) staining and IHC staining of MMP-9 and pSTAT1 within the skin lesions of GA and sarcoidosis were analyzed, and random forest was applied for developing a predictive model. Results. Significantly greater expressions of MMP-9 (especially in elastic fibers, EFs, P < 0.0001) and pSTAT1 (P = 0.0003) were observed in lesion samples of GA versus sarcoidosis patients. In GA patients, MMP-9 was significantly upregulated in the interstitial type (P = 0.0222), while staining of pSTAT1 was positively correlated with the area of mucinous collagen in palisading GA (R = 0.5356 , P = 0.0484). In sarcoidosis patients, MMP-9 (R = − 0.7127 , P = 0.0009) and pSTAT1 (R = − 0.5604 , P = 0.0067) were found to show stronger expressions in lesions with less lymphocyte infiltration. The predictive model demonstrated an AUC of 0.9675. Conclusion. These results indicate that MMP-9 and pSTAT1 might exert roles in granulomatous inflammation in different modes, and the presence of more robust MMP-9 staining in EFs appears to be more suggestive of GA. [ABSTRACT FROM AUTHOR]

CRISPR/Cas9 is emerging as a platform for gene therapeutics, and the treatment efficiency is expected to be enhanced by combination with other therapeutic agents. Herein, we report a proton‐activatable DNA‐based nanosystem that enables co‐delivery of Cas9/sgRNA and DNAzyme for the combined gene therapy of cancer. Ultra‐long ssDNA chains, which contained the recognition sequences of sgRNA in Cas9/sgRNA, DNAzyme sequence and HhaI enzyme cleavage site, were synthesized as the scaffold of the nanosystem. The DNAzyme cofactor Mn2+ was used to compress DNA chains to form nanoparticles and acid‐degradable polymer‐coated HhaI enzymes were assembled on the surface of nanoparticles. In response to protons in lysosome, the polymer coating was decomposed and HhaI enzyme was consequently exposed to recognize and cut off the cleavage sites, thus triggering the release of Cas9/sgRNA and DNAzyme to regulate gene expressions to achieve a high therapeutic efficacy of breast cancer. [ABSTRACT FROM AUTHOR]

Neuraminidase (NA) inhibitors are one of the two major classes of antivirals available for the treatment and prevention of influenza. X‐ray crystal structure determination of NA head domains and their complexes with various inhibitors are of importance for the design and optimization of anti‐influenza drugs. However, the globular tetrameric properties of NA head domains may produce crystals with pathological imperfections, lattice‐translocation defects, making structure determination no longer straightforward. In this report, using a crystal of the NA head domain from the Wuhan Asiatic toad influenza virus as an example, the identification and solution of this type of crystal pathology are presented. Furthermore, its underlying mechanism of formation is explored. [ABSTRACT FROM AUTHOR]

Image steganography is the technique of hiding secret information within images. It is an important research direction in the security field. Benefitting from the rapid development of deep neural networks, many steganographic algorithms based on deep learning have been proposed. However, two problems remain to be solved in which the most existing methods are limited by small image size and information capacity. In this paper, to address these problems, we propose a high capacity image steganographic model named HidingGAN. The proposed model utilizes a new secret information preprocessing method and Inception‐ResNet block to promote better integration of secret information and image features. Meanwhile, we introduce generative adversarial networks and perceptual loss to maintain the same statistical characteristics of cover images and stego images in the high‐dimensional feature space, thereby improving the undetectability. Through these manners, our model reaches higher imperceptibility, security, and capacity. Experiment results show that our HidingGAN achieves the capacity of 4 bits‐per‐pixel (bpp) at 256 × 256 pixels, improving over the previous best result of 0.4 bpp at 32 × 32 pixels. [ABSTRACT FROM AUTHOR]

In intervertebral disc degeneration (IDD), increased proinflammatory molecules secreted by human nucleus pulposus cells (HNPCs) could promote the expression of extracellular matrix (ECM)‐degrading enzymes. IDD could be affected by both genetic and environmental factors, including microRNAs (miRNAs). Aucubin, the active ingredient of a traditional Chinese medicine herb Du Zhong, has been reported to promote osteogenic differentiation; however, the role of aucubin in IDD and the underlying mechanism remain unclear. Herein, we evaluated the effect of aucubin on TNF‐α‐ or IL‐1β‐induced ECM degradation in HNPCs. By using online tools, miR‐140 was selected as a candidate miRNA that is related to TNF‐α or IL‐1β signaling. Overexpression of miR‐140 enhanced the effect of aucubin on ECM degradation. Moreover, cAMP responsive element binding protein 1 (CREB1), a major transcriptional factor in immune‐related signaling, was a direct downstream target of miR‐140. CREB1 knockdown mimicked the function of miR‐140 overexpression on ECM degradation. In summary, aucubin might ameliorate IL‐1β‐ or TNF‐α‐induced ECM degradation in HNPCs through regulating miR‐140/CREB1. [ABSTRACT FROM AUTHOR]

Two‐dimensional materials have large specific area, high electron transfer capability and abundant exposed active sites, which are beneficial to improve their catalytic properties. Here, we used a simple salt‐template method to construct ultrathin graphene‐like Fe/N−C nanosheets (named as Fe/GNS‐1.5). During the synthesis process, NaCl crystallite serves as a rigid template of two‐dimensional mesoscopic structure. Iron nitrate acts as a gas‐foaming agent, which plays pivotal part in the morphology and structure of catalysts. The obtained Fe/GNS‐1.5 nanosheets with a thickness of 3 nm have a large specific surface area (705 m2 g−1). Benefiting from the structure advantages, Fe/GNS‐1.5 exhibits a great bifunctional catalytic performance. The Fe/GNS‐1.5 catalyst is employed as air cathode of zinc−air battery to examine its practical application, which presents excellent power density (156 mW cm−2) and favorable cyclic stability for more than 600 cycles. [ABSTRACT FROM AUTHOR]

A novel super‐resolution (SR) reconstruction algorithm based on multisource bidirectional similarity and non‐local similarity matching for multi‐exposure dynamic image sequences is proposed in this study. First, luminance compensation for multi‐exposure dynamic images is implemented based on multisource bidirectional similarity. Then, combining a self‐adaptive regional correlation evaluation strategy and a weighting strategy based on pseudo‐Zernike moment feature similarity and structural similarity yields a novel and robust non‐local similarity matching scheme (PZ‐NSM) to learn non‐local similarity priors between low‐ and high‐resolution dynamic image patches at different spatio‐temporal scales without additional training. Finally, SR reconstruction is implemented based on PZ‐NSM and spatio‐temporal trans‐scale fusion of non‐local similarities between dynamic images. The proposed algorithm does not rely on accurate estimation of subpixel motion and can therefore be adapted to more complex motion patterns. It has high rotation invariance effectiveness and is robust to noise and illumination. Experimental results demonstrate that the proposed algorithm outperforms existing algorithms in terms of both subjective and objective evaluations. [ABSTRACT FROM AUTHOR]

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • An increasing number of drugs on the market or under development have been identified as substrates of the ATP-binding cassette drug efflux transporter breast cancer resistance protein (BCRP; ABCG2), which can affect the pharmacokinetics of drugs by reducing absorption and/or increasing biliary elimination. • ABCG2 C421A, a single nucleotide polymorphism associated with decreased protein expression/transport activity in vitro and higher anti-cancer drug concentrations in carriers of the C421A polymorphism, may contribute to the intersubject pharmacokinetic variability of BCRP substrates. • Predicting the potential influence of BCRP on drug disposition or drug interactions is challenging because of the lack of a well-characterized, BCRP-selective clinical probe substrate. • Nitrofurantoin is potentially a suitable clinical BCRP probe substrate based on preclinical and clinical information available (e.g. in vitro transport studies, Bcrp knockout mouse studies, inhibition studies in rats, and milk secretion studies in rats and humans). WHAT THIS STUDY ADDS • The ABCG2 C421A SNP had no effect on oral nitrofurantoin plasma and urine pharmacokinetic parameters in healthy male Chinese subjects. • Nitrofurantoin does not appear to be a useful clinical BCRP probe. AIMS A number of drugs are substrates or inhibitors of the efflux transporter breast cancer resistance protein (BCRP; ABCG2), which can limit systemic exposure by reducing absorption and/or increasing biliary elimination. The identification of a BCRP-selective clinical probe drug would provide a useful tool to understand the effect of genetic polymorphisms and transporter-based drug interactions on drug pharmacokinetics. The aim of this study was to assess the utility of nitrofurantoin as a clinical probe substrate for BCRP activity by evaluating the impact of genetic variation on nitrofurantoin pharmacokinetics. METHODS Nitrofurantoin pharmacokinetics were studied in an open-label, single-oral dose (100 mg) study in 36 male Chinese subjects who were pre-screened for ABCG2 421 CC, CA and AA genotypes ( n = 12 each). Plasma and urine concentrations of nitrofurantoin were determined by LC/MS/MS and LC/UV respectively.anova was used to compare pharmacokinetic parameters among genotypes. RESULTS There were no significant differences in nitrofurantoin pharmacokinetics among the genotypic cohorts. The geometric mean nitrofurantoin plasma AUC(0-∞) (95% confidence interval) values were 2.21 (2.00, 2.45), 2.42 (2.11, 2.78) and 2.32 (1.99, 2.70) µg h ml−1 and half-life values were 0.79 (0.59, 1.0), 0.76 (0.64, 0.89) and 0.72 (0.62, 0.84) h for ABCG2 421 genotypes CC, CA and AA, respectively. The percentage of dose excreted unchanged in the urine was 43, 44 and 39%, respectively. CONCLUSIONS The ABCG2 C421A polymorphism had no effect on nitrofurantoin plasma and urine pharmacokinetic parameters in healthy Chinese subjects. These results indicate that nitrofurantoin is not a suitable clinical probe substrate for assessing BCRP activity. [ABSTRACT FROM AUTHOR]

Aim: To characterize the formation and urinary elimination of metabolites of S-(+) and R-(-) methamphetamine (MA) in humans., Methods: In this 12-subject, six-session, double-blind, placebo-controlled, balanced, crossover design study, the formation of the MA metabolites para hydroxymethamphetamine (pOH-MA) and amphetamine (AMP) were determined in urine after intravenous doses of S-(+)-MA 0.25 and 0.5 mg kg(-1), R-(-)-MA 0.25 and 0.5 mg kg(-1), racemic MA 0.5 mg kg(-1), or placebo. Parent drug and metabolite levels in urine and plasma were measured by gas chromatography-mass spectrometry. Pharmacokinetic parameters were calculated by noncompartmental models using WinNonlin., Results: An approximately threefold enantioselectivity difference in elimination was observed for AMP, with 7% of the dose converted to S-(+)-AMP vs. 2% to R-(-)-AMP (P < 0.001). Furthermore, less R-(-)-pOH-MA was excreted in the urine compared with S-(+)-pOH-MA (8% vs. 11%, P= 0.02). Correspondingly, S-(+)-MA excretion was less than R-(-)-MA (42% vs. 52%; P= 0.005)., Conclusions: The metabolism of MA is enantioselective, with formation of AMP having the highest isomer selectivity. A greater percentage of MA is converted to pOH-MA (8-11%) than AMP (2-7%). The formation of pOH-MA was less affected by the MA enantiomer administered, suggesting that urine pOH-MA may be a more stable biomarker of MA metabolism.