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The design of highly electron-active and stable heterogeneous catalysts for the ambient nitrogen reduction reaction is challenging due to the inertness of the N

Rechargeable magnesium batteries (RMBs) are considered as potential energy storage devices due to their high volumetric specific capacity, good safety, as well as source abundance. Despite extensive efforts devoted to constructing an efficient magnesium battery system, the sluggish Mg

Arsenene, a two-dimensional (2D) monoelemental layered nanosheet composed of arsenic, was recently reported to feature outstanding anticancer activities. However, the specific biological mechanism of action remains unknown. In this work, we extensively analyzed the mechanism of arsenene

Thymic stromal lymphopoietin (TSLP), long known to be involved in Th2 response, is also implicated in multiple inflammatory dermatoses and cancers. The purpose of this study was to improve our understanding of the expression of TSLP in the skin of those dermatoses. Lesional specimens of representative immune-related dermatoses, including lichen planus (LP), discoid lupus erythematosus (DLE), eczema, bullous pemphigoid (BP), psoriasis vulgaris (PsV), sarcoidosis, and mycosis fungoides (MF), were retrospectively collected and analyzed by immunohistochemistry. Morphologically, TSLP was extensively expressed in the epidermis of each dermatosis, but the expression was weak in specimens of DLE. In a semiquantitative analysis, TSLP was significantly expressed in the epidermis in LP, BP, eczema, PsV, sarcoidosis, and MF. TSLP expression was higher in the stratum spinosum in LP, eczema, BP, PsV, and MF and higher in the stratum basale in sarcoidosis and PsV. Moreover, we found positive TSLP staining in the dermal infiltrating inflammatory cells of BP, PsV, and sarcoidosis. Our observation of TSLP in different inflammatory dermatoses might provide a novel understanding of TSLP in the mechanism of diseases with distinctly different immune response patterns and suggest a potential novel therapeutic target of those diseases.

We investigate the spatial distribution and dynamics of the vortices in rotating Rayleigh-B\'enard convection in a reduced Rayleigh-number range $1.3{\le}Ra/Ra_{c}{\le}166$. Under slow rotations ($Ra{\gtrsim}10Ra_{c}$), the vortices are randomly distributed. The size-distribution of the Voronoi cells of the vortex centers is well described by the standard $\Gamma$ distribution. In this flow regime the vortices exhibit Brownian-type horizontal motion. The probability density functions of the vortex displacements are, however, non-Gaussian at short time scales. At modest rotating rates ($4Ra_{c}{\le}Ra{\lesssim}10Ra_{c}$) the centrifugal force leads to radial vortex motions, i.e., warm cyclones (cold anticyclones) moving towards (outward from) the rotation axis. The mean-square-displacements of the vortices increase faster than linearly at large time. This super-diffusive behavior can be satisfactorily explained by a Langevin model incorporating the centrifugal force. In the rapidly rotating regime ($1.6Ra_{c}{\le}Ra{\le}4Ra_{c}$) the vortices are densely distributed, with the size-distribution of their Voronoi cells differing significantly from the standard $\Gamma$ distribution. The hydrodynamic interaction of neighboring vortices results in formation of vortex clusters. Inside clusters the correlation of the vortex velocity fluctuations is scale free, with the correlation length being approximately $30\%$ of the cluster length. We examine the influence of cluster forming on the dynamics of individual vortex. Within clusters, cyclones exhibit inverse-centrifugal motion as they submit to the motion of strong anticyclones, while the velocity for outward motion of the anticyclones is increased. Our analysis show that the mobility of isolated vortices, scaled by their vorticity strength, is a simple power function of the Froude number.

Yang Wang,1,* Zheng Wang,1,* Xiao Wu,1,* Song Zhu,2,* Qiru Guo,1 Zhong Jin,1 Zixian Chen,3 Delai Zhang,2 Wangming Hu,1 Huan Xu,1 Liangqin Shi,1 Lan Yang,1 Yong Wang1 1College of Basic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China; 2Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China; 3School of Ethnic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yong Wang, College of Basic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, People’s Republic of China, Tel +86 18280350393, Email yongwang1008@hotmail.com; wangyong@cdutcm.edu.cnPurpose: Dysfunction of endothelium is associated with multiple pathological vascular diseases. However, how to regulate reendothelialization after vascular injury is not well defined. This study aims to determine whether and how Paeonol controls reendothelialization following artery injury.Methods: The endothelium of murine carotid artery was denuded by catheter guide wires injury. H&E staining and IF staining were performed to determine whether Paeonol is critical for reendothelialization. BRDU Incorporation Assay, Boyden Chamber Migration Assay, Tube Formation Assay, and Spheroid Sprouting Assay were used to investigate whether Paeonol is involved in regulating proliferation and migration of endothelial cells. The underlying mechanism of how Paeonol regulates reendothelialization was determined by Molecular docking simulation and CO-IP Assay.Results: Paeonol treatment significantly inhibits neointima formation in carotid artery ligation model by promoting proliferation and migration of endothelial cells. Mechanistically, Paeonol enhances c-Myc expression, consequently interacts with VEGFR2 results in activating VEGF signaling pathway, and eventually promotes reendothelialization after vascular injury.Conclusion: Our data demonstrated that Paeonol plays a critical role in regulating vascular reendothelialization, which may be therapeutically used for treatment of pathological vascular diseases.Graphical Abstract: Keywords: Paeonol, c-Myc, VEGFR2, vascular injury, reendothelialization

The kinetic process of a slow oxygen evolution reaction (OER) always constrains the efficiency of overall water electrolysis for H2 production. In particular, nonprecious metal electrodes for the OER have difficulty simultaneously possessing good electrocatalytic activity and long-term stability in pH-universal media. In this work, urea is first used as a pore-forming agent and active C/N source to fabricate a nanoporous NiFeCoCN medium-entropy alloy (MEA) by high-temperature sintering based on the nanoscale Kirkendall effect. The NiFeCoCN MEA achieves an overpotential of 432 mV at a current density of 10 mA cm-2 and a lower Tafel slope of 52.4 mV dec-1 compared to the IrO2/Ti electrode (58.6 mV dec-1) in a 0.5 M H2SO4 solution. In a 1 M KOH solution, the NiFeCoCN MEA obtains an overpotential of 177 mV for 10 mA cm-2 and a Tafel slope of 36.1 mV dec-1, which is better than IrO2/Ni foam. This work proves a novel strategy to design and prepare nanoporous MEA materials with desirable C/N species, which provides promising prospects for the industrial production of H2 energy.

Background Erythrodermic psoriasis (EP) is a rare and life-threatening disease, the pathogenesis of which remains to be largely unknown. The dysregulated metabolites could be tightly associated with the disease pathogenesis.Objectives To explore the distinctive serum metabolic signature of EP.Methods Serum samples of 20 EP patients and 20 matched healthy controls were collected. Non-targeted metabolomics based on a high-throughput ultra-performance liquid chromatography mass spectrometry (UHPLC-MS) was conducted. Principal components analysis (PCA), partial least squares discriminant analysis (PLS-DA) and pathway analysis were performed.Results 65 metabolites of known identity were significantly changed in EP patients compared to controls, including 24 up-regulated metabolites and 41 down-regulated metabolites. EP patients had lower levels of glycerophosphocholines, including lysophosphatidylcholine (LPC), phosphatidylcholine (PC), and lysophosphatidyl ethanolamine (LPE). EP patients had lower levels of bile acids, including 7-ketodeoxycholic, deoxycholic and lithocholic acid. EP patients had lower esculetin and 3-hexenedioic acid levels. The area under the curve (AUC) value of esculetin, 7-ketodeoxycholic acid and 3-hexenedioic acid was higher than 0.90. Dysregulated metabolites were significantly enriched in the glycerophospholipid metabolism pathway.Conclusions The serum metabolic signature of EP was discovered. The down-regulated glycerophosphocholines and bile acids might take part in the development of EP. The dysregulated metabolites might be associated with damaged skin barriers and extensive skin inflammation. The metabolite differences help elucidate the development and pathogenesis of EP and they may provide insights for therapeutic interventions.

IntroductionOcular abnormalities and the development of retinal vasculature may cause postnatal retinopathy. In the past decade, tremendous progress has been made in identifying the mechanisms that regulate retina vasculature. However, the means of regulating embryonic hyaloid vasculature development is largely unknown. This study aims to determine whether and how andrographolide regulates embryonic hyaloid vasculature development.MethodsMurine embryonic retinas were used in this study. Whole mount isolectin B4 (IB4) staining, hematoxylin and eosin (H&E) staining, immunohistochemistry (IHC), and immunofluorescence staining (IF) were performed to determine whether andrographolide is critical for embryonic hyaloid vasculature development. BrdU incorporation assay, Boyden chamber migration assay, spheroid sprouting assay, and Matrigel-based tube formation assay were performed to evaluate whether andrographolide regulates the proliferation and migration of vascular endothelial cells. Molecular docking simulation and Co-immunoprecipitation assay were used to observe protein interaction.ResultsHypoxia conditions exist in murine embryonic retinas. Hypoxia induces HIF-1a expression; high-expressed HIF-1a interacts with VEGFR2, resulting in the activation of the VEGF signaling pathway. Andrographolide suppresses hypoxia-induced HIF-1a expression and, at least in part, interrupts the interaction between HIF-1a and VEGFR2, causing inhibiting endothelial proliferation and migration, eventually inhibiting embryonic hyaloid vasculature development.ConclusionOur data demonstrated that andrographolide plays a critical role in regulating embryonic hyaloid vasculature development.

Impairment of vascular endothelial integrity is associated with various vascular diseases. Our previous studies demonstrated that andrographolide is critical to maintaining gastric vascular homeostasis, as well as to regulating pathological vascular remodeling. Potassium dehydroandrograpolide succinate (PDA), a derivative of andrographolide, has been clinically used for the therapeutic treatment of inflammatory diseases. This study aimed to determine whether PDA promotes endothelial barrier repair in pathological vascular remodeling. Partial ligation of the carotid artery in ApoE−/− mice was used to evaluate whether PDA can regulate pathological vascular remodeling. A flow cytometry assay, BRDU incorporation assay, Boyden chamber cell migration assay, spheroid sprouting assay and Matrigel-based tube formation assay were performed to determine whether PDA can regulate the proliferation and motility of HUVEC. A molecular docking simulation and CO-immunoprecipitation assay were performed to observe protein interactions. We observed that PDA induced pathological vascular remodeling characterized by enhanced neointima formation. PDA treatment significantly enhanced the proliferation and migration of vascular endothelial cells. Investigating the potential mechanisms and signaling pathways, we observed that PDA induced endothelial NRP1 expression and activated the VEGF signaling pathway. Knockdown of NRP1 using siRNA transfection attenuated PDA-induced VEGFR2 expression. The interaction between NRP1 and VEGFR2 caused VE-Cad-dependent endothelial barrier impairment, which was characterized by enhanced vascular inflammation. Our study demonstrated that PDA plays a critical role in promoting endothelial barrier repair in pathological vascular remodeling.

Structure-based virtual screening is a key, routine computational method in computer-aided drug design. Such screening can be used to identify potentially highly active compounds, to speed up the progress of novel drug design. Molecular docking-based virtual screening can help find active compounds from large ligand databases by identifying the binding affinities between receptors and ligands. In this study, we analyzed the challenges of virtual screening, with the aim of identifying highly active compounds faster and more easily than is generally possible. We discuss the accuracy and speed of molecular docking software and the strategy of high-throughput molecular docking calculation, and we focus on current challenges and our solutions to these challenges of ultra-large-scale virtual screening. The development of Web services helps lower the barrier to drug virtual screening. We introduced some related web sites for docking and virtual screening, focusing on the development of pre- and post-processing interactive visualization and large-scale computing.