[Mechanism of Alisma orientale in treating nonalcoholic fatty liver disease].

In this study, network pharmacology technology was combined with molecular docking technology and experimental verification to clarify the active ingredients, potential targets and mechanism of Alisma orientale for nonalcoholic fatty liver disease(NAFLD), providing a basis for its clinical application. The active ingredients of A. orientale were screened through traditional Chinese medicine systems pharmacology database(TCMSP), and the potential targets related to both active ingredients and NAFLD were predicted through protein databases by considering the oral bioavailability(OB) and drug-likeness(DL). The "active ingredient-potential target" network was constructed by using Cytoscape software, and the molecular docking was performed between active ingre-dients and potential targets. KEGG pathway analysis and enrichment analysis were performed through DAVID biological information annotation databases. ClueGO software was used to analyze target GO annotation. Western blot and immunocytochemistry were used to detect the protein expression levels, and fluorescent probe was used to detect the reactive oxygen species(ROS) generation level. The results revealed that 7 active ingredients of A. orientale were obtained from TCMSP database and analysis platform, 140 ingredient-related targets were screened, and 59 potential targets were obtained by intersecting disease targets with ingredient-related targets. Molecular docking showed that 7 active ingredients of A. orientale could act on the potential targets including 3-hydroxy-3-methylglutaryl-coenzyme A reductase(HMGCR) and tyrosine-protein phosphatase non-receptor type 1(PTPN1). In addition, KEGG enrichment analysis showed that the potential targets were mainly enriched in inflammatory mediator regulation, insulin resistance, neuroactive ligand-receptor interaction, vascular smooth muscle contraction, FcγR-mediated phagocytosis and other related pathways of tryptophan(TRP) channel. GO enrichment analysis showed that potential targets mainly affected the biological processes of G-protein coupled receptor signaling pathway, organic hydroxyl compound transport, positive regulation of lipid biosynthesis process, positive regulation of lipid metabolic process. Western blot, immunocytochemistry and fluorescent probe confirmed that the extract of A. orientale could reduce HMGCR and PTPN1 protein expression levels effectively, and also could reduce ROS production level of HepG2 cells. This study systematically revealed the material basis and mechanism of A. orientale in regulating NAFLD through multi-component, multi-target, and multi-pathway characteristics, which provided a theoretical basis and scientific basis for the clinical application of A. orientale.

Anti-PD-L1 antibody reverses the immune tolerance induced by multiple MUC1-MBP vaccine immunizations by increasing the CD80/PD-L1 ratio, resulting in DC maturation, and decreasing Treg activity in B16-MUC1 melanoma-bearing mice.

In this study, we explored the possible mechanism of tumor tolerance induced by multiple repeated immunizations with a tumor vaccine (MUC1-MBP fusion protein plus CpG2006). We first analyzed the mechanism of tolerance by immunizing tumor-bearing mice 2, 5, or 8 times and found that compared with five immunizations with the M-M vaccine, eight immunizations increased tumor volume and weight and Treg levels, while the proportions of Th1 and Tc1 cells in the spleen and lymph nodes were decreased. In particular, the M-M vaccine induced PD-L1 expression in CD11c + DCs and decreased their CD80/PD-L1 ratio. Therefore, the mechanism of tolerance induction by multiple immunizations with the M-M vaccine was investigated by focusing on the CD80/PD-L1 ratio, and an anti-PD-L1 antibody (αPD-L1) and the M-M vaccine were used in combination to treat melanoma. The results showed that αPD-L1 increased the CD80/PD-L1 ratio and enhanced the maturation of cDC1s by blocking PD-L1 on DCs, which potentially increased the activity of Th1 and Tc1 cells. Furthermore, the combination of the M-M vaccine with αPD-L1 decreased the activity and proportion of Tregs, which reversed the immune tolerance induced by eight immunizations with the vaccine. This study reveals the mechanism of the combination of M-M and αPD-L1 and provides a new combination strategy for improving the therapeutic effect of the M-M vaccine, laying a theoretical basis for the clinical application of the vaccine.

The anatomic relationship around the horizontal segment of petrous internal carotid artery: a study based on reconstructed computed tomography angiography.

PURPOSE: The anatomic relationship around the horizontal segment of petrous internal carotid artery (ICA) is complicated. Relative researches on human patients using radiographic technique are scarce. It is essential to get adequate anatomic knowledge about this region for performing some bypass procedures. METHODS: Using the independent software Mimics, we prospectively studied the 0.45-mm-thick computed tomography angiography (CTA) images of 29 patients (58 sides). All patients' middle cranial fossa and related critical anatomic structures were reconstructed in 3D. Some measurements were established on the multiplanar reconstructed images, including the distance from foramen ovale and foramen spinosum to the petrous ICA; the distance from the lumen of cochlea to the edge of trigeminal impression and petrous ICA; and the length of the horizontal segment of petrous ICA. RESULTS: The horizontal segment of petrous ICA was surrounded by the trigeminal impression, the cochlea and the auditory tube spatially. On the multiplanar reconstructed CTA images, the average distances from foramen ovale and foramen spinosum to the petrous ICA were 4.1 mm and 5.8 mm, respectively; the average distance from the lumen of cochlea to the edge of trigeminal impression and petrous ICA were 8.2 mm and 2.0 mm, respectively; and the mean length of the horizontal segment of petrous ICA was 15.8 mm. CONCLUSIONS: Our results indicate adequate and reliable anatomic information can be obtained using reconstructed CTA on an individualized basis.

Bi2S3 quantum dots in situ grown on MoS2 nanoflowers: An efficient electron-rich interface for photoelectrochemical N2 reduction.

Photoelectrocatalysis is considered a green, environmentally friendly, sustainable technology for NH3 synthesis. However, the low efficiency of ammonia synthesis is currently the primary problem in photoelectrochemical nitrogen reduction reactions (PEC NRR). Herein, a nanocomposite BQD/MS developed through the in-situ growth of Bi2S3 quantum dots (BQD) on MoS2 (MS) nanoflowers was demonstrated as an efficient PEC NRR catalyst. Experimental results showed that the strong interaction between BQD and MS modulated the interfacial charge distribution and increased the electron density on the MS side. Meanwhile, the excellent structure of BQD/MS promoted the effective migration of photogenerated electrons from excited BQD to the MS surface. The electron-rich MS reaction interface was conducive to cleaving the stable NN bond and improving the N2 reduction performance. As a result, the prepared BQD/15MS photocathode obtained an excellent Faradaic efficiency of 33.2% and an NH3 yield of 18.5 µg h-1 mg-1, which was about three times that of bare MS.

C-H Direct Arylated 6H-Indolo[2,3-b]quinoxaline Derivative as a Thickness-Dependent Hole-Injection Layer.

A novel perfluoro-1,4-phenylenyl 6H-indolo[2,3-b]quinoxaline derivative (TFBIQ) was designed and synthesized by using a C-H direct arylation method. The optoelectrical properties of the obtained TFBIQ were fully characterized by UV/Vis spectroscopy, photoluminescence spectroscopy, cyclic voltammetry, and a group of Alq3 -based green organic light-emitting diodes (OLEDs). Device A, which used 0.5 nm-thick TFBIQ as the interfacial modification layer, exhibited the five best advantages of device performance including a minimum turn-on voltage as low as 3.1 V, a maximum luminescence intensity as high as 26564 cd m-2 , a highest current density value of 348.9 mA cm-2 at a voltage of 11 V, the smallest efficiency roll-off, as well as the greatest power efficiency of 1.46 lm W-1 relative to all of the other tested devices with thicker TFBIQ and also 10 nm-thick MoO3 as hole-injection layers (HILs). As a promising candidate for an organic HIL material, the as-prepared TFBIQ exhibited a strong thickness effect on the performance of corresponding OLEDs. Furthermore, the theoretical calculated vertical ionization potential of the fluorinated TFBIQ suggests better anti-oxidation stability than that of the non-fluorinated structure.

Pi-Extended Diindole-Fused Azapentacenone: Synthesis, Characterization, and Photophysical and Lithium-Storage Properties.

Pi-extended polyaromatics tend to exhibit improved electronic properties with respect to the intrinsic structures. Herein, the rational design of a π-extended diindole-fused diazapentacenone (IP), with a nine-ring-fused core, obtained by applying an intramolecular Friedel-Crafts diacylation synthetic routine, is reported. The chemical structure, physical properties, and morphology of IP were fully characterized. Serving as an organic cathode material for a lithium-ion battery, the as-prepared nanorods of π-extended IP display higher conductivity and superior electrochemical performance than those of the naked diazapentacenone without diindole fusion.