Pharmacological Mechanism of Ganlu Powder in the Treatment of NASH Based on Network Pharmacology and Molecular Docking.

Nonalcoholic steatohepatitis (NASH), a progression of nonalcoholic fatty liver disease (NAFLD), is a clinical syndrome characterized by liver steatosis, inflammation, and hepatocellular damage. Ganlu powder (GLP) is a classic traditional Chinese medicine prescription that has shown favorable treatment effects on NASH. However, the underlying therapeutic mechanisms are still poorly understood. This study is aimed at exploring the potential mechanism of GLP in the treatment of NASH via network pharmacology and molecular docking. PubMed and CNKI databases were used to identify the components of GLP. Swiss and STITCH databases were employed to obtain corresponding drug targets. NASH targets were adopted from the Therapeutic Target Database (TTD), DisGeNET, DrugBank, GeneCards, and MalaCards databases. Cytoscape software was utilized to construct "drug-ingredient-target-disease" networks and the protein-protein interaction (PPI) network of GLP in NASH. AKT1 was identified as the key target. The GO functional enrichment analysis revealed that GLP might treat NASH by modulating the inflammatory response and regulating phosphatidylinositol 3-kinase signaling. The KEGG analysis showed that GLP might treat NASH by regulating the tumor necrosis factor (TNF) signal pathway by affecting the role of AKT1. According to the network pharmacology results, a virtual docking of active compounds with AKT1 was carried out, and the results indicated that the 7 components, berberine, epiberberine, jatrorrhizine, coptisine, palmatine, evodiamine, and rutecarpine, can bind stably with AKT1 and have higher binding energy than AKT1 inhibitors. The overall study findings suggest that GLP may treat NASH by regulating AKT1.

Uncovering the mechanism of Huanglian-Wuzhuyu herb pair in treating nonalcoholic steatohepatitis based on network pharmacology and experimental validation.

ETHNOPHARMACOLOGICAL RELEVANCE: The Huanglian-Wuzhuyu herb pair (HWHP) is a classic Chinese herbal formula consisting of the root of Coptis chinensis Franch and dried, nearly mature scented fruit of Tetradium ruticarpum (A.Juss.) T.G.Hartley. It is widely utilized to treat gastrointestinal and liver diseases such as diarrhea, dysentery, cholestasis, hepatocellular carcinoma, and nonalcoholic steatohepatitis (NASH). However, the mechanism of HWHP in treating NASH remains poorly understood. AIM OF THE STUDY: This study investigated the mechanisms of HWHP in NASH treatment via network pharmacology and validated the results through in vivo experiment using mouse models. MATERIALS AND METHODS: The compounds and targets corresponding to the active ingredients of HWHP were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) database. The genes associated with NASH were obtained from the DisGeNET database. Cytoscape software was employed to construct a "drug-ingredient-target-disease" network. Furthermore, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were employed to analyze the related signaling pathways affected by HWHP. Moreover, AutoDock software was used to assess the potential binding affinity between the key targets of the hub pathway and the bioactive compounds. Subsequently, in vivo experiment was conducted to verify the findings of network pharmacology. RESULTS: A total of 41 active compounds and 198 targets of HWHP were screened, of which 51 common targets were related to NASH. GO functional enrichment analysis revealed that HWHP may affect NASH by modulating inflammatory response. KEGG pathway enrichment suggested that the NOD-like receptor (NLR) signaling pathway may play an important role in treating NASH. Molecular docking results demonstrated that most HWHP components were successfully docked to NLRP3 with good binding energy. In vivo experiments revealed that HWHP alleviated liver inflammation, improved liver steatosis, reduced TC, TG, LDL-C, ALT, and AST, decreased mRNA expressions of IL-6, IL-18, and TNF-α in the liver, and lowered the expressions of NLRP3, pro-IL-1ß, and ASC protein. Also, immunohistochemical findings presented downregulation of caspase-1 and IL-1ß by HWHP. CONCLUSIONS: The results disclosed that HWHP ameliorates NASH in mice by reducing inflammation and liver steatosis via inhibition of NLRP3 inflammasome. This study revealed the mechanism of HWHP in treating NASH through experiments.

Novel photosensitive dual-anisotropic conductive Janus film endued with magnetic-luminescent properties and derivative 3D structures.

A new photosensitive dual-anisotropic conductive Janus film (PDCJF) is proposed for the first time. It is rationally designed and manufactured by facile electrospinning. PDCJF is firstly constructed using 2,7-dibromo-9-fluorenone (DBF) with photoconductive and luminescent properties. Janus nanofibers are respectively used as the building units to construct the top layer (T-PDCJF) and the bottom layer (B-PDCJF) of PDCJF. The two layers are tightly bonded to form PDCJF. Under light irradiation, there is photosensitive dual-anisotropic conduction in PDCJF, but there is no anisotropic conduction without light. Thus, the transition of PDCJF from mono-functional magnetism to tri-functionalities is realized under light and without light. The luminescence color of PDCJF is tunable and it emits white-light. This is made possible by modulating the amounts of luminescent substances and excitation wavelength. The microscopic Janus nanofibers used as building units and macroscopic Janus film structure ensure high photosensitive dual-anisotropic conduction and excellent fluorescence in PDCJF. The two-dimensional (2D) PDCJF is rolled to obtain three-dimensional (3D) Janus-type tubes and 2D plus 3D complete flag-like structures with exceptional multi-functionalities. The new findings can strongly guide in developing advanced multi-functional nanostructures.

Uncovering Abnormal Behavior Patterns from Mobility Trajectories.

Using personal trajectory information to grasp the spatiotemporal laws of dangerous activities to curb the occurrence of criminal acts is a new opportunity and method for security prevention and control. This paper proposes a novel method to discover abnormal behaviors and judge abnormal behavior patterns using mobility trajectory data. Abnormal behavior trajectory refers to the behavior trajectory whose temporal and spatial characteristics are different from normal behavior, and it is an important clue to discover dangerous behavior. Abnormal patterns are the behavior patterns summarized based on the regular characteristics of criminals' activities, including wandering, scouting, random walk, and trailing. This paper examines the abnormal behavior patterns based on mobility trajectories. A Long Short-Term Memory Network (LSTM)-based method is used to extract personal trajectory features, and the K-means clustering method is applied to extract abnormal trajectories from the trajectory dataset. Based on the characteristics of different abnormal behaviors, the spatio-temporal feature matching method is used to identify the abnormal patterns based on the filtered abnormal trajectories. Experimental results showed that the trajectory-based abnormal behavior discovery method can realize a rapid discovery of abnormal trajectories and effective judgment of abnormal behavior patterns.

A network pharmacology based approach for predicting active ingredients and potential mechanism of Lianhuaqingwen capsule in treating COVID-19.

The outbreak of severe respiratory disease caused by SARS-CoV-2 has led to millions of infections and raised global health concerns. Lianhuaqingwen capsule (LHQW-C), a traditional Chinese medicine (TCM) formula widely used for respiratory diseases, shows therapeutic efficacy in the application of coronavirus disease 2019 (COVID-19). However, the active ingredients, drug targets, and the therapeutic mechanisms of LHQW-C in treating COVID-19 are poorly understood. In this study, an integrating network pharmacology approach including pharmacokinetic screening, target prediction (targets of the host and targets from the SARS-CoV-2), network analysis, GO enrichment analysis, KEGG pathway enrichment analysis, and virtual docking were conducted. Finally, 158 active ingredients in LHQW-C were screen out, and 49 targets were predicted. GO function analysis revealed that these targets were associated with inflammatory response, oxidative stress reaction, and other biological processes. KEGG enrichment analysis indicated that the targets of LHQW-C were highly enriched to several immune response-related and inflammation-related pathways, including the IL-17 signaling pathway, TNF signaling pathway, NF-kappa B signaling pathway, and Th17 cell differentiation. Moreover, four key components (quercetin, luteolin, wogonin, and kaempferol) showed a high binding affinity with SARS-CoV-2 3-chymotrypsin-like protease (3CL pro). The study indicates that some anti-inflammatory ingredients in LHQW-C probably modulate the inflammatory response in severely ill patients with COVID-19.

Network pharmacology based virtual screening of active constituents of Prunella vulgaris L. and the molecular mechanism against breast cancer.

Prunella vulgaris L, a perennial herb widely used in Asia in the treatment of various diseases including cancer. In vitro studies have demonstrated the therapeutic effect of Prunella vulgaris L. against breast cancer through multiple pathways. However, the nature of the biological mechanisms remains unclear. In this study, a Network pharmacology based approach was used to explore active constituents and potential molecular mechanisms of Prunella vulgaris L. for the treatment of breast cancer. The methods adopted included active constituents prescreening, target prediction, GO and KEGG pathway enrichment analysis. Molecular docking experiments were used to further validate network pharmacology results. The predicted results showed that there were 19 active ingredients in Prunella vulgaris L. and 31 potential gene targets including AKT1, EGFR, MYC, and VEGFA. Further, analysis of the potential biological mechanisms of Prunella vulgaris L. against breast cancer was performed by investigating the relationship between the active constituents, target genes and pathways. Network analysis showed that Prunella vulgaris L. exerted a promising preventive effect on breast cancer by acting on tumor-associated signaling pathways. This provides a basis to understand the mechanism of the anti-breast cancer activity of Prunella vulgaris L.

Identification of urban regions' functions in Chengdu, China, based on vehicle trajectory data.

Data about human trajectories has been widely used to study urban regions that are attractive to researchers and are considered to be hotspots. It is difficult, however, to quantify the function of urban regions based on the varieties of human behavior. In this research, we developed a clustering method to help discover the specific functions that exist within urban regions. This method applies the Gaussian Mixture Model (GMM) to classify regions' inflow and trip count characteristics. It regroups these urban regions using the Pearson Correlation Coefficient (PCC) clustering method based on those typical characteristics. Using a large amount of vehicle trajectory data (approximately 1,500,000 data points) in the Chinese city of Chengdu, we demonstrate that the method can discriminate between urban functional regions, by comparing the proportion of surface objects within each region. This research shows that vehicle trajectory data in different functional urban regions possesses different time-series curves, while similar types of functional regions can be identified by these curves. Compared with remote sensing images and other statistical methods which can provide only static results, our research can provide a timely and effective approach to determine an urban region's functions.

The influences of accelerated aging on mechanical properties of veneering ceramics used for zirconia restorations.

This study evaluated the influences of accelerated aging on the mechanical properties of veneering ceramics used for zirconia frameworks. Five different veneering ceramics for zirconia frameworks were used. Twenty specimens were fabricated for each veneering ceramic. All specimens were divided into two groups. One was subjected to accelerated aging and the other was used as a control. Accelerated aging was performed in distilled water for 5 h at 200ºC and 2 atm. The density, open porosity, surface roughness, three-point flexural strength, and Vickers hardness were measured. The results showed that the density, open porosity, and surface roughness of all examined veneering ceramics were changed by the accelerated aging process. Accelerated aging was also found to have a positive effect on strength and a negative effect on the hardness.

Influences of multiple firings and aging on surface roughness, strength and hardness of veneering ceramics for zirconia frameworks.

OBJECTIVES: To evaluate the effects of multiple firings and aging on surface roughness, strength, and hardness of veneering ceramics for zirconia frameworks. METHODS: Five different veneering ceramics for zirconia frameworks were used: Vintage ZR (ZR), Cerabien ZR (CZR), VitaVM9 (VM9), Cercon ceram KISS (KISS), and IPS e.max ceram (e.max). Specimens were fired 2 or 10 times in order to accelerate aging. Surface roughness was evaluated using laser profilometry. Flexural strength and Vickers hardness were also measured. Surface topography was observed using scanning electron microscopy. RESULTS: After accelerated aging, the surface roughness of all specimens fired 10 times was significantly lower than that of the same specimens fired 2 times (P=0.000). Except for VM9, the flexural strength of all specimens fired 10 times was greater than that of the same specimens fired 2 times, and the differences were significant for ZR and CZR (P<0.01). The flexural strength of VM9 fired 10 times was significantly lower than that of VM9 fired 2 times (P=0.034). The Vickers hardness of ZR and VM9 fired 10 times was significantly higher than that of the same specimens fired 2 times (P<0.05), but that of KISS fired 10 times was significantly lower than that of KISS fired 2 times (P=0.000). CONCLUSIONS: Multiple firings had a positive effect on the surface roughness of all aged veneering ceramics used for zirconia restorations and on the strength and hardness of many aged veneering ceramics used for zirconia restorations.

The effects of repeated heat-pressing on the mechanical properties and microstructure of IPS e.max Press.

OBJECTIVES: We evaluated the effects of repeated heat-pressing on the mechanical properties and microstructure of IPS e.max Press. METHODS: A total of 20 specimens were fabricated including 10 heat-pressed once and another 10 heat-pressed twice. The density, porosity, and surface roughness (Ra) were evaluated. Three-point flexural strength following the ISO 6872 and Vickers hardness were measured, and fracture toughness (KIC) was calculated. Specimens were characterized using X-ray diffraction (XRD) and scanning electron microscopy (SEM). RESULTS: Compared to a single heat-press treatment, the density decreased and porosity increased after two heat-pressing events. A significant difference in density was observed. The flexural strength, Vickers hardness and fracture toughness significantly decreased after two heat-pressing events. The XRD patterns show that the intensity of the crystalline phase better corresponds to lithium disilicate (Li2Si2O5) after two heat-presses than only one. The SEM images detailed the interlocking microstructure of rod-shaped Li2Si2O5 crystals after one heat-press. These became oriented after two heat-presses, and the crystal size became larger. CONCLUSION: This study showed that repeated heat-pressing was detrimental to the density, porosity, strength, hardness, and toughness of IPS e.max Press.

MicroRNA networks in regulatory T cells.

MicroRNAs (miRNAs) are small regulatory RNAs that bind directly to complementary sequences on target messenger RNA (mRNA) transcripts, resulting in translational repression and/or target mRNA degradation. MiRNAs have been proven to play critical roles on the development, differentiation, and function of immune cells. Regulatory T cells (Tregs) are of importance in maintaining immune homeostasis and self-tolerance. Although many transcription factors and cytokines are known to regulate Tregs, scientists began to focus on the role of noncoding RNA on the regulation of Treg cells. This review provides an overview of the entire microRNA network and specific miRNAs in the development, differentiation, and function of Tregs.

Effects of ageing on surface textures of veneering ceramics for zirconia frameworks.

OBJECTIVES: To evaluate the effects of ageing on surface textures of veneering ceramics for zirconia frameworks. METHODS: Five different veneering ceramics for zirconia frameworks, Vintage ZR (ZR), Cerabien ZR (CZR), VitaVM9 (VM9), Cercon ceram KISS (KISS), and IPS e.max ceram (e.max), and one veneering ceramic with metal frameworks, Vintage MP (MP), were evaluated. Twenty specimens were fabricated from each veneering ceramic. All specimens were divided into two groups, one of which was subjected to accelerated ageing. The other was used as the control. Accelerated ageing was performed on the distilled water for 5h at 200°C and 2 atm. Surface textures were examined using laser profilometry, X-ray diffraction (XRD), scanning electron microscopy (SEM), and energy dispersive spectroscopy (EDS). RESULTS: Compared to unaged specimens, surface roughness parameters (Ra, Rp, Rv) of all aged specimens except e.max were significantly greater (P=0.000). Compared to the unaged specimens, sodium and potassium on the surfaces of all the aged specimens significantly decreased (P<0.05). However, oxygen levels increased significantly (P<0.05). Silicon showed a tendency to decrease in all aged specimens, and that of ZR, KISS and e.max have a significant decrease (P<0.01). Numerous ruffled cracks were observed on the surfaces of all aged specimens, as shown by SEM. The peaks of all crystalline phases on the surfaces of all specimens changed after accelerated ageing. CONCLUSION: Surface textures of all examined veneering ceramics were changed by the accelerated ageing test.

Effects of multiple firings on the mechanical properties and microstructure of veneering ceramics for zirconia frameworks.

OBJECTIVES: The purpose of this study is to evaluate the effects of multiple firings on the mechanical properties and microstructure of veneering ceramics used with zirconia frameworks. METHODS: Five different veneering ceramics for zirconia frameworks were used: Vintage ZR (ZR), Cerabien ZR (CZR), Vita VM9 (VM9), Cercon ceram KISS (KISS), IPS e.max ceram (e.max), and one veneering ceramic used for PFM frameworks: Vintage MP (MP). Twenty specimens were fabricated of each veneering ceramic. Ten specimens were fired twice and another ten specimens were fired ten times. Three-point flexural strength following the ISO 6872 and Vickers hardness were measured, and fracture toughness (K(IC)) was calculated. Density and porosity were determined. Specimens were characterized using X-ray diffraction (XRD) and scanning electron microscopy (SEM). RESULTS: For all materials, density increased and porosity decreased after 10 firings. Significant differences in density and porosity were observed between 2 and 10 firings, with the exception of VM9 (P<0.05). There were no significant differences in flexural strength between 2 and 10 firings except for MP. The Vickers hardness of ZR, VM9, KISS and MP increased significantly after 10 firings (P<0.001). There were no significant differences in fracture toughness for ZR, CZR, VM9 and MP between 2 and 10 firings. However, e.max underwent a significant increase in fracture toughness (P=0.000), and there was a significant decrease in the toughness of KISS after 10 firings (P=0.007). CONCLUSION: Multiple firings could be effective for improving the densification and the hardness of veneering ceramics for zirconia restorations. CLINICAL SIGNIFICANCE: By 10 firings, the density and hardness of the veneering ceramics used with zirconia frameworks were raised, and porosity was reduced. However, no significant changes occurred in flexural strength, fracture toughness or microstructure.

The relationship between milling a new silica-doped zirconia and its resistance to low-temperature degradation (LTD): a pilot study.

The aim of this study was to determine the machinability of new silica-doped Y-TZP by CAD/CAM and the resistance to low temperature degradation of the milled sample by comparing with a commercial HIP type Y-TZP material. The copings could be milled from silica-doped Y-TZP blocks without chipping, and there was no significant difference between the two types of Y-TZP materials in either the marginal or the inner gap between the abutment and the coping. After aging, the monoclinic content in the commercial Y-TZP copings increased from 25% before testing to 65%, while that of silica-doped Y-TZP copings slightly increased from 23% to 30%. The silica-doped Y-TZP copings did not have any significant difference in fracture load in a comparison between the control group and the aging group, while the commercial Y-TZP copings had a significantly lower fracture load for the aging group than for the control group.