d_abstr_R Rhizoma drynariae is the main traditional Chinese medicine used for the treatment of osteoporosis, but its anti-osteoporotic targeting mechanism has not been fully elucidated due to the ...complexity of its active ingredients. In this study, the pharmacological mechanism of action of Rhizoma drynariae against osteoporosis was studied by integrating pharmacological concepts. The pharmacokinetic characteristics of selected major active constituents of Rhizoma drynariae and the SMILES structural similarity were used to predict related targets. A literature search was conducted to identify known osteoporosis treatment targets, which were then combined with the predicted targets to construct the direct or indirect target interaction network map of Rhizoma drynariae against osteoporosis. Finally, data on the key targets of the interactions, ranked according to relevant node parameters obtained through pathway enrichment analysis and screening of key targets and active ingredients of Rhizoma drynariae, were used to perform molecular docking simulation. We screened 16 active ingredients of Rhizoma drynariae, and 7 key targets with direct or indirect effects with a high frequency were obtained. These main pathways were found to play important roles in the PI3k-akt signaling pathway, osteoclast differentiation, Wnt signaling pathway, and estrogen signaling pathway. Molecular docking showed that most active ingredients of Rhizoma drynariae had strong binding efficiency with key targets. Based on network pharmacology, we conclude that Rhizoma drynariae plays an anti-osteoporotic role by directly or indirectly targeting multiple major signaling pathways and influencing the proliferation and differentiation of multiple types of cells.
Online product reviews are becoming increasingly important due to their guidance function in people’s purchase decisions. As being highly subjective, online reviews are subject to opinion spamming, ...i.e., fraudsters write fake reviews or give unfair ratings to promote or demote target products. Although there have been much efforts in this field, the problem is still left open due to the difficulties in gathering ground-truth data. As more and more people are using Internet in everyday life, group review spamming, which involves a group of fraudsters writing hype-reviews (promote) or defaming-reviews (demote) for one or more target products, becomes the main form of review spamming. In this paper, we propose a LDA-based computing framework, namely GSLDA, for group spamming detection in product review data. As a completely unsupervised approach, GSLDA works in two phases. It first adapts LDA (Latent Dirichlet Allocation) to the product review context in order to bound the closely related group spammers into a small-sized reviewer cluster, and then it extracts high suspicious reviewer groups from each LDA-clusters. Experiments on three real-world datasets show that GSLDA can detect high quality spammer groups, outperforming many state-of-the-art baselines in terms of accuracy.
•An Ohno continuous casting was applied to purify the copper of scrap copper.•Numerical simulation of solidification model can clarify the OCC process.•Morphology and EBSD analysis showed the ...structure of single crystal copper.•Resistance of single crystal copper is smaller than ordinary copper wire.
How to realize the high value-added utilization of scrap copper from e-waste is a meaningful topic. In the study, an Ohno Continuous Casting (OCC) process is an existing method you applied to purify the copper. Based onthe model of diffusion-controlled grain growth kinetics, the redistribution of impurity of tin in the scrap copper were studied under the different continuous casting speed and mold temperature. On the centerline, macrosegregation in the axial direction of the tin was more obvious with the decrease of continuous casting speed. The small continuous casting rate was beneficial to the segregation and enrichment of tin. The axial segregation gradually decreased with the increase of the mold temperature. The flattening of the liquid–solid interface resulted in a weakening of the solute enrichment at the root of the interface with the increase of temperature. Morphology, electron backscattered diffraction (EBSD) analysis showed the structure of single crystal copper. The range of resistance of single crystal copper was from 5 × 10-6 to 3 × 10-5 Ω m. Obviously, the resistance of the single crystal copper was significantly smaller than that of ordinary copper wire (9.0 × 10-3 Ω m). This study provided a key theoretical and practical basis for the high value-added reuse of copper in e-waste.
Farnesoid X receptor (FXR), a nuclear receptor mainly expressed in enterohepatic tissues, is a master for bile acid, lipid and glucose homeostasis. Additionally, it acts as a cell protector with ...unclear mechanism but may be implicated in combating against inflammation, fibrosis and cancers. FXR is thus accepted as a promising target particularly for the enterohepatic diseases, and numerous FXR modulators have been patented and developed.
This review provides an update on the development of FXR modulators for enterohepatic diseases and offers an in-depth perspective on new strategies for the development of novel FXR modulators.
Despite the development of numerous FXR modulators, which culminated in the successful launch of obeticholic acid (OCA), it remains a matter of debate on how the function of FXR should be exploited for therapeutic purposes. The improvement for obesity achieved by either FXR agonists or antagonists is still in confusion. Whether the side effect of pruritus induced by OCA could be exempted for non-steroidal FXR agonists needs further validation. Apart from the development of conventional FXR ligands, emerging evidence support that restoration of FXR protein level may represent a new strategy in targeting FXR for enterohepatic and metabolic diseases.
Newly synthesized H3.1 and H3.3 histones are assembled into nucleosomes by different histone chaperones in replication-coupled and replication-independent pathways, respectively. However, it is not ...clear how parental H3.3 molecules are transferred following DNA replication, especially when compared to H3.1. Here, by monitoring parental H3.1- and H3.3-SNAP signals, we show that parental H3.3, like H3.1, are stably transferred into daughter cells. Moreover, Mcm2-Pola1 and Pole3-Pole4, two pathways involved in parental histone transfer based upon the analysis of modifications on parental histones, participate in the transfer of both H3.1 and H3.3 following DNA replication. Lastly, we found that Mcm2, Pole3 and Pole4 mutants defective in parental histone transfer show defects in chromosome segregation. These results indicate that in contrast to deposition of newly synthesized H3.1 and H3.3, transfer of parental H3.1 and H3.3 is mediated by these shared mechanisms, which contributes to epigenetic memory of gene expression and maintenance of genome stability.
As fossil fuels continue to be extracted and used, issues such as environmental pollution and energy scarcity are surfacing. For the transportation industry, the best way to achieve the goal of ...“carbon neutrality” is to research efficient power systems and develop new alternative fuels. As the world’s largest product of chemicals, ammonia is a new renewable fuel with good combustion energy. It can be used as an alternative fuel to reduce carbon emissions because of its proven production process, low production and transportation costs, safe storage, the absence of carbon-containing compounds in its emissions, and its future recyclability. This paper firstly introduces the characteristics of ammonia fuel engine and its problems; then it summarizes the effects of various ammonia-blended fuels on the combustion and emission characteristics of the engine from the combustion problem of ammonia-blended engine; then the fuel storage of ammonia-blended hydrogen is discussed, the feasibility of hydrogen production instead of hydrogen storage is introduced.
The association among pathological response, recurrence-free survival (RFS) and overall survival (OS) with neoadjuvant therapy in melanoma remains unclear. In this study, we pooled data from six ...clinical trials of anti-PD-1-based immunotherapy or BRAF/MEK targeted therapy. In total, 192 patients were included; 141 received immunotherapy (104, combination of ipilimumab and nivolumab; 37, anti-PD-1 monotherapy), and 51 received targeted therapy. A pathological complete response (pCR) occurred in 40% of patients: 47% with targeted therapy and 33% with immunotherapy (43% combination and 20% monotherapy). pCR correlated with improved RFS (pCR 2-year 89% versus no pCR 50%, P < 0.001) and OS (pCR 2-year OS 95% versus no pCR 83%, P = 0.027). In patients with pCR, near pCR or partial pathological response with immunotherapy, very few relapses were seen (2-year RFS 96%), and, at this writing, no patient has died from melanoma, whereas, even with pCR from targeted therapy, the 2-year RFS was only 79%, and OS was only 91%. Pathological response should be an early surrogate endpoint for clinical trials and a new benchmark for development and approval in melanoma.
BiVO4 has become the top-performing semiconductor among photoanodes for photoelectrochemical water oxidation. However, BiVO4 photoanodes are still limited to a fraction of the theoretically possible ...photocurrent at low applied voltages because of modest charge transport properties and a trade-off between light absorption and charge separation efficiencies. Here, we investigate photoanodes composed of thin layers of BiVO4 coated onto Sb-doped SnO2 (Sb:SnO2) nanorod-arrays (Sb:SnO2/BiVO4 NRAs) and demonstrate a high value for the product of light absorption and charge separation efficiencies (ηabs × ηsep) of ∼51% at an applied voltage of 0.6 V versus the reversible hydrogen electrode, as determined by integration of the quantum efficiency over the standard AM 1.5G spectrum. To the best of our knowledge, this is one of the highest ηabs × ηsep efficiencies achieved to date at this voltage for nanowire-core/BiVO4-shell photoanodes. Moreover, although WO3 has recently been extensively studied as a core nanowire material for core/shell BiVO4 photoanodes, the Sb:SnO2/BiVO4 NRAs generate larger photocurrents, especially at low applied voltages. In addition, we present control experiments on planar Sb:SnO2/BiVO4 and WO3/BiVO4 heterojunctions, which indicate that Sb:SnO2 is more favorable as a core material. These results indicate that integration of Sb:SnO2 nanorod cores with other successful strategies such as doping and coating with oxygen evolution catalysts can move the performance of BiVO4 and related semiconductors closer to their theoretical potential.
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