Triptolide (TP) is a diterpene triepoxide with various biological activities, but its clinical applications have been limited by potential hepatotoxicity, which can be attributed to T helper 17 ...(Th17)/T regulatory (Treg) cell imbalance. Quercetin (QE), a natural flavonoid, has been reported to have many benefits and medicinal properties, including hepatoprotective activity against TP-induced liver injury. However, the hepatoprotection mechanisms have not been clarified. The present study was designed to explore the protective effect and the mechanism of QE against TP-induced liver injury. Treatment with QE (20, 50 and 80mg/kg) prior to TP administration restored TP-induced alterations in a certain dose range indicating that QE was able to inhibit TP-induced liver injury. One mechanism underlying this effect was the shifting balance in Th17 and Treg cells from Th17 dominance to Treg dominance. Furthermore, QE markedly decreased the expression level of the Th17-related pro-inflammatory cytokines interleukin (IL)-17 and IL-6, as well as the Th17 transcription factor retinoid-related orphan receptor-γt (ROR-γt). TP induced downregulation in the expression of anti-inflammatory cytokine IL-10, but the expression of Treg transcription factor forkhead/winged-helix family transcriptional repressor p3 (FoxP3) was restored by QE. In the process of exploring the possible hepatoprotective mechanisms of QE, we found that QE significantly reduced both protein and mRNA expression of Toll-like receptor 4 (TLR4), which in turn not only inactivated myeloid differentiation primary response gene 88 (MYD88), nuclear factor kappa B (NF-κB) and related inflammatory cytokines IL-6 and IL-17, but also simultaneously increased the levels of T-cell immunoglobulin and mucin domain-containing protein 3 (Tim-3). Furthermore, blocking of TLR4 enhanced the effect of QE in regulating the Th17/Treg imbalance. In summary, this report has demonstrated for the first time that the protection afforded by QE against TP-induced liver injury was associated with a shift in the balance of Th17 and Treg cells to Treg dominance, which was regulated by Tim-3 and TLR4-MyD88-NF-κB signaling pathway.
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•Quercetin could protect liver injury induced by triptolide.•Quercetin could restore Th17/Treg balance.•The protective effect of Quercetin is mediated via Tim-3 and TLR4-MyD88-NF-κB pathway.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Extended Redundancy Analysis is a statistical tool for exploring the directional relationships of multiple sets of exogenous variables on a set of endogenous variables. This approach posits that the ...endogenous and exogenous variables are related via latent components, each of which is extracted from a set of exogenous variables, that account for the maximum variation of the endogenous variables. However, it is often difficult to distinguish between the true variables that form the latent components and the false variables that do not, especially when the association between the true variables and the exogenous set is weak. To overcome this limitation, we propose a Sparse Extended Redundancy Analysis via the Exclusive LASSO that performs variable selection while maintaining model specification. We validate the performance of the proposed approach in a simulation study. Finally, the empirical utility of this approach is demonstrated through two examples-one on a study of youth academic achievement and the other on a text analysis of newspaper data.
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BFBNIB, NUK, PILJ, SAZU, UL, UM, UPUK
As a typical keratinous material, the mechanical properties of pangolin scales are affected by hydration. Clarifying the mechanism of influence of hydration on dynamic response of materials may ...provide valuable inspiration for bio-inspired design. In this study, mechanical properties and impact wear behaviors of pangolin scales from different hydrated levels were investigated on a low-velocity impact wear tester. The dynamic response and damage behavior of these pangolin scales were systematically analyzed. Results showed that the energy absorption and impact contact force were considerably distinct with different hydrated levels. The maximum values of the impact contact force are similar to each other in various impact cycles. However, the damage extent of scales was not the same in varied impact cycles. Impact worn scars size of scales increased as the impact cycles increased. Under varied hydrated levels, energy absorption initially decreased and then increased with the increase in moisture content. Specifically, for a hydrated level of 10.5%, the energy absorption had the lowest rate, down to 26.6%, and the impact force decreased. Finally, the mechanisms and factors affecting the dynamic response and impact wear of scales were investigated. This study promoted a bio-inspired design for improving impact wear resistance properties.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, SIK, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Power data transaction is significant to the benefit increment of power enterprises and revitalization of social resources. Blockchain has a wide application prospect in data trading, but its ...concrete implementation faces many difficulties. This article proposes an obstacle analysis framework to understand the barriers of application of blockchain technology in power data trading, aiming to provide a decision-making guidance and management suggestions to relevant personnel. Firstly, an obstacle index system with 11 barriers is determined from three aspects of application, technology and legal policy. Secondly, a quantitative analysis model is constructed with (IT2TrFN), improved hesitant fuzzy linguistic term set (HFLTS), decision-making trial and evaluation laboratory (DEMATEL) and interpretive structural modeling (ISM). And the K-means method is employed to optimize the discrimination of influence relations among indicators. Then, the model is applied in a case study to testify its applicability. The result shows that the difficulty in data maintenance is fundamental obstacle, the barriers of smart contract and supervision in transaction are important factors. Finally, a series of optimization measures and suggestions are put forward for different obstacles.
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•A quantitative decision framework to analyze the obstacles of blockchain application in power data trading is established.•The obstacle factors of blockchain application in power data trading are identified and explained in detail.•The interrelationships between the obstacles are analyzed and suggestions are made to overcome them.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide and shows a propensity to metastasize and infiltrate adjacent and more distant tissues. HCC is associated with multiple risk ...factors, including hepatitis B virus (HBV) infection, which is especially prevalent in China. Here, we used exome sequencing to identify somatic mutations in ten HBV-positive individuals with HCC with portal vein tumor thromboses (PVTTs), intrahepatic metastases. Both C:G>A:T and T:A>A:T transversions were frequently found among the 331 non-silent mutations. Notably, ARID1A, which encodes a component of the SWI/SNF chromatin remodeling complex, was mutated in 14 of 110 (13%) HBV-associated HCC specimens. We used RNA interference to assess the roles of 91 of the confirmed mutated genes in cellular survival. The results suggest that seven of these genes, including VCAM1 and CDK14, may confer growth and infiltration capacity to HCC cells. This study provides a view of the landscape of somatic mutations that may be implicated in advanced HCC.
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DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Abstract
Acute respiratory tract infections (ARI) constitute a substantial disease burden in adults and elderly individuals. We aimed to identify all case-control studies investigating the potential ...role of respiratory viruses in the etiology of ARI in older adults aged ≥65 years. We conducted a systematic literature review (across 7 databases) of case-control studies published from 1996 to 2017 that investigated the viral profile of older adults with and those without ARI. We then computed a pooled odds ratio (OR) with a 95% confidence interval and virus-specific attributable fraction among the exposed (AFE) for 8 common viruses: respiratory syncytial virus (RSV), influenza virus (Flu), parainfluenza virus (PIV), human metapneumovirus (HMPV), adenovirus (AdV), rhinovirus (RV), bocavirus (BoV), and coronavirus (CoV). From the 16 studies included, there was strong evidence of possible causal attribution for RSV (OR, 8.5 95% CI, 3.9–18.5; AFE, 88%), Flu (OR, 8.3 95% CI, 4.4–15.9; AFE, 88%), PIV (OR, not available; AFE, approximately 100%), HMPV (OR, 9.8 95% CI, 2.3–41.0; AFE, 90%), AdV (OR, not available; AFE, approximately 100%), RV (OR, 7.1 95% CI, 3.7–13.6; AFE, 86%) and CoV (OR, 2.8 95% CI, 2.0–4.1; AFE, 65%) in older adults presenting with ARI, compared with those without respiratory symptoms (ie, asymptomatic individuals) or healthy older adults. However, there was no significant difference in the detection of BoV in cases and controls. This review supports RSV, Flu, PIV, HMPV, AdV, RV, and CoV as important causes of ARI in older adults and provides quantitative estimates of the absolute proportion of virus-associated ARI cases to which a viral cause can be attributed. Disease burden estimates should take into account the appropriate AFE estimates (for older adults) that we report.
It's under control: In the presence of an artificial double‐hydrophilic block copolymer, poly(ethylene glycol)‐b‐poly(L‐glutamic acid), highly monodisperse vaterite microspheres crystallize from a ...mixture of N,N‐dimethylformamide and water (see picture). Varying the ratio of the solvents can control the morphology of the CaCO3 crystals.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
In video surveillance and intelligent traffic, bad weather such as foggy, rainy and snowy can seriously affect the visibility of video images.Therefore, it is very important to quickly identify the ...current weather conditions and make adaptive clearness processing of surveillance videos.Aiming at the problems of poor effect of traditional weather recognition methods and lack of weather image data sets, a multi-class weather image blocks data set is constructed, and a weather recognition algorithm based on image blocks and feature fusion is proposed.The algorithm uses traditional methods to extract four features, namely average gradient, contrast, saturation and dark channel, which are taken as the shallow features of weather images.The algorithm uses transfer learning to fine-tune the VGG16 pre-training model, and extracts the full-connection layer features of the fine-tuning model, which are taken as the deep features of the weather image.The shallow and deep features of weather images are fused and used as t
Although human IgG heavy chain genes encode a C-terminal lysine, this residue is mostly absent from the endogenous antibodies isolated from serum. Some low but variable level of C-terminal lysine is ...present on therapeutic antibodies expressed in mammalian cell culture systems. Here, we monitored the C-terminal lysine processing of a recombinant human IgG2 antibody after intravenous injection into human subjects. Peptide mapping of the therapeutic antibody isolated from serum samples by affinity purification was used to quantify the C-terminal lysine levels over time in vivo. The C-terminal lysine residue was found to be rapidly lost in vivo with a half life of about an hour (62 min). In vivo C-terminal lysine processing could be reproduced in vitro, but at a faster rate, by incubating in human serum. Pretreated serum, under conditions used to inactivate carboxypeptidase U, generated in vitro C-terminal lysine processing rates that more closely matched those in vivo. Endogenous IgG, isolated from human blood, contained very low levels of C-terminal lysine (∼0.02%), consistent with the expected circulating half life of antibodies and the calculated C-terminal lysine processing rate. Thus, the low residual IgG2 C-terminal lysine is rapidly processed in vivo and such processing likely occurs on endogenous antibodies in circulation. Biotechnol. Bioeng. 2011;108: 404-412.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
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