To explore the role of the abnormal expression of the bile salt export pump (BSEP) and multidrug resistance protein 2 (MRP2) in isoniazid (INH)-induced liver injury, we assessed the liver injury ...induced by INH in rats and HepG2 cells in vitro. The regulatory pathways via Sirtuin 1 (SIRT1) and farnesoid X receptor (FXR) were also determined. Rat liver injury was assessed by histopathological and biochemical analysis and HepG2 cytotoxicity was assessed by a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test. The levels of protein were determined by Western blot. The results indicated that INH could induce hepatotoxicity in vivo and in vitro in a dose dependent manner. The liver index and serum biochemical analysis, especially the levels of total bile acids (TBA), total bilirubin (TBIL), and direct bilirubin (DBIL), were significantly increased in rats. The INH hepatotoxicity was severe in the high dose group, and occurred alongside the down-regulation of BSEP and MRP2 in vivo and in vitro, leading to the accumulation of toxic substrates in the hepatocytes. The SIRT1/FXR pathway was identified as being important for the down-regulation of transporters. In summary, our study indicated that the down-regulation of BSEP and MRP2 represents one mechanism of INH-induced liver injury and the down-regulation of SIRT1/FXR may be a key regulator. This will inform the development of novel therapies and enable the prevention of INH-induced liver injury.
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•Hollow Cu doped g-C3N4 microspheres with outstanding photocatalytic H2O2 production ability and stability are prepared.•The Cu+ doping sites serve as active sites to adsorb and ...activate O2 molecules.•DFT simulation confirms the O2 activation process on the Cu+ doping sites.
H2O2 is produced industrially by the anthraquinone method, in which energy consumption is high because of its multistep hydrogenation and oxidation reactions. In this work, hollow copper-doped graphitic carbon nitride (g-C3N4) microspheres with outstanding photocatalytic H2O2 production ability are prepared. The characterization results demonstrate that Cu+ is not present as the oxide but instead inserts at the interstitial position through coordinative Cu(I)-N bonds. These Cu(I)-N active sites can act as chemical adsorption sites to activate molecular O2. Moreover, as an “electron transfer bridge”, Cu(I)-N active sites promote electron transfer from the catalyst to the adsorbed O2 molecules. The as-prepared copper-doped g-C3N4 displays much higher H2O2 equilibrium concentration and formation rate than neat g-C3N4 prepared by calcination does, as well as excellent structural stability. Density functional theory simulations show that Cu(I)-N active sites can adsorb the O2 molecules with high adsorption energy and elongate the OO bond. Charge density difference results confirm the electron transfer from the Cu+ doping sites to the O2 molecules. The Mulliken charge is −0.51 when the O2 adsorbed on Cu+ doping sites. This electron-rich environment is beneficial to the H+ attack to form H2O2.
The aim of this study was to explore the role of the NOD-like receptor family, pyrin domain containing (NLRP3) inflammasome and autophagy in Astragaloside IV (AS IV)-mediated protection against ...cisplatin-induced liver and kidney injury in rats. Rats were intraperitoneally administered cisplatin at a dose of 15 mg/kg and orally administered AS IV for 7 days. Histopathological and biochemical analysis were used to assess liver and kidney function. The levels and localization of NLRP3 and autophagy-associated protein were determined by Western blot and immunohistochemistry. Intraperitoneal administration of cisplatin induced acute liver and kidney injury, and activated the NLRP3 inflammasome. Oral administration of AS IV for 7 days protected against the cisplatin-induced injury, and inhibited the expression of NLRP3, as well as the production of pro-inflammatory cytokines. Moreover, cisplatin modulated the conversion of LC3 II and the expression of p62, thereby inhibiting autophagy and the activation of NLRP3. AS IV effectively protected against cisplatin-induced injury by inducing autophagy and limiting the expression of NLRP3. Autophagy-mediated NLRP3 inhibition might play a crucial role in AS IV-mediated protection against cisplatin-induced toxicity. These results provide evidence of a novel therapeutic that may be used to alleviate the toxic effects of platinum-based chemotherapy.
Xyloglucan endotransglucosylase/hydrolase genes (XTHs) are a multigene family and play key roles in regulating cell wall extensibility in plant growth and development. Brassica rapa and Brassica ...oleracea contain XTHs, but detailed identification and characterization of the XTH family in these species, and analysis of their tissue expression profiles, have not previously been carried out.
In this study, 53 and 38 XTH genes were identified in B. rapa and B. oleracea respectively, which contained some novel members not observed in previous studies. All XTHs of B. rapa, B. oleracea and Arabidopsis thaliana could be classified into three groups, Group I/II, III and the Early diverging group, based on phylogenetic relationships. Gene structures and motif patterns were similar within each group. All XTHs in this study contained two characteristic conserved domains (Glyco_hydro and XET_C). XTHs are located mainly in the cell wall but some are also located in the cytoplasm. Analyses of the mechanisms of gene family expansion revealed that whole-genome triplication (WGT) events and tandem duplication (TD) may have been the major mechanisms accounting for the expansion of the XTH gene family. Interestingly, TD genes all belonged to Group I/II, suggesting that TD was the main reason for the largest number of genes being in these groups. B. oleracea had lost more of the XTH genes, the conserved domain XET_C and the conserved active-site motif EXDXE compared with B. rapa, consistent with asymmetrical evolution between the two Brassica genomes. A majority of XTH genes exhibited different tissue-specific expression patterns based on RNA-seq data analyses. Moreover, there was differential expression of duplicated XTH genes in the two species, indicating that their functional differentiation occurred after B. rapa and B. oleracea diverged from a common ancestor.
We carried out the first systematic analysis of XTH gene families in B. rapa and B. oleracea. The results of this investigation can be used for reference in further studies on the functions of XTH genes and the evolution of this multigene family.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The limitation of doxorubicin (DOX), which is widely used for the treatment of solid tumors and hematologic malignancies, is a vital problem in clinical application. The most serious of limit factors ...is cardiotoxicity. Calycosin (CA), an isoflavonoid that is the major active component in Radix astragali, has been reported in many bioactivities including antitumor, anti‐inflammatory, and cardioprotection. The aim of the study was to investigate the effects and mechanisms of CA on DOX‐induced cardiotoxicity in vitro and in vivo. CA increased H9c2 cell viability and reduced apoptosis induced by DOX via Bcl‐2, Bax, and the PI3K‐Akt signaling pathway. Moreover, CA prevented DOX‐induced oxidative stress in cells by decreasing the generation of reactive oxygen species. Similarly, oxidative stress was inhibited by CA through the increased activities of antioxidant enzymes such as glutathione peroxidase, catalase, and superoxide dismutase and decreased the levels of aspartate aminotransferase, lactate dehydrogenase, and malondialdehyde in vivo. Furthermore, the levels of sirtuin 1 (Sirt1)–NOD‐like receptor protein 3 (NLRP3) and related proteins were ameliorated by CA in cells and in mice hearts. When H9c2 cells were treated by Ex527 (Sirt1 inhibitor), the effect of CA on expressions of NLRP3 and thioredoxin‐interacting protein was suppressed. In conclusion, the results suggested that CA might be a cotreatment with DOX to ameliorate cardiotoxicity by Sirt1–NLRP3 pathway.
Anchor piles are widely used in marine aquaculture, and the safety is largely determined by the uplift resistance capacity,especially in harsh ocean environments. However, there are few practical ...guides to the design and installation of the anchor piles for mooring the body of marine aquaculture equipment. Laboratory experiments were conducted to investigate the effect of the initial tension angle, pile diameter, embedded depth, and pile configuration on the uplift resistance capacity of anchor piles under oblique loads. CCD camera and load cell were utilized to measure the corresponding displacement and load, respectively. The results show that increasing the initial tension angle of circular and square single piles can significantly improve the uplift resistance capacity. The failure load of the square single pile was slightly higher than that of the circular single pile. Increasing the pile diameter can effectively improve the failure load and delay the development speed of the pile top displacement. Increasing the embedded depth can effectively improve the failure load and increase the lateral displacement of the pile top. The uplift resistance capacity of the dual anchor piles was better than that of the single anchor piles. The layout configuration has little effect on the failure load, but has a large effect on the displacement development.
•37 and 35 metabolite levels changed in rat urine and kidneys by CDDP-induced AKI.•7 key metabolic pathways were significantly disrupted by CDDP-induced AKI.•11 sensitive metabolites in urine were ...screened as potential biomarkers of AKI.•4 off these biomarkers were quantified and confirmed as sensitive biomarkers.
Kidney injury is a major adverse effect of cisplatin use. Metabolomics has been used to characterize physiological or pathological conditions through identification of metabolites and characterization of the metabolic pathway. Metabolomics profiling could allow for identification of nephrotoxic mechanisms of cisplatin and identification of biomarkers of cisplatin-induced injury. In this study, we performed metabolomics analysis to characterize key changes in metabolite levels during cisplatin-induced acute kidney injury (AKI) in rats, and screened for sensitive biomarkers for early diagnosis using HPLC-TOF/MS. Rats were intraperitoneally injected with 7.5 mg/kg or 15 mg/kg of cisplatin, or normal saline, and 12 h urine and kidney samples were collected after 72 h. Serum biochemical parameters and kidney histological evaluations showed dose-dependent AKI in response to cisplatin. Metabolomics analysis showed that 37 and 35 endogenous metabolite levels changed in rat urine and kidneys, respectively. Seven key metabolic pathways were disrupted, including the tricarboxylic acid cycle (TCA cycle), phenylalanine, tyrosine, and tryptophan biosynthesis, phenylalanine metabolism, glycerophospholipid metabolism, taurine and hypotaurine metabolism, d-glutamine and d-glutamate metabolism, and nicotinate and nicotinamide metabolism. These pathways are involved in energy generation, and amino acid and lipid metabolism, and disruption of these pathways could contribute to oxidative stress injury, inflammation, and cell membrane damage. Furthermore, 11 sensitive metabolites in urine were screened as potential biomarkers of AKI. To validate these biomarkers, we quantified 4 off these biomarkers, and confirmed that levels of these metabolites were altered in urine of rats treated with CDDP.
This study constructs a theoretical model to test and prove that organizational forgetting influences cross-boundary innovation and testifies to the moderating role of Institutionalized ...organizational mission in the said relationship. Data was collected through a convenient sampling technique from 353 middle and senior managers of entrepreneurial enterprises in China through online and offline modes. Additionally, we used confirmatory factor analysis, multiple regression, and bootstrap analysis to verify hypotheses using Analysis of a moment structures and Statistical Package for the Social Sciences latest versions. The results show that organizational forgetting has a significantly positive impact on cross-boundary innovation and binary knowledge sharing plays a mediating role in the relationship between organizational forgetting and cross-boundary innovation. Moreover, the mediating effect of exploitative knowledge sharing on the relationship between organizational forgetting and cross-boundary innovation is more substantial than exploratory knowledge sharing. This study separates the impact mechanism of exploitative and exploratory knowledge sharing as a mediator unanimously and proves that Institutionalized organizational mission has a significant moderating role in the relationship between organizational forgetting and cross-boundary innovation. This research offers significant implications for Chinese enterprises to bolster cross-boundary innovation to achieve growth.
•Quercetin inhibited INH-induced liver injury.•Quercetin regulated NLRP3 inflammasome via SIRT1 in INH-induced hepatotoxicity.•SIRT1 participatedin the protective effects of quercetin.
Severe ...hepatotoxicity greatly limits the clinical application of the first-line anti-tuberculosis drug isoniazid(INH). Quercetin(Que) has multiple pharmacological properties, and is regarded as a potential protective agent against a variety of organ injuries. However, the exact effect of quercetin on INH-induced hepatotoxicity and the underlying mechanisms are not yet completely understood. In this study, liver injury models were established in rats and L02 cells toreveal the protective effect of Que on INH-induced hepatotoxicity and the relevant mechanism. The in vivo results indicated that Que pretreatment reduced the level of ALT/AST, improved the liver histopathological changes and substantially mitigated apoptosis in rats. In vitro, it evidently relieved INH-induced cell viability loss and apoptosis in L02 cells. Furthermore, thestudiesonmechanisms elucidated that Que remarkably elevated the expression of SIRT1 and suppressed NLRP3 inflammasome activation. Meanwhile, Que significantly inhibited the level of tumor suppressor P53, Bax, cleaved-cas3 expressionl and increased Bcl-2 expression to reduce apoptosis in vivo and in vitro. However, SIRT1 inhibitor EX527 reversed the suppression of Que on NLRP3 inflammasome activation and the protection of Que on rat liver injury and cell apoptosis. In short, our findings showed that Que exhibited protective effects against INH-induced liver damage via inhibiting the activation of NLRP3 inflammasome and apoptosis in a SIRT-dependent manner.
The purpose is to coordinate the relationship between innovation and entrepreneurship education (IEE) and professional education. This exploration is based on the entrepreneurial spirit of young ...entrepreneurs and the re-integration of IEE and music education in colleges. First, the IEE is studied in theory. Then, the basic criteria for integrating IEE and professional education are studied, and 305 students from a music college in Xi’an are taken as the survey sample. The questionnaire is adopted to investigate the current situation of the integration of IEE and professional education. The results show that 52.1% of students believe that IEE is closely related to professional education. In terms of self entrepreneurship awareness, males’ awareness of self entrepreneurship is higher than females’, and the willingness of self entrepreneurship from freshman to senior is 3.1, 15.5, 26.1, and 30.8%, respectively. For the dominant position in the integrated curriculum, 55.6% hold that professional courses should dominate innovative professional courses, and 25.9% believe that innovation and entrepreneurship courses should be dominated. Besides, 16.5% think that the proportion of the two should be the same, and 2% hold that it doesn’t matter. For the enthusiasm of innovative professional courses, only 14.1% of students are very positive. The survey results show that the integration of IEE and professional education needs to be improved, and there is a lack of pertinence and guidance for students of different genders and grades. Students are not clear about the position of IEE and lack enthusiasm. Finally, reasonable suggestions are put forward in view of the above problems. The results are conducive to promoting and accelerating the process of talent training mode combining professional education and IEE. It has a certain reference value for college education and teaching reform.
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