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It has been recognized that protease-activated receptors (PARs), interleukin (IL)-4 and IL-6 are involved in the pathogenesis of allergic diseases, and that IL-12 plays a role in adaptive immune response. However, little is known of the effect of IL-12 on protease-induced cytokine release from mast cells. In the present study, we examined potential influence of IL-12 on mast cell PAR expression and IL-4 and IL-6 release. The results showed that IL-12 downregulated the expression of PAR-2 and upregulated expression of PAR-4 on P815 cells. It also downregulated expression of PAR-2 mRNA, and upregulated expression of PAR-1, PAR-3 and PAR-4 mRNAs. However, IL-12 enhanced trypsin- and tryptase-induced PAR-2 and PAR-2 mRNA expression. It was observed that IL-12 induced release of IL-4, but reduced trypsin- and tryptase-stimulated IL-4 secretion from P815 cells. PD98059, U0126 and LY294002 not only abolished IL-12-induced IL-4 release but also inhibited IL-12-induced phosphorylation of extracellular signal-regulated kinase and Akt. In conclusion, IL-12 may serve as a regulator in keeping the balance of Th1 and Th2 cytokine production in allergic inflammation.Immunology and Cell Biology (2007) 85, 558–566; doi:10.1038/sj.icb.7100085; published online 26 June 2007 [ABSTRACT FROM AUTHOR]

In this study, an ultrasound/CCl4 system was used to degrade the fluoroquinolone antibiotic, ciprofloxacin, in aqueous solution. The effect of CCl4 concentration and initial solution pH on ciprofloxacin degradation were investigated. The results showed that ciprofloxacin degraded effectively under an ultrasound/CCl4 system, with degradation efficiency increasing from 0.51% to 50.92%, when the CCl4 concentration ranged from 0.0 to 41.4 mmol/L in 40 min. Radical scavenging experiments certified that both •OH and chlorine-containing radicals contributed to ciprofloxacin degradation. Eight intermediates were detected using ultra high-performance liquid chromatography-mass spectrometry (UHPLC-MS) method, including three chloro-intermediates. Based on these results, the possible degradation pathways of ciprofloxacin are proposed. Agar diffusion tests with E. coli and S. aureus showed that ciprofloxacin's antibacterial activity was completely removed in 40 min. This study indicates that an ultrasound/CCl4 system can degrade ciprofloxacin and remove its antibacterial activity, and thus is a promising process for treating fluoroquinolone antibiotics in wastewater. [ABSTRACT FROM AUTHOR]

Purpose: The use of convolution neural networks (CNN) to accurately predict dose distributions can accelerate intensity-modulated radiation therapy (IMRT) planning. The purpose of our study is to develop a novel deep learning architecture for precise voxel-level dose prediction on brain tumors. Methods: A dataset of 120 patients with brain tumors is built for the retrospective study. The dose distributions are predicted by a designed end-to-end model called TS-Net, in which the transformer encoder module is utilized to obtain abundant global features by learning long-range correlations of the input sequence. In addition, semantic field alignment (SFA) block is proposed in decoding path to ensure effective propagation of strong semantic information from deep to shallow. Five images from different channels are fed into the architecture, including a computed tomography (CT) image, a planning target volumes (PTV) image, an organs-at-risk (OARs) image, a beam configuration image, and a distance image, and the predicted dose distributions are taken as outputs. We use different evaluation metrics to evaluate the performance of the model and discuss the role of the auxiliary beam configuration information provided by non-modulated dose distributions. Results: The TS-Net prediction accuracies in terms of mean absolute error (MAE) are 2.98% for PTV, 7.19% for brainstem, 1.88% for left len, 2.48% for right len, 9.61% for left optic nerve, 9.10% for right optic nerve, 8.99% for optic chiasma, and 8.28% for pituitary. There is no statistically significant difference between the predicted results and clinical dose distributions for clinical indexes including homogeneity index (HI), D50, and D95 for PTV; V40, mean dose, and max dose for OARs; except for conformation index (CI) and D2 for PTV. The model has dice similarity coefficient (DSC) values of above 0.91 for most isodose volumes, clearly outperforming HD U-Net, and being slightly better than U-Net and DCNN. Conclusion: The proposed TS-Net with beam configuration input can achieve accurate voxel-level dose prediction for brain tumors, and is a usable tool for improving the efficiency and quality of radiotherapy. [ABSTRACT FROM AUTHOR]

This study proposes a novel prediction model for uni- and multi-variable forecast, where error feedback is added to the original forecast value predicted using the persistence model. The error feedback mechanism is constructed to find out the relationship between the errors and the original forecast values. Simulation studies are carried out using wind power data obtained from two databases, and the results demonstrate that the proposed model provides a more accurate and stable forecast compared to other methods. Based on this, the economic benefit of accurate wind power forecast has been analysed for power system dispatch, which aims to minimise the operation cost. The dispatch results of two scenarios have shown that accurate forecast result decreases the cost of reserve capacity, balancer set invoking capacity and the possibility of wind curtailment, which leads to more economic dispatch of power systems. [ABSTRACT FROM AUTHOR]

Rapamycin, an immunosuppressant, is widely used in patients with kidney transplant. However, the therapeutic effects of rapamycin remain controversial. Additionally, previous studies have revealed deleterious effects of rapamycin predominantly when administered for =24 h. Few studies, however, have focused on the short-term effects of rapamycin administered only during the initial reperfusion phase. As such, we designed this study to explore the potential effects and mechanisms of rapamycin under a specific therapeutic regimen in which rapamycin is mixed in the perfusate during the initial reperfusion phase (within 24 h). Interestingly, we found that rapamycin maintained renal function and attenuated ischemia-reperfusion (I/R)-induced apoptosis in vivo and in vitro during the initial reperfusion phase, especially at 8 h after reperfusion. Simultaneously, rapamycin activated autophagy and inhibited endoplasmic reticulum (ER) stress and 3 pathways of unfolding protein response: ATF6, PERK, and IRE1a. Interestingly, we further found that the protective effects of rapamycin were suppressed when autophagy was inhibited by chloroquine and 3-methyladenine or when ER stress was induced by thapsigargin. Moreover, in terms of the regulatory effects of rapamycin, a negative-feedback loop between autophagy and ER stress occurred, with autophagy inhibiting ER stress and increased ER stress promoting autophagy during the initial reperfusion phase of renal I/R injury. Our study provides evidence that immediate reperfusion with rapamycin during the initial reperfusion phase repairs renal function and reduces apoptosis via activating autophagy, which could further inhibit ER stress. These results suggest a novel treatment modality for application during the initial reperfusion phase of renal I/R injury caused by kidney transplantation. [ABSTRACT FROM AUTHOR]

Separation of germ cells from somatic cells is a widespread feature of animal sexual reproduction, with a core set of germ cell factors conserved among diverse animals. It is not known what controls their conserved gonad-specific expression. Core components of epigenetic machinery are ancient, but its role in conserved tissue expression regulation remains unexplored. We found that promoters of the reproductive genes BOULE and DAZL exhibit differential DNA methylation, consistent with their gonad-specific expression in humans and mice. Low or little promoter methylation from the testicular tissue is attributed to spermatogenic cells of various stages in the testis. Such differential DNA methylation is present in the orthologous promoters not only of other mammalian species, but also of chickens and fish, supporting a highly conserved epigenetic mechanism. Furthermore, hypermethylation of DAZL and BOULE promoters in human sperm is associated with human infertility. Our data strongly suggest that epigenetic regulation may underlie conserved germ-cell-specific expression, and such a mechanism may play an important role in human fertility. [ABSTRACT FROM AUTHOR]