Search

1. Si-Ni-San (SNS) possesses extensive therapeutic effects, however, the extent to which main components are absorbed and the mechanisms involved are controversial. 2. In this study, MDCK cell model was used to determine the permeability characteristics and interaction between the major components of Si-Ni-San, including saikosaponin a, paeoniflorin, naringin and glycyrrhizic acid. 3. The transport of the major components was concentration-dependent in both directions. Moreover, the transport of paeoniflorin, naringin and glycyrrhizic acid was significantly reduced at 4 °C or in the presence of NaN3. Additionally, the efflux of paeoniflorin and naringin were apparently reduced in the presence of P-gp inhibitor verapamil. The transport of glycyrrhizic acid was clearly inhibited by the inhibitors of MRP2, indicating that MRP2 may be involved in the transport of glycyrrhizic acid. However, the results indicated that saikosaponin a was absorbed mainly by passive diffusion. Furthermore, the combined incubation of four major components had a powerful sorbefacient effect than a single drug used alone which may be regulated by tight junctions. 4. Taken together, our study provides useful information for pharmacological applications of Si-Ni-San and offers new insights into this ancient decoction for further researches, especially in drug synergism.

Background/purposes Treatment of Staphylococcus aureus infections is challenging owing to widespread multidrug resistance. There is now considerable interest in the potential of combination therapies. Although linezolid/fosfomycin combination appears to be a promising treatment option based on in vitro data, further preclinical work is needed. In this study, the Galleria mellonella system was employed to study the in vivo efficacy of this combination in order to determine whether it should be explored further for the treatment of S. aureus infections. Methods The antimicrobial activity of linezolid and fosfomycin alone and in combination was assessed versus four S. aureus. Synergy studies were performed using the microtitre plate chequerboard assay and time-kill methodology. The in vivo activity of linezolid/fosfomycin combination was assessed using a G. mellonella larvae model. Results The combination of linezolid and fosfomycin was synergistic and bacteriostatic against four tested strains. Treatment of G. mellonella larvae infected with lethal doses of S. aureus resulted in significantly enhanced survival rates when low-dose of combination has no significant differences with high-dose combination (P > 0.05), G. mellonella hemolymph burden of S. aureus suggest that combination therapy with rapid and sustained bacteriostatic activity compared monotherapy. Conclusion This work indicated that linezolid combination with fosfomycin has synergistic effect against S. aureus in vitro and in an experimental G. mellonella model, and it suggests that high-dose of linezolid and fosfomycin may not necessary.

Long noncoding RNA (lncRNA) is a newly identified type of noncoding RNA with a length of more than 200 nucleotides. The latest research shows that lncRNAs play important roles in the occurrence and development of human tumours by acting both as carcinogenic genes and as tumour suppressor genes. LncRNAs plays a role in various biological processes, such as cell growth, apoptosis, migration and invasion. The newly discovered lncRNA DDX11-AS1 is abnormally highly expressed in various malignant tumours, such as hepatocellular carcinoma, colorectal cancer, osteosarcoma, bladder cancer, NSCLC and gastric cancer. DDX11-AS1 mainly regulates the expression of related genes through direct or indirect ways to perform its functions in carcinogenicity. These results indicate that DDX11-AS1 may be a marker or therapeutic target of tumours. This review summarizes the biological function and mechanism of DDX11-AS1 in the process of tumour development.

Objectives To explore the in vitro and in vivo antibacterial activity of linezolid/fosfomycin combination against vancomycin-susceptible and -resistant enterococci (VSE and VRE), and provide a theoretical basis for the treatment of VRE. Methods The checkerboard method and time-kill curve study were used to evaluate the efficacy of linezolid combined with fosfomycin against VSE and VRE. The transmission electron microscopy (TEM) was employed to observe the cell morphology of bacteria treated with each drug alone or in combination, which further elucidate the mechanism of action of antibiotic combination therapy. The Galleria mellonella infection model was constructed to demonstrate the in vivo efficacy of linezolid plus fosfomycin for VSE and VRE infection. Results The fractional inhibitory concentration index (FICI) values of all strains suggested that linezolid showed synergy or additivity in combination with fosfomycin against five of the six strains. Time-kill experiments demonstrated that the combination of linezolid-fosfomycin at 1×MIC or 2×MIC led to higher degree of bacterial killing without regrowth for all isolates tested than each monotherapy. TEM images showed that the combination treatment damaged the bacterial cell morphology more obviously than each drug alone. In the Galleria mellonella infection model, the enhanced survival rate of the combination treatment compared with linezolid monotherapy (P

Objectives Linezolid combination therapy is recommended for the treatment of Staphylococcus aureus (S. aureus) infections. However, the optimal regimen of the combination therapy for S. aureus is unknown. The objective of this study was to investigate the antibacterial activity, post-antibiotic effect (PAE), and post-antibiotic subminimum inhibitory concentration (MIC) effect (PA-SME) of linezolid alone and in combination with fosfomycin against eleven clinical isolates of S. aureus. Methods The synergistic effects and antibacterial activity of linezolid and fosfomycin were assessed by checkerboard and time-kill assays. To determine the PAE and PA-SME, S. aureus strains in the logarithmic phase of growth were exposed for 1, 2, and 3 hours to the antibiotics, alone and in combination. Recovery periods of test strains were evaluated using viable counting after dilution. Results Synergistic effects were observed for eight strains and no antagonism was found with any combination. Moreover, linezolid combined with fosfomycin at 4x MIC showed the best synergistic antibacterial effect, and this effect was retained after 24 hours. In addition, both the antibiotics alone and in combination showed increased PAE and PA-SME values in a concentration- and time-dependent manner. Conclusion Linezolid combined with fosfomycin exerted a good antibacterial effect against S. aureus, and the combinations have significant PAE and PA-SME.

Introduction: Methicillin-resistant Staphylococcus aureus (MRSA) is an important cause of serious infections. Linezolid and teicoplanin are widely used in the treatment of infections caused by MRSA. However, the efficacy and safety of linezolid compared with teicoplanin remains controversial. The purpose of this study was to systematically review the efficacy and safety of linezolid versus teicoplanin for the treatment of MRSA infections. Methodology: A meta-analysis was performed on the published studies. Pooled relative risk (RR) and 95% confidence interval (95% CI) were calculated to determine whether there were significant differences between the linezolid group and the teicoplanin group on the efficacy and safety. Results: Seventeen studies were included, involving 2,040 patients. The results showed that linezolid was associated with better clinical cure rate (RR = 1.14, 95% CI = 1.08-1.21, p < 0.00001) and microbiological eradication rate (RR = 1.28, 95% CI = 1.18-1.39, p < 0.00001) compared with teicoplanin. There were no statistically significant differences between the two groups in the treatment of MRSA infections regarding the adverse events (RR = 1.15, 95% CI = 0.97-1.35, p = 0.10) and the mortality (RR = 0.85, 95% CI = 0.61-1.18, p = 0.33). Conclusions: The results suggest that linezolid may be a better choice for the treatment of patients with MRSA infections. However, our recommendation is that the decision about treating MRSA infections with linezolid or with teicoplanin should depend on local availability, patient population, dosage regimens, costs and safety, rather than presumed differences in efficacy.

Phase change materials (PCMs) is an excellent performance candidate for thermal energy storage and utilization. However, low thermal conductivity and low light-to-thermal conversion efficiency of PCMs are the serious limitation factors for highly efficient energy storage and photothermal conversion. In this paper, we reported a novel composite PCM based on lauric acid (LA) as the PCM supported by Ag nanoparticles modified expanded graphite (Ag-EG). The composite PCM of Ag-EG/LA possessed good energy thermal storage properties, which melted at 47.2 °C with the latent heat of 129.5 J/g at the LA maximum loading of 70.2%. Meanwhile, based on the high thermal conductivity and local surface plasma resonance effect of Ag, the composite (Ag-EG/LA) exhibits improved thermal conductivities (2.85 W/(m•K)) and high light-to-thermal energy conversion efficiency (η=81.2%). Moreover, the TGA and thermal cycles test results shown that Ag-EG/LA have good thermal stability and reliability. Hence, this novel composite of Ag-EG/LA could be potentially applicated in solar energy harvesting system and electric devices for thermal energy management.

Liver fibrosis is a health concern that leads to organ failure mediated via production of inflammatory cytokines and fibrotic biomarkers. To date, there was no direct approved antifibrotic therapy, and current treatment was mainly the removal of the causative factor. Recent studies demonstrated that aberrant expression of miR-124 was involved in the progression of various liver diseases including hepatocellular carcinoma (HCC). However, whether miR-124 could function as a transcriptional regulator in the inflammatory cytokines secretion of liver fibrosis remains unclear. In this study, we demonstrated that the expression of miR-124 was downregulated in liver fibrosis tissues and TNF-α-induced LX-2 cells, concomitant with the upregulated expression of IQGAP1, suggesting that miR-124 and IQGAP1 might be associated with the development of inflammation in liver fibrosis. Therefore, we demonstrated that the overexpression of miR-124 and knockdown of IQGAP1 could lead to the downregulation of TNF-α, IL-1β and IL-6. While knockdown of miR-124 or overexpression of IQGAP1 showed reversed results. Moreover, dual luciferase reporter assays demonstrated that miR-124 specifically targeted the 3'-UTR of IQGAP1, and thus inhibited the expression of IQGAP1. Mechanistically, we found that the expression changes of miR-124 and IQGAP1 could be involved in inhibition or activation of NF-κB signaling pathway in response to TNF-α. In conclusion, these results indicated that miR-124 plays a crucial role in TNF-α-induced LX-2 cells via regulating NF-κB signaling pathway.

1. Ginkgolide B (GB), the most active of the ginkgolides, has been developed as a new drug for the treatment of vascular insufficiency; however, the pharmacokinetics of GB remain unclear. Here, we investigated the pharmacokinetics and urine excretion properties of GB in healthy Chinese subjects administered single- and multiple-dose injectable GB based on a new LC-MS/MS method. 2. GB pharmacokinetics were found to be dose-dependent from 20 to 60 mg. GB reached a steady state by day 6 with once-daily dosing at 40 mg. Systemic exposure to GB, as characterised by AUC0–∞, indicated accumulation following repeated once-daily dosing for seven consecutive days. The mean urinary cumulative excretion rate of GB in response to 20, 40, and 60 mg GB was 41.9 ± 18.5%, 32.9 ± 12.2%, and 43.9 ± 8.5%, respectively. 3. Dose-proportional pharmacokinetics of GB were observed after intravenous administration in healthy subjects. A gradual reduction in the volume of distribution and slight change in mean resistance time led us to conjecture the limited accumulation of GB based on distribution equilibrium in vivo. 4. This comprehensive study of the clinical pharmacokinetics of GB will provide useful information for its application and further development.

As part of the Lancaster GUIDE II project, we have developed a novel wireless access point protocol designed to support the development of next generation mobile context-aware applications in our local environs. Once deployed, this architecture will allow ordinary citizens secure, accountable and convenient access to a set of tailored applications including location, multimedia and context based services, and the public Internet. Our architecture utilises packet marking and network level packet filtering techniques within a modified Mobile IPv6 protocol stack to perform access control over a range of wireless network technologies. In this paper, we describe the rationale for, and components of, our architecture and contrast our approach with other state-of-the-art systems. The paper also contains details of our current implementation work, including preliminary performance measurements.

The paper proposes a cloud-based framework to abstract and analyze the meaningful rules among great amount of students' raw information. The authors abstract a set of learning skills based on the course outline from The Open University of China. The authors also present a cloud-based Apriori association algorithm to abstract the rules, followed by a reasonable analysis on educational aspect supported by cloud-based k-means clustering algorithm and learning skills identification.

This paper studied the cloud-based Hadoop shared storage and analysis system and its related technologies, to build a small Hadoop platform on the basis of this study, combined with the technical work of the field of electric power marketing, design a modern power system architecture - grid smart marketing architecture based on Hadoop, from the perspective of the functional level of the marketing. Energy consumption statistics module as an example, simulation to achieve the statistics of large-scale clients electricity consumption.

Augmented Reality technology is widely used. In this paper, we proposed an efficient method to obtain the satisfied SFM result in real-time using clustering method. First we use Lucas-Kanade method to calculate the optical flow of adjacent frames. We take advantage of the better movement features to calculate the fundamental matrix and use Sturm’s method to restore the camera intrinsic parameters. We further use SVD decomposition to obtain the extrinsic parameters of adjacent frames. In order to obtain more accurate camera intrinsic and extrinsic parameters, we use clustering method to get the reconstruction result and further to amend the intrinsic and extrinsic parameters. Further experiments proved the validity of the method. The proposed method is a real-time algorithm and can meet the requirements of the study of augmented reality.

A novel technique for reconstructing fluid surface from video is introduced. Both fluid motion vectors as well as Lattice Boltzmann Method (LBM) are employed in the study. Region-based correlation method is used to initialize motion vectors field, after clustering fluid motion vector results can be obtained. Then the height geometry information of fluid surface can be calculated from fluid motion vector further. At last, the distribution of fluid particle is interpolated and the height field can be further refined. Reconstruction results are demonstrated with several challenge videos. The experimental results show that the method is convenient and efficient. The calculation results can reflect the characteristics of the fluid movement, and it is a valid method for reconstructing fluid surface.