A multichannel thiacalix[4]arene-based fluorescent chemosensor for Zn²⁺, F⁻ ions and imaging of living cells

The fluorescent sensor (3) based on the 1,3-alternate conformation of the thiacalix[4]arene bearing the coumarin fluorophore, appended via an imino group, has been synthesised. Sensing properties were evaluated in terms of a colorimetric and fluorescence sensor for Zn 2+ and F - . High selectivity and excellent sensitivity were exhibited, and off-on optical behaviour in different media was observed. All changes were visible to the naked eye, whilst the presence of the Zn 2+ and F - induces fluorescence enhancement and the formation of a 1:1 complex with 3. In addition, 3 exhibits low cytotoxicity and good cell permeability and can readily be employed for assessing the change of intracellular levels of Zn 2+ and F -

Self-adaptive clock synchronisation based on clock precision difference

This paper presents an innovative strategy to synchronize all virtual clocks in asynchronous Internet environments. Our model is based on the architecture of one reference clock and many slave clocks communicating with each other over the Internet. The paper makes three major contributions to this research area. Firstly, one-way information transmission is applied to reduce traffic overhead on the Internet for the purpose of clock synchronization. Secondly, the slave nodes use local virtual time and the arrival timestamp, from the reference node, to create linear mathematical trend models and to retrieve the clock precision differences between reference clock and slave clocks. Finally, a fault-tolerant and self-adaptive model executed by each slave node based on the above linear trend model is created in order to ensure that the virtual clock is running normally, even when the link between the reference node and this slave node has crashed. We also present detailed simulations of this strategy and mathematical analysis on real Internet environments.<br /

A web-DB model on multicast and anycast

Most of the current web-based database systems suffer from poor performance, complicated heterogeneity, and synchronization issues. In this paper, we propose a novel mechanism for web-based database system on multicast and anycast protocols to deal with these issues. In the model, we put a castway, a network interface for database server, between database server and Web server. Castway deals with the multicast and anycast requests and responses. We propose a requirement-based server selection algorithm and an atomic multicast update algorithm for data queries and synchronizations. The model is independent from the Internet environment, it can synchronise the databases efficiently and automatically. Furthermore, the model can reduce the possibility of transaction deadlocks.<br /

Coordinated Damping Control Design for Power System With Multiple Virtual Synchronous Generators Based on Prony Method

With more renewables integrated into power grids, the systems are being transformed into low inertia power electronic dominated systems. In this situation, the virtual synchronous generator (VSG) control strategy was proposed to deal with insufficient inertia challenge caused by the reduction of synchronous generation. However, as the VSG control method emulates the dynamic behavior of traditional synchronous machines, the interaction between multiple VSG controllers and synchronous generators (SGs) may cause low-frequency oscillation similar to that caused by the interaction between multiple SGs. This paper reveals that the system low-frequency oscillatory modes are affected by multiple VSGs. Then Prony analysis is utilized to extract the system mode information which will be subsequently used for VSG controller design, and a decentralized sequential coordinated method is proposed to design the supplementary damping controller (SDC) for multiple VSGs. The system low-frequency oscillation is first analyzed based on a modified two-area system with a linearized state-space model, and a further case study based on a revised New England 10-machine 39-bus system is used to demonstrate the effectiveness of the proposed coordinated method for multiple VSGs

Improved oral bioavailability of poorly water-soluble indirubin by a supersaturatable self-microemulsifying drug delivery system

Zhi-Qiang Chen, Ying Liu, Ji-Hui Zhao, Lan Wang, Nian-Ping FengSchool of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, People&amp;#39;s Republic of ChinaBackground: Indirubin, isolated from the leaves of the Chinese herb Isatis tinctoria L, is a protein kinase inhibitor and promising antitumor agent. However, the poor water solubility of indirubin has limited its application. In this study, a supersaturatable self-microemulsifying drug delivery system (S-SMEDDS) was developed to improve the oral bioavailability of indirubin.Methods: A prototype S-SMEDDS was designed using solubility studies and phase diagram construction. Precipitation inhibitors were selected from hydrophilic polymers according to their crystallization-inhibiting capacity through in vitro precipitation tests. In vitro release of indirubin from S-SMEDDS was examined to investigate its likely release behavior in vivo. The in vivo bioavailability of indirubin from S-SMEDDS and from SMEDDS was compared in rats.Results: The prototype formulation of S-SMEDDS comprised Maisine&amp;trade; 35-1:Cremophor&amp;reg; EL:Transcutol&amp;reg; P (15:40:45, w/w/w). Polyvinylpyrrolidone K17, a hydrophilic polymer, was used as a precipitation inhibitor based on its better crystallization-inhibiting capacity compared with polyethylene glycol 4000 and hydroxypropyl methylcellulose. In vitro release analysis showed more rapid drug release from S-SMEDDS than from SMEDDS. In vivo bioavailability analysis in rats indicated that improved oral absorption was achieved and that the relative bioavailability of S-SMEDDS was 129.5% compared with SMEDDS.Conclusion: The novel S-SMEDDS developed in this study increased the dissolution rate and improved the oral bioavailability of indirubin in rats. The results suggest that S-SMEDDS is a superior means of oral delivery of indirubin.Keywords: supersaturatable self-microemulsifying drug delivery system, indirubin, bioavailability, oral drug delivery, hydrophilic polyme

An earthworm protease cleaving serum fibronectin and decreasing HBeAg in HepG2.2.15 cells

<p>Abstract</p> <p>Background</p> <p>Virus-binding activity is one of the important functions of fibronectin (FN). It has been reported that a high concentration of FN in blood improves the transmission frequency of hepatitis viruses. Therefore, to investigate a protease that hydrolyzes FN rapidly is useful to decrease the FN concentration in blood and HBV infection. So far, however, no specific protease digesting FN in serum has been reported.</p> <p>Methods</p> <p>We employed a purified earthworm protease to digest serum proteins. The rapidly cleaved protein (FN) was identified by MALDI-TOF MS and western blotting. The cleavage sites were determined by N-terminus amino acid residues sequencing. The protease was orally administrated to rats to investigate whether serum FN <it>in vivo </it>became decreased. The serum FN was determined by western blotting and ELISA. In cytological studies, the protease was added to the medium in the culture of HepG2.2.15 cells and then HBsAg and HBeAg were determined by ELISA.</p> <p>Results</p> <p>The protease purified from earthworm <it>Eisenia fetida </it>was found to function as a fibronectinase (FNase). The cleavage sites on FN by the FNase were at R and K, exhibiting a trypsin alkaline serine-like function. The earthworm fibronectinase (EFNase) cleaved FN at four sites, R₂₅₉, R₁₀₀₅, K₁₅₅₇and R₂₀₃₉, among which the digested fragments at R₂₅₉, K₁₅₅₇and R₂₀₃₉were related to the virus-binding activity as reported. The serum FN was significantly decreased when the earthworm fibronectinase was orally administrated to rats. The ELISA results showed that the secretion of HBeAg from HepG2.2.15 cells was significantly inhibited in the presence of the FNase.</p> <p>Conclusion</p> <p>The earthworm fibronectinase (EFNase) cleaves FN much faster than the other proteins in serum, showing a potential to inhibit HBV infection through its suppressing the level of HBeAg. This suggests that EFNase is probably used as one of the candidates for the therapeutic agents to treat hepatitis virus infection.</p

Non-traditional CD4+CD25−CD69+ regulatory T cells are correlated to leukemia relapse after allogeneic hematopoietic stem cell transplantation

Background: Non-traditional CD4+CD25-CD69+ T cells were found to be involved in disease progression in tumor-bearing mouse models and cancer patients recently. We attempted to define whether this subset of T cells were related to leukemia relapse after allogeneic hematopoietic cell transplantation (allo-HSCT). Methods: The frequency of CD4+CD25-CD69+ T cells among the CD4+ T cell population from the bone marrow of relapsed patients, patients with positive minimal residual disease (MRD+) and healthy donors was examined by flow cytometry. The CD4+CD25-CD69+ T cells were also stained with the intracellular markers to determine the cytokine (TGF-beta, IL-2 and IL-10) secretion. Results: The results showed that the frequency of CD4+CD25-CD69 + T cells was markedly increased in patients in the relapsed group and the MRD + group compared to the healthy donor group. The percentage of this subset of T cells was significantly decreased after effective intervention treatment. We also analyzed the reconstitution of CD4+CD25-CD69+ T cells at various time points after allo-HSCT, and the results showed that this subset of T cells reconstituted rapidly and reached a relatively higher level at +60 d in patients compared to controls. The incidence of either MRD+ or relapse in patients with a high frequency of CD4+CD25-CD69+ T cells (&gt;7%) was significantly higher than that of patients with a low frequency of CD4+CD25-CD69+ T cells at +60 d, +90 d and +270 d after transplant. However, our preliminary data indicated that CD4+CD25-CD69+ T cells may not exert immunoregulatory function via cytokine secretion. Conclusions: This study provides the first clinical evidence of a correlation between non-traditional CD4+CD25-CD69+ Tregs and leukemia relapse after allo-HSCT and suggests that exploration of new methods of adoptive immunotherapy may be beneficial. Further research related to regulatory mechanism behind this phenomenon would be necessary.Medicine, Research &amp; ExperimentalSCI(E)[email protected]

ADRENALINE INHIBITED CELL PROLIFERATION AND REGULATED EXPRESSION OF TGF-BETA1 AND BFGF IN CULTURED HUMAN HYPERTROPHIC SCAR FIBROBLASTS VIA α-RECEPTOR

a These authors contributed equally to this study ABSTRACT Adrenaline has been shown to modulate proliferation of mouse fibroblasts, adventitial fibroblasts and synovial B (fibroblasts-like) cells. However, little is known about the response of cultured human hypertrophic scar fibroblasts to adrenaline. In this study, we investigated cell proliferation and involved mechanisms in hypertrophic scar fibroblasts in response to adrenaline. Population doubling time (PDT) assay and MTT assay were performed to determine the cell proliferation and cell viability, respectively. The expression of bFGF and TGF-β1 was measured by reverse transcriptase-polymerase chain reaction (RT-PCR) and enzyme linked immunosorbent assay (ELISA). The results showed that adrenaline inhibited proliferation of normal and hypertrophic scar fibroblasts in a dose-dependent manner. Moreover, adrenaline up-regulated the expression of bFGF and down-regulated the expression of TGF-β1 in normal and hypertrophic scar fibroblasts. Interestingly incubation with the α receptor antagonist regitine indicated that adrenaline mediated inhibition of cell proliferation and regulation of TGF-β1 and bFGF in cultured normal and hypertrophic scar fibroblasts were mediated by the α receptor. These studies suggest that adrenaline inhibits proliferation and alters the expression of TGF-β1 and bFGF in human hypertrophic scar fibroblast involving an α receptor mediated pathway