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Globally exponential stability of Complex (with coupling) Nonlinear Singular Impulsive Networked Control Systems (CNSINCS) with packet dropouts and time-delay is investigated. Firstly, the mathematic model of CNSINCS is established. Then, by employing themethod of Lyapunov functional, exponential stability criteria are obtained and the impulsive controller design method is given. Finally, some simulation results are provided to demonstrate the effectiveness of the proposed method. [ABSTRACT FROM AUTHOR]

Cytokinin is required for the initiation of leguminous nitrogen fixation nodules elicited by rhizobia and the delay of the leaf senescence induced by drought stress. A few free-living rhizobia have been found to produce cytokinin. However, the effects of engineered rhizobia capable of synthesizing cytokinin on host tolerance to abiotic stresses have not yet been described. In this study, two engineered Sinorhizobium strains overproducing cytokinin were constructed. The tolerance of inoculated alfalfa plants to severe drought stress was assessed. The engineered strains, which expressed the Agrobacterium ipt gene under the control of different promoters, synthesized more zeatins than the control strain under free-living conditions, but their own growth was not affected. After a 4-week inoculation period, the effects of engineered strains on alfalfa growth and nitrogen fixation were similar to those of the control strain under nondrought conditions. After being subjected to severe drought stress, most of the alfalfa plants inoculated with engineered strains survived, and the nitrogenase activity in their root nodules showed no apparent change. A small elevation in zeatin concentration was observed in the leaves of these plants. The expression of antioxidant enzymes increased, and the level of reactive oxygen species decreased correspondingly. Although the ¿pf gene was transcribed in the bacteroids of engineered strains, the level of cytokinin in alfalfa nodules was identical to that of the control. These findings suggest that engineered Sinorhizobium strains synthesizing more cytokinin could improve the tolerance of alfalfa to severe drought stress without affecting alfalfa nodulation or nitrogen fixation. [ABSTRACT FROM AUTHOR]

Objective: The G-403A polymorphism in RANTES gene may be involved in the development of coronary artery disease (CAD) through increasing RANTES-mediated leukocyte trafficking and activation. However, studies investigating the relationship between G-403A polymorphism and CAD yielded contradictory and inconclusive results. In order to shed some light on these inconsistent findings, a meta analysis was performed to clarify the role of G-403A polymorphism of RANTES gene in the susceptibility of CAD. Methods: A systemic literature search of PubMed and EMBASE was conducted from their inception to March 23, 2012, to retrieve related studies. In addition, Conference Proceedings Citation Index-Science was searched, authors of relevant studies were contacted, and reference lists of the included studies and their related citations in PubMed were reviewed for additional pertinent studies. Results: A total of 8 eligible studies were identified, with a total of 4252 CAD cases and 2150 controls. There was no evidence of significant association between G-403A polymorphism and CAD risk in any genetic model or pairwise comparisons (additive model: OR = 1.046, 95% CI = 0.883-1.239, I² = 65.9%; recessive model: OR = 1.140, 95% CI = 0.774-1.678, I² = 53.1%; dominant model: OR = 1.000, 95% CI = 0.820-1.21), I² = 62.6%; AA vs GG: OR = 1.141, 95% CI = 0.734-1.773, I² = 61.2%; GA vs GG: OR = 0.993, 95% CI = 0.800-1.232, I² = 64.6%). Subgroup analysis and meta regression indicated that ethnicity and genotyping method accounted for the significant heterogeneity among studies. In the stratified analysis by ethnic group, G-403A polymorphism was found to be associated with increased CAD risk in Caucasian population whereas its protective role was observed in Asian population in some but not all comparisons. Conclusion: Data from the current meta-analysis do not support the existence of a relationship between G-403A polymorphism and the development of CAD, and large sample size study employing unified genotyping method is needed to further evaluate the influence of G-403A polymorphism on susceptibility of CAD. [ABSTRACT FROM AUTHOR]

Human prostate tumor vaccine and gene therapy trials using ex vivo methods to prime dendritic cells (DCs) with prostate specific membrane antigen (PSMA) have been somewhat successful, but to date the lengthy ex vivo manipulation of DCs has limited the widespread clinical utility of this approach. Our goal was to improve upon cancer vaccination with tumor antigens by delivering PSMA via a CD40-targeted adenovirus vector directly to DCs as an efficient means for activation and antigen presentation to T-cells. To test this approach, we developed a mouse model of prostate cancer by generating clonal derivatives of the mouse RM-1 prostate cancer cell line expressing human PSMA (RM-1-PSMA cells). To maximize antigen presentation in target cells, both MHC class I and TAP protein expression was induced in RM-1 cells by transduction with an Ad vector expressing interferon-gamma (Ad5-IFNγ). Administering DCs infected ex vivo with CD40-targeted Ad5-huPSMA, as well as direct intraperitoneal injection of the vector, resulted in high levels of tumor-specific CTL responses against RM-1- PSMA cells pretreated with Ad5-IFNγ as target cells. CD40 targeting significantly improved the therapeutic antitumor efficacy of Ad5-huPSMA encoding PSMA when combined with Ad5-IFNγ in the RM-1-PSMA model. These results suggest that a CD-targeted adenovirus delivering PSMA may be effective clinically for prostate cancer immunotherapy. [ABSTRACT FROM AUTHOR]

We previously showed that introduction of transporter associated with antigen processing (TAP) 1 into TAP-negative CMT.64, a major histocompatibility complex class I (MHC-I) down-regulated mouse lung carcinoma cell line, enhanced T-cell immunity against TAP-deficient tumour cells. Here, we have addressed two questions: (1) whether such immunity can be further augmented by co-expression of TAP1 with B7.1 or H-2Kb genes, and (2) which T-cell priming mechanism (tumour direct priming or dendritic cell cross-priming) plays the major role in inducing an immune response against TAP-deficient tumours. We introduced the B7.1 or H-2Kb gene into TAP1-expressing CMT.64 cells and determined which gene co-expressed with TAP1 was able to provide greater protective immunity against TAP-deficient tumour cells. Our results show that immunization of mice with B7.1 and TAP1 co-expressing but not H-2Kb and TAP1 co-expressing CMT.64 cells dramatically augments T-cell-mediated immunity, as shown by an increase in survival of mice inoculated with live CMT.64 cells. In addition, our results suggest that induction of T-cell-mediated immunity against TAP-deficient tumour cells could be mainly through tumour direct priming rather than dendritic cell cross-priming as they show that T cells generated by tumour cell-lysate-loaded dendritic cells recognized TAP-deficient tumour cells much less than TAP-proficient tumour cells. These data suggest that direct priming by TAP1 and B7.1 co-expressing tumour cells is potentially a major mechanism to facilitate immune responses against TAP-deficient tumour cells. [ABSTRACT FROM AUTHOR]

Tumors deficient in expression of the transporter associated with antigen processing (TAP) usually fail to induce T-cellmediated immunity and are resistant to T-cell lysis. However, we have found that introduction of the B7.1 gene into TAP-negative (TAP-) or TAP1-transfected (TAP1+) murine lung carcinoma CMT.64 cells can augment the capacity of the cells to induce a protective immune response against wild-type tumor cells. Differences in the strength of the protective immune responses were observed between TAP- and TAP1+ B7.1 expressing CMT.64 cells depending on the doses of γ-irradiated cell immunization. While mice immunized with either high or low dose of B7.1-expressing TAP1+ cells rejected TAP- tumors, only high dose immunization with B7.1-expressing TAP- cells resulted in tumor rejection. The induced protective immunity was T-cell dependent as demonstrated by dramatically reduced antitumor immunity in mice depleted of CD8 or CD4 cells. Augmentation of T-cell mediated immune response against TAP2 tumor cells was also observed in a virally infected tumor cell system. When mice were immunized with a high dose of γ-irradiated CMT.64 cells infected with vaccinia viruses carrying B7.1 and/or TAP1 genes, we found that the cells co-expressing B7.1 and TAP1, but not those expressing B7.1 alone, induced protective immunity against CMT.64 cells. In addition, inoculation with live tumor cells transfected with several different gene(s) revealed that only B7.1- and TAP1-coexpressing tumor cells significantly decreased tumorigenicity. These results indicate that B7.1-provoked antitumor immunity against TAP2 cancer is facilitated by TAP1-expression, and thus both genes should be considered for cancer therapy in the future. [ABSTRACT FROM AUTHOR]

Wideband frequency electromagnetic (EM) noise generated during the turn-ON and turn-OFF processes of thyristor valves in converter stations is conducted along the primary circuitry, and may interfere with secondary systems. The EM interference (EMI) problem in a ±800 kV ultra-HVdc converter station is an important issue that should be studied carefully in the design stage. A method to analyze the conducted EM disturbance (EMD) based on time-domain wideband circuit simulation is proposed here, which is verified through the field test results of a ±500 kV converter station. Models of major equipment are described. The EMD levels of a ±800 kV converter station, which is currently being planned and built in China, are calculated, and compared with those of a ±500 kV converter station. [ABSTRACT FROM AUTHOR]

A split root device was designed to assess the possible role of AMF in translocation and detoxification of As by maize plants. Half of each maize root system grew in As-amended or unamended soil and the remainder was inoculated with either Glomus mosseae or Acaulospora morrowiae. External mycelium was collected from a third compartment. Neither shoot nor root As concentrations were affected by inoculation with either fungus. Soil As amendment produced higher As concentrations in roots in the second compartment and in the external mycelium. The As concentrations in the matrix solution of the second root compartment were lower in mycorrhizal treatments with no differences in soluble As in the hyphal compartments. Mycorrhiza exerted little effect on As translocation within plants but may have influenced root As efflux. Deposition of As in external mycelium indicates a possible role of mycorrhizal fungi in the detoxification of As in the host plants. [ABSTRACT FROM AUTHOR]

The transporter associated with antigen processing (TAP) and the major histocompatibility complex class I (MHC-I), two important components of the MHC-I antigen presentation pathway, are often deficient in tumor cells. The restoration of their expression has been shown to restore the antigenicity and immunogenicity of tumor cells. However, it is unclear whether TAP and MHC-I expression in tumor cells can affect the induction phase of the T cell response. To address this issue, we expressed viral antigens in tumors that are either deficient or proficient in TAP and MHC-I expression. The relative efficiency of direct immunization or immunization through cross-presentation in promoting adaptive T cell responses was compared. The results demonstrated that stimulation of animals with TAP and MHC-I proficient tumor cells generated antigen specific T cells with greater killing activities than those of TAP and MHC-I deficient tumor cells. This discrepancy was traced to differences in the ability of dendritic cells (DCs) to access and sample different antigen reservoirs in TAP and MHC-I proficient versus deficient cells and thereby stimulate adaptive immune responses through the process of crosspresentation. In addition, our data suggest that the increased activity of T cells is caused by the enhanced DC uptake and utilization of MHC-I/peptide complexes from the proficient cells as an additional source of processed antigen. Furthermore, we demonstrate that immune-escape and metastasis are promoted in the absence of this DC 'arming' mechanism. Physiologically, this novel form of DC antigen sampling resembles trogocytosis, and acts to enhance T cell priming and increase the efficacy of adaptive immune responses against tumors and infectious pathogens. [ABSTRACT FROM AUTHOR]

Abstract  To minimize the execution time of a sensing task over a multi-hop hierarchical sensor network, we present a coordinated scheduling method following the divisible load scheduling paradigm. The proposed scheduling strategy builds on eliminating transmission collisions and idle gaps between two successive data transmissions. We consider a sensor network consisting of several clusters. In a cluster, after related raw data measured by source nodes are collected at the fusion node, in-network data aggregation is further considered. The scheduling strategies consist of two phases: intra-cluster scheduling and inter-cluster scheduling. Intra-cluster scheduling deals with assigning different fractions of a sensing workload among source nodes in each cluster; inter-cluster scheduling involves the distribution of fused data among all fusion nodes. Closed-form solutions to the problem of task scheduling are derived. Finally, numerical examples are presented to demonstrate the impacts of different system parameters such as the number of sensor nodes, measurement, ommunication, and processing speed, on the finish time and energy consumption. [ABSTRACT FROM AUTHOR]

Abstract Background  In view of the limited success of available treatment modalities for a wide array of cancer, alternative and complementary therapeutic strategies need to be developed. Virotherapy employing conditionally replicative adenoviruses (CRAds) represents a promising targeted intervention relevant to a wide array of neoplastic diseases. Critical to the realization of an acceptable therapeutic index using virotherapy in clinical trials is the achievement of oncolytic replication in tumor cells, while avoiding non-specific replication in normal tissues. In this report, we exploited cancer-specific control of mRNA translation initiation in order to achieve enhanced replicative specificity of CRAd virotherapy agents. Heretofore, the achievement of replicative specificity of CRAd agents has been accomplished either by viral genome deletions or incorporation of tumor selective promoters. In contrast, control of mRNA translation has not been exploited for the design of tumor specific replicating viruses to date. We show herein, the utility of a novel approach that combines both transcriptional and translational regulation strategies for the key goal of replicative specificity. Methods  We describe the construction of a CRAd with cancer specific gene transcriptional control using the CXCR4 gene promoter (TSP) and cancer specific mRNA translational control using a 5′-untranslated region (5′-UTR) element from the FGF-2 (Fibroblast Growth Factor-2) mRNA. Results  Both in vitro and in vivo studies demonstrated that our CRAd agent retains anti-tumor potency. Importantly, assessment of replicative specificity using stringent tumor and non-tumor tissue slice systems demonstrated significant improvement in tumor selectivity. Conclusions  Our study addresses a conceptually new paradigm: dual targeting of transgene expression to cancer cells using both transcriptional and mRNA translational control. Our novel approach addresses the key issue of replicative specificity and can potentially be generalized to a wide array of tumor types, whereby tumor selective patterns of gene expression and mRNA translational control can be exploited. [ABSTRACT FROM AUTHOR]

Extracorporeal shock wave treatment appears to be effective in patients with avascular necrosis of the femoral head. However, the pathway of biological events whereby this is accomplished has not been fully elucidated. The purpose of this study was to investigate the effect of extracorporeal shock waves on vascular endothelial growth factor (VEGF) expression in necrotic femoral heads of rabbits. VEGF expression was assessed by immunohistochemistry, quantitative real-time PCR, and Western blot analysis. The degree of angiogenesis was also assessed, as determined by the microvessel density (MVD), the assessment of which was based on CD31-expressing vessels. Bilateral avascular necrosis of femoral heads was induced with methylprednisolone and lipopolysaccharide in 30 New Zealand rabbits. The left limb (the study side) received shock wave therapy to the femoral head. The right limb (the control side) received no shock wave therapy. Biopsies of the femoral heads were performed at 1, 2, 4, 8, and 12 weeks. Western blot analysis and real-time PCR showed that shock wave therapy significantly increased VEGF protein and mRNA expression, respectively, in the subchondral bone of the treated necrotic femoral heads. Compared with the contralateral control without shock wave treatment, the VEGF mRNA expression levels increased to a peak at 2 weeks after the shock wave treatment and remained high for 8 weeks, then declined at 12 weeks, whereas the VEGF protein expression levels increased to a peak at 4 weeks after the shock wave treatment and remained high for 12 weeks. The immunostaining of VEGF was weak in the control group, and the immunoreactivity level in the shock-wave-treated group increased at 4 weeks and persisted for 12 weeks. The most intensive VEGF immunoreactivity was observed in the proliferative zone above the necrotic zone. At 4, 8, and 12 weeks after the shock wave treatment, MVD in subchondral bone from treated femoral heads was significantly higher than that in subchondral bone from untreated femoral heads. These data clearly show that extracorporeal shock waves can significantly upregulate the expression of VEGF. The upregulation of VEGF may play a role in inducing the ingrowth of neovascularization and in improving the blood supply to the femoral head. [ABSTRACT FROM AUTHOR]

In this paper, we describe how WO3 hollow spheres have been synthesized in solution phase by the controlled hydrolysis of WCI6 using novel carbon microspheres as the templates. All of the products were characterized by X-ray powder diffraction (XRD), scanning electronic microscopy (SEM), and transmission electron microscopy (TEM). The as-synthesized spheres had large diameters of about 400 nm and thin shells of about 30 nm composed of numerous small nanocrystals. Prompted by the porous structure and small crystal size of the shell wall, we constructed WO3 hollow-sphere gas sensors and found that these sensors had good sensitivity to alcohol, acetone, CS2, and other organic gases. [ABSTRACT FROM AUTHOR]

Abstract Background Acetaminophen (APAP) overdose is one of the most common causes of acute liver failure in many countries. The aim of the study was to describe the profiling of phosphatidylcholine (PC) and phosphatidylethanolamine (PE) in the plasma and liver of Acetaminophen -induced liver injured mice. Methods A time course study was carried out using C57BL/6 mice after intraperitoneal administration of 300 mg/kg Acetaminophen 1 h, 3 h, 6 h, 12 h and 24 h. A high-throughput liquid chromatography mass spectrometry (LC-MS) lipidomic method was utilized to detect phosphatidylcholine and phosphatidylethanolamine species in the plasma and liver. The expressions of phosphatidylcholine and phosphatidylethanolamine metabolism related genes in liver were detected by quantitative Reverse transcription polymerase chain reaction (qRT-PCR) and Western-blot. Results Following Acetaminophen treatment, the content of many PC and PE species in plasma increased from 1 h time point, peaked at 3 h or 6 h, and tended to return to baseline at 24 h time point. The relative contents of almost all PC species in liver decreased from 1 h, appeared to be lowest at 6 h, and then return to normality at 24 h, which might be partly explained by the suppression of phospholipases mRNA expressions and the induction of choline kinase (Chka) expression. Inconsistent with PC profile, the relative contents of many PE species in liver increased upon Acetaminophen treatment, which might be caused by the down-regulation of phosphatidylethanolamine N-methyltransferase (Pemt). Conclusions Acetaminophen overdose induced dramatic change of many PC and PE species in plasma and liver, which might be caused by damaging hepatocytes and interfering the phospholipid metabolism in Acetaminophen -injured liver.

Abstract Background Alpha 1-antitrypsin (α1-AT) may affect the susceptibility of mastitis in dairy cattle for its possible role in the protection of lactoferrin from proteolytic degradation in the mammary. Milk somatic cell score (SCS) is a logarithmic transformation of the milk somatic cell count widely used as an index to evaluate mastitis. To study the relationships of α1-AT gene and SCS in Chinese Holstein cows, methods of PCR-SSCP, DNA sequencing, PCR-RFLP, and CRS-PCR technologies were used to detect single nucleotide polymorphisms sites in α1-AT gene. Results Two polymorphic sites at G5503A and G5746C of α1-AT gene were found. AA (0.3633), AB (0.4644) and BB (0.1723) genotypes were detected at G5503A site, CC (0.3483), CD (0.4906) and DD (0.1611) genotypes were found at G5746C in Chinese Holstein cows. Least squares mean of SCS for individuals with BB genotype was significantly lower than that with AA and AB genotype (p 0.05). Least squares mean of SCS for individuals with BBDD genotype combination were significantly lower than those with AACC and AACD (p

Proposes a tracking/level set algorithm that is conservative even at discontinuities and that improves by one order of accuracy over conventional algorithms. Use of hyperbolic conservation laws in many branches of continuum physics; Conservation laws in integral form; Ghost-cell extrapolation tracking methods.

OBJECTIVE: To investigate the feasibility of using free gracilis muscle transfer along with the brachialis muscle branch of the musculocutaneous nerve to restore finger and thumb flexion in lower trunk brachial plexus injury according to an anatomical study and a case report. METHODS: Thirty formalin-fixed upper extremities from 15 adult cadavers were used in this study. The distance from the point at which the brachialis muscle branch of the musculocutaneous nerve originates to the midpoint of the humeral condylar was measured, as well as the length, diameter, course and branch type of the brachialis muscle branch of the musculocutaneous nerve. An 18-year-old male who sustained an injury to the left brachial plexus underwent free gracilis transfer using the brachialis muscle branch of the musculocutaneous nerve as the donor nerve to restore finger and thumb flexion. Elbow flexion power and hand grip strength were recorded according to British Medical Research Council standards. Postoperative measures of the total active motion of the fingers were obtained monthly. RESULTS: The mean length and diameter of the brachialis muscle branch of the musculocutaneous nerve were 52.66±6.45 and 1.39±0.09 mm, respectively, and three branching types were observed. For the patient, the first gracilis contraction occurred during the 4th month. A noticeable improvement was observed in digit flexion one year later; the muscle power was M4, and the total active motion of the fingers was 209°. CONCLUSIONS: Repairing injury to the lower trunk of the brachial plexus by transferring the brachialis muscle branch of the musculocutaneous nerve to the anterior branch of the obturator nerve using a tension-free direct suture is technically feasible, and the clinical outcome was satisfactory in a single surgical patient.

Vascularization of acellular nerves has been shown to contribute to nerve bridging. In this study, we used a 10-mm sciatic nerve defect model in rats to determine whether cartilage oligomeric matrix protein enhances the vascularization of injured acellular nerves. The rat nerve defects were treated with acellular nerve grafting (control group) alone or acellular nerve grafting combined with intraperitoneal injection of cartilage oligomeric matrix protein (experimental group). As shown through two-dimensional imaging, the vessels began to invade into the acellular nerve graft from both anastomotic ends at day 7 post-operation, and gradually covered the entire graft at day 21. The vascular density, vascular area, and the velocity of revascularization in the experimental group were all higher than those in the control group. These results indicate that cartilage oligomeric matrix protein enhances the vascularization of acellular nerves.

Acellular nerve allografts can help preserve normal nerve structure and extracellular matrix composition. These allografts have low immunogenicity and are more readily available than autologous nerves for the repair of long-segment peripheral nerve defects. In this study, we repaired a 40-mm ulnar nerve defect in rhesus monkeys with tissue-engineered peripheral nerve, and compared the outcome with that of autograft. The graft was prepared using a chemical extract from adult rhesus monkeys and seeded with allogeneic Schwann cells. Pathomorphology, electromyogram and immunohistochemistry findings revealed the absence of palmar erosion or ulcers, and that the morphology and elasticity of the hypothenar eminence were normal 5 months postoperatively. There were no significant differences in the mean peak compound muscle action potential, the mean nerve conduction velocity, or the number of neurofilaments between the experimental and control groups. However, outcome was significantly better in the experimental group than in the blank group. These findings suggest that chemically extracted allogeneic nerve seeded with autologous Schwann cells can repair 40-mm ulnar nerve defects in the rhesus monkey. The outcomes are similar to those obtained with autologous nerve graft.

To study phosphorus (P) depletion and soil pH changes at the root-soil interface (rhizosphere) and at the hyphae-soil interface, mycorrhizal and non-mycorrhizal white clover (Trifolium repens L.) plants were grown for 7 wk in two sterilized soils (Luvisol and Cambisol) in pots comprising five compartments: a central one for root growth, two adjacent compartments, separated from the central compartment by a nylon net of 30 μm mesh size, for growth of vesicular-arbuscular (VA) mycorrhizal [Glomus mosseae (Nicol. & Gerd.) Gerdemann & Trappe] hyphae (hyphal compartments), and two outer compartments, separated from the hyphal compartments by a 0.45 μm membrane, which neither roots nor hyphae could penetrate (bulk soil compartments). Phosphorus was supplied as Ca(H2PO4)2 at a rate of 50 mg P kg-1 soil in the root compartment and 150 mg P kg-1 soil in the hyphal and bulk soil compartments. Nitrogen was supplied as (NH4)2SO4 at the rate of 300 mg N kg-1 soil uniformly to all compartments. In both soils, shoot dry weight and P uptake were much higher in mycorrhizal plants compared with non-mycorrhizal plants. Hyphae of VA mycorrhizal fungi contributed 70 % (Cambisol) or 80% (Luvisol) to total P uptake of mycorrhizal plants. In the hyphal compartments, concentrations of both H2O-extractabe soil P (Cambisol and Luvisol) and NaHCO3-extractable soil P (Luvisol) were decreased drastically. Soil P depletion profiles developed not only at the root--soil interface (rhizosphere), but also at the hyphae-soil interface and extended several millimetres from the hyphae surface into the soil. Likewise, the soil pH was decreased at the root-soil interface, in the hyphal compartment and also at the hyphae soil interface. [ABSTRACT FROM AUTHOR]

Regorafenib is an oral small-molecule multi kinase inhibitor. Recently, several clinical trials have revealed that regorafenib has an anti-tumor activity in gastric cancer. However, only part of patients benefit from regorafenib, and the mechanisms of regorafenib's anti-tumor effect need further demonstrating. In this study, we would assess the potential anti-tumor effects and the underlying mechanisms of regorafenib in gastric cancer cells, and explore novel biomarkers for patients selecting of regorafenib.The anti-tumor effects of regorafenib on gastric cancer cells were analyzed via cell proliferation and invasion. The underlying mechanisms were demonstrated using molecular biology techniques.We found that regorafenib inhibited cell proliferation and invasion at the concentration of 20μmol/L and in a dose dependent manner. The anti-tumor effects of regorafenib related to the decreased expression of CXCR4, and elevated expression and activation of CXCR4 could reverse the inhibition effect of regorafenib on gastric cancer cells. Further studies revealed that regorafenib reduced the transcriptional activity of Wnt/β-Catenin pathway and led to decreased expression of Wnt pathway target genes, while overexpression and activation of CXCR4 could attenuate the inhibition effect of regorafenib on Wnt/β-Catenin pathway.Our findings demonstrated that regorafenib effectively inhibited cell proliferation and invasion of gastric cancer cells via decreasing the expression of CXCR4 and further reducing the transcriptional activity of Wnt/β-Catenin pathway.

Metastasis of tumor cells occurs through lymphatic vessels, blood vessels and transcoelomic spreading. Growing evidence from in vivo and in vitro studies has indicated that tumor lymphangiogenesis facilitates metastasis. However, the regulation of lymphangiogenesis in colon cancer remains unclear. The aims of this study were to identify key miRNAs in colon cancer lymphangiogenesis and to investigate its target and mechanism.miRNA microarray analysis was conducted to identify miRNAs in human lymphatic endothelial cells (HLECs) that were regulated by co-cultured human colon cancer cells. Gain- and loss-of-function studies were performed to determine the function of miR-27a, a top hint, on lymphangiogenesis and migration in HLECs. Furthermore, bioinformatics prediction and experimental validation were performed to identify miR-27a target genes in lymphangiogenesis.We found that expression of miR-27a in HLECs was induced by co-culturing with colon cancer cells. Over-expression of miR-27a in HLECs enhanced lymphatic tube formation and migration, whereas inhibition of miR-27a reduced lymphatic tube formation and migration. Luciferase reporter assays showed that miR-27a directly targeted SMAD4, a pivotal component of the TGF-β pathway. In addition, gain-of-function and loss-of-function experiments showed that SMAD4 negatively regulated the length of lymphatic vessels formed by HLECs and migration.Our data indicated that colon cancer cell induced the expression of miR-27a in HLECs, which promoted lymphangiogenesis by targeting SMAD4. Our finding implicated miR-27a as a potential target for new anticancer therapies in colon cancer.

Vortex shedding from a moving obstacle potential in a two-component Bose–Einstein condensate is investigated numerically. For a miscible two-component condensate composed of 23Na and 87Rb atoms, in the wake of obstacle, the Kármán vortex street is discovered in one component, while the Kármán-like vortex street named ‘half-quantum vortex street’ is formed in another component. The other patterns of vortex shedding, such as the vortex dipoles, V-shaped vortex pairs and corresponding ‘half-quantum vortex shedding’, can also be found. The drag force acting on obstacle potential is calculated and discussed. The parameter region for various vortex patterns and critical velocity for vortex emission are presented. In addition, a 85Rb–87Rb mixture is also considered, where the Kármán vortex street and other typical patterns exist in both components. Finally, we provide an experimental protocol for the above realization and observation. [ABSTRACT FROM AUTHOR]

A practical three-step synthetic approach to gimeracil in a 68% overall yield is described, using 2,4-dimethoxypyridine as the starting material with 3,5-dichloro-2,4-dimethoxypyridine and 3,5-dichloro-2,4-dihydroxypyridine as intermediates. The advantages of this procedure include short reaction steps, simple operation and good yield. [ABSTRACT FROM AUTHOR]

Prunus is an economically important genus well-known for cherries, plums, almonds, and peaches. The genus can be divided into three major groups based on inflorescence structure and ploidy levels: (1) the diploid solitary-flower group (subg. Prunus, Amygdalus and Emplectocladus); (2) the diploid corymbose group (subg. Cerasus); and (3) the polyploid racemose group (subg. Padus, subg. Laurocerasus, and the Maddenia group). The plastid phylogeny suggests three major clades within Prunus: Prunus-Amygdalus-Emplectocladus, Cerasus, and Laurocerasus-Padus-Maddenia, while nuclear ITS trees resolve Laurocerasus-Padus-Maddenia as a paraphyletic group. In this study, we employed sequences of the nuclear loci At103, ITS and s6pdh to explore the origins and evolution of the racemose group. Two copies of the At103 gene were identified in Prunus. One copy is found in Prunus species with solitary and corymbose inflorescences as well as those with racemose inflorescences, while the second copy (II) is present only in taxa with racemose inflorescences. The copy I sequences suggest that all racemose species form a paraphyletic group composed of four clades, each of which is definable by morphology and geography. The tree from the combined At103 and ITS sequences and the tree based on the single gene s6pdh had similar general topologies to the tree based on the copy I sequences of At103, with the combined At103-ITS tree showing stronger support in most clades. The nuclear At103, ITS and s6pdh data in conjunction with the plastid data are consistent with the hypothesis that multiple independent allopolyploidy events contributed to the origins of the racemose group. A widespread species or lineage may have served as the maternal parent for multiple hybridizations involving several paternal lineages. This hypothesis of the complex evolutionary history of the racemose group in Prunus reflects a major step forward in our understanding of diversification of the genus and has important implications for the interpretation of its phylogeny, evolution, and classification.

The loss of microRNA-122 (miR-122) expression is strongly associated with increased invasion and metastasis, and poor prognosis of hepatocellular carcinoma (HCC), however, the underlying mechanisms remain poorly understood. In the present study, we observed that miR-122 over-expression in HCC cell lines Sk-hep-1 and Bel-7402 triggered the mesenchymal-epithelial transition (MET), as demonstrated by epithelial-like morphological changes, up-regulated epithelial proteins (E-cadherin, ZO-1, α-catenin, occludin, BVES, and MST4), and down-regulated mesenchymal proteins (vimentin and fibronectin). The over-expression of miRNA-122 also caused cytoskeleton disruption, RhoA/Rock pathway inactivation, enhanced cell adhesion, and suppression of migration and invasion of Sk-hep-1 and Bel-7402 cells, whereas, these effects could be reversed through miR-122 inhibition. Additional studies demonstrated that the inhibition of wild-type RhoA function induced MET and inhibited cell migration and invasion, while RhoA over-expression reversed miR-122-induced MET and inhibition of migration and invasion of HCC cells, suggesting that miR-122 induced MET and suppressed the migration and invasion of HCC cells by targeting RhoA. Moreover, our results demonstrated that HNF4α up-regulated its target gene miR-122 that subsequently induced MET and inhibited cell migration and invasion, whereas miR-122 inhibition reversed these HNF4α-induced phenotypes. These results revealed functional and mechanistic links among the tumor suppressors HNF4α, miR-122, and RhoA in EMT and invasive and metastatic phenotypes of HCC. Taken together, our study provides the first evidence that the HNF4α/miR-122/RhoA axis negatively regulates EMT and the migration and invasion of HCC cells.

BACKGROUND: Osteosarcoma is the most common primary bone cancer in growing adolescents and young adults. The prognostic role of C-reactive protein (CRP) in patients with osteosarcoma is not fully investigated. The purpose of this study is to perform a meta-analysis and literature review on the role of CRP in osteosarcoma and to assess the potential role of serum CRP as a prognostic factor for patients with osteosarcoma. METHODS: A detailed literature search was made in Medline for related research publications written in English. Methodological quality of the studies was also evaluated. The data were extracted and assessed by two reviewers independently. Analysis of pooled data were performed, risk ratio (RR) and corresponding confidence intervals (CIs) were calculated and summarized respectively. RESULTS: Final analysis of 397 patients from 2 eligible studies was performed. Combined RR of CRP expression suggested that the raised serum CRP level had an adverse prognostic effect on overall survival of patients with osteosarcoma (n = 397 in 2 studies; RR = 0.35; 95% CI: 0.18-0.68; p = 0.002). In the uni- and multivariate survival analysis, response rate and CRP levels were the only independent prognostic variables. CONCLUSIONS: The results of this meta-analysis suggest that CRP expression confers a worse prognosis in patients with osteosarcoma. Large prospective studies are necessary to provide solid data to confirm the prognostic significance of CRP.

C13H16N2O2, orthorhombic, P212121 (no. 19), a = 7.488(2) Å, b = 9.633(2) Å, c = 16.933(3) Å, V = 1221.4 ų, Z = 4, Rgt(F) = 0.0671, wRref(F²) = 0.1661, T = 293 K. [ABSTRACT FROM AUTHOR]

C13H16N2O2, orthorhombic, P212121 (no. 19), a = 7.488(2) Å, b = 9.633(2) Å, c = 16.933(3) Å, V = 1221.4 ų, Z = 4, Rgt(F) = 0.0671, wRref(F²) = 0.1661, T = 293 K. [ABSTRACT FROM AUTHOR]

DPoS (delegated proof of stake) is one of the current mainstream blockchain consensus mechanisms,and the unique node election mechanism makes it form an evolving blockchain community.Analyzing the evolution model of the blockchain community can discover the potential risks of the consensus mechanism,which has very important research significance.For the DPoS consensus mechanism blockchain data,a novel combination analysis method of the consensus mechanism effectiveness is proposed,and a set of visual analysis methods are designed to help users analyze the evolutionary model of the blockchain community from multiple angles.First,it quantifies the difference between the degree of completion of the work and the voting ranking before and after the node ranking change and analyzes the selection efficiency and incentive efficiency of the consensus mechanism;then,it focuses on the combined efficiency of the consensus mechanism,the evolution of the geographical distribution of nodes,and the comparison of the evolutionary differences between nodes and designs visual views and interactive means;finally,it designs and implements a visual analysis system of blockchain community evolution based on the DPoS consensus mechanism based on the real data of the EOS main chain and verifies the usability and effectiveness of this method through case studies and expert evaluation.

We present an element-free Galerkin method for electromechanical coupled fracture analysis in piezoelectric materials. Singularity terms were introduced into the approximation function of the new method to describe the displacement and electric fields near the crack. The new method requires a smaller domain to describe the crack-tip singular field compared with the finite element method. Then, we computed the J-integrals of piezoelectric materials and investigated the effects of crack length on the computational precision. Numerical examples were used to highlight the accuracy of the new method compared with the analytical solutions and finite element method.

Based on the finite element software ABAQUS and graded element method, we developed a dummy node fracture element, wrote the user subroutines UMAT and UEL, and solved the energy release rate component of functionally graded material (FGM) plates with cracks. An interface element tailored for the virtual crack closure technique (VCCT) was applied. Fixed cracks and moving cracks under dynamic loads were simulated. The results were compared to other VCCT-based analyses. With the implementation of a crack speed function within the element, it can be easily expanded to the cases of varying crack velocities, without convergence difficulty for all cases. Neither singular element nor collapsed element was required. Therefore, due to its simplicity, the VCCT interface element is a potential tool for engineers to conduct dynamic fracture analysis in conjunction with commercial finite element analysis codes.

Background The objective of this study was to determine whether vascular endothelial growth factor (VEGF)-A subtypes improve cardiac stem cell (CSC) engraftment and promote CSC-mediated myocardial repair in the infarcted heart. Methods CSCs were treated with VEGF receptor (VEGFR) inhibitors, VCAM-1 antibody (VCAM-1-Ab), or PKC-α inhibitor followed by the treatment with VEGF-A. CSC adhesion assays were performed in vitro. In vivo, the PKH26-labeled and VCAM-1-Ab or PKC-α inhibitor pre-treated CSCs were treated with VEGF-A followed by implantation into infarcted rat hearts. The hearts were then collected for measuring CSC engraftment and evaluating cardiac fibrosis and function 3 or 28 days after the CSC transplantation. Results All three VEGF-A subtypes promoted CSC adhesion to extracellular matrix and endothelial cells. VEGF-A-mediated CSC adhesion required VEGFR and PKCα signaling. Importantly, VEGF-A induced VCAM-1, but not ICAM-1 expression in CSCs through PKCα signaling. In vivo, VEGF-A promoted the engraftment of CSCs in infarcted hearts, which was attenuated by PKCα inhibitor or VCAM-1-Ab. Moreover, VEGF-A-mediated CSC engraftment resulted in a reduction in infarct size and fibrosis. Functional studies showed that the transplantation of the VEGF-A-treated CSCs stimulated extensive angiomyogenesis in infarcted hearts as indicated by the expression of cardiac troponin T and von Willebrand factor, leading to an improved performance of left ventricle. Blockade of PKCα signaling or VCAM-1 significantly diminished the beneficial effects of CSCs treated with VEGF-A. Conclusion VEGF-A promotes myocardial repair through, at least in part, enhancing the engraftment of CSCs mediated by PKCα/VCAM-1 pathway. [ABSTRACT FROM AUTHOR]

Background/aims: Bile is the main cause of poor bowel preparation for capsule endoscopy (CE). We aimed to determine whether cholestyramine and hydrotalcite can eliminate bile in the bowel., Patients and Methods: Patients undergoing CE were randomized into two groups. Group A patients (n = 75) received 250 mL 20% mannitol and 1 L 0.9% saline orally at 20:00 hours on the day before and at 05:00 hours on the day of CE and 20 mL simethicone 30 min before CE. Group B patients (n = 73) were treated identically, except for taking oral cholestyramine and hydrotalcite, starting 3 days before CE. Greenish luminal contents were assessed by four tissue color bar segments using Color Area Statistics software. Bowel cleanliness was evaluated by visualized area percentage assessment of cleansing (AAC) score., Result: Bowel cleanliness (82.7% [62/75] vs 46.6% [34/73]; χ2 = 14.596, P = 0.000). and detected greenish luminal contents (20.0% [15/75] vs 8.2% [6/73]; χ2 = 4.217, P = 0.040) were significantly greater in Group A than in Group B. Greenish luminal contents in the two groups differed significantly in the captured small-bowel (t = -13.74, P = 0.000) segments and proximal small-bowel (t = -0.7365, P = 0.000) segments, but not for the distal small-bowel (t = -0.552, P = 0.581) segments., Conclusions: Cholestyramine and hydrotalcite were ineffective in eliminating bile and improving small-bowel preparation.

Gastric cancer is one of the most frequent neoplasms and a main cause of death worldwide, especially in China and Japan. Numerous epidemiological, animal and experimental studies support a positive association between chronic Helicobacter pylori (H. pylori) infection and the development of gastric cancer. However, the exact mechanism whereby H. pylori causes gastric carcinogenesis remains unclear. It has been demonstrated that expression of cyclooxygenase-2 (COX-2) is elevated in gastric carcinomas and in their precursor lesions. In this review, we present the latest clinical and experimental evidence showing the role of gastrin and COX-2 in H. pylori-infected patients and their possible association with gastric cancer risk.