Aim:Sphingosine kinase 1 (SPHK1) is involved in various cellular functions, including cell growth, migration, apoptosis, cytoskeleton architecture and calcium homoeostasis, etc. As an oncogenic ...kinase, SPHK1 is associated with the development and progression of cancers. The aim of this study was to investigate whether SPHK1 was involved in hepatocarcinogenesis induced by the hepatitis B virus X protein (HBx).Methods:The expression of SPHK1 in hepatocellular carcinoma (HCC) tissue and hepatoma cells were measured using qRT-PCR and Western blot analysis. HBx expression levels in hepatoma cells were modulated by transiently transfected with HBx or psi-HBx plasmids. The SPHK1 promoter activity was measured using luciferase reporter gene assay, and the interaction of the transcription factor AP2α with the SPHK1 promoter was studied with chromatin immunoprecipitation assay. The growth of hepatoma cells was evaluated in vitro using MTT and colony formation assays, and in a tumor xenograft model.Results:A positive correlation was found between the mRNA levels of SPHK1 and HBx in 38 clinical HCC samples (r=+0.727, P<0.01). Moreover, the expression of SPHK1 was markedly increased in the liver cancer tissue of HBx-transgenic mice. Overexpressing HBx in normal liver cells LO2 and hepatoma cells HepG2 dose-dependently increased the expression of SPHK1, whereas silencing HBx in HBx-expressing hepatoma cells HepG2-X and HepG2.2.15 suppressed SPHK1 expression. Furthermore, overexpressing HBx in HepG2 cells dose-dependently increased the SPHK1 promoter activity, whereas silencing HBx in HepG2-X cells suppressed this activity. In HepG2-X cells, AP2α was found to directly interact with the SPHK1 promoter, and silencing AP2α suppressed the SPHK1 promoter activity and SPHK1 expression. Silencing HBx in HepG2-X cells abolished the HBx-enhanced proliferation and colony formation in vitro, and tumor growth in vivo.Conclusion:HBx upregulates SPHK1 through the transcription factor AP2α, which promotes the growth of human hepatoma cells
Aiming at meeting the requirement of modularization for megawatt wind power converter, the paralleling structure of IGBT modules was designed. Fast transient response and current sharing capabilities ...of the paralleled IGBT modules were regarded as the main research object, the drive circuit and adapter plate was also designed. utilizing the new type of protection circuit on the adapter plate to ensure reliability of the paralleled IGBT modules. As one of the most promising technologies, Digital drive technology was applied as the conception of the driver, and the core of the driver is FPGA and A/D sampling circuit. Using digital driver had the advantages of good consistency pulse parameters, flexible software programming and high anti-jamming ability. The current equalization among the IGBT modules was verified by means of the field test. Based on the experiment, the characteristics of balancing parallel IGBTs' currents were better than previous designs. It is concluded that the whole design of the system was reasonable and can meet the demands of the engineering applications.
Since plague is an important natural focus zoonosis, the typing of natural plague foci becomes one of the elements in understanding the nature and developing related prevention program of the ...disease. Natural foci of plague are composed by four fundamental parts which include Eco-geographical landscape (natural plague foci), hosts, vectors and pathogens (Yersinia pestis) that comprehensively interact through the large temporal scale of evolution. Human activities have had great impact on the foci of natural plague. Based on the published serial research papers, we tried to integrate the knowledge of each factor in natural plague foci and focusing on theoretical aspects, so as to strengthen the prevention and surveillance programs of plague to be extrapolated to other zoonosis.
Objectives. The aim of this study was to assess the value of diagnosis of endometrial hyperplasia by curettage and to determine the results of proliferating cell nuclear antigen (PCNA) immunostaining ...in differentiating endometrial carcinoma from endometrial hyperplasia.
Methods. According to Kurman's criteria, we treated 150 patients with endometrial hyperplasia detected by curettage and compared retrospectively the diagnosis by curettage with that by hysterectomy. PCNA expression was examined using immunohistochemostaining on 60 patients with complex atypical hyperplasia detected by curettage.
Results. Simple hyperplasia was found by curettage in 53 patients, complex hyperplasia in 11, simple atypical hyperplasia in 26, and complex atypical hyperplasia in 60. All patients were rediagnosed after hysterectomy. As a result, 65 were found to have simple hyperplasia, 7 complex hyperplasia, 15 simple atypical hyperplasia, 29 complex atypical hyperplasia, and 34 endometrial carcinoma. The accuracy of histological diagnosis by curettage was 76.7–92.0% and was dependent on different types of hyperplasia. Simple atypical hyperplasia and complex atypical hyperplasia were more likely to coexist with endometrial carcinoma than both simple hyperplasia and complex hyperplasia (χ2 = 26.3, P < 0.001), and complex atypical hyperplasia was more likely to coexist with endometrial carcinoma than simple atypical hyperplasia (χ2 = 9.78, P < 0.005). In complex atypical hyperplasia patients, coexistence with endometrial carcinoma was more common after menopause than before menopause (χ2 = 3.93, P < 0.05). In complex atypical hyperplasia patients, the expression of PCNA in cases associated with endometrial carcinoma was higher or stronger than in cases associated without endometrial carcinoma (χ2 = 7.68, P < 0.01, or U = 252.00, P < 0.01).
Conclusions. Curettage tends to be more highly accurate in diagnosing simple hyperplasia than complex atypical hyperplasia, which is often found by hysterectomy to be associated with endometrial carcinoma. The expression of PCNA may be helpful in differentiating complex atypical hyperplasia from endometrial carcinoma.
Objective LcrV is an important component for the development of a subunit vaccine against plague.To reduce immunosuppressive activity of LcrV,a recombinant LcrV variant lacking amino acids 271 to 326 ...（rV270） was prepared by different methods in this study.Methods A new strategy that produced non-tagged or authentic rV270 protein was designed by insertion of rV270-thrombin-hexahistidine fusion gene into the vector pET24a,or by insertion of hexahistidine-enterokinase-rV270 or hexahistitine-factor Xa-rV270 fusion gene into the vector pET32a.After Co2＋ affinity chromatography,a purification strategy was developed by cleavage of His tag on column,following Sephacryl S-200HR column filtration chromatography.Results Removal of His tag by thrombin,enterokinase and factor Xa displayed a yield of 99.5%,32.4% and 15.3%,respectively.Following Sephacryl S-200HR column filtration chromatography,above 97% purity of rV270 protein was obtained.Purified rV270 that was adsorbed to 25% （v/v） Al（OH）3 adjuvant in phosphate-buffered saline （PBS） induced very high titers of antibody to rV270 in BALB/c mice and protected them （100% survival） against subcutaneous challenge with 106 CFU of Y.pestis virulent strain 141.Conclusion The completely authentic rV270 protein can be prepared by using enterokinase or factor Xa,but they exhibited extremely low cleavage activity to the corresponding recognition site.Thrombin cleavage is an efficient strategy to prepare non-tagged rV270 protein and can be easily operated in a large scale due to its relatively low cost and high cleavage efficacy.The recombinant rV270 can be used as a key component to develop a subunit vaccine of plague.
Deuterated potassium dihydrogen phosphate damage performance at 351 nm is studied on a large-aperture laser system. Bulk and rear-surface damage are initiated under the 3ω fluences of 6.7 J/cm2 and 3 ...J/cm2, and show different growth characteristics under multiple laser irradiations with the fluence of 6 J/cm2. The size and number of bulk damage keep unchanged once initiated. However, surface damage size also does not grow, while surface damage number increases linearly with laser shots. Different damage thresholds and growth behaviors suggest different formations of bulk and surface damage precursors. The cause of surface damage is supposed to be near-surface absorbing particles buried under the sol-gel coating.
The doubly charmed baryon \(\Xi_{cc}^{++}\) has been observed by LHCb through the non-leptonic decay modes of \(\Xi_{cc}^{++}\to\Lambda_{c}^{+}K^{-}\pi^{+}\pi^{+}\) and \(\Xi_{c}^{+}\pi^{+}\) in ...2017. After that, the experimentalists turn their attention to finding other doubly charmed baryons \(\Xi_{cc}^{+}\) and \(\Omega_{cc}^{+}\). In this work, we investigate the nonleptonic weak decays of doubly charmed baryons \({\cal B}_{cc}\to{\cal B}_{c}P\), where \({\cal B}_{cc}\) denotes the doubly charmed baryons \((\Xi_{cc}^{++},\Xi_{cc}^{+},\Omega_{cc}^{+})\), \({\cal B}_{c}\) represents the singly charmed baryons \(({\cal B}_{\bar{3}},{\cal B}_{6})\) and \(P\) is the light pseudoscalar. For these non-leptonic decay modes, their short-distance contributions can be accurately estimated in theoretical calculations. However, dealing with the long-distance contributions for final-state-interaction effects is challenging. To address this, we use the rescattering mechanism to calculate the long-distance contributions and first derive the whole hadronic loop contributions for these two-body nonleptonic decays of doubly charmed baryons. Then the decay widths and branching ratios of the 45 nonleptonic decays of doubly charmed baryon are predicted. Among that, the ratio of the branching ratios \({\cal RB}=\frac{{\cal B}(\Xi_{cc}^{++}\to\Xi_{c}^{\prime+}\pi^{+})}{{\cal B}(\Xi_{cc}^{++}\to\Xi_{c}^{+}\pi^{+})}=1.15\pm0.45\) is consistent with the experimental results within statistical errors.
To determine the effect of Qufeng Tongluo Recipe (QFTLR) on the expressions of connexin 36 (Cx36) protein and gene in rat mesangial cells (MCs) and the proliferation of the MCs.
Serum samples ...containing Benazepril (Bena) and QFTLR were prepared in line with serum pharmacology methodology. The MCs cultured in vitro were divided into normal control and Lipopolysaccharide (LPS), Bena and QFTLR treated groups. The expressions of Cx36 protein and gene were detected by laser scanning confocal microscope (LSCM), Western blot, immunohistochemical assay and quantitative real time polymerase chain reaction (QRT-PCR) respectively.
Compared with the control, higher level of Cx36 protein expression was found in the MCs than treated with LPS (P < 0.01). Both Bena and QFTLR lowered the level of Cx36 protein expression in the MCs treated with LPS significantly (P < 0.01 or P < 0.05). Similar results were found with the expression of Cx36 mRNA.
QFTLR inhibits the proliferation of rat MCs, possibly through down-regulating the
Empirical relationships between carbon dioxide emission, imports, exports, and population have been investigated. An empirical model with carbon dioxide emissions, structure and scale of import and ...exports, populations was built. Using ridge regression analysis and observed data from 1985 to 2006 in China, we examined the relationship between each part of carbon dioxide emission and corresponding coefficients, including GIV (gross imports value), GXV (gross exports value), and P (populations). The results have shown that the increasing trend in TCOE (total carbon dioxide emissions) was determined by the exports, while its standard level is determined by population. Increasing the imports may reduce TCOE. Considering working to expand economy, the best ways for China to reduce TCOE are to introduce advanced technology and take actions to guarantee strict execution of cut-emission policy. Although the increasing imports also can reduce TCOE, it is not reasonable for the global cut-emission policy. To control population is not applicable as the immense population base, so government's publicity for low-carbon live is a necessary and feasible way to reduce carbon dioxide emission.
Diabetes frequently presents accumulation of advanced glycation end products (AGEs), which might induce excessive TNF-alpha production from macrophages to cause impaired wound healing. Recent studies ...have shown that activation of alpha7 nicotinic acetylcholine receptor (alpha7nAChR) on macrophages efficiently suppressed TNF-alpha synthesis. The aim of this study was to investigate the accumulation of AGEs in the wounds and determine whether PNU282987, an alpha7nAChR agonist, can improve wound repair by inhibiting AGE-mediated TNF-alpha production in a streptozotocin (STZ)-induced diabetic mouse model. Animals were assigned into four groups: wounded control group, wounded diabetic group, wounded diabetic group treated intraperitoneally with PNU282987, or wounded diabetic group treated intraperitoneally with vehicle. Compared with the non-diabetic control mice, the diabetic mice exhibited delayed wound healing that was characterized by elevated accumulation of AGEs, increased TNF-alpha level and macrophage infiltration, and decreased fibroblast number and collagen deposition at the late stage of repair. Besides, macrophages of diabetic wounds showed expression of alpha7nAChR. During late repair, PNU282987 treatment of diabetic mice significantly reduced the level of TNF-alpha, accelerated wound healing, and elevated fibroblast number and collagen deposition. To investigate the cellular mechanism of these observations, RAW 264.7 cells, a macrophage cell line, were incubated with AGEs in the presence or absence of PNU282987. TNF-alpha production from AGE-stimulated macrophages was significantly decreased by PNU282987 in a dose-dependent manner. Furthermore, PNU282987 significantly inhibited AGE-induced nuclear factor-kappaB (NF-kappaB) activation and receptor for AGE (RAGE) expression. These results strongly suggest that activating alpha7nAChR can promote diabetic wound healing by suppressing AGE-induced TNF-alpha production, which may be closely associated with the blockage of NF-kappaB activation in macrophages.
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