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To evaluate the effectiveness of urban construction projects onThe data pertaining to the endemic situation of schistosomiasis, schistosomiasis control data, the construction of the Yangtze River Bridge, marshland management and park constructions were collected from Wuhan City from 1990 to 2020. The changes of areas of snail habitats and high-risk settings were compared before and after implementation of these urban construction projects to evaluate the effectiveness of urban construction projects onThe number of schistosomiasis cases decreased by 97.35%, and the number of cattle with schistosomiasis decreased by 100% in Wuhan City from 1990 to 2020, with a 41.99% reduction in areas of snail habitats, including 94.97% and 34.40% reductions in snail habitats inside and outside the embankment decreased. During the period from 1990 through 2020, a total of 10 Yangtze River bridges were built in Wuhan City, and areas of snail habitats around the bridges reduced from 11 699.05 hmSimultaneous implementation of urban construction projects and schistosomiasis control measures is effective to shrink snail-infested setting and high-risk settings and control the endemic situation of schistosomiasis in endemic foci in Wuhan City.

Purpose To use statistical process control for intensity-modulated radiation therapy (IMRT) quality assurance (QA) and improve tolerance limits and action limits. Methods An electronic portal imaging device (EPID) was selected to verify IMRT QA. The I-chart and the exponentially weighted moving averages (EWMA) chart were used to analyze the corresponding results. Results Twenty samples were used to enable the sampling requirements for building the control limits to be met. The I-chart showed that isolated data points beyond the control limits were mainly derived from complex plans. The EWMA made predictions of systematic errors earlier than the I-chart. Systematic errors primarily originated from the dose calibration on the EPID, and recalibrating the EPID could eliminate such errors. Conclusion Statistical process control is an effective tool to detect controllable and can be used in IMRT QA. After calibrating the EPID, the tolerance and action limits all improved and satisfied the requirements/recommended values of the AAPM TG-218 report.

Soil-transmitted nematodiasis was once widely prevalent in Jiangsu Province, which seriously threatened human health and hindered socioeconomic development. The control efforts over decades resulted in a remarkable decline in the prevalence of soil-transmitted nematode human infections in Jiangsu Province, with a reduction from 59.32% in 1989 to 0.12% in 2019, and the human prevalence remains at0.5% since 2013. Since 1987, an integrated strategy has been adopted for the control of soil-transmitted nematodiasis in Jiangsu Province; however, the core interventions varies at different stages, which mainly include deworming, water and sanitation service improvement, health education, and monitoring and assessment. The criteria of effective soil-transmitted nematodiasis control had been achieved in all epidemic counties (districts) of Jiangsu Province by 2019. Further actions to strengthen health education and monitoring and implement precision control measures are required to consolidate the achievements of soil-transmitted nematodiasis control and eliminate the harm of soil-transmitted nematodiasis to humans. This review summarizes the epidemiology, control progress and evolution of control strategy of soil-transmitted nematodiasis in Jiangsu Province.

Long noncoding RNA (lncRNA) is emerging as a vital regulator in various tumors. However, the biological function of ZFPM2-antisense RNA 1 (ZFPM2-AS1) in hepatocellular carcinoma (HCC) remains unclear. The present study aims to explore the function and mechanism of ZFPM2-AS1 in hepatocellular carcinoma progression.The ZFPM2-AS1 expression in HCC cells and tissues was measured by quantitative real-time polymerase chain reaction (qRT-PCR). Effects of ZFPM2-AS1 on tumor cell proliferation and invasion were detected by CCK8 assay or EdU assay or matrigel migration assay and Western blot. The Luciferase reporter assay, RNA pulldown assay, qRT-PCR, and Western blot were performed to explore and confirm the interaction between ZFPM2-AS1 and miR-1226-3p and integrin β1 (ITGB1).ZFPM2-AS1 was overexpressed in HCC tissues and cell lines. High levels of ZFPM2-AS1 were correlated with advanced TNM stage, distant metastasis and a poorer overall survival rate. ZFPM2-AS1 knockdown inhibited cell proliferation and invasion. ZFPM2-AS1 could directly bind to and negatively regulate miR-1226-3p expression. Moreover, ITGB1 was identified as a target gene of miR-1226-3p. ITGB1 was found to be directly negatively regulated by miR-1226-3p and indirectly upregulated by ZFPM2-AS1. Rescue assays demonstrated that ZFPM2-AS1 promotes HCC cell proliferation and invasion through modulating miR-1226/ITGB1 axis.ZFPM2-AS1 promotes cell proliferation and migration by regulating miR-1226-3p/ITGB1 axis in HCC.

The safety evaluation of power distribution is of great importance. Based on the concept of intrinsic safety, two dimensions that affect the intrinsic safety of distribution are proposed herein with the perspective of operation and management in power companies. Two dimensions are "unsafe behavior of human-beings" and "unsafe state of things ". The former includes organization and management, team building, risk control, emergency disposal, and the latter includes physical base guarantee, equipment quality control, hidden trouble identification, technological innovation. Taking the affecting factors of the two dimensions as the first-level indices, thirty second-level indices are constructed. By calculation of the second-level indices, the intrinsic safety evaluation of power distribution can be obtained. The proposed method is utilized to calculate the intrinsic safety of an actual power distribution in a selected city in China. The result shows that the proposed method is capable of comprehensively evaluating the level of intrinsic safety of power distribution, and can provide the clues to find safety enhancements.

To investigate the risk ofThree counties along the coastal areas of Jiangsu Province were selected as the study sites in 2018, including Rudong County in Nantong City, Haizhou District in Lianyungang City and Dongtai City in Yancheng City. The knowledge, attitude and practice (KAP) of anisakiasis prevention and control, and the prevalence of serum specific IgG antibody againstA total of 625 high-risk populations were investigated, including 349 men (55.8%). Only 13.0% of the subjects heard about anisakiasis, and a low awareness rate of anisakiasis prevention and control knowledge was seen among these three types of high-risk populations. There were 21.6% of the subjects eating raw or half-cooked marine fish, 5.8% eating undercooked marine fish, 3.2% presenting vomiting, nausea and diarrhea after eating marine fish, 5.1% developing systemic allergic symptoms, and 65.6% using the same chopping board for raw and cooked food. The sero-prevalence of the anti-The awareness of anisakiasis prevention and control knowledge is low among the high-risk populations living along the coastal areas of Jiangsu Province, and there are high-risk behaviors, such as eating raw or half-cooked food, using the same chopping board for raw and cooked food. In addition, the prevalence of

Acetylation of histone proteins is a major determinant of chromatin structure and function. Fertilisation triggers a round of chromatin remodelling that prepares the genome for the first round of transcription from the new embryonic genome. In this study we confirm that fertilisation leads to a marked progressive increase in the level of histone 3 lysine 9 acetylation in both the paternally and maternally derived genomes. The culture of zygotes in simple defined media caused a marked increase in the global level of acetylation and this affected the male pronucleus more than the female. The culture created a marked asymmetry in staining between the two pronuclei that was not readily detected in zygotes collected directly from the reproductive tract and was ameliorated to some extent by optimized culture media. The increased acetylation caused by culture resulted in increased transcription ofHspa1b, a marker of embryonic genome activation. Pharmacological analyses showed the hyperacetylation of H3K9 and the increased expression ofHspa1bcaused by culture were due to the altered net activity of a range of histone acetylases and deacetylases. The marked hyperacetylation of histone 3 lysine 9 caused by culture of zygotes may serve as an early biomarker for the effects of culture on the normal function of the embryo. The results also provide further evidence for an effect of the stresses associated with assisted reproductive technologies on the normal patterns of epigenetic reprogramming in the early embryo.

MYC-induced long non-coding RNA (MINCR) has been shown to be a long noncoding RNA that facilitates the progression of a number of malignancies, including hepatocellular carcinoma (HCC). However, few studies have explored the expression and role of MINCR in HCC. In this study, we aimed to investigate the clinical significance of MINCR in HCC.MINCR expression levels in 161 pairs of HCC tissues and pair-matched adjacent normal tissues were examined by qRT-PCR. The correlation between clinicopathological features and MINCR expression was analyzed by x2 test. Differences in patient survival were determined using the Kaplan-Meier method and a log-rank test. The significance of survival variables was analyzed using the Cox multivariate proportional hazards model.Our results showed that MINCR was significantly upregulated in HCC tissues, compared with paired adjacent nontumor tissue samples. MINCR upregulation was correlated with TNM stage (p = 0.005) and histological grade (p = 0.001). The results of Kaplan-Meier method and log-rank test indicated that the 5-years overall survival of the high MINCR group was significantly lower than that of low MINCR group (p = 0.0035). Univariate and multivariate analysis results indicated that MINCR was an independent prognostic factor in HCC (p0.05).We firstly provided the possibility that evaluating MINCR in HCC tissues may have prognostic and predictive value in the clinical management of HCC patients.

This article develops two statistical rough surface models to investigate the material removal rate in surface polishing. Model I implies that the contact between two surfaces is equivalent to that between a composite surface and a plane; but Model II is without the equivalent surface concept. The prediction differences of the two models were first investigated with the aid of contact mechanics. The analysis shows that the relative error of the predictions by the two models could be minimized by considering the interactions between asperities, and that this error increases with the separation of the mean planes, but decreases with the asperity density, asperity radius and standard deviation of the asperity height. By extending the models to study the material removal rate in polishing, it was found that asperity interaction is an important factor in a statistical modelling of polishing, and that with a given separation of the reference planes of the pad and workpiece surfaces, the material removal rate in...

In this paper, a supply and demand matching algorithm for industry park level energy systems is proposed. The algorithm can provide the configuration scheme of distributed generators installed capacity in line with the given load demand. Comprehensively considering the output characteristics of distributed sources such as wind and photovoltaic generators in different timeframes, the outputs of distributed generators are classified into several typical modes, and the installed capacity of distributed generator is matched in line with the representative output mode and the load demand curve so as to realize the balance of energy supply and demand in the industry park. The energy storage device is used to balance the energy due to the asynchronism of the distributed generator output and the load demand. The capacity requirements of the battery under various installed capacities of distributed generators are provided. The proposed algorithm is programmed in MATLAB and verified by the actual data of an industry park in northeast China. The results show that the proposed algorithm can comprehensively consider the output characteristics of distributed generator in different time ranges, and provide reasonable matching schemes of energy supply.

The dual objectives of this study are to: (1) examine the relationship between COD and BOD in seawater environment with a rapid but reliable method for the measurement of BOD in seawater, and (2) establish the relationship model between BOD5 and COD in the firth of Dongbao River to predict the values of BOD5. The first objective is met by the successful development of a technique utilizing bacteria-immobilized membrane flow cell for biodegradation process, coupled with fibre optic fluorescence detection for oxygen depletion quantitation. The technique has been applied to coastal seawater samples collected in the coastal area of Shenzhen, China. The BOD5 and COD values for the samples are acquired and the results show that there is no apparent linear relationship existing between BOD5 and COD in relatively clean seawater samples away from the shore. However, in estuary water samples containing relatively high concentration of sewage contamination, a linear correlation does exist between BOD5 and COD. The linear relationship between the two parameters allows for the calculation of BOD5 values based on COD data which can be measured more readily and precisely.

The dual objectives of this study are to: (1) examine the relationship between COD and BOD in seawater environment with a rapid but reliable method for the measurement of BOD in seawater, and (2) establish the relationship model between BOD5 and COD in the firth of Dongbao River to predict the values of BOD5. The first objective is met by the successful development of a technique utilizing bacteria-immobilized membrane flow cell for biodegradation process, coupled with fibre optic fluorescence detection for oxygen depletion quantitation. The technique has been applied to coastal seawater samples collected in the coastal area of Shenzhen, China. The BOD5 and COD values for the samples are acquired and the results show that there is no apparent linear relationship existing between BOD5 and COD in relatively clean seawater samples away from the shore. However, in estuary water samples containing relatively high concentration of sewage contamination, a linear correlation does exist between BOD5 and COD. The linear relationship between the two parameters allows for the calculation of BOD5 values based on COD data which can be measured more readily and precisely.

Fluid—structure interaction (FSI) problems simultaneously bring together some of the critical aspects associated with both fluid dynamics and structural dynamics. In this research, the simulation of the three-dimensional flexible fluid-filled drum in the crash is achieved through multi-material arbitrary Lagrangian-Eulerian (ALE) finite-element method because of its ability to control mesh geometry independently from geometry. The ALE description is adopted for the fluid domain, whereas for the structural domain the Lagrangian formulation is adopted. The computation of the FSI and the crash contact between the drum and the ground is realized by the penalty-based coupling method. Then the dynamic behaviour of the drum in the crash is analysed and the parallelism is discussed because the computation of the FSI and the crash contact is quite time-consuming. Based on domain decomposition, the recursive coordinate bisection (RCB) is improved according to the time-consuming characteristics of the fluid-filled container in the crash. The results indicate, in comparison with RCB method, the improved recursive coordinate bisection method has improved the speedup and the parallel efficiency.

A full-scale vehicle—pedestrian crash simulation has been applied to pedestrian accident reconstruction worldwide in the past decade. Considering that the optimization method and pedestrian human model play an important role in this simulation, this study makes some improvements in them according to the characteristics of real-world pedestrian accidents. On the one hand, the sequential linear programming method replaces classical manual optimization for pedestrian accident reconstruction which can automatically vary pre-impact parameters to minimize the error between simulation and real data. On the other hand, new anthropometry results and coupled finite element (FE)—multi-body (MB) modelling technology are applied to pedestrian human modelling. A Chinese pedestrian model generator is developed in order to avoid using the Western human population in China, and an FE leg model is combined into the MB pedestrian model to perform a more detailed analysis of long bone fracture. The purpose of this paper is to evaluate the capability of and necessity for the above improvements. The evaluation is conducted by the reconstruction of three fatal pedestrian accidents. The first two cases are mathematically reconstructed on the basis of the rest position and pedestrian injury respectively. The influence of the anthropometry parameters is illustrated by the reconstruction of the last case.

Gene expression from the new embryonic genome is required for normal preimplantation embryo development. Two members of the cAMP-responsive element-binding protein (Creb) family of transcription factors, Creb1 and activating transcription factor 1 (Atf1), are essential for normal preimplantation development. These transcription factors are activated by phosphorylation. Creb1 mRNA was expressed throughout the preimplantation phase. Cytoplasmic immunolocalization of Creb1 was detected in all preimplantation embryo stages. The antigen was largely excluded from the pronuclei/nuclei at embryonic stages except in the mid-cycle two-cell and compacted eight-cell embryo. Activation-state-specific antibodies showed serine 133 phosphorylated Creb1 localization was similar to Creb1 staining, except that there was no increase in staining at the eight-cell stage. Increased staining of phosphorylated Creb1 was observed in the nucleus of mid-cycle two-cell embryos. Increased expression of phosphorylated Creb1 in the two-cell embryo was induced by brief exposure of embryos to ionomycin, but not by a dibutyryl cAMP. This was blocked by buffering intracellular calcium with 1,2-bis(2-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid tetrakis (acetoxymethyl ester), but not by a cAMP antagonist, Rp-cyclic 3′,5′-hydrogen phosphorothioate adenosine. Calmodulin is an intracellular receptor for calcium. Calmodulin mRNA was expressed throughout the preimplantation phase of development. The calmodulin antagonist, W-7, inhibited the ionomycin-induced localization of phosphorylated Creb1 in the nucleus. Treatment of embryos with W-7 caused a dose-dependent inhibition of normal development of zygotes to the blastocysts stage. The study shows Creb1 expression and nuclear localization was dynamically regulated in the early embryo. The marked nuclear accumulation and phosphorylation of Creb1 at the two-cell stage occurred at the time of transcription from the embryonic genome and was regulated in a calcium- and calmodulin-dependent manner.

Background/Aims: Vascular endothelial growth factor C (VEGF-C) and vascular endothelial growth factor D (VEGF-D) are potent lymphangiogenic and angiogenetic mediators in many kinds of tumors. However, the exact impacts of VEGF-C and VEGF-D on the prognosis of colorectal cancer (CRC) remain elusive. The aims of this study were to demonstrate the expression of VEGF-C and VEGF-D and to correlate their expression levels with clinicopathological factors and long-term survival in patients with CRC. Patients and Methods: Between January 1996 and January 1998, 69 patients with pathologically confirmed CRC who received routine follow-up at the Ruijin Hospital were included in this study. VEGF-C and VEGF-D protein expression and microvessel density of 69 surgical specimens were assessed by immunohistochemistry, with 20 samples of normal colorectal tissues as controls. All patients were followed up for 108 months or until death. The Immunohistochemical stains were quantified and analyzed by means of a Zeiss Axioplan 2 imaging analysis system. Results: The protein expression of VEGF-C and VEGF-D in tumor tissues was much higher than that in normal colorectal tissues (p < 0.01). The VEGF-C expression significantly correlated with lymph node metastasis (p = 0.011) and clinical stages of CRC (p < 0.01). The VEGF-D expression correlated with patient ages (p = 0.013), depth of tumor invasion (p = 0.013), and lymph node metastasis (p = 0.028). The expression of VEGF-C and VEGF-D was significantly correlated with the microvessel density. Both overall survival and disease-free survival at 108 months were significantly lower in the CRC patients with a high VEGF-C and/or a high VEGF-D expression, and the patients with a high expression of both VEGF-C and VEGF-D had the shortest overall survival and disease-free survival when compared with other patients. Conclusion: The VEGF-C or VEGF-D expression was significantly correlated with lymph node metastasis and long-term prognosis and could be applied as prognostic markers in CRC.

The La2Zr2O7/SrZrO3 composite with a mol ratio of 1:2 named (La0.5Sr0.5)ZrO3.25 (LSZ) was in-situ synthesized by co-precipitation method using ammonia and ammonium oxalate as precipitants. The synthesized LSZ powder showed good phase stability not only from room temperature to 1400°C but also at higher temperature of 1450°C for a long period, as analyzed by thermogravimetry, differential scanning calorimetry and X-ray diffraction, respectively. The bulk LSZ with relative density >95% was prepared by pressureless sintering at 1500°C for 2 h and spark plasma sintering (SPS) at 1300°C for 5 min, respectively. The fracture toughness of the bulk LSZ prepared by both pressureless sintering and SPS were 1.80±0.20 MPa·m1/2 and 1.95±0.09 MPa·m1/2, respectively, which are higher than that of both bulk SrZrO3 and La2Zr2O7. The coefficients of thermal expansion (CTEs) of the bulk LSZ were 8.4-9.5×10-6 K-1 in a temperature range of 200-1200°C, which are higher than that of La2Zr2O7 but lower than that of SrZrO3. The thermal conductivity of the bulk LSZ prepared by pressureless sintering was ~1.1 W·m-1·K-1 at 1000°C, which is lower than that of both bulk SrZrO3 and La2Zr2O7. The LSZ composite is considered as a promising thermal barrier coating material.

The development of the preimplantation embryo (from fertilisation until the formation of the differentiated blastocyst) occurs without a requirement for exogenous mitogenic or survival signals. This distinguishes the behaviour of cells in the early embryo from all other normal cells. The discovery that fertilisation triggers the production and release of potent bioactive mediators by the embryo that act back on membrane receptors demonstrated the presence of closed autocrine embryotrophic loops. It is now clear that these ligands act in concert with paracrine mediators normally present within the reproductive tract to support the normal development of the embryo. These ligands act via receptors expressed by the embryo to activate signalling transduced by 1-o-phosphatidylinositol-3-kinase and the resultant formation of phosphatidylinositol-3,4,5-trisphosphate. This polyphosphorylated membrane phospholipid acts as a docking site for proteins possessing the PH domain. These include PDK1, AKT and phospholipase C. The activation of these proteins accounts for the initiation of new transcription from the embryonic genome to form a pro-survival, anti-apoptotic transcriptome and the post-transcriptional activation of pro-survival signalling within embryonic cells. This includes the attenuation of action of pro-apoptotic signals, such as P53. The production of embryotrophic ligands after fertilisation bootstraps development by the activation of transcription from the embryonic genome, followed by the activation of pro-survival settings within embryo cells.

Homozygous deletion of the Lis1 gene (Lis1−/−) in mouse resulted in early embryonic lethality immediately after embryo implantation by an undefined mechanism. We seek to define the nature of this demise. LIS1 (pafah1b1) is a 46 kDa protein with seven tryptophan-aspartate (WD) repeats. It docks with many proteins and has been implicated in microtubular function, cell division, intercellular transport, and nuclear and cellular motility. Combined Western and quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) analyses showed that LIS1 expression from the blastocyst stage required new transcription from the embryonic genome. Consequently, the death of post-implantation embryos may not reflect the first time during development that LIS1 was required, rather, it may reflect the first time following depletion of gametic stores that its actions were essential. Following culture of blastocysts in vitro for 96 hr the inner cell mass (ICM) of null embryos were significantly smaller than ICM of wild-type siblings. Normal blastocyst outgrowths after 96-hr culture had high levels of LIS1 expression in the outer cells of developing ICM and extensive expression in trophoblast cells. Lis1−/− embryos had significantly smaller trophoblast nuclei than wild-type embryos. The results show that LIS1 expression is required for the continued normal development of the ICM and optimal trophoblast giant cell formation. Mol. Reprod. Dev. 66: 134–142, 2003. © 2003 Wiley-Liss, Inc.

Alpha (α)-particle radiation has been thoroughly studied in the occupational and residential environments, but biological mechanisms induced by α-particle radiation on plants are not clearly understood. In this study, radiation effects were examined using different total doses (1, 10, 100 Gy, respectively) of 241Am, α-particle on Arabidopsis embryos. No significant difference in the germination percentage was observed between the 3 levels of doses and the control. Germination speed and root length were increased by treatment with the 1-Gy dose of a-particles, and decreased by treatment with 10- and 100-Gy doses. Moreover, the bending degree of roots increased with radiation dose, and the roots showed an "S" shape when treated with the 100-Gy dose. Root bending under the 100-Gy dose was inhibited by scavengers of reactive oxygen species (ROS). Root gravitropism and root length may respond to the consistency of ROS induced by irradiation. Further analysis of the physiological effects revealed that an increase in a-particle radiation intensity enhanced the activity of catalase and the content of malondialdehyde, but superoxide dismutase activity was reduced by treatment with 100-Gy radiation of a-particles, suggesting that the high linear energy transfer of a-particles may cause a relatively high level of membrane lipid preoxidation and high accumulation of ROS. ROS showed both physiological and morphological responses following exposure to α-particle radiation in Arabidopsis embryos.

The co-expression of the CREB and ATF1 transcription factors is required for the development of preimplantation embryos. Embryotropin-mediated, calcium/calmodulin-dependent signalling activates CREB-induced transcription in the two-cell embryo, but the regulation ofATF1in the embryo is not known. This study demonstrates that ATF1 begins to accumulate within both pronuclei of the mouse zygote by 20 h post-human chorionic gonadotrophin. This did not require new transcription (not blocked by α-amanitin), but was dependent upon protein synthesis (blocked by puromycin) and the activity of P38 MAP kinase. ATF1 becomes an active transcription factor upon being phosphorylated. A marked accumulation of phosphorylatedATF1was evident in two-cell embryos and this persisted in subsequent stages of development. This phosphorylation was enhanced by the actions of autocrine embryotropic mediators (including Paf) and required the mutual actions of P38 MAP kinase and calmodulin-dependent pathways for maximum levels of phosphorylation. The combined inhibition of these two pathways blocked embryonic genome activation (EGA) and caused embryos to enter a developmental block at the two-cell stage. The members of the CREB family of transcription factors can generate one of the most diverse transcriptomes of any transcription factor. The demonstration of the presence of activatedCREBandATF1within the embryonic nucleus at the time of EGA places these transcription factors as priority targets as key regulators of EGA.

The Emx1 gene is a mouse homologue of a Drosophila head gap gene, empty spiracles. Corpus callosum defects have been reported for mutant mice lacking the Emx1 gene, indicating a possible involvement of the Emx1 gene in the regulation of axon guidance during development. However, it has recently come to light that genetic background could influence the outcome of the corpus callosum defects in mutant mice generated by ES cell technology. To investigate whether the corpus callosum defects resulted directly from Emx1 gene inactivation, we backcrossed the Emx1 mutant mice into the C57BL/6 background and found that the Emx1 homozygous mutant mice with the C57BL/6 background showed a normal corpus callosum score even though the cross-sectional area was 8% less than that of their wild-type littermates, indicating that genetic background could change the pattern of corpus callosum defects in Emx1 mutant mice. Furthermore, the indusium griseum and taenia tecta were always present and the cerebral cortical layers were well differentiated in Emx1 mutant mice. These results suggest that inactivation of the Emx1 gene does not contribute directly to the defects of corpus callosum and other brain structures associated with Emx1 mutant mice derived from a 129/Sv background.

The gadolinium complex with L-proline, [Gd2(L-Pro)6(H2O)6](ClO4)6, has been synthesised and characterised by single crystal X-ray analysis (P1; a = 9.906(3) Å, b = 13.052(5) Å, c = 13.703(5) Å, α = 109.63(3)°, β = 110.31(2)°, γ = 100.72(3)°. The repeated fragment in the polymeric chain is the [Gd2(L-Pro)6(H2O)6]6+ ion. Each Gd3+ centers a distorted square antiprism of eight oxygen atoms provided by four bridging carboxyl groups, a non-bridging carboxyl group and three water molecules. A comparison with the structures of the Pr3+ and Nd3+ complex compounds with L-proline is presented.

The nonstationary probability densities of system responses are obtained for nonlinear multi-degree-of-freedom systems subject to stochastic parametric and external excitations. First, the stochastic averaging method is used to obtain the averaged Ito equation for amplitude envelopes of the system response. Then, the corresponding Fokker-Planck-Kolmogorov equation governing the nonstationary probability density of the amplitude envelopes is deduced. By applying the Galerkin method, the nonstationary probability density can be expressed as a series expansion in terms of a set of orthogonal base functions with time-dependent coefficients. Finally, the nonstationary probability densities for the amplitude response, as well as those for the state-space response, are solved approximately. To illustrate the applicability, the proposed method is applied to a two-degree-of-freedom van der Pol oscillator subject to external excitations of Gaussian white noises.

Summary form only given. Microwave Tube Simulator Suite (MTSS) is a full-featured, tightly integrated software package for microwave tube analysis and design. It includes a friendly user interface module and five physics simulators. Microwave Tube Design Environment (MTDE) is the user interface module, which provides a powerful solid modeling front-end and graphical and computational post-processing functionality. Electron Optics Simulator (EOS) is a fully three-dimensional finite-element design tool for microwave tube electron guns and collectors. High Frequency Circuit Simulator (HFCS) is an advanced, three-dimensional electromagnetic simulation tool for RF components. Beam Wave Interaction Simulator (BWIS) is a design tool for the electron beam and electromagnetic wave interaction. Magnet Simulator (MS) is a magnetic focus system simulation tool. Windows Simulator (WS) is an advanced S-Parameter simulator based on three-dimensional finite element method. Researchers and designers can use MTSS to model and simulate the entire microwave tube, including solid modeling, simulation of all components and post-processing. The data exchange between all modules is automatic. Application and validation of MTSS will be presented.

The expression of two members of an important family of transcription factors, cAMP response element-binding protein (CREB) and cAMP-dependent transcription factor ATF1 (ATF1), is essential for normal preimplantation development. There is a high degree of functional similarity between these two transcription factors, and they can both homodimerize and heterodimerize with each other to form active transcription factors. CREB is present in all stages of mouse preimplantation embryo, and we show here that ATF1 is localized to the nucleus in all preimplantation stages. Activation of these transcription factors requires their phosphorylation, and this was only observed to occur for both transcription factors (serine 133 phosphorylation of CREB and serine 63 phosphorylation of ATF1) at the two-cell stage. Nuclear localization and phosphorylation of ATF1 were constitutive. The nuclear localization and phosphorylation of CREB showed a constitutive component that was further induced by the autocrine embryotropin Paf (1-o-alkyl-2-acetyl-sn-glycero-3-phosphocholine). Activation of CREB by Paf was independent of cAMP but was dependent on calcium, calmodulin, and calmodulin-dependent kinase activity. ATF1 nuclear localization was unaffected by inhibition of the calcium/calmodulin pathway. A complex pattern of expression of calmodulin-dependent kinases was observed throughout preimplantation development. At the two-cell stage, only mRNAs coding for calmodulin-dependent protein kinase kinase beta, calmodulin-dependent protein kinase II gamma, and calmodulin-dependent protein kinase IV were detected. A selective antagonist for calmodulin-dependent protein kinase kinase (STO-609) and calmodulin-dependent protein kinases I, II, and IV (KN-62) blocked the Paf-induced phosphorylation of CREB. The study demonstrates a role for trophic signaling and constitutive activation of two essential transcription factors at the time of zygotic genome activation.

A universal response to cellular stress is the expression of transformation-related protein 53 (TRP53). This transcription factor reduces cell proliferation and/or survival and is classed as a tumour suppressor protein. Several stresses (including culture) cause increased TRP53 expression in blastocysts and their reduced long-term developmental potential. This study shows that culture from the zygote stage (but not the 2-cell stage) reduced the development of C57BL6 inbred (but not hybrid) strain mouse embryos. Reduced viability was TRP53 dependent, being partially reversed by a TRP53 inhibitor (Pifithrin-alpha). However, the presence of culture did not cause an increase in Trp53 mRNA levels (levels were reduced following culture, P < 0.001). Transformed mouse 3T3 cell double minute 2 (MDM2) causes the ubiquitination and degradation of TRP53. MDM2 activation is accompanied by phosphorylation of Ser-166, and this is commonly catalyzed by the phosphatidylinositol-3 kinase and RAC-alpha serine/threonine-protein kinase (AKT) signaling pathway. Paf is an autocrine embryotrophin that activates the phosphatidylinositol-3 kinase/AKT pathway. High levels of TRP53 expression occurred following the culture of zygotes lacking the Paf receptor (Ptafr−/−) and following inhibition of phosphatidylinositol-3 kinase or AKT. Inhibition of MDM2 caused a Trp53-dependent reduction in zygote development. Inbred strain embryos cultured from the zygote stage expressed less phosphorylated MDM2 than similar embryos collected from the uterus. The addition of Paf to the media caused increased phosphorylation of MDM2, and this was blocked by inhibitors of phosphatidylinositol-3 kinase and AKT. The study identifies trophic ligand signaling via the activation of phosphatidylinositol-3 kinase and AKT as a mechanism resulting in the activation of MDM2.

Anion exchanger 2 (AE2), which mediates exchange of Cl(-)/HCO3(-) across the plasma membrane, is widely expressed in body tissues. It is most abundantly expressed in stomach and is responsible for the uptake of Cl(-) ions that are destined to become HCl molecules.To determine whether AE2 expression was altered in gastric tumors.We have studied AE2 expression in normal human gastric tissues (n =16) and in gastric tumors (n = 33) using immunohistochemistry and immunofluorescent labeling.In normal gastric tissue positive staining was observed in gastric fundus gland, suggesting parietal cell-related expression of AE2, and AE2 expression was localized in the nuclear membrane and even in cell nuclei. For assay of cancerous gastric tissues, specimens of human gastric cancer arising from the region of the fundus (2 cases), the body (14 cases) and the antrum (17 cases) were randomly selected. Immunohistochemical staining has showed that AE2 was down-regulated in all 14 cancerous gastric body specimens, whereas staining for AE2 in cancerous antrum was less intense and had a diffuse profile.The data suggest that AE2 might be associated with gastric carcinogenesis and the achlorhydria experienced by gastric cancer patients.

A high performance liquid chromatography with fluorescence detection has been developed for determination of puerarin in plasma using a column of YWG-C16 (10 microns) and mobile phase of methanol (450 ml)-water (522.5 ml)-0.1 mol.L-1 phosphate buffer (pH 7.4, 27.5 ml). The preparation of samples was as follows: Transfer 0.1 ml of plasma into a 1 ml stoppered glass tube containing daidzein as internal standard, add 0.4 ml of absolute alcohol to deproteinize the plasma, vortex for 2 min, centrifuge for 15 min at 2800 r.min-1 and inject 20 microliters of the supernatant into the HPLC column. Linear calibration curve was obtained by plotting concentration vs peak height ratio over the range 0.03-12.00 micrograms.ml-1 with a correlation coefficient of 0.999. The average recovery of puerarin was 95.3% and the average RSD was 4.8%. The minimum detectable quantity of puerarin was 0.04 ng, equivalent to 10 ng.ml-1 plasma. This method is highly sensitive, specific, simple and rapid. The plasma concentration-time course of puerarin given i.v. 2.25 mg.kg-1 to two dogs determined by this method was found to fit a two-compartments open model with T1/2 alpha of 6.0 min and T1/2 beta of 57.4 min.

The aim of the present study was to study the effect and mechanism of action of intraduodenal and intrajejunal dai-kenchu-to, an herbal medicine clinically effective for uncomplicated postoperative adhesive intestinal obstruction, on upper gastrointestinal motility. Five mongrel dogs were equipped with four strain-gauge force transducers on the antrum, duodenum, and proximal and distal jejunum to measure contractile activity. Dai-kenchu-to (0.5, 1.5, and 3.0 g) was administered into the duodenal or proximal jejunal lumen. The effect of atropine, hexamethonium, phentolamine, propranolol, and ondansetron on intraduodenal and intrajejunal dai-kenchu-to-induced contractions was studied. Plasma motilin was measured by specific radioimmunoassay. Intraduodenal and intrajejunal dai-kenchu-to induced phasic contractions in the duodenum and proximal jejunum, respectively, and those contractions migrated distally. Phasic contractions induced by intraduodenal and intrajejunal dai-kenchu-to were inhibited by atropine and hexamethonium at all sites. Plasma motilin was not affected by dai-kenchu-to. Intraduodenal and intrajejunal dai-kenchu-to stimulates upper gastrointestinal motility at and distal to the administration sites through cholinergic receptors.

To study the effects of tetrahydroprotoberberines (THPB) on rat liver and brain lipid peroxidation (LPO) and oxygen free radicals generation.The malondialdehyde (MDA) levels in rat brain and liver homogenates, induction of MDA by Fe(2+)-Vit C in mitochondria, OH. generation by Fenton reaction, and O2.- generation by pyrogallol oxidation were observed in vitro.(1) THPB lowered the MDA contents in the liver homogenate and mitochondria, and the IC50 values of l-THPB-18 and l-stepholidine (SPD) in the liver mitochondria were 3.1 and 12.7 mumol.L-1 respectively. SPD decreased the MDA contents in the brain homogenate and mitochondria with IC50 values of 102 and 35.0 mumol.L-1 respectively. (2) THPB scavenged OH., and the IC50 values of l-THPB-18 and SPD were 0.21 and 3.8 mumol.L-1 respectively, but no effect on O2.- was observed.THPB could reduce the MDA contents and scavenge OH. and THPB-18 was the most potent amongst them.

This paper presents the results of a study on simplified surveillance methods conducted in 23 pilot counties in 11 provinces and municipalities in China where reside 15 million people and malaria control has been in the late consolidation phase. Two simplified surveillance Schemes (A and B) taking treatment of clinical cases as the main measure were implemented in 1992-1994. The rate of annual blood examination for case detection was 1.0% in pilot Scheme A, while in areas of scheme B it was 0.3%. The implementation of both Scheme A and Scheme B, simplified or without treatment of infection foci and management of mobile populations, acquired satisfactory effects against malaria. Consequently, malaria incidence was declining steadily, only a few indigenous and introduced cases were detected. The parasite rate in residents and the IFA positive rate in children were very low. The results of pilot studies and cost-effectiveness analysis indicated that Scheme B is effective, rational and economic, and can be implemented to replace the routine surveillance measures in areas where malaria has been at the late consolidation phase in China.

Ohmefentanyl (OMF) is a new mu opioid receptor agonist with high affinity and selectivity, and possesses anesthetic activity. With radioimmunoassay, the plasma levels of cortisol (C), corticosterone (CS) and antidiuretic hormone (ADH) in rats were measured. The results indicated that no significant differences in the plasma C, CS and ADH levels were observed between the saline control group and the OMF-treated group. Trauma (bone-crush injury) increased significantly the plasma CS level. However, pretreatment with OMF 4.0 micrograms.kg-1 reduced markedly the CS plasma levels in trauma-treated rats. The results suggest that OMF anesthesia itself showed no obvious effect on the plasma concentration of C, CS and ADH, but blocked the hormoral stress responses such as the increment of plasma CS level caused by trauma stimulus.

This paper presented the clinicopathologic features of 83 cases of malignant pleomorphic adenomas(MPA) of the salivary glands.The average age of the patients was 53 years old.The ratio from male to female was 1.24 to 1.Thirty nine tumors located in parotid glands,twenty in submandibular glands and seventeen in palate.Histopathologically,the malignant component of 76 tumors was identified as carcinoma and 7 tumours as carcinosarcoma both in various types.The statistic analysis showed the factors which influenced the prognosis(P0.05) included 1. location,2. histologic subtype of malignant component,3.differentiation grade,4.infiltration status,and 5.with or without lymph node metastasis in the initial operation.The prognosis of MPA was more ominous than that of/the conventional types of carcinoma,with only 52.7% of year survival rate.The authors concluded that the pleomorphic adenoma was the pre-cancerous lesion of MPA.Therefore,it is necessary to resect the pleomorphic adenoma as early as possible in order to prevent the occurence of the MPA.

Although macrophages account for 70-90% of the adherent cells in mouse long-term bone marrow cultures (LTBMC) and CFU-F colonies, the predominant nonhematopoietic stromal cell is endothelial-like (EL), expressing cytoplasmic collagen IV, laminin, and an antigen recognized by the monoclonal antibody MECA-10. We report the isolation of this stromal cell lineage from primary LTBMC by immunomagnetic cell selection using MECA-10. More than 95% of the cells in the MECA-10-positive fraction are EL cells as judged by morphology, surface staining for MECA-10, cytoplasmic staining for collagen IV, and electrophoretic analysis of MECA-10-positive cells isolated from radiation chimeras. When plated under LTBMC conditions, EL cell monolayers recharged with either wild-type or Sl/Sld marrow support an increased density and number of clonogenic and mature hematopoietic cells in short-term cultures. In accord with this finding, Northern blots of mRNA from unstimulated EL cells demonstrate constitutive expression of Kit ligand (KL). Moreover, in situ two-color immunofluorescence staining for cytoplasmic collagen IV and surface KL suggests that EL cells are the exclusive source of membrane-bound KL in mouse cultures. The ability to isolate EL cells from primary cultures without the need for repeated cell passage or immortalization provides a novel approach to dissecting the molecular basis of stem cell-stromal cell interactions.

The constituents of Herba Cistanche (C. salsa used in Japan and C. deserticola used in China) are described. The review indicates that some cistanosides are the main active constituents of Herba Cistanche, and may be taken as the guide and precursor compounds for synthesizing new tonic drugs.

Development of the preimplantation embryo requires survival signalling by autocrine embryotrophins. Paf is the first defined embryotrophin and acts via a receptor- and phosphatidylinositol-3-kinase -dependent induction of intracellular calcium transients.1,2 These calcium transients induce a calmodulin-dependent nuclear accumulation and phosphorylation of the Creb transcription factor at the time that definitive transcription from the embryonic gene is initiated in the 2-cell embryo.3 A round 4084 loci possess CRE elements including Bcl2 and Fos.4 In this study we examined the role of Paf in the transcription of the key proto-oncogenes, Bcl2 and Fos in the early mouse embryo. Quantitative RT-PCR detected Bcl2 and Fos in oocytes and some cohorts of zygotes , but not in 2-cell, 8-cell and blastocysts. Immunolocalization of Bcl2 and Fos showed little staining in oocytes and zygotes but increased staining in the 2-cell to blastocyst stages. Paf treatment of 2-cell embryos caused an α-amanitin-sensitive expression of Bcl2 and Fos for 20 min that subsided by 40 min. This transcription was blocked by inhibition of calcium (BAPTA-AM) or phosphatidylinositol-3-kinase signa l ling (LY 294002). Analysis of individual embryos showed most zygotes , but only ~12 % of 2-cell embryos had detectable Bcl2 and Fos. A significantly smaller proportion of Ptafr–/– (Paf-receptor null) 2-cell embryos had detectable Bcl2 transcript and embryo culture (which diminishes Paf signalling) decreased transcription of Bcl2. This dichotomous pattern of transcript expression is consistent with the known periodic actions of Paf (with a periodicity of 90–120 min)2 and the relatively short-half life of the resulting transcripts. Bcl2 antagonist (HA14-1) caused a dose-dependent inhibition of cultured zygotes to develop to morphological blastocysts , which was partially reversed by exogenous Paf. The results show for the first time the autocrine embryotrophi n Paf induces periodic transient expression of key proto-oncogenes and provides evidence for a role of embryotrophins in the onset of gene expression in preimplantation embryo. (1) O’Neill C. Hum Reprod Update 2005; 11: 215–228.(2) Emerson M, et al J Biol Chem 2000; 275: 21 905–21 913.(3) Jin XL, O’Neill C. Biology of Reproduction 2010; 82: 459–468.(4) Zhang X, et al. Proc Natl Acad Sci USA 2005; 102: 4459–4464.

Genotoxic cellular stressors induce damage to the structure of DNA. This potentially compromises the genetic integrity of the cell. Such damage is particularly dangerous in the early embryo since transmission of defects can affect most cells in the body. Canonical responses of cells to such stress include delaying or blocking mitosis to allow DNA repair to occur or induction of cell death (apoptosis) to ensure that damage is not propagated. To date there have been only limited studies of the response of the preimplantation embryo to genotoxic stress. Ultra violet (UV) irradiation typically induces single strand DNA breaks while drugs such as the chemotherapeutic cisplatin commonly induce double strand breaks. ATM (Ataxia telangiectasia mutated) and ATR (Ataxia telangiectasia and rad3 related) are checkpoint kinase that mediate early responses of the cell to DNA damage. ATM primarily responds to DNA double strand breaks while ATR typically responds to single strand breaks and stalled replication forks. However, ATM and ATR may have partially overlapping and complementary functions. Both kinases can exert P53 dependent and independent responses. ATR protein was detected by immunofluorescence in all preimplantation stages up to the morulae stage. ATM protein was detected in oocytes and all stages. Cisplatin or UV-irradiation at the 2-cell stage caused increased nuclear staining of both ATM and ATR. UV-irradiation of 2-cell embryos induced irreversible, ATR-dependent, P53-independent cell-cycle block without apoptosis. Cisplatin allowed cell-cycle progression with progressive ATR and ATM-dependent, P53-independent apoptosis over subsequent cell-cycles. UV-irradiation of morula caused an ATR and ATM-dependent, P53-independent block of blastocyst formation while the block caused by cisplatin was ATR and ATM-dependent and at least partially P53-dependent. The results demonstrate complexity and maturation of the cellular responses of the embryo to defined genotoxic stressors and help to define the nature of embryopathy under these circumstances.

MBD1 is one of five proteins which bind methylated DNA and regulate gene transcription. The binding of these proteins, particularly MBD1, is commonly used as a proxy measurement of global CpG methylation. Since methylation is reported to be highly dynamic during the first cell-cycle, with reported asymmetric global demethylation of the paternal and maternal genomes by the time of syngamy, we were interested to assess the pattern of staining of the MBD1 during this stage of development. A specific antibody to MBD1 was shown by Western analysis to detect in zygotes a protein of predicted mass. Using immunolocalization, however, we found no staining in pronuclei. Brief acid treatment (10min, 4M HCl) followed by immunolabelling revealed strong pronuclear MBD1 staining throughout the maturation of the zygote and on metaphase chromosomes, indicative of epitope masking under normal staining conditions. Upon unmasking by acid treatment zygotes collected fresh from the oviduct did not show consistent differences in MBD1 staining between the maternal or paternal chromosomes or pronuclei, but for those embryos produced by IVF we found more MBD1 staining in the male paternal pronucleus. Brief treatment with trypsin caused a marked loss of MBD1 staining and this treatment increased the extent of staining of 5-methylcytosine. These results show that MBD1 antigen persists on DNA after treatments normally used for the detection of 5-methylcytosine. MBD1 at least partially masks methylcytosine from immunological detection and the results therefore raise the possibility that the reported changes in genome methylation in the zygote are a consequence of the binding of MBD1. If MBD1 binding is truly a proxy for methylation, the persistence of high levels of MBD1 throughout the first cell-cycle questions the current paradigm of global demethylation during zygote maturation.

The puerarin was determined by HPLC with fluorescence detection. The plasma concentration-time course of puerarin in rats and dogs after iv was best fitted to a two-compartment open model, while that in rabbits was best fitted to a three-compartment open model. Species specificity was found among rats, rabbits, and dogs, calculated with compartment model program. The T1/2 beta after iv puerarin 9 mg.kg-1 in rats, rabbits, and dogs were 11, 21, and 67 min, respectively. There were no significant differences in pharmacokinetic parameters after iv 4.5-30 mg.kg-1 to rabbits and dogs.

Many extracellular ligands activate adenylyl cyclase and then alter the intracellular concentrations of the second messenger, cAMP. High intracellular concentrations of cAMP activate cAMP-dependent protein kinase A (PKA), which regulates the meiotic arrest of oocytes at the germinal vesicle (GV) stage. In this study, we investigated the expression patterns of PKA subunits in porcine oocytes during meiotic maturation. Porcine oocytes were matured in the NCSU-23 medium supplemented with 10% (v/v) porcine follicular fluid, 10 ng mL–1 of EGF, 25 µm β-mercaptoethanol, 0.57 mm cysteine, 10 IU mL–1 of pregant mare serum gonadotropin, 10 IU mL–1 of hCG, 1 mm dbcAMP for 22 h and further cultured without dbcAMP and hormone for 22 h. All experiments were repeated more than 3 times. All data were analyzed by using Duncan's test of ANOVA by Statistical Analysis System (SAS Institute Inc., Cary, NC, USA). We found that the expression of type I and type II regulatory subunits (RI and RII) of PKA were higher in the GV stage than those of metaphase II stage porcine oocytes. In addition, their expressions were dynamically changed from the metaphase I to metaphase II stage. The expression levels of PKA regulatory subunits type I and type II were evaluated byWestern blot analysis by using specific antibodies such as anti-PKAc, anti-PKARIα, anti-PKARIIα, and anti-PKARIIβ in porcine GV and metaphase II oocytes (n = 25). To confirm the relationship between PKA and cell cycle regulators such as MPF or MAPK during meiosis, the expression of maturation-promoting factor or mitogen-activated protein kinase were examined by Western blot with anti-cdc2 or anti-ERK1/2. The expressions of the RI and RII subunits of PKA were decreased, whereas the expression of maturation-promoting factor (cdc2) or mitogen-activated protein kinase (ERK1/2) were increased in metaphase II stage oocytes. In conclusion, our findings indicate that the dynamic change of PKA subunits plays an important role not only in cAMP/PKA signaling pathway but also in the regulation of meiotic progression beyond the metaphase II stage in porcine oocytes.

TRP53 is a tumour suppressor that causes cell-cycle arrest or cell death in response to a range of stressors. Normal preimplantation embryo development requires that TRP53 is maintained in a labile state1. Culture of mouse C57BL6 preimplantation embryos causes this latency to be breached and this is a cause of the low embryo viability following culture. MDM2 is an ubiquitin ligase that targets TRP53 for degradation by the proteosome. MDM2 is activated by Serine 166 phosphorylation (pMDM2). This is commonly catalysed by the phosphatidylinositol-3 kinase (PI3K) and AKT signalling pathway. A range of embryotrophins activate the PI3K and AKT pathway. This study tested the hypothesis that TRP53 is maintained in a latent state in the normal embryo by the activation of MDM2 by the actions of embryotrophins via a PI3K and AKT signalling pathway. Genetic deletion of Mdm2 prevents normal preimplantation development in a Trp53 dependent manner2. Addition of an MDM2 inhibitor (Nutlin-3) to culture medium caused a dose-dependent inhibition of zygote development (P < 0.001) that did not occur in Trp53−/−embryos. Immunofluorescence and western blot analysis detected pMDM2 throughout mouse preimplantation development. Zygote culture reduced the levels of pMDM2 formation. Furthermore, blocking the actions of Paf, PI3K or AKT in vitro reduced in the expression of pMDM2, and also resulted in higher levels of TRP53 expression in embryos. The embryopathy resulting from increased TRP53 could be partially ameliorated by the addition of the TRP53 antagonist α-pifithrin to media (P < 0.05). The results show MDM2 was activated by an embryotrophin (Paf), PI3K and AKT signalling pathway and was required for the latency of TRP53 expression in the preimplantation embryos. (1) Li A, Chandrakanthan V, Chami O, O’Neill C. (2007) Biology of Reproduction 76: 362–367. (2) Montes de Oca Luna R, Wagner DS, Lozano G. (1995) Nature 378: 203–205.