Search

Objectives: Dimeric pyruvate kinase (PK) M2 (PKM2) plays an important role in promoting the accumulation of hypoxia-inducible factor (HIF)-1α, mediating aberrant glycolysis and inducing fibrosis in diabetic kidney disease (DKD). The aim of this work was to dissect a novel regulatory mechanism of Yin and Yang 1 (YY1) on lncRNA-ARAP1-AS2/ARAP1 to regulate EGFR/PKM2/HIF-1α pathway and glycolysis in DKD.Materials and methods: We used adeno-associated virus (AAV)-ARAP1 shRNA to knocked down ARAP1 in diabetic mice and overexpressed or knocked down YY1, ARAP1-AS2 and ARAP1 expression in human glomerular mesangial cells. Gene levels were assessed by Western blotting, RT-qPCR, immunofluorescence staining and immunohistochemistry. Molecular interactions were determined by RNA pull-down, co-immunoprecipitation, ubiquitination assay and dual-luciferase reporter analysis.Results: YY1, ARAP1-AS2, ARAP1, HIF-1α, glycolysis and fibrosis genes expressions were upregulated and ARAP1 knockdown could inhibit dimeric PKM2 expression and partly restore tetrameric PKM2 formation, while downregulate HIF-1α accumulation and aberrant glycolysis and fibrosis in in-vivo and in-vitro DKD models. ARAP1 knockdown attenuates renal injury and renal dysfunction in diabetic mice. ARAP1 maintains EGFR overactivation in-vivo and in-vitro DKD models. Mechanistically, YY1 transcriptionally upregulates ARAP1-AS2 and indirectly regulates ARAP1 and subsequently promotes EGFR activation, HIF-1α accumulation and aberrant glycolysis and fibrosis.Conclusion: Our results first highlight the role of the novel regulatory mechanism of YY1 on ARAP1-AS2 and ARAP1 in promoting aberrant glycolysis and fibrosis by EGFR/PKM2/HIF-1α pathway in DKD and provide potential therapeutic strategies for DKD treatments.

The aim of this study is to apply a Mendelian randomization (MR) design to investigate the potential causal associations between the body mass index (BMI), body fat mass such as trunk fat mass and waist circumference (WC), and diabetic kidney disease (DKD). A two-sample MR study was conducted to obtain exposure and outcome data from previously published studies. The instrumental variables for BMI, trunk fat mass, and WC were selected from genome-wide association study datasets based on summary-level statistics. The random-effects inverse-variance weighted (IVW) method was used for the main analyses, and the weighted median and MR-Egger approaches were complementary. In total, three MR methods suggested that genetically predicted BMI, trunk fat mass, and WC were positively associated with DKD. Using IVW, we found evidence of causal relationships between BMI [odds ratio (OR) = 1.99; 95% confidence interval (CI), 1.47–2.69; p = 7.89 × 10−6], trunk fat mass (OR = 1.80; 95% CI, 1.28–2.53; p = 6.84 × 10−4), WC (OR = 2.48; 95% CI, 1.40–4.42; p = 1.93 × 10−3), and DKD. MR-Egger and weighted median regression also showed directionally similar estimates. Both funnel plots and MR-Egger intercepts showed no directional pleiotropic effects involving the aforementioned variables and DKD. Our MR analysis supported the causal effect of BMI, trunk fat mass, and WC on DKD. Individuals can substantially reduce DKD risk by reducing body fat mass and modifying their body fat distribution.

We measured saturated hysteresis loops of a MuMETAL ring using a computerized, high-resolution apparatus by both extrapolated continuous recording and automatic ballistic methods. The recording time per loop varied from 17.7 to 141.6 s. The loops obtained for short recording times were significantly wider than the loop obtained by the ballistic method. By extrapolating the magnetic field of different loops at the same flux density values linearly to zero flux density rate, the resultant dc loop had coercivity in agreement with its ballistic value. The results are quantitatively analyzed and discussed on the basis of eddy current models. The intolerably large variation and bias in the measured coercivity stated in a current ASTM standard may be resolved by this technique.

Physical attributes of Chinese herbal extracts are determined by their chemical components, and the physical and chemical attributes jointly affect the preparation process performance and the final product quality. Therefore, in order to improve the quality control of Chinese herbal extracts, we should comprehensively study the batch-to-batch consistency of physical and chemical attributes as well as the correlations between them. This paper first explored the physical attributes affecting the preparation process performance of the compound Danshen extract and developed a method for characterizing the texture attributes. With such main chemical components as water, phenolic acids, saponins, and saccharides and texture, rheology, and other physical attributes taken into consideration, the batch-to-batch quality fluctuation of products from different production lines and time was analyzed by principal components analysis(PCA). Finally, the correlation and partial least squares(PLS) analysis was conducted, and the regression equation was established. The fitting result of the PLS model for dynamic viscosity was satisfying(R~2Y=0.857, Q~2=0.793), suggesting that the chemical components could be adjusted by the component transfer rate in the extraction process, the impurity removal rate in the alcohol precipitation process, and the water retention rate of the concentration process to meet the control of the extract dynamic viscosity. This study clarified the correlations between physical and chemical attributes of the compound Danshen extract and established a method for controlling its physical attributes based on process regulation, which would provide reference for improving the quality control of Chinese herbal extracts.

The effective magnetic path length l m for a 25 cm Epstein frame test is studied on the basis of a relevant demagnetizing model and determined by a comparative measurement of dc and ac hysteresis loops at each value of peak flux density B p, with the field recorded by H-coils placed above the mid-section of the limbs or calculated from the magnetizing current. The obtained B p and frequency dependences of l m for testing core loss P s and peak field H p of an electrical steel are explained in terms of differential susceptibility along the measured loops and demagnetizing and eddy-current effects on local magnetization processes.

The outbreak of novel coronavirus disease 2019 (COVID-19) has become a pandemic. Drug repurposing may represent a rapid way to fill the urgent need for effective treatment. We evaluated the clinical utility of chloroquine and hydroxychloroquine in treating COVID-19.Forty-eight patients with moderate COVID-19 were randomized to oral treatment with chloroquine (1000 mg QD on Day 1, then 500 mg QD for 9 days; n=18), hydroxychloroquine (200 mg BID for 10 days; n=18), or control treatment (n=12).Adverse events were mild, except for one case of Grade 2 ALT elevation. Adverse events were more commonly observed in the chloroquine group (44.44%) and the hydroxychloroquine group (50.00%) than in the control group (16.67%). The chloroquine group achieved shorter time to clinical recovery (TTCR) than the control group (P=0.019). There was a trend toward reduced TTCR in the hydroxychloroquine group (P=0.049). The time to reach viral RNA negativity was significantly faster in the chloroquine group and the hydroxychloroquine group than in the control group (P=0.006 and P=0.010, respectively). The median numbers of days to reach RNA negativity in the chloroquine, hydroxychloroquine, and control groups was 2.5 (IQR: 2.0-3.8) days, 2.0 (IQR: 2.0-3.5) days, and 7.0 (IQR: 3.0-10.0) days, respectively. The chloroquine and hydroxychloroquine groups also showed trends toward improvement in the duration of hospitalization and findings on lung computerized tomography (CT). This study provides evidence that (hydroxy)chloroquine may be used effectively in treating moderate COVID-19 and supports larger trials.

China healthcare industry has gradually developed the consumer-centric integrated service model. To satisfy consumers' increasing demands on pluralistic, personalized and transparent healthcare services, pharmaceutical manufacturing enterprises must provide high-quality, precise and flexible medicines. This can be achieved by accelerating implementation of intelligent manufacturing, which is the core competitiveness of pharmaceutical manufacturing enterprises. According to the authors' intelligent manufacturing projects in a traditional Chinese medicine(TCM) factory, study and industrial practice on intelligent manufacturing were presented in this paper. First, the quality digitalization-based intelligent manufacturing methodology of TCM was proposed in this paper. The methodology mainly included three digitalized technologies in process and quality design, manufacturing process control and product batch evaluation. Next, the architectural design of intelligent manufacturing systems in one TCM factory was introduced, and the functional modules and data transmission relationships covering seedling, cultivation, herbal slices, preparation, storage and quality management systems were described. Finally, these technologies were fully used, and an integrated quality digitalization system was successfully established in the production workshop of a TCM product Compound Danshen Dripping Pills. The actual operation and application of process analyzers, supervisory control and data acquisition(SCADA), manufacturing execution system(MES), data analysis system, and enterprise resource planning system(ERP) were introduced. This paper provides reference for technical path planning and systematic architecture of TCM intelligent manufacturing.

Schistosomiasis is a parasitic helminth disease that can cause organ lesions leading to health damage. During a schistosome infection, schistosome eggs can flow into the liver along the portal vein. Numerous inflammatory cells gather around the eggs, causing granulomas and fibrosis in the liver. In this process, many molecules are involved in the initiation and regulation of the fibrous scar formation. However, the precise molecular mechanisms responsible for the progression of granuloma formation and fibrosis initiation caused by schistosome infection have not been extensively studied. In this study, C57BL/6 wild-type mice and Stat3flox/flox Alb-Cre mice were infected with cercariae of Schistosoma japonicum. Liver injury, effector molecule levels, and RNA transcriptome resequencing of liver tissue were detected at 4, 5, and 6 weeks postinfection. We investigated the role of STAT3 (signal transducer and activator of transcription 3) in Schistosoma-induced liver injury in mice. After 6 weeks postinfection, there was obvious liver fibrosis. A sustained pathological process (inflammation, oxidative stress, proliferation, and apoptosis) occurred in S. japonicum-induced liver fibrosis initiation. Meanwhile, we observed activation of the STAT3 pathway in hepatic injury during S. japonicum infection by RNA transcriptome resequencing. Liver deficiency of phospho-STAT3 alleviated infection-induced liver dysfunction, hepatic granuloma formation, and fibrosis initiation. It also promoted STAT3-dependent apoptosis and reduced liver inflammation, oxidative stress, and proliferation. Our results suggest that STAT3 signal pathway and its mediating inflammation, oxidative stress, proliferation, and apoptosis are involved in S. japonicum-induced liver injury and may be a new potential guideline for the treatment of schistosomiasis.

A technique is developed to calibrate the performance of a permeameter for measuring soft magnetic materials, having a C-shaped magnetic potential H-coil near the sample surface and a B-coil surrounding the sample, by using cylindrical standard samples. The true M ( H ) curve for the standard samples of large length-to-diameter ratios is obtained by the demagnetizing-corrected solenoid method recently developed.

A technique is proposed for demagnetizing correction of the measured magnetization curve and hysteresis loop, i.e., the M ∗ ( H a ) curve, of a ferromagnetic cylinder into the true M ( H ) curve of the material, where H a is the uniform applied field provided by a long solenoid and M ∗ is the magnetization measured by a fluxmeter with the measuring coil surrounding the cylinder midplane. Different from ordinary demagnetizing correction by using a fixed demagnetizing factor, an ( H a , M ∗ ) -dependent fluxmetric demagnetizing factor N f ( γ , χ d ) is used in this technique, where γ is the ratio of cylinder length to diameter, χ d is the differential susceptibility on the corrected M ( H ) curve, and N f ( γ , χ d ) is approximated by accurately calculated N f ( γ , χ ) of paramagnetic cylinders of the same γ and χ = χ d . The validity of the technique is studied by comparing results for several samples of different lengths cut from the same cylinder. Such a demagnetizing correction is unambiguous but its success requires very high accuracy in the N f determination and M ∗ ( H a ) measurements.

In schistosomiasis, egg-induced hepatic granuloma formation is a cytokine-mediated, predominantly CD4+ Th2 immune response that can give rise to hepatic fibrosis. Hepatic fibrosis is the main cause of increased morbidity and mortality in humans with schistosome infection. Taurine has various physiological functions and hepatoprotective properties as well as anti-inflammatory and immunomodulatory activity. However, little is known about the role of taurine in schistosome egg-induced granuloma formation and fibrosis. We aimed to evaluate the therapeutic potential of taurine as preventative treatment for Schistosoma japonicum infection. Mice infected with S. japonicum cercariae were supplied with taurine drinking water (1% w/v) for 4 weeks starting at 4 weeks post-infection. Taurine supplementation significantly improved the liver pathologic findings, reduced the serum levels of aminotransferases and area of hepatic granuloma, and prevented fibrosis progression. In addition, taurine decreased the expression of the granulomatous and fibrogenic mediators transforming growth factor β1, tumor necrosis factor α, monocyte chemotactic protein 1α and macrophage inflammatory protein 1α as well as the endoplasmic reticulum stress marker glucose-regulated protein 78. Thus, taurine can significantly attenuate S. japonicum egg-induced hepatic granuloma and fibrosis, which may depend in part on the downregulation of some relevant cytokine/chemokines and reducing the endoplasmic reticulum stress response., Graphical abstract, Highlights • Taurine has potential as preventative & therapeutic treatment for schistosomiasis. • Taurine reduced the development of liver pathology caused by S. japonicum infection. • Taurine attenuated S. japonicum egg-induced hepatic granuloma and fibrosis.

In the firing process of ceramic products, the sintering conditions vary from firing phase to firing phase. In different firing phases, flame texture changes obviously, so it can be used as a important parameter of burning zone identification for ceramic roller kiln. In this paper, both flame image recognition of simulating artificial-look-fire and multi-point temperature detection technology are used to detect burning zone working conditions of ceramic roller kiln so as to greatly improve detection accuracy. The key data fusion algorithm of PTCR-based point detection temperature and flame image recognition–based detection method of burning zone working condition for ceramic roller kiln are proposed. The temperature measurement experiment system scheme of ceramic roller kiln burning zone is also given. The system can fuse the key process data with flame image characteristics so as to get the comprehensive database used to judge burning zone working conditions and temperatures. In the end, The testing experiment was carried out. The experimental results show that the method proposed above is feasible and effective.

In order to obtain efficiency and economy of a ceramic tunnel kiln’s flue gas heat exchanger, firstly, the exchanger’s sizes and thermal parameters on operative conditions were measured. Secondly, flow field and temperature field in the operative exchanger were numerically simulated by using FLUENT, a computational fluid dynamics soft ware. Finally, on base of the simulation, the exchanger’s efficiency and economy were calculated. The calculation results are listed as the following: (1) Energy savings in per unit time for utilizing the heat exchanger to recycle and reuse the flue gas’s waste heat is 112.2kW. (2) Efficiency of the heat exchanger equals 77%.

Roller kiln is a kind of advanced fast sintering kiln. In production process of roller kiln, materials sintering of burning zone is the key working procedure which affects product quality directly. Hence, the temperature detection process of burning zone became the key link in roller kiln control system. This paper proposed a kind of fusion method of both temperature point detection and flame image recognition of imitating ‘artificial-look-fire’. Flame image processing-based temperature detection scheme was also given. In the scheme, expert system fuses temperature data detected by the thermocouple with flame image data of burning zone detected by CCD so as to obtain the actual temperature of burning zone. The method proposed greatly improves the temperature detection precision of burning zone working conditions. The experimental results show that the proposed method is feasible and effective.

The linear dynamic Hammerstein model presents some static nonlinearity. The predominant method to estimate the components of this model is to minimize the error between the simulated and measured outputs. Taking the Gaussian input signals into account, we can estimate the linear part of the Hammerstein model by using the Buss gang’s classic theory. Accordingly, considering the case in point with the general disturbances, we come up with the maximum likelihood methodology.

In this paper, we presented a constrained multi-degree reduction algorithm of DP curves based on the transformation between the DP and Bézier curves. We first correct the conversion formula between Bernstein basis and DP basis. And then, we deal with multi-degree reduction of NP curves by degree reduction of Bézier curve.

An NN-based output feedback stabilization problem is studied via passivation of a class of multi-input multi-output nonlinear systems with unknown nonlinear input matrix and unknown parameters. Neural networks are used to identify unknown nonlinearities, and the update laws of weight parameters are proposed. The design methods of the adaptive passive controllers for this class of systems are discussed in the paper. The corresponding adaptive passive controllers and parametric adaptive laws are designed and presented respectively. It is proved that the closed-loop system composed of the original system and the designed controller is stable by the Lyapunov method, and the controller designed can render the closed system adaptive passive. Finally, a simulation example is given to prove the effectiveness and feasibility of the proposed method.

The paper researches flow field and temperature field characteristics of one rocket charge with complicated structure by numerical method. The charge, in which there exist the conduction, convection and radiation, consists of the metal shell, seven propellant columns and air gaps. For the reasons, to solve temperature field of the charge is to solve a complex heat transfer problem in a complicated calculation region. A mathematical and physical model for the flow and heat transfer process in the charge is established and unstructured meshes are applied to disperse the complicated calculation region. The SIMPLE algorithm is used to solve the partial differential equations, and the calculation results are in good agreement with the experimental data. On basis of the numerical simulation, the flow field and temperature field characteristics of the charge are researched and subsequently some valuable conclusions are gotten.

Flame image processing-based intelligent networked control system scheme of roller kiln is proposed in the paper. Flame image recognition method of simulating artificial-look-fire is proposed for the auxiliary detection of roller kiln burning zone conditions so as to improve the real-time detection accuracy of roller kiln burning zone and the control effect. The hardware and software platform of the system are also designed. The system proposed is mainly composed of six module such as key process detection module, flame process module, recognition model for burning zone, industrial control computer, network transmission module, and actuators. System software is mainly composed of five modules. In conclusion, the paper provides a kind of new method and new idea for research and design on flame image processing-based intelligent networked control system of roller kiln.

Recently, our research team has been considering to applying shape memory alloys (SMA) constitutive model to analyze the large and small deformation about the SMA materials because of the thermo-dynamics and phase transformation driving force. Accordingly, our team use simulations method to illustrate the characteristics of the model in large strain deformation and small strain deformation when different loading, uniaxial tension, and shear conditions involve in the situations. Furthermore, the simulation result unveils that the difference is nuance concerning the two method based on the uniaxial tension case, while the large deformation and the small deformation results have huge difference based on shear deformation case. This research gives the way to the further research about the constitutive model of SMA, especially in the multitiaxial non-proportional loading aspects.

In order to stimulate the movement of small scale helicopters, DOF flight test platform based on the similarity theory has been thought out. Accordingly, considering the platform to be the researching object and combing the Lagrange-Euler equation with the equivalent moment method, the system kinetic model is worked out and the physical parameter is pre-estimated. The relationship between the lift force and the change of the rotation speed is acquired by the experiment with the fixed collective angle. According to the dynamic equation, a PID revised feed-forward controlling algorithm with robust characteristic was devised and the MATLAB simulation is applied to verify fast astringency and validity of the controller

Wavelet neural network based adaptive robust output tracking control approach is proposed for a class of MIMO nonlinear systems with unknown nonlinearities in this paper. A wavelet network is constructed as an alternative to a neural network to approximate unknown nonlinearities of the classes of systems. The proposed WNN adaptive law is used to compensate the dynamic inverse errors of the classes of systems. The robust control law is designed to attenuate the effects of approximate errors and external disturbances. It is proved that the controller proposed can guarantee that all the signals in the closed-loop control system are uniformly ultimately bounded (UUB) in the sense of Lyapunov. In the end, a simulation example is presented to illustrate the effectiveness and the applicability of the suggested method.

At first, according to the feature of ceramic kiln, this paper studies a fundamental data fusion method which is applied to ceramic kiln temperature control system. This method is used to solve the parameter estimation problem in measurement noise environment. Then, it proposes a kind of intelligent control structure of ceramic kiln temperature control system based on multi-sensor data fusion technology. At last, this data fusion method is applied to intelligent temperature control system of ceramic kiln. The result shows that the method proposed is effective and feasible.

This paper applies multi-sensor information fusion technology to intelligent control system of ceramic kiln and proposes a corresponding control scheme. The control scheme is composed of six-layer structures which include four subsystems. Then, compositions, functions and adoptive algorithms of the four subsystems are analyzed. In the end, the whole system control scheme and its work process are analyzed.

AIM To investigate hepatitis E virus (HEV) infection among different animals and workers in pig farms and slaughterhouses, and analyze the genotype of HEV isolated in this study. METHODS Serum samples were collected from adult swine, cows, sheep, younger swine (< 3 months), and workers in pig farms and slaughterhouses (professional group). Fecal samples were collected from younger swine in the south suburbs of Beijing. Anti-HEV antibody was evaluated by direct sandwich enzyme immunoassay. HEV RNA was extracted from fecal samples and amplified by nested reverse transcription polymerase chain reaction (RT-nPCR). The PCR products were sequenced, and the sequence homology and phylogenetics of the HEV strains isolated from swine were analyzed. RESULTS The anti-HEV positivity rates in adult swine, cows, sheep, younger swine, professional group and general population were 98.23% (222/226), 29.35% (54/184), 9.80% (20/207), 60.73% (99/164), 42.51% (105/247) and 20.29% (522/2572), respectively. The HEV RNA positivity rate of fecal samples was 22.89% (19/83) and 16/19 samples were positive for HEV RNA amplified with both primers, HEV open reading frame (ORF)1 and HEV ORF2. Sequence analysis of these 16 samples showed that there were two groups, designated BJ-1 and BJ-2. The nucleotide homology of BJ-1 and BJ-2 was 99%. Phylogenetic analysis indicated that both of these groups belonged to genotype 4d. CONCLUSION Workers in pig farms and slaughterhouses were more likely to contract HEV infection than the general population because of close contact with swine with a high prevalence of anti-HEV.

Background: Hepatitis E virus (HEV) is one of the leading causes of the enteric-transmitted acute hepatitis. Many studies have found high identities between human and animal HEV isolates using partial sequence comparison analysis. Aims: To determine and phylogenetically analyse the complete genome of the swGX40 isolate from the Guangxi Zhuang autonomous region. Methods: The overlapping fragments of HEV isolate swGX40 were amplified with reverse transcription-nested polymerase chain reaction (PCR) and the 5′ and 3′ ends of viral genome were amplified with rapid amplification of cDNA ends. The PCR products were cloned and sequenced. The sequence and phylogenetic analysis of swGX40 were performed. Results: The full genome of the swGX40 strain consisted of 7233 nucleotides, excluding the poly (A) tail of 36 residues. There are three open reading frames (ORFs), encoding 1705, 674 and 114 amino acids (aa) respectively. The full-genomic sequencing showed that the swGX40 strain shared similarity with all known HEV genotype 1, 2 and 3 isolates by 73.4–76.5% and with an identity of 83.1–91.2% among genotype 4 HEV isolates. The partial ORF2 sequencing (249 nt) showed that swGX40 shared a high nucleotide identity of 94 and 97% with the Chinese human strain LZ-105 and the Vietnamese human strain HE-JVN-1 respectively. Conclusions: The swine isolate swGX40 was closely related to the human isolate LZ-105, both of which were collected from Liuzhou, the same district in the Guangxi Zhuang autonomous region. This molecular biological evidence strongly supported the zoonosis hypothesis of hepatitis E.

A series of R and S enantiomers of 7-(3-methylpiperazin-1-yl) quinolone derivatives were synthesized from (R)- and (S)-tert-butyl 2-methylpiperazine-1-carboxylate and tested for their antibacterial activities on 14 kinds of bacteria. Although no distinct difference in in vitro antibacterial activities was observed, 2-64-fold difference between R and S enantiomers was observed in approximately 52% of cases.

Due to the influence of factors such as environment, materials and so on in the ceramic production process, different levels and different kinds of defects such as crack, fall slag, deformation, roast flower sticky glaze and so on appeared on ceramic products. In this case, the artificial discerning and classification efficiency is very low. In order to improve ceramic products quality classification efficiency and intelligent level, a kind of method of applying multi-agent technology to ceramic products quality grade classification is presented, and the ceramic classification system structure and function implementation scheme based on multi-agent technology are also given in the paper. At the same time, Kalman filtering algorithm and C4.5 classification algorithm is effectively fused to process data by the multi-agent. In the end, an application example is given. Through applying the method proposed to the sampling daily-use porcelain classification, the result shows that the method proposed is effective and feasible in the daily-use porcelain classification. This will provide a new approach and new idea for the application of multi-agent technology to the ceramics field.

Our previous study has shown that chronic exposure to tamoxifen (TAM) induced formation of high levels of DNA adducts in the liver, the target tissue of TAM-induced carcinogenesis in rats. One of the major DNA adducts (spot 1), as detected by 32P-postlabeling, accounted for 53% of the total adducts. To characterize this major adduct, the current study has compared spot 1 with two previously identified TAM-DNA adducts, i.e. alpha-TAM-N2-deoxyguanine (alpha-TAM-N2-dG) and alpha-N-desmethyl TAM-N2-deoxyguanine (alpha-N-dmTAM-N2-dG) by various rechromatography methods. It was found that spot 1 was further resolved into two fractions during rechromatography analysis, one fraction co-migrated with the alpha-TAM-N2-dG and the other fraction co-migrated with the alpha-N-dmTAM-N2-dG. These findings have demonstrated that chronic exposure to tamoxifen induced the same major DNA adducts, i.e. alpha-TAM-N2-dG and alpha-N-dmTAM-N2-dG as those detected in acutely exposed rats.

To determine the expression of O6-methylguanine-DNA methyltransferase (MGMT) in pituitary adenomas and its association with tumour aggressiveness.From October 2011 to August 2012, all the patients with pathologically confirmed pituitary adenomas in our hospital were recruited for this study. The expression of MGMT in the tumor tissues was detected with immunohistochemistry.A total of 138 (including 71 male) patients participated in this study. The majority of the participants had nonfunctional (71%) and macroadenomas (92.8%). Aggressive and relapsed pituitary adenomas accounted for 31.2% and 8.7% of the cases, respectively. Low MGMT expression was found in 79 cases. The MGMT expression had no significant associations with gender, age, aggressiveness and relapse of tumors. However, prolactinomas were more likely to have low MGMT expression than nonfunctional adenomas (P = 0.025) and growth hormone adenomas (P = 0.043).The expression of MGMT has no associations with the aggressiveness and relapse of pituitary adenomas. Prolactinomas are more likely to have low expression of MGMT, which indicates that temozolomide might become an alternative treatment for aggressive and dopamine resistant prolactinomas.

Ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UPLC–Q-TOF/MS) was developed to identify the absorbed parent components and metabolites in rat bile, plasma and urine after oral administration of Radix Paeoniae Alba extract (RPAE). A total of 65 compounds were detected in rat bile, plasma and urine samples, including 11 parent compounds and 54 metabolites. The results indicated that glucuronidation, hydroxylation and methylation were the major metabolic pathways of the components of RPAE. Furthermore, the results of this work demonstrated that UPLC–Q-TOF/MS combined with MetaboLynx™ software and mass defect filtering (MDF) could provide unique high throughput capabilities for drug metabolism study, with excellent MS mass accuracy and enhanced MSE data acquisition. With the MSE technique, both precursor and fragment mass spectra can be simultaneously acquired by alternating between high and low collision energy during a single chromatographic run.

Based on thermodynamics and phase transformation driving force, a SMA constitutive model is provided. Simulations under different loading illustrate the influence of large strain deformation and small strain deformation on the characteristics of the model. The results indicate that the difference between the two methods is small under uniaxial tension, while the influence is very different under shear deformation case. The result has been stimulated by a example which test efficiently the result.

To investigate the prevalence of anti-hepatitis E virus (HEV) and genotypes of hepatitis E virus in 8 species of animals including swine, cattle, sheep, horse, donkey, dog, chicken and duck in the suburb of Beijing.Serum samples were collected from the 8 species of animals, and fecal samples of younger swine were collected from 2 stock farms. Anti-HEV was detected by Double Antigen Sandwich Assay. HEV RNA from fecal samples was detected by a reverse transcription nested polymerase chain reaction (RT-nPCR). Parts of the PCR products were cloned and sequenced. The swine HEV sequences were analyzed genetically.The positive rates of anti-HEV in serum specimens of swine, cattle, horse, donkey, sheep, dog, duck and chicken were 80.43% (481/598), 15.02% (52/346), 14.29% (40/280), 0 (0/26), 9.88% (33/334), 0 (0/21), 3.03% (7/231) and 2.53% (8/316), respectively. The anti-HEV prevalence of adult swine (/= 6 months) and younger swine (/ = 3 months) were 87.86% (369/420) and 62.92% (112/178) respectively. 74 of 111 (66.67%) pig faces were positive for HEV RNA. Sequence analysis on these positive samples showed that there were 6 groups of HEV designated as bjsw1, bjsw2, bjsw3, bjsw4, bjsw5 and bjsw6. The 6 strains of HEV shared 94.5% - 99.6% sequence identity of partial HEV ORF2 nucleotide with each other. The identities of HEV ORF2 nucleotide sequences between the 6 strains and genotype 1, 2, 3 and 4 were 75.6% - 78.6%, 75.6% - 76.2%, 77.1% - 80.7% and 83.7% - 94.5%, respectively. The sequence identity between the 6 strains and human HEV genotype 4d was 90.0% - 94.5%.HEV infection was seen in swine, cattle, horse, sheep, duck and chicken in the suburbs of Beijing. The anti-HEV positive rate appeared the highest in swine and the lowest in dog and donkey. The six strains of HEV isolated from younger swine belonged to genotype 4d.

SPECIFIC AIMSThe goals of this study were to: 1) determine whether vascular smooth muscle cell (SMC) apoptosis is coordinated with degradation of elastin in collagen gels; 2) determine the nature of the elastin degrading enzyme released by apoptotic SMCs; 3) determine whether caspases were exteriorized or released by apoptotic SMCs that can degrade elastin at the cell surface; 4) use relatively selective substrates and inhibitors to better define the caspases that could degrade elastin upon release from apoptotic cells; 5) determine which candidate elastin-degrading caspases specifically localized to smooth muscle cell surfaces in apoptotic cells; and 6) determine whether caspase inhibitors can prevent elastolysis by apoptotic SMCs.PRINCIPAL FINDINGS1. Apoptosis in vascular SMCs is coordinated with ECM/elastin degradationWe first documented that SMCs derived from a rat aorta cell line (A10) undergo apoptosis when placed on floating vs. attached collagen gels for 48 h, consistent with our studies using pul...

In eukaryotes protein phosphorytion is a key event. By reversible protein phosphorylation eukaryotes control many cellular processes including signal transduction, gene expression, the cell cycle etc. Phosphoproteomics involves identification of phosphoproteins and phosphopeptides, localization of the exact residues that are phosphorylated and quantitation of phosphorylation. Because protein phosphorylation is a dynamic process, and it is present at low abundance within cells, and the phosphorylated sites on proteins might vary, and mass spectrometry (MS) signals from phosphopeptides are usually suppressed etc., so phosphoprotein analysis have more difficulties than nonphosphoprotein. In this article, we outline several analysis techniques for separation, identification and quantitation of phosphorylated proteins and peptides, and discuss the progress in these techniques. At present, MS is still an essential core identification technology for phosphoproteomic studies, To search better enrichment strategies are the main challenges in this rapidly evolving field. A major goal of quantitative proteomics is precise quantification and identification of proteins in complex mixtures. A common method for quantitative proteome analysis is the stable isotope labeling method. Today there is no single method that supersedes all others techniques for Phosphoproteomic studies. With continued development of sample preparation techniques and instrumentation, it should be possible to perform a global analysis of protein phosphorylation.

To investigate the prevalence of anti-HEV among swine, sheep and chickens.Totally 498 sera of swine, sheep and chickens collected from Xingjiang, Guangxi, Guangdong, Beijing and Hebei were detected for the anti-HEV by an enzyme linked immunoassay.The anti-HEV positive rate of swine was 67.53%(104/154), in pigs between 4-5 months of age the rate was 100.00%(9/9) from Xingjiang. The rate in pigs under 3 months of age from Guangxi was 36.00%(9/25) and in pigs older than six months of age was 71.67% (86/120), respectively. The 108 sera of sheep collected from Xingjiang were all negative. The positive rate of chickens was only 1.27% (3/236). The anti-HEV prevalence rates of chickens from Luoding, Shenzhen, Liuzhou, Beijing and Hebei were 4.00%, 1.49%, 1.49%, 0, 0 respectively.HEV infection does exist among swine and chickens. The anti-HEV prevalence of swine was the highest among domestic animals. The role of swine and chickens in transmission of HEV needs to be further studied.

To investigate HEV infection in swine and the genotype relationship between swine and human HEV.Anti-HEV IgG antibody was detected in the sera of swine using enzyme linked immunoassay (EIA), and HEV RNA was amplified by reverse transcription nested polymerase chain reaction (RT-nPCR). The Vector NTI Suite 7 and TreeView softwares were used for nucleotide sequences phylogenetic analysis of HEV isolated from human and swine.The anti-HEV IgG positive rate was 16.67% (18/108). Among the 18 anti-HEV IgG positive sera, 2 sequences (11.11%, called S18 and S43, respectively) of HEV ORF1 (102-387bp) were amplified, with the identity of 99% between them. They had 76% to 77%, 78%, 76% to 79%, 85% to 86%, 77%, 80%, 79% and 75% - 79% homology at the nucleotide level with human HEV genotypes 1 to 8, respectively. One (S18) of them was also amplified out in ORF2 region (5,994-6 297bp) and showed 76% to 78%, 74%, 74% to 77%, and 85% to 94% identity with human HEV genotypes 1 to 4 at the nucleotide level, respectively.HEV sequences isolated from swine belong to human HEV genotype 4.

Evidence that hepatitis E is zoonotic is accumulating. Serum samples were collected from pigs, cattle, and goats from various regions of China to determine whether they had been infected with hepatitis E virus (HEV). An in-house enzyme immunoassay (EIA) and reverse transcriptase-polymerase chain reaction (RT-PCR) with primers from open reading frame (ORF) 2 were used to detect anti-HEV antibodies and HEV RNA. The mean positivity rates of anti-HEV antibody for pigs and cattle were 78.8% and 6.3% but none of the goat sera were positive. Pigs may be more susceptible to infection with HEV than cattle or goats. Five of 263 pig sera were positive for HEV RNA and four of these five were also positive for anti-HEV. The PCR products (nt 6007-6354) were cloned and sequenced and compared to other HEV sequences in the nucleotide databases. The five sequences shared 83-93% identity to each other at the nucleotide level and 74-79%, 73-74%, 73-78%, and 83-99% identity to HEV genotypes 1, 2, 3, and 4, respectively. They were closely related to human isolates of HEV genotype 4. Phylogenetic analyses also place these swine sequences in HEV genotype 4, resembling most closely viruses isolated from Chinese patients with acute hepatitis. These data support the hypothesis that sporadic hepatitis E in China is zoonotic.

The use of cyclosporin A has contributed greatly to the success of organ transplantation. However, cyclosporin-associated side effects of hypertension, nephrotoxicity, and dyslipoproteinemia have tempered these benefits. Cyclosporin-induced dyslipoproteinemia may be an important risk factor for the accelerated atherosclerosis observed posttransplantation. Using a mouse model, we treated Swiss-Webster mice for 6 days with a daily dose of 20 μg/g body wt of cyclosporin and observed significant elevations of plasma cholesterol, triglyceride, and apolipoprotein B (apoB) levels relative to vehicle-alone treated control animals. Measurement of the rate of secretion of very low-density lipoprotein (VLDL) by the liver in vivo showed that cyclosporin treatment led to a significant increase in the rate of hepatic VLDL triglyceride secretion. Total apoB secretion was unaffected. Northern analysis showed that cyclosporin A treatment increased the abundance of hepatic mRNA levels for a number of key genes involved in cholesterol biosynthesis relative to vehicle-alone treated animals. Two key transcriptional factors, sterol regulatory element-binding protein (SREBP)-1 and SREBP-2, also showed differential expression; SREBP-2 expression was increased at the mRNA level, and there was an increase in the active nuclear form, whereas the mRNA and the nuclear form of SREBP-1 were reduced. These results show that the molecular mechanisms by which cyclosporin causes dyslipoproteinemia may, in part, be mediated by selective activation of SREBP-2, leading to enhanced expression of lipid metabolism genes and hepatic secretion of VLDL triglyceride.