Noise-Adaptive State Estimators with Change-Point Detection.

Aiming at tracking sharply maneuvering targets, this paper develops novel variational adaptive state estimators for joint target state and process noise parameter estimation for a class of linear state-space models with abruptly changing parameters. By combining variational inference with change-point detection in an online Bayesian fashion, two adaptive estimators-a change-point-based adaptive Kalman filter (CPAKF) and a change-point-based adaptive Kalman smoother (CPAKS)-are proposed in a recursive detection and estimation process. In each iteration, the run-length probability of the current maneuver mode is first calculated, and then the joint posterior of the target state and process noise parameter conditioned on the run length is approximated by variational inference. Compared with existing variational noise-adaptive Kalman filters, the proposed methods are robust to initial iterative value settings, improving their capability of tracking sharply maneuvering targets. Meanwhile, the change-point detection divides the non-stationary time sequence into several stationary segments, allowing for an adaptive sliding length in the CPAKS method. The tracking performance of the proposed methods is investigated using both synthetic and real-world datasets of maneuvering targets.

Simulation research on the protection performance of fall protection net at the end of truck escape ramp.

INTRODUCTION: Although the fall protection net installed at the end of the truck escape ramp has a protective effect on trucks and drivers, but lacks sufficient theoretical basis and verification method. OBJECTIVES: The primary objective of this paper was to design a fall protection net that meets the regulations and research its protection performance. METHODS: The finite-element method was used to design the overall size, material, mesh length, mesh type, shape, and supporting structure of the fall protection net installed at the end of truck escape ramp, then dummy and truck models were used to impact the fall protection net to verify the rationality of the design. After the design completed, the truck model was used to impact the fall protection net twice to research the cumulative protection performance. RESULTS: A fall protection net with a width of 6000 mm, a span of 6000 mm, a depth of 5196 mm, a mesh length of 150 mm, a mesh type of diamond mesh, a shape of 60-degree V-shaped, a supporting structure of steel pipe supporting has a better effect on energy absorption and protection. Within the two consecutive impacts, the residual plastic deformation and stress of the fall protection net generated in the first impact severely affect the protection performance in the second impact. CONCLUSION: It is feasible to use the finite-element method to design and research the fall prevention net installed at the end of the truck escape ramp, and the fall protection net can indeed protect the trucks and drivers, and it should be inspected and maintained after impact to ensure the protective performance in subsequent use.

Oxymatrine inhibits proliferation and apoptosis of human breast cancer cells through the regulation of miRNA-140-5P.

OBJECTIVE: Oxymatrine has shown strong anti-cancer ability, but its mechanism is not well-studied. METHODS: The inhibitory rates of oxymatrine with various concentrations (0, 1, 2, 4, 6, 8, 16, 32 mg/ml) on MCF-7 cells were detected by CCK-8. The effects of oxymatrine on the expression of miRNA-140-5P in MCF-7 cells were detected by real-time fluorescent quantitative PCR (RT-PCR). miRNA-140-5P mimics or NC mimics were transfected into cells using Lipofectamine 2000. Eventually, the cells were divided into control-group, drug-group, miRNA-140-5P mimics group, NC mimics group, and miRNA-140-5P mimics + drug group. Cell viability was detected by CCK-8 assay and apoptosis rate of each group were measured by using Flow cytometry. Western blot was carried out to detect the protein expression of TGFBR1 and FGF9. RESULTS: Oxymatrine at various concentrations had conspicuous inhibitory effect on the proliferation of MCF-7 cells (P<0.05), and the inhibitory effect of oxymatrine on MCF-7 cells showed both dose- and time-dependent manners. The relative expression of miRNA-140-5P in MCF cells was remarkably lower than that in MCF-10A. Oxymatrine could effectively promote the expression of miRNA-140-5P in MCF-7 cells, and the relative expression of miRNA-140-5P increased significantly with the increased dose of oxymatrine (P<0.05). Both transfection of miRNA-140-5P mimics and oxymatrine treatment could reduce the proliferation of MCF-7 cells (P<0.05), and the proliferation of cells in miRNA-140-5P mimics + drug-group was significantly lower than that of other groups (P<0.05). Compared with the control-group, the protein expressions of TGFbR1 and FGF9 in low-dose, medium-dose and high-dose groups were dramatically decreased (P<0.05), in a dose-dependent manner (P<0.05). CONCLUSION: Oxymatrine inhibits proliferation and promotes cell apoptosis of breast cancer MCF-7 cells. The mechanism may contribute to the regulation of miRNA-140-5p and its target genes.

[The influence of inhibiting angiopoietin-2 on the biological characteristics of bronchogenic adenocarcinoma].

BACKGROUND AND OBJECTIVE: It is well-known that angiopoietin-2 (Ang-2) plays an important role in the formation of the blood vascular system. Angiopoietin is involved in many diseases about angiogenesis such as tumor, so may have great prospects for the treatment of these diseases. The aim of this study is to evaluate the influence of inhibiting Ang-2 via adeno-associated virus induced RNA interference (RNAi) on the biological characteristics of bronchogenic adenocarcinoma. METHODS: AAV-Ang-2shRNA driven by H1 promoter was constructed to transfect A549 cell line. Normal and AAV-Null cell line were utilized in the control groups. The influence of RNAi on Ang-2 expression as well as the growth rate, tumorigenic efficiency, proliferation rate, apoptosis, and microvessel density of A549 cell line were analyzed. RESULTS: In vitro experiment indicated that the Ang-2 expression level (P<0.001) and growth rate (P<0.001) of A549 cell line 48 h transfected with AAV-Ang-2shRNA were significantly lower than those in the normal and AAV-Null cell lines. Cell cycle analysis showed the proliferation index (PI) of normal, AAV-Null, and AAV-Ang-2shRNA transfected A549 cell line were 0.51± 0.43, 0.48 ± 0.29, and 0.26 ± 0.31, respectively, which indicated the PI of AAV-Ang-2shRNA transfected cell line was significantly lower, compared with the normal and AAV-Null cell lines. In vivo experiment exhibited that AAV-Ang-2shRNA transfected cell line possessed a lower mass and volume of tumor relative to two control groups. In addition, the apoptosis index (AI) of AAV-Ang-2shRNA transfected, normal, and AAV-Null cell lines were (5.98 ± 3.11)%, (7.51 ± 4.42)% and (17.06 ± 7.43)% respectively, which manifested that AAV-Ang-2shRNA transfected cell line possessed a higher AI (P=0.005, P=0.007). A lower percentage of PCNA-positive cell was observed in AAV-Ang-2shRNA transfected cell line (92.75 ± 9.7)% as well, compared with the normal (85.8 ± 11.8)% and AAV-Null (69.8 ± 16.5)% cell lines. CONCLUSIONS: AAV-mediated expression of shRNA significantly reduces concentration of Ang-2 in A549 cell line, lowers proliferation and growth rate and induce .apoptosis of A549 cell line.

Chronic ethanol feeding impairs AMPK and MEF2 expression and is associated with GLUT4 decrease in rat myocardium.

Chronic and heavy alcohol consumption is one of the causes of heart diseases. However, the effects of ethanol on insulin sensitivity in myocardium has been unclear. To investigate the effects of ethanol on the expression of AMP-activated protein kinase (AMPK), myocyte enhancer factor 2 (MEF2) and glucose transporter 4 (GLUT4), all of which are involved in the regulation of insulin sensitivity, in the myocardium, we performed three parts of experiments in vivo and in vitro. I: Rats were injected with 5-amino-4-imidazolecarboxamide ribonucleotide (AICAR, 0.8 mg.kg(-l)) for 2 h. II: Rats received different dose (0.5, 2.5 or 5 g.kg(-l).d(-l)) of ethanol for 22-week. III: Primary neonatal rat cardiomyocytes were isolated and treated with or without 100 mM ethanol or 1 mM AICAR for 4 h. The cardiac protein and mRNA expression of AMPKalpha subunits, MEF2 and GLUT4 were observed by western-blotting and RT-PCR, respectively. Serum TNFalpha levels were assessed by ELISA. The results showed chronic ethanol exposure induced insulin resistance. Ethanol decreased the mRNA levels of AMPKalpha1 and alpha2, the protein levels of total- and phospho-AMPKalpha in cardiomyocytes. Similarly, ethanol showed inhibitory effects on both the mRNA and protein levels of MEF2A and 2D, and GLUT4 in a dose-response-like fashion. Correlation analysis implied an association between phospho-AMPKalpha and MEF2A or MEF2D, and between the levels of MEF2 protein and GLUT4 transcription. In addition, ethanol elevated serum TNFalpha level. Taken together, chronic ethanol exposure decreases the expression of AMPKalpha and MEF2, and is associated with GLUT4 decline in rat myocardium.

Long-term ethanol exposure inhibits glucose transporter 4 expression via an AMPK-dependent pathway in adipocytes.

AIM: The roles of AMP-activated protein kinase (AMPK) and myocyte enhancer factor 2 isoforms (MEF2A, D) as mediators of the effects of ethanol on glucose transporter 4 (GLUT4) expression are unclear. We studied the effects of ethanol in adipocytes in vivo and in vitro. METHODS: Thirty-six male Wistar rats were divided into three groups and given ethanol in a single daily dose of 0, 0.5, or 5 g/kg for 22 weeks. The expression of AMPK, MEF2 isoforms A and D, and GLUT4 was measured and compared in the three groups. The existence of the AMPK/MEF2/GLUT4 pathway in adipocytes and the effects of ethanol on this pathway were studied in (a) epididymal adipose tissue from six male Wistar rats subcutaneously injected with 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR, an AMPK activator) or with 0.9% NaCl (control); and (b) isolated rat and human adipocytes treated with or without ethanol, AICAR, and compound C (a selective AMPK inhibitor). Expression of AMPK, MEF2, and GLUT4 was measured by RT-PCR and Western blotting. RESULTS: (1) Long-term ethanol exposure decreased activated AMPK, MEF2A, MEF2D, and GLUT4 expression in rat adipose tissue. (2) In rat and human adipocytes, AICAR-induced AMPK activation, with subsequent elevation of MEF2 and GLUT4 expression, was inhibited by compound C. (3) In vitro ethanol-treatment suppressed the AMPK/MEF2/GLUT4 pathway. CONCLUSION: The AMPK/MEF2/GLUT4 pathway exists in both rat and human adipocytes, and activated AMPK may positively regulate MEF2 and GLUT4 expression. Ethanol inhibition of this pathway leads to decreased GLUT4 expression, thus reducing insulin sensitivity and glucose tolerance.

[Recombinant adeno-associated virus mediated RNA interference of angiogenin expression inhibits cell growth of human lung adenocarcinoma].

OBJECTIVE: To study the inhibition of angiogenin (ANG) expression in human lung squamous cancer cell strain-A549 through adeno-associated virus (AAV)-mediated RNA-interference, and therefore to observe its effect on the growth of cancer cells and tumor formation. METHODS: Recombinant AAV expressing H1-promoter-induced small-interference- RNA (siRNA) targeting ANG (AAV-shANG) was constructed, and then transfected into A549 cells. A549 cells and cells transfected with AAV-Null were used as the control groups. The effects of the reduced expression of ANG by RNAi from AAV-shANG on the growth, formation, reproduction, apoptosis, and microvessel-density of the carcinoma were observed. RESULTS: In vitro experiment showed that AAV-shANG was constructed successfully, There was an significant decrease in the expression of ANG protein 72 h after transfection, compared with the normal A459 cells and AAV-Null cells (P < 0.01). Cell cycle analysis showed that the proliferation index (PI) of normal A549 cells, AAV-Null cells and AAVshANG cells were 0.32 +/- 0.29, 0.35 +/- 0.38 and 0.31 +/- 0.43, respectively. There was no statistic difference in the PIs among the 3 groups (P > 0.05). In vivo experiment using thymus-defect mice showed that, there was an remarkable reduction in the mass and volume of tumors in AAV-shANG transfected group, compared to the control groups. Microvessel-density was 9.4 +/- 1.5, 9.8 +/- 2.1 and 5.7 +/- 1.9, respectively in the 3 groups, a statistic difference among the AAV-shANG-transfected group, the normal A549 group and the AAV-Null transfected group. The percentages of apoptotic cells in each group were (7.7 +/- 3.1)%, (8.5 +/- 5.4)%, (17.1 +/- 8.6)%, respectively, the experimental group being higher than those of the control groups. Positive rates of PCNA were (84.8 +/- 9.7)%, (85.8 +/- 9.8)%, and (70.4 +/- 10.1)%, respectively, the AAV-shANG transfected cancer cells showing a lower PCNA index than the control groups. CONCLUSION: AAV-mediated expression of siRNA could reduce the expression of ANG in cancer cells, significantly enough to inhibit cell proliferation, promote cell apoptosis and inhibit tumor growth.

Chronic ethanol consumption resulting in the downregulation of insulin receptor-beta subunit, insulin receptor substrate-1, and glucose transporter 4 expression in rat cardiac muscles.

The objective of this study was to investigate the effect of chronic ethanol intake on the expression of insulin receptor beta subunit (IR-beta), insulin receptor substrate-1 (IRS-1), and glucose transporter 4 (Glut4) in rat cardiac muscle. Forty-eight male Wistar rats were randomly classified into four groups and to each group, ethanol was administered daily at the respective doses of 0 (control, C), 0.5 g kg(-1) (low ethanol, L), 2.5 g kg(-1) (middle ethanol, M), and 5 g kg(-1) (high ethanol, H). Twenty-two weeks later, the rats were anesthetized, and the left ventricle muscles were excised. The IR-beta, IRS-1, and Glut4 mRNA levels in the cardiac muscle tissues were detected by reverse-transcription polymerase chain reaction (RT-PCR); the IR-beta, tyrosine phosphorylation of IR-beta (PY-IR-beta), IRS-1, tyrosine phosphorylation of IRS-1 (PY-IRS-1), and Glut4 protein levels were measured by Western blotting. Compared to the control group, the IR-beta, IRS-1, and Glut4 mRNA levels in groups H and M decreased remarkably. In addition, the protein levels of IR-beta, IRS-1, and Glut4 showed a corresponding decline in ethanol-treated groups, especially in group H. Moreover, the PY-IR-beta and PY-IRS-1 protein levels decreased in the hearts of ethanol-treated rats with corresponding changes in the IR-beta and IRS-1 protein levels. The present study showed that chronic ethanol intake could downregulate the expression levels of IR-beta, IRS-1, and Glut4 in rat cardiac muscles.

Long-term moderate ethanol consumption restores insulin sensitivity in high-fat-fed rats by increasing SLC2A4 (GLUT4) in the adipose tissue by AMP-activated protein kinase activation.

The sole effect of either saturated fatty acid or moderate ethanol consumption on SLC2A4 (GLUT4) expression is widely reported but the combined effects of them remain obscure. Here, we observed their combined effects on SLC2A4 expression, explored the underlying mechanism mediated by AMP-activated protein kinase alpha (PRKAA2) and myocyte enhancer factor 2 (MEF2) both in vivo and in vitro. In the in vivo experiments, 36 male Wistar rats, divided into three groups, were fed with normal diet, high-fat (HF) diet, or HF diet plus ethanol for 22 weeks. We measured the expressions of total-PRKAA2 (T-PRKAA2), phosphorylated-PRKAA2 (pPRKAA2, activated form of PRKAA2), MEF2, and SLC2A4 in epididymal adipose tissues. In the in vitro experiments, primary adipocytes, isolated from normal Wistar rats, were incubated in the presence or absence of palmitate, ethanol, and compound C (an PRKAA2 inhibitor) for 1 h. Thereafter, T-PRKAA2, pPRKAA2, MEF2, and SLC2A4 expressions were measured. We found that both HF diet and in vitro exposition to palmitate impaired SLC2A4 expression in rat adipocytes with a parallel reduction in PRKAA2 activation and MEF2 expression. This impairment was reversed by ethanol administration. We further demonstrated that ethanol-mediated PRKAA2 activation stimulates MEF2 and SLC2A4 expressions in adipocytes, as evidenced by compound C blockade of these effects. In summary, long-term moderate ethanol consumption reversed the adverse effect of saturated fatty acid on SLC2A4 expression in adipocytes, which was likely to be a result of PRKAA2 activation and subsequent up-regulation of MEF2 and SLC2A4 expressions.

[Effects of Xuefu Zhuyu Capsule on endothelin-1 release in myocardium and vascular endothelium and nitric oxide/nitric oxide synthase system of swines after acute myocardial infarction and reperfusion].

OBJECTIVE: To observe the effects of Xuefu Zhuyu Capsule (XFZYC), a compound traditional Chinese herbal medicine, on endothelin-1 (ET-1) release in myocardium and vascular endothelium and nitric oxide (NO)/nitric oxide synthase (NOS) system of swines after acute myocardial infarction (AMI) and reperfusion, and to explore the action mechanisms of XFZYC in improving the endothelium function. METHODS: Forty-five Yorkshire swines were randomized into 3 groups: sham-operated group, untreated group and XFZYC-treated group. A Yorkshire swine model of reperfusion in AMI was established by ligation of left anterior descending coronary artery for 90 min followed by 2 h relaxation. The content of serum ET-1 and NO was measured by radioimmunoassay before and after AMI and after reperfusion, respectively. Twenty-four hours after operation, all Yorkshire swines underwent diagnostic coronary angiography to delineate coronary arteries. The expressions of ET-1 and endothelial nitric oxide synthase (eNOS) in myocardial tissue of ischemic area were quantified with Western blotting. Microvessel density of the implanting sites was assessed by using HE staining. RESULTS: Compared with the untreated group, the levels of serum ET-1 after AMI and reperfusion were significantly decreased in XFZYC-treated group (P<0.01), while the NO levels after AMI and reperfusion in XFZYC-treated group were significantly increased (P<0.01). There was no significant difference in diagnostic coronary angiography between XFZYC-treated group and untreated group (P=0.253). Western blotting showed that the level of ET-1 in ischemic area in XFZYC-treated group was lower than that in the untreated group (P<0.01), while the eNOS protein expression in XFZYC-treated group was higher than that in the untreated group (P<0.01). The results of HE staining and microvessel density analysis of the implanting sites all showed that the degree of telangiectasis was reduced, the cardiac muscle damage was improved, and the density of capillaries was increased obviously in XFZYC-treated group as compared with the untreated group. CONCLUSION: The endothelium injury may be one of the important mechanisms for no-reflow phenomenon. XFZYC may reduce the no-reflow by protecting endothelium cells.

[Prevalence of coronary artery disease in patients with rheumatic heart disease in China].

OBJECTIVE: To investigate the prevalence of coronary artery disease (CAD) and the atherosclerotic risk factors in the patients undergoing valvular surgery due to rheumatic heart disease. METHODS: Consecutive 651 patients with rheumatic heart disease aged > 40 who were scheduled for valve surgery underwent diagnostic coronary angiography to delineate coronary arteries. Significant coronary artery disease was considered to be present if one or more single coronary branches showed 50% or more luminal stenosis. Symptoms, such chest pain, were evaluated. Established risk factors for CAD, such as diabetes mellitus, systemic hypertension, smoking, and dyslipidemia were evaluated. Previous history of myocardial infarction and coronary artery bypass surgery was also recorded. RESULTS: Seventy-one patients (10.91%), 54 males and 17 females, were detected as with CAD. The mean age of the patients with CAD was (63 +/- 9), significantly higher than that of the patients with normal coronary arteries [(54 +/- 9), P < 0.01]. The atheromatous lesion mostly involved the left descending branch (38.12%), and 38 patients (53.52%) showed lesions in 2 or more branches. The prevalence rates of diabetes mellitus and hypertension in the CAD group were 32.39% and 29.58% respectively, both significantly higher than those in the non-CAD group (7.41% and 19.48% respectively; P < 0.01 and P = 0.047). The smoking rate of the CAD group was 36.62%, significantly higher than that of the non-CAD group (12.93%; P < 0.01). However, there were not significant differences in the prevalence rates of dyslipidemia and ECG ST-T changes between these 2 groups (both P > 0.05). No relation was found between the rheumatic disease and coronary disease distribution (P > 0.05). CONCLUSION: Coronary angiography should be performed in all patients clinically suspected with CAD, aged > 50 and the patients with angina and/or coronary risk factors in order to decrease the occurrence of operative complications.