Background: The signal-to-noise ratio (SNR) is recognized as an index of measurements reproducibility. We derive the maximum likelihood estimators of SNR and discuss confidence interval construction on the difference ...Background: The signal-to-noise ratio (SNR) is recognized as an index of measurements reproducibility. We derive the maximum likelihood estimators of SNR and discuss confidence interval construction on the difference between two correlated SNRs when the readings are from bivariate normal and bivariate lognormal distribution. We use the Pearsons system of curves to approximate the difference between the two estimates and use the bootstrap methods to validate the approximate distributions of the statistic of interest. Methods: The paper uses the delta method to find the first four central moments, and hence the skewness and kurtosis which are important in the determination of the parameters of the Pearsons distribution. Results: The approach is illustrated in two examples;one from veterinary microbiology and food safety data and the other on data from clinical medicine. We derived the four central moments of the target statistics, together with the bootstrap method to evaluate the parameters of Pearsons distribution. The fitted Pearsons curves of Types I and II were recommended based on the available data. The R-codes are also provided to be readily used by the readers.展开更多
YTB block in Sichuan basin is a favorable area to exploit oil and gas in shallow tight rock. 3D seismic project of this zone has two characteristics. Firstly, it has high requirements for the tolerance rate of the con...YTB block in Sichuan basin is a favorable area to exploit oil and gas in shallow tight rock. 3D seismic project of this zone has two characteristics. Firstly, it has high requirements for the tolerance rate of the construction process and the acquisition of high signal-to-noise ratio seismic data;Second, there are widely obstacles and noises that lead to difficult acquisition construction organization. In acquisition practice, high signal-to-noise ratio seismic data was obtained by reasonable design of construction scheme, optimization of excitation parameters, improvement of receiving conditions and optimization of obstacle crossing observation system. .展开更多
AIMTo investigate whether the abnormal differentiation of the pterygium epithelium is related to the extracellular signal-regulated kinase (ERK) signaling pathway in vitro.METHODSThe expression levels of phosphorylate...AIMTo investigate whether the abnormal differentiation of the pterygium epithelium is related to the extracellular signal-regulated kinase (ERK) signaling pathway in vitro.METHODSThe expression levels of phosphorylated ERK (P-ERK), keratin family members including K19 and K10 and the ocular master control gene Pax-6 were measured in 16 surgically excised pterygium tissues and 12 eye bank conjunctiva. In colony-forming cell assays, the differences in clone morphology and in K10, K19, P-ERK and Pax-6 expression between the head and body were investigated. When cocultured with the ERK signaling pathway inhibitor PD98059, the changes in clone morphology, colony-forming efficiency, differentiated marker K10, K19 and Pax-6 expression and P-ERK protein expression level were examined by immunoreactivity and Western blot analysis.RESULTSThe expression of K19 and Pax-6 decreased in the pterygium, especially in the head. No staining of K10 was found in the normal conjunctiva epithelium, but it was found to be expressed in the superficial cells in the head of the pterygium. Characteristic upregulation of P-ERK was observed by immunohistochemistry. The clone from the head with more differentiated cells in the center expressed more K10, and the clone from the body expressed more K19. The P-ERK protein level increased in the pterygium epithelium compared with conjunctiva and decreased when cocultured with PD98059. The same medium with the ERK inhibitor PD98059 was more effective in promoting clonal growth than conventional medium with 3T3 murine feeder layers. It was observed that the epithelium clone co-cultured with the inhibitor had decreased K10 expression and increased K19 and Pax-6 expression.CONCLUSIONWe suggest ERK signaling pathway activation might play a role in the pterygium epithelium abnormal differentiation.展开更多
BACKGROUND: The pathogenesis of hepatic fibrosis and cirrhosis is still not fully understood. The extracellular signal-regulated kinase (ERK) pathway is involved in the regulation of cell proliferation and differentia...BACKGROUND: The pathogenesis of hepatic fibrosis and cirrhosis is still not fully understood. The extracellular signal-regulated kinase (ERK) pathway is involved in the regulation of cell proliferation and differentiation. The aim of this study was to investigate the effects of PD98059, a specific inhibitor of ERK, on the cell cycle, cell proliferation, secretion of type I collagen and expression of cyclin D1 mRNA, CDK4 mRNA and transforming growth factor-beta 1 (TGF-beta 1) mRNA in rat hepatic stellate cells (HSCs) stimulated by acetaldehyde. METHODS: Rat HSCs stimulated by acetaldehyde were incubated with PD98059 at different concentrations. The cell cycle was analysed by flow cytometry. Cell proliferation was assessed by the methyl thiazolyl tetrazolium colorimetric assay. The mRNA expression of cyclin D1, CDK4 and TGF-beta 1 was examined using the reverse transcriptase-polymerase chain reaction. Type I collagen in the culture medium was detected by enzyme-linked immunosorbent assay. RESULTS: 20, 50 and 100 mu mol/L PD98059 significantly inhibited the proliferation and provoked a G0/G1-phase arrest of acetaldehyde-induced HSCs in a dose-dependent manner. The secretion of type I collagen and the expression of cyclin D1, CDK4 and TGF-beta 1 mRNA in acetaldehyde-induced HSCs were markedly inhibited by 50 and 100 mu mol/L PD98059, respectively. CONCLUSIONS: The ERK pathway regulates the cell proliferation, secretion of type I collagen and the expression of TGF-beta 1 mRNA in rat HSCs stimulated by acetaldehyde, which is likely related to its regulative effect on the cell cycle.展开更多
Objective:To explore the protective effect and its molecular mechanism of apoptosis signalregulating kinase 1(ASK1) inhibitor(GS-459679) on acetaminophen-induced liver injury in mice.Methods:The model of liver injury ...Objective:To explore the protective effect and its molecular mechanism of apoptosis signalregulating kinase 1(ASK1) inhibitor(GS-459679) on acetaminophen-induced liver injury in mice.Methods:The model of liver injury was established by administration of acetaminophen(APAP)(300 mg/kg,i.p.) on C57BL/6 mice.Forty-eight male C57BL/6 mice were randomly divided into four groups,consisting of control group,GS group(GS-459679,30 mg/kg,i.p.),APAPinduced group,and GS combined with APAP-induced group.For GS combined with APAPinduced group,mice were treated with GS 30 min prior to administration of APAP.After mice were euthanized at 6 h or 12 h.respectively,serum levels of alanine aminotransferase(ALT) and aspartate aminotransferase(AST) were analyzed,and mRNA levels of TNF- α,IL-6 and IL-1βwere tested.The activity of glutathione(GSH),oxidized GSH(GSSG) and malondialdehyde were quantified.In addition,ASK1,P-ASK1,JNK and P-JNK protein levels were tested in all groups.Results:The ASK1 and P-ASK1 levels were up-regulated in APAP-induced group.Compared to the control group,serum levels of ALT and AST.and mRNA levels of TNF- a,IL-6 and IL-1(3were increased in APAP-induced group.Meanwhile,the levels of MAD and GSSG.and the ratio of GSSG/GSH were higher and the JNK was activatedin APAP-induced group compared with that in control group.However,compared to APAP-induced group,GS combined with APAP-induced group displayed a decrease of protein expression levels of ASK 1,P-ASKI and P-JNK,a reduction of serum levels of ALT and AST,a decrease in TNF- a.IL-6 and IL-1(3 mRNA levels,and a low ration of GSSG/GSH.Conclusions:GS-459679 treatment effectively down-regulates ASK1 and P-ASK 1 expression.Addition of GS-459679 decreases the generation of liver metabolites and inflammatory factors,reduces oxidative stress reaction,inhibits JNK activation,and then protects the responsiveness to APAP-induced liver injury.展开更多
Aim： To assess the spatiotemporal changes in the expression of extracellular signal-regulated kinases 1 and 2 （ERK1/ 2）, c-Jun N-terminal kinases （JNK） and p38 mitogen-activated protein kinases （MAPK） in respon...Aim： To assess the spatiotemporal changes in the expression of extracellular signal-regulated kinases 1 and 2 （ERK1/ 2）, c-Jun N-terminal kinases （JNK） and p38 mitogen-activated protein kinases （MAPK） in response to heat stress in the cryptorchid testis, and to investigate a possible relation to Sertoli cell dedifferentiation. Methods： Immunohistochemistry and western blot were used to examine the expression and activation of ERK1/2, p38 and JNK in the cryptorchid testis at various stages after experimental cryptorchidism. Results： The abdominal temperature did not obviously change the total ERK1/2 expression but significantly activated phospho-ERK1/2 in the Sertoli cells of the cryptorchid testis. Heat stress increased total JNK expression in the Sertoli cells of the cryptorchid testis but did not activate phospho-JNK. Neither total p38 nor phospho-p38 was induced by heat stress in the Sertoli cells of the cryptorchid testis. Changes in the spatiotemporal expression of cytokeratin 18 （CK18）, a marker of immature or undifferentiated Sertoli cells, were induced in the cryptorchid testis in a pattern similar to the activation of ERK1/2. Condusion： The activation of ERK1/2 in the testis may be related to dedifferentiation of Sertoli cells under heat stress induced by experimental cryptorchidism.展开更多
BACKGROUND： Studies have shown that electro-acupuncture at the Ren meridian could improve proliferation of subventricular zone neural stem cells in cerebral-ischemic rats. However, there are few reports on the influe...BACKGROUND： Studies have shown that electro-acupuncture at the Ren meridian could improve proliferation of subventricular zone neural stem cells in cerebral-ischemic rats. However, there are few reports on the influence of electro-acupuncture at the Du meridian on neural stem cell proliferation. OBJECTIVE： To observe the influence of electro-acupuncture at Ren and Du meridians on neural stem cell proliferation in the subventricular zone and altered signal transduction in cerebral ischemia rats. DESIGN, TIME AND SETTING： A randomized, controlled, animal experiment was performed at the Laboratory of Human Anatomy, Medical College of Sun Yat-sen University from May 2006 to February 2008. MATERIALS： Mouse anti-rat bromodeoxyuridine （BrdU） monoclonal antibody was provided by Sigma, USA; mouse anti-rat nestin monoclonal antibody and extracellular signal-regulated protein kinase （ERK） specific inhibitor PD98059 were provided by Calbiochem, Germany; acupuncture needle was provided by Suzhou Acupuncture Supplies, China. METHODS： A total of 126 rats were randomly assigned to four groups： model （n = 36）, Du meridian （n = 36）, Ren/Du meridian （n = 36）, and Ren/Du meridian ＋ PD98059 （n = 18）. Rats in the Ren/Du meridian ＋ PD98059 group were observed on days 7 （n = 6） and 14 （n = 12） after cerebral ischemia injury. Rats in the model, Du meridian, and Ren/Du meridian groups were observed on days 7, 14, and 28 after cerebral ischemia injury, with 12 rats per group at each time point. Thread occlusion was used to establish middle cerebral artery occlusion models. Electro-acupuncture was performed at Renzhong （DU 26） and Baihui （DU 20） acupoints in the Du meridian group, as well as Chengjiang （RN 24）, Guanyuan （RN 4）, Renzhong, and Baihuiacupoints in the Ren/Du meridian and Ren/Du meridian ＋ PD98059 groups 2 days after model establishment. In addition, electro-acupuncture stimulation with disperse-dense waves was performed, with 30 Hz disperse wave, 100 Hz dense wave, and 5 V intensity for 20 minutes. Rats in the Ren/Du meridian ＋ PD98059 group were treated with 0.2 pg PD98059 injection into the subventricular zone, 2 pL per rat. Rats in the model group were not treated with electro-acupuncture. MAIN OUTCOME MEASURES： BrdU/nestin immunofluorescent staining was used to detect proliferating neural stem cells in the subventricular zone of cerebral ischemia rats; Western blot was used to determine phosphorylated ERK1 and 2 （pERK1/2） expression in the subventricular zone. RESULTS： On days 14 and 28 after cerebral ischemia, there were significantly more BrdU-positive and BrdU/nestin-positive cells in the Ren/Du meridian group compared with the Du meridian group （P 〈 0.05）. PD98059 decreased the number of BrdU-positive and BrdU/nestin-positive cells induced by electro-acupuncture at the/：ten and Du meridians （P 〈 0.05）. On days 7, 14, and 28 after treatment, pERK1/2 expression was significantly greater in the Du meridian and Ren/Du meridian groups compared with the model group （P 〈 0.05）. The promoting effect of electro-acupuncture at Ren and Du meridians on ERK1/2 phosphorylation was superior to electro-acupuncture at the Du meridian alone on day 14 after model induction （P 〈 0.05）. However, PD98059 completely abolished the promoting effect of electro-acupuncture at Ren/Du meridians on pERK1/2 expression （P 〈 0.05）. CONCLUSION： Electro-acupuncture at Ren and Du meridians increased proliferation of subventricular zone neural stem cells, which was related to activation of the ERK pathway in a rat model of cerebral ischemia injury.展开更多
Activation of extracellular signal-regulated kinase 1/2 has been demonstrated in acute brain ischemia. We hypothesized that activated extracellular signal-regulated kinase 1/2 can protect hippocampal neurons from inju...Activation of extracellular signal-regulated kinase 1/2 has been demonstrated in acute brain ischemia. We hypothesized that activated extracellular signal-regulated kinase 1/2 can protect hippocampal neurons from injury in a diabetic model after cerebral ischemia/reperfusion. In this study, transient whole-brain ischemia was induced by four-vessel occlusion in normal and diabetic rats, and extracellular signal-regulated kinase 1/2 inhibitor （U0126） was administered into diabetic rats 30 minutes before ischemia as a pretreatment. Results showed that the number of surviving neurons in the hippocampal CA1 region was reduced, extracellular signal-regulated kinase 1/2 phosphorylation and KuT0 activity were decreased, and pro-apoptotic Bax expression was upregulated after intervention using U0126. These findings demonstrate that inhibition of extracellular signal-regulated kinase 1/2 activity aggravated neuronal loss in the hippocampus in a diabetic rat after cerebral ischemia/reperfusion, further decreased DNA repairing ability and ac- celerated apoptosis in hippocampal neurons. Extracellular signal-regulated kinase 1/2 activation plays a neuroprotective role in hippocampal neurons in a diabetic rat after cerebral ischemia/ reperfusion.展开更多
Aim： To determine the mechanisms of glucocorticoids in inhibiting advanced prostate cancer growth. Methods： The cell proliferation and cell cycle of prostate cancer DU145 cells following dexamethasone treatment were...Aim： To determine the mechanisms of glucocorticoids in inhibiting advanced prostate cancer growth. Methods： The cell proliferation and cell cycle of prostate cancer DU145 cells following dexamethasone treatment were determined by proliferation assay and fluorescence-activated cell sorter. Western blot analysis was carried out to evaluate the effects of dexamethasone on phosphorylation of extracellular signal-regulated kinase （ERK）1/2 and expression of cyclin D1 in DU145 cells with or without glucocorticoid receptor （GR） antagonist RU486. Reverse transcription- polymerase chain reaction verified the expression of GR mRNA in DU145 cells. Results： Dexamethasone significantly inhibited DU 145 cell proliferation at the G0/G1 phase. Westem blot analysis showed a dramatic reduction of ERK1/2 activity and cyclin D1 expression in dexamethasone-treated cells. The decreased phosphorylation of ERK1/2 in dexamethasone-treated cells was attenuated by GR blockade. Additionally, the effects of dexamethasone in inhibiting cyclin D1 expression were altered by GR blockade. Conclusion： Dexamethasone suppresses DU145 cell proliferation and cell cycle, and the underlying mechanisms are through the inhibition of phosphorylation of ERK1/2 and cyclin D1 expression. The inhibition of ERK1/2 phosphorylation and cyclin D1 expression is attenuated by GR blockade, suggesting that GR regulates ERK1/2 and cyclin D1 pathways. These observations suggest that dexamethasone has a potential clinical application in prostate cancer therapy.展开更多
BACKGROUND： Previous studies have shown that extracellular signal-regulated kinase 1/2 （ERK1/2） and nitric oxide activation play a pivotal role in central sensitization and long-term neuronal plasticity induced by ...BACKGROUND： Previous studies have shown that extracellular signal-regulated kinase 1/2 （ERK1/2） and nitric oxide activation play a pivotal role in central sensitization and long-term neuronal plasticity induced by noxious stimulation. However, their effects on compressive neuralgia formation and maintenance remain poorly understood.OBJECTIVE： To investigate effects of the specific inhibitor of ERK1/2 signal pathway U0126 on neuronal nitric oxide synthase （nNOS） expression in the dorsal horn of the spinal cord in a compressive neuralgia rat model.DESIGN, TIME AND SETTING： A randomized, controlled experiment was performed at the Institute of Otolaryngology, Head and Neck Surgery, First Hospital of Jilin University from July 2008 to March 2009.MATERIALS： U0126 （Bio-Mol, USA） was used in this study.METHODS： A total of 84 rats were randomly assigned to two groups. In the first part of the experiment, 24 rats were used for behavioral testing, and they were randomly assigned to three sub-groups （n =8）： U0126, dimethyl sulfoxide （DMSO） and model control. In the second part of the experiment, 60 rats were used for immunofluorescence and Western blot analysis, and they were randomly assigned to six sub-groups （n = 10）： sham surgery, model control, U0126 post-injection at 0.5, 2, 12 and 24 hours. Neuropathic pain was produced by chronic compression to the dorsal root ganglion in rats from each sub-group. Rats in the U0126 group were administered a 5-ug U0126 intrathecal injection, and rats in the DMSO group were administered a 10-μL 5% DMSO intrathecal injection.MAIN OUTCOME MEASURES： Changes in mechanical and thermal hyperalgesia were observed using von Frey filaments and thermalqia stimular. Thermal and mechanical hyperalgesia were stimulated at different time points following intrathecal injection of U0126. nNOS activation and expression in the spinal cord dorsal horn were determined by immunofluorescence and Western blot analysis.RESULTS： Intrathecal injection of U0126 significantly attenuated chronic compression of dorsal root ganglion-induced mechanical and thermal hyperalgesia. Immunofluorescence staining results demonstrated that, compared to the sham surgery group, the number of nNOS-positive neurons was significantly increased in the injured spinal dorsal horn in the model control group （P〈0.01）. However, compared to the model control group, there were significantly decreasing numbers of nNOS-positive neurons in the U0126 post-injection groups at 0.5-hour, 2-hour, and 12-hour （P〈0.05）. Western blot analysis revealed similar results. CONCLUSION： Decreased activity in the ERK signal pathway resulted in down regulated nNOS expression in the dorsal horn of the spinal cord. These results suggested that ERK is involved in nitric oxide reaction to neuropathic pain.展开更多
Objective To investigate the role of extracellular signal-regulated kinase1/2（ERK1/2） pathway in the regulation of aquaporin 4（AQP4） expression in cultured astrocytes after scratch-injury. Methods The scratch-inju...Objective To investigate the role of extracellular signal-regulated kinase1/2（ERK1/2） pathway in the regulation of aquaporin 4（AQP4） expression in cultured astrocytes after scratch-injury. Methods The scratch-injury model was produced in cultured astrocytes of rat by a 10-μL plastic pipette tip. The morphological changes of astrocytes and lactate dehydrogenase（LDH） leakages were observed to assess the degree of scratch-injury. AQP4 expression was detected by immunofluorescence staining and Western blot, and phosphorylated-ERK1/2（p-ERK1/2） expression was determined by Western blot. To explore the effect of ERK1/2 pathway on AQP4 expression in scratch-injured astrocytes, 10 μmol/L U0126（ERK1/2 inhibitor） was incubated in the medium at 30 min before the scratch-injury in some groups. Results Increases in LDH leakage were observed at 1, 12, and 24 h after scratch-injury, and AQP4 expression was reduced simultaneously. Decrease in AQP4 expression was associated with a significant increase in ERK1/2 activation. Furthermore, pretreatment with U0126 blocked both ERK1/2 activation and decrease in AQP4 expression induced by scratch-injury. Conclusion These results indicate that ERK1/2 pathway down-regulates AQP4 expression in scratch-injured astrocytes, and ERK1/2 pathway might be a novel therapeutic target in reversing the effects of astrocytes that contribute to traumatic brain edema.展开更多
BACKGROUND： Very few studies have addressed neuronal injury in cerebral vasospasm and subarachnoid hemorrhage （SAH）, and the role of neurotransmitters in the regulation of extracellular signal-regulated kinase 1/2 ...BACKGROUND： Very few studies have addressed neuronal injury in cerebral vasospasm and subarachnoid hemorrhage （SAH）, and the role of neurotransmitters in the regulation of extracellular signal-regulated kinase 1/2 （ERK1/2） expression following SAH. OBJECTIVE： To analyze neurotransmitter regulation of ERK1/2 expression through the use of signal transduction, and to investigate cerebral injury mechanisms following SAH. DESIGN, TIME AND SETTING： A completely randomized grouping and controlled animal experiment was performed at the Experimental Center of Medical College of Xi＇an Jiaotong University from March to December 2008. MATERIALS： Extraceliular signal-regulated ERK1/2 polyclonal antibody and streptavidin-peroxidase method kits were purchased from Beijing Biosynthesis Biotechnology, China; DAB kit was purchased from Zhongshan Golden Bridge Biotechnology, China; TUNEL kit was purchased from Promega, USA. METHODS： A total of 114 male, Sprague Dawley rats, aged 55-63 days old, were randomly assigned to five groups： SAH （n = 30）, saline control （n = 30）, puncture control （n = 30）, normal control （n = 6）, and neurotransmitter-treated （n = 18）. The SAH model was established by twice injecting blood through the cisterna magna. The neurotransmitters-treated group was subdivided into three groups according to drugs injected into the lateral cerebral ventricle： acetylcholine chloride, norepinephrine, and saline, with six animals in each group. MAIN OUTCOME MEASURES： Rats from the SAH, saline control, and puncture control groups were respectively sacrificed at 6, 12, and 24 hours, as well as 3 and 5 days, with six rats at each time point. The normal control group rats were sacrificed at 6 hours, and the neurotransmitter group rats were sacrificed 3 days following neurotransmitter injection. Morphological cellular changes were observed by hematoxylin and eosin staining. Immunohistochemical SP method was used to detect expression of ERK1/2 in the cortex, and cortical apoptosis was detected using the TUNEL method. RESULTS： Neural tissue edema, apoptosis, and necrosis occurred in the cortex of the SAH group. ERK1/2-positive cells were first observed at 6 hours, peaked at 12 hours following SAH in the cortex, and gradually decreased thereafter. Cellular apoptosis was observed in the cortex at 6 hours and peaked at 24 hours following SAH. ERK1/2 distribution in the brain overlapped apoptotic cells to a great degree. The number of ERK1/2-positive and apoptotic cells was significantly greater in the SAH group compared with the three control groups （P 〈 0.05）. Compared to the number of ERK1/2-positive cells in the saline-treated group, acetylcholine chloride treatment resulted in decreased ERK1/2 expression and apoptosis （P 〈 0.05）. Norepinephrine resulted in increased ERK1/2 expression, but there was no significance in apoptosis compared to the saline-treated group （P 〉 0.05）. CONCLUSION： Apoptosis was observed early in the rat cortex following SAH. In addition, ERK1/2 was expressed earlier than apoptosis. Acetylcholine chloride treatment resulted in decreased numbers of apoptotic cells following SAH, possibly by down-regulating ERK1/2 expression.展开更多
The results of comparative theoretical analyzes of the behavior of internal low-frequency noises, signal-to-noise ratio and sensitivity to DNA molecules for EIS and ISFET based nanosize biosensors are presented. It is...The results of comparative theoretical analyzes of the behavior of internal low-frequency noises, signal-to-noise ratio and sensitivity to DNA molecules for EIS and ISFET based nanosize biosensors are presented. It is shown that EIS biosensor is more sensitive to the presence of DNA molecules in aqueous solution than ISFET sensor. Internal electrical noises level decreases with the increase of concentration of DNA molecules in aqueous solution. In the frequency range 10−3 - 103 Hz noises level for EIS sensor about in three orders is higher than for ISFET sensor. In the other hand, signal-to-noise ratio for capacitive EIS biosensor is much higher than for ISFET sensor.展开更多
Factors influencing the signal-to-noise ratio （SNR） of lensless ghost interference with thermal incoherent light are investigated. Our result shows that the SNR of lensless ghost interference is related to the trans...Factors influencing the signal-to-noise ratio （SNR） of lensless ghost interference with thermal incoherent light are investigated. Our result shows that the SNR of lensless ghost interference is related to the transverse length of the object, the position of the object in the imaging system and the transverse size of the light source. Furthermore, the effects of these factors on the SNR are discussed in detail by numerical simulations.展开更多
This article extends a signal-based approach formerly proposed by the authors, which utilizes the fractal dimension of time frequency feature （FDTFF） of displacements, for earthquake damage detection of moment resis...This article extends a signal-based approach formerly proposed by the authors, which utilizes the fractal dimension of time frequency feature （FDTFF） of displacements, for earthquake damage detection of moment resist frame （MRF）, and validates the approach with shaking table tests. The time frequency feature （TFF） of the relative displacement at measured story is defined as the real part of the coefficients of the analytical wavelet transform. The fractal dimension （FD） is to quantify the TFF within the fundamental frequency band using box counting method. It is verified that the FDTFFs at all stories of the linear MRF are identical with the help of static condensation method and modal superposition principle, while the FDTFFs at the stories with localized nonlinearities due to damage will be different from those at the stories without nonlinearities using the reverse-path methodology. By comparing the FDTFFs of displacements at measured stories in a structure, the damage-induced nonlinearity of the structure under strong ground motion can be detected and localized. Finally shaking table experiments on a 1：8 scale sixteen-story three-bay steel MRF with added frictional dampers, which generate local nonlinearities, are conducted to validate the approach.展开更多
Herb-partitioned moxibustion can effectively mitigate visceral pain, a major symptom in inflammatory bowel disease, but the analgesic lnechanism is still unclear. Moreover, extracellular signal-regulated kinase, subst...Herb-partitioned moxibustion can effectively mitigate visceral pain, a major symptom in inflammatory bowel disease, but the analgesic lnechanism is still unclear. Moreover, extracellular signal-regulated kinase, substance P, and neurokinin-1 are involved in formation of central hyperalgesia. Thus, we postulated that the analgesic effect of herb-partitioned moxibustion may be associated with these factors. Accordingly, in this study, we established an inflammatory bowel disease visceral pain model in rat by enema with a mixed solution of 5% trinitrobenzenesulfonic acid and 50% ethanol. Bilateral Tianshu （ST25） and Qihai （CV6） points were selected for herb-partitioned moxi- bustion. Our results showed that herb-partitioned moxibustion improved visceral pain and down-regulated extracellular signal-regulated kinase, substance P, and neurokinin-1 protein and mRNA expression in dorsal root ganglia. These results indicate that down-regulation of extracellular signal-regulated kinase, substance E and neurokinin-1 protein and mRNA may be a central mechanism for the analgesic effect of herb-partitioned moxibustion.展开更多
Grating-based x-ray phase contrast imaging has the potential to be applied in future medical applications as it is compatible with both laboratory and synchrotron source. However, information retrieval methods are imp...Grating-based x-ray phase contrast imaging has the potential to be applied in future medical applications as it is compatible with both laboratory and synchrotron source. However, information retrieval methods are important because acquisition speed, scanning mode, image quality, and radiation dose depend on them. Phase-stepping （PS） is a widely used method to retrieve information, while angular signal radiography （ASR） is a newly established method. In this manuscript, signal-to-noise ratios （SNRs） of ASR are compared with that of PS. Numerical experiments are performed to validate theoretical results. SNRs comparison shows that for refraction and scattering images ASR has higher SNR than PS method, while for absorption image both methods have same SNR. Therefore, our conclusions would have guideline in future preclinical and clinical applications.展开更多
We report a method of high-sensitively detecting the weak signal in photoassociation （PA） spectra of ultracold NaCs molecules by phase sensitive-demodulated trap-loss spectra of Na atoms from a photomultiplier tube....We report a method of high-sensitively detecting the weak signal in photoassociation （PA） spectra of ultracold NaCs molecules by phase sensitive-demodulated trap-loss spectra of Na atoms from a photomultiplier tube. We find that the signal-to-noise ratio （SNR） of the PA spectra is strongly dependent on the integration time and the sensitivity of the lock-in amplifier, and our results show reasonable agreement with the theoretical analyses of the SNR with the demodulation parameters. Meanwhile, we investigate the effect of the interaction time of the PA laser with the colliding Na-Cs atom pairs on the SNR of the PA spectra. The atom loss rate is dependent on both the PA-induced atom loss and the loading of the MOT. The high-sensitive detection of the excited ultracold NaCs molecules lays a solid foundation for further study of the formation and application of ultracold NaCs molecules.展开更多
Objective To investigate whether extracellular signal-regulated kinase (ERK1/2) was involved in changes of vascular smooth muscle cell (VSMC) under hypertension.Methods Two-kidney one clip Wistar hypertensive rats (WH...Objective To investigate whether extracellular signal-regulated kinase (ERK1/2) was involved in changes of vascular smooth muscle cell (VSMC) under hypertension.Methods Two-kidney one clip Wistar hypertensive rats (WHR) were sacrificed and their right kidneys were harvested 4 weeks after surgery.The spontaneously hypertensive rats (SHR) were divided into 4, 8, and 16 weeks old groups (SHR4w, SHR8w, and SHR16w), respectively.The control group were sham operated age-matched Wistar rats.Immunohistochemical technique and Western blotting were applied to study ERK1/2 protein expression in VSMC of the renal vascular trees in WHR, SHR, and control rats.Results Blood pressure in two-kidney one clip WHR obviously increased at one week after surgery, and reached to 198.00±33.00 mm Hg at the end of experiment, significantly higher than that in the control rats (P<0.01).Blood pressure in SHR4w (108.00±11.25 mm Hg) was similar to that in the controls.However, it rose to 122.25±21.75 mm Hg in SHR8w, and even up to 201.75±18.00 mm Hg in SHR16w, which were significantly higher than that of both the SHR4w and the controls (P<0.01).The rate and degree of glomerular fibrosis in WHR were significantly higher than controls (P<0.05).Hyaline degeneration of the afferent arterioles was found in WHR.In contrast, either fibrosis of glomerulus or hyaline degeneration of the arterioles or protein casts was not observed in SHR4w, SHR8w, and SHR16w.Immunohistochemical staining results showed expression of ERK1 was similar to that of ERK2.The positive rates of ERK2 staining in VSMC of afferent arterioles, interlobular, interlobar, and arcuate arteries in two-kidney one clip WHR were significantly higher (7.09%±1.75%, 14.57%±4.58%, 29.44%±7.35%, and 13.63%±3.85%, respectively) than that of the controls(P<0.01).The positive rates of ERK2 staining in VSMC at afferent arterioles, interlobular, interlobar, and arcuate arteries in SHR16w were significantly higher (12.09%±1.40%, 24.17%±6.92%, 32.44%±4.05%, and 18.61%±3.35%, respectively) than that of the controls (P<0.01), too.The expression of ERK1/2 protein of kidney in WHR and SHR16w was significantly higher than that in the controls by Western blotting assay (P<0.01).Conclusion Extracellular signal transduction system are highly expressed in kidney VSMC of two-kidney one clip WHR and SHR.Phospho-ERK1/2 may play an important role in VSMC hypertrophy and hyperplasia under hypertension.展开更多
BACKGROUND： The onset of focal cerebral ischemia activates extracellular signal-regulated kinases 1 and 2, regulates cell cycle, promotes cell proliferation and differentiation, and affects the normal stage and funct...BACKGROUND： The onset of focal cerebral ischemia activates extracellular signal-regulated kinases 1 and 2, regulates cell cycle, promotes cell proliferation and differentiation, and affects the normal stage and function of brain cells. OBJECTIVE： To observe the effects of electroacupuncture at the Ren channel on extracellular signal-regulated kinases 1/2 expression in the lateral cerebral ventricle wall of rats with focal cerebral ischemia. The effects were analyzed at different time points after intervention. DESIGN： Randomized controlled study. SETTING： Department of Anatomy, Sun Yat-Sen University. MATERIALS： A total of 60 healthy adult male Wistar rats weighing （250±10） g were provided by the Experimental Animal Center, Medical College of Sun Yat-Sen University. The animal experiment was conducted with confirmed consent by the local ethics committee. The GB6805-Ⅱ electric acupuncture apparatus was provided by Shanghai Medical Equipment High-techno Company. METHODS： The experiment was performed at the Laboratory of Anatomy, Sun Yat-Sen University, from February to July 2007. All experimental animals were randomly divided into the following groups： normal group （n = 6）, sham operation group （n = 18）, model group （n = 18）, and electroacupuncture group （n = 18）. Middle cerebral artery occlusion （MCAO） was performed in the model group and electroacupuncture group. Zea Longa＇s grading standard was used to assess neurological impairment after reperfusion; animals whose grades were between l and 4 were included in this study. The normal control group was not exposed to MCAO. In sham operation animals, the right common carotid artery （CCA） was isolated, and the external carotid artery （ECA） was damaged, but no embolism was induced. The electroacupuncture group was given acupuncture on the second day after surgery. The acupoint locations were chosen according to Experimental Acupuncture （People＇s Publishing House; 1997; First Edition）. The Chengjiang, Qihai, and Guanyuan acupoints were labeled and connected to a G6805 electroacupuncture apparatus with sparse-dense waves （sparse waves were 30 Hz, dense waves were 100 Hz）, with a frequency of 6-15 V. The duration was 20 minutes. Two days after surgery, the model and sham operation groups were placed with their backs on the operating table, but they received no acupuncture. However, the normal group received acupuncture. The experimental animals under anesthesia were sacrificed on days 7, 14, and 28 post-surgery. Western blot analysis was used to measure expression of extracellular signal-regulated kinases 1/2 in the inferior region of the lateral cerebral ventricle wall. Expression was measured in the normal group at time points corresponding to the sham operation group. MAIN OUTCOME MEASURES： Expression of extracellular signal-regulated kinases 1/2 in the inferior region of the lateral cerebral ventricle wall at different time points after intervention. RESULTS： All 60 rats were included in the final analysis, without any loss. Seven days after MCAO, there was no significant difference in extracellular signal-regulated kinases 1/2 expression in the electroacupuncture group compared to the model group （P 〉 0.05）. However, extracellular signal-regulated kinases 1/2 expression significantly increased in the model group at 14 and 28 days after treatment （P 〈 0.05）. CONCLUSION： Electroacupuncture at the Ren channel can enhance extracellular signal-regulated kinasesl/2 expression in the inferior region of the lateral cerebral ventricle wall of rats with focal cerebral ischemia. However, this effect is not apparent until 14 days after electroacupuncture intervention.展开更多
文摘Background: The signal-to-noise ratio (SNR) is recognized as an index of measurements reproducibility. We derive the maximum likelihood estimators of SNR and discuss confidence interval construction on the difference between two correlated SNRs when the readings are from bivariate normal and bivariate lognormal distribution. We use the Pearsons system of curves to approximate the difference between the two estimates and use the bootstrap methods to validate the approximate distributions of the statistic of interest. Methods: The paper uses the delta method to find the first four central moments, and hence the skewness and kurtosis which are important in the determination of the parameters of the Pearsons distribution. Results: The approach is illustrated in two examples;one from veterinary microbiology and food safety data and the other on data from clinical medicine. We derived the four central moments of the target statistics, together with the bootstrap method to evaluate the parameters of Pearsons distribution. The fitted Pearsons curves of Types I and II were recommended based on the available data. The R-codes are also provided to be readily used by the readers.
文摘YTB block in Sichuan basin is a favorable area to exploit oil and gas in shallow tight rock. 3D seismic project of this zone has two characteristics. Firstly, it has high requirements for the tolerance rate of the construction process and the acquisition of high signal-to-noise ratio seismic data;Second, there are widely obstacles and noises that lead to difficult acquisition construction organization. In acquisition practice, high signal-to-noise ratio seismic data was obtained by reasonable design of construction scheme, optimization of excitation parameters, improvement of receiving conditions and optimization of obstacle crossing observation system. .
基金Supported by National Natural Science Foundation of China (No.81100649)
文摘AIMTo investigate whether the abnormal differentiation of the pterygium epithelium is related to the extracellular signal-regulated kinase (ERK) signaling pathway in vitro.METHODSThe expression levels of phosphorylated ERK (P-ERK), keratin family members including K19 and K10 and the ocular master control gene Pax-6 were measured in 16 surgically excised pterygium tissues and 12 eye bank conjunctiva. In colony-forming cell assays, the differences in clone morphology and in K10, K19, P-ERK and Pax-6 expression between the head and body were investigated. When cocultured with the ERK signaling pathway inhibitor PD98059, the changes in clone morphology, colony-forming efficiency, differentiated marker K10, K19 and Pax-6 expression and P-ERK protein expression level were examined by immunoreactivity and Western blot analysis.RESULTSThe expression of K19 and Pax-6 decreased in the pterygium, especially in the head. No staining of K10 was found in the normal conjunctiva epithelium, but it was found to be expressed in the superficial cells in the head of the pterygium. Characteristic upregulation of P-ERK was observed by immunohistochemistry. The clone from the head with more differentiated cells in the center expressed more K10, and the clone from the body expressed more K19. The P-ERK protein level increased in the pterygium epithelium compared with conjunctiva and decreased when cocultured with PD98059. The same medium with the ERK inhibitor PD98059 was more effective in promoting clonal growth than conventional medium with 3T3 murine feeder layers. It was observed that the epithelium clone co-cultured with the inhibitor had decreased K10 expression and increased K19 and Pax-6 expression.CONCLUSIONWe suggest ERK signaling pathway activation might play a role in the pterygium epithelium abnormal differentiation.
文摘BACKGROUND: The pathogenesis of hepatic fibrosis and cirrhosis is still not fully understood. The extracellular signal-regulated kinase (ERK) pathway is involved in the regulation of cell proliferation and differentiation. The aim of this study was to investigate the effects of PD98059, a specific inhibitor of ERK, on the cell cycle, cell proliferation, secretion of type I collagen and expression of cyclin D1 mRNA, CDK4 mRNA and transforming growth factor-beta 1 (TGF-beta 1) mRNA in rat hepatic stellate cells (HSCs) stimulated by acetaldehyde. METHODS: Rat HSCs stimulated by acetaldehyde were incubated with PD98059 at different concentrations. The cell cycle was analysed by flow cytometry. Cell proliferation was assessed by the methyl thiazolyl tetrazolium colorimetric assay. The mRNA expression of cyclin D1, CDK4 and TGF-beta 1 was examined using the reverse transcriptase-polymerase chain reaction. Type I collagen in the culture medium was detected by enzyme-linked immunosorbent assay. RESULTS: 20, 50 and 100 mu mol/L PD98059 significantly inhibited the proliferation and provoked a G0/G1-phase arrest of acetaldehyde-induced HSCs in a dose-dependent manner. The secretion of type I collagen and the expression of cyclin D1, CDK4 and TGF-beta 1 mRNA in acetaldehyde-induced HSCs were markedly inhibited by 50 and 100 mu mol/L PD98059, respectively. CONCLUSIONS: The ERK pathway regulates the cell proliferation, secretion of type I collagen and the expression of TGF-beta 1 mRNA in rat HSCs stimulated by acetaldehyde, which is likely related to its regulative effect on the cell cycle.
基金supported by Soft Science Foundation of Yongchuan District of Chongqing City(Grant No.YCSTC.2011BE5015)
文摘Objective:To explore the protective effect and its molecular mechanism of apoptosis signalregulating kinase 1(ASK1) inhibitor(GS-459679) on acetaminophen-induced liver injury in mice.Methods:The model of liver injury was established by administration of acetaminophen(APAP)(300 mg/kg,i.p.) on C57BL/6 mice.Forty-eight male C57BL/6 mice were randomly divided into four groups,consisting of control group,GS group(GS-459679,30 mg/kg,i.p.),APAPinduced group,and GS combined with APAP-induced group.For GS combined with APAPinduced group,mice were treated with GS 30 min prior to administration of APAP.After mice were euthanized at 6 h or 12 h.respectively,serum levels of alanine aminotransferase(ALT) and aspartate aminotransferase(AST) were analyzed,and mRNA levels of TNF- α,IL-6 and IL-1βwere tested.The activity of glutathione(GSH),oxidized GSH(GSSG) and malondialdehyde were quantified.In addition,ASK1,P-ASK1,JNK and P-JNK protein levels were tested in all groups.Results:The ASK1 and P-ASK1 levels were up-regulated in APAP-induced group.Compared to the control group,serum levels of ALT and AST.and mRNA levels of TNF- a,IL-6 and IL-1(3were increased in APAP-induced group.Meanwhile,the levels of MAD and GSSG.and the ratio of GSSG/GSH were higher and the JNK was activatedin APAP-induced group compared with that in control group.However,compared to APAP-induced group,GS combined with APAP-induced group displayed a decrease of protein expression levels of ASK 1,P-ASKI and P-JNK,a reduction of serum levels of ALT and AST,a decrease in TNF- a.IL-6 and IL-1(3 mRNA levels,and a low ration of GSSG/GSH.Conclusions:GS-459679 treatment effectively down-regulates ASK1 and P-ASK 1 expression.Addition of GS-459679 decreases the generation of liver metabolites and inflammatory factors,reduces oxidative stress reaction,inhibits JNK activation,and then protects the responsiveness to APAP-induced liver injury.
基金Acknowledgment This study was supported by the National Natural Science Foundation of China （30230190）, the National Basic Science Research and Development Project （973） （G1999055901） and the Chinese Academy of Sciences （CAS） Knowledge Innovation Program （KSCX-2-SW-201）.
文摘Aim： To assess the spatiotemporal changes in the expression of extracellular signal-regulated kinases 1 and 2 （ERK1/ 2）, c-Jun N-terminal kinases （JNK） and p38 mitogen-activated protein kinases （MAPK） in response to heat stress in the cryptorchid testis, and to investigate a possible relation to Sertoli cell dedifferentiation. Methods： Immunohistochemistry and western blot were used to examine the expression and activation of ERK1/2, p38 and JNK in the cryptorchid testis at various stages after experimental cryptorchidism. Results： The abdominal temperature did not obviously change the total ERK1/2 expression but significantly activated phospho-ERK1/2 in the Sertoli cells of the cryptorchid testis. Heat stress increased total JNK expression in the Sertoli cells of the cryptorchid testis but did not activate phospho-JNK. Neither total p38 nor phospho-p38 was induced by heat stress in the Sertoli cells of the cryptorchid testis. Changes in the spatiotemporal expression of cytokeratin 18 （CK18）, a marker of immature or undifferentiated Sertoli cells, were induced in the cryptorchid testis in a pattern similar to the activation of ERK1/2. Condusion： The activation of ERK1/2 in the testis may be related to dedifferentiation of Sertoli cells under heat stress induced by experimental cryptorchidism.
基金the National Natural Science Foundation of China,No.30371808the Natural Science Foundation of Guangdong Province,No.5009688
文摘BACKGROUND： Studies have shown that electro-acupuncture at the Ren meridian could improve proliferation of subventricular zone neural stem cells in cerebral-ischemic rats. However, there are few reports on the influence of electro-acupuncture at the Du meridian on neural stem cell proliferation. OBJECTIVE： To observe the influence of electro-acupuncture at Ren and Du meridians on neural stem cell proliferation in the subventricular zone and altered signal transduction in cerebral ischemia rats. DESIGN, TIME AND SETTING： A randomized, controlled, animal experiment was performed at the Laboratory of Human Anatomy, Medical College of Sun Yat-sen University from May 2006 to February 2008. MATERIALS： Mouse anti-rat bromodeoxyuridine （BrdU） monoclonal antibody was provided by Sigma, USA; mouse anti-rat nestin monoclonal antibody and extracellular signal-regulated protein kinase （ERK） specific inhibitor PD98059 were provided by Calbiochem, Germany; acupuncture needle was provided by Suzhou Acupuncture Supplies, China. METHODS： A total of 126 rats were randomly assigned to four groups： model （n = 36）, Du meridian （n = 36）, Ren/Du meridian （n = 36）, and Ren/Du meridian ＋ PD98059 （n = 18）. Rats in the Ren/Du meridian ＋ PD98059 group were observed on days 7 （n = 6） and 14 （n = 12） after cerebral ischemia injury. Rats in the model, Du meridian, and Ren/Du meridian groups were observed on days 7, 14, and 28 after cerebral ischemia injury, with 12 rats per group at each time point. Thread occlusion was used to establish middle cerebral artery occlusion models. Electro-acupuncture was performed at Renzhong （DU 26） and Baihui （DU 20） acupoints in the Du meridian group, as well as Chengjiang （RN 24）, Guanyuan （RN 4）, Renzhong, and Baihuiacupoints in the Ren/Du meridian and Ren/Du meridian ＋ PD98059 groups 2 days after model establishment. In addition, electro-acupuncture stimulation with disperse-dense waves was performed, with 30 Hz disperse wave, 100 Hz dense wave, and 5 V intensity for 20 minutes. Rats in the Ren/Du meridian ＋ PD98059 group were treated with 0.2 pg PD98059 injection into the subventricular zone, 2 pL per rat. Rats in the model group were not treated with electro-acupuncture. MAIN OUTCOME MEASURES： BrdU/nestin immunofluorescent staining was used to detect proliferating neural stem cells in the subventricular zone of cerebral ischemia rats; Western blot was used to determine phosphorylated ERK1 and 2 （pERK1/2） expression in the subventricular zone. RESULTS： On days 14 and 28 after cerebral ischemia, there were significantly more BrdU-positive and BrdU/nestin-positive cells in the Ren/Du meridian group compared with the Du meridian group （P 〈 0.05）. PD98059 decreased the number of BrdU-positive and BrdU/nestin-positive cells induced by electro-acupuncture at the/：ten and Du meridians （P 〈 0.05）. On days 7, 14, and 28 after treatment, pERK1/2 expression was significantly greater in the Du meridian and Ren/Du meridian groups compared with the model group （P 〈 0.05）. The promoting effect of electro-acupuncture at Ren and Du meridians on ERK1/2 phosphorylation was superior to electro-acupuncture at the Du meridian alone on day 14 after model induction （P 〈 0.05）. However, PD98059 completely abolished the promoting effect of electro-acupuncture at Ren/Du meridians on pERK1/2 expression （P 〈 0.05）. CONCLUSION： Electro-acupuncture at Ren and Du meridians increased proliferation of subventricular zone neural stem cells, which was related to activation of the ERK pathway in a rat model of cerebral ischemia injury.
基金supported by the Hebei Province Natural Science Program,No.H2012401007a grant from the foundation Key Project of Hebei Province Education Ministry,No.ZD2010106
文摘Activation of extracellular signal-regulated kinase 1/2 has been demonstrated in acute brain ischemia. We hypothesized that activated extracellular signal-regulated kinase 1/2 can protect hippocampal neurons from injury in a diabetic model after cerebral ischemia/reperfusion. In this study, transient whole-brain ischemia was induced by four-vessel occlusion in normal and diabetic rats, and extracellular signal-regulated kinase 1/2 inhibitor （U0126） was administered into diabetic rats 30 minutes before ischemia as a pretreatment. Results showed that the number of surviving neurons in the hippocampal CA1 region was reduced, extracellular signal-regulated kinase 1/2 phosphorylation and KuT0 activity were decreased, and pro-apoptotic Bax expression was upregulated after intervention using U0126. These findings demonstrate that inhibition of extracellular signal-regulated kinase 1/2 activity aggravated neuronal loss in the hippocampus in a diabetic rat after cerebral ischemia/reperfusion, further decreased DNA repairing ability and ac- celerated apoptosis in hippocampal neurons. Extracellular signal-regulated kinase 1/2 activation plays a neuroprotective role in hippocampal neurons in a diabetic rat after cerebral ischemia/ reperfusion.
文摘Aim： To determine the mechanisms of glucocorticoids in inhibiting advanced prostate cancer growth. Methods： The cell proliferation and cell cycle of prostate cancer DU145 cells following dexamethasone treatment were determined by proliferation assay and fluorescence-activated cell sorter. Western blot analysis was carried out to evaluate the effects of dexamethasone on phosphorylation of extracellular signal-regulated kinase （ERK）1/2 and expression of cyclin D1 in DU145 cells with or without glucocorticoid receptor （GR） antagonist RU486. Reverse transcription- polymerase chain reaction verified the expression of GR mRNA in DU145 cells. Results： Dexamethasone significantly inhibited DU 145 cell proliferation at the G0/G1 phase. Westem blot analysis showed a dramatic reduction of ERK1/2 activity and cyclin D1 expression in dexamethasone-treated cells. The decreased phosphorylation of ERK1/2 in dexamethasone-treated cells was attenuated by GR blockade. Additionally, the effects of dexamethasone in inhibiting cyclin D1 expression were altered by GR blockade. Conclusion： Dexamethasone suppresses DU145 cell proliferation and cell cycle, and the underlying mechanisms are through the inhibition of phosphorylation of ERK1/2 and cyclin D1 expression. The inhibition of ERK1/2 phosphorylation and cyclin D1 expression is attenuated by GR blockade, suggesting that GR regulates ERK1/2 and cyclin D1 pathways. These observations suggest that dexamethasone has a potential clinical application in prostate cancer therapy.
基金Science and Technology Development Project Program of Jilin Province,China,No. 200505195
文摘BACKGROUND： Previous studies have shown that extracellular signal-regulated kinase 1/2 （ERK1/2） and nitric oxide activation play a pivotal role in central sensitization and long-term neuronal plasticity induced by noxious stimulation. However, their effects on compressive neuralgia formation and maintenance remain poorly understood.OBJECTIVE： To investigate effects of the specific inhibitor of ERK1/2 signal pathway U0126 on neuronal nitric oxide synthase （nNOS） expression in the dorsal horn of the spinal cord in a compressive neuralgia rat model.DESIGN, TIME AND SETTING： A randomized, controlled experiment was performed at the Institute of Otolaryngology, Head and Neck Surgery, First Hospital of Jilin University from July 2008 to March 2009.MATERIALS： U0126 （Bio-Mol, USA） was used in this study.METHODS： A total of 84 rats were randomly assigned to two groups. In the first part of the experiment, 24 rats were used for behavioral testing, and they were randomly assigned to three sub-groups （n =8）： U0126, dimethyl sulfoxide （DMSO） and model control. In the second part of the experiment, 60 rats were used for immunofluorescence and Western blot analysis, and they were randomly assigned to six sub-groups （n = 10）： sham surgery, model control, U0126 post-injection at 0.5, 2, 12 and 24 hours. Neuropathic pain was produced by chronic compression to the dorsal root ganglion in rats from each sub-group. Rats in the U0126 group were administered a 5-ug U0126 intrathecal injection, and rats in the DMSO group were administered a 10-μL 5% DMSO intrathecal injection.MAIN OUTCOME MEASURES： Changes in mechanical and thermal hyperalgesia were observed using von Frey filaments and thermalqia stimular. Thermal and mechanical hyperalgesia were stimulated at different time points following intrathecal injection of U0126. nNOS activation and expression in the spinal cord dorsal horn were determined by immunofluorescence and Western blot analysis.RESULTS： Intrathecal injection of U0126 significantly attenuated chronic compression of dorsal root ganglion-induced mechanical and thermal hyperalgesia. Immunofluorescence staining results demonstrated that, compared to the sham surgery group, the number of nNOS-positive neurons was significantly increased in the injured spinal dorsal horn in the model control group （P〈0.01）. However, compared to the model control group, there were significantly decreasing numbers of nNOS-positive neurons in the U0126 post-injection groups at 0.5-hour, 2-hour, and 12-hour （P〈0.05）. Western blot analysis revealed similar results. CONCLUSION： Decreased activity in the ERK signal pathway resulted in down regulated nNOS expression in the dorsal horn of the spinal cord. These results suggested that ERK is involved in nitric oxide reaction to neuropathic pain.
基金supported by the National Natural Science Foundation of China,No.81271286 to YUAN Fang and No.81228009 to YANG Shao Hua
文摘Objective To investigate the role of extracellular signal-regulated kinase1/2（ERK1/2） pathway in the regulation of aquaporin 4（AQP4） expression in cultured astrocytes after scratch-injury. Methods The scratch-injury model was produced in cultured astrocytes of rat by a 10-μL plastic pipette tip. The morphological changes of astrocytes and lactate dehydrogenase（LDH） leakages were observed to assess the degree of scratch-injury. AQP4 expression was detected by immunofluorescence staining and Western blot, and phosphorylated-ERK1/2（p-ERK1/2） expression was determined by Western blot. To explore the effect of ERK1/2 pathway on AQP4 expression in scratch-injured astrocytes, 10 μmol/L U0126（ERK1/2 inhibitor） was incubated in the medium at 30 min before the scratch-injury in some groups. Results Increases in LDH leakage were observed at 1, 12, and 24 h after scratch-injury, and AQP4 expression was reduced simultaneously. Decrease in AQP4 expression was associated with a significant increase in ERK1/2 activation. Furthermore, pretreatment with U0126 blocked both ERK1/2 activation and decrease in AQP4 expression induced by scratch-injury. Conclusion These results indicate that ERK1/2 pathway down-regulates AQP4 expression in scratch-injured astrocytes, and ERK1/2 pathway might be a novel therapeutic target in reversing the effects of astrocytes that contribute to traumatic brain edema.
基金the National Natural Science Foundation of China, No. 30870844 the National High Technology Research and Development Program of China (863 Program), No. 2006AA02Z4Z4the New Century Excellent Talents in University, Ministry of Education, No. NECT-05-0831
文摘BACKGROUND： Very few studies have addressed neuronal injury in cerebral vasospasm and subarachnoid hemorrhage （SAH）, and the role of neurotransmitters in the regulation of extracellular signal-regulated kinase 1/2 （ERK1/2） expression following SAH. OBJECTIVE： To analyze neurotransmitter regulation of ERK1/2 expression through the use of signal transduction, and to investigate cerebral injury mechanisms following SAH. DESIGN, TIME AND SETTING： A completely randomized grouping and controlled animal experiment was performed at the Experimental Center of Medical College of Xi＇an Jiaotong University from March to December 2008. MATERIALS： Extraceliular signal-regulated ERK1/2 polyclonal antibody and streptavidin-peroxidase method kits were purchased from Beijing Biosynthesis Biotechnology, China; DAB kit was purchased from Zhongshan Golden Bridge Biotechnology, China; TUNEL kit was purchased from Promega, USA. METHODS： A total of 114 male, Sprague Dawley rats, aged 55-63 days old, were randomly assigned to five groups： SAH （n = 30）, saline control （n = 30）, puncture control （n = 30）, normal control （n = 6）, and neurotransmitter-treated （n = 18）. The SAH model was established by twice injecting blood through the cisterna magna. The neurotransmitters-treated group was subdivided into three groups according to drugs injected into the lateral cerebral ventricle： acetylcholine chloride, norepinephrine, and saline, with six animals in each group. MAIN OUTCOME MEASURES： Rats from the SAH, saline control, and puncture control groups were respectively sacrificed at 6, 12, and 24 hours, as well as 3 and 5 days, with six rats at each time point. The normal control group rats were sacrificed at 6 hours, and the neurotransmitter group rats were sacrificed 3 days following neurotransmitter injection. Morphological cellular changes were observed by hematoxylin and eosin staining. Immunohistochemical SP method was used to detect expression of ERK1/2 in the cortex, and cortical apoptosis was detected using the TUNEL method. RESULTS： Neural tissue edema, apoptosis, and necrosis occurred in the cortex of the SAH group. ERK1/2-positive cells were first observed at 6 hours, peaked at 12 hours following SAH in the cortex, and gradually decreased thereafter. Cellular apoptosis was observed in the cortex at 6 hours and peaked at 24 hours following SAH. ERK1/2 distribution in the brain overlapped apoptotic cells to a great degree. The number of ERK1/2-positive and apoptotic cells was significantly greater in the SAH group compared with the three control groups （P 〈 0.05）. Compared to the number of ERK1/2-positive cells in the saline-treated group, acetylcholine chloride treatment resulted in decreased ERK1/2 expression and apoptosis （P 〈 0.05）. Norepinephrine resulted in increased ERK1/2 expression, but there was no significance in apoptosis compared to the saline-treated group （P 〉 0.05）. CONCLUSION： Apoptosis was observed early in the rat cortex following SAH. In addition, ERK1/2 was expressed earlier than apoptosis. Acetylcholine chloride treatment resulted in decreased numbers of apoptotic cells following SAH, possibly by down-regulating ERK1/2 expression.
文摘The results of comparative theoretical analyzes of the behavior of internal low-frequency noises, signal-to-noise ratio and sensitivity to DNA molecules for EIS and ISFET based nanosize biosensors are presented. It is shown that EIS biosensor is more sensitive to the presence of DNA molecules in aqueous solution than ISFET sensor. Internal electrical noises level decreases with the increase of concentration of DNA molecules in aqueous solution. In the frequency range 10−3 - 103 Hz noises level for EIS sensor about in three orders is higher than for ISFET sensor. In the other hand, signal-to-noise ratio for capacitive EIS biosensor is much higher than for ISFET sensor.
基金supported by the National Natural Science Foundation of China (Grant Nos. 11074307 and 10774192)the Opening Research Foundation of State Key Laboratory of Precision Spectroscopy,ECNU
文摘Factors influencing the signal-to-noise ratio （SNR） of lensless ghost interference with thermal incoherent light are investigated. Our result shows that the SNR of lensless ghost interference is related to the transverse length of the object, the position of the object in the imaging system and the transverse size of the light source. Furthermore, the effects of these factors on the SNR are discussed in detail by numerical simulations.
基金National Natural Science Foundation under Grant No.51161120359Ministry of Education under Grant No.20112302110050Special Fund for Earthquake Scientific Research in the Public Interest under Grant No.201308003
文摘This article extends a signal-based approach formerly proposed by the authors, which utilizes the fractal dimension of time frequency feature （FDTFF） of displacements, for earthquake damage detection of moment resist frame （MRF）, and validates the approach with shaking table tests. The time frequency feature （TFF） of the relative displacement at measured story is defined as the real part of the coefficients of the analytical wavelet transform. The fractal dimension （FD） is to quantify the TFF within the fundamental frequency band using box counting method. It is verified that the FDTFFs at all stories of the linear MRF are identical with the help of static condensation method and modal superposition principle, while the FDTFFs at the stories with localized nonlinearities due to damage will be different from those at the stories without nonlinearities using the reverse-path methodology. By comparing the FDTFFs of displacements at measured stories in a structure, the damage-induced nonlinearity of the structure under strong ground motion can be detected and localized. Finally shaking table experiments on a 1：8 scale sixteen-story three-bay steel MRF with added frictional dampers, which generate local nonlinearities, are conducted to validate the approach.
基金supported by the National Natural Science Foundation of China,No.81273843,81674073a grant from the National Key Basic Research Program of China(973 Program)+1 种基金No.2015CB554501the Project Fund of Shanghai Municipal Commission of Health and Family Planning of China,No.20144Y0153,2017BR047
文摘Herb-partitioned moxibustion can effectively mitigate visceral pain, a major symptom in inflammatory bowel disease, but the analgesic lnechanism is still unclear. Moreover, extracellular signal-regulated kinase, substance P, and neurokinin-1 are involved in formation of central hyperalgesia. Thus, we postulated that the analgesic effect of herb-partitioned moxibustion may be associated with these factors. Accordingly, in this study, we established an inflammatory bowel disease visceral pain model in rat by enema with a mixed solution of 5% trinitrobenzenesulfonic acid and 50% ethanol. Bilateral Tianshu （ST25） and Qihai （CV6） points were selected for herb-partitioned moxi- bustion. Our results showed that herb-partitioned moxibustion improved visceral pain and down-regulated extracellular signal-regulated kinase, substance P, and neurokinin-1 protein and mRNA expression in dorsal root ganglia. These results indicate that down-regulation of extracellular signal-regulated kinase, substance E and neurokinin-1 protein and mRNA may be a central mechanism for the analgesic effect of herb-partitioned moxibustion.
基金Project supported by the National Research and Development Project for Key Scientific Instruments(Grant No.CZBZDYZ20140002)the National Natural Science Foundation of China(Grant Nos.11535015,11305173,and 11375225)+2 种基金the project supported by Institute of High Energy Physics,Chinese Academy of Sciences(Grant No.Y4545320Y2)the Fundamental Research Funds for the Central Universities(Grant No.WK2310000065)Wali Faiz,acknowledges and wishes to thank the Chinese Academy of Sciences and The World Academy of Sciences(CAS-TWAS)President’s Fellowship Program for generous financial support
文摘Grating-based x-ray phase contrast imaging has the potential to be applied in future medical applications as it is compatible with both laboratory and synchrotron source. However, information retrieval methods are important because acquisition speed, scanning mode, image quality, and radiation dose depend on them. Phase-stepping （PS） is a widely used method to retrieve information, while angular signal radiography （ASR） is a newly established method. In this manuscript, signal-to-noise ratios （SNRs） of ASR are compared with that of PS. Numerical experiments are performed to validate theoretical results. SNRs comparison shows that for refraction and scattering images ASR has higher SNR than PS method, while for absorption image both methods have same SNR. Therefore, our conclusions would have guideline in future preclinical and clinical applications.
基金Project supported by the National Key Research and Development Program of China(Grant No.2017YFA0304203)the Chang Jiang Scholars and Innovative Research Team in the University of the Ministry of Education of China(Grant No.IRT13076)+2 种基金the National Natural Science Foundation of China(Grant Nos.91436108,61378014,61675121,61705123,and 61722507)the Fund for Shanxi“1331 Project”Key Subjects Construction,Chinathe Foundation for Outstanding Young Scholars of Shanxi Province,China(Grant No.201601D021001)
文摘We report a method of high-sensitively detecting the weak signal in photoassociation （PA） spectra of ultracold NaCs molecules by phase sensitive-demodulated trap-loss spectra of Na atoms from a photomultiplier tube. We find that the signal-to-noise ratio （SNR） of the PA spectra is strongly dependent on the integration time and the sensitivity of the lock-in amplifier, and our results show reasonable agreement with the theoretical analyses of the SNR with the demodulation parameters. Meanwhile, we investigate the effect of the interaction time of the PA laser with the colliding Na-Cs atom pairs on the SNR of the PA spectra. The atom loss rate is dependent on both the PA-induced atom loss and the loading of the MOT. The high-sensitive detection of the excited ultracold NaCs molecules lays a solid foundation for further study of the formation and application of ultracold NaCs molecules.
文摘Objective To investigate whether extracellular signal-regulated kinase (ERK1/2) was involved in changes of vascular smooth muscle cell (VSMC) under hypertension.Methods Two-kidney one clip Wistar hypertensive rats (WHR) were sacrificed and their right kidneys were harvested 4 weeks after surgery.The spontaneously hypertensive rats (SHR) were divided into 4, 8, and 16 weeks old groups (SHR4w, SHR8w, and SHR16w), respectively.The control group were sham operated age-matched Wistar rats.Immunohistochemical technique and Western blotting were applied to study ERK1/2 protein expression in VSMC of the renal vascular trees in WHR, SHR, and control rats.Results Blood pressure in two-kidney one clip WHR obviously increased at one week after surgery, and reached to 198.00±33.00 mm Hg at the end of experiment, significantly higher than that in the control rats (P<0.01).Blood pressure in SHR4w (108.00±11.25 mm Hg) was similar to that in the controls.However, it rose to 122.25±21.75 mm Hg in SHR8w, and even up to 201.75±18.00 mm Hg in SHR16w, which were significantly higher than that of both the SHR4w and the controls (P<0.01).The rate and degree of glomerular fibrosis in WHR were significantly higher than controls (P<0.05).Hyaline degeneration of the afferent arterioles was found in WHR.In contrast, either fibrosis of glomerulus or hyaline degeneration of the arterioles or protein casts was not observed in SHR4w, SHR8w, and SHR16w.Immunohistochemical staining results showed expression of ERK1 was similar to that of ERK2.The positive rates of ERK2 staining in VSMC of afferent arterioles, interlobular, interlobar, and arcuate arteries in two-kidney one clip WHR were significantly higher (7.09%±1.75%, 14.57%±4.58%, 29.44%±7.35%, and 13.63%±3.85%, respectively) than that of the controls(P<0.01).The positive rates of ERK2 staining in VSMC at afferent arterioles, interlobular, interlobar, and arcuate arteries in SHR16w were significantly higher (12.09%±1.40%, 24.17%±6.92%, 32.44%±4.05%, and 18.61%±3.35%, respectively) than that of the controls (P<0.01), too.The expression of ERK1/2 protein of kidney in WHR and SHR16w was significantly higher than that in the controls by Western blotting assay (P<0.01).Conclusion Extracellular signal transduction system are highly expressed in kidney VSMC of two-kidney one clip WHR and SHR.Phospho-ERK1/2 may play an important role in VSMC hypertrophy and hyperplasia under hypertension.
基金the National Natural Science Foundation of China, No. 30371808Post-doctor's Project of Guangzhou University of Traditional Chinese Medicine, No.106B3YH0411
文摘BACKGROUND： The onset of focal cerebral ischemia activates extracellular signal-regulated kinases 1 and 2, regulates cell cycle, promotes cell proliferation and differentiation, and affects the normal stage and function of brain cells. OBJECTIVE： To observe the effects of electroacupuncture at the Ren channel on extracellular signal-regulated kinases 1/2 expression in the lateral cerebral ventricle wall of rats with focal cerebral ischemia. The effects were analyzed at different time points after intervention. DESIGN： Randomized controlled study. SETTING： Department of Anatomy, Sun Yat-Sen University. MATERIALS： A total of 60 healthy adult male Wistar rats weighing （250±10） g were provided by the Experimental Animal Center, Medical College of Sun Yat-Sen University. The animal experiment was conducted with confirmed consent by the local ethics committee. The GB6805-Ⅱ electric acupuncture apparatus was provided by Shanghai Medical Equipment High-techno Company. METHODS： The experiment was performed at the Laboratory of Anatomy, Sun Yat-Sen University, from February to July 2007. All experimental animals were randomly divided into the following groups： normal group （n = 6）, sham operation group （n = 18）, model group （n = 18）, and electroacupuncture group （n = 18）. Middle cerebral artery occlusion （MCAO） was performed in the model group and electroacupuncture group. Zea Longa＇s grading standard was used to assess neurological impairment after reperfusion; animals whose grades were between l and 4 were included in this study. The normal control group was not exposed to MCAO. In sham operation animals, the right common carotid artery （CCA） was isolated, and the external carotid artery （ECA） was damaged, but no embolism was induced. The electroacupuncture group was given acupuncture on the second day after surgery. The acupoint locations were chosen according to Experimental Acupuncture （People＇s Publishing House; 1997; First Edition）. The Chengjiang, Qihai, and Guanyuan acupoints were labeled and connected to a G6805 electroacupuncture apparatus with sparse-dense waves （sparse waves were 30 Hz, dense waves were 100 Hz）, with a frequency of 6-15 V. The duration was 20 minutes. Two days after surgery, the model and sham operation groups were placed with their backs on the operating table, but they received no acupuncture. However, the normal group received acupuncture. The experimental animals under anesthesia were sacrificed on days 7, 14, and 28 post-surgery. Western blot analysis was used to measure expression of extracellular signal-regulated kinases 1/2 in the inferior region of the lateral cerebral ventricle wall. Expression was measured in the normal group at time points corresponding to the sham operation group. MAIN OUTCOME MEASURES： Expression of extracellular signal-regulated kinases 1/2 in the inferior region of the lateral cerebral ventricle wall at different time points after intervention. RESULTS： All 60 rats were included in the final analysis, without any loss. Seven days after MCAO, there was no significant difference in extracellular signal-regulated kinases 1/2 expression in the electroacupuncture group compared to the model group （P 〉 0.05）. However, extracellular signal-regulated kinases 1/2 expression significantly increased in the model group at 14 and 28 days after treatment （P 〈 0.05）. CONCLUSION： Electroacupuncture at the Ren channel can enhance extracellular signal-regulated kinasesl/2 expression in the inferior region of the lateral cerebral ventricle wall of rats with focal cerebral ischemia. However, this effect is not apparent until 14 days after electroacupuncture intervention.
