ABSTRACT
In order to explore the mechanism of gefitinib-acquired resistance in lung cancer, a new biomarker has been developed for early clinical diagnosis and intervention; human NSCLC (Non-Small Cell Lung Cancer) cell lines H292 (denoted as H292S) and PC9 (denoted as PC9S) were used to establish gefitinib-resistant NSCLC cell lines H292 and PC9 models. CCK-8 (Cell Counting Kit-8) method was used to test the drug resistance of the cells. circRNAs (circular RNAs) that were differentially expressed before and after resistance were screened by RNA sequencing technology. The effects of circSETD3 overexpression and interference on the sensitivity of gefitinib was observed to analyze the nuclear localization of circSETD3 and verify the interaction between circSETD3-miR-520h-ABCG2. The results showed that the most significant change in differential expression of human NSCLC cell lines before and after drug resistance was hsa_circ_0000567, that is, circSETD3, which is mainly present in the cytoplasm. In H292S and PC9S, compared with the negative control group, the cell proliferation ability of the overexpression group was significantly increased, and the apoptosis ability was significantly decreased. In H292R and PC9R, compared with the negative control group, the proliferation ability of the interference group was significantly decreased, and the apoptosis ability was significantly increased. Overexpression of circSETD3 to H292S and PC9S, the expression of ABCG2 increased significantly. Also, the expression of ABCG2 decreased significantly after transfection with miR-520h mimics. H292R and PC9R interfered with circSETD3, the expression of ABCG2 decreased significantly. Moreover, the expression of ABCG2 increased significantly after transfection with miR-520h inhibitor. In conclusion, circSETD3 can be used as a novel biomarker for lung cancer. It relieves miR-520h degradation of the transporter ABCG2 by down-regulating the miR-520h expression, causing gefitinib to be pumped out of the cell.
Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , MicroRNAs , Biomarkers , Carcinoma, Non-Small-Cell Lung/genetics , Cell Line, Tumor , Cell Proliferation , Drug Resistance, Neoplasm/genetics , Gefitinib/pharmacology , Humans , Lung Neoplasms/genetics , MicroRNAs/geneticsABSTRACT
We present the first experimental evidence supported by simulations of kinetic effects launched in the interpenetration layer between the laser-driven hohlraum plasma bubbles and the corona plasma of the compressed pellet at the Shenguang-III prototype laser facility. Solid plastic capsules were coated with carbon-deuterium layers; as the implosion neutron yield is quenched, DD fusion yield from the corona plasma provides a direct measure of the kinetic effects inside the hohlraum. An anomalous large energy spread of the DD neutron signal (â¼282 keV) and anomalous scaling of the neutron yield with the thickness of the carbon-deuterium layers cannot be explained by the hydrodynamic mechanisms. Instead, these results can be attributed to kinetic shocks that arise in the hohlraum-wall-ablator interpenetration region, which result in efficient acceleration of the deuterons (â¼28.8 J, 0.45% of the total input laser energy). These studies provide novel insight into the interactions and dynamics of a vacuum hohlraum and near-vacuum hohlraum.
ABSTRACT
Objective: To explore the characteristics of plasma Epstein-Barr virus (EBV) DNA in primary infection in pediatric cases. Methods: The laboratory and clinical data of 571 children diagnosed with EBV primary infection in Children's Hospital of Fudan University during September 1st, 2017 to September 30th, 2018 were retrospectively analyzed. According to the results of plasma EBV DNA, they were divided into positive group and negative group. According to the EBV DNA, they were devided into high plasma virol load group and low plasma virol load group. The Chi-square test, Wilcoxon rank sum test were used to compare the differences between groups. Results: Among the 571 children with EBV primary infection, 334 were males and 237 were females. The age of first diagnosis was 3.8 (2.2, 5.7) years. There were 255 cases in positive group and 316 cases in negative group. The percentage of cases with fever,hepatomegaly and (or) splenomegaly, elevated transaminase in the positive group were higher than those in the negative group (235 cases (92.2%) vs. 255 cases (80.7%), χ2=15.22, P<0.001; 169 cases (66.3%) vs. 85 cases (26.9%), χ2=96.80, P<0.001; and 144 cases (56.5%) vs. 120 cases (38.0%), χ2=18.27, P<0.001; respectively).In the positive group, 70 cases were followed up for 46 (27, 106) days, 68 cases (97.1%) turned negative within 28 days, with the exception of 2 cases (2.9%) developed chronic active EBV infection by follow-up revision.There were 218 cases in high plasma viral DNA copies group and 37 cases in low copies group. More cases presented with elevated transaminases in the high plasma viral DNA copies group than those in the low group (75.7% (28/37) vs. 56.0%(116/207), χ2=5.00, P=0.025).Both the positive rate of EBV DNA in peripheral blood leukocytes (84.2% (266/316) vs. 44.7% (255/571), χ2=76.26, P<0.001) and the copies of EBV DNA (7.0×107 (1.3×107, 3.0×108) vs. 3.1×106 (1.6×106, 6.1×106) copies /L, Z=15.23, P<0.001) were higher than that of plasma. Conclusions: In immunocompetent pediatric cases diagnosed as EBV primary infection, cases with positive plasma EBV DNA were prone to have fever, hepatomegaly and (or) splenomegaly, and elevated transaminase than those with negative plasma viral DNA. The plasma EBV DNA usually turns negative within 28 days after initial diagnosis.Most cases with high viral load in plasma showed elevated aminotransferase.
Subject(s)
DNA, Viral , Epstein-Barr Virus Infections , Female , Male , Humans , Child , Herpesvirus 4, Human , Hepatomegaly , Retrospective Studies , Splenomegaly , Fever , TransaminasesABSTRACT
Objective: To explore the risk factors and regularity of pediatric primary Epstein-Barr virus (EBV) infection accompanied with elevated transaminase. Methods: Clinical data of 399 children diagnosed as primary EBV infection in the outpatient department, Children's Hospital of Fudan University from September 2016 to October 2017 were analyzed retrospectively. Logistic regression analysis was performed to determine the potential correlations between elevated alanine transaminase (ALT) or aspartate transaminase (AST) and age, gender, course of fever and plasma EBV-DNA load. The cumulative rates of elevated transaminase recovery to nomal at different times were caculated. Results: Among 399 children diagnosed with primary EBV infection, there were 219 males and 180 females. The age was (4.2±2.7) years. Among all cases, 51.9% (207/399) had elevated transaminase. In patients who had elevated ALT, 74.5% (149/200), 21.0% (42/200) and 4.5% (9/200) had mild (40-160 U/L), moderate (160-400 U/L) and severe (>400 U/L) elevation of ALT, respectively. In patients who had elevated AST, 83.8% (155/185), 11.9% (22/185) and 4.3% (8/185) had mild (40-160 U/L), moderate (160-400 U/L) and severe (>400 U/L) elevation of AST, respectively. Only age was correlated with the occurrence of elevated transaminase (OR=1.13, 1.10, both P<0.05). A total of 167 repeated tests were ordered in patients with elevated ALT and/or AST, including 113 cases with elevated ALT and 104 cases with elevated AST. The time of ALT and AST returned to normal were (24±13) days and (25±18) days respectively. The cumulative rates for ALT returned to normal within 1, 1-<4, 4-<8 weeks and more than 8 weeks were 2.7% (3/113), 54.0% (61/113), 79.6% (90/113) and 81.4% (92/113) respectively, and were 1.9% (2/104), 48.1% (50/104), 71.2% (74/104) and 74.0% (77/104) for AST. Conclusions: Age is a risk factor for transaminase elevation associated with primary EBV infection in children. The transaminases returned to normal within 3 weeks in half of the cases, and within 8 weeks in most cases.
Subject(s)
Epstein-Barr Virus Infections , Herpesvirus 4, Human , Alanine Transaminase , Aspartate Aminotransferases , Child , Child, Preschool , Epstein-Barr Virus Infections/epidemiology , Female , Humans , Infant , Male , Retrospective Studies , Risk FactorsABSTRACT
We report the creation of solid-density aluminum plasma using free-electron laser (FEL) radiation at 13.5nm wavelength. Ultrashort pulses were focused on a bulk Al target, yielding an intensity of 2x10;{14}Wcm;{2} . The radiation emitted from the plasma was measured using an xuv spectrometer. Bremsstrahlung and line intensity ratios yield consistent electron temperatures of about 38eV , supported by radiation hydrodynamics simulations. This shows that xuv FELs heat up plasmas volumetrically and homogeneously at warm-dense-matter conditions, which are accurately characterized by xuv spectroscopy.
ABSTRACT
In this paper, the synthesis of core-shell particles (i.e. temperature-sensitive ferrite (TSF) covered with silica) has been investigated. At first, TSF (mean diameter of 10 nm) was prepared by the coprecipitation method in an alkaline solution. Then, silica coating on the TSF surface was carried out by the controlled hydrolysis and condensation of tetraethyl orthosilicate (TEOS). The core-shell particles were formed by a surface precipitation procedure using TSF nanoparticles as a core material. The particles of silica were formed and these particles were then absorbed on the TSF nanoparticles. The coating procedure was described and explained by calculating the potential energies of interaction between the TSF and SiO(2) nanoparticles, according to the Derjarguin-Landau-Verwey-Overbeck (DLVO) theory. The coating process was found to be influenced by the pH and concentration of the TEOS precursor. The thickness of the silica layer on TSF cores was observed by means of transmission electron microscopy (TEM). The results showed that the optimum thickness of the SiO(2) layer on TSF core particles was obtained at pH 7.5, while the TEOS concentration was kept at 9 mM.
ABSTRACT
Computed Tomography (CT) is a powerful method for non-destructive testing (NDT) and metrology awakes with expanding application fields. To improve the spatial resolution of high energy CT, a micro-spot gamma-ray source based on bremsstrahlung from a laser wakefield accelerator was developed. A high energy CT using the source was performed, which shows that the resolution of reconstruction can reach 100 µm at 10% contrast. Our proof-of-principle demonstration indicates that laser driven micro-spot gamma-ray sources provide a prospective way to increase the spatial resolution and toward to high energy micro CT. Due to the advantage in spatial resolution, laser based high energy CT represents a large potential for many NDT applications.
ABSTRACT
The following experiments were conducted to evaluate the genotoxic effects of GMA (glycidyl methacrylate) on mammalian and human cells. (1) Using the absorption spectrum shift method in vitro, we observed that the maximums of calf thymus DNA and GMA were shifted toward longer wavelengths (a change of more than 15 nm) and the absorbance decreased after incubation at room temperature for 15 min or more. The result indicates that binding of DNA and GMA had occurred. The binding force is strong, not affected by the addition of concentrated sodium chloride solution, and only slightly decreased by the addition of 8 M urea solution. Therefore the bond between DNA and GMA might be covalent. (2) In cell cultures, unscheduled DNA synthesis (UDS) in human and/or rat lymphocyte was induced and DNA semiconservative replication was inhibited by GMA at concentrations of less than 5.2 mM. (3) Sperm abnormality tests and assays of UDS in germ cells of male mice were conducted to study the in vivo genotoxicity of GMA. The results revealed that GMA could damage DNA, increase sperm abnormality frequency, and reduce the number of sperm cells.
Subject(s)
Epoxy Compounds/toxicity , Methacrylates/toxicity , Mutagens , Animals , Cell Survival/drug effects , Cells, Cultured , DNA/biosynthesis , DNA/metabolism , DNA Replication/drug effects , Humans , Lymphocytes/drug effects , Lymphocytes/metabolism , Male , Mice , Sperm Count/drug effects , Spermatozoa/drug effects , Spermatozoa/metabolismABSTRACT
OBJECTIVE: To determine the effect of climatic factors on immune markers in children with Dermatophagoides farinae induced asthma. METHODS: Serum concentrations of macrophage migration inhibitory factor (MIF), eosinophil cationic protein (ECP) and D. farinae-specific immunoglobulin E (DF-sIgE), together with peripheral blood eosinophil counts, were measured in children with D. farinae induced (n = 75) or non-D. farinae-induced asthma (n = 17), and in healthy controls (n = 30). Mean temperature and relative humidity in the month before enrolment were calculated from meteorological data. RESULTS: MIF, ECP and eosinophil counts were significantly higher in children with D. farinae-induced asthma than in controls, but comparable with non-D. farinae-induced asthma. Children with D. farinae-induced asthma in a low temperature (< 16 °C) or low relative humidity (< 70%) climate had significantly lower DF-sIgE, MIF, ECP and eosinophil counts than those in a high temperature or high humidity climate. DF-sIgE correlated positively with MIF, ECP and eosinophil count in D. farinae-induced asthma. CONCLUSIONS: Temperature and humidity influenced MIF, ECP, eosinophil count and DF-sIgE in D. farinae-induced asthma. Understanding this relationship may provide new strategies for asthma prevention and treatment.
Subject(s)
Antigens, Dermatophagoides/immunology , Asthma/immunology , Climate , Dermatophagoides farinae/immunology , Eosinophil Cationic Protein/blood , Immunity, Innate , Immunoglobulin E/blood , Intramolecular Oxidoreductases/blood , Macrophage Migration-Inhibitory Factors/blood , Animals , Child , Eosinophils , Female , Humans , Humidity , Leukocyte Count , Male , TemperatureABSTRACT
The strengthening of an Al-Mg-Si-Cu alloy during natural ageing and subsequent short artificial ageing was investigated using three-dimensional atom probe (3DAP) analysis and tensile testing. The contingency table and Markov chain analyses confirmed that non-random arrangements of atoms already exist after a natural ageing time of only 3.5h. Extensive use of particle analysis tools in the IVAS and PoSAP software packages revealed that whilst the commonly used minimum aggregate size (N(min)) of 10 is a reasonable choice, much more useful information about the system can be gained by additionally employing a wide range of larger and smaller N(min) values. In particular, it was found that the density and volume fraction of solute aggregates increased with increasing natural ageing time in the T4 condition. After a 0.5h artificial ageing treatment at 170 °C (designated as T6), the size, volume fraction and Mg/Si ratio of the aggregates were all found to decrease with increasing prior natural ageing time. These findings are used to discuss the detrimental effect of natural ageing, where the T6 strength has been observed to decrease rapidly with increasing prior natural ageing time before stabilising after several hours of natural ageing.