TrkB is highly expressed in NSCLC and mediates BDNF-induced the activation of Pyk2 signaling and the invasion of A549 cells

<p>Abstract</p> <p>Background</p> <p>Aberrant regulation in the invasion of cancer cells is closely associated with their metastatic potentials. TrkB functions as a receptor tyrosine kinase and is considered to facilitate tumor metastasis. Pyk2 is a non-receptor tyrosine kinase and integrates signals in cell invasion. However, little is known about the expression of TrkB in NSCLC and whether Pyk2 is involved in TrkB-mediated invasion of A549 cells.</p> <p>Methods</p> <p>The expression of TrkB was investigated in NSCLC by immunohistochemical staining. Both HBE and A549 cells were treated with BDNF. The expression of TrkB, Pyk2 and ERK phosphorylations were assessed by western blot. Besides, A549 cells were transfected with TrkB-siRNA or Pyk2-siRNA, or treated with ERK inhibitor where indicated. Transwell assay was performed to evaluate cell invasion.</p> <p>Results</p> <p>40 cases (66.7%) of NSCLC were found higher expression of TrkB and patients with more TrkB expression had significant metastatic lymph nodes (p = 0.028). BDNF facilitated the invasion of A549 cells and the activations of Pyk2 in Tyr402 and ERK. However, the effects of BDNF were not observed in HBE cells with lower expression of TrkB. In addition, the increased Pyk2 and ERK activities induced by BDNF were significantly inhibited by blocking TrkB expression, so was the invasion of A549 cells. Knockdown studies revealed the essential role of Pyk2 for BDNF-induced cell invasion, since the invasion of A549 cells was abolished by Pyk2-siRNA. The application of ERK inhibitor also showed the suppressed ERK phosphorylation and cell invasion.</p> <p>Conclusion</p> <p>These data indicated that higher expression of TrkB in NSCLC was closely correlated with lymph node metastasis, and BDNF probably via TrkB/Pyk2/ERK promoted the invasion of A549 cells.</p

Analysis of Low-Velocity Impact Resistance of Carbon Fiber Reinforced Polymer Composites Based on the Content of Incorporated Graphite Fluoride

As a graphite derivative, graphite fluoride (GrF) has a remarkable fracture toughness improvement effect on epoxy materials. The fracture toughness variation of the epoxy could exert an influence on the low velocity impact resistance of the corresponding carbon fiber reinforced polymer (CFRP) composite. Therefore, the dependence of the low velocity impact resistance of the incorporated CFRP on the GrF content is worth analyzing. Here, different contents of GrF were applied to incorporate CFRP laminates and planned to find the optimal GrF content, in turn leading to the best impact resistance. Using a drop-weight impact test, the load vs. time curves and load vs. displacement curves were obtained. The incipient damage loads and maximum loads of various GrF contents of the samples were compared carefully. The absorbed energies during the impact process were calculated. The trend of absorbed energy decreased up to the 1 wt% sample, then increased significantly with the rise of GrF content. This deflection behavior can be explained by the combination of crack pinning, crack deflection and crack propagation, due to the rise in GrF content. Through the ultrasonic C-scan evaluation, the delamination areas of different GrF content of samples were measured. The trend of delamination area variation was accordant with the trend of absorbed energy variation. This presents a demonstration of the correlation between the absorbed energy and the damage level. The SEM images of the fracture surfaces were analyzed for the deflection behavior of the fracture toughness with various GrF contents. The plot of residual compression strength versus GrF content further indicated the 1 wt% was the optimal content at which the incorporated GrF endowed the most impact-resistant property to the CFRP laminates

Canopy and Terrain Interactions Affecting Snowpack Spatial Patterns in the Sierra Nevada of California

Airborne light detection and ranging is an emerging measurement tool for snowpack estimation, and data are now emerging to better assess multiscale snow depth patterns. We used airborne light detection and ranging measurements from four sites in the southern Sierra Nevada to determine how snow depth varies with canopy structure and the interactions between canopies and terrain. We processed the point clouds into snow depth rasters at 0.5x0.5-m(2) resolution and performed statistical analysis on the processed snow depth data, terrain attributes, and vegetation attributes, including the individual tree bole locations, canopy crown area, and canopy height. We studied the snow depth at such a fine scale due in part to the spatial heterogeneity introduced by canopy interception and enhanced melting caused by tree trunks in forested areas. We found that the dominant direction of a tree well, the area around the tree bole that has shallower snowpack, is correlated with the local aspect of the terrain, and the gradient of the snow surface in a tree well is correlated with the tree's crown area. The regression-tree based XGBoost model was fitted with the topographic variables and canopy variables, and about 71% of snow depth variability can be explained by the model

Design and Construction of a Laboratory-Scale Direct-Current Electric Arc Furnace for Metallurgical and High-Titanium Slag Smelting Studies

A novel direct-current electric arc furnace (DC-EAF) was designed and constructed in this study for experimentally investigating high-titanium slag smelting, with an emphasis on addressing the issues of incomplete separation of metal and slag as well as poor insulation effects. The mechanical components (crucible, electrode, furnace lining, etc.) were designed and developed, and an embedded crucible design was adopted to promote metal-slag separation. The lining and bottom thicknesses of the furnace were determined via calculation using the heat balance equations, which improved the thermal insulation. To monitor the DC-EAF electrical parameters, suitable software was developed. For evaluating the performance of the furnace, a series of tests were run to determine the optimal coke addition under the conditions of constant temperature (1607 °C) and melting time (90 min). The results demonstrated that for 12 kg of titanium-containing metallized pellets, 4% coke was the most effective for enrichment of TiO2 in the high-titanium slag, with the TiO2 content reaching 93.34%. Moreover, the DC-EAF met the design requirements pertaining to lining thickness and facilitated metal-slag separation, showing satisfactory performance during experiments

The 2nd sialic acid-binding site of influenza A virus neuraminidase is an important determinant of the hemagglutinin-neuraminidase-receptor balance.

Influenza A virus (IAV) neuraminidase (NA) receptor-destroying activity and hemagglutinin (HA) receptor-binding affinity need to be balanced with the host receptor repertoire for optimal viral fitness. NAs of avian, but not human viruses, contain a functional 2nd sialic acid (SIA)-binding site (2SBS) adjacent to the catalytic site, which contributes to sialidase activity against multivalent substrates. The receptor-binding specificity and potentially crucial contribution of the 2SBS to the HA-NA balance of virus particles is, however, poorly characterized. Here, we elucidated the receptor-binding specificity of the 2SBS of N2 NA and established an important role for this site in the virion HA-NA-receptor balance. NAs of H2N2/1957 pandemic virus with or without a functional 2SBS and viruses containing this NA were analysed. Avian-like N2, with a restored 2SBS due to an amino acid substitution at position 367, was more active than human N2 on multivalent substrates containing α2,3-linked SIAs, corresponding with the pronounced binding-specificity of avian-like N2 for these receptors. When introduced into human viruses, avian-like N2 gave rise to altered plaque morphology and decreased replication compared to human N2. An opposite replication phenotype was observed when N2 was combined with avian-like HA. Specific bio-layer interferometry assays revealed a clear effect of the 2SBS on the dynamic interaction of virus particles with receptors. The absence or presence of a functional 2SBS affected virion-receptor binding and receptor cleavage required for particle movement on a receptor-coated surface and subsequent NA-dependent self-elution. The contribution of the 2SBS to virus-receptor interactions depended on the receptor-binding properties of HA and the identity of the receptors used. We conclude that the 2SBS is an important and underappreciated determinant of the HA-NA-receptor balance. The rapid loss of a functional 2SBS in pandemic viruses may have served to balance the novel host receptor-repertoire and altered receptor-binding properties of the corresponding HA protein

The 2nd sialic acid-binding site of influenza A virus neuraminidase is an important determinant of the hemagglutinin-neuraminidase-receptor balance

Influenza A virus (IAV) neuraminidase (NA) receptor-destroying activity and hemagglutinin (HA) receptor-binding affinity need to be balanced with the host receptor repertoire for optimal viral fitness. NAs of avian, but not human viruses, contain a functional 2nd sialic acid (SIA)-binding site (2SBS) adjacent to the catalytic site, which contributes to sialidase activity against multivalent substrates. The receptor-binding specificity and potentially crucial contribution of the 2SBS to the HA-NA balance of virus particles is, however, poorly characterized. Here, we elucidated the receptor-binding specificity of the 2SBS of N2 NA and established an important role for this site in the virion HA-NA-receptor balance. NAs of H2N2/1957 pandemic virus with or without a functional 2SBS and viruses containing this NA were analysed. Avian-like N2, with a restored 2SBS due to an amino acid substitution at position 367, was more active than human N2 on multivalent substrates containing α2,3-linked SIAs, corresponding with the pronounced binding-specificity of avian-like N2 for these receptors. When introduced into human viruses, avian-like N2 gave rise to altered plaque morphology and decreased replication compared to human N2. An opposite replication phenotype was observed when N2 was combined with avian-like HA. Specific bio-layer interferometry assays revealed a clear effect of the 2SBS on the dynamic interaction of virus particles with receptors. The absence or presence of a functional 2SBS affected virion-receptor binding and receptor cleavage required for particle movement on a receptor-coated surface and subsequent NA-dependent self-elution. The contribution of the 2SBS to virus-receptor interactions depended on the receptor-binding properties of HA and the identity of the receptors used. We conclude that the 2SBS is an important and underappreciated determinant of the HA-NA-receptor balance. The rapid loss of a functional 2SBS in pandemic viruses may have served to balance the novel host receptor-repertoire and altered receptor-binding properties of the corresponding HA protein

Disease burden and antimicrobial resistance of invasive group B streptococcus among infants in China: a protocol for a national prospective observational study

Abstract Background Group B Streptococcus (GBS) is a cause of neonatal sepsis, pneumonia, and meningitis that can lead to neurological sequelae in infants less than 3 months of age. The GBS disease burden is not known in China, therefore it cannot receive major attention. The main objectives of this study are the evaluation of the incidence of neonatal GBS infection, GBS case-fatality ratio, its serotypes and genotypes, bacterial resistance, clinical treatment and outcomes in China. Methods We are conducting a nation-wide, population-based, multi-center, prospective, observational cohort study in China from May 2016 to December 2017. Eighteen large urban tertiary care hospitals from 16 provinces were selected that cover the eastern, southern, western, northern and central regions of China. Meanwhile, we retrospectively collected data and GBS strains from January 2015 to April 2016 from selected hospitals. The incidence rate per 1000 live births will be defined as the total number of confirmed GBS cases born in the selected hospitals divided by the number of live births in the hospitals during the study period. All GBS cases detected in selected hospitals will be used to calculate the case-fatality ratio and for the typing analysis. GBS isolates will be serotyped using the Strep-B-Latex® rapid latex agglutination test for serotyping of Group B streptococci. Multi-locus sequence typing (MLST) will be performed by sequencing the internal fragments of seven house-keeping genes. Antimicrobial susceptibility will be tested per interpretive standards established by the Clinical and Laboratory Standards Institute. The presence of the common resistance genes ermA, ermB, mefA, tetI, tetO and tetM will be tested by PCR. Discussion We are conducting the first national study to estimate the invasive GBS disease burden and antimicrobial resistance of GBS among infants in China. Study findings will provide important evidence for improving clinical practice to ensure timely diagnosis of GBS disease and decisions for preventive measures. Surveillance of antimicrobial resistance will promote the rational use of antimicrobials. Trial registration The study was retrospectively registered at http://clinicaltrials.gov on June 13, 2016. It was granted a registration number of “NCT02812576”