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Abstract: The airway mucosal epithelium is the first site of virus contact with the host, and the main site of infection and inflammation. Nitric oxide (NO) produced by the airway epithelium is vital to antiviral inflammatory and immune defense in the lung. Multiple mechanisms function coordinately to support high-level basal NO synthesis in healthy airway epithelium and further induction of NO synthesis in the infected airway of normal hosts. Hosts deficient in NO synthesis, such as those patients with cystic fibrosis, have impaired antiviral defense and may benefit from therapies to augment NO levels in the airways. [Copyright &y& Elsevier]

Mitochondrial dysfunction has emerged to be associated with a broad spectrum of diseases, and there is an increasing demand for accurate detection of mitochondrial DNA (mtDNA) variants. Whole genome sequencing (WGS) has been the dominant sequencing approach to identify genetic variants in recent decades, but most studies focus on variants on the nuclear genome. Whole genome sequencing is also costly and time consuming. Sequencing specifically targeted for mtDNA is commonly used in the diagnostic settings and has lower costs. However, there is a lack of pairwise comparisons between these two sequencing approaches for calling mtDNA variants on a population basis. In this study, we compared WGS and mtDNA-targeted sequencing (targeted-seq) in analyzing mitochondrial DNA from 1499 participants recruited into the Severe Asthma Research Program (SARP). Our study reveals that targeted-sequencing and WGS have comparable capacity to determine genotypes and to call haplogroups and homoplasmies on mtDNA. However, there exists a large variability in calling heteroplasmies, especially for low-frequency heteroplasmies, which indicates that investigators should be cautious about heteroplasmies acquired from different sequencing methods. Further research is highly desired to improve variant detection methods for mitochondrial DNA. [ABSTRACT FROM AUTHOR]

Acute lung injury (ALI) is a severe lung disease with high mortality rate. Research has highlighted that the immune response to ALI is associated with significant changes in the expression of several microRNAs (miRNAs) in the lungs. In our research, we speculated that miR-124 moderated the severity of ALI through comprehensive suppression of the mitogen-activated protein kinase (MAPK) signaling pathway activation by targeting MAPK14. A mouse model of ALI was established by array of experiments. The expression of MAPK14 and miR-124 was assessed in the tissues of ALI mice and the expression of inflammatory cytokines in ALI mice was determined. The expression of the related kinases in the MAPK signaling pathway and key cytokines in the pro-inflammatory response were assessed by a series of experiments. Immunohistochemistry and TUNEL staining were adopted to detect lung tissue cell proliferation and apoptosis in mice with ALI. MiR-124 was poorly expressed and MAPK14 was highly expressed in tissues of ALI mice. Overexpression of miR-124 or silence of MAPK14 alleviated the symptoms of ALI by down-regulating inflammatory cytokines expression, which could intrinsically suppress the expression of associated proteins in the MAPK signaling pathway and the downstream pro-inflammatory response factors, promote proliferation and inhibit apoptosis of lung tissue cells. Overexpression of MAPK14 inverted the phenotypic changes induced by overexpressing miR-124. These results indicated that miR-124 could alleviate the symptoms of ALI by inhibiting the activation of MAPK signaling pathway via subsequent targeting of MAPK14. Additionally, miR-124 may serve as a useful biomarker to alleviate the severity of septic shock-induced lung injury. • Our study reported the function of miR-124 in ALI. • miR-124 was poorly expressed and MAPK14 was highly expressed in ALI mice. • miR-124 inactivates MAPK signaling pathway by targeting MAPK14 to relieve ALI. • miR-124 promotes proliferation and inhibits apoptosis of cells by suppressing MAPK14. • Our study provides a theoretical basis for the treatment of acute lung injury. [ABSTRACT FROM AUTHOR]

The roles of long non-coding RNA (lncRNA) FENDRR in non-small cell lung cancer (NSCLC) cells progression have never been revealed. As cancer stem cells (CSCs) act important roles in tumor progression, here, we focused on FENDRR roles in NSCLC cell stemness. We found that lncRNA FENDRR expression was significantly decreased in lung cancer tissues and cells, especially in NSCLC cells. Then we constructed NSCLC cells with FENDRR stable overexpression and revealed that FENDRR overexpression attenuated the stemness of NSCLC cells, evident by decreased stemness markers expression and capacity of cell spheroid formation. Mechanistically, we found that FENDRR could directly and specifically bind to the 3′ untranslated region (3′UTR) of multidrug resistance gene 1 (MDR1), hinder the binding of RNA binding protein HuR to MDR1 3′UTR and thus decrease MDR1 expression. Finally, we demonstrated that FENDRR exerted its effects on NSCLC cell stemness through the HuR/MDR1 axis. Our results suggest that FENDRR attenuates NSCLC cell stemness through inhibiting the HuR/MDR1 axis. [ABSTRACT FROM AUTHOR]

• The eutectic region strength of SAC305 solder decreases with aging by nanoindentation analysis. • The dual-phase RVE CPFEM can simulate aging effect of SAC305 solder. • The simulated strain "hot zones" by DP CPFEM are consistent with SEM-DIC calculation. Because typical solder joints undergo thermal aging during use, models simulating the behaviors of solder under mechanical stress must accurately reflect the changes in properties caused by thermal aging effects. The uniaxial deformation of SAC305 (96.5Sn–3.0Ag–0.5Cu wt.%) solder under different aging conditions indicates that the mechanical properties of solder are weakened with aging. In this study, the nanoindentation method was used to evaluate the effect of aging on the mechanical properties of the β-Sn dendritic regions and eutectic regions of SAC305. Based on this evaluation, a dual-phase (DP) representative volume element (RVE) crystal plasticity finite-element method (CPFEM) model was developed to simulate the thermal aging effects of SAC305 solder. In situ tensile tests performed with scanning electron microscopy (SEM) showed that the tensile deformation was concentrated in the β-Sn dendritic regions of the solder. The DP CPFEM model was established based on the microstructures shown by electron backscatter diffraction (EBSD) analysis performed during the in situ tensile tests. This model was used to verify the accuracy of the DP CPFEM in simulating the deformation localization by comparison with the strain field distribution observed via SEM–digital image correlation (DIC) technology. The developed DP CPFEM model allows the prediction of the potential failure locations of a microscale solder joint. [Display omitted] [ABSTRACT FROM AUTHOR]

Abstract: Reactive oxygen species have been implicated in the pathogenesis of asthma and, in atopic asthmatics, endogenous superoxide dismutase (SOD) enzyme levels are known to decrease. This suggests that replacing a failed endogenous SOD enzyme system with a mimetic of the endogenous enzyme would be beneficial and protective. In this study we demonstrate that removal of superoxide by the SOD mimetic (SODm) M40403 reduces the respiratory and histopathological lung abnormalities due to ovalbumin (OA) aerosol in a model of allergic asthma-like reaction in sensitized guinea pigs. Both respiratory abnormalities and bronchoconstriction in response to OA challenge are nearly absent in naïve animals, while they sharply became severe in sensitized animals. In addition, OA aerosol induced a reduction of MnSOD activity which was paralleled with bronchiolar lumen reduction, pulmonary air space hyperinflation, mast cell degranulation, eosinophil infiltration, bronchial epithelial cell apoptosis, increase in myeloperoxidase activity, malonyldialdehyde production and 8-hydroxy-2′-deoxyguanosine formation in the lung tissue, as well as elevation of PGD2 in the bronchoalveolar lavage fluid. Treatment with M40403 restored the levels of MnSOD activity and significantly reduced all the above parameters. In summary, our findings support the potential therapeutic use of SOD mimetics in asthma and anaphylactic reactions and account for a critical role for superoxide in acute allergic asthma-like reaction in actively sensitized guinea pig. [Copyright &y& Elsevier]

• A new unified constitutive model is proposed to describe the thermomechanical response of solder. • The model is capable of predicting the in-phase (IP) and out-phase (OP) hysteresis loop of solder under thermomechanical symmetrical loading very well. • The model can accurately simulate the thermo-mechanical ratcheting behavior under IP, OP, and isothermal loading conditions. To describe the mechanical properties of SAC305 under comprehensive loading conditions, a new model was proposed based on the internal variable theory. The tensile property of SAC305 can be normalized by dividing the stress with the saturated stress. The flow law and kinematic hardening rule can be determined by relating the property to the evolution of internal variables. Since SAC305 had no obvious yield stress, strain hardening/softening was simulated by the evolution of drag stress. The model can be used to accurately simulate the hysteresis loop and ratcheting tests at constant temperature. However, the unified model greatly overpredicted the ratcheting strain associated with thermomechanical ratcheting. Thus, a correlation term for the rate of temperature change must be introduced to adjust the back stress with changing temperature. Therefore, the modulus of back stress will be less than that of saturated stress during the entire loading process. By correlating with the kinematic hardening rule, the model could be used to simulate the thermo-mechanical ratcheting behavior, and the results were well in agreement with experimental results. Image, graphical abstract [ABSTRACT FROM AUTHOR]