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Aim. Ozone is a main component of secondary pollutants of vehicle exhausts, and ozone exposure to children in urban areas may be associated with the development of asthma. However, little is known about the mechanism(s) by which ozone affects human airway epithelium and subsequent airway inflammation. Methods. Human bronchial epithelial cells were exposed to ozone at 0.16 mg/m3 for varying periods. The concentrations of IL-1 and IL-6 secreted by the cells were measured by enzyme-linked immunosorbent assay (ELISA) and the contents of intracellular malondialdehyde (MDA) were determined. Furthermore, the conditional medium from the ozone-exposed cells was examined for stimulating human peripheral T lymphocytes from asthmatic patients and healthy subjects, and the production of cytokines was characterized by ELISA and quantitative real-time polymerase chain reaction (RT-PCR). Results. Ozone stimulated the IL-1 and IL-6 production by BEAS-2B cells and its stimulatory effects were time dependent. Furthermore, ozone exposure significantly increased the levels of MDA in BEAS-2B cells, as compared with that of the cells without ozone exposure, in a time-dependent manner. In addition, the conditional medium from the cells exposed to ozone, but not control condition medium, significantly increased the relative levels of IL-1 mRNA transcripts in human peripheral T lymphocytes from asthmatic patients, but not healthy subjects. However, the conditional medium did not induce significantly increased levels of IL-2 production by peripheral T cells. Conclusions. Our data indicated that exposure to low levels of ozone for a short period induced increases in the pro-inflammatory markers and oxidative stress in epithelial cells, which might contribute to airway inflammation particularly in asthmatic children. [ABSTRACT FROM AUTHOR]

Next generation sequencing (NGS) technology is an increasingly important clinical tool for therapeutic decision-making. However, interpretation of NGS data presents challenges at the point of care, due to limitations in understanding the clinical importance of gene variants and efficiently translating results into actionable information for the clinician. The present study compared two approaches for annotating and reporting actionable genes and gene mutations from tumor samples: The traditional approach of manual curation, annotation and reporting using an experienced molecular tumor bioinformationist; and a cloud-based cognitive technology, with the goal to detect gene mutations of potential significance in Chinese patients with lung cancer. Data from 285 gene-targeted exon sequencing previously conducted on 115 patient tissue samples between 2014 and 2016 and subsequently manually annotated and evaluated by the Guangdong Lung Cancer Institute (GLCI) research team were analyzed by the Watson for Genomics (WfG) cognitive genomics technology. A comparative analysis of the annotation results of the two methods was conducted to identify quantitative and qualitative differences in the mutations generated. The complete congruence rate of annotation results between WfG analysis and the GLCI bioinformatician was 43.48%. In 65 (56.52%) samples, WfG analysis identified and interpreted, on average, 1.54 more mutation sites in each sample than the manual GLCI review. These mutation sites were located on 27 genes, including EP300, ARID1A, STK11 and DNMT3A. Mutations in the EP300 gene were most prevalent, and present in 30.77% samples. The Tumor Mutation Burden (TMB) interpreted by WfG analysis (1.82) was significantly higher than the TMB (0.73) interpreted by GLCI review. Compared with manual curation by a bioinformatician, WfG analysis provided comprehensive insights and additional genetic alterations to inform clinical therapeutic strategies for patients with lung cancer. These findings suggest the valuable role of cognitive computing to increase efficiency in the comprehensive detection and interpretation of genetic alterations which may inform opportunities for targeted cancer therapies. [ABSTRACT FROM AUTHOR]

Chimeric antigen receptor (CAR) T cell immunotherapies have shown remarkable efficacy in treating multiple types of hematological malignancies but are not sufficiently effective at treating solid tumors. NKG2D is a strong activating receptor for NK cells and a co-stimulatory receptor for T cells. NKG2D signal transduction depends on DNAX-activating protein 10 (DAP10). Here, we introduced the cytoplasmic domain of DAP10 into the second-generation CARs M28z and G28z to generate M28z10 and G28z10, which target mesothelin (MSLN) and glypican 3 (GPC3), respectively. T cells expressing M28z10 or G28z10 showed enhanced and prolonged effector function against MSLN+ lung cancer or GPC3+ hepatocellular carcinoma cell lines in culture and secreted elevated levels of cytokines, including IL-2, IFN-γ, granzyme B, and GM-CSF. In addition, M28z10 CAR-T cells showed greater anti-tumor activity than those expressing M28z in both A549 cell line xenografts and human lung cancer patient-derived xenografts (PDX). Similarly, G28z10 exhibited higher efficacy in causing tumor regression than did G28z in hepatocellular carcinoma PDX. Therefore, our results show that DAP10 signaling contributes to the function of CAR-T cells in both lung cancer and hepatocellular carcinoma and can enhance the efficacy of CAR-T cells. [ABSTRACT FROM AUTHOR]

Curcumin, which is extracted from the traditional Chinese medicine turmeric, is a polyphenolic compound with a variety of biological activities, including immunoenhancement, antioxidant, and antibacterial properties. Singapore grouper iridovirus (SGIV) is a highly contagious viral pathogen that is capable of interfering with the organ function and destroying the immune system of the host, resulting in fish mortality and it has caused significant economic losses to the grouper aquaculture industry. The antiviral activity of curcumin has been demonstrated, but its protective effect against fish virus-induced liver injury requires further investigation. In this study, healthy grouper were infected with SGIV after receiving a curcumin gavage once a day for 15 days and the liver health was assessed. Our results showed that SGIV infection of grouper resulted in severe liver injury as evidenced by histopathological abnormalities, elevated hepatic reactive oxygen species and malondialdehyde, apoptosis and endoplasmic reticulum (ER) stress. On the other hand, we discovered that gavage with curcumin boosted fish immunity and reduced SGIV-induced mortality. Curcumin also ameliorated SGIV-induced liver injury, which might be a result of the modulation of the nuclear factor kappa-B (NF-κB) signaling pathway to reduce liver inflammation, the increase of liver antioxidant levels, the reduction of caspase families-dependent hepatocyte apoptosis, and the relief of liver ER stress by inhibiting heavy-chain binding protein (BIP)/ PKR-like ER kinase (PERK)/ eukaryotic initiation factor 2α (eIF2α)/ activating transcription factor 4 (ATF4) but not inosital-requiring enzyme-1 (IRE1)/ X-box binding protein 1 (XBP1) or ATF6 signaling pathways. This study demonstrated that curcumin possessed strong antiviral activity in fish and highlighted its protective effect on liver of grouper infected with SGIV, providing a theoretical foundation for the functional development of curcumin in aquaculture. • Curcumin treatment reduced SGIV-induced mortality. • Curcumin treatment boosted fish immunity. • Curcumin treatment attenuated liver injury of grouper infected with SGIV. [ABSTRACT FROM AUTHOR]

Background: Intratumoral epidermal growth factor receptor (EGFR) mutational heterogeneity is yet controversial in non-small cell lung cancer (NSCLC) patients. Single-cell analysis provides the genetic profile of single cancer cells and an in-depth understanding of the heterogeneity of a tumor.Methods: Firstly, single H1975 cells harboring the EGFR L858R mutation were submitted to flow cytometry isolation, nested polymerase chain reaction (nested-PCR) amplification, and direct DNA sequencing to assess the feasibility of single-cell direct DNA sequencing. Then, the single cells of patients with lung adenocarcinoma receiving gefitinib were captured by laser capture microdissection and analyzed by the above methods to identify the intratumoral heterogeneity of the EGFR L858R mutant. Three patients with progression-free survival (PFS) > 14 months were categorized as the long PFS group, and 3 patients with PFS < 6 months as the short PFS group. The correlation between the abundance of EGFR L858R mutant and PFS was analyzed.Results: 104 single H1975 cells were isolated. 100/104 were amplified by nested-PCR and confirmed by direct sequencing. We captured 135 tumor cells from the tissues of six patients. 120 single tumor cells were successfully amplified and sequenced. The rate of EGFR exon 21 mutation was only 77.5% (93/120). Furthermore, the rate of mutation in exon 21 of EGFR was significantly higher in the long PFS group than in the short PFS group (86.4 ± 4.9% vs. 68.9 ± 2.8%, P = 0.021).Conclusion: Our study suggested the intratumoral heterogeneity of EGFR-activating mutations in lung adenocarcinoma confirmed on the single-cell level, which might be associated with EGFR-TKIs response in lung adenocarcinoma patients harboring the EGFR L858R mutation. [ABSTRACT FROM AUTHOR]

Natural gas/diesel RCCI mode is considered as a high-efficiency clean low-temperature combustion strategy with great application prospects. In order to solve the problem that RCCI engines are prone to knock combustion under high load, the effects of diesel start of main-injection (SOI main), start of pilot-injection (SOI pilot) and pilot-injection quantity (PIQ) on in-cylinder combustion and pollutant emissions of RCCI engine were systematically investigated. Results show that the advance of SOI main effectively reduces CO, HC, soot and CH 4 emissions of RCCI engine, but increases knock tendency and NOx emissions. Split injection strategy makes combustion exothermic of RCCI mode present two-stage heat release phenomenon. When SOI pilot is advanced from −15°CA ATDC to −27°CA ATDC, the IMEP and combustion pressure peak increase, the knock tendency significantly decreases, and CO, HC, soot and CH 4 emissions are reduced by 55.6%, 43.1%, 28.8% and 39.1% respectively. With the increase of PIQ, the in-cylinder combustion of RCCI engine gradually changes from single-stage to two-stage heat release, the ignition delay is shortened, and the knock tendency is enhanced. Compared with single injection strategy, split injection strategy can simultaneously reduce HC, CO and greenhouse gas emissions, as well as maximum pressure oscillation amplitude and pressure rise rate in RCCI mode. • Combustion stability and GHG emissions of natural gas/diesel RCCI engine is explored. • Split injection strategy can reduce CO and GHG emissions, and inhibit knock tendency. • The advance of SOI main decreases HC, CO, CH 4 and soot, and increases knock tendency. • The advance of SOI pilot decreases CO, HC, soot and CH 4 emissions and knock tendency. • The increase of PIQ would shorten ignition delay period and enhance knock tendency. [ABSTRACT FROM AUTHOR]

• A noise robust phase unwrapping algorithm based on the combination of global Zernike polynomials fitting and the wrapped Kalman filter (WKF) is proposed. • An efficient weight strategy based on quality map is applied in the proposed method. The results show that the proposed method can obtain a satisfactory unwrapped phase map even in a very harsh noise condition without sacrificing too much time. • The convergence of WKF method is analyzed in this paper and different factors affecting the convergence of WKF are studied. We propose a noise robust phase unwrapping algorithm based on the state-space model of Zernike polynomials fitting and the Wrapped Kalman Filter. In our method, the phase map is modeled as the linear combination of Zernike polynomials and the phase unwrapping problem reduces to the estimation of the fitting coefficients. To accurately calculate those coefficients under a noisy condition, the Wrapped Kalman Filter with a weighting strategy based on the second difference of the wrapped phase map is developed. As a result, our proposed method can successfully recover an absolute phase from a wrapped phase map corrupted by heavy noise. The results of synthetic data and experimental data show the outperformance of the proposed methods against other three representative algorithms. [ABSTRACT FROM AUTHOR]