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On a non-road, high-pressure common-rail engine, natural gas/diesel dual-fuel (NDDF) combustion mode was performed. The way natural gas energy substitution percentage (ESP) and pilot diesel injection timing affected the combustion process, emission properties and fuel economy regarding NDDF engine with single injection strategy and split injection strategy was experimentally investigated at 25% load of 1800 rpm. Results show that under the two injection strategies, as ESP increased, NDDF combustion altered from single-stage to two-stage slowly, the combustion center (CA50) was delayed, the combustion duration increased, the soot and NO emissions declined, and the brake thermal efficiency (BTE) presented an increase-to-decrease change trend. As the combustion phase of split injection strategy was wholly advanced, the ignition delay period was shortened, the cyclic coefficient of variation (COV) and HC emission declined, and the BTE elevated. Additionally, the advanced injection timing would make NDDF heat release gradually advance, resulting in advanced CA50, extended ignition delay, lengthened combustion duration, lowered unregulated emissions, and increased BTE. The increase in peak heat release rate and BTE of split injection strategy was accompanied by decreased HC and aldehyde emissions. For NDDF engine possessing optimized split injection strategy, the BTE reached 37.79% and the COV reached 1.49% at ESP= 60%. [Display omitted] • The increase of ESP reduces the soot and NO, while increases combustion instability. • Split injection strategy reduces the HC, HCHO and NO 2 , and improves the COV and BTE. • Advancing SOI main decreases the soot, CO, HC, HCHO and CH 3 CHO, and improves the BTE. • NDDF engine with split injection strategy can achieve the BTE of 37.79% at low load. [ABSTRACT FROM AUTHOR]

Semantic Inpainting on Segmentation Map (SISM) aims to manipulate segmentation maps by semantics. Recent works show SISM provides semantic-aware auxiliary information for better style or structure manipulations. Providing structural assistance, segmentation maps have been broadly used as an intermediate interface to achieve better image manipulation. Mainstream solutions of image manipulation use Generative Adversarial Net (GAN) globally, locally or jointly. It is also applicable to SISM. However, the discriminator of global GAN is easier fooled, because the majority of its input is the same as the ground-truth, which is hard to fully mitigate the inconsistency between inpainted areas and the context. The inconsistency is more difficult for local GAN to address, due to the lack of context in its input. To mitigate the inconsistency, we propose a novel Multi-Expansion (MEx) loss. It is implemented by the adversarial loss on MEx areas. Each MEx area has the inpainted area as dominance and keeps knowledge of the scene context, so the consistency of the SISM results can be boosted. We propose an approximation of MEx loss, i.e., A-MEx loss, to further enhance the stability and usability. Besides performing well on SISM tasks, MEx loss also performs impressively on natural image inpainting. Extensive experiments on the two tasks demonstrate the advantages of our model over existing methods on four challenging datasets, such as a 2.59% increase in Hamm on SISM in Cityscape and a decrease of 5.00% FID on natural image inpainting in CMP Facade. The code of our work is available at: https://github.com/he159ok/AMEx-MEx-Loss. [ABSTRACT FROM AUTHOR]

Many invertebrate species possess the metabolic ability to synthesize long-chain ω3 polyunsaturated fatty acids (PUFA) de novo. Due to their diverse effects on membrane architecture, neuroplasticity, growth and reproduction, PUFA have a high potential to positively influence the fitness of an organism. But how and when do these supposed advantages actually come into play? Other species, that are often closely related, pass natural selection without this special metabolic ability. The ω3-PUFA rich model organism Caenorhabditis elegans (Nematoda) and its mutant fat-1(wa9) , lacking these PUFA, are a suitable test system. We analyzed potential impairments in reproduction and growth in a soil assay. Further, chemotaxis after aversive olfactory, associative learning and integration of a second sensory signal were assessed on agar plates. Moreover, we analyzed the phospholipid pattern of both C. elegans strains and further free-living nematodes species at different temperatures. While the phenotypic effects were rather small under standard conditions, lowering the temperature to 15 or even 10 °C or reducing the soil moisture, led to significant limitations, with the investigated parameters for neuroplasticity being most impaired. The ω3-PUFA free C. elegans mutant strain fat-1 did not adapt the fatty acid composition of its phospholipids to a decreasing temperature, while ω3-PUFA containing nematodes proportionally increased this PUFA group. In contrats, other ω3-PUFA free nematode species produced significantly more ω6-PUFA. Thus, the ability to synthesize long-chain ω3-PUFA de novo likely is fundamental for an increase in neuroplasticity and an efficient way for regulating membrane fluidity to maintain their functionality. [Display omitted] • ω3-PUFA containing nematodes increase these PUFA in response to falling temperature. • Nematodes that only contain ω6-PUFA greatly increase its content in their membranes. • ω3-PUFA are needed when the temperature is near the end of the reproductive window. • ω3-PUFA are prominent regulators of AWA olfaction and following signal transduction. • C. elegans fat-1 mutant is unable to adapt PUFA to a falling ambient temperature. [ABSTRACT FROM AUTHOR]

In this study, the effects of varying diesel/biodiesel blending ratios on exhaust emissions and particle physicochemical characteristics were conducted on a four-cylinder high-pressure common-rail diesel engine. The experiment involved the application of reference diesel (B0) and several diesel/biodiesel blends (B20, B50, B70 and B100) as the alternative fuels for diesel engine. The results indicated that the addition of biodiesel resulted in a significant reduction of HC, CO and soot emissions except for NOx, the generation of soot precursors such as polycyclic aromatic hydrocarbons (PAHs), ethylene and acetylene were inhibited, and the unregulated emissions of formaldehyde and acetaldehyde increased slightly, while they still were <45 ppm. At rated load, the soot and PAHs emissions of B70 fuel decreased by 28% and 24%, respectively. With the increase of biodiesel blending ratio, the molar and mass ratios of O/C, aliphatic hydrocarbon functional groups (C H) and oxygen-containing functional groups (-OH and -C=O), as well as the degree of disorder (sp3/sp2) on soot surface increased. Furthermore, the initial oxidation temperature and burnout temperature of B20, B50 and B70 soot samples were lower than those of B0 soot samples, and their apparent activation energy decreased by 4.67%, 9.76% and 17.09%, respectively. • Biodiesel addition results in a significant reduction of HC, CO and soot except NOx. • Biodiesel blends inhibit soot precursors formation of ethylene, acetylene and PAHs. • Biodiesel addition increases molar ratio of O/C and functional group on soot surface. • Biodiesel addition could improve the surface obstinate structure of soot particles. • Biodiesel blends could reduce soot activation energy and motivate DPF regeneration. [ABSTRACT FROM AUTHOR]

Background Epidermal growth factor receptor-tyrosine kinase inhibitors ( EGFR- TKIs) are remarkably effective for treating EGFR-mutant non-small cell lung cancer ( NSCLC). However, the individual role of EGFR- TKIs in patients with brain metastasis ( BM) arising from EGFR-mutant NSCLC remains unclear. Methods Patients with BM secondary to NSCLC and harboring EGFR-activating mutations were retrospectively screened. Patients who received gefitinib or erlotinib to control both extracranial lesions ( ECLs) and intracranial lesions ( ICLs) were eligible. If ECLs remained stable or remissive while ICLs progressed; asymptomatic BM progressed to symptomatic BM; BM symptoms were not alleviated within two weeks; or BM symptoms deteriorated after initial release, patients received brain radiotherapy or other local treatments and continued taking TKIs until ECLs progression occurred. Results In 43 eligible patients, the objective response and disease control rates for ICLs were 57% and 91%, respectively. Median progression-free survival ( PFS) was 9.3 months. The median PFS for ICLs and ECLs was 9.7 and 13.7 months, respectively. Non-smokers and second-line TKIs were found to be independent positive prognostic factors for PFS and overall survival ( OS) respectively, with a hazard ratio of 0.29 (95% confidence interval [ CI] 0.14-0.61; P = 0.001) and 0.34 (95% CI 0.16-0.70; P = 0.003). No significant difference in median OS was observed between patients who did or did not receive brain radiotherapy (23.6 vs. 18.7 months; P = 0.317). Conclusion EGFR-TKIs alone are effective for treating BM arising from EGFR-mutant NSCLC. The efficacy of TKIs in ICLs and ECLs should be evaluated separately. [ABSTRACT FROM AUTHOR]

Objective: To identify the clinicopathological characteristics and clinical outcomes of Chinese patients with non-small cell lung cancer (NSCLC) and to investigate possible associations of NSCLC with echinoderm microtubule-associated protein-like 4 (EML4)-anaplastic lymphoma kinase (ALK) and epidermal growth factor receptor (EGFR) mutations. Methods: Patients with stage IV NSCLC were screened for EML4-ALK rearrangement and EGFR mutations at the Peking University Cancer Hospital. EML4-ALK was identified using fluorescent in situ hybridization and confirmed by immunohistochemistry. EGFR mutations were determined using denaturing high-performance liquid chromatography. Results: The incidence of EML4-ALK was 9.7% (11/113). Patients with EML4-ALK were more likely to present the EGFR wild type (WT; p = 0.033). Response to EGFR-tyrosine kinase inhibitor (TKI) was similar between patients with EML4-ALK rearrangement and EGFR mutation (33.3 vs. 46.9%, p = 0.451), but progression-free survival (PFS) was inferior compared to those with EGFR mutation (2.1 vs. 8.8 months, p = 0.032), and similar to patients with WT/nonrearrangement (2.1 vs. 2.2 months, p = 0.696; and general p = 0.023 between the three cohorts). Moreover, 2 patients with concurrent EML4-ALK and EGFR mutations had superior PFS after EGFR-TKI compared to patients with single EML4-ALK rearrangement. Conclusions: Patients with EML4-ALK conferred similar objective response rates after EGFR-TKI although inferior PFS compared to those with EGFR mutation. Coexistence of EML4-ALK and EGFR mutation might represent a separate NSCLC genotype. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Objective: Isolated intra‐articular anterior cruciate ligament (ACL) reconstruction is not capable of restoring instability in many cases leading some to recommend concomitant anterolateral ligament (ALL) reconstruction. The satisfactory fixation site and graft length change are crucial in ligament reconstruction to restore the ALL function and avoid some unwanted graft behavior. The purpose of this investigation is to determine the optimal isometric region on the anterolateral aspect of the knee for ALL reconstruction using a three‐dimensional optical instrument and a suture similar to an intraoperative isometric test. Methods: Six freshly frozen cadaveric human knees were used in this study. Data regarding the anterolateral surface were obtained using an optical measurement system to create a three‐dimensional model. Nine points were selected on the femur (F1‐F9) and tibia (Ta‐Ti) respectively. The three‐dimensional length change between each pair of tibial and femoral points was measured during passive knee flexion from 0° to 90° in 15° increments. Subsequently, five femoral points (A–E) were selected from the lateral femur, located in different areas relative to the lateral femoral epicondyle, and three tibial reference points (T1‐T3) were selected in the isometric test. The changes in the length between each pair of reference points were measured using sutures. The 95% confidence interval for the rate of length change was estimated using the mean and standard deviation of the maximum rate of length change at different flexion angles, and the data were expressed as the mean (95% confidence interval) and compared with the maximum acceptable rate of change (10%). Results: The maximum acceptable change rate for ligament reconstruction is 10%, and the mean maximum rates and the 95% confidence interval (CI) of length change for the point combinations were calculated. Among all the combined points measured using the optical measurement system and the suture, the qualified point combination for reconstruction was F3 (8mm posterior and 8mm proximal to the lateral femoral epicondyle)‐Tb (8mm proximal to the midpoint between the center of Gerdy's tubercle and the fibula head), A (posterior and proximal to the lateral femoral epicondyle)‐T2 (10mm below the joint line)and A‐T3 (15 mm below the joint line). The position of F3‐Tb and A‐T2 are close to each other. Conclusion: The most isometric area of the femur for ALL reconstruction was posterior and proximal to the lateral femoral epicondyle. We recommend that the initial location of the femoral point be set at 8 mm posterior and 8 mm proximal to the lateral femoral epicondyle and the tibial point at approximately 10 mm below the joint line, midway between Gerdy's tubercle and fibular head, and subsequently adjusted to the most satisfactory position according to the isometric test. [ABSTRACT FROM AUTHOR]

Background: Age is an independent prognostic factor for small cell lung cancer (SCLC). We aimed to construct a nomogram survival prediction for elderly SCLC patients based on the Surveillance, Epidemiology, and End Results (SEER) database. Methods: A total of 2851 elderly SCLC patients from the SEER database were selected as a primary cohort, which were randomly divided into a training cohort and an internal validation cohort. Additionally, 512 patients from two institutions in China were identified as an external validation cohort. We used univariate and multivariate to determine the independent prognostic factors and establish a nomogram to predict survival. The value of the nomogram was evaluated by calibration plots, concordance index (C-index) and decision curve analysis (DCA). Results: Ten independent prognostic factors were determined and integrated into the nomogram. Calibration plots showed an ideal agreement between the nomogram predicted and actual observed probability of survival. The C-indexes of the training and validation groups for cancer-specific survival (CSS) (0.757 and 0.756, respectively) based on the nomogram were higher than those of the TNM staging system (0.631 and 0.638, respectively). Improved AUC value and DCA were also obtained in comparison with the TNM model. The risk stratification system can significantly distinguish individuals with different survival risks. Conclusion: We constructed and externally validated a nomogram to predict survival for elderly patients with SCLC. Our novel nomogram outperforms the traditional TNM staging system and provides more accurate prediction for the prognosis of elderly SCLC patients. [ABSTRACT FROM AUTHOR]

Background and Purpose: Tissue microRNAs (miRNAs) can detect cancers and predict prognosis. Several recent studies reported that tissue, plasma, and saliva miRNAs share similar expression profiles. In this study, we investigated the discriminatory power of salivary miRNAs (including whole saliva and saliva supernatant) for detection of esophageal cancer. Materials and Methods: By Agilent microarray, six deregulated miRNAs from whole saliva samples from seven patients with esophageal cancer and three healthy controls were selected. The six selected miRNAs were subjected to validation of their expression levels by RT-qPCR using both whole saliva and saliva supernatant samples from an independent set of 39 patients with esophageal cancer and 19 healthy controls. Results: Six miRNAs (miR-10b*, miR-144, miR-21, miR-451, miR-486-5p, and miR-634) were identified as targets by Agilent microarray. After validation by RT-qPCR, miR-10b*, miR-144, and miR-451 in whole saliva and miR-10b*, miR-144, miR-21, and miR-451 in saliva supernatant were significantly upregulated in patients, with sensitivities of 89.7, 92.3, 84.6, 79.5, 43.6, 89.7, and 51.3% and specificities of 57.9, 47.4, 57.9%, 57.9, 89.5, 47.4, and 84.2%, respectively. Conclusions: We found distinctive miRNAs for esophageal cancer in both whole saliva and saliva supernatant. These miRNAs possess discriminatory power for detection of esophageal cancer. Because saliva collection is noninvasive and convenient, salivary miRNAs show great promise as biomarkers for detection of esophageal cancer in areas at high risk. [ABSTRACT FROM AUTHOR]

Purpose: Previous studies have demonstrated that sunitinib has the anti-tumor activity in human non-small cell lung cancer (NSCLC). This study was aimed to investigate the efficacy of single use of sunitinib and that of concurrent or sequential administration of sunitinib and docetaxel in NSCLC cell lines that are resistant to EGFR TKIs. Methods: NSCLC cell lines with EGFR T790M mutation and K-ras mutation were exposed to either sunitinib or docetaxel or both based on various sequential administrations. After exposure, the cell viability was measured by MTT assay, cell cycle distribution was analyzed by flow cytometry, and alterations in signaling pathway were determined by immunoblotting. Results: Sunitinib exhibited dose-dependent growth inhibition in NSCLC cell lines and arrested cell cycle at G1 phase, whereas docetaxel arrested at S phase. Although single or concurrent use of sunitinib and docetaxel has some anti-proliferative effects, the sequential administrations of both drugs remarkably enhanced anti-tumor activity. When cells were exposed to docetaxel followed by sunitinib, synergism was observed. The molecular basis of this synergism is that the signaling pathways that were initially activated by docetaxel exposure were efficiently suppressed by the subsequent exposure to sunitinib. In contrast, the reverse of this sequential administration resulted in antagonism, which may be due to differential effects on cell cycle arrest. Conclusions: Sunitinib as a single agent exhibits anti-proliferative effects in vitro in NSCLC cell lines with EGFR T790M and K-ras mutations but the sequential administration of docetaxel followed by sunitinib is superior to sunitinib followed by docetaxel and concurrent administration. [ABSTRACT FROM AUTHOR]

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]

Nasopharyngeal carcinoma (NPC) is an endemic malignant disease of the head and neck region with unique features including striking ethnic and geographic variations as well as multifactorial etiology. Previous studies have demonstrated the anticancer properties of genistein, the major soy isoflavonoid, in several human cancer cells such as breast, prostate, colon, gastric, lung, and hepatoma. However, the action of genistein in NPC cells has not been determined. In this study, we investigated the inhibitory effects of genistein on NPC cells and its possible underlying mechanisms. We found that genistein dose-dependently inhibited the proliferation of human NPC cell line CNE2 cells. DNA flow cytometric analysis revealed that 30 to 120 μM genistein induced dramatic G2/M phase arrest in NPC cells. The mRNA expression levels, as shown by gene expression array and quantitative real-time polymerase chain reaction, and the protein expression levels of the cell cycle regulators p21Cip1 and ATR (Ataxia telangiectasia and Rad3 related) were elevated following genistein treatment. Interestingly, we also observed concomitant induction of p15Ink4b in genistein induced inhibitory effects in NPC cells. Moreover, selective estrogen receptor modulators did not affect genistein induced growth inhibition. These findings provide new insights into the potential intervention of NPC with genistein. [ABSTRACT FROM AUTHOR]

Background: This study aimed to explore the potentially predictive role and dynamic changes of immune checkpoints on T cell subsets in patients with breast cancer receiving neoadjuvant chemotherapies. Methods: Fluorescent multiplex immunohistochemistry (mIHC) was used to stain CD4, CD8, PD1, TIM3, and cytokeratins simultaneously in paired breast cancer samples before and after neoadjuvant therapies (NAT) in a prospective cohort (n = 50). Singleplex IHC was conducted to stain for CD3 in 100 cases with inclusion of extra retrospective 50 cases. Cell levels were correlated with clinicopathological parameters and pathological complete response (pCR). Results: In pretreatment tumors, the percentages of infiltrating CD8+, PD1+, PD1+CD8+, and the ratio of PD1+CD8+/CD8+ cells, were higher in pCR than non‐pCR patients in either the stromal or intratumoral area, but PD1+CD4+, TIM3+CD4+, TIM3+CD8+ cells and CD4+/CD8+ ratio was not. Multivariate analyses showed that the percentage of intratumoral CD8+ cells (OR, 1.712; 95% CI: 1.052–2.786; P = 0.030) and stromal PD1+CD8+/CD8+ ratio (OR, 1.109; 95% CI: 1.009–1.218; P = 0.032) were significantly associated with pCR. Dynamically, reduction in the percentages of PD1+, CD8+ and PD1+CD8+ cells after therapy strongly correlated with pCR. Notably, incremental percentages of PD1+CD8+ cells, rather than TIM3+CD8+, were shown in tumors from non‐pCR patients after NAT. CD3 staining confirmed the percentage of T cells were associated with pCR. Conclusions: PD1+CD8+ rather than TIM3+CD8+ cells are main predictive components within tumor‐infiltrating T cells in NAT breast cancer patients. Dynamically incremental levels of PD1+CD8+ cells occurred in non‐pCR cases after NAT, suggesting the combination of chemotherapy with PD1 inhibition might benefit these patients. Key points: Significant findings of the study: PD1+CD8+, rather than TIM3+CD8+, T cells are the main component to predict the response of neoadjuvant therapies in breast cancer. What this study adds: Incremental levels of PD1+CD8+ T cells in non‐pCR post‐NAT tumors suggest PD1 inhibition might benefit in the neoadjuvant setting. [ABSTRACT FROM AUTHOR]

A 53‐year‐old man diagnosed with disease stage IIIB pulmonary adenocarcinoma underwent chemotherapy and radiotherapy in the first‐line setting. After disease progression, he received targeted therapy because of subsequent detection of EGFR exon 19 del mutation. Following an increase in his adrenal metastases, a combination of immunotherapy and antiangiogenic therapy (sintilimab plus bevacizumab) was commenced. After one month, imaging showed that the adrenal metastases had shrunk and a progression‐free survival (PFS) of 6.0 months was achieved. In this case, we showed that the PD1 inhibitor sintilimab plus bevacizumab was effective in a refactory advanced EGFR‐mutant NSCLC with positive PD‐L1 expression. Key points: Our case report provides clinical evidence of the durable response of a patient with advanced EGFR‐mutant lung adenocarcinoma to a combination of immunotherapy and anti‐angiogenic agent, sintilimab and bevacizumab, as subsequent‐line therapy. Sintilimab and bevacizumab combination therapy was well‐tolerated and effective, resulting in dramatic tumor reduction and improvement in clinical symptoms. [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]

For refractory or resistant small cell lung cancer (SCLC), there is no standard treatment. We report a case of refractory SCLC achieving complete remission and then developing fatal interstitial pneumonitis after treatment with single-agent nab-paclitaxel. The relevant literature has also been reviewed. In terms of effectiveness, evidences exists that some refractory or resistant SCLC patients respond to paclitaxel, including nab-paclitaxel and solvent-based paclitaxel. Paclitaxel-related fatal interstitial pneumonitis is an uncommon event, with five fatal cases reported in the literature. It appears to occur in weekly paclitaxel-treated patients and develop during the middle-to-late phase of treatment. Therefore, further randomized clinical trials should be encouraged. In our case, positive immunohistochemical analysis for caveolin-1 in the tumor vascular endothelia suggests that the complete response may have been facilitated by enhanced transportation of paclitaxel through the tumor vascular barrier via caveolin-1, despite being negative for secreted protein acidic and rich in cysteine (SPARC) in tumor cells. Further molecular investigations of gp60, caveolin-1 and SPARC will shed light on tailored treatment in this setting. [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]

The natural gas hydrate (NGH) reservoir in China is mainly distributed in the continental shelf with water depths ranging from 600–1500 m, about 90% of which is stored in the shallow area of the deep sea, with weak cementation and non-diagenetic characteristics. In order to test and study this type of NGH, samples must be prepared in situ, in large quantities, and at fast speed. At present, there are problems with the common stirring, spraying, and bubbling preparation techniques available, such as slow generation rate, low gas storage density, and lack of rapid preparation. Therefore, the rapid preparation of large samples of non-diagenetic natural gas hydrate has received extensive attention at home and abroad. In view of this technical bottleneck, Southwest Petroleum University innovatively established a rapid preparation kettle of 1062 L. In this paper, the preparation experiment of natural gas hydrate in the South China Sea (the pressure of the preparation kettle was reduced from 7 MPa to 3.3 MPa) was carried out in the preparation method of the 'three-in-one' (stirring method, spraying method, bubbling method) and experimental test method. In the process of preparation of non-diagenetic gas hydrate, the data of dynamic image, temperature, pressure, electrical resistivity, and reaction time are tested. During the preparation of natural gas hydrate, temperature, pressure, and electrical resistivity curves in four preparation methods were made, respectively. Through the experimental data analysis of different preparation methods of natural gas hydrate, it has been found that the preparation time of natural gas hydrate using the stirring method, the spraying method, and the bubbling method alone require a longer preparation time. However, when the three-in-one method is used to prepare natural gas hydrate, the preparation cycle of natural gas hydrate is obviously shortened. The preparation time of the single method of stirring method, spraying method, and bubbling method is respectively about 5.13, 3.59, and 3.37 times as long as that of three-in-one method. The three-in-one method for preparing natural gas hydrate greatly improves the preparation efficiency, which has a great significance to the scientific and technological progress of experimental research and evaluation methods of natural gas hydrate. [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]

In recent years, immunotherapies, such as those involving chimeric antigen receptor (CAR) T cells, have become increasingly promising approaches to non-small-cell lung cancer (NSCLC) treatment. In this study, we explored the antitumor potential of prostate stem cell antigen (PSCA)-redirected CAR T and mucin 1 (MUC1)-redirected CAR T cells in tumor models of NSCLC. First, we generated patient-derived xenograft (PDX) mouse models of human NSCLC that maintained the antigenic profiles of primary tumors. Next, we demonstrated the expression of PSCA and MUC1 in NSCLC, followed by the generation and confirmation of the specificity and efficacy of PSCA- and MUC1-targeting CAR T cells against NSCLC cell linesin vitro. Finally, we demonstrated that PSCA-targeting CAR T cells could efficiently suppress NSCLC tumor growth in PDX mice and synergistically eliminate PSCA+MUC1+tumors when combined with MUC1-targeting CAR T cells. Taken together, our studies demonstrate that PSCA and MUC1 are both promising CAR T cell targets in NSCLC and that the combinatorial targeting of these antigens could further enhance the antitumor efficacy of CAR T cells. [ABSTRACT FROM AUTHOR]