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Background: Although the associations between genetic variations and lung cancer risk have been explored, the epigenetic consequences of DNA methylation in lung cancer development are largely unknown. Here, the genetically predicted DNA methylation markers associated with non–small cell lung cancer (NSCLC) risk by a two‐stage case‐control design were investigated. Methods: The genetic prediction models for methylation levels based on genetic and methylation data of 1595 subjects from the Framingham Heart Study were established. The prediction models were applied to a fixed‐effect meta‐analysis of screening data sets with 27,120 NSCLC cases and 27,355 controls to identify the methylation markers, which were then replicated in independent data sets with 7844 lung cancer cases and 421,224 controls. Also performed was a multi‐omics functional annotation for the identified CpGs by integrating genomics, epigenomics, and transcriptomics and investigation of the potential regulation pathways. Results: Of the 29,894 CpG sites passing the quality control, 39 CpGs associated with NSCLC risk (Bonferroni‐corrected p ≤ 1.67 × 10−6) were originally identified. Of these, 16 CpGs remained significant in the validation stage (Bonferroni‐corrected p ≤ 1.28 × 10−3), including four novel CpGs. Multi‐omics functional annotation showed nine of 16 CpGs were potentially functional biomarkers for NSCLC risk. Thirty‐five genes within a 1‐Mb window of 12 CpGs that might be involved in regulatory pathways of NSCLC risk were identified. Conclusions: Sixteen promising DNA methylation markers associated with NSCLC were identified. Changes of the methylation level at these CpGs might influence the development of NSCLC by regulating the expression of genes nearby. Plain Language Summary: The epigenetic consequences of DNA methylation in lung cancer development are still largely unknown.This study used summary data of large‐scale genome‐wide association studies to investigate the associations between genetically predicted levels of methylation biomarkers and non–small cell lung cancer risk at the first time.This study looked at how well larotrectinib worked in adult patients with sarcomas caused by TRK fusion proteins.These findings will provide a unique insight into the epigenetic susceptibility mechanisms of lung cancer. Sixteen promising DNA methylation markers associated with non–small cell lung cancer (NSCLC) were identified. Changes of the methylation level at these CpGs might influence the development of NSCLC by regulating the expression of genes nearby. [ABSTRACT FROM AUTHOR]

Vinylene‐linked covalent organic frameworks (COFs) have attracted enormous attention for photocatalytic H2 evolution from water because of their fully conjugated structures, high chemical stabilities, and enhanced charge‐carrier mobilities. In this work, two novel vinylene‐linked COFs with tuned cyano contents were successfully synthesized and then employed as photocatalysts for H2 generation. Notably, the photocatalytic H2 production rate of the COF with the higher cyano content reached 73 μmol h−1 under visible light irradiation, which is 2.4 times higher than that with the lower content (30 μmol h−1). Both the experimental and computational results demonstrated that the rational design incorporating cyano groups into COF skeletons could precisely tune the corresponding energy levels, expand the visible‐light absorption, and improve the photoinduced charge separation. This work not only provides a simple method for modulating the photocatalytic activities of COFs at the molecular level, but also affords interesting insights into the relationship between their structures and photocatalytic performance. [ABSTRACT FROM AUTHOR]

In this article, the network‐based iterative learning guaranteed cost control problem for the linear systems subject to denial‐of‐service (DoS) attacks at input and output (I/O) sides is studied via faded channels. First, the DoS attacks are modeled by independent Bernoulli sequences, where the expectation and variance are known. The fading measurements in I/O channels are described as independent Gaussian distributions with known expectations and variances respectively. Then, the repetitive system and the proposed ILC scheme involving both the iteration and time axes are transformed into a random two‐dimensional (2D) Roesser model by using the 2D system theory. The mean‐square asymptotic stability is introduced and followed by the definition of guaranteed cost function. Next, sufficient conditions that can not only ensure the asymptotic stability but also the cost index are derived. By applying the linear matrix inequality technology, the gain matrices and the upper bound of the control cost are further obtained. After exploring the adverse effect brought by the random fading phenomenon, a compensation algorithm is then designed and the analysis is strictly deduced. Finally, an injection molding process example is given to confirm the validity of the design. [ABSTRACT FROM AUTHOR]

The main purpose of this work is to address the problem of robust grid voltage sensor fault‐tolerant control for a single‐phase two‐level rectifier. First, considering a rectifier with disturbances and grid voltage sensor fault, the standard switched system model is constructed. Based on identical transformation, the original system is converted into an augmented system. In the augmented system, the information of the grid voltage sensor fault is included in the state vector. Second, an unknown input observer is designed for the augmented system for sensor fault estimation. The observer error is totally robust against independent deterministic disturbances. In addition, the effect of the disturbance caused by unknown disturbances or a modelling error is minimised with respect to a prescribed H∞ performance index. Finally, the sensor fault‐tolerant control is realised by fault compensation technique, which protects the rectifier from serious performance degradation in the presence of the grid voltage sensor fault. The proposed fault‐tolerant control strategy requires no supplementary hardware and all the inputs involved in the algorithm are directly available. Simulation and experimental results are exhibited to illustrate the capability of the proposed method to tolerate the grid voltage sensor fault. [ABSTRACT FROM AUTHOR]

In this article, a novel iterative learning control (ILC) scheme is presented for the operation control of high‐speed train (HST), where the velocity and displacement of HST are strictly limited to ensure safety and comfort. The model of HST constructed in the article is practical in the sense that both parametric and nonparametric uncertainties of system are addressed simultaneously. Backstepping design with the newly proposed barrier Lyapunov function is incorporated in analysis to ensure the uniform convergence of the state tracking error and that the constraint requirements on velocity and displacement would not be violated during the whole operation process. In the end, a simulation study is presented to demonstrate the efficacy of the proposed ILC law. [ABSTRACT FROM AUTHOR]

Hollmann built a theoretical framework for subspace regenerating storage code. In this framework, a storage node is equipped with a constant dimension subspace chosen from an overall message space Fqm${\bm{F}}_{\bm{q}}^{\bm{m}}$. The projection of user message on the subspace is stored on the corresponding node. A subspace code needs to fulfil decoding and repairing functionality. The framework stipulates the property for subspace storage code, but a simple implementable construction is still missing. To decrease the complexity of code design as well as encoding and decoding, this article proposed a subspace code implementation over F2 with the parameters of (m,m,2,⌈m2⌉,r,β)$({\bm{m}},{\bm{m}},2,\lceil {\frac{{\bm{m}}}{2}} \rceil ,{\bm{\ r}},{\bm{\beta }})$. It is proved theoretically the code is characterized by minimum decoding bandwidth, minimum storage, and exact repair. Still, the code is explicit, feasible and lightweight. A series of examples are given to elucidate the encoding, decoding and repairing procedures, which show in cases of m ≤ 5, the code could achieve high repair efficiency by combining with network coding. [ABSTRACT FROM AUTHOR]

Background & Aims: Previous genome‐wide association studies (GWAS) have identified multiple susceptible variants associated with persistent hepatitis B virus (HBV) infection. However, most of these variants are located in the noncoding regions, which make it difficult to determine the effective genes underlying these associations. We performed a two‐stage study, in the first stage we integrated RNA sequencing data of liver tissues and high‐density genotyping data from the Genotype‐Tissue Expression (GTEx) project with our previous GWAS data to conduct a transcriptome‐wide association study (TWAS) on HBV infection. Firstly, the cis‐heritable genes were screened by a genetic relatedness matrix of genome‐wide complex trait analysis (GCTA) from GTEx data. Then, the genetic expression of 2587 cis‐heritable genes was predicted by restricted maximum likelihood (REML) of genome‐wide efficient mixed‐model association (GEMMA) in our GWAS data with 951 HBV carrier cases and 937 HBV cleared controls. Next, we investigated the associations between predictive expression levels and persistent HBV infection risk. Gene set enrichment analysis (GSEA) was applied to infer the function of the identified genes. To identify the causal single nucleotide polymorphisms (SNPs) of HBV infection risk, we conducted the expression quantitative trait loci (eQTL)‐based stepwise logistic regression analysis in the regions around 1 Mb of these genes and validated the association between 994 health controls and 994 HBV‐persistent infection cases by genotyping experiment. In the second stage, 1538 HBV‐related hepatocellular carcinoma (HCC) cases and 1465 persistent HBV infection controls were collected to determine the effect of these variants on HBV‐related HCC as well, which were examined by the additive model in logistic regression analysis. We identified seven genes associated with HBV infection. In the classic human leukocyte antigen (HLA) region, three novel genes BAK1, HLA‐DOB and C4A (Z range from −3.95 to −3.64, P range from 7.84 × 10−5 to 2.00 × 10−4), as well as two genes (HLA‐DPA1 and HLA‐DPB1) were reported by previous GWAS. In the non‐HLA region, immune related at newly identified loci, PARP9 (Z = 3.69, P = 2.20 × 10−4) at 3q21.1. At 22q11.21, we identified TMEM191A (Z = 3.55, P = 3.80 × 10−4) as a target gene in addition to the reported non‐cis‐heritable gene UBE2L3. After further stepwise logistic regression analysis and validation, we identified eight variants independently associated with persistent HBV infection. Among those variants, the additive model showed that two SNPs associated with HBV‐related HCC risk (rs9272714 and rs9394194, OR range from 1.20 to 1.25, P range from 1.19 × 10−4 to 3.97 × 10−4). By integrating transcriptome data, our study not only identified new susceptibility loci of persistent HBV infection but also determined the potential target genes at reported loci, which provided insight into the genetic aetiology of persistent HBV infection and related HCC. [ABSTRACT FROM AUTHOR]

Many studies have shown that there were similarity between tumorigenesis and gametogenesis. Our previous work found that cancer‐testis (CT) genes could serve as a novel source of candidate of cancer. Here, by analysing The Cancer Genome Atlas (TCGA) database, we characterized a CT gene, SPANXC, which is expressed only in testis. The SPANXC was reactivated in lung adenocarcinoma (LUAD) tissues. And the expression of SPANXC was associated with prognosis of LUAD. We also found that the activation of SPANXC was due to the promoter hypomethylation of SPANXC. Moreover, SPANXC could modulate cell metastasis both in vitro and in vivo. Mechanistically, we found that SPANXC could bind to ROCK1, a metastasis‐related gene, and thus SPANXC may regulate cell metastasis partly through interaction with ROCK1 in LUAD. Together, our results demonstrated that the CT expression pattern of SPANXC served as a crucial role in metastasis of LUAD. And these data further corroborated the resemblance between processes of germ cell development and tumorigenesis, including migration and invasion. [ABSTRACT FROM AUTHOR]

Cancer‐testis (CT) genes are a group of genes restrictedly expressed in testis and multiple cancers and can serve as candidate driver genes participating in the development of cancers. Our previous study identified a number of CT genes in nongerm cell tumors, but their expression pattern in testicular germ cell tumor (TGCT), a cancer type characterized by less genomic alterations, remained largely unknown. In this study, we systematically investigated the expression pattern of CT genes in TGCT samples and evaluated the transcriptome difference between TGCT and normal testis tissues, using datasets from the UCSC Xena platform, The Cancer Genome Atlas (TCGA) and the Genotype‐Tissue Expression (GTEx) project. Pathway enrichment analysis and survival analysis were conducted to evaluate the biological function and prognostic effect of expressed CT genes. We identified that 1036 testis‐specific expressed protein‐coding genes and 863 testis‐specific expressed long noncoding RNAs (lncRNAs) were expressed in TGCT samples, including 883 CT protein‐coding genes and 710 CT lncRNAs defined previously. The number of expressed CT genes was significantly higher in seminomas (P = 3.48 × 10−13) which were characterized by frequent mutations in driver genes (KIT, KRAS and NRAS). In contrast, the number of expressed CT genes showed a moderate negative correlation with the fraction of copy number altered genomes (cor = −0.28, P = 1.20 × 10−3). Unlike other cancers, our analysis revealed that 96.16% of the CT genes were down‐regulated in TGCT samples, while CT genes in stem cell maintenance related pathways were up‐regulated. Further survival analysis provided evidence that CT genes could also predict the prognosis of TGCT patients with both disease‐free interval and progression‐free interval as clinical endpoints. Taken together, our study provided a global view of CT genes in TGCT and provided evidence that CT genes played important roles in the progression and maintenance of TGCT. [ABSTRACT FROM AUTHOR]

Our previous work demonstrated cancer‐testis (CT) genes as a new source of candidate driver of cancer. Recently, mounting evidence indicates that long noncoding RNAs (lncRNAs) with CT expression pattern could play a pivotal role in cancer biology. Here, we characterized a conserved CT long noncoding RNA (CT‐lncRNA), PCAT6, which is expressed exclusively in the testis and is reactivated in liver hepatocellular carcinoma (LIHC) tissues due to the highly frequent amplification. The expression in LIHC was correlated with clinical prognosis in TCGA data. Knockdown of PCAT6 could inhibit cell proliferation and migration in hepatocellular carcinoma (LIHC) cells. Gene set enrichment analysis (GSEA) based on coexpression network revealed that PCAT6 was involved in similar cilium‐related pathways in the testis and LIHC tissues. However, PCAT6 was mainly positively correlated with gametogenesis‐related pathways in the testis but was coexpressed with mitotic cell cycle genes in LIHC. Together, our data demonstrated that CT‐lncRNA PCAT6 represents the similarity and difference between tumorigenesis and gametogenesis. The CT expression pattern and important role in LIHC oncogenesis make PCAT6 an ideal target for LIHC diagnosis and therapy. [ABSTRACT FROM AUTHOR]

Abstract: Emerging evidence indicates that circular RNAs (circRNAs) are implicated in cancer development. This study aimed to evaluate whether circulating circRNAs may serve as novel biomarkers for non‐small cell lung cancer (NSCLC). We used RNA sequencing (RNA‐seq) and quantitative real‐time PCR to explore cancer‐related circRNAs. Bioinformatics and functional analyses were performed to reveal biological effects of circRNAs on lung cancer cells. A total of 5471 distinct circRNAs were identified by total RNA‐seq, in which 185 were differentially expressed between cancerous and adjacent normal tissues. A circRNA derived from exon 5–7 of the FARSA gene, termed circFARSA, was observed to increase in cancerous tissues (P = 0.016), and was more abundant in patients’ plasma than controls (P < 0.001). Overexpression of circFARSA in A549 cell line significantly promoted cell migration and invasion. In silico analysis suggested that circFARSA might sponge miR‐330‐5p and miR‐326, thereby relieving their inhibitory effects on oncogene fatty acid synthase. Summarily, this study revealed circRNA profile of NSCLC for the first time and provided the evidence of plasma circFARSA as a potential noninvasive biomarker for this malignancy. [ABSTRACT FROM AUTHOR]

Background and Aim Although several variants located at coding and non-coding regions were evaluated by previous studies, the evidence for associations between variants located in DNase I-hypersensitive sites (DHSs) and hepatocellular carcinoma (HCC) risk was still limited. Recent advances using ENCODE data indicated that genetic variants in DHSs played an important role in carcinogenesis. Therefore, systematically investigating the associations between regulatory variants in DHSs and HCC risk should be put on the agenda. Methods We conducted a case-control design (1538 HCC cases vs 1465 normal controls) to evaluate the effects on HCC for the variants located at the uniform DNase I hypersensitive sites sequencing peaks in a Chinese population. Results We found two novel single nucleotide polymorphisms rs12309362 (odds ratio = 0.64, P = 5.61 × 10−6) and rs9970827 (odds ratio = 0.73, P = 7.23 × 10−6) significantly associated with decreased risk of HCC. Conditional analysis proved that both of them independently contributed to the susceptibility of HCC. Expression quantitative trait loci analysis found that A allele of rs12309362 was significantly associated with an elevated expression of phosphatase phosphoglycerate mutase 5 in liver tissues. In addition, gene-based analysis indicated that CEBPB ( P = 1 × 10−4) was associated with the risk of HCC, and the expression of CEBPB was significantly lower in 50 The Cancer Genome Atlas HCC tumor tissues compared with matched normal tissues. Conclusions Our results indicated that rs12309362 (G > A), rs9970827 (A > G) in DHSs, and elevated expression of CEBPB were associated with a decreased risk of HCC. These results may contribute us to understand the function of regulatory DNA sequences in HCC development. [ABSTRACT FROM AUTHOR]

It has been proposed that the majority of disease-associated loci identified by genome-wide association studies (GWAS) are enriched in non-coding regions, such as the promoter, enhancer or non-coding RNA genes. Thus, we performed a two-stage case-control study to systematically evaluate the association of genetic variants in miRNA regulatory regions (promoter and enhancer) with lung cancer risk in 7,763 subjects (discovery stage: 2,331 cases and 3,077 controls; validation stage: 1,065 cases and 1,290 controls). As a result, we identified that rs12740674 (C > T) in miR-1262 enhancer was significantly associated with the increased risk of lung cancer (additive model in discovery stage: adjusted OR = 1.31, 95%CI = 1.13-1.53, p = 3.846 × 10−4 in Nanjing GWAS; adjusted OR = 1.20, 95%CI = 1.00-1.44, p = 0.041 in Beijing GWAS; validation stage: adjusted OR = 1.20, 95%CI = 1.03-1.41, p = 0.024). In meta-analysis, the p value for the association between rs12740674 and lung cancer risk reached 6.204 × 10−6 (adjusted OR = 1.24, 95%CI = 1.13-1.36). Using 3DSNP database, The Cancer Genome Atlas (TCGA) data and functional assays, we observed that the risk T allele of rs12740674 reduced the expression level of miR-1262 in lung tissue through chromosomal looping, and overexpression of miR-1262 inhibited lung cancer cell proliferation probably through targeting the expression levels of ULK1 and RAB3D. Our findings confirmed the important role that genetic variants of noncoding sequence play in lung cancer susceptibility and indicated that rs12740674 in miR-1262 may be biologically relevant to lung carcinogenesis. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the utilisation of ginger extract and vinegar for retarding decomposition of inosine monophosphate ( IMP), and IMP-related enzyme activity (the activity of acid phosphatase ( ACP) and alkaline phosphatase ( ALP)) in salted silver carp ( Hypophthalmichthys molitrix) during early postslaughter and chilled storage. We also quantified the decomposition pathway of ATP-related compounds, the reducing and phosphorylated sugar, and free amino acids ( FAAs) in samples. Rapid glycolysis in control occurred during postmortem storage. Vinegar and ginger extract inhibited the activity of ACP and ALP, thereby inhibiting the decomposition of IMP and the increase in hypoxanthine (Hx). IMP concentrations in treated sample were significantly higher than those of the control. Moreover, vinegar and ginger extract promoted the increase in FAAs. Therefore, vinegar and ginger extract could inhibit ACP and ALP activities and contributed to the accumulation of IMP and FAAs in silver carp during chilled storage. [ABSTRACT FROM AUTHOR]

Differences between white and dark muscles from common carp ( Cyprinus carpio) in sensory assessment, total viable counts ( TVC), total volatile basic nitrogen ( TVB-N), pH, electrical conductivity ( EC), biogenic amines ( BAs), nucleotide degradation products and colours were investigated under air and vacuum conditions during refrigerated (4 °C) storage. Compared with white muscle, dark muscle had a higher lipid content, but lower crude protein and moisture content. TVC, TVB-N, pH, and L* value were higher in white muscle, while K value and a* value were higher in dark muscle. Under both conditions, white and dark muscles had significant ( P < 0.05) differences in tyramine and cadaverine content. Although dark muscle was significantly ( P < 0.05) lower in ATP content, it had higher rate of IMP degradation and K value increase. Taking sensory and microbial indexes into consideration, dark muscle appeared to have a longer shelf life than white muscle under both conditions. [ABSTRACT FROM AUTHOR]

Background To explore the efficacy and safety of crizotinib versus platinum-based double agent chemotherapy as the first-line treatment in patients with advanced anaplastic lymphoma kinase (ALK)-positive lung adenocarcinoma. Method We retrospectively analyzed data from 19 patients with advanced ALK-positive lung adenocarcinoma who had received no previous systemic treatment for advanced disease. Seven patients received oral crizotinib at a dose of 250 mg twice daily; 12 patients were administered standard chemotherapy (pemetrexed, paclitaxel, vinorelbine or gemcitabine plus either cisplatin or carboplatin) every three weeks for up to six cycles. The primary endpoint was overall response rate ( ORR), disease control rate ( DCR), and safety. Results The ORR was significantly higher with crizotinib than with chemotherapy (83.3% in the crizotinib vs. 25.0% in the chemotherapy group, P < 0.05); the DCRs were 100% and 75%, respectively ( P < 0.05). The common adverse events associated with crizotinib were visual abnormality and diarrhea, whereas those associated with chemotherapy were neutropenia and nausea. In the crizotinib group, liver aminotransferase elevation (adverse events grade 3 or 4) occurred in one patient (14.3%). In the chemotherapy group, the same grade neutropenia adverse event occurred in two patients (16.6%). The incidence of treatment-related grade 3 or 4 adverse events was similar in both groups. Compared with chemotherapy, crizotinib was associated with a greater reduction in lung cancer symptoms and a greater improvement in quality of life. Conclusion As a first-line treatment, crizotinib was superior to platinum-based double chemotherapy in patients with previously untreated advanced ALK-positive lung adenocarcinoma. Therefore, crizotinib is an optimal therapy as a first-line treatment in these patients. [ABSTRACT FROM AUTHOR]

Background Epidermal growth factor receptor-tyrosine kinase inhibitors ( EGFR-TKIs) effectively treat advanced non-small cell lung cancer with EGFR-mutation. However, most patients develop acquired resistance without effective therapy subsequent to EGFR-TKI failure. We evaluated the efficacy of subsequent treatment strategies for EGFR-TKI resistance. Methods We retrospectively analyzed 240 patients with advanced lung adenocarcinoma with EGFR-TKI failure and following subsequent treatment. According to the first subsequent strategies after EGFR- TKI failure, patients were divided into groups of EGFR-TKI continuation (21 cases), EGFR-TKI continuation with chemotherapy (23 cases), chemotherapy alone (143 cases), and best supportive care ( BSC) (53 cases). Results Except for 53 cases of BSC, the disease control rates ( DCR) of the remaining 187 patients in the EGFR-TKI continuation, EGFR-TKI continuation with chemotherapy, and chemotherapy alone groups were 66.7%, 73.9%, and 44.8%, respectively. The median post-progression progression-free survival ( PFS) for the three groups was 3.0, 3.3, and 2.0 months, respectively. The DCR for the EGFR-TKI continuation with chemotherapy group was significantly higher than the chemotherapy alone group ( P = 0.006). The post-progression PFS of the EGFR-TKI continuation with chemotherapy group was significantly longer than the chemotherapy alone group ( P = 0.037). The median overall survival in the EGFR-TKI continuation, EGFR-TKI continuation with chemotherapy, chemotherapy alone, and BSC groups were 6.9, 11.6, 8.8, and 0.9 months, respectively. Compared to the BSC group, all groups achieved a survival benefit ( P < 0.001). Conclusions EGFR-TKI continuation with chemotherapy could provide benefits for patients with acquired resistance to EGFR-TKI. [ABSTRACT FROM AUTHOR]

BACKGROUND Biogenic amines have gained a great deal of attention due to their toxic potential in humans. Carp is one of the most important freshwater fish species in China. Salt and sugar are capable of preserving food. There is a limited amount of information on the changes of biogenic amines in freshwater fish influenced by salt and sugar. This study aimed to detect the changes in biogenic amines, sensory attributes, total volatile basic nitrogen ( TVB-N) and total viable counts ( TVC) of carp influenced by different concentrations of salt and sugar stored at 4 °C. RESULTS TVB-N and TVC increased with storage time, which was in accordance with the changes of sensory scores. The eight biogenic amines were detected in fresh carp. Putrescine and cadaverine were the main biogenic amines found in carp fillets stored at 4 °C; they had a significant ( P < 0.05) correlation with TVB-N. CONCLUSION Salt processing was found to inhibit the increase of TVB-N, TVC, putrescine and cadaverine in carp. High salt concentration had a positive effect on extending the shelf-life of the carp, compared to low salt concentration. © 2014 Society of Chemical Industry [ABSTRACT FROM AUTHOR]

Background To evaluate the efficacy and safety of Icotinib - an orally administered, highly potent selective inhibitor of epidermal growth factor receptor ( EGFR) and its active mutations, in the treatment of patients with advanced non-small cell lung cancer ( NSCLC). Methods A total of 101 patients with stage IIIb/ IV NSCLC were treated with 125 mg Icotinib three times a day until disease progression or intolerable toxicity. Response rate was evaluated using response evaluation criteria in solid tumors and progression-free survival ( PFS) was collected. Results The overall response rate ( ORR) and disease control rate ( DCR) were 37.6% (38/101) and 79.2% (80/101), respectively. The median PFS was 6.5 months. Multivariate analysis showed that female gender ( P = 0.048, 95% confidence interval [ CI] 1.010-6.016) and occurrence of rash ( P = 0.002, 95% CI 1.667-9.809) were the independent predictive factors for ORR, while a performance status ( PS) score of 0-1 ( P = 0.001, 95% CI 0.024-0.402) and rash ( P = 0.042, 95% CI 1.089-76.557) were the independent predictive factors for DCR. In addition, PS scores of 0-1 ( P < 0.001, 95% CI 0.135-0.509), and non-smoking ( P = 0.017, 95% CI 0.342-0.900) were found to be independent influencing factors for PFS. Moreover, patients with EGFR mutations had better PFS than patients with wild type EGFR, while patients with EGFR exon 19 deletion had better survival than those with EGFR exon 21 mutation. The most common adverse effects of Icotinib were rash (35.6%) and diarrhea (17.8%), which was tolerable. Conclusion Treatment of stage IIIb/ IV NSCLC patients with Icotinib was effective and tolerable, specifically in patients with EGFR mutation. [ABSTRACT FROM AUTHOR]

Deinked paper sludge (DPS) was pyrolyzed at 600°C, 750°C, and 900°C in dry nitrogen to synthesize adsorbents. The performance of the pyrolyzed DPS for the gas-phase adsorption of elemental mercury (Hg0) was investigated, and the performance was compared with that of BPL activated carbon as received (Calgon Carbon Corporation). In addition, the adsorption capacities of pyrolyzed DPS for Hg0 were compared with those published for other activated carbon adsorbents. The physical and chemical properties of pyrolyzed DPS and BPL were characterized to assess their differences, and those differences were used to hypothesize reasons for differences in their adsorption performance for Hg0. Characterization of the adsorbents was conducted using BET surface area, X-ray diffraction, thermal gravimetric analyses, scanning electron microscopy, electron dispersion spectroscopy, and Fourier transform spectroscopy. Pyrolyzed DPS performed better than BPL for Hg0 adsorption, despite the significant difference in surface area (pyrolyzed DPS ∼50 m2/g; BPL 1100 m2/g). Reasons for differences in adsorption performance are likely due to the pore size distribution, presence of and access to surface active sites, and morphology of the pyrolyzed deinked paper sludge compared with BPL. © 2012 American Institute of Chemical Engineers Environ Prog, 32: 524-534, 2013 [ABSTRACT FROM AUTHOR]

The new 4-amino-1,2,4-triazole asymmetric bridging ligand 4-amino-5-(pyridin-3-yl)-3-[4-(pyridin-4-yl)phenyl]-4 H-1,2,4-triazole ( L) has been used to generate three novel isomorphic one-dimensional coordination polymers, viz. catena-poly[[tris[dichloridomercury(II)]-bis{μ3-4-amino-5-(pyridin-3-yl)-3-[4-(pyridin-4-yl)phenyl]-4 H-1,2,4-triazole}] acetonitrile monosolvate], {[Hg3Cl6(C18H14N6)2]·CH3CN} n, (I), and the bromido, {[Hg3Br6(C18H14N6)2]·CH3CN} n, (II), and iodido, {[Hg3I6(C18H14N6)2]·CH3CN} n, (III), analogs. The asymmetric ligand acts as a tridentate ligand to coordinate the three different HgII centers (two of which are symmetry-related). Two ligands and two symmetry-related HgII centers form centrosymmetric rectangular units which are linked into one-dimensional chains via the other unique Hg atoms, which sit on mirror planes. The chains are elaborated into a three-dimensional structure via interchain hydrogen bonds. The acetonitrile solvent molecules are located in ellipsoidal cavities. The luminescent character of these three coordination complexes was investigated in the solid state. [ABSTRACT FROM AUTHOR]

The new ether-bridged dipyridyl ligand 1,2-bis[4-(pyridin-3-yl)phenoxy]ethane ( L) has been used to synthesize three isostructural centrosymmetric binuclear HgII macrocycles, namely bis{μ-1,2-bis[4-(pyridin-3-yl)phenoxy]ethane-κ2 N: N′}bis[dichloridomercury(II)], [Hg2Cl4(C24H20N2O2)2], and the bromido, [Hg2Br4(C24H20N2O2)2], and iodido, [Hg2I4(C24H20N2O2)2], analogues. The Hg atoms adopt a highly distorted tetrahedral coordination environment consisting of two halides and two pyridine N-donor atoms from two bridging ligands. In the solid state, the macrocycles form two-dimensional sheets in the bc plane through noncovalent Hg... X and X... X ( X = Cl, Br and I) interactions. [ABSTRACT FROM AUTHOR]

CD137 is a promising target for immunostimulation strategies against cancer. Previous studies showed that CD137+CD8+ T cells are enriched in antitumour effector T cells in both preclinical tumour models and cancer patients, but to date, such T cells in the blood of lung cancer patients have not been sufficiently investigated. In this study, circulating antigen‐activated CD8+ T cell subsets, identified as CD137+CD8+ or PD‐1+ (programmed cell death protein 1) CD8+, and regulatory T cells (Treg), identified as CD4+CD25+CD127low/−, in 40 untreated lung cancer patients and in 49 age‐ and sex‐matched healthy controls (HCs) were assessed by flow cytometry. Results were evaluated for associations with lung cancer patient clinical characteristics. Correlations between antigen‐activated CD8+ T cells and effector Treg (CTLA‐4+ [cytotoxic T‐lymphocyte antigen 4] CD4+CD25+CD127low/−) were also investigated. Higher percentages of PD‐1+, CD137+ and PD‐1+CD137+ amongst CD8+ T cells were observed in lung cancer patients compared with HCs. The percentages of CD137+CD8+ and PD‐1+CD137+CD8+ T cell subsets amongst CD8+ T cells were positively correlated with thoracic tumour burden and were strongly positively correlated with the percentage of effector Treg subset. Smoking patients harboured higher percentages of the PD‐1+CD8+ T cell subset compared with non‐smoking patients. This study demonstrated that circulating antigen‐activated CD8+ T cells accumulated in lung cancer patients along with increased effector Treg and thoracic tumour burden. These findings aid a better understanding of immune‐host interactions in lung cancer patients using peripheral blood, and further support immunotherapeutic intervention strategies using combination therapy for differential control of Treg and activation of tumour‐specific effector T cells. [ABSTRACT FROM AUTHOR]

A newly synthesized NHC-Pd(II)-morpholine complex shows efficient catalytic activity toward Suzuki-Miyaura coupling of aryl sulfamates (I) with arylboronic acids (II) or potassium phenyltrifluoroborate (IV). [ABSTRACT FROM AUTHOR]

The new ether-bridged dipyridyl ligand 1,2-bis[4-(pyridin-3-yl)phenoxy]ethane (L) has been used to synthesize three isostructural centrosymmetric binuclear Hg(II) macrocycles, namely bis{μ-1,2-bis[4-(pyridin-3-yl)phenoxy]ethane-κ(2)N:N'}bis[dichloridomercury(II)], [Hg(2)Cl(4)(C(24)H(20)N(2)O(2))(2)], and the bromido, [Hg(2)Br(4)(C(24)H(20)N(2)O(2))(2)], and iodido, [Hg(2)I(4)(C(24)H(20)N(2)O(2))(2)], analogues. The Hg atoms adopt a highly distorted tetrahedral coordination environment consisting of two halides and two pyridine N-donor atoms from two bridging ligands. In the solid state, the macrocycles form two-dimensional sheets in the bc plane through noncovalent Hg...X and X...X (X = Cl, Br and I) interactions.

The new 4-amino-1,2,4-triazole asymmetric bridging ligand 4-amino-5-(pyridin-3-yl)-3-[4-(pyridin-4-yl)phenyl]-4H-1,2,4-triazole (L) has been used to generate three novel isomorphic one-dimensional coordination polymers, viz. catena-poly[[tris[dichloridomercury(II)]-bis{μ(3)-4-amino-5-(pyridin-3-yl)-3-[4-(pyridin-4-yl)phenyl]-4H-1,2,4-triazole}] acetonitrile monosolvate], {[Hg(3)Cl(6)(C(18)H(14)N(6))(2)]·CH(3)CN}(n), (I), and the bromido, {[Hg(3)Br(6)(C(18)H(14)N(6))(2)]·CH(3)CN}(n), (II), and iodido, {[Hg(3)I(6)(C(18)H(14)N(6))(2)]·CH(3)CN}(n), (III), analogs. The asymmetric ligand acts as a tridentate ligand to coordinate the three different Hg(II) centers (two of which are symmetry-related). Two ligands and two symmetry-related Hg(II) centers form centrosymmetric rectangular units which are linked into one-dimensional chains via the other unique Hg atoms, which sit on mirror planes. The chains are elaborated into a three-dimensional structure via interchain hydrogen bonds. The acetonitrile solvent molecules are located in ellipsoidal cavities. The luminescent character of these three coordination complexes was investigated in the solid state.