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Natural medicine, such as traditional Chinese medicine, plays a role in treating ulcerative colitis (UC) because of its action on multiple targets. Here we have improved the effectiveness of a traditional Chinese medicinal herb, Huangqin decoction (HQD), on UC via the nuclear factor-κB (NF-κB) p65 signaling pathway in a mouse model. NF-κB is a crucial regulator of inflammation, cancer, and autoimmunity. It may be related to the initiation and development of UC. Histopathological changes in colon show that Huangqin Decoction can improve colon tissue environment In addition, the Western blots of the inflammatory cytokines related to the NF-κB p65 pathway suggest that HQD inhibits the development of UC by regulating the NF-κB p65 signaling pathway. These findings provide a basis for the clinical application of HQD and suggest a new strategy for treating UC in the future.

Previous research found that HOTAIR, a long non-coding RNA, is aberrantly expressed and associated with tumor invasion, metastasis and chemo-resistance in many cancers. The aim of this study was to investigate the role of HOTAIR in resistance of EGFR-TKIs in NSCLC.HOTAIR expression level was detected by quantitative reverse transcription polymerase chain reaction (qRT-PCR) in NSCLC cell lines or tumor tissues. A total of 62 samples with EGFR-mutant and EGFR-TKI-sensitive NSCLCs, 42 with acquired resistance and 27 with primary resistance to EGFR-TKIs were analyzed. The effect of HOTAIR on cell proliferation and apoptosis was undergone by CCK-8 and flow cytometry assays. The expression of EMT proteins was assessed by western blot.HOTAIR was significantly down-regulated in lung cancer cells (PC9/R, H1975, H1299 and A549) and patients with primary and acquired resistance to EGFR-TKIs. In clinical setting, high levels of HOTAIR expression was significantly correlated with longer progression-free survival (PFS) [P 0.01] compared with low HOTAIR expression subgroup in tumors which respond to EGFR-TKIs. In vitro, over-expression HOTAIR could restore gefitinib sensitivity in gefitinib-resistant cells (PC9/R, H1299 and A549), but this change in sensitivity was not observed in H1975. Up-regulated HOTAIR induced cell apoptosis in PC9/R, H1299 and A549, and activated epithelial-mesenchymal transition (EMT).HOTAIR expression was associated with primary and acquired resistance to EGFR-TKIs and could regulate cell proliferation through activating cell apoptosis and EMT, which suggest that HOTAIR might be able to act as a biomarker to predict the EGFR-TKIs resistance.

Too many reviews lead to information overload, which makes it vital for an effective review system to identify helpful ones. Extensive empirical studies have shown that review helpfulness is affected by many factors, two of which are review sentiment and rating. However, almost all the existing studies assumed that the effects of these factors are time-invariant, and the review system is static. This study challenges such unrealistic yet prevalent assumption. Using 82, 703 phone review data from Amazon.com, we examine how review rating and sentiment impact review helpfulness and how such impact varies with time. Echoing the mixed results on the effects of rating or sentiment on perceived review helpfulness, our results suggest that in a decade before, rating and sentiment were positively associated with review helpfulness, while in recent years the relationship became negative instead. Our findings offer theoretical and managerial insights for both researchers and practitioners.

Background Severe fever with thrombocytopenia syndrome (SFTS) is a severe emerging disease caused by SFTS virus (SFTSV), and the geographical distribution of SFTS has been increasing throughout China in recent years. To assess SFTSV-specific antibody seroprevalence, a cross-sectional study was conducted for healthy people in high SFTS endemic areas of Henan province in 2016. Methods This study used a stratified random sampling method to select 14 natural villages as the investigation sites. From April to May 2016, participants completed a questionnaire survey and serum samples were collected. All serum samples were subjected to ELISA to detect SFTSV-specific IgM and IgG. All IgM-positive samples were further tested by real-time RT-PCR, and isolation of virus from serum was attempted. Any participant who was IgM-positive was followed up with a month later to confirm health status. Results In total, 1463 healthy people participated in this study. The average seropositive rates for SFTSV-specific IgG and IgM were 10.46% (153/1463) and 0.82% (12/1463), respectively. IgM was detected in 12 individuals, and SFTSV RNA was detected in six of them. Virus was isolated from five of the six SFTSV RNA-positive individuals, and phylogenetic analyses revealed that all five isolates belonged to SFTSV group A. No IgM-positive participants exhibited any symptoms or other signs of illness at the one-month follow up. Conclusions This study identified a relatively high incidence of SFTSV-specific antibody seropositivity in healthy people in Xinyang city. Moreover, our data provide the first evidence for asymptomatic SFTSV infections, which may have significant implications for SFTS outbreak control., Author summary Severe fever with thrombocytopenia syndrome (SFTS) is a severe emerging infectious disease caused by SFTS virus (SFTSV) that was first discovered in rural areas of China. Henan province has had the largest number of SFTS cases in China every year since the disease was discovered, however, seropositivity for SFTSV-specific antibodies in healthy people in this region is still not clear. To address this issue, a cross-sectional survey was performed in high endemic areas from April to May 2016. The results showed that SFTSV seroprevalence was relatively high and possibly increasing. Notably, SFTSV RNA, as well as virus itself, was isolated from specimens obtained from healthy people. This study confirmed there are asymptomatic SFTSV infections in humans, and it is the first to report SFTSV isolation from healthy people.

We report herein the synthesis of a series of novel quinoline derivatives, based on the lead compound 1a, identified from a rRSV-mGFP high-throughput screening assay. Our results revealed that target compounds 1b, 1g-h, 1af and 1ah (IC50 = 3.10–6.93 μM) had good in vitro activity against RSV, which were better than 1a and ribavirin. In addition, we found that compound 1g displayed the lower cytotoxicity (CC50: 2490.33 μM) and the highest selective index (SI = 673.06), suggesting its promising potential as a candidate for further development. On the other hand, compounds 1a, 1m, 1v, 1ad-1af and 1ah-1ai (IC50s: 1.87–14.28 μM) were more active against IAV than or comparable to ribavirin (IC50: 15.36 ± 0.93 μM). Particularly, the most active compound 1ae (IC50: 1.87 ± 0.58 μM) was found to be 8.2-fold more potent than the reference drug, which could inhibit the virus transcription and replication cycle at an early stage.

Amphipathic lignin derivatives (A-LDs) prepared from the black liquor of soda pulping of Japanese cedar are strong accelerators for bioethanol production under a fed-batch simultaneous enzymatic saccharification and fermentation (SSF) process. To improve the bioethanol production concentration, conditions such as reaction temperature, stirring program, and A-LDs loadings were optimized in both small scale and large scale fed-batch SSF. The fed-batch SSF in the presence of 3.0 g/L A-LDs at 38 degrees C gave the maximum ethanol production and a high enzyme recovery rate. Furthermore, a jar-fermenter equipped with a powerful mechanical stirrer was designed for 1.5 L-scale fed-batch SSF to achieve rigorous mixing during high substrate loading. Finally, the 1.5 L fed-batch SSF with a substrate loading of 30% (w/v) produced a high ethanol concentration of 87.9 g/L in the presence of A-LDs under optimized conditions.

Amphipathic lignin derivatives (ALDs), prepared from hardwood acetic acid lignin and softwood soda lignin via coupling with a mono-epoxylated polyethylene glycol, have been reported to improve the enzymatic saccharification efficiency of lignocellulose while maintaining significant residual cellulase activity after saccharification. We previously demonstrated that the effect of ALDs was caused by a direct interaction between ALDs and Cel6A (or CBH II). In this study, a different ALD was prepared from softwood kraft lignin in addition to aforementioned ALDs. The interactions between all the ALDs and the enzymes other than Cel6A, such as Cel7A and Cel7B, in a cellulase cocktail were investigated using surface plasmon resonance. The kraft lignin-based ALD showed the highest residual cellulase activity among all ALDs and an improved cellulolytic enzyme efficiency similar to those of the other ALDs. All ALDs were found to directly associate with major enzymes in the cellulase cocktail, Cel6A and Cel7A (or CBH I), but not with Cel7B (or EG I). In addition, the ALDs showed a much higher affinity to amino groups than to hydroxy and carboxy groups. In contrast, polyethylene glycol (molecular mass 4000 Da), one part of the ALD and a previously reported enzymatic saccharification enhancer, did not adsorb onto any enzymes in the cellulase cocktail or the amino group. Size exclusion chromatography demonstrated that the ALDs formed self-aggregates in both water and chloroform; the formation process in the latter was especially unique. Therefore, we conclude that the high residual cellulase activity is attributed to the direct association of ALD aggregates with the CBH group.

// Qi Wang 1, * , Ningning Cheng 2, * , Xuefei Li 3 , Hui Pan 1 , Chunyu Li 4 , Shengxiang Ren 1 , Chunxia Su 1 , Weijing Cai 1 , Chao Zhao 3 , Limin Zhang 1 , Caicun Zhou 1 1 Department of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University, Tongji University Medical School Cancer Institute, Shanghai, 200433, P.R. China 2 Department of Radiation Oncology, Shanghai General Hospital, Shanghai Jiaotong University, Shanghai, 201620, P. R. China 3 Department of Lung Cancer and Immunology, Shanghai Pulmonary Hospital, Tongji University, Tongji University Medical School Cancer Institute, Shanghai, 200433, P.R. China 4 International Medical School, Tianjin Medical University, Tianjin, 300070, P.R. China * These authors contributed equally to this work Correspondence to: Caicun Zhou, email: caicunzhoudr@163.com Keywords: long non-coding RNA, lung adenocarcinoma, H19, cisplatin, A549/DDP cells Received: June 29, 2016 Accepted: November 21, 2016 Published: November 29, 2016 ABSTRACT The acquired drug resistance would influence the efficacy of cisplatin-based chemotherapy in non-small-cell lung cancer. The present study aimed to investigate the correlation of long non-coding RNA (lncRNA) H19 with cisplatin-resistance and clinical outcome in lung adenocarcinoma. In our study, the expression of H19 in cisplatin-resistant A549/DDP cells was unregulated. Knockdown of H19 restored the response of A549/DDP cells to cisplatin. H19 -mediated chemosensitivity enhancement was associated with metastasis, induction of G0/G1 cell-cycle arrest, cell proliferation, and increased apoptosis. Furthermore, lncRNA H19 expression was significantly related to TNM stage and metastasis ( P = 0.012). Overexpression of H19 was negatively correlated with cisplatin-based chemotherapy response in patients. Patients with high H19 expression exhibited a significantly shorter median progression-free survival (PFS) [4.7 months] than the low-expression patients (6.3months) [ P = 0.002]. In summary, H19 -mediated regulation of cisplatin resistance in human lung adenocarcinoma cells is demonstrated for the first time. H19 could potentially serve as a molecular marker to predict the clinical outcomes of lung adenocarcinoma patients.

Purpose Local persistence and relapse of disease in the gross tumor volume (GTV) account for the majority of treatment failures after standard chemoradiation therapy. The primary objective of this phase 1 trial was to define the maximum tolerated dose (MTD) of a hyperfractionated radiation therapy (HFRT) boost to the GTV with concurrent weekly paclitaxel and carboplatin after standard-dose chemoradiation therapy, using image guided intensity modulated radiation therapy techniques. Methods and Materials Eligible patients were given weekly doses of paclitaxel (45 mg/m2) and carboplatin (area under the curve 1.5) for 5 weeks with concurrent radiation therapy (50 Gy), immediately followed by an HFRT boost to the GTV with the same chemotherapy regimen. The boost doses were escalated in increments of 7.2 Gy delivered in 6 twice-daily fractions of 1.2 Gy using a modified Fibonacci design. Once the MTD was established, additional patients were treated at that dose to determine the safety. Results Thirty-one patients fulfilled the inclusion criteria. The incidence of dose-limiting toxicity was 0 of 3, 0 of 3, 0 of 3, 1 of 6 (grade 4 esophagitis), 0 of 3, and 2 of 3 (1 case each of grade 5 esophageal fistula and grade 3 pneumotitis) at 7.2, 14.4, 21.6, 28.8, 36, and 43.2 Gy, respectively, indicating an MTD of 36 Gy. Ten patients treated with this MTD showed no dose-limiting toxicities. The most common acute grade 3 or greater toxicities were esophagitis (26%) and neutropenia (19%). Late toxicity of grade 2 esophageal stricture occurred in 4 patients. The overall response rate was 84% (95% confidence interval, 42%-93%) in the entire cohort. The 1-year local control rate was 100% among those receiving a cumulative dose of the MTD or greater. Conclusions The MTD of the HFRT boost after standard chemoradiation therapy in the setting of concurrent chemotherapy was 36 Gy, resulting in the cumulative tumor dose of 86 Gy in patients primarily with advanced intrathoracic/cervical esophageal squamous cell carcinomas and not adenocarcinomas of the gastroesophageal junction. A phase 2 study to further evaluate this regimen is underway.

Background:Severe fever with thrombocytopenia syndrome (SFTS) is a severe emerging disease, and its incidence has been increasing in recent years. A cross-sectional study was conducted for healthy people in high SFTS endemic areas of Henan province in 2016.Methods:This study used stratified random sampling method and finally 14 natural villages were selected as the investigation site. The questionnaire survey and serum collection were carried out from April to May in 2016. All the serum samples were detected by SFTSV IgM and IgG antibodies by ELISA. Only positive samples of SFTSV IgM antibody need be tested SFTSV RNA and virus cultured. A month after the specimen collection, all persons positive for IgM antibody were followed up one by one to confirm whether he or she was recessive infection.Results:1463 healthy persons were investigated in total. The average seropositive rates of SFTS virus specific IgG and IgM antibodies were 10.46% (153/1463) and 0.82% (12/1463), respectively. IgM antibody was positive in 12 individuals, and 6 of them SFTS virus RNA were also detected. In addition, 5 SFTS virus were isolated from the 6 SFTS virus RNA (+) individuals. By genomic sequencing and phylogenetic analysis, 5 new isolates from healthy crowd all belonged to groups A, which were similar to other isolates from SFTS patients. After one month, all people with SFTS virus IgM antibody had no illness or symptoms.Conclusions:This study confirmed there is SFTS recessive infection in human, and it is the first report about SFTS virus isolation in healthy people.Author Summary:Severe fever with thrombocytopenia syndrome (SFTS), a severe emerging infectious disease, was discovered in rural areas of China. The first SFTS case was found in Henan province, which has had the largest number of SFTS cases in China every year since the disease was discovered. However, as a high incidence area of SFTS in Henan province, the serum prevalence rate of the virus in healthy people is still not clear. Therefore, a cross-sectional survey was performed in high endemic areas and epidemic seasons in 2016. The results showed that the level of specific SFTS seroprevlence was relatively higher and possibility increasing. SFTS RNA were positive and SFTS virus was isolated from the specimens of healthy people. This study confirmed there is SFTS recessive infection in human, and it is the first report about SFTS virus isolation in healthy people.

The harm of trans-fatty acids to health has aroused public concern. It is believed that the main source of trans-fatty acids in diets is the isomerization of unsaturated fatty acids in edible oils during cooking. However, the information on the isomerization mechanism is very limited. In this paper, we used oleic acid, an unsaturated fatty acid, as a simplified model for edible oil and investigated the mechanism of cis/trans isomerization by computation and experiments. The computational results show that Rc-O-O-H is a very important intermediate, and the cleavage of O-O bond in Rc-O-O-H is the rate-controlling step during the cis/trans isomerization. Using the ATR-FTIR measurements, the contents of elaidic acid were measured quantitatively in sites. The experimental results indicate that the cis/trans isomerization of oleic acid can occur obviously only under oxidizing condition when the temperature is higher than 120 °C.

// Hui Pan 1, * , Tao Jiang 1, * , Ningning Cheng 1 , Qi Wang 1 , Shengxiang Ren 1 , Xuefei Li 2 , Chao Zhao 2 , Limin Zhang 1 , Weijing Cai 1 , Caicun Zhou 1 1 Department of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Yangpu District, Shanghai, China 2 Department of Lung Cancer and Immunology, Shanghai Pulmonary Hospital, Tongji University, Tongji University Medical School Cancer Institute, Shanghai, P. R. China * These authors contributed equally to this work Correspondence to: Caicun Zhou, email: caicunzhou_dr@163.com Keywords: long non-coding RNA, non-small-cell lung cancer, non-T790M mutation, acquired resistance, EGFR-TKIs Received: April 10, 2016 Accepted: June 13, 2016 Published: July 09, 2016 ABSTRACT Our previous study demonstrated that long non-coding RNA (lncRNA) BC087858 could stimulate acquired resistance to EGFR-TKIs in non-small cell lung (NSCLC) but the specific regulatory mechanism remained unknown. We aimed to explore the role and mechanism of lncRNA BC087858 on EGFR-TKIs acquired resistance. LncRNA BC087858 mRNA expression was detected by reverse transcription polymerase chain reaction in different NSCLC cell lines and tissues. The relationship between BC087858 expression and clinicopathological factors was performed by Cox multivariate regression analysis. Small-interfering RNA, flow cytometry and trans-well assay were conducted to explore the biological functions of BC087858. Western blotting was used to analyze the target proteins expression. Over-expression was observed in NSCLC cells and patients with acquired resistance to EGFR-TKIs and significantly associated with a shorter progression-free survival (PFS) (12.0 vs. 17.0 months, P = 0.0217) in tumors with respond to EGFR-TKIs. The significant relationship was not observed in patients with T790M mutation (median PFS 17.6 vs. 12.5 months, P = 0.522) but in patients with non-T790M (median PFS 8.0 vs. 18.25 months, P = 0.0427). Down-regulation of BC087858 could significantly promote PC9/R and PC9/G2 cells invasion ( P < 0.05; respectively). BC087858 knockdown restored gefitinib sensitivity in acquired resistant cells with non-T790M and inhibited the activation of the PI3K/AKT and MEK/ERK pathways and epithelial-mesenchymal transition (EMT) via up- regulating ZEB1 and Snail. In conclusion, LncRNA BC087858 could promote cells invasion and induce non-T790M mutation acquired resistance to EGFR-TKIs by activating PI3K/AKT and MEK/ERK pathways and EMT via up- regulating ZEB1 and Snail in NSCLC.

// Ningning Cheng 1,* , Weijing Cai 1,* , Shengxiang Ren 1 , Xuefei Li 2 , Qi Wang 1 , Hui Pan 1 , Mingchuan Zhao 1 , Jiayu Li 1 , Yishi Zhang 1 , Chao Zhao 2 , Xiaoxia Chen 1 , Ke Fei 3 , Caicun Zhou 1 and Fred R. Hirsch 4 1 Department of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University, Tongji University Medical School Cancer Institute, Shanghai, P. R. China 2 Department of Lung Cancer and Immunology, Shanghai Pulmonary Hospital, Tongji University, Tongji University Medical School Cancer Institute, Shanghai, P. R. China 3 Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University, Tongji University Medical School Cancer Institute, Shanghai, P. R. China 4 Department of Medical and Pathology, University of Colorado Cancer Center, Aurora, Colorado, USA * These authors have contributed equally to this work Correspondence to: Caicun Zhou, email: // Keywords : UCA1, EGFR-TKIs, acquired resistance, non-small cell lung cancer Received : February 09, 2015 Accepted : June 01, 2015 Published : June 08, 2015 Abstract The aim of this study was to explore the role of long non-coding RNA UCA1 (urothelial cancer-associated 1) in acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors ( EGFR -TKIs) in EGFR -mutant non-small cell lung cancer (NSCLC). In our study, UCA1 expression was significantly increased in lung cancer cells and patients with acquired resistance to EGFR -TKIs. Over-expression of UCA1 was significantly associated with a shorter progression-free survival (PFS) [13.0 vs . 8.5 months, P < 0.01] in tumors with respond to EGFR -TKIs. The significant relationship was not observed in patients with T790M mutation (10.5 vs . 12.0 months, P = 0.778), but in patients with non-T790M (19.0 vs. 9.0 months, P = 0.023). UCA1 knockdown restored gefitinib sensitivity in acquired resistant cells with non-T790M and inhibited the activation of the AKT/mTOR pathway and epithelial-mesenchymal transition (EMT). The mTOR inhibitor was effective in UCA1 -expressing cell PC9/R. Inhibiting mTOR could change the expression of UCA1 , although there was no significant difference. In conclusion, the influence of over-expression of UCA1 on PFS for patients with acquired resistance to EGFR -TKIs was from the subgroup with non-T790M mutation. UCA1 may induce non-T790M acquired resistance to EGFR -TKIs by activating the AKT/mTOR pathway and EMT.

// Jiayu Li 1 , Xuefei Li 2 , Shengxiang Ren 1 , Xiaoxia Chen 1 , Yishi Zhang 1 , Fei Zhou 1 , Mingchuan Zhao 1 , Chao Zhao 2 , Xiu Chen 3 , Ningning Cheng 1 , Yinmin Zhao 4 , Caicun Zhou 1 , Fred R.Hirsch 5 1 Department of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Tongji University Medical School Cancer Institute, Shanghai, China 2 Department of Lung Cancer and Immunology, Shanghai Pulmonary Hospital, Tongji University, Tongji University Medical School Cancer Institute, Shanghai, China 3 Department of Respiration, Zaozhuang Municipal Hospital, Zaozhuang, Shandong, China 4 Department of Central Laboratory, Shanghai Pulmonary Hospital, Tongji University, Shanghai, China 5 Departments of Medicine and Pathology, University of Colorado Cancer Center, Aurora, Colorado, USA. Correspondence to: Dr. Caicun Zhou, e-mail: caicunzhoudr@163.com Key Words: Non-small cell lung cancer, MiR-200c, Epidermal growth factor receptor, Wild type, Tyrosine-kinase inhibitor Received: July 05, 2014 Accepted: July 29, 2014 Published: August 08, 2014 ABSTRACT Several randomized trials have demonstrated non-small cell lung cancer (NSCLC) patients with activating epidermal growth factor receptor (EGFR) mutations can achieve favorable clinical outcomes on treatment with EGFR tyrosine kinase inhibitors (TKIs). EGFR mutation is considered as a predictive marker for efficacy of EGFR-TKIs in NSCLC. Here we show miR-200c overexpression was correlated with the epithelial phenotype and sensitivity to gefitinib in EGFR wild-type NSCLC cell lines. Up-regulated miR-200c could regain the sensitivity to gefitinib in the EGFR wild-type cell lines and miR-200c could regulate epithelial to mesenchymal transition through PI3K/AKT and MEK/ERK pathways. NSCLC patients at advanced stage (N=150) who received EGFR-TKIs (gefitinib or erlotinib) as second- or third-line therapy from September 2008 to December 2012 were included in the study. In 66 NSCLC patients with wild-type EGFR , high levels of miR-200c expression was associated with higher disease control rate (DCR), longer progression-free survival (PFS) and longer overall survival (OS) compared with low miR-200c expression subgroup. In the subgroup with EGFR mutation, the trend remained the same but not statistically significant. Overall, these findings indicated that miR-200c might be a predictive biomarker for sensitivity to EGFR-TKIs in advanced NSCLC patients with wild-type EGFR .

BACKGROUND Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are widely used for the treatment of patients with advanced non–small cell lung cancer (NSCLC) who have EGFR mutations. Recent studies have indicated that some patients with positive mutations were refractory to EGFR TKIs if they harbored a B-cell chronic lymphocytic leukemia/lymphoma (Bcl-2)-like 11 (Bim) deletion polymorphism. The objective of the current work was to retrospectively study the Bim deletion polymorphism in Chinese patients with NSCLC and its correlation with the efficacy of EGFR TKIs. METHODS Distribution of the Bim polymorphism was detected using polymerase chain reaction analysis and direct sequencing of DNA from peripheral neutrophils in samples from 352 patients with NSCLC. Of the 352 patients, 166 who received TKI therapy and had an activating mutation identified were involved in further analysis. Progression-free survival (PFS) was the primary endpoint of the subsequent analyses, and the incidence of the Bim polymorphism and its relation to clinical benefit from EGFR TKIs also were investigated. RESULTS In total, 45 of 352 patient samples (12.8%) had the Bim deletion polymorphism, which was distributed randomly with regard to various clinical characteristics. In patients with EGFR mutations who received treatment with TKIs, the median PFS and the median objective response rate were 4.7 months and 25%, respectively, for those with the Bim deletion polymorphism versus 11 months (P = .003) and 66% (P = .001), respectively, for those with wild-type Bim. Cox regression analysis identified Bim status (P = .016) and sex (P = .002) as independent factors predicting clinical benefit from EGFR TKIs in patients with EGFR-mutated NSCLC. CONCLUSIONS The incidence of the Bim deletion polymorphism was approximately 13% in this study, and it was associated with a poor clinical response to EGFR TKIs in patients who had NSCLC with EGFR mutations. Cancer 2014;120:2299–2307. © 2014 American Cancer Society.

To investigate the etiology of severe hand-foot-mouth disease (HFMD) in children in Henan province.A total of 244 HFMD cases admitted to a hospital in Zhengzhou from April to June of 2014 were recruited for research sampling, Real-time RT-PCR, virus isolation, VP1 sequencing and alignment methods were used to test the enterovirus-related etiology. SPSS 17.0 was used in performing statistical analysis.There were 109 severe and 135 mild cases among all the 244 HFMD cases. The number of enterovirus positive stool samples was 229, with positive rate as 93.85%. EV71, Cox A16 and Cox A10 made up 83.84%, 5.68% and 8.30% of the enterovirus etiologicy, strains, respectively. EV71 infection caused 8 HFMD cases with heart-lung failure and 2 death, Cox A10 infection led to 1 HFMD case with heart-lung failure and death. There were statistically differences seen regarding the enterovirus infection rates between severe and the mild HFMD cases (χ(2)=5.312,P=0.021). Statistically significant difference was seen in the constituent ratio of EV71, Cox A16 and the others by Fisher' s exact test (P=0.048). There was statistically significant difference seen between the cardiorespiratory failure rate and the fatality rate by EV71 and Cox A10 infection (χ(2)=0.051,P=0.821; χ(2)=2.198,P=0.138). Cox A10 strains idenfied in Henan in 2014 belonged to genotype 6. The rates on homology of nucleotide and amino acid among the Cox A10 strains in Henan in 2014 were 94.3%-99.7% and 96.3%-100.0% respectively.EV71 still remained the most common pathogen that causing severe HFMD in children, with the increasing Cox A10 percentage in the pathogens spectrum of HFMD infection. Cox A10 strains in Henan in 2014 belonged to genotype 6. Genotype 6 Cox A10 had appeared and widely distributed in Henan for long time, but not yet variated or reconstructed. Cox A10 infection could lead to cardio-respiratory failure thus called for the monitoring program on non-EV71 and non-Cox A16 enterovirus, especially Cox A10 to be strenthened.

Smartphones are closely coupled with their users and smartphone sensors can perceive users' private information. The existing studies in this area focus on user activity recognition and short-term context detection. In this paper, we show that smartphone sensors are able to profile users' long-term privacy and more sensitive information. We present the techniques of discovering users' spending level by merely using smartphone sensors. We do not access users' contacts, calendar, or call log, so that the profiling is performed in a non-intrusive manner. This paper is an alert towards the public that the privacy leakage could be far worse than imagination by just carrying smartphones.

Five complexes have been synthesized by the reaction of lanthanide(III) nitrate with 2-thenoyltrifluoroacetone (HTTA) and p-hydroxybenzoic acid (L). The complexes have been characterized by elemental analysis, molar conductivity, FT-IR, UV-Vis, 1H NMR, TG-DTA, XPS, and transmission electron microscope. The general formula of the complexes is Na[Ln(TTA)3L] (Ln = La3+, Ce3+, Nd3+, Eu3+, Er3+). The antibacterial activities indicate that all five complexes exhibit antibacterial ability against Escherichia coli and Staphylococcus aureus with broad antimicrobial spectrums. The antitumor activity of the five complexes against K562 tumor cell in vitro is measured using methyl thiazolyl tetrazolium (MTT) colorimetry. The results show that the complexes induce K562 tumor cell apoptosis, and the complexes exhibit inhibitory effect on leukemia K562 cells.

Four new solid ternary complexes of lanthanide with 2,6-pyridine dicarboxylic acid and α-picolinic acid [Ln(DPA)(Lα)(H2O)] · 2H2O (Ln = La3+, Ce3+, Eu3+, or Gd3+; DPA = 2,6-pyridine dicarboxylic acid; HLα = α-picolinic acid) have been synthesized and characterized by elemental analysis, molar conductance, FT-IR, UV–Vis, and TG–DTA. The antibacterial activities indicate that all the complexes exhibit antibacterial ability against Escherichia coli and Staphylococcus aureus with broad antimicrobial spectra. The anticancer activity of the La complex against K562 tumor cell in vitro is measured using methyl thiazolyl tetrazolium (MTT) colorimetry and flow cytometry. The La complex can induce K562 tumor cell apoptosis, presenting the best apoptosis effect by acting on the S period after inducing K562 tumor cell for 72 h.

Recent studies demonstrate that progesterone (PROG) significantly reduces cerebral edema and enhances functional recovery from traumatic brain injury (TBI) and stroke in several animal models, but its concrete mechanism is still unknown. This study was designed to investigate the inhibitory effects of PROG on inflammatory response after stroke and its influence on the structure of blood-brain barrier (BBB). In the treatment group, PROG was dissolved in 22.5% 2-hydroxypropyl-bcyclodextrin and given in a dose of 8 mg/kg by intraperitoneal injection 1h and 6h after permanent occlusion of middle cerebral artery (pMCAO). Additional injections of 15 mg/kg were administered subcutaneously once a day after pMCAO. The expression of tumor necrosis factor-alpha (TNF-alpha), matrix metalloproteinase-9 (MMP-9) and claudin5 was measured by western blot technique. Evan's blue extravasation and brain water content in the ipsilateral hemisphere was also detected to evaluate the permeability of BBB. Western blot analysis revealed that the expression of TNF-alpha and MMP-9 were reduced while claudin5 was up-regulated in brain tissues of PROG-treated rats. In addition, examination of BBB permeability also showed that administration of PROG significantly reduced Evan's blue extravasation and brain water content in the ipsilateral hemisphere compared to vehicle-treated rats. Our findings reveal that PROG inhibited the inflammatory response after experimental stroke and mitigated the severity of brain damage, suggesting a role for PROG in the integrity of the BBB and subsequent edema formation following cerebral ischemia.

PurposeContext correctness and fault handling are very important to the quality of service in context‐aware applications. However, they are often ignored by researchers and application developers. This paper aims to present a model for context‐aware applications.Design/methodology/approachThis paper proposes a transaction model for context‐aware applications, in order to provide a uniform infrastructure for service quality management.FindingsThe paper finds that, in this model, context‐aware applications are organized as a number of logic units and each unit may have a compensation module, which will be executed when errors or exceptions occur during the execution of those applications in order to minimize the bad infection. This model supports nested scopes and the number of levels of subtransactions is unlimited.Practical implicationsThe paper also presents an implementation of this transaction model, which is specialized for context‐aware use.Originality/valueThis paper utilized a novel transaction model to manage the quality of context‐aware applications. The authors have not seen similar work on this topic.

Alfalfa (Medicago sativa L.) is one of the most widely cultivated perennial forage legumes worldwide. Fall dormancy is an adaptive character related to the biomass production and winter survival in alfalfa. The physiological, biochemical and molecular mechanisms causing fall dormancy and the related genes have not been well studied. In this study, we sequenced two standard varieties of alfalfa (dormant and non-dormant) at two time points and generated approximately 160 million high quality paired-end sequence reads using sequencing by synthesis (SBS) technology. The de novo transcriptome assembly generated a set of 192,875 transcripts with an average length of 856 bp representing about 165.1 Mb of the alfalfa leaf transcriptome. After assembly, 111,062 (57.6%) transcripts were annotated against the NCBI non-redundant database. A total of 30,165 (15.6%) transcripts were mapped to 323 Kyoto Encyclopedia of Genes and Genomes pathways. We also identified 41,973 simple sequence repeats, which can be used to generate markers for alfalfa, and 1,541 transcription factors were identified across 1,350 transcripts. Gene expression between dormant and non-dormant alfalfa at different time points were performed, and we identified several differentially expressed genes potentially related to fall dormancy. The Gene Ontology and pathways information were also identified. We sequenced and assembled the leaf transcriptome of alfalfa related to fall dormancy, and also identified some genes of interest involved in the fall dormancy mechanism. Thus, our research focused on studying fall dormancy in alfalfa through transcriptome sequencing. The sequencing and gene expression data generated in this study may be used further to elucidate the complete mechanisms governing fall dormancy in alfalfa.

Background POTEE (POTE ankyrin domain family, member E) is a newly identified cancer-testis antigen that has been found to be expressed in a wide variety of human cancers including cancers of the colon, prostate, lung, breast, ovary, and pancreas. Aim To measure the serum levels of POTEE in patients with non-small-cell lung cancer (NSCLC) and to explore the clinical significance of POTEE in NSCLC. Patients and Methods 104 NSCLC patients, 66 benign lung disease patients and 80 healthy volunteers were enrolled in this study from May 2013 to February 2014. Serum POTEE levels were measured using enzyme-linked immunosorbent assay (ELISA). Numerical variables were recorded as means ± standard deviation (SD) and analyzed by independent t tests. Categorical variables were calculated as rates and were analyzed using a χ2 test or Fisher’s exact test. Survival curves were estimated and compared using the Kaplan-Meier method and log-rank tests. Results Serum POTEE levels were significantly higher in NSCLC patients than in benign lung disease patients and healthy controls (mean ± SD [pg/ml], 324.38± 13.84 vs. 156.93 ± 17.38 and 139.09 ± 15.80, P

Background: Epithelial-mesenchymal transition (EMT) is of great importance in tumor metastasis. Our previous study demonstrates that epithelial phenotype is related to epidermal growth factor receptor (EGFR) mutation and the sensitivity of EGFR tyrosine kinase inhibitors (TKIs) in advanced non-small cell lung cancer (NSCLC) patients. However, the role of EMT phenotype in malignant pleural effusions in predicting prognosis is unknown in lung adenocarcinoma patients. Method: Pleural effusions of lung adenocarcinoma patients were collected and made into cell block (CB). EGFR mutation was detected using amplification refractory mutation system (ARMS) PCR method and H-score system was applied to evaluate the staining intensity of EMT marker and tumor cell ratio. Results: Forty-three CB samples, including 22 samples before any treatment (baseline, group 1) and 21 with disease progression (group 2) after first-line chemotherapy, were enrolled in this study. The expression of N-cadherin and vimentin were low in the CB tumor cells. There was no significant difference in the tumor cell radio and E-cadherin expression in the two groups. E-cadherin expression had no association with sex, age and smoking status and also patient response in both the two groups. However, high E-cadherin expression was related to EGFR mutation (P = 0.032) and long progression-free survival (PFS) (P = 0.015) in group 1 but not group 2 samples. Conclusion: E-cadherin expression in CB samples was associated with EGFR mutation status and patient prognosis in lung adenocarcinoma patients in first-line chemotherapy.

The application of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) is limited by drug resistance in non-small cell lung cancer (NSCLC). Long non-coding RNAs (lncRNAs) are known to be involved in tumor development and metastasis, as well as chemotherapy resistance. To gain insight into the molecular mechanisms of EGFR-TKIs resistance, EGFR-TKIs‑sensitive and ‑resistant human lung cancer cells were analyzed by lncRNA microarray. In the present study, we found a total of 22,587 lncRNAs expressed in lung cancer cells. Of these, the expression level of 1,731 lncRNAs was upregulated >2-fold compared with gefitinib-sensitive cells while that of 2,936 was downregulated. Bioinformatics analysis (GO and pathway analyses) revealed that some classical pathways participating in cell proliferation and apoptosis were aberrantly expressed in these cells (P-value cut-off was 0.05). Enhancer-like lncRNAs and their nearby coding genes were analyzed. Six lncRNAs were identified as potential enhancers. Several lncRNAs were validated in lung cancer cell lines using RT-qPCR. To the best of our knowledge, the results showed for the first time that differentially expressed lncRNAs responded to EGFR-TKIs resistance in NSCLC cells. LncRNAs may therefore be novel candidate biomarkers and potential targets for EGFR-TKIs therapy in the future.

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are widely used for the treatment of patients with advanced non-small cell lung cancer (NSCLC) who have EGFR mutations. Recent studies have indicated that some patients with positive mutations were refractory to EGFR TKIs if they harbored a B-cell chronic lymphocytic leukemia/lymphoma (Bcl-2)-like 11 (Bim) deletion polymorphism. The objective of the current work was to retrospectively study the Bim deletion polymorphism in Chinese patients with NSCLC and its correlation with the efficacy of EGFR TKIs.Distribution of the Bim polymorphism was detected using polymerase chain reaction analysis and direct sequencing of DNA from peripheral neutrophils in samples from 352 patients with NSCLC. Of the 352 patients, 166 who received TKI therapy and had an activating mutation identified were involved in further analysis. Progression-free survival (PFS) was the primary endpoint of the subsequent analyses, and the incidence of the Bim polymorphism and its relation to clinical benefit from EGFR TKIs also were investigated.In total, 45 of 352 patient samples (12.8%) had the Bim deletion polymorphism, which was distributed randomly with regard to various clinical characteristics. In patients with EGFR mutations who received treatment with TKIs, the median PFS and the median objective response rate were 4.7 months and 25%, respectively, for those with the Bim deletion polymorphism versus 11 months (P = .003) and 66% (P = .001), respectively, for those with wild-type Bim. Cox regression analysis identified Bim status (P = .016) and sex (P = .002) as independent factors predicting clinical benefit from EGFR TKIs in patients with EGFR-mutated NSCLC.The incidence of the Bim deletion polymorphism was approximately 13% in this study, and it was associated with a poor clinical response to EGFR TKIs in patients who had NSCLC with EGFR mutations.

International audience; With ever increasing usage of handheld devices and vast deployment of wireless networks, we observe that it is possible to collect data from mobile devices and reveal personal relationships of their owners. In the paper, we exploit the hidden information collected from WLAN devices and infer individual relationships between device pairs based on three observation dimensions: network association history, physical proximity and spatio-temporal behavior. By measuring WLAN data, we demonstrate that device owners with social relationship tend to share access points, or show similar behavior patterns in wireless communications (e.g. go to the same place periodically to access the same WLAN network). These results can be exploited for various network analytic purposes.

Aim: To determine the leucine-rich repeat-containing G-protein coupled receptor 5 (LGR5) level in human pituitary adenomas and the role of LGR5 in the development of human pituitary adenomas. Methods: Immunohistochemistry is performed to determine the expression of LGR5 in pituitary adenomas and normal pituitaries. LGR5 expression level is determined by the criteria as follows. The one-way analysis of variance (ANOVA) was used to evaluate any significant differences of LGR5 among individual groups. The correlation between expression and the other clinical factors were evaluated by using the Mann-Whitney test and one-way ANOVA. Results: LGR5 is significantly overexpressed in pituitary adenomas compared to normal pituitaries. Conclusion: The overexpression of LGR5 may facilitate the growth of these tumors. Potentially, the finding in the study could be exploited to develop innovative molecular targeted diagnosis and treatment for human pituitary adenomas.

Transmit power estimation is widely used in network monitoring, power-aware design of MANETs, primary user detection in cognitive radio networks and many other areas. Traditional methods for transmit power estimation are trilateration-based, which require an underlying infrastructure with at least three monitors. In this paper, we propose a novel transmit power estimation method which utilizes the nuance of the received signal strength at different frequencies. Our method only needs one monitor, thus has less hardware requirement and is much easier to carry around. We use a support vector machine to facilitate the estimation, and conduct real-world experiments to validate our method. The experimental results demonstrate that our method is able to achieve the accuracy as high as 90%, which in practice outperforms the trilateration method using multiple monitors.

Development of network of nodes connected with their trust values and the propagation of these trust values to far away nodes are basic operations of the modern day trustworthy networks. Trust can be exploited to mitigate the security threats in wireless network. Most of the existing trust propagation methods are based on flooding trust information, which puts a heavy burden on wireless communication, especially in ad hoc network and sensor network. In this paper, we propose a rendezvous based trust propagation scheme. Trust requester and trust provider send out trust-request and computed-trust tickets respectively, which will meet in some common rendezvous node with certain probability. Computed-trust will then be propagated to the requester. We carry out detailed performance evaluations of our scheme. The results show that our method achieves up to 66% overhead reduction in trust propagation compared to flood based methods.

e19079 Background: Previous research found that HOTAIR, a long non-coding RNA, aberrantly expressed and associated with tumor invasion, metastasis and chemo-resistance in many cancers. The aim of t...

The growth superiority of hybrid scallop Chlamys farreri (♀) × Patinopecten yessoensis (♂), as the following successive generation selection have been reported. However, the data about the genetic diversity in those population remains unexplored. In this study, the genetic structure analysis of F1, F2 and F3 were conducted by PCR with 10 Simple Sequence Repeats (SSR) primers. It showed that a total of 68 alleles were detected, and the number of alleles per locus ranged from 3 to 11, Polymorphism Information Content (PIC) per locus ranged from 0.4729 to 0.8429. And, the average observed heterozygosity (Ho) of the three populations were 0.6100, 0.6975 and 0.7750, while the average expected heterozygosity (He) were 0.7607, 0.7751 and 0.7379 respectively. Fst values among the three populations were also low (Fst