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1.  Solution-processed small-molecule solar cells: breaking the 10% power conversion efficiency 
Scientific Reports  2013;3:3356.
A two-dimensional conjugated small molecule (SMPV1) was designed and synthesized for high performance solution-processed organic solar cells. This study explores the photovoltaic properties of this molecule as a donor, with a fullerene derivative as an acceptor, using solution processing in single junction and double junction tandem solar cells. The single junction solar cells based on SMPV1 exhibited a certified power conversion efficiency of 8.02% under AM 1.5 G irradiation (100 mW cm−2). A homo-tandem solar cell based on SMPV1 was constructed with a novel interlayer (or tunnel junction) consisting of bilayer conjugated polyelectrolyte, demonstrating an unprecedented PCE of 10.1%. These results strongly suggest solution-processed small molecular materials are excellent candidates for organic solar cells.
doi:10.1038/srep03356
PMCID: PMC3842540  PMID: 24285006
2.  MiR-194, commonly repressed in colorectal cancer, suppresses tumor growth by regulating the MAP4K4/c-Jun/MDM2 signaling pathway  
Cell Cycle  2015;14(7):1046-1058.
Tumor growth cascade is a complicated and multistep process with numerous obstacles. Until recently, evidences have shown the involvement of microRNAs (miRNAs) in tumorigenesis and tumor progression of various cancers, including colorectal cancer (CRC). In this study, we explored the role of miR-194 and its downstream pathway in CRC. We acquired data through miRNA microarray profiles, showing that the expression of miR-194 was significantly suppressed in CRC tissues compared with corresponding noncancerous tissues. Decreased miR-194 expression was obviously associated with tumor size and tumor differentiation, as well as TNM stage. Both Kaplan–Meier and multivariate survival analysis showed that downregulated miR-194 was associated with overall survival. Moreover, functional assays indicated that overexpression of miR-194 in CRC cell lines inhibited cell proliferation both in vitro and in vivo. In addition, using dual-luciferase reporter gene assay, we found MAP4K4 was the direct target of miR-194. Silencing of MAP4K4 resulted in similar biological behavior changes to that of overexpression of miR-194. We also observed through Human Gene Expression Array that MDM2 was one of the downstream targets of MAP4K4. Knockdown of MAP4K4 downregulated MDM2 expression through transcription factor c-Jun binding to the −1063 to -1057 bp of the promoter. These results suggest that miR-194, regulating the MAP4K4/c-Jun/MDM2 signaling pathway, might act as a tumor suppressor and serve as a novel target for CRC prevention and therapy.
doi:10.1080/15384101.2015.1007767
PMCID: PMC4615039  PMID: 25602366
apoptosis; c-Jun; colorectal cancer; miR-194; MAP4K4; MDM2; proliferation
3.  Enantio-alteration of gene transcription associated with bioconcentration in adult zebrafish (Danio rerio) exposed to chiral PCB149 
Scientific Reports  2016;6:19478.
Enantioselective enrichment of chiral PCB149 (2,2’,3,4’,5’,6-hexachlorobiphenyl) was analysed in adult zebrafish (Danio rerio) exposed to the racemate, (−)-PCB149, and (+)-PCB149. Greater enrichment of (−)-PCB149 compared to (+) PCB149 was observed following 0.5 ng/L exposure; however, as the exposure time and concentration increased, racemic enrichment was observed in adult fish exposed to the racemate. No biotransformation between the two isomers was observed in fish exposed to single enantiomers. When zebrafish were exposed to different forms of chiral PCB149, enantioselective expression of genes associated with polychlorinated biphenyls (PCBs) was observed in brain and liver tissues and enantioselective correlations between bioconcentration and target gene expression levels were observed in brain and liver tissues. The strong positive correlations between expression levels of target genes (alox5a and alox12) and PCB149 bioconcentration suggest that prolonged exposure to the racemate of chiral PCB149 may result in inflammation-associated diseases. Prolonged exposure to (−)-PCB149 may also affect metabolic pathways such as dehydrogenation and methylation in the brain tissues of adult zebrafish. Hepatic expression levels of genes related to the antioxidant system were significantly negatively correlated with bioconcentration following exposure to (+)-PCB149.
doi:10.1038/srep19478
PMCID: PMC4726444  PMID: 26786282
4.  The Hydroxyl at Position C1 of Genipin Is the Active Inhibitory Group that Affects Mitochondrial Uncoupling Protein 2 in Panc-1 Cells 
PLoS ONE  2016;11(1):e0147026.
Genipin (GNP) effectively inhibits uncoupling protein 2 (UCP2), which regulates the leakage of protons across the inner mitochondrial membrane. UCP2 inhibition may induce pancreatic adenocarcinoma cell death by increasing reactive oxygen species (ROS) levels. In this study, the hydroxyls at positions C10 (10-OH) and C1 (1-OH) of GNP were hypothesized to be the active groups that cause these inhibitory effects. Four GNP derivatives in which the hydroxyl at position C10 or C1 was replaced with other chemical groups were synthesized and isolated. Differences in the inhibitory effects of GNP and its four derivatives on pancreatic carcinoma cell (Panc-1) proliferation were assessed. The effects of GNP and its derivatives on apoptosis, UCP2 inhibition and ROS production were also studied to explore the relationship between GNP’s activity and its structure. The derivatives with 1-OH substitutions, geniposide (1-GNP1) and 1-ethyl-genipin (1-GNP2) lacked cytotoxic effects, while the other derivatives that retained 1-OH, 10-piv-genipin (10-GNP1) and 10-acetic acid-genipin (10-GNP2) exerted biological effects similar to those of GNP, even in the absence of 10-OH. Thus, 1-OH is the key functional group in the structure of GNP that is responsible for GNP’s apoptotic effects. These cytotoxic effects involve the induction of Panc-1 cell apoptosis through UCP2 inhibition and subsequent ROS production.
doi:10.1371/journal.pone.0147026
PMCID: PMC4714807  PMID: 26771380
5.  Polysaccharide-based Noncovalent Assembly for Targeted Delivery of Taxol 
Scientific Reports  2016;6:19212.
The construction of synthetic straightforward, biocompatible and biodegradable targeted drug delivery system with fluorescent tracking abilities, high anticancer activities and low side effects is still a challenge in the field of biochemistry and material chemistry. In this work, we constructed targeted paclitaxel (Taxol) delivery nanoparticles composed of permethyl-β-cyclodextrin modified hyaluronic acid (HApCD) and porphyrin modified paclitaxel prodrug (PorTaxol), through host-guest and amphiphilic interactions. The obtained nanoparticles (HATXP) were biocompatible and enzymatic biodegradable due to their hydrophilic hyaluronic acid (HA) shell and hydrophobic Taxol core, and exhibited specific targeting internalization into cancer cells via HA receptor mediated endocytosis effects. The cytotoxicity experiments showed that the HATXP exhibited similar anticancer activities to, but much lower side effects than commercial anticancer drug Taxol. The present work would provide a platform for targeted paclitaxel drug delivery and a general protocol for the design of advanced multifunctional nanoscale biomaterials for targeted drug/gene delivery.
doi:10.1038/srep19212
PMCID: PMC4725941  PMID: 26759029
6.  Association between Time of Day of Sports-Related Physical Activity and the Onset of Acute Myocardial Infarction in a Chinese Population 
PLoS ONE  2016;11(1):e0146472.
Objective
To investigate the association between the time of day of sports-related physical activity and the onset of acute myocardial infarction (AMI) in a coronary artery disease (CAD) population in China.
Methods
Between February 2014 and March 2015, a total of 696 patients from Nanjing, China, who had CAD were studied and divided into two groups (Non-AMI and AMI groups). The work-related activity and sports-related physical activity information were obtained from a self-reporting predesigned patient questionnaire.
Results
Sports-related physical activity was associated with a lower risk of the onset of AMI, after adjusting the established and potential confounders, with an adjusted odds ratio (OR) of 0.67 (95% CI, 0.47–0.94) compared with those who did not have any sports-related physical activity. A dose–response relationship was observed for intensity, duration, and frequency of sports-related physical activity. Further stratification analysis revealed that the protective effects of sports-related physical activity were significant in the morning and evening groups, and patients who exercised in the evening were at a lower risk of AMI than those doing sports-related physical activity in the morning. The adjusted ORs for doing sports-related physical activity in the morning and evening groups were 0.60(0.36–0.98) and 0.56(0.37–0.87), respectively, compared with inactivity (all P<0.05). On the occurrence of AMI, doing sports-related physical activity in the evening had an adjusted OR of 0.93 (95% CI, 0.54–1.64, P = 0.824) compared with in the morning group.
Conclusions
Sports-related physical activity is associated with a lower risk of onset of AMI than inactivity in Chinese people. For CAD patients, we suggest they participate in sports-related physical activity of high intensity, long duration, and high frequency. Doing sports-related physical activity in the evening and in the morning have similar benefits on the prevention of the onset of AMI.
doi:10.1371/journal.pone.0146472
PMCID: PMC4709000  PMID: 26752185
7.  Altered functional connectivity in persistent developmental stuttering 
Scientific Reports  2016;6:19128.
Persistent developmental stuttering (PDS) is a speech disorder that impairs communication skills. Despite extensive research, the core causes of PDS are elusive. Converging evidence from task-induced neuroimaging methods has demonstrated the contributions of the basal ganglia and the cerebellum to PDS, but such task-state neuroimaging findings are often confounded by behavioral performance differences between subjects who stutter and normal controls. Here, using resting-state functional magnetic resonance imaging, we investigated functional connectivity within cerebellar-cortical and basal ganglia-thalamocortical networks in 16 adults who stutter and 18 age-matched fluent speakers. Seed-to-voxel analysis demonstrated that, compared to controls, adults who stutter showed alternations in functional connectivity of cerebellum to motor cortex as well as connectivity among different locals within cerebellum. Additionally, we found that functional connectivity within cerebellar circuits was significantly correlated with severity of stuttering. The alternations of functional connectivity within basal ganglia-thalamocortical networks were identified as the reduced connectivity of the putamen to the superior temporal gyrus and inferior parietal lobules in adults who stutter. The abnormalities of resting state functional connectivity are assumed to affect language planning and motor execution critical for speaking fluently. Our findings may yield neurobiological cues to the biomarkers of PDS.
doi:10.1038/srep19128
PMCID: PMC4705486  PMID: 26743821
8.  Elderly male smokers with right lung tumors are viable candidates for KRAS mutation screening 
Scientific Reports  2016;6:18566.
Genetic aberrations in tumor driver genes provide specific molecular targets for therapeutic intervention, which can greatly improve therapeutic outcomes. Here, we analyzed the mutational frequency of EGFR and KRAS gene, as well as EML4-ALK rearrangement, and summarized the clinicopathological characters of Chinese lung cancer patients. We detected the mutation spectrum of 1033 primary lung cancer patients. The analyzed clinicopathological parameters included gender, age at diagnosis, smoking status, pathological TNM stage, tumor morphology and location, visceral pleural invasion, and histological type. A total of 618 patients had mutations in EGFR or KRAS gene as well as rearrangement of EML4-ALK. Exon 19 deletions and L858R in the EGFR gene were the most frequent mutations. Left-side lung cancer was more common in female patients carrying the KRAS mutation. Rearrangement of EML4-ALK was more common in non-tobacco-using male patients, who also exhibited a higher likelihood of visceral pleura invasion. Elderly females who never smoked and possessed 1–20 mm stage I adenocarcinomas in the right side exhibited a higher frequency of EGFR mutations. Elderly male smokers with right lung tumors were viable candidates for KRAS mutation screening.
doi:10.1038/srep18566
PMCID: PMC4703983  PMID: 26739511
10.  Improvement of Liver Transplantation Outcome by Heme Oxygenase-1-Transduced Bone Marrow Mesenchymal Stem Cells in Rats 
Stem Cells International  2016;2016:9235073.
Bone marrow mesenchymal stem cells (BMMSCs) exert immunosuppressive activity in transplantation, and heme oxygenase-1 (HO-1) enhances their immunomodulatory effects. The aim of this study was to determine whether HO-1-transduced BMMSCs (HO-1/MSCs) improve rat liver transplantation (LTx) outcomes. Orthotopic LTx rejection models were treated with HO-1/MSCs, BMMSCs, HO-1, or normal saline, respectively. Our results showed a significant improvement in survival rates in the HO-1/BMMSCs group compared to the control groups. At all time points, liver function marker levels in the HO-1/MSCs group were significantly lower than in the other three groups; on POD 1, 7, and 14, the degree of rejection and apoptotic cells was significantly less in the HO-1/MSCs group than in the other three groups. Interleukin- (IL-) 10 and transforming growth factor-β levels were significantly increased, while IL-2, IL-6, IL-17, IL-23, tumor necrosis factor-α, and interferon-γ levels were significantly decreased in the HO-1/MSCs group when compared to the other groups. Splenocyte Tregs were significantly increased by HO-1/MSCs compared with controls on POD 3, 5, 7, 10, 14, and 28. Summarily, we provide evidence that HO-1/MSCs improved allogeneic LTx outcomes by attenuating inflammatory responses and acute cellular rejection, as well as enhanced immunomodulatory effects compared with BMMSCs.
doi:10.1155/2016/9235073
PMCID: PMC4736423  PMID: 26862332
11.  Telomerase reverse transcriptase acts in a feedback loop with NF-κB pathway to regulate macrophage polarization in alcoholic liver disease 
Scientific Reports  2016;6:18685.
Activation of Kupffer cells (KCs) plays a central role in the pathogenesis of alcoholic liver disease (ALD). C57BL/6 mice fed EtOH-containing diet showed a mixed induction of hepatic classical (M1) and alternative (M2) macrophage markers. Since telomerase activation occurs at critical stages of myeloid and lymphoid cell activation, we herein investigated the role of telomerase reverse transcriptase (TERT), the determining factor of telomerase, in macrophage activation during ALD. In our study, TERT expression and telomerase activity (TA) were remarkably increased in liver tissue of EtOH-fed mice. Moreover, EtOH significantly up-regulated TERT in isolated KCs and RAW 264.7 cells and LPS induced TERT production in vitro. These data indicate that up-regulation of TERT may play a critical role in macrophages during ALD. Furthermore, loss- and gain-of-function studies suggested that TERT switched macrophages towards M1 phenotype by regulating NF-κB signaling, but had limited effect on M2 macrophages polarization in vitro. Additionally, PDTC, a chemical inhibitor of NF-κB, could dramatically down-regulate TERT expression and the hallmarks of M1 macrophages. Therefore, our study unveils the role of TERT in macrophage polarization and the cross-talk between TERT and p65, which may provide a possible explanation for the ethanol-mediated hepatic proinflammatory response and M1 macrophage polarization.
doi:10.1038/srep18685
PMCID: PMC4698632  PMID: 26725521
12.  Geographic Variation of Diapause and Sensitive Stages of Photoperiodic Response in Laodelphax striatellus Fallén (Hemiptera: Delphacidae) 
Journal of Insect Science  2016;16(1):13.
Large numbers of the small brown planthopper Laodelphax striatellus (Fallén) (Hemiptera: Delphacidae) occur in temperate regions, causing severe losses in rice, wheat, and other economically important crops. The planthoppers enter diapause in the third- or fourth-instar nymph stage, induced by short photoperiods and low temperatures. To investigate the geographic variation in L. striatellus diapause, we compared the incidence of nymphal diapause under various constant temperature (20 and 27°C) and a photoperiod of 4:20, 8:16, 10:14, 12:12, 14:10, and 16:8 (L:D) h regimes among three populations collected from Hanoi (21.02° N, 105.85° E, northern Vietnam), Jiangyan (32.51° N, 120.15° E, eastern China), and Changchun (43.89° N, 125.32° E, north-eastern China). Our results indicated that there were significant geographic variations in the diapause of L. striatellus. When the original latitude of the populations increased, higher diapause incidence and longer critical photoperiod (CP) were exhibited. The CPs of the Jiangyan and Changchun populations were ∼12 hr 30 min and 13 hr at 20°C, and 11 hr and 11 hr 20 min at 27°C, respectively. The second- and third-instar nymphs were at the stage most sensitive to the photoperiod. However, when the fourth- and fifth-instar nymphs were transferred to a long photoperiod, the diapause-inducing effect of the short photoperiod on young instars was almost reversed. The considerable geographic variations in the nymphal diapause of L. striatellus reflect their adaptation in response to a variable environment and provide insights to develop effective pest management strategies.
doi:10.1093/jisesa/iev161
PMCID: PMC4735830  PMID: 26839318
diapause; geographic variation; Laodelphax striatellus; sensitive stage
13.  Loss of Runx2 in Committed Osteoblasts Impairs Postnatal Skeletogenesis 
The Runx2 transcription factor is critical for commitment to the osteoblast lineage. However, its role in committed osteoblasts and its functions during postnatal skeletogenesis remain unclear. We established a Runx2-floxed line with insertion of loxP sites around exon 8 of the Runx2 gene. Runx2 protein lacking the region encoded by exon 8 is imported into the nucleus and binds target DNA, but exhibits diminished transcriptional activity. We specifically deleted the Runx2 gene in committed osteoblasts using 2.3kb col1a-Cre transgenic mice. Surprisingly, the homozygous Runx2 mutant mice were born alive. The Runx2 heterozygous and homozygous null were grossly indistinguishable from wild-type littermates at birth. Runx2 deficiency did not alter proliferative capacity of osteoblasts during embryonic development (E18). Chondrocyte differentiation and cartilage growth in mutants was similar to wild-type mice from birth to 3 months of age. Analysis of the embryonic skeleton revealed poor calcification in homozygous mutants, which was more evident in bones formed by intramembranous ossification. Runx2 mutants showed progressive retardation in postnatal growth and exhibited significantly low bone mass by 1 month of age. Decreased bone formation was associated with decreased gene expression of osteoblast markers and impaired collagen assembly in the extracellular matrix. Consequently, Runx2 mutant bones exhibited decreased stiffness and structural integrity. By 3 months of age, bone acquisition in mutant mice was roughly half that of wild-type littermates. In addition to impaired osteoblast function, mutant mice showed markedly decreased osteoclast number and postnatal bone resorption. Taken together, functional deficiency of Runx2 in osteoblasts does not result in failed embryonic skeletogenesis, but disrupts postnatal bone formation.
doi:10.1002/jbmr.2321
PMCID: PMC4280286  PMID: 25079226
Genetic animal models < ANIMAL MODELS, BONE MODELING AND REMODELING; Molecular pathways - development < BONE MODELING AND REMODELING; Osteoblasts < CELLS OF BONE; Osteoclasts < CELLS OF BONE
14.  Risk Distribution of Human Infections with Avian Influenza H7N9 and H5N1 virus in China 
Scientific Reports  2015;5:18610.
It has been documented that the epidemiological characteristics of human infections with H7N9 differ significantly between H5N1. However, potential factors that may explain the different spatial distributions remain unexplored. We use boosted regression tree (BRT) models to explore the association of agro-ecological, environmental and meteorological variables with the occurrence of human cases of H7N9 and H5N1, and map the probabilities of occurrence of human cases. Live poultry markets, density of human, coverage of built-up land, relative humidity and precipitation were significant predictors for both. In addition, density of poultry, coverage of shrub and temperature played important roles for human H7N9 infection, whereas human H5N1 infection was associated with coverage of forest and water body. Based on the risks and distribution of ecological characteristics which may facilitate the circulation of the two viruses, we found Yangtze River Delta and Pearl River Delta, along with a few spots on the southeast coastline, to be the high risk areas for H7N9 and H5N1. Additional, H5N1 risk spots were identified in eastern Sichuan and southern Yunnan Provinces. Surveillance of the two viruses needs to be enhanced in these high risk areas to reduce the risk of future epidemics of avian influenza in China.
doi:10.1038/srep18610
PMCID: PMC4686887  PMID: 26691585
15.  Increased norovirus activity was associated with a novel norovirus GII.17 variant in Beijing, China during winter 2014–2015 
BMC Infectious Diseases  2015;15:574.
Background
Norovirus (NoV) is a leading cause of sporadic cases and outbreaks of acute gastroenteritis (AGE). Increased NoV activity was observed in Beijing, China during winter 2014–2015; therefore, we examined the epidemiological patterns and genetic characteristics of NoV in the sporadic cases and outbreaks.
Methods
The weekly number of infectious diarrhea cases reported by all hospitals in Beijing was analyzed through the China information system for disease control and prevention. Fecal specimens were collected from the outbreaks and outpatients with AGE, and GI and GII NoVs were detected using real time reverse transcription polymerase chain reaction. The partial capsid genes and RNA-dependent RNA polymerase (RdRp) genes of NoV were both amplified and sequenced, and genotyping and phylogenetic analyses were performed.
Results
Between December 2014 and March 2015, the number of infectious diarrhea cases in Beijing (10,626 cases) increased by 35.6 % over that of the previous year (7835 cases), and the detection rate of NoV (29.8 %, 191/640) among outpatients with AGE was significantly higher than in the previous year (12.9 %, 79/613) (χ2 = 53.252, P < 0.001). Between November 2014 and March 2015, 35 outbreaks of AGE were reported in Beijing, and NoVs were detected in 33 outbreaks, all of which belonged to the GII genogroup. NoVs were sequenced and genotyped in 22 outbreaks, among which 20 were caused by a novel GII.17 strain. Among outpatients with AGE, this novel GII.17 strain was first detected in an outpatient in August 2014, and it replaced GII.4 Sydney_2012 as the predominant variant between December 2014 and March 2015. A phylogenetic analysis of the capsid genes and RdRp genes revealed that this novel GII.17 strain was distinct from previously identified GII variants, and it was recently designated as GII.P17_GII.17. This variant was further clustered into two sub-groups, named GII.17_2012 and GII.17_2014. During winter 2014–2015, GII.17_2014 caused the majority of AGE outbreaks in China and Japan.
Conclusions
During winter 2014–2015, a novel NoV GII.17 variant replaced the GII.4 variant Sydney 2012 as the predominant strain in Beijing, China and caused increased NoV activity.
doi:10.1186/s12879-015-1315-z
PMCID: PMC4683961  PMID: 26678989
Norovirus; Acute gastroenteritis; Outbreak; Genotype
16.  Severe Pelvic Obliquity Affects Femoral Offset in Patients with Total Hip Arthroplasty but Not Leg-Length Inequality 
PLoS ONE  2015;10(12):e0144863.
Leg-length inequality is an extensively studied complication of total hip arthroplasty in normal patients. However, few studies have focused on the pelvic obliquity of coronal pelvic malrotation. We hypothesized that pelvic obliquity with a fixed abduction/adduction contracture deformity of the hip may intraoperatively affect the release of soft tissues, ultimately resulting in a leg-length inequality. This study also investigated whether the femoral and vertical offsets of total hip arthroplasty were correlated with pelvic obliquity. This prospective study divided 98 patients into six groups based on the inclination of pelvic obliquity before total hip arthroplasty. Leg-length inequality, variation of pelvic obliquity, offset, and vertical offset were measured after total hip arthroplasty. Leg-length inequality and vertical offset were not significantly different among groups, whereas the variation of pelvic obliquity was significantly higher in type IIC pelvic obliquity than in other groups. Type IC pelvic obliquity had a significantly shorter offset than did the other groups, which may have been an important factor leading to type IC pelvic obliquity. Pelvic obliquity exhibited no significant effect on leg-length inequality in patients with total hip arthroplasty. A shorter offset may be caused by the higher tension of the abductor in the operated hip, which may result in the formation of type IC pelvic obliquity. Releasing the abductor contracture and restoring femoral offset are important for increasing hip stability and maintaining pelvic balance following total hip arthroplasty.
doi:10.1371/journal.pone.0144863
PMCID: PMC4689514  PMID: 26673427
17.  The Role of FGFR1 Gene Amplification as a Poor Prognostic Factor in Squamous Cell Lung Cancer: A Meta-Analysis of Published Data 
BioMed Research International  2015;2015:763080.
Objectives. The prognostic factors of the fibroblast growth factor receptor 1 (FGFR1) in non-small cell lung cancer (NSCLC) remain controversial. Methods. We conducted a meta-analysis of published studies from 1974 to February 2015. In absence of quality difference between studies of reporting significant and nonsignificant results, the relationship between FGFR1 amplification and clinicopathological parameters in NSCLC was analyzed. And also the combined hazard ratio (HR) and their corresponding 95% confidence interval (CI) were calculated in terms of overall survival. Results. 3178 patients (12 studies) were included in the analysis. It was shown that FGFR1 amplification was significantly more prevalent among male patients (RR 2.03, 95% CI 1.57–2.63) with squamous cell lung cancer (SQCC) (RR 3.49, 95% CI 2.62–4.64) and current smokers (RR 2.63, 95% CI 1.92–3.60). The pooled data also showed that the FGFR1 amplification was a poor prognostic factor in SQCC (HR 1.38, 95% CI 1.07–1.78), Asian patients (HR 1.78, 95% CI 1.22–2.60), and fluorescence in situ hybridization (FISH) method (HR 1.30, 95% CI 1.06–1.58). Conclusions. This meta-analysis strongly suggests that FGFR1 amplification occurs more frequently in male, SQCC and smokers, and it is a risk factor for poor prognosis among Asian patients with SQCC.
doi:10.1155/2015/763080
PMCID: PMC4695660  PMID: 26788508
18.  Saw Palmetto Extract Inhibits Metastasis and Antiangiogenesis through STAT3 Signal Pathway in Glioma Cell 
Signal transducer and activator of transcription factor 3 (STAT3) plays an important role in the proliferation and angiogenesis in human glioma. Previous research indicated that saw palmetto extract markedly inhibited the proliferation of human glioma cells through STAT3 signal pathway. But its effect on tumor metastasis and antiangiogenesis is not clear. This study is to further clear the impact of saw palmetto extract on glioma cell metastasis, antiangiogenesis, and its mechanism. TUNEL assay indicated that the apoptotic cells in the saw palmetto treated group are higher than that in the control group (p < 0.05). The apoptosis related protein is detected and the results revealed that saw palmetto extract inhibits the proliferation of human glioma. Meanwhile pSTAT3 is lower in the experimental group and CD34 is also inhibited in the saw palmetto treated group. This means that saw palmetto extract could inhibit the angiogenesis in glioma. We found that saw palmetto extract was an important phytotherapeutic drug against the human glioma through STAT3 signal pathway. Saw palmetto extract may be useful as an adjunctive therapeutic agent for treatment of individuals with glioma and other types of cancer in which STAT3 signaling is activated.
doi:10.1155/2015/926946
PMCID: PMC4692995  PMID: 26788112
19.  The Role of Immune Cells in Chronic HBV Infection 
Hepatitis B virus (HBV) infection is a major cause of chronic liver diseases that may progress to liver cirrhosis and hepatocellular carcinoma. Host immune responses are important factors that determine whether HBV infection is cleared or persists. After infection, viral replication occurs inside hepatocytes, and the secretion of infectious virions can take place at high rates for decades. Consequently, HBV DNA and viral proteins, like HBV early antigen (HBeAg) and HBV surface antigen (HBsAg), can be easily detected in serum. Chronic infection with HBV is the result of an ineffective antiviral immune response towards the virus. In this review, we discuss the role of immune cells in chronic HBV infection.
doi:10.14218/JCTH.2015.00026
PMCID: PMC4721896  PMID: 26807384
Immune cells; Natural killer cells; CD8+ T cells; Hepatitis B virus
20.  Berberine Attenuates Myocardial Ischemia/Reperfusion Injury by Reducing Oxidative Stress and Inflammation Response: Role of Silent Information Regulator 1 
Berberine (BBR) exerts potential protective effect against myocardial ischemia/reperfusion (MI/R) injury. Activation of silent information regulator 1 (SIRT1) signaling attenuates MI/R injury by reducing oxidative damage and inflammation response. This study investigated the antioxidative and anti-inflammatory effects of BBR treatment in MI/R condition and elucidated its potential mechanisms. Sprague-Dawley rats were treated with BBR in the absence or presence of the SIRT1 inhibitor sirtinol (Stnl) and then subjected to MI/R injury. BBR conferred cardioprotective effects by improving postischemic cardiac function, decreasing infarct size, reducing apoptotic index, diminishing serum creatine kinase and lactate dehydrogenase levels, upregulating SIRT1, Bcl-2 expressions, and downregulating Bax and caspase-3 expressions. Stnl attenuated these effects by inhibiting SIRT1 signaling. BBR treatment also reduced myocardium superoxide generation, gp91phox expression, malondialdehyde (MDA) level, and cardiac inflammatory markers and increased myocardium superoxide dismutase (SOD) level. However, these effects were also inhibited by Stnl. Consistently, BBR conferred similar antioxidative and anti-inflammatory effects against simulated ischemia reperfusion injury in cultured H9C2 cardiomyocytes. SIRT1 siRNA administration also abolished these effects. In summary, our results demonstrate that BBR significantly improves post-MI/R cardiac function recovery and reduces infarct size against MI/R injury possibly due to its strong antioxidative and anti-inflammatory activity. Additionally, SIRT1 signaling plays a key role in this process.
doi:10.1155/2016/1689602
PMCID: PMC4691633  PMID: 26788242
21.  IM3D: A parallel Monte Carlo code for efficient simulations of primary radiation displacements and damage in 3D geometry 
Scientific Reports  2015;5:18130.
SRIM-like codes have limitations in describing general 3D geometries, for modeling radiation displacements and damage in nanostructured materials. A universal, computationally efficient and massively parallel 3D Monte Carlo code, IM3D, has been developed with excellent parallel scaling performance. IM3D is based on fast indexing of scattering integrals and the SRIM stopping power database, and allows the user a choice of Constructive Solid Geometry (CSG) or Finite Element Triangle Mesh (FETM) method for constructing 3D shapes and microstructures. For 2D films and multilayers, IM3D perfectly reproduces SRIM results, and can be ∼102 times faster in serial execution and > 104 times faster using parallel computation. For 3D problems, it provides a fast approach for analyzing the spatial distributions of primary displacements and defect generation under ion irradiation. Herein we also provide a detailed discussion of our open-source collision cascade physics engine, revealing the true meaning and limitations of the “Quick Kinchin-Pease” and “Full Cascades” options. The issues of femtosecond to picosecond timescales in defining displacement versus damage, the limitation of the displacements per atom (DPA) unit in quantifying radiation damage (such as inadequacy in quantifying degree of chemical mixing), are discussed.
doi:10.1038/srep18130
PMCID: PMC4676036  PMID: 26658477
22.  Anticancer effect of eupatilin on glioma cells through inhibition of the Notch-1 signaling pathway 
Molecular Medicine Reports  2015;13(2):1141-1146.
Eupatilin, one of the major flavonoids in Artemisia asiatica Nakai (Asteraceae), has been reported to possess antitumor properties. However, thus far there have been no reports regarding the effects of eupatilin on glioma. Therefore, in the current study the effects of eupatilin on glioma and the underlying molecular mechanism were explored. The effect of eupatilin on cell viability was detected by the MTT assay. Cell invasion and migration were performed with Transwell assays and cell apoptosis was determined by flow cytometric analysis. Notch-1 knockdown cells were established by transfection with Notch-1 small interfering RNA (siRNA). The expression levels of Notch-1 were detected by quantitative reverse transcription-polymerase chain reaction and western blotting. The results of the present study indicated that eupatilin exhibits an anticancer effect on glioma cells. Eupatilin inhibited proliferation, reduced cell invasion and migration, and promoted the apoptosis of glioma cells. Additionally, it suppressed Notch-1 expression. Knockdown of Notch-1 by siRNA contributed to the inhibitory effect of eupatilin on proliferation and invasion of glioma cells. In conclusion, eupatilin had an inhibitory effect on proliferation, invasion and migration, and promoted apoptosis of glioma cells through suppression of the Notch-1 signaling pathway. Therefore, eupatilin may have potential as an effective agent for the treatment of glioma.
doi:10.3892/mmr.2015.4671
PMCID: PMC4732834  PMID: 26676446
eupatilin; glioma; proliferation; invasion; Notch-1
23.  Selenite-induced autophagy antagonizes apoptosis in colorectal cancer cells in vitro and in vivo 
Oncology Reports  2015;35(3):1255-1264.
In the present study, we aimed to investigate the relationship between autophagy and apoptosis in selenite-treated colorectal cancer (CRC) cells. The effects of selenite on HCT116 and SW480 cell apoptosis were investigated with an Annexin V/propidium iodide (PI) double staining kit by flow cytometry. The punctate of LC3 protein following treatment with selenite was observed by a laser scanning confocal microscope and by transmission electron microscopy. Using western blot assays, we detected the apoptotic and autophagic markers in both CRC cells and mouse xenograft tumor models. We found that sodium selenite induced autophagy in the two CRC cell lines. Consistent with the in vitro results, we observed that the expression of autophagy marker LC3 was increased. Finally, we discovered that modulation of reactive oxygen species by MnTMPyP inhibited autophagy, while H2O2 activated autophagy. These results help to elucidate the anticancer effect of selenium, providing further evidence to exploit novel anticancer drugs targeting selenium.
doi:10.3892/or.2015.4484
PMCID: PMC4750746  PMID: 26676801
selenite; apoptosis; autophagy; colorectal cancer cells; reactive oxygen species
24.  Synthesis of Nitriles via Palladium-Catalyzed Water Shuffling from Amides to Acetonitrile 
Organic & biomolecular chemistry  2014;12(45):9109-9112.
Palladium-catalyzed synthesis of nitriles from amides has been described. Two similar, but complementary reaction conditions have been identified to convert various amides including α,β,γ,δ-unsaturated amides, cinnamides, aromatic amides and alkyl amides to the corresponding nitriles in good to excellent yield.
doi:10.1039/c4ob01825g
PMCID: PMC4213294  PMID: 25316145
25.  Middle East respiratory syndrome coronavirus ORF4b protein inhibits type I interferon production through both cytoplasmic and nuclear targets 
Scientific Reports  2015;5:17554.
Middle East respiratory syndrome coronavirus (MERS-CoV) is a novel and highly pathogenic human coronavirus and has quickly spread to other countries in the Middle East, Europe, North Africa and Asia since 2012. Previous studies have shown that MERS-CoV ORF4b antagonizes the early antiviral alpha/beta interferon (IFN-α/β) response, which may significantly contribute to MERS-CoV pathogenesis; however, the underlying mechanism is poorly understood. Here, we found that ORF4b in the cytoplasm could specifically bind to TANK binding kinase 1 (TBK1) and IκB kinase epsilon (IKKε), suppress the molecular interaction between mitochondrial antiviral signaling protein (MAVS) and IKKε, and inhibit IFN regulatory factor 3 (IRF3) phosphorylation and subsequent IFN-β production. Further analysis showed that ORF4b could also inhibit IRF3 and IRF7-induced production of IFN-β, whereas deletion of the nuclear localization signal of ORF4b abrogated its ability to inhibit IRF3 and IRF7-induced production of IFN-β, but not IFN-β production induced by RIG-I, MDA5, MAVS, IKKε, and TBK-1, suggesting that ORF4b could inhibit the induction of IFN-β in both the cytoplasm and nucleus. Collectively, these results indicate that MERS-CoV ORF4b inhibits the induction of type I IFN through a direct interaction with IKKε/TBK1 in the cytoplasm, and also in the nucleus with unknown mechanism. Viruses have evolved multiple strategies to evade or thwart a host’s antiviral responses. A novel human coronavirus (HCoV), Middle East respiratory syndrome coronavirus (MERS-CoV), is distinguished from other coronaviruses by its high pathogenicity and mortality. However, virulence determinants that distinguish MERS-CoV from other HCoVs have yet to be identified. MERS-CoV ORF4b antagonizes the early antiviral response, which may contribute to MERS-CoV pathogenesis. Here, we report the identification of the interferon (IFN) antagonism mechanism of MERS-CoV ORF4b. MERS-CoV ORF4b inhibits the production of type I IFN through a direct interaction with IKKε/TBK1 in the cytoplasm, and also in the nucleus with unknown mechanism. These findings provide a rationale for the novel pathogenesis of MERS-CoV as well as a basis for developing a candidate therapeutic against this virus.
doi:10.1038/srep17554
PMCID: PMC4668369  PMID: 26631542

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