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1.  The Impact of Coexisting Asthma, Chronic Obstructive Pulmonary Disease and Tuberculosis on Survival in Patients with Lung Squamous Cell Carcinoma 
PLoS ONE  2015;10(7):e0133367.
Background
Pulmonary diseases [asthma, chronic obstructive pulmonary disease (COPD), and tuberculosis (TB)] are associated with lung cancer mortality. However, the relationship between coexisting pulmonary diseases and survival in patients with lung squamous cell carcinoma (SqCC) has not been well defined.
Methods
Patients newly diagnosed with SqCC between 2003 and 2008 were identified by linking the National Health Insurance Research Database and Taiwan Cancer Registry Database. Cases with SqCC were followed up until death, loss to follow-up, or study end in 2010. Information on health status, date of death and the main causes of death was ascertained from the National Death Registry Database. Cox proportional hazard regression was used to calculate the hazard ratio (HR) of coexisting asthma, COPD and/or TB.
Results
During the study period, a total of 5406 cases with SqCC were enrolled. For all cause-mortality, HRs were 1.08 [95% confidence interval (CI), 0.99–1.18], 1.04 (95% CI, 0.97–1.12), and 1.14 (95% CI, 1.00–1.31) for individuals with asthma, COPD, and TB, respectively. Specifically, among men with coexisting pulmonary diseases, the HRs were 1.56 (95% CI, 1.23–1.97) and 1.11 (95% CI, 1.00–1.24) for individuals with asthma+COPD+TB and asthma+COPD, respectively. Among male patients with stage III SqCC, HRs were 3.41 (95%CI, 1.27–9.17) and 1.65 (95%CI, 1.10–2.47) for individuals with asthma+TB and asthma+COPD+TB, respectively. Among male patients with stage IV SqCC, HRs were 1.40 (95%CI, 1.00–1.97) and 1.25 (95%CI, 1.03–1.52) for individuals with asthma+ COPD+TB and asthma. Among female patients with stage I and II, HR was 0.19 (95%CI, 005–0.77) for individuals with asthma.
Conclusions
Coexisting pulmonary diseases increased the risk of mortality from SqCC in male patients. For female patients with early stage SqCC, pre-existing asthma decreased mortality. These patients deserve greater attention while undergoing cancer treatment.
doi:10.1371/journal.pone.0133367
PMCID: PMC4510446  PMID: 26196516
2.  Long non-coding RNA ROR decoys gene-specific histone methylation to promote tumorigenesis 
Genome Biology  2015;16(1):139.
Background
Long non-coding RNAs (lncRNAs) are not translated into proteins and were initially considered to be part of the ‘dark matter’ of the genome. Recently, it has been shown that lncRNAs play a role in the recruitment of chromatin modifying complexes and can influence gene expression. However, it is unknown if lncRNAs function in a similar way in cancer.
Results
Here, we show that the lncRNA ROR occupies and activates the TESC promoter by repelling the histone G9A methyltransferase and promoting the release of histone H3K9 methylation. Suppression of ROR in tumors results in silencing of TESC expression, and G9A-mediated histone H3K9 methylation in the TESC promoter is restored, which significantly reduces tumor growth and metastasis. Without ROR silencing, TESC knockdown presents consistent and significant reductions in tumor progression.
Conclusions
Our results reveal a novel mechanism by which ROR may serve as a decoy oncoRNA that blocks binding surfaces, preventing the recruitment of histone modifying enzymes, thereby specifying a new pattern of histone modifications that promote tumorigenesis.
Electronic supplementary material
The online version of this article (doi:10.1186/s13059-015-0705-2) contains supplementary material, which is available to authorized users.
doi:10.1186/s13059-015-0705-2
PMCID: PMC4499915  PMID: 26169368
3.  Prevalence of Obesity and Related Factors among Bouyei and Han Peoples in Guizhou Province, Southwest China 
PLoS ONE  2015;10(6):e0129230.
Objective
To investigate the prevalence of general and abdominal obesity and associated factors in Bouyei and Han peoples.
Design
A cross-sectional study was carried out in Guizhou province, southwest China in 2012, with multi-stage sampling to enroll 4551 participants aged 20 to 80 years. General and abdominal obesity were defined by World Health Organization (WHO) for Chinese. A design-based analysis was performed to evaluate prevalence of obesity and its related factors.
Results
Bouyei people had a significantly lower prevalence of general obesity (4.8% vs. 10.9%, p < 0.05) and abdominal obesity (13.6% vs. 26.8%, p < 0.05) than that in Han people. Prevalence of obesity increased with age until middle-age period and declined thereafter. Men aged 40–49 years group and women aged 50–59 years group have the highest prevalence of general obesity. Prevalence of abdominal obesity was higher than that of general obesity. Middle-age, Higher income, Han people were significantly associated with an increased risk of General/abdominal obesity.
Conclusions
Bouyei people had a lower prevalence of general and abdominal obesity than the Han people. Etiological studies should be conducted to determine underlying genetic factors and dietary factors.
doi:10.1371/journal.pone.0129230
PMCID: PMC4468129  PMID: 26075708
4.  Role of M2, M3, and M4 Muscarinic Receptor Subtypes in the Spinal Cholinergic Control of Nociception Revealed Using siRNA in Rats 
Journal of neurochemistry  2009;111(4):1000-1010.
Muscarinic acetylcholine receptors (mAChRs) are involved in the control of nociception in the spinal cord. The M2, M3, and M4 mAChR subtypes are present in the spinal dorsal horn. However, the role of the individual subtypes in the antinociceptive effect produced by mAChR agonists is uncertain. Here we determined the contribution of M2, M3, and M4 subtypes to spinal muscarinic analgesia by using small-interference RNA (siRNA) targeting specific mAChR subtypes in rats. The neuronal uptake and distribution of a chitosan-siRNA conjugated fluorescent dye in the spinal cord and dorsal root ganglion were confirmed after intrathecal injection. The control and gene-specific siRNA-chitosan complexes were injected intrathecally for 3 consecutive days. Quantitative RT-PCR analysis showed that treatment with siRNA targeting M2, M3, or M4 subtype produced a large reduction in the corresponding mRNA levels in the dorsal root ganglion and dorsal spinal cord. Also, the protein levels of the mAChR subtypes in the spinal cord were significantly downregulated by siRNA treatment, as determined by the immunoprecipitation and receptor binding assay. Treatment with the M2-siRNA caused a large reduction in the inhibitory effect of muscarine on the nociceptive withdrawal threshold. Furthermore, M4 knockdown at the spinal level significantly reduced the antinociceptive effect of muscarine. However, the antinociceptive effect of muscarine was not significantly changed by the M3-specific siRNA. Our study suggests that chitosan nanoparticles can be used for efficient delivery of siRNA into the neuronal tissues in vivo. Our findings also provide important functional evidence that M2 and M4, but not M3, contribute to nociceptive regulation by mAChRs at the spinal level.
doi:10.1111/j.1471-4159.2009.06396.x
PMCID: PMC4435670  PMID: 19780895
5.  A novel model of bisphosphonate-related osteonecrosis of the jaw in rats 
Objective: To establish a rat model of bisphosphonate-related osteonecrosis of the jaw (BRONJ) that realistically mimics major clinical manifestations of the disease. Methods: Female Sprague Dawley rats received intravenous zoledronate 80 μg/kg once a week via the tail vein. Three weeks after intravenous injection, maxillary first molars were extracted under general anesthesia. Then 1, 4 and 12 weeks after tooth extraction, the rats were euthanized, and the intact maxillas were harvested en bloc. Macroscopic analysis, histological analysis and cytokine analysis were performed. Untreated rats with tooth extraction were used as controls. Results: 12 weeks after extraction, rats treated with zoledronate developed BRONJ-like disease, including characteristic features of impaired soft tissue healing, exposed necrotic bone or sequestra, increased inflammatory infiltrates, while the controls showed normal bone healing. 4 weeks after extraction, rats treated with zoledronate exhibited the decreased receptor activator of nuclear factor kappa-B ligand (RANKL) values, the increased osteoprotegerin (OPG) values and the remarkable decreased RANKL/OPG ratio when compared with the controls. Conclusion: The rats treated with zoledronate can be considered a novel, reliable and reproducible animal model to better understand the pathophysiology and pathogenesis of BRONJ and to develop a therapeutic approach.
PMCID: PMC4503084  PMID: 26191212
Bisphosphonates; BRONJ; animal model; pathogenesis; RANKL; OPG
6.  Cardiac output measurement using a modified carbon dioxide Fick method: comparison analysis with pulmonary artery catheter method and pulse induced contour cardiac output method 
Objectives: In the present study, cardiac output in mechanically ventilated patients were determined using three methods including modified CO2-Fick (mCO2F), pulmonary artery catheter (PAC), and pulse induced contour cardiac output (PiCCO) methods and the results were compared to assess the effectiveness of mCO2F method in measuring the cardiac output. Method: Mechanically ventilated and hemodynamically unstable patients (n=39) were sedated and intubated with Swan-Ganz or PiCCO arterial catheters. At the beginning of the experiment and at 4 h after the experiment, the CO2 concentration in expiratory air was measured through a CO2 monitor and it was used further in the cardiac output calculation using mCO2F method. The cardiac output was also determined using PAC and PiCCO methods. Results: The cardiac output determined by PAC and mCO2F method was not significantly (P>0.05) different [5.53±2.85 L.min-1 (PAC) and 5.96±2.92 L.min-1 (mCO2F)] at the beginning of the experiment and [6.22±2.7 L.min-1 (PAC) and 6.36±2.35 L.min-1 (mCO2F)] at 4 h after the experiment; however, they were highly correlated (r=0.939 and 0.908, P<0.001). The cardiac output determined by PiCCO and mCO2F method was also not significantly (P>0.05) different [6.05±2.49 L.min-1 (PiCCO) and 5.44±1.64 L.min-1 (mCO2F)] at the beginning of the experiment, and [6.17±2.04 L.min-1 (PiCCO) and 5.70±1.72 L.min-1 (mCO2F)] at 4 h after the experiment; however, they were highly correlated (r=0.776 and 0.832, P<0.001). Conclusion: The mCO2F method could accurately measure the cardiac output in mechanically ventilated patients without using any expensive equipment’s and invasive procedures.
PMCID: PMC4443079  PMID: 26064245
Cardiac output; modified Fick method; mechanical ventilation; thermo dilution; pulse induced contour cardiac output; pulmonary artery catheter
7.  Viral aetiology of acute respiratory infections among children and associated meteorological factors in southern China 
BMC Infectious Diseases  2015;15:124.
Background
Acute respiratory infections (ARIs) are common in children and mostly caused by viruses, but the significance of the detection of multiple viruses in ARIs is unclear. This study investigated 14 respiratory viruses in ARIs among children and associated meteorological factors in Shantou, southern China.
Methods
Paired nasal/throat-flocked swabs collected from 1,074 children with ARIs, who visited outpatient walk-in clinics in a tertiary hospital between December 2010 and November 2011, were examined for fourteen respiratory viruses - influenza viruses (FluA, FluB), respiratory syncytial viruses (RSV A and B), human coronaviruses (hCoV: 229E, OC43, HKU1, NL63), human metapneumoviruses (hMPV A and B), parainfluenza viruses (PIV1-4), human rhinoviruses (HRV A, B, C), enteroviruses (EV), adenoviruses (ADV), human bocavirus (hBoV), and human parechoviruses (hPeV) - by multiplex real-time PCR.
Results
We identified at least one virus in 82.3% (884/1,074) and multiple viruses in 38.6% (415/1,074) of patients. EV and HRV were the most frequently detected single viruses (42.3%, 374/884 and 39.9%, 353/884 respectively) and co-detected pair (23.1%, 96/415). Overlapping seasonal trends of viruses were recorded over the year, with dual peaks for EV and single peaks for the others. By logistic regression analysis, EV was positively associated with the average temperature and humidity, hCoV, and PIV4, but negatively with HRV, PIV3, and hBoV. HRV was inversely associated with EV and PIV3.
Conclusions
This study reports high viral detection and co-detection rates in pediatric ARI cases mainly due to EV and HRV. Many viruses circulated throughout the year with similar seasonal trends in association with temperature, humidity, and wind velocity. Statistically significant associations were present among the viruses. Understanding the polyviral etiology and viral interactions in the cases with multiple viruses warrants further studies.
Electronic supplementary material
The online version of this article (doi:10.1186/s12879-015-0863-6) contains supplementary material, which is available to authorized users.
doi:10.1186/s12879-015-0863-6
PMCID: PMC4365542  PMID: 25884513
Virus; Acute respiratory infection; Meteorological factor; Children; China
8.  Correlation between ELISA and pseudovirion-based neutralisation assay for detecting antibodies against human papillomavirus acquired by natural infection or by vaccination 
A pseudovirion-based neutralisation assay (PBNA) has been considered the gold standard for measuring specific antibody responses against human papillomavirus (HPV). However, this assay is labor intensive and therefore very difficult to implement in large-scale studies. Previous studies have evaluated the agreement between virus-like particle (VLP)-based ELISA and PBNA for measuring HPV vaccine-induced antibodies. However, the concordance of these assays to detect antibodies induced by natural infection has not yet been fully elucidated. In this study, the results of an Escherichia coli (E. coli)-expressed VLP-based ELISA were found to be highly concordant with those of a baculovirus-expressed VLP-based ELISA (r = 0.96 and 0.97 for HPV-16 and HPV-18) when detecing HPV vaccine induced antibodies and the concordance was medium (r = 0.68 and 0.68 for HPV-16 and HPV-18) when assessing natural infection induced antibodies. The results of the E. coli expressed VLP-based ELISA correlated well with those of the PBNA when testing 1020 post-vaccination human sera collected at one month after vaccination with the E. coli expressed VLP-based bivalent HPV vaccine (r = 0.83 and 0.81 for HPV-16 and HPV-18). The agreement and correlation were moderate (kappa < 0.3 for both HPV types 16 and 18, r = 0.59 and 0.68 for HPV-16 and HPV-18, respectively) when assessing 1600 serum samples from unvaccinated women of age 18–25 years. In conclusion, the VLP-based ELISA is an acceptable surrogate for the neutralizing antibody assay in measuring vaccine responses. However, the use of the VLP-based ELISA in epidemiological studies should be carefully considered.
doi:10.4161/hv.27619
PMCID: PMC4130265  PMID: 24384608
human papillomavirus; pseudovirion-based neutralisation assay; antibody; ELISA; vaccine
9.  Magnetic and Electronic Evolutions of Hydrogenated VTe2 Monolayer under Tension 
Scientific Reports  2014;4:7524.
Two-dimensional nanostructures with controllable magnetic and electronic properties are desirable for their versatile applications in quantum devices. Here, we present a first-principles design on their magnetic and electronic switching controlled by tension. We find that hydrogenated VTe2 monolayer experiences a transfer from anti-ferromagnetism to ferromagnetism via a turning-point of paramagnetism, and switches from semiconductor, to metal, further to half-metal as tension increases. We show that its anti-ferromagnetism with semiconducting or metallic character under low tension is contributed to super-exchange or mobile-carrier enhanced super-exchange, while the ferromagnetism with half-metallic character under high tension is induced by carrier-mediated double exchange. We further show that the magnetic and electronic evolutions of hydrogenated VS2 and VSe2 monolayers under tension follow the same trend as those of hydrogenated VTe2 monolayer. We predict that tension is efficient and simple to control the magnetic and electronic properties of hydrogenated vanadium dichalcogenides monolayers. The monolayers with controllable magnetism and conductivity may find applications in multi-functional nanodevices.
doi:10.1038/srep07524
PMCID: PMC4268636  PMID: 25516240
10.  PM2.5 in Beijing – temporal pattern and its association with influenza 
Environmental Health  2014;13:102.
Background
Air pollution in Beijing, especially PM2.5, has received increasing attention in the past years. Despite Beijing being one of the most polluted cities in the world, there has still been a lack of quantitative research regarding the health impact of PM2.5 on the impact of diseases in Beijing. In this study, we aimed to characterize temporal pattern of PM2.5 and its potential association with human influenza in Beijing.
Methods
Based on the data collected on hourly ambient PM2.5 from year 2008 to 2013 and on monthly human influenza cases from 2008 and 2011, we investigated temporal patterns of PM2.5 over the five-year period and utilized the wavelet approach to exploring the potential association between PM2.5 and influenza.
Results
Our results found that ambient PM2.5 pollution was severe in Beijing with PM2.5 concentrations being significantly higher than the standards of the World Health Organization, the US EPA, and the Chinese EPA in the majority of days during the study period. Furthermore, PM2.5 concentrations in the winter heating seasons were higher than those in non-heating seasons despite high variations. We also found significant association between ambient PM2.5 peak and human influenza case increase with a delayed effect (e.g. delayed effect of PM2.5 on influenza).
Conclusions
Ambient PM2.5 concentrations were significantly associated with human influenza cases in Beijing, which have important implications for public health and environmental actions.
doi:10.1186/1476-069X-13-102
PMCID: PMC4271358  PMID: 25471661
Air pollution; PM2.5; Temporal pattern; Association; Influenza; Beijing
11.  Mastering tricyclic ring systems for desirable functional cannabinoid activity 
There is growing interest in using cannabinoid receptor 2 (CB2) agonists for the treatment of neuropathic pain and other indications. In continuation of our ongoing program aiming for the development of new small molecule cannabinoid ligands, we have synthesized a novel series of carbazole and γ-carboline derivatives. The affinities of the newly synthesized compounds were determined by a competitive radioligand displacement assay for human CB2 cannabinoid receptor and rat CB1 cannabinoid receptor. Functional activity and selectivity at human CB1 and CB2 receptors were characterized using receptor internalization and [35S]GTP-γ-S assays. The structure-activity relationship and optimization studies of the carbazole series have led to the discovery of a non-selective CB1 and CB2 agonist, compound 4. Our subsequent research efforts to increase CB2 selectivity of this lead compound have led to the discovery of CB2 selective compound 64, which robustly internalized CB2 receptors. Compound 64 had potent inhibitory effects on pain hypersensitivity in a rat model of neuropathic pain. Other potent and CB2 receptor–selective compounds, including compounds 63 and 68, and a selective CB1 agonist, compound 74 were also discovered. In addition, we identified the CB2 ligand 35 which failed to promote CB2 receptor internalization and inhibited compound CP55,940-induced CB2 internalization despite a high CB2 receptor affinity. The present study provides novel tricyclic series as a starting point for further investigations of CB2 pharmacology and pain treatment.
doi:10.1016/j.ejmech.2013.09.038
PMCID: PMC3909471  PMID: 24125850
Cannabinoid; CB2; GPCR; neuropathic pain; carbazole; CB1
12.  Ab initio design of nanostructures for solar energy conversion: a case study on silicon nitride nanowire 
Nanoscale Research Letters  2014;9(1):531.
Design of novel materials for efficient solar energy conversion is critical to the development of green energy technology. In this work, we present a first-principles study on the design of nanostructures for solar energy harvesting on the basis of the density functional theory. We show that the indirect band structure of bulk silicon nitride is transferred to direct bandgap in nanowire. We find that intermediate bands can be created by doping, leading to enhancement of sunlight absorption. We further show that codoping not only reduces the bandgap and introduces intermediate bands but also enhances the solubility of dopants in silicon nitride nanowires due to reduced formation energy of substitution. Importantly, the codoped nanowire is ferromagnetic, leading to the improvement of carrier mobility. The silicon nitride nanowires with direct bandgap, intermediate bands, and ferromagnetism may be applicable to solar energy harvesting.
doi:10.1186/1556-276X-9-531
PMCID: PMC4186815  PMID: 25294975
Silicon nitride nanowire; Solar energy harvesting; Doping; First-principles calculation
13.  Impact of EGFR mutation status on tumor response and progression free survival after first-line chemotherapy in patients with advanced non-small-cell lung cancer: a meta-analysis 
Journal of Thoracic Disease  2014;6(9):1239-1250.
Objectives
Non-small-cell lung cancer (NSCLC) patients harboring sensitive epidermal growth factor receptor (EGFR) mutations derive greater benefits from EGFR-tyrosine kinase inhibitors (EGFR-TKIs) than those with wild type tumors. However, whether EGFR mutation status is associated with the efficacy of cytotoxic chemotherapy or prognosis in advanced NSCLC patients remained controversial. Thus, we sought to conduct a meta-analysis to answer this question.
Methods
Electronic databases were searched for eligible literatures. The primary outcomes were objective response rate (ORR) and 6-month progression-free survival (PFS) rate. The pooled odds ratio (OR) was calculated using random-effects model. Subgroup analyses stratified by study types, EGFR mutation detection methods, chemotherapy regimens, and patient origins were proposed.
Results
A total of 14 studies involving 1,772 advanced NSCLC patients with known EGFR mutation status who had received first-line chemotherapy were included. Patients with positive EGFR mutation had numerically higher ORR than wild type patients (36.2% vs. 30.1%) without significant differences (OR 1.24, 95% CI, 0.90 to 1.70; P=0.19). However, patients with EGFR mutants had significantly superior 6-month PFS rate than wild-type patients (58.6% vs. 47.2%; OR 1.88, 95% CI, 1.33 to 2.65; P=0.0003). Results of the subgroup analyses were concordant with the overall ones.
Conclusions
This comprehensive analysis revealed that advanced NSCLC patients with sensitivity EGFR mutation had higher 6-month PFS rate and potentially greater ORR compared with wild-type patients after first-line chemotherapy. It suggested that EGFR mutation status should be considered a significant factor for patient stratification in evaluating the efficacy of antitumor agents in addition to EGFR-TKIs.
doi:10.3978/j.issn.2072-1439.2014.07.33
PMCID: PMC4178107  PMID: 25276366
Non-small-cell lung cancer (NSCLC); epidermal growth factor receptor (EGFR) mutation; first-line chemotherapy; meta-analysis
14.  Regulation of Hypothalamic Presympathetic Neurons and Sympathetic Outflow by Group II Metabotropic Glutamate Receptors in Spontaneously Hypertensive Rats 
Hypertension  2013;62(2):255-262.
Increased glutamatergic input in the hypothalamic paraventricular nucleus (PVN) plays an important role in the development of hypertension. Group II metabotropic glutamate receptors (mGluRs) are expressed in the PVN, but their involvement in regulating synaptic transmission and sympathetic outflow in hypertension is unclear. Here we show that the group II mGluRs agonist (2S,2'R,3'R)-2-(2',3'-dicarboxycyclopropyl)glycine (DCG-IV) produced a significantly greater reduction in the frequency of spontaneous and miniature excitatory postsynaptic currents and the amplitude of electrically evoked excitatory postsynaptic currents in retrogradely labeled spinally projecting PVN neurons in spontaneously hypertensive rats (SHRs) than in normotensive control rats. DCG-IV similarly decreased the frequency of GABAergic inhibitory postsynaptic currents of labeled PVN neurons in the two groups of rats. Strikingly, DCG-IV suppressed the firing of labeled PVN neurons only in SHRs. DCG-IV failed to inhibit the firing of PVN neurons of SHRs in the presence of ionotropic glutamate receptor antagonists. Lowering blood pressure with celiac ganglionectomy in SHRs normalized the DCG-IV effect on excitatory postsynaptic currents to the same level seen in control rats. Furthermore, microinjection of DCG-IV into the PVN significantly reduced blood pressure and sympathetic nerve activity in SHRs. Our findings provide new information that presynaptic group II mGluR activity at the glutamatergic terminals increases in the PVN in SHRs. Activation of group II mGluRs in the PVN inhibits sympathetic vasomotor tone through attenuation of increased glutamatergic input and neuronal hyperactivity in SHRs.
doi:10.1161/HYPERTENSIONAHA.113.01466
PMCID: PMC3734791  PMID: 23716583
hypertension; hypothalamus; sympathetic nervous activity; synaptic transmission; glutamate receptors
15.  Population Structure of the Greenhouse Whitefly, Trialeurodes vaporariorum (Westwood), an Invasive Species from the Americas, 60 Years after Invading China 
Though the greenhouse whitefly, Trialeurodes vaporariorum (Westwood) (Hemiptera: Aleyrodidae) was introduced into China more than 60 years ago, the genetic diversity and structure of this exotic insect pest and virus vector have not been studied. To investigate the population genetic characteristics of this invasive species and to identify potential invasion routes, the genetic diversity and population structure of 17 collections of T. vaporariorum from nine provinces in China were analyzed using seven microsatellite loci. The results of the analyses indicated that the genetic diversity for the populations examined from the four provinces: Jilin, Ningxia, Guizhou and Qinghai, was lower than the genetic diversity of populations from the five provinces: Yunnan, Shandong, Shanxi, Liaoning, and Gansu. The T. vaporariorum populations analyzed in this study grouped as two distinct genetic clusters based on the analysis using STRUCTURE, whereas, 8 clusters were identified based on the BAPS analysis. Of the 136 genetic distance (Fst) values, 128 (94%) were associated with a significant exact test. There was a significant relationship between Fst and geographical distance. These results demonstrate that populations of T. vaporariorum in China exhibit significant genetic differentiation, indicating the likelihood that multiple introductions of T. vaporariorum into China have occurred. Also, the populations collected from the provinces of Jilin, Ningxia, Guizhou and Qinghai appear to represent secondary introductions originating from other Chinese provinces.
doi:10.3390/ijms150813514
PMCID: PMC4159808  PMID: 25093716
biological invasion; exotic introduction; genetic differentiation; genetic structure
16.  Distinct Intrinsic and Synaptic Properties of Pre-sympathetic and Pre-parasympathetic Output Neurons in Barrington’s Nucleus 
Journal of neurochemistry  2013;126(3):338-348.
Barrington’s nucleus (BN) controls micturition and other visceral functions through projections to the spinal cord. In this study, we developed a rat brain slice preparation to determine the intrinsic and synaptic mechanisms regulating pre-sympathetic output (PSO) and pre-parasympathetic output (PPO) neurons in the BN by using patch-clamp recordings. The PSO and PPO neurons were retrogradely labeled by injecting fluorescent tracers into the intermediolateral region of the spinal cord at T13-L1 and S1-S2 levels, respectively. There were significantly more PPO than PSO neurons within the BN. The basal activity and membrane potential were significantly lower in PPO than in PSO neurons, and A-type K+ currents were significantly larger in PPO than in PSO neurons. Blocking A-type K+ channels increased the excitability more in PPO than in PSO neurons. Also, stimulating µ-opioid receptors inhibited firing more in PPO than in PSO neurons. The glutamatergic EPSC frequency was much lower, whereas the glycinergic IPSC frequency was much higher, in PPO than in PSO neurons. Although blocking GABAA receptors increased the excitability of both PSO and PPO neurons, blocking glycine receptors increased the firing activity of PPO neurons only. Furthermore, blocking ionotropic glutamate receptors decreased the excitability of PSO neurons but paradoxically increased the firing activity of PPO neurons by reducing glycinergic input. Our findings indicate that the membrane and synaptic properties of PSO and PPO neurons in the BN are distinctly different. This information improves our understanding of the neural circuitry and central mechanisms regulating the bladder and other visceral organs.
doi:10.1111/jnc.12290
PMCID: PMC3716857  PMID: 23647148
pontine micturition center; micturition reflex; autonomic nervous system; voltage-activated K+ channels; synaptic transmission
17.  Protective roles of erythropoiesis-stimulating proteins in chronic heart failure with anemia 
Anemia is a common comorbidity in patients with chronic heart failure (CHF) and is frequently treated with erythropoiesis-stimulating proteins (ESPs). Previous studies, however, have been relatively short in duration and have not provided conclusive data on the safety or clinical efficacy of ESP treatment. The aim of this study was to explore the safety and therapeutic effects of ESPs in patients with anemia and CHF. A systematic literature search in EMBASE and MEDLINE from their inception to July 2013 was performed, and clinical studies that evaluated the effects of ESPs among patients with CHF were identified. Randomized clinical trials comparing the effects of ESP treatment with those of placebo treatment or usual care regimes in anemic patients with CHF were included. Nine randomized, controlled trials were identified, comprising 750 patients with CHF and anemia receiving ESP treatment for between three months and one year. ESP treatment had a significantly lower risk of CHF hospitalization [relative risk (RR), 0.47; 95% confidence interval (CI), 0.32–0.70; P=0.0002] and a moderate reduction in mortality risk (RR, 0.68; 95% CI, 0.38–1.19; P=0.18). Treatment with ESPs in patients with symptomatic CHF and anemia resulted in significant improvements in hemoglobin, hematocrit and brain natriuretic peptide levels, as well as exercise capacity, renal function, New York Heart Association class and left ventricular ejection fraction. In conclusion, this study found that treatment with ESPs exerts beneficial effects against CHF and is not associated with a higher mortality rate or adverse effects. These outcomes support the instigation of a trial evaluating the treatment of anemia with ESPs in patients with chronic CHF.
doi:10.3892/etm.2014.1845
PMCID: PMC4113650  PMID: 25120615
anemia; chronic heart failure; erythropoiesis-stimulating proteins; hospitalization; mortality
18.  Telomerase Cajal body protein 1 depletion inhibits telomerase trafficking to telomeres and induces G1 cell cycle arrest in A549 cells 
Oncology Letters  2014;8(3):1009-1016.
Telomerase Cajal body protein 1 (TCAB1) is a telomerase holoenzyme, which is markedly enriched in Cajal bodies (CBs) and facilitates the recruitment of telomerase to CBs in the S phase of the cell cycle. This recruitment is dependent on TCAB1 binding to a telomerase RNA component. The majority of cancer cells are able to grow indefinitely due to telomerase and its mechanism of trafficking to telomeres. In the present study, a certain level of TCAB1 expression in A549 human lung cells was identified and TCAB1 knockdown exhibited a potent antiproliferative effect on these cells, which was coupled with a decrease in the cell density and activity of the cellular enzymes. In addition, TCAB1-depletion was demonstrated to inhibit telomerase trafficking to telomeres in the A549 cells, leading to subsequent G1 cell cycle arrest without inducing apoptotic cell death. Overall, these observations indicated that TCAB1 may be essential for A549 cell proliferation and cell cycle regulation, and may be a potential candidate for the development of a therapeutic target for lung adenocarcinomas.
doi:10.3892/ol.2014.2306
PMCID: PMC4114580  PMID: 25120649
telomerase Cajal body protein 1; telomerase trafficking; antiproliferation; cell cycle arrest
19.  Metal Dichalcogenides Monolayers: Novel Catalysts for Electrochemical Hydrogen Production 
Scientific Reports  2014;4:5348.
Catalyst-driven electrolysis of water is considered as a “cleanest” way for hydrogen production. Finding cheap and abundant catalysts is critical to the large-scale implementation of the technology. Two-dimensional metal dichalcogenides nanostructures have attracted increasing attention because of their catalytic performances in water electrolysis. In this work, we systematically investigate the hydrogen evolution reduction of metal dichalcogenides monolayers based on density-functional-theory calculations. We find that metal disulfide monolayers show better catalytic performance on hydrogen production than other metal dichalcogenides. We show that their hydrogen evolution reduction strongly depends on the hydrogen coverage and the catalytic performance reduces with the increment of coverage because of hydrogenation-induced lower conductivity. We further show that the catalytic performance of vanadium disulfide monolayer is comparable to that of Pt at lower hydrogen coverage and the performance at higher coverage can be improved by hybridizing with conducting nanomaterials to enhance conductivity. These metal disulfide monolayers with lower overpotentials may apply to water electrolysis for hydrogen production.
doi:10.1038/srep05348
PMCID: PMC4071773  PMID: 24967679
20.  Comparison of the Effects of Air Pollution on Outpatient and Inpatient Visits for Asthma: A Population-Based Study in Taiwan 
PLoS ONE  2014;9(5):e96190.
Background
A nationwide asthma survey on the effects of air pollution is lacking in Taiwan. The purpose of this study was to evaluate the time trend and the relationship between air pollution and health care services for asthma in Taiwan.
Methods
Health care services for asthma and ambient air pollution data were obtained from the National Health Insurance Research database and Environmental Protection Administration from 2000 through 2009, respectively. Health care services, including those related to the outpatient and inpatient visits were compared according to the concentration of air pollutants.
Results
The number of asthma-patient visits to health-care facilities continue to increase in Taiwan. Relative to the respective lowest quartile of air pollutants, the adjusted relative risks (RRs) of the outpatient visits in the highest quartile were 1.10 (P-trend  = 0.013) for carbon monoxide (CO), 1.10 (P-trend  = 0.015) for nitrogen dioxide (NO2), and 1.20 (P-trend <0.0001) for particulate matter with an aerodynamic diameter ≦10µm (PM10) in the child group (aged 0–18). For adults aged 19–44, the RRs of outpatient visits were 1.13 (P-trend = 0.078) for CO, 1.17 (P-trend = 0.002) for NO2, and 1.13 (P-trend <0.0001) for PM10. For adults aged 45–64, the RRs of outpatient visits were 1.15 (P-trend = 0.003) for CO, 1.19 (P-trend = 0.0002) for NO2, and 1.10 (P-trend = 0.001) for PM10. For the elderly (aged≥ 65), the RRs of outpatient visits in were 1.12 (P-trend  = 0.003) for NO2 and 1.10 (P-trend  = 0.006) for PM10. For inpatient visits, the RRs across quartiles of CO level were 1.00, 1.70, 1.92, and 1.86 (P-trend  = 0.0001) in the child group. There were no significant linear associations between inpatient visits and air pollutants in other groups.
Conclusions
There were positive associations between CO levels and childhood inpatient visits as well as NO2, CO and PM10 and outpatient visits.
doi:10.1371/journal.pone.0096190
PMCID: PMC4006842  PMID: 24789041
21.  Evaluation of Osteoconductive Scaffolds in the Canine Femoral Multi-Defect Model 
Tissue Engineering. Part A  2013;19(5-6):634-648.
Treatment of large segmental bone defects remains an unsolved clinical challenge, despite a wide array of existing bone graft materials. This project was designed to rapidly assess and compare promising biodegradable osteoconductive scaffolds for use in the systematic development of new bone regeneration methodologies that combine scaffolds, sources of osteogenic cells, and bioactive scaffold modifications. Promising biomaterials and scaffold fabrication methods were identified in laboratories at Rutgers, MIT, Integra Life Sciences, and Mayo Clinic. Scaffolds were fabricated from various materials, including poly(L-lactide-co-glycolide) (PLGA), poly(L-lactide-co-ɛ-caprolactone) (PLCL), tyrosine-derived polycarbonate (TyrPC), and poly(propylene fumarate) (PPF). Highly porous three-dimensional (3D) scaffolds were fabricated by 3D printing, laser stereolithography, or solvent casting followed by porogen leaching. The canine femoral multi-defect model was used to systematically compare scaffold performance and enable selection of the most promising substrate(s) on which to add cell sourcing options and bioactive surface modifications. Mineralized cancellous allograft (MCA) was used to provide a comparative reference to the current clinical standard for osteoconductive scaffolds. Percent bone volume within the defect was assessed 4 weeks after implantation using both MicroCT and limited histomorphometry. Bone formed at the periphery of all scaffolds with varying levels of radial ingrowth. MCA produced a rapid and advanced stage of bone formation and remodeling throughout the defect in 4 weeks, greatly exceeding the performance of all polymer scaffolds. Two scaffold constructs, TyrPCPL/TCP and PPF4SLA/HAPLGA Dip, proved to be significantly better than alternative PLGA and PLCL scaffolds, justifying further development. MCA remains the current standard for osteoconductive scaffolds.
doi:10.1089/ten.tea.2012.0289
PMCID: PMC3568967  PMID: 23215980
22.  Ultra-Flexibility and Unusual Electronic, Magnetic and Chemical Properties of Waved Graphenes and Nanoribbons 
Scientific Reports  2014;4:4198.
Two-dimensional materials have attracted increasing attention because of their particular properties and potential applications in next-generation nanodevices. In this work, we investigate the physical and chemical properties of waved graphenes/nanoribbons based on first-principles calculations. We show that waved graphenes are compressible up to a strain of 50% and ultra-flexible because of the vanishing in-plane stiffness. The conductivity of waved graphenes is reduced due to charge decoupling under high compression. Our analysis of pyramidalization angles predicts that the chemistry of waved graphenes can be easily controlled by modulating local curvatures. We further demonstrate that band gaps of armchair waved graphene nanoribbons decrease with the increase of compression if they are asymmetrical in geometry, while increase if symmetrical. For waved zigzag nanoribbons, their anti-ferromagnetic states are strongly enhanced by increasing compression. The versatile functions of waved graphenes enable their applications in multi-functional nanodevices and sensors.
doi:10.1038/srep04198
PMCID: PMC3935201  PMID: 24569444
23.  Serum Levels of the Adipokine Zinc-α2-glycoprotein Are Decreased in Patients with Hypertension 
ISRN Endocrinology  2014;2014:374090.
Objective. Zinc-α2-glycoprotein (ZAG) has recently been proposed as a new adipokine involved in body weight regulation. The purpose of this study is to investigate serum levels of ZAG in patients with hypertension and its association with related characteristics. Methods. 32 hypertension patients and 42 normal controls were recruited and the relationship between serum ZAG, total and high molecular weight (HMW) adiponectin, and tumor necrosis factor-α (TNFα) determined by enzyme-linked immunosorbent assay (ELISA) and metabolic-related parameters was investigated. Results. Serum ZAG concentrations were significantly lowered in patients with hypertension compared with healthy controls (61.4 ± 32 versus 78.3 ± 42 μg/mL, P < 0.05). The further statistical analysis demonstrated that serum ZAG levels were negatively correlated with waist-to-hip ratio (WHR) (r = −0.241, P < 0.05) and alanine aminotransferase (ALT) (r = −0.243, P < 0.05). Additionally, serum HMW adiponectin significantly decreased, while TNFα greatly increased in hypertension patients as compared with healthy controls (2.32 ± 0.41 versus 5.24 ± 1.02 μg/mL, 3.30 ± 1.56 versus 2.34 ± 0.99 pg/mL, P < 0.05). Conclusions. Serum ZAG levels are significantly lowered in hypertension patients and negatively correlated with obesity-related item WHR, suggesting ZAG is a factor associated with hypertension.
doi:10.1155/2014/374090
PMCID: PMC3934454  PMID: 24665369

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