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1.  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.
PMCID: PMC4268636  PMID: 25516240
2.  PM2.5 in Beijing – temporal pattern and its association with influenza 
Environmental Health  2014;13(1):102.
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.
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.
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).
Ambient PM2.5 concentrations were significantly associated with human influenza cases in Beijing, which have important implications for public health and environmental actions.
PMCID: PMC4271358  PMID: 25471661
Air pollution; PM2.5; Temporal pattern; Association; Influenza; Beijing
3.  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.
PMCID: PMC3909471  PMID: 24125850
Cannabinoid; CB2; GPCR; neuropathic pain; carbazole; CB1
4.  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.
PMCID: PMC4186815  PMID: 25294975
Silicon nitride nanowire; Solar energy harvesting; Doping; First-principles calculation
5.  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.
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.
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.
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.
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.
PMCID: PMC4178107  PMID: 25276366
Non-small-cell lung cancer (NSCLC); epidermal growth factor receptor (EGFR) mutation; first-line chemotherapy; meta-analysis
6.  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.
PMCID: PMC3734791  PMID: 23716583
hypertension; hypothalamus; sympathetic nervous activity; synaptic transmission; glutamate receptors
7.  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.
PMCID: PMC4159808  PMID: 25093716
biological invasion; exotic introduction; genetic differentiation; genetic structure
8.  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.
PMCID: PMC3716857  PMID: 23647148
pontine micturition center; micturition reflex; autonomic nervous system; voltage-activated K+ channels; synaptic transmission
9.  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.
PMCID: PMC4113650  PMID: 25120615
anemia; chronic heart failure; erythropoiesis-stimulating proteins; hospitalization; mortality
10.  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.
PMCID: PMC4114580  PMID: 25120649
telomerase Cajal body protein 1; telomerase trafficking; antiproliferation; cell cycle arrest
11.  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.
PMCID: PMC4071773  PMID: 24967679
12.  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.
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.
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.
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.
There were positive associations between CO levels and childhood inpatient visits as well as NO2, CO and PM10 and outpatient visits.
PMCID: PMC4006842  PMID: 24789041
13.  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.
PMCID: PMC3568967  PMID: 23215980
14.  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.
PMCID: PMC3935201  PMID: 24569444
15.  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.
PMCID: PMC3934454  PMID: 24665369
18.  Chemotherapy for patients with gastric cancer after complete resection: A network meta-analysis 
AIM: To conduct a network meta-analysis to evaluate the effectiveness of different chemotherapy regimens for patients with gastric cancer.
METHODS: PubMed (1966-2011.12), the Cochrane Library (2011 Issue 2) and EMBASE (1974-2011.12) were searched with the terms “gastric cancer” and “chemotherapy”, as well as the medical subject headings. References from relevant articles and conferences were also included. Patients who had previous gastric surgery, radiation before or after surgery or chemotherapy before surgery were excluded. In this study, only randomized controlled trials (RCTs) were considered, and the end-point was the overall mortality. Direct comparisons were performed using traditional meta-analysis whereas indirect comparisons were performed using network meta-analysis.
RESULTS: In total, 31 RCTs with 7120 patients were included. Five chemotherapy regimens, fluorouracil (FU) + BCNU, FU + methyl-CCNU (mCCNU), FU + cisplatin, FU + anthracyclines and FU + mitomycin c (MMC) + cytarabine (Ara-c), were found to be less beneficial in terms of overall mortality. In contrast, four chemotherapy regimens were effective for the patients after surgery, including FU + MMC + adriamycin (FMA), FU + MMC (FM), Tegafur and MMC, There was no significant difference in terms of overall mortality among these regimens. The evidence for the FM regimen and MMC regimen was poor. Additionally, the FMA regimen, which includes a variety of chemotherapy drugs and causes many side effects, was not better than the Tegafur regimen.
CONCLUSION: Although the four chemotherapy regimens were effective in patients with gastric cancer after surgery and the overall mortality revealed no significant difference among them in the network meta-analysis, thorough analysis of the results recommends Tegafur as the first-line adjuvant chemotherapy regimen for patients after complete resection.
PMCID: PMC3923035  PMID: 24574729
Gastric cancer; Chemotherapy; Randomized controlled trials; Indirect treatment comparison; Network meta-analysis
19.  In Vivo Transplantation of Autogenous Marrow-Derived Cells Following Rapid Intraoperative Magnetic Separation Based on Hyaluronan to Augment Bone Regeneration 
Tissue Engineering. Part A  2012;19(1-2):125-134.
This project was designed to test the hypothesis that rapid intraoperative processing of bone marrow based on hyaluronan (HA) could be used to improve the outcome of local bone regeneration if the concentration and prevalence of marrow-derived connective tissue progenitors (CTPs) could be increased and nonprogenitors depleted before implantation.
HA was used as a marker for positive selection of marrow-derived CTPs using magnetic separation (MS) to obtain a population of HA-positive cells with an increased CTP prevalence. Mineralized cancellous allograft (MCA) was used as an osteoconductive carrier scaffold for loading of HA-positive cells. The canine femoral multidefect model was used and four cylindrical defects measuring 10 mm in diameter and 15 mm in length were grafted with MCA combined with unprocessed marrow or with MS processed marrow that was enriched in HA+ CTPs and depleted in red blood cells and nonprogenitors. Outcome was assessed at 4 weeks using quantitative 3D microcomputed tomography (micro-CT) analysis of bone formation and histomorphological assessment.
Histomorphological assessment showed a significant increase in new bone formation and in the vascular sinus area in the MS-processed defects. Robust bone formation was found throughout the defect area in both groups (defects grafted with unprocessed marrow or with MS processed marrow.) Percent bone volume in the defects, as assessed by micro-CT, was greater in defects engrafted with MS processed cells, but the difference was not statistically significant.
Rapid intraoperative MS processing to enrich CTPs based on HA as a surface marker can be used to increase the concentration and prevalence of CTPs. MCA grafts supplemented with heparinized bone marrow or MS processed cells resulted in a robust and advanced stage of bone regeneration at 4 weeks. A greater new bone formation and vascular sinus area was found in defects grafted with MS processed cells. These data suggest that MS processing may be used to enhance the performance of marrow-derived CTPs in clinical bone regeneration procedures. Further assessment in a more stringent bone defect model is proposed.
PMCID: PMC3593694  PMID: 23082937
20.  Characterization of Endothelin-converting Enzyme-2 
The Journal of biological chemistry  2003;278(17):10.1074/jbc.M211242200.
Most neuroendocrine peptides are generated by proteolysis of the precursors at basic residue cleavage sites. Prohormone convertases belonging to the subtilisin family of serine proteases are primarily responsible for processing at these “classical sites.” In addition to the classical cleavages, a subset of bioactive peptides is generated by processing at “nonclassical” sites. The proteases responsible for these cleavages have not been well explored. Members of several metalloprotease families have been proposed to be involved in nonclassical processing. Among them, endothelin-converting enzyme-2 (ECE-2) is a good candidate because it exhibits a neuroendocrine distribution and an acidic pH optimum. To examine the involvement of this protease in neuropeptide processing, we purified the recombinant enzyme and characterized its catalytic activity. Purified ECE-2 efficiently processes big endothelin-1 to endothelin-1 by cleavage between Trp21 and Val22 at acidic pH. To characterize the substrate specificity of ECE-2, we used mass spectrometry with a panel of 42 peptides as substrates to identify the products. Only 10 of these 42 peptides were processed by ECE-2. A comparison of residues around the cleavage site revealed that ECE-2 exhibits a unique cleavage site selectivity that is related to but distinct from that of ECE-1. ECE-2 tolerates a wide range of amino acids in the P1-position and prefers aliphatic/aromatic residues in the P1′-position. However, only a small fraction of the aliphatic/aromatic amino acid-containing sites were cleaved, indicating that there are additional constraints beyond the P1- and P1′-positions. The enzyme is able to generate a number of biologically active peptides from peptide intermediates, suggesting an important role for this enzyme in the biosynthesis of regulatory peptides. Also, ECE-2 processes proenkephalin-derived bovine adrenal medulla peptides, and this processing leads to peptide products known to have differential receptor selectivity. Finally, ECE-2 processes PEN-LEN, an endogenous inhibitor of prohormone convertase 1, into products that do not inhibit the enzyme. Taken together, these results are consistent with an important role for ECE-2 in the processing of regulatory peptides at nonclassical sites.
PMCID: PMC3862352  PMID: 12560336
21.  Spatial Genetic Heterogeneity in Populations of a Newly Invasive Whitefly in China Revealed by a Nation-Wide Field Survey 
PLoS ONE  2013;8(11):e79997.
Even though introductions of exotic species provide ready-made experiments of rapid evolution, few studies have examined the genetic structure of an exotic species shortly after its initial introduction and subsequent spread. To determine the genetic structure of its populations during the initial introduction, we investigated the invasive sweet potato whitefly (Bemisia tabaci Q, commonly known as B. tabaci biotype Q) in China, which was introduced in approximately 2003. A total of 619 B. tabaci Q individuals in 20 provinces throughout China were collected and analyzed using five microsatellite loci.
The introduced populations of B. tabaci Q in China represent eight genetic clusters with different geographic distributions. The populations in Yunnan Province, where B. tabaci Q was first detected, are genetically different from the other populations in China.
The introduced populations of B. tabaci Q in China have high spatial genetic heterogeneity. Additional research is required to determine whether the heterogeneity results from multiple introductions, rapid evolution following one or few introductions, or some combination of multiple introductions and rapid evolution. The heterogeneity, however, is inconsistent with a single introduction at Yunnan Province, where B. tabaci Q was first detected, followed by spread.
PMCID: PMC3841195  PMID: 24302995
22.  Incongruence between Nuclear and Chloroplast DNA Phylogenies in Pedicularis Section Cyathophora (Orobanchaceae) 
PLoS ONE  2013;8(9):e74828.
Pedicularis section Cyathophora is a monophyletic group characterized by perfoliate leaf and/or bract bases at each node. This section comprises four series, corresponding to four general corolla types of Pedicularis, i.e. toothless, toothed, beaked and long-tubed corollas. In this study, we aim to reconstruct a comprehensive phylogeny of section Cyathophora, and compare phylogenetic incongruence between nuclear and chloroplast datasets. Sixty-seven accessions belonging to section Cyathophora and 9 species for other Pedicularis were sampled, and one nuclear gene (nrITS) and four chloroplast genes (matK, rbcL, trnH-psbA and trnL-F) were sequenced. Phylogenetic analyses show that the topologies and networks inferred from nrITS and the concatenated chloroplast datasets were incongruent, and the nrITS phylogenies and network agreed with the morphology-based taxonomy to some degree. The chloroplast genome of two Sichuan samples of P. cyathophylloides (E4 and E5) may show introgression from an ancestor of P. cyathophylla. Neither the nrITS dataset nor the concatenated chloroplast dataset were able to adequately resolve relationships among species in the series Reges; this is most likely due to incomplete lineage sorting and/or introgression/hybridization. The nrITS phylogeny indicates the beakless (toothed and toothless) and beaked galeas may have evolved independently within section Cyathophora, and the chloroplast phylogeny reveals that the long corolla tube with beaked galea is derived from the short one.
PMCID: PMC3777957  PMID: 24069353
23.  Progress and prospects in stem cell therapy 
Acta Pharmacologica Sinica  2013;34(6):741-746.
In the past few years, progress being made in stem cell studies has incontestably led to the hope of developing cell replacement based therapy for diseases deficient in effective treatment by conventional ways. The induced pluripotent stem cells (iPSCs) are of great interest of cell therapy research because of their unrestricted self-renewal and differentiation potentials. Proof of principle studies have successfully demonstrated that iPSCs technology would substantially benefit clinical studies in various areas, including neurological disorders, hematologic diseases, cardiac diseases, liver diseases and etc. On top of this, latest advances of gene editing technologies have vigorously endorsed the possibility of obtaining disease-free autologous cells from patient specific iPSCs. Here in this review, we summarize current progress of stem cell therapy research with special enthusiasm in iPSCs studies. In addition, we compare current gene editing technologies and discuss their potential implications in clinic application in the future.
PMCID: PMC3674518  PMID: 23736002
induced pluripotent stem cells (iPSCs); stem cell therapy; gene editing; neurological disorders; hematologic diseases; cardiac diseases; liver diseases
24.  Nerve Injury Increases Brain-Derived Neurotrophic Factor Levels to Suppress BK Channel Activity in Primary Sensory Neurons 
Journal of Neurochemistry  2012;121(6):944-953.
Abnormal hyperexcitability of primary sensory neurons contributes to neuropathic pain development after nerve injury. Nerve injury profoundly reduces the expression of big conductance Ca2+-activated K+ (BK) channels in the dorsal root ganglion (DRG). However, little is known about how nerve injury affects BK channel activity in DRG neurons. In this study, we determined the changes in BK channel activity in different sizes of DRG neurons in a rat model of neuropathic pain and the contribution of brain-derived neurotrophic factor (BDNF) to reduced BK channel activity. The BK channel activity was present predominantly in small and medium DRG neurons, and ligation of L5 and L6 spinal nerves profoundly decreased the BK current density in these neurons. Blocking BK channels significantly increased the excitability of DRG neurons in sham control, but not in nerve-injured, rats. The BDNF concentration in the DRG was significantly greater in nerve-injured rats than in control rats. BDNF treatment largely reduced BK currents in DRG neurons in control rats, which was blocked by either anti-BDNF antibody or K252a, a Trk receptor inhibitor. Furthermore, either anti-BDNF antibody or K252a reversed reduction in BK currents in injured DRG neurons. BDNF treatment reduced the mRNA levels of BKα1 subunit in DRG neurons, and anti-BDNF antibody attenuated the reduction in the BKα1 mRNA level in injured DRG neurons. These findings suggest that nerve injury primarily diminishes the BK channel activity in small and medium DRG neurons. Increased BDNF levels contribute to reduced BK channel activity in DRG neurons in neuropathic pain.
PMCID: PMC3371106  PMID: 22428625
25.  Inhibition of preadipocyte differentiation and adipogenesis by zinc‐α2‐glycoprotein treatment in 3T3‐L1 cells 
Zinc‐α2‐glycoprotein (ZAG) is associated with the loss of adipose tissue in cancer cachexia, and has recently been proposed to be a candidate factor in the regulation of bodyweight. The aim of the study was to investigate the effects of ZAG on the proliferation and differentiation of 3T3‐L1 preadipocytes.
Materials and Methods
3‐(4,5‐Dimethylthiazol‐2‐yl) 2,5‐diphenyl tetrazolium bromide (MTT) spectrophotometry, Oil Red O staining, intracellular triglyceride assays, real‐time quantitative reverse transcription polymerase chain reaction and transient transfection methods were used to explore the action of ZAG.
Ectopic ZAG expression significantly stimulates 3T3‐L1 cells proliferation in a dose‐ and time‐dependent manner. The maximum influence of ZAG on proliferation was 1.43‐fold higher than what was observed in control cells. This effect was observed 144 h after transfection with 0.16 μg of murine ZAG (mZAG) plasmid (P < 0.001). The intracellular lipids content in mZAG over‐expressing cells were decreased as much as 37% when compared with the control cells after differentiation (P < 0.05, P < 0.01). The messenger ribonucleic acid levels of peroxisome proliferators‐activated receptor‐γ (PPARγ), CCAAT enhancer‐binding protein‐α (C/EBPα) and the critical lipogenic gene, fatty acid synthase (FAS), are also downregulated by up to 50% in fully differentiated ZAG‐treated adipocytes. ZAG suppresses FAS messenger ribonucleic acid expression by reducing FAS promoter activity.
Zinc‐α2‐glycoprotein stimulates the proliferation and inhibits the differentiation of 3T3‐L1 murine preadipocytes. The inhibitory action of ZAG on cell differentiation might be a result of the attenuation of the expression of PPARγ, C/EBPα and the lipogenic‐specific enzyme FAS by reducing FAS promoter activity.
PMCID: PMC4015661  PMID: 24843663
3T3‐L1 preadipocytes; Differentiation; Zinc‐α2‐glycoprotein

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