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1.  Using the CT features to differentiate invasive pulmonary adenocarcinoma from pre-invasive lesion appearing as pure or mixed ground-glass nodules 
The British Journal of Radiology  2015;88(1053):20140811.
Objective:
To differentiate pre-invasive lesion from invasive pulmonary adenocarcinoma (IPA) appearing as ground-glass nodules (GGNs) using CT features.
Methods:
149 GGNs were enrolled in this study, with 74 pure GGNs (p-GGNs) and 75 mixed GGNs (m-GGNs). Firstly, univariate analysis was used to analyse the difference of CT features between pre-invasive lesion and IPA. Then, multivariate analysis was conducted to identify variables that could independently differentiate pre-invasive lesion from IPA. Receiver operating characteristic curve analysis was performed to evaluate the differentiating value of identified variables.
Results:
In the p-GGNs, multivariate analysis showed that the amount of blood vessels was an independent risk factor. Using the amount of blood vessels “≥1” as the diagnostic criterion, we could diagnose IPA with a sensitivity of 100%. Using the amount of blood vessels “=0” as the diagnostic criterion, we could diagnose pre-invasive lesions with a specificity of 100%. In the m-GGNs, multivariate analysis showed that the volume of solid portion (VSolid) and pleural indentation were two independent risk factors. One further model was constructed using these two variables: model = 2.508 × (VSolid + 1.407) × (pleural indentation − 1.016). Using the new model, improved diagnostic ability was achieved compared with using VSolid or pleural indentation alone.
Conclusion:
The amount of blood vessels through the p-GGNs would be an important criterion during clinical management, while VSolid and pleural indentation seemed important for m-GGNs. Moreover, the new model could further improve the differentiating value for m-GGNs.
Advances in knowledge:
CT features are useful in differentiating pre-invasive lesion from IPA appearing as GGNs.
doi:10.1259/bjr.20140811
PMCID: PMC4743560  PMID: 26090823
3.  Histidine-tryptophan-ketoglutarate solution decreases mortality and morbidity in high-risk patients with severe pulmonary arterial hypertension associated with complex congenital heart disease: an 11-year experience from a single institution 
Cardioplegic reperfusion during a long term ischemic period interrupts cardiac surgery and also increases cellular edema due to repeated solution administration. We reviewed the clinical experiences on myocardial protection of a single perfusion with histidine-tryptophan-ketoglutarate (HTK) for high-risk patients with severe pulmonary arterial hypertension associated with complex congenital heart disease. This retrospective study included 101 high-risk patients undergoing arterial switch operation between March 2001 and July 2012. We divided the cohort into two groups: HTK group, myocardial protection was carried out with one single perfusion with HTK solution; and St group, myocardial protection with conventional St. Thomas' crystalloid cardioplegic solution. The duration of cardiopulmonary bypass did not differ between the two groups. The mortality, morbidity, ICU stay, post-operative hospitalization time, and number of transfusions in HTK group were lower than those in St group (P<0.05). Univariate and multivariate analysis showed that HTK is a statistically significant independent predictor of decreased early mortality and morbidity (P<0.05). In conclusion, HTK solution seems to be an effective and safe alternative to St. Thomas' solution for cardioplegic reperfusion in high-risk patients with complex congenital heart disease.
doi:10.1590/1414-431X20165208
PMCID: PMC4869826  PMID: 27191607
Histidine-tryptophan-ketoglutarate; Myocardial protection; Cardiac surgery
4.  Antiferromagnetic proximity effect in epitaxial CoO/NiO/MgO(001) systems 
Scientific Reports  2016;6:22355.
Magnetic proximity effect between two magnetic layers is an important focus of research for discovering new physical properties of magnetic systems. Antiferromagnets (AFMs) are fundamental systems with magnetic ordering and promising candidate materials in the emerging field of antiferromagnetic spintronics. However, the magnetic proximity effect between antiferromagnetic bilayers is rarely studied because detecting the spin orientation of AFMs is challenging. Using X-ray linear dichroism and magneto-optical Kerr effect measurements, we investigated antiferromagnetic proximity effects in epitaxial CoO/NiO/MgO(001) systems. We found the antiferromagnetic spin of the NiO underwent a spin reorientation transition from in-plane to out-of-plane with increasing NiO thickness, with the existence of vertical exchange spring spin alignment in thick NiO. More interestingly, the Néel temperature of the CoO layer was greatly enhanced by the adjacent NiO layer, with the extent of the enhancement closely dependent on the spin orientation of NiO layer. This phenomenon was attributed to different exchange coupling strengths at the AFM/AFM interface depending on the relative spin directions. Our results indicate a new route for modifying the spin configuration and ordering temperature of AFMs through the magnetic proximity effect near room temperature, which should further benefit the design of AFM spintronic devices.
doi:10.1038/srep22355
PMCID: PMC4773757  PMID: 26932164
5.  Characterizing the Activation of the Wnt Signaling Pathway in Hilar Cholangiocarcinoma Using a Tissue Microarray Approach 
Hilar cholangiocarcinoma (HCCA) is an invasive hepatic malignancy that is difficult to biopsy; therefore, novel markers of HCCA prognosis are needed. Here, the level of canonical Wnt activation in patients with HCCA, intrahepatic cholangiocarcinoma (IHCC), and congenital choledochal cysts (CCC) was compared to understand the role of Wnt signaling in HCCA. Pathology specimens from HCCA (n=129), IHCC (n=31), and CCC (n=45) patients were used to construct tissue microarrays. Wnt2, Wnt3, β-catenin, TCF4, c-Myc, and cyclin D1 were detected by immunohistochemistry. Parallel correlation analysis was used to analyze differences in protein levels between the HCCA, IHCC, and CCC groups. Univariate and multivariate analyses were used to determine independent predictors of successful resection and prognosis in the HCCA group. The protein levels of Wnt2, β-catenin, TCF4, c-Myc, and cyclin D1 were significantly higher in HCCA compared to IHHC or CCC. Wnt signaling activation (Wnt2+, Wnt3+, nuclear β-catenin+, nuclear TCF4+) was significantly greater in HCCA tissues than CCC tissues. Univariable analyses indicated that expression of cyclin D1 as well as Wnt signaling activation, and partial Wnt activation (Wnt2+ or Wnt3+ and nuclear β-catenin+ or nuclear TCF4+) predicted successful resection, but only cyclin D1 expression remained significant in multivariable analyses. Only partial Wnt activation was an independent predictor of survival time. Proteins in the canonical Wnt signaling pathway were present at higher levels in HCCA and correlated with tumor resecility and patient prognosis. These results suggest that Wnt pathway analysis may be a useful marker for clinical outcome in HCCA.
doi:10.4081/ejh.2016.2536
PMCID: PMC4800245  PMID: 26972709
Hilar cholangiocarcinoma; Wnt signaling pathway; tissue microarray; β-catenin; c-Myc; cyclin D1
6.  Association of tamoxifen use and increased diabetes among Asian women diagnosed with breast cancer 
British Journal of Cancer  2014;111(9):1836-1842.
Background:
We conducted a population-based cohort study to assess whether tamoxifen treatment is associated with an increased incidence of diabetes.
Methods:
Data obtained from the Taiwanese National Health Insurance Research Database were used for a population-based cohort study. The study cohort included 22 257 breast cancer patients diagnosed between 1 January 2000 and 31 December 2004. Among them, 15 210 cases received tamoxifen treatment and 7047 did not. Four subjects without breast cancer were frequency-matched by age and index year as the control group. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using multivariate Cox proportional hazards regression analysis.
Results:
Breast cancer patients exhibited a 14% higher rate of developing diabetes (adjusted HR=1.14, 95% CI=1.08–1.20) compared with non-breast cancer controls, but the significant difference was limited to tamoxifen users. In addition, tamoxifen users exhibited a significantly increased risk of diabetes compared with non-tamoxifen users among women diagnosed with breast cancer (adjusted HR=1.31, 95% CI=1.19–1.45). Stratification by age groups indicated that both younger and older women diagnosed with breast cancer exhibited a significantly higher risk of diabetes than the normal control subjects did, and tamoxifen users consistently exhibited a significantly higher diabetes risk than non-tamoxifen users or normal control subjects did, regardless of age. Both recent and remote uses of tamoxifen were associated with an increased likelihood of diabetes.
Conclusions:
The results of this population-based cohort study suggested that tamoxifen use in breast cancer patients might increase subsequent diabetes risk. The underlying mechanism remains unclear and further larger studies are mandatory to validate our findings.
doi:10.1038/bjc.2014.488
PMCID: PMC4453737  PMID: 25225901
tamoxifen; breast cancer; diabetes; population-based; cohort study
7.  Folic acid supplementation and dietary folate intake, and risk of preeclampsia 
Wang, Y | Zhao, N | Qiu, J | He, X | Zhou, M | Cui, H | Lv, L | Lin, X | Zhang, C | Zhang, H | Xu, R | Zhu, D | Dang, Y | Han, X | Zhang, H | Bai, H | Chen, Y | Tang, Z | Lin, R | Yao, T | Su, J | Xu, X | Liu, X | Wang, W | Ma, B | Liu, S | Qiu, W | Huang, H | Liang, J | Wang, S | Ehrenkranz, RA | Kim, C | Liu, Q | Zhang, Y
European journal of clinical nutrition  2015;69(10):1145-1150.
BACKGROUND/OBJECTIVES
Folic acid supplementation has been suggested to reduce the risk of preeclampsia. However, results from few epidemiologic studies have been inconclusive. We investigated the hypothesis that folic acid supplementation and dietary folate intake before conception and during pregnancy reduce the risk of preeclampsia.
SUBJECTS/METHODS
A birth cohort study was conducted in 2010–2012 at the Gansu Provincial Maternity & Child Care Hospital in Lanzhou, China. A total of 10 041 pregnant women without chronic hypertension or gestational hypertension were enrolled.
RESULTS
Compared with nonusers, folic acid supplement users had a reduced risk of preeclampsia (OR = 0.61, 95% CI: 0.43–0.87). A significant dose–response of duration of use was observed among women who used folic acid supplemention during pregnancy only (P-trend = 0.007). The reduced risk associated with folic acid supplement was similar for mild or severe preeclampsia and for early- or late-onset preeclampsia, although the statistical significant associations were only observed for mild (OR = 0.50, 95% CI: 0.30–0.81) and late-onset (OR = 0.60, 95% CI: 0.42–0.86) preeclampsia. The reduced risk associated with dietary folate intake during pregnancy was only seen for severe preeclampsia (OR = 0.52, 95% CI: 0.31–0.87, for the highest quartile of dietary folate intake compared with the lowest).
CONCLUSIONS
Our study results suggest that folic acid supplementation and higher dietary folate intake during pregnancy reduce the risk of preeclampsia. Future studies are needed to confirm the associations.
doi:10.1038/ejcn.2014.295
PMCID: PMC4517985  PMID: 25626412
8.  Molecular Weight, Protein Binding Affinity and Methane Mitigation of Condensed Tannins from Mangosteen-peel (Garcinia mangostana L) 
The objectives of this study were to determine the molecular weight of condensed tannins (CT) extracted from mangosteen (Garcinia mangostana L) peel, its protein binding affinity and effects on fermentation parameters including total gas, methane (CH4) and volatile fatty acids (VFA) production. The average molecular weight (Mw) of the purified CT was 2,081 Da with a protein binding affinity of 0.69 (the amount needed to bind half the maximum bovine serum albumin). In vitro gas production declined by 0.409, 0.121, and 0.311, respectively, while CH4 production decreased by 0.211, 0.353, and 0.549, respectively, with addition of 10, 20, and 30 mg CT/500 mg dry matter (DM) compared to the control (p<0.05). The effects of CT from mangosteen-peel on in vitro DM degradability (IVDMD) and in vitro N degradability was negative and linear (p<0.01). Total VFA, concentrations of acetic, propionic, butyric and isovaleric acids decreased linearly with increasing amount of CT. The aforementioned results show that protein binding affinity of CT from mangosteen-peel is lower than those reported for Leucaena forages, however, the former has stronger negative effect on IVDMD. Therefore, the use of mangosteen-peel as protein source and CH4 mitigating agent in ruminant feed requires further investigations.
doi:10.5713/ajas.13.0834
PMCID: PMC4554851  PMID: 26323400
Condensed Tannins; Mangosteen-peel; Methane Production; Molecular Weight; Protein Binding Affinity
9.  Far upstream element-binding protein 1 is a prognostic biomarker and promotes nasopharyngeal carcinoma progression 
Cell Death & Disease  2015;6(10):e1920-.
Nasopharyngeal carcinoma (NPC) is a malignant epithelial tumor with tremendous invasion and metastasis capacities, and it has a high incidence in southeast Asia and southern China. Previous studies identified that far upstream element-binding protein 1 (FBP1), a transcriptional regulator of c-Myc that is one of the most frequently aberrantly expressed oncogenes in various human cancers, including NPC, is an important biomarker for many cancers. Our study aimed to investigate the expression and function of FBP1 in human NPC. Quantitative real-time RT-PCR (qRT-PCR), western blot and immunohistochemical staining (IHC) were performed in NPC cells and biopsies. Furthermore, the effect of FBP1 knockdown on cell proliferation, colony formation, side population tests and tumorigenesis in nude mice were measured by MTT, clonogenicity analysis, flow cytometry and a xenograft model, respectively. The results showed that the mRNA and protein levels of FBP1, which are positively correlated with c-Myc expression, were substantially higher in NPC than that in nasopharyngeal epithelial cells. IHC revealed that the patients with high FBP1 expression had a significantly poorer prognosis compared with the patients with low expression (P=0.020). In univariate analysis, high FBP1 and c-Myc expression predicted poorer overall survival (OS) and poorer progression-free survival. Multivariate analysis indicated that high FBP1 and c-Myc expression were independent prognostic markers. Knockdown of FBP1 reduced cell proliferation, clonogenicity and the ratio of side populations, as well as tumorigenesis in nude mice. These data indicate that FBP1 expression, which is closely correlated with c-Myc expression, is an independent prognostic factor and promotes NPC progression. Our results suggest that FBP1 can not only serve as a useful prognostic biomarker for NPC but also as a potential therapeutic target for NPC patients.
doi:10.1038/cddis.2015.258
PMCID: PMC4632288  PMID: 26469968
10.  Quantum Phase Coherence in Mesoscopic Transport Devices with Two-Particle Interaction 
Scientific Reports  2015;5:12873.
In this paper we demonstrate a new type of quantum phase coherence (QPC), which is generated by the two-body interaction. This conclusion is based on quantum master equation analysis for the full counting statistics of electron transport through two parallel quantum-dots with antiparallel magnetic fluxes in order to eliminate the Aharonov-Bohm interference of either single-particle or non-interacting two-particle wave functions. The interacting two-particle QPC is realized by the flux-dependent oscillation of the zero-frequency cumulants including the shot noise and skewness with a characteristic period. The accurately quantized peaks of cumulant spectrum may have technical applications to probe the two-body Coulomb interaction.
doi:10.1038/srep12873
PMCID: PMC4530461  PMID: 26255858
12.  Photon Devil’s staircase: photon long-range repulsive interaction in lattices of coupled resonators with Rydberg atoms 
Scientific Reports  2015;5:11510.
The realization of strong coherent interactions between individual photons is a long-standing goal in science and engineering. In this report, based on recent experimental setups, we derive a strong photon long-range repulsive interaction, by controlling the van der Waals repulsive force between Cesium Rydberg atoms located inside different cavities in extended Jaynes-Cummings-Hubbard lattices. We also find novel quantum phases induced by this photon long-range repulsive interaction. For example, without photon hopping, a photon Devil’s staircase, induced by the breaking of long-range translation symmetry, can emerge. If photon hopping occurs, we predict a photon-floating solid phase, due to the motion of particle- and hole-like defects. More importantly, for a large chemical potential in the resonant case, the photon hopping can be frozen even if the hopping term exists. We call this new phase the photon-frozen solid phase. In experiments, these predicted phases could be detected by measuring the number of polaritons via resonance fluorescence.
doi:10.1038/srep11510
PMCID: PMC4479987  PMID: 26108705
13.  Neurocognitive correlates of obesity and obesity-related behaviors in children and adolescents 
Childhood obesity rates have risen dramatically over the past few decades. Although obesity has been linked to poorer neurocognitive functioning in adults, much less is known about this relationship in children and adolescents. Therefore, we conducted a systematic review to examine the relationship between obesity and obesity-related behaviors with neurocognitive functioning in youth. We reviewed articles from 1976 to 2013 using PsycInfo, PubMed, Medline and Google Scholar. Search terms included cognitive function, neurocognitive function/performance, executive function, impulsivity, self-regulation, effortful control, cognitive control, inhibition, delayed gratification, memory, attention, language, motor, visuo-spatial, academic achievement, obesity, overweight, body mass index, waist-hip ratio, adiposity and body fat. Articles were excluded if participants had health problems known to affect cognitive functioning, the study used imaging as the only outcome measure, they were non-peer-reviewed dissertations, theses, review papers, commentaries, or they were non-English articles. Sixty-seven studies met inclusion criteria for this review. Overall, we found data that support a negative relationship between obesity and various aspects of neurocognitive functioning, such as executive functioning, attention, visuo-spatial performance, and motor skill. The existing literature is mixed on the effects among obesity, general cognitive functioning, language, learning, memory, and academic achievement. Executive dysfunction is associated with obesity-related behaviors, such as increased intake, disinhibited eating, and less physical activity. Physical activity is positively linked with motor skill. More longitudinal research is needed to determine the directionality of such relationships, to point towards crucial intervention time periods in the development of children, and to inform effective treatment programs.
doi:10.1038/ijo.2013.142
PMCID: PMC4456183  PMID: 23913029
neurocognition; cognitive functioning; pediatric obesity; treatment implications; obesity-related behaviors; children
14.  Haemophilus parainfluenzae prosthetic valve endocarditis complicated by septic emboli to brain 
BMJ Case Reports  2013;2013:bcr2013009744.
A 51-year-old man with a history of injection drug use presented to the emergency roomwith fevers, chills and headaches. Five months earlier, he had undergone bioprosthetic aortic valve replacement for infective endocarditis owing to Corynebacterium auricumosum involving a bicuspid aortic valve. Blood cultures obtained during current hospitalisation grew Haemophilus parainfluenzae and patient underwent a transesophageal echocardiogram that revealed a large mitral valve vegetation. Owing to persistent headache and right lower extremity weakness, MRI of the brain was performed which demonstrated multifocal, acute infarctions secondary to septic embolisation. He was initiated on parenteral antibiotics and experienced no further neurological setbacks. After 2 weeks of antibiotic therapy, he underwent bioprosthetic aortic and mitral valve replacement, aortic root debridement and replacement, and reconstruction of the intravalvular fibrosa without complication. He was discharged to a skilled nursing facility to complete six more weeks of intravenous ceftriaxone.
doi:10.1136/bcr-2013-009744
PMCID: PMC3702980  PMID: 23737586
15.  Effects of Supplementation of Mulberry (Morus alba) Foliage and Urea-rice Bran as Fermentable Energy and Protein Sources in Sheep Fed Urea-treated Rice Straw Based Diet 
A digestibility study was conducted to evaluate the effects of supplementing mulberry foliage and urea rice-bran as a source of fermentable energy and protein to 12 sheep fed diets based on urea-treated rice straw (TRS). The three dietary treatments were: T1, TRS with mulberry; T2, TRS with 50% mulberry replaced with rice bran and urea; and T3, TRS with rice bran and urea. The study was arranged in a completely randomized design with four replications for each treatment. The sheep were fed one of the three diets and the supplements were offered at 1.2% of the body weight (BW) and the TRS was provided ad libitum. There were no differences (p>0.05) among the three treatment groups with respect to dry matter (DM) intake (76.8±4.2 g/kg BW0.75) and DM, organic matter (OM), and crude protein (CP) digestibility (55.3±1.22; 69.9±0.85; 46.3±1.65% respectively for DM, OM, and CP). The digestibility of fiber (neutral detergent fiber [NDF] and acid detergent fiber) was significantly lower (p<0.05) for T3 (46.2 and 46.6 respectively) compared to T1 (55.8 and 53.7 respectively) and T2 (54.1 and 52.8 respectively). Nitrogen (N) intake by sheep on diet T3 was significantly (p<0.05) higher than sheep fed diet T1. However, N balance did not differ among the three diets (3.0±0.32 g/d). In contrast, the rumen ammonia (NH3-N) concentrations in sheep fed T2 and T3 were significantly (p<0.05) higher than in sheep fed T1. The NH3-N concentrations for all three diets were above the critical value required for optimum rumen microbial growth and synthesis. Total volatile fatty acid concentrations were highest (p<0.05) in T1 (120.3 mM), whilst the molar proportion of propionic acid was highest in T3 (36.9%). However, the microbial N supply in sheep fed T1 and T3 was similar but was significantly (p<0.05) higher than for sheep fed T2. It was concluded that mulberry foliage is a potential supplement of fermentable energy and protein for sheep fed TRS based diet. The suggested level of supplementation is 1.2% of BW or 32% of the total diet since it resulted in similar effects on the intake of DM, OM, and NDF, digestibility of DM, OM, and CP, N utilization and microbial supply when compared to rice bran and urea supplementation.
doi:10.5713/ajas.14.0406
PMCID: PMC4341098  PMID: 25656207
Mulberry (Morus alba); Fermentable Energy; Fermentable Protein; Feed Supplementation; Sheep
16.  Racial Disparities in Trajectories of Dental Caries Experience* 
Objectives
This study charted the trajectories of dental caries, including decayed teeth, missing teeth, and filled teeth among older Americans over a 5-year period. In particular, it focused on racial differences in the levels of and rates of change in dental caries experience.
Methods
Data came from the Piedmont Dental Study. The sample included 810 older Americans who were dentate at the baseline with up to 4 repeated observations between 1988 and 1994. Hierarchical linear models were employed in depicting intrapersonal and interpersonal differences in dental caries experience.
Results
Different measures of caries outcomes exhibited distinct trajectories. On average, the number of decayed teeth decreased over time, whereas missing teeth increased. In contrast, the number of filled teeth remained stable during a 5-year period. Relative to their white counterparts, older black Americans had more decayed teeth and missing teeth but fewer filled teeth. Blacks and whites differed in the levels of dental caries but not in their rates of change except for missing teeth. Even when demographic and socioeconomic attributes were adjusted, racial variations in dental caries experience remained significant.
Conclusions
Though significantly correlated, various dental caries outcomes move along different paths over time. In view of the persistent racial disparities in dental caries trajectories, future interventions to minimize such variations among older Americans in the levels of and the rates of change in dental caries experience are clearly warranted.
doi:10.1111/cdoe.12045
PMCID: PMC4324468  PMID: 23465078
17.  Phosphorene nanoribbon as a promising candidate for thermoelectric applications 
Scientific Reports  2014;4:6452.
In this work, the electronic properties of phosphorene nanoribbons with different width and edge configurations are studied by using density functional theory. It is found that the armchair phosphorene nanoribbons are semiconducting while the zigzag nanoribbons are metallic. The band gaps of armchair nanoribbons decrease monotonically with increasing ribbon width. By passivating the edge phosphorus atoms with hydrogen, the zigzag series also become semiconducting, while the armchair series exhibit a larger band gap than their pristine counterpart. The electronic transport properties of these phosphorene nanoribbons are then investigated using Boltzmann theory and relaxation time approximation. We find that all the semiconducting nanoribbons exhibit very large values of Seebeck coefficient and can be further enhanced by hydrogen passivation at the edge. Taking pristine armchair nanoribbons and hydrogen-passivated zigzag naoribbons with width N = 7, 8, 9 as examples, we calculate the lattice thermal conductivity with the help of phonon Boltzmann transport equation and evaluate the width-dependent thermoelectric performance. Due to significantly enhanced Seebeck coefficient and decreased thermal conductivity, we find that at least one type of phosphorene nanoribbons can be optimized to exhibit very high figure of merit (ZT values) at room temperature, which suggests their appealing thermoelectric applications.
doi:10.1038/srep06452
PMCID: PMC4171703  PMID: 25245326
18.  Expression pattern of tumour-associated antigens in hepatocellular carcinoma: association with immune infiltration and disease progression 
British Journal of Cancer  2013;109(4):1031-1039.
Background:
The distinct expression pattern of tumour-associated antigens (TAAs) might be a critical reason for the inefficacy of immunity-based treatments and heterogeneous postsurgical recovery in patients with solid tumours, including hepatocellular carcinoma (HCC). However, little is known about the clinical value of the coexpression patterns of multiple TAAs.
Methods:
We determined the expression of multiple TAAs with identified immunogenicity (GPC3, AFP, SSX-2, NY-ESO-1, EpCAM, midkine) and the density of tumour-infiltrating immune cells by immunohistochemistry in a panel of 362 primary HCC patients. We evaluated the association between the TAAs, immune cell infiltration, clinicopathological parameters, and prognosis.
Results:
Patients who coexpressed more TAAs had better prognosis (P<0.00001, overall survival). The integrated pattern of TAA was associated with good differentiation and small tumour size, and with more CD57+ natural killer and CD20+ B-cell infiltration (P<0.05). Multivariate Cox proportional hazards analysis identified the TAA index as an independent prognostic indicator (hazard ratio 0.625; 95% confidence interval 0.467–0.837; P=0.002), and could further predict patient prognosis in collaboration with local immune infiltration.
Conclusion:
Our results could provide new evidence for the improvement of prognostic molecular signatures in HCC, and a novel rationale for patient enrolment in future immunotherapeutic trials and/or clinical treatments.
doi:10.1038/bjc.2013.390
PMCID: PMC3749565  PMID: 23868000
tumour-associated antigen; immune infiltration; prognosis; hepatocellular carcinoma
19.  Chicken domestication: an updated perspective based on mitochondrial genomes 
Heredity  2012;110(3):277-282.
Domestic chickens (Gallus gallus domesticus) fulfill various roles ranging from food and entertainment to religion and ornamentation. To survey its genetic diversity and trace the history of domestication, we investigated a total of 4938 mitochondrial DNA (mtDNA) fragments including 2843 previously published and 2095 de novo units from 2044 domestic chickens and 51 red junglefowl (Gallus gallus). To obtain the highest possible level of molecular resolution, 50 representative samples were further selected for total mtDNA genome sequencing. A fine-gained mtDNA phylogeny was investigated by defining haplogroups A–I and W–Z. Common haplogroups A–G were shared by domestic chickens and red junglefowl. Rare haplogroups H–I and W–Z were specific to domestic chickens and red junglefowl, respectively. We re-evaluated the global mtDNA profiles of chickens. The geographic distribution for each of major haplogroups was examined. Our results revealed new complexities of history in chicken domestication because in the phylogeny lineages from the red junglefowl were mingled with those of the domestic chickens. Several local domestication events in South Asia, Southwest China and Southeast Asia were identified. The assessment of chicken mtDNA data also facilitated our understanding about the Austronesian settlement in the Pacific.
doi:10.1038/hdy.2012.83
PMCID: PMC3668654  PMID: 23211792
chicken; mtDNA; domestication; phylogeny; Austronesian
20.  Quantum phases in circuit QED with a superconducting qubit array 
Scientific Reports  2014;4:4083.
Circuit QED on a chip has become a powerful platform for simulating complex many-body physics. In this report, we realize a Dicke-Ising model with an antiferromagnetic nearest-neighbor spin-spin interaction in circuit QED with a superconducting qubit array. We show that this system exhibits a competition between the collective spin-photon interaction and the antiferromagnetic nearest-neighbor spin-spin interaction, and then predict four quantum phases, including: a paramagnetic normal phase, an antiferromagnetic normal phase, a paramagnetic superradiant phase, and an antiferromagnetic superradiant phase. The antiferromagnetic normal phase and the antiferromagnetic superradiant phase are new phases in many-body quantum optics. In the antiferromagnetic superradiant phase, both the antiferromagnetic and superradiant orders can coexist, and thus the system possesses symmetry. Moreover, we find an unconventional photon signature in this phase. In future experiments, these predicted quantum phases could be distinguished by detecting both the mean-photon number and the magnetization.
doi:10.1038/srep04083
PMCID: PMC3923215  PMID: 24522250
21.  Aphid Feeding Activates Expression of a Transcriptome of Oxylipin-Based Defense Signals in Wheat Involved in Resistance to Herbivory 
Journal of chemical ecology  2010;36(3):10.1007/s10886-010-9756-8.
Damage by the Russian wheat aphid (RWA), Diuraphis noxia, significantly reduces wheat and barley yields worldwide. In compatible interactions, virulent RWA populations flourish and susceptible plants suffer extensive leaf chlorophyll loss. In incompatible interactions, RWA reproduction and population growth are significantly reduced and RWA-related chlorophyll loss in resistant plants is minor. The objectives of this study were to develop an understanding of the molecular and phytochemical bases of RWA resistance in plants containing the Dnx resistance gene. Microarray, real-time polymerase chain reaction, and phytohormone assays were conducted to identify transcriptome components unique to RWA-infested Dnx plants and susceptible (Dn0) plants, and to identify and characterize putative genes involved in Dnx plant defense responses. We found that RWA-infested Dnx plants upregulated > 180 genes related to reactive oxygen species, signaling, pathogen defense, and arthropod allelochemical and physical defense. The expression of several of these genes in RWA-infested Dnx plants increased significantly from 6- to 24-h post infestation (hpi), but their expression in Dn0 plants, when present, was delayed until 48- to 96 hpi. Concentrations of 16- and 18-carbon fatty acids, trans-methyl-12-oxophytodienoic acid, and abscisic acid were significantly greater in Dnx foliage than in Dn0 foliage after RWA infestation, suggesting that Dnx RWA defense and resistance genes may be regulated via the oxylipin pathway. These findings provide a foundation for the elucidation of the molecular basis for compatible- and incompatible plant-aphid interactions.
doi:10.1007/s10886-010-9756-8
PMCID: PMC3831272  PMID: 20229216
Diuraphis noxia; Insect; Microarray; Northern blot; Oxylipin signaling; Plant defense; Real-time polymerase chain reaction (PCR); Russian wheat aphid; Triticum aestivum; Wheat
22.  Orbit-induced spin squeezing in a spin-orbit coupled Bose-Einstein condensate 
Scientific Reports  2013;3:3166.
In recent pioneer experiment, a strong spin-orbit coupling, with equal Rashba and Dresselhaus strengths, has been created in a trapped Bose-Einstein condensate. Moreover, many exotic superfluid phenomena induced by this strong spin-orbit coupling have been predicted. In this report, we show that this novel spin-orbit coupling has important applications in quantum metrology, such as spin squeezing. We first demonstrate that an effective spin-spin interaction, which is the heart for producing spin squeezing, can be generated by controlling the orbital degree of freedom (i.e., the momentum) of the ultracold atoms. Compared with previous schemes, this realized spin-spin interaction has advantages of no dissipation, high tunability, and strong coupling. More importantly, a giant squeezing factor (lower than −30 dB) can be achieved by tuning a pair of Raman lasers in current experimental setup. Finally, we find numerically that the phase factor of the prepared initial state affects dramatically on spin squeezing.
doi:10.1038/srep03166
PMCID: PMC3819609  PMID: 24196590
23.  Piperlongumine induces autophagy by targeting p38 signaling 
Cell Death & Disease  2013;4(10):e824-.
Piperlongumine (PL), a natural product isolated from the plant species Piper longum L., can selectively induce apoptotic cell death in cancer cells by targeting the stress response to reactive oxygen species (ROS). Here we show that PL induces cell death in the presence of benzyloxycarbonylvalyl-alanyl-aspartic acid (O-methyl)-fluoro-methylketone (zVAD-fmk), a pan-apoptotic inhibitor, and in the presence of necrostatin-1, a necrotic inhibitor. Instead PL-induced cell death can be suppressed by 3-methyladenine, an autophagy inhibitor, and substantially attenuated in cells lacking the autophagy-related 5 (Atg5) gene. We further show that PL enhances autophagy activity without blocking autophagy flux. Application of N-acetyl-cysteine, an antioxidant, markedly reduces PL-induced autophagy and cell death, suggesting an essential role for intracellular ROS in PL-induced autophagy. Furthermore, PL stimulates the activation of p38 protein kinase through ROS-induced stress response and p38 signaling is necessary for the action of PL as SB203580, a p38 inhibitor, or dominant-negative p38 can effectively reduce PL-mediated autophagy. Thus, we have characterized a new mechanism for PL-induced cell death through the ROS-p38 pathway. Our findings support the therapeutic potential of PL by triggering autophagic cell death.
doi:10.1038/cddis.2013.358
PMCID: PMC3824668  PMID: 24091667
piperlongumine; autophagy; p38; reactive oxygen species
24.  Saccharomyces cerevisiae Live Cells Decreased In vitro Methane Production in Intestinal Content of Pigs 
An in vitro gas production technique was used in this study to elucidate the effect of two strains of active live yeast on methane (CH4) production in the large intestinal content of pigs to provide an insight to whether active live yeast could suppress CH4 production in the hindgut of pigs. Treatments used in this study include blank (no substrate and no live yeast cells), control (no live yeast cells) and yeast (YST) supplementation groups (supplemented with live yeast cells, YST1 or YST2). The yeast cultures contained 1.8×1010 cells per g, which were added at the rates of 0.2 mg and 0.4 mg per ml of the fermented inoculum. Large intestinal contents were collected from 2 Duroc×Landrace×Yorkshire pigs, mixed with a phosphate buffer (1:2), and incubated anaerobically at 39°C for 24 h using 500 mg substrate (dry matter (DM) basis). Total gas and CH4 production decreased (p<0.05) with supplementation of yeast. The methane production reduction potential (MRP) was calculated by assuming net methane concentration for the control as 100%. The MRP of yeast 2 was more than 25%. Compared with the control group, in vitro DM digestibility (IVDMD) and total volatile fatty acids (VFA) concentration increased (p<0.05) in 0.4 mg/ml YST1 and 0.2 mg/ml YST2 supplementation groups. Proportion of propionate, butyrate and valerate increased (p<0.05), but that of acetate decreased (p<0.05), which led to a decreased (p<0.05) acetate: propionate (A: P) ratio in the both YST2 treatments and the 0.4 mg/ml YST 1 supplementation groups. Hydrogen recovery decreased (p<0.05) with yeast supplementation. Quantity of methanogenic archaea per milliliter of inoculum decreased (p<0.05) with yeast supplementation after 24 h of incubation. Our results suggest that live yeast cells suppressed in vitro CH4 production when inoculated into the large intestinal contents of pigs and shifted the fermentation pattern to favor propionate production together with an increased population of acetogenic bacteria, both of which serve as a competitive pathway for the available H2 resulting in the reduction of methanogenic archaea.
doi:10.5713/ajas.2012.12663
PMCID: PMC4093248  PMID: 25049860
In vitro Gas Production; Methane; Methanogenic Archaea; Pig; Saccharomyces cerevisiae; Volatile Fatty Acid
25.  Effects of Enzyme Treated Palm Kernel Expeller on Metabolizable Energy, Growth Performance, Villus Height and Digesta Viscosity in Broiler Chickens 
This study examined whether pre-treating palm kernel expeller (PKE) with exogenous enzyme would degrade its fiber content; thus improving its metabolizable energy (ME), growth performance, villus height and digesta viscosity in broiler chickens fed diets containing PKE. Our results showed that enzyme treatment decreased (p<0.05) hemicellulose and cellulose contents of PKE by 26.26 and 32.62%, respectively; and improved true ME (TME) and its nitrogen corrected value (TMEn) by 38% and 33%, respectively, compared to the raw sample. Average daily gain (ADG), feed intake and feed conversion ratio (FCR) of chickens fed on different dietary treatments in the grower period were not significantly different. Although there was no difference in feed intake (p>0.05) among treatment groups in the finisher period, ADG of chickens in the control (PKE-free diet) was higher (p<0.05) than in all treatment groups fed either 20 or 30% PKE, irrespective of with or without enzyme treatment. However, ADG of birds fed with 20% PKE was higher than those fed with 30% PKE. The FCR of chickens in the control was the lowest (2.20) but not significantly different from those fed 20% PKE diets while birds in the 30% PKE diets recorded higher (p>0.05) FCR. The intestinal villus height and crypt depth (duodenum, jejunum and ileum) were not different (p>0.05) among treatments except for duodenal crypt depth. The villus height and crypt depth of birds in enzyme treated PKE diets were higher (p<0.05) than those in the raw PKE groups. Viscosity of the intestinal digesta was not different (p>0.05) among treatments. Results of this study suggest that exogenous enzyme is effective in hydrolyzing the fiber (hemicellulose and cellulose) component and improved the ME values of PKE, however, the above positive effects were not reflected in the growth performance in broiler chickens fed the enzyme treated PKE compared to those received raw PKE. The results suggest that PKE can be included up to 5% in the grower diet and 20% in the finisher diet without any significant negative effect on FCR in broiler chickens.
doi:10.5713/ajas.2012.12463
PMCID: PMC4093377  PMID: 25049820
Palm Kernel Expeller; True Metabolizable Energy; Enzyme; Broiler

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