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1.  Predictive Value of Serum IFN-γ inducible Protein-10 and IFN-γ/IL-4 Ratio for Liver Fibrosis Progression in CHB Patients 
Scientific Reports  2017;7:40404.
Noninvasive serum markers for assessment of liver fibrosis in chronic hepatitis B (CHB) patients have not been well-studied. The present study was to evaluate the predictive value of serum interferon gamma-inducible protein-10 (IP-10/CXCL10) and the interferon (IFN)-γ/interleukin (IL)-4 ratio for liver fibrosis progression in CHB patients. A total of 180 CHB patients were categorized into four groups: no fibrosis, mild fibrosis, moderate fibrosis, and severe fibrosis. Serum and intrahepatic levels of IP-10, IFN-γ, and IL-4 were examined, from which the IFN-γ/IL-4 ratio was calculated. We found that the serum IP-10 levels were positively correlated with the severity of liver fibrosis, whereas the IFN-γ/IL-4 ratio was negatively associated with the progression of hepatic fibrosis. Multivariate logistic regression analysis revealed that the serum IP-10 was an independent predictor for significant fibrosis. For predicting significant fibrosis, the IP-10 cut-off value of 300 ng/mL had a sensitivity of 92.7% and a specificity of 68.6%. When the IP-10 level was combined with the IFN-γ/IL-4 ratio, the specificity and positive predictive value were 93.8% and 94.6%, respectively; thus, the discriminatory ability was much improved. In conclusion, the serum IP-10 level and the IFN-γ/IL-4 ratio have great potential to predict significant fibrosis among CHB patients.
doi:10.1038/srep40404
PMCID: PMC5220308  PMID: 28067328
2.  Trend in young coronary artery disease in China from 2010 to 2014: a retrospective study of young patients ≤ 45 
Background
The incidence of young coronary heart disease (CHD, ≤45 years) in China is increasing. Secondary prevention to counter this trend is an important contemporary public health issure.
Methods
A total of 5288 patients (≤45 years) diagnosed with CHD and hospitalized at the Chinese PLA General Hospital and Anzhen Hospital, both in Beijing, were enrolled after satisfying the inclusion criteria.
Results
Young CHD patients increased in number from 2010 to 2014, especially men. Among the studied patients, there was no significant change over those years in blood pressure, but heart rate increased significantly (P < 0.05) and body mass index showed a rising trend (P > 0.05). The incidence of hypertension increased from 40.7 to 47.5%, diabetes from 20.3 to 26.1%, and hyperlipidemia from 27.3 to 35.7% (P < 0.05). However, the incidences of smoking and drinking both trended downward (P < 0.05). The levels of total cholesterol and triglycerides also showed a downward trend (P < 0.05), as did levels of low-density lipoprotein, but not to the point of statistical significance (P > 0.05). Mortality during hospitalization decreased significantly from 2010 to 2014 (P < 0.05), but there was no significant improvement in the incidences of cardiac death and major adverse cardiovascular events (MACE) after 1-year follow-up (P > 0.05).
Conclusions
Over the 5 years studied, the overall incidence of cardiac death and MACE for young CHD patients (≤45 years) has shown little improvement. Secondary prevention of young CHD, and its risk factors, as well as appropriate courses of medical treatment must be further elucidated.
Electronic supplementary material
The online version of this article (doi:10.1186/s12872-016-0458-1) contains supplementary material, which is available to authorized users.
doi:10.1186/s12872-016-0458-1
PMCID: PMC5219759  PMID: 28061763
Young; Coronary heart disease; Risk factors; Prevention; Prognosis
3.  Dominant Negative Consequences of a hERG 1b-Specific Mutation Associated with Intrauterine Fetal Death 
The human ether-a-go-go related gene (hERG) encodes two subunits, hERG 1a and hERG 1b, that combine in vivo to conduct the rapid delayed rectifier potassium current (IKr). Reduced IKr slows cardiac action potential (AP) repolarization and is an underlying cause of cardiac arrhythmias associated with long QT syndrome (LQTS). Although the physiological importance of hERG 1b has been elucidated, the effects of hERG 1b disease mutations on cardiac IKr and AP behavior have not been described. To explore the disease mechanism of a 1b-specific mutation associated with a case of intrauterine fetal death, we examined the effects of the 1b-R25W mutation on total protein, trafficking and membrane current levels in HEK293 cells at physiological temperatures. By all measures the 1b-R25W mutation conferred diminished expression, and exerted a temperature-sensitive, dominant-negative effect over the WT hERG 1a protein with which it was co-expressed. Membrane currents were reduced by 60% with no apparent effect on voltage dependence or deactivation. The dominant-negative effects of R25W were demonstrated in iPSC-CMs, where 1b-R25W transfection diminished native IKr compared to controls. R25W also slowed AP repolarization, and increased AP triangulation and variability in iPSC-CMs, reflecting cellular manifestations of pro-arrhythmia. These data demonstrate that R25W is a dominant-negative mutation with significant pathophysiological consequences, and provide the first direct link between hERG 1b mutation and cardiomyocyte dysfunction.
doi:10.1016/j.pbiomolbio.2016.01.002
PMCID: PMC4821159  PMID: 26772437
hERG; KCNH2; cardiomyocyte; arrhythmia; long QT syndrome
4.  Injury mediated vascular regeneration requires endothelial ER71/ETV2 
Objective
Comprehensive understanding of the mechanisms regulating angiogenesis might provide new strategies for angiogenic therapies for treating diverse physiologic and pathologic ischemic conditions. The ETS factor ETV2 (aka ER71) is essential for the formation of hematopoietic and vascular systems. Despite its indispensable function in vessel development, ETV2 role in adult angiogenesis has not yet been addressed. We have therefore investigated the role of ETV2 in vascular regeneration.
Approach and Results
We utilized endothelial Etv2 conditional knockout (CKO) mice and ischemic injury models to assess the role of ETV2 in vascular regeneration. While Etv2 expression was not detectable under steady state conditions, its expression was readily observed in endothelial cells following injury. Mice lacking endothelial Etv2 displayed impaired neovascularization in response to eye injury, wounding, or hindlimb ischemic injury. Lentiviral Etv2 expression in ischemic hindlimbs led to improved recovery of blood flow with enhanced vessel formation. Following injury, Flk1 expression and neovascularization were significantly upregulated by Etv2, while Flk1 expression and VEGF response were significantly blunted in Etv2 deficient endothelial cells. Conversely, enforced Etv2 expression enhanced VEGF mediated endothelial sprouting from embryoid bodies. Lentiviral Flk1 expression rescued angiogenesis defects in endothelial Etv2 CKO mice following hindlimb ischemic injury. Furthermore, Etv2+/−; Flk1+/− double heterozygous mice displayed a more severe hindlimb ischemic injury response compared to Etv2+/− or Flk1+/− heterozygous mice, revealing an epistatic interaction between ETV2 and FLK1 in vascular regeneration.
Conclusion
Our study demonstrates a novel obligatory role for the ETV2 in postnatal vascular repair and regeneration.
doi:10.1161/ATVBAHA.115.306430
PMCID: PMC4690812  PMID: 26586661
ETV2/ER71; FLK1/VEGFR2; Tie2-Cre; VEcadherin-Cre; injury-induced neovascularization; vascular regeneration
5.  Psychometric properties of the Anxiety Inventory for Respiratory Disease in patients with COPD in China 
Background
Anxiety is a common comorbidity in patients with COPD in China, and it can significantly decrease patients’ quality of life. Almost all anxiety measurements contain somatic items that can overlap with symptoms of COPD and side effects of medicines, which can lead to bias in measuring anxiety in patients with COPD. Therefore, a brief and disease-specific non-somatic anxiety measurement scale, the Anxiety Inventory for Respiratory Disease (AIR), which has been developed and validated in its English version, is needed for patients with COPD in China.
Methods
A two-center study was conducted in two tertiary hospitals in Tianjin, China. A total of 181 outpatients with COPD (mean age 67.21±8.10 years, 32.6% women), who met the inclusion and exclusion criteria, were enrolled in the study. Test–retest reliability was examined using intraclass correlation coefficients. The internal consistency was calculated by Cronbach’s α. Content validity was examined using the Content Validity Index (CVI), scale-level CVI/universal agreement, and scale-level CVI/average agreement (S-CVI/Ave). Besides, convergent validity and construct validity were also examined.
Results
The AIR-C (AIR-Chinese version) scale had high test–retest reliability (intraclass correlation coefficient =0.904) and internal consistency (Cronbach’s α=0.914); the content validity of the AIR-C scale was calculated by CVI, scale-level CVI/universal agreement, and S-CVI/Ave at values of 0.89–1, 0.90, and 0.98, respectively. Meanwhile, the AIR-C scale had good convergent validity, correlating with the Hospital Anxiety and Depression Scale-Anxiety (r=0.81, P<0.01), and there were significant correlations between the AIR-C and Clinical COPD Questionnaire (CCQ; r=0.44, P<0.01) and Activities of Daily Living Scale (ADLS; r=0.36, P<0.01). A two-factor model of general anxiety and panic symptoms in the AIR-C scale had the best fit according to Confirmatory Factor Analysis (CFA).
Conclusion
The AIR-C scale had a good reliability and validity for patients with COPD and can be used as a user-friendly and valid tool for measuring anxiety symptoms among patients with COPD in China.
Video abstract
doi:10.2147/COPD.S117626
PMCID: PMC5191851  PMID: 28053516
COPD; Anxiety Inventory for Respiratory Disease; reliability; validity
6.  Anti-melanoma activity of Forsythiae Fructus aqueous extract in mice involves regulation of glycerophospholipid metabolisms by UPLC/Q-TOF MS-based metabolomics study 
Scientific Reports  2016;6:39415.
Metabolomics is a comprehensive assessment of endogenous metabolites of a biological system in a holistic context. In this study, we evaluated the in vivo anti-melanoma activity of aqueous extract of Forsythiae Fructus (FAE) and globally explored the serum metabolome characteristics of B16-F10 melanoma-bearing mice. UPLC/Q-TOF MS combined with pattern recognition approaches were employed to examine the comprehensive metabolic signatures and differentiating metabolites. The results demonstrated that FAE exhibited remarkable antitumor activity against B16-F10 melanoma in C57BL/6 mice and restored the disturbed metabolic profile by tumor insult. We identified 17 metabolites which were correlated with the antitumor effect of FAE. Most of these metabolites are involved in glycerophospholipid metabolisms. Notably, several lysophosphatidylcholines (LysoPCs) significantly decreased in tumor model group, while FAE treatment restored the changes of these phospholipids to about normal condition. Moreover, we found that lysophosphatidylcholine acyltransferase 1 (LPCAT1) and autotaxin (ATX) were highly expressed in melanoma, and FAE markedly down-regulated their expression. These findings indicated that modulation of glycerophospholipid metabolisms may play a pivotal role in the growth of melanoma and the antitumor activity of FAE. Besides, our results suggested that serum LysoPCs could be potential biomarkers for the diagnosis and prognosis of melanoma and other malignant tumors.
doi:10.1038/srep39415
PMCID: PMC5171915  PMID: 27991567
7.  Lrp4 in astrocytes modulates glutamatergic transmission 
Nature neuroscience  2016;19(8):1010-1018.
Neurotransmission requires precise control of neurotransmitter release from axon terminals. This process is regulated by glial cells; however, underlying mechanisms are not fully understood. Here we report that glutamate release in the brain is impaired in mice lacking low density lipoprotein receptor-related protein 4 (Lrp4), a protein critical for neuromuscular junction formation. Electrophysiological studies indicate compromised release probability in astrocyte-specific Lrp4 knockout mice. Lrp4 mutant astrocytes suppress glutamate transmission by enhancing the release of ATP, whose levels are elevated in the hippocampus of Lrp4 mutant mice. Consequently, the mutant mice are impaired in locomotor activity and spatial memory and are resistant to seizure induction. These impairments could be ameliorated by adenosine A1 receptor antagonist. The results reveal a critical role of Lrp4, in response to agrin, in modulating astrocytic ATP release and synaptic transmission. Our study provides insight into the interaction between neurons and astrocytes for synaptic homeostasis and/or plasticity.
doi:10.1038/nn.4326
PMCID: PMC4961622  PMID: 27294513
8.  Global Deletion of TSPO Does Not Affect the Viability and Gene Expression Profile 
PLoS ONE  2016;11(12):e0167307.
Translocator Protein (18kDa, TSPO) is a mitochondrial outer membrane transmembrane protein. Its expression is elevated during inflammation and injury. However, the function of TSPO in vivo is still controversial. Here, we constructed a TSPO global knockout (KO) mouse with a Cre-LoxP system that abolished TSPO protein expression in all tissues and showed normal phenotypes in the physiological condition. The birth rates of TSPO heterozygote (Het) x Het or KO x KO breeding were consistent with Mendel’s Law, suggesting a normal viability of TSPO KO mice at birth. RNA-seq analysis showed no significant difference in the gene expression profile of lung tissues from TSPO KO mice compared with wild type mice, including the genes associated with bronchial alveoli immune homeostasis. The alveolar macrophage population was not affected by TSPO deletion in the physiological condition. Our findings contradict the results of Papadopoulos, but confirmed Selvaraj’s findings. This study confirms TSPO deficiency does not affect viability and bronchial alveolar immune homeostasis.
doi:10.1371/journal.pone.0167307
PMCID: PMC5131929  PMID: 27907096
9.  Different effect of testosterone and oestrogen on urinary excretion of metformin via regulating OCTs and MATEs expression in the kidney of mice 
Abstract
The aim of this study was to investigate the effect of testosterone and oestrogen on regulating organic cation transporters (Octs) and multidrug and toxin extrusions (Mates) expression in the kidney of mice and urinary excretion of metformin. 8 week‐old male db/db mice were treated with estradiol (5 mg/kg), testosterone (50 mg/kg) or olive oil with same volume. Metformin (150 mg/kg) was injected in daily for successive 7 days. Plasma, urine and tissue concentrations of metformin were determined by liquid chromatography‐tandem mass spectrometry (LCMS) assay. Western blotting and Real‐time PCR analysis were successively used to evaluate the renal protein and mRNA expression of Octs and MATEs. After treatment, the protein expression of Mate1 and Oct2 in testosterone group was significantly increased than those in control group (both P < 0.05). The protein expression of Mate1 and Oct2 in estradiol group was significantly reduced by 29.4% and 43.3%, respectively, compared to those in control group (all P < 0.05). These data showed a good agreement with the change in mRNA level (all P < 0.05). The plasma metformin concentration (ng/ml) in mice treated with estradiol was significantly higher than control and testosterone group (677.56 ± 72.49 versus 293.92 ± 83.27 and 261.46 ± 79.45; P < 0.01). Moreover, testosterone increased the metformin urine excretion of mice while estradiol decreasing (both P < 0.01). Spearman correlation analysis showed that gonadal hormone was closely associated with Mate1 and Oct2 expression and metformin urine excretion in db/db mice (all P < 0.05). Testosterone and oestrogen exerted reverse effect on metformin urinary excretion via regulating Octs and Mates expression in the kidney of mice.
doi:10.1111/jcmm.12922
PMCID: PMC5134372  PMID: 27469532
gonadal hormone; OCT2; MATE1; metformin; kidney
10.  Preparation of a Bis-GMA-Free Dental Resin System with Synthesized Fluorinated Dimethacrylate Monomers 
With the aim of reducing human exposure to Bisphenol A (BPA) derivatives in dentistry, a fluorinated dimethacrylate monomer was synthesized to replace 2,2-bis[4-(2-hydroxy-3-methacryloy-loxypropyl)-phenyl]propane (Bis-GMA) as the base monomer of dental resin. After mixing with reactive diluent triethyleneglycol dimethacrylate (TEGDMA), fluorinated dimethacrylate (FDMA)/TEGDMA was prepared and compared with Bis-GMA/TEGDMA in physicochemical properties, such as double bond conversion (DC), volumetric shrinkage (VS), water sorption (WS) and solubility (WSL), flexural strength (FS) and modulus (FM). The results showed that, when compared with Bis-GMA based resin, FDMA-based resin had several advantages, such as higher DC, lower VS, lower WS, and higher FS after water immersion. All of these revealed that FDMA had potential to be used as a substitute for Bis-GMA. Of course, many more studies, such as biocompatibility testing, should be undertaken to prove whether FDMA could be applied in clinic.
doi:10.3390/ijms17122014
PMCID: PMC5187814  PMID: 27916947
dental resin; Bis-GMA free; fluorinated dimethacrylate; physicochemical properties
11.  Cellular Recognition and Repair of Monofunctional–Intercalative Platinum–DNA Adducts 
Chemical research in toxicology  2015;28(11):2170-2178.
The cellular recognition and processing of monofunctional–intercalative DNA adducts formed by [PtCl(en)(L)](NO3)2 (P1-A1; en = ethane-1,2-diamine; L = N-[2-(acridin-9-ylamino)ethyl]-N-methylpropionamidine, acridinium cation), a cytotoxic hybrid agent with potent anticancer activity, was studied. Excision of these adducts and subsequent DNA repair synthesis were monitored in plasmids modified with platinum using incubations with mammalian cell-free extract. On the basis of the levels of [α-32P]-dCTP incorporation, P1-A1–DNA adducts were rapidly repaired with a rate approximately 8 times faster (t1/2 ≈ 18 min at 30 °C) than the adducts (cross-links) formed by the drug cisplatin. Cellular responses to P1-A1 and cisplatin were also studied in NCI-H460 lung cancer cells using immunocytochemistry in conjunction with confocal fluorescence microscopy. At the same dose, P1-A1, but not cisplatin, elicited a distinct requirement for DNA double-strand break repair and stalled replication fork repair, which caused nuclear fluorescent staining related to high levels of MUS81, a specialized repair endonuclease, and phosphorylated histone protein γ-H2AX. The results confirm previous observations in yeast-based chemical genomics assays. γ-H2AX fluorescence is observed as a large number of discrete foci signaling DNA double-strand breaks, pan-nuclear preapoptotic staining, and unique circularly shaped staining around the nucleoli and nuclear rim. DNA cleavage assays indicate that P1-A1 does not act as a typical topoisomerase poison, suggesting the high level of DNA double-strand breaks in cells is more likely a result of topoisomerase-independent replication fork collapse. Overall, the cellular response to platinum–acridines shares striking similarities with that reported for DNA adduct-forming derivatives of the drug doxorubicin. The results of this study are discussed in light of the cellular mechanism of action of platinum–acridines and their ability to overcome resistance to cisplatin.
doi:10.1021/acs.chemrestox.5b00327
PMCID: PMC4712070  PMID: 26457537
12.  31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016): part one 
Lundqvist, Andreas | van Hoef, Vincent | Zhang, Xiaonan | Wennerberg, Erik | Lorent, Julie | Witt, Kristina | Sanz, Laia Masvidal | Liang, Shuo | Murray, Shannon | Larsson, Ola | Kiessling, Rolf | Mao, Yumeng | Sidhom, John-William | Bessell, Catherine A. | Havel, Jonathan | Schneck, Jonathan | Chan, Timothy A. | Sachsenmeier, Eliot | Woods, David | Berglund, Anders | Ramakrishnan, Rupal | Sodre, Andressa | Weber, Jeffrey | Zappasodi, Roberta | Li, Yanyun | Qi, Jingjing | Wong, Philip | Sirard, Cynthia | Postow, Michael | Newman, Walter | Koon, Henry | Velcheti, Vamsidhar | Callahan, Margaret K. | Wolchok, Jedd D. | Merghoub, Taha | Lum, Lawrence G. | Choi, Minsig | Thakur, Archana | Deol, Abhinav | Dyson, Gregory | Shields, Anthony | Haymaker, Cara | Uemura, Marc | Murthy, Ravi | James, Marihella | Wang, Daqing | Brevard, Julie | Monaghan, Catherine | Swann, Suzanne | Geib, James | Cornfeld, Mark | Chunduru, Srinivas | Agrawal, Sudhir | Yee, Cassian | Wargo, Jennifer | Patel, Sapna P. | Amaria, Rodabe | Tawbi, Hussein | Glitza, Isabella | Woodman, Scott | Hwu, Wen-Jen | Davies, Michael A. | Hwu, Patrick | Overwijk, Willem W. | Bernatchez, Chantale | Diab, Adi | Massarelli, Erminia | Segal, Neil H. | Ribrag, Vincent | Melero, Ignacio | Gangadhar, Tara C. | Urba, Walter | Schadendorf, Dirk | Ferris, Robert L. | Houot, Roch | Morschhauser, Franck | Logan, Theodore | Luke, Jason J. | Sharfman, William | Barlesi, Fabrice | Ott, Patrick A. | Mansi, Laura | Kummar, Shivaani | Salles, Gilles | Carpio, Cecilia | Meier, Roland | Krishnan, Suba | McDonald, Dan | Maurer, Matthew | Gu, Xuemin | Neely, Jaclyn | Suryawanshi, Satyendra | Levy, Ronald | Khushalani, Nikhil | Wu, Jennifer | Zhang, Jinyu | Basher, Fahmin | Rubinstein, Mark | Bucsek, Mark | Qiao, Guanxi | MacDonald, Cameron | Hylander, Bonnie | Repasky, Elizabeth | Chatterjee, Shilpak | Daenthanasanmak, Anusara | Chakraborty, Paramita | Toth, Kyle | Meek, Megan | Garrett-Mayer, Elizabeth | Nishimura, Michael | Paulos, Chrystal | Beeson, Craig | Yu, Xuezhong | Mehrotra, Shikhar | Zhao, Fei | Evans, Kathy | Xiao, Christine | Holtzhausen, Alisha | Hanks, Brent A. | Scharping, Nicole | Menk, Ashley V. | Moreci, Rebecca | Whetstone, Ryan | Dadey, Rebekah | Watkins, Simon | Ferris, Robert | Delgoffe, Greg M. | Peled, Jonathan | Devlin, Sean | Staffas, Anna | Lumish, Melissa | Rodriguez, Kori Porosnicu | Ahr, Katya | Perales, Miguel | Giralt, Sergio | Taur, Ying | Pamer, Eric | van den Brink, Marcel R. M. | Jenq, Robert | Annels, Nicola | Pandha, Hardev | Simpson, Guy | Mostafid, Hugh | Harrington, Kevin | Melcher, Alan | Grose, Mark | Davies, Bronwyn | Au, Gough | Karpathy, Roberta | Shafren, Darren | Ricca, Jacob | Merghoub, Taha | Wolchok, Jedd D. | Zamarin, Dmitriy | Batista, Luciana | Marliot, Florence | Vasaturo, Angela | Carpentier, Sabrina | Poggionovo, Cécile | Frayssinet, Véronique | Fieschi, Jacques | Van den Eynde, Marc | Pagès, Franck | Galon, Jérôme | Hermitte, Fabienne | Smith, Sean G. | Nguyen, Khue | Ravindranathan, Sruthi | Koppolu, Bhanu | Zaharoff, David | Schvartsman, Gustavo | Bassett, Roland | McQuade, Jennifer L. | Haydu, Lauren E. | Davies, Michael A. | Tawbi, Hussein | Glitza, Isabella | Kline, Douglas | Chen, Xiufen | Fosco, Dominick | Kline, Justin | Overacre, Abigail | Chikina, Maria | Brunazzi, Erin | Shayan, Gulidanna | Horne, William | Kolls, Jay | Ferris, Robert L. | Delgoffe, Greg M. | Bruno, Tullia C. | Workman, Creg | Vignali, Dario | Adusumilli, Prasad S. | Ansa-Addo, Ephraim A | Li, Zihai | Gerry, Andrew | Sanderson, Joseph P. | Howe, Karen | Docta, Roslin | Gao, Qian | Bagg, Eleanor A. 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Seongho | Kim, Heejin | Silski, Cynthia | Suisham, Stacey | Heath, Elisabeth | Vaishampayan, Ulka | Vandeven, Natalie | Viller, Natasja Nielsen | O’Connor, Alison | Chen, Hui | Bossen, Bolette | Sievers, Eric | Uger, Robert | Nghiem, Paul | Johnson, Lisa | Kao, Hsiang-Fong | Hsiao, Chin-Fu | Lai, Shu-Chuan | Wang, Chun-Wei | Ko, Jenq-Yuh | Lou, Pei-Jen | Lee, Tsai-Jan | Liu, Tsang-Wu | Hong, Ruey-Long | Kearney, Staci J. | Black, Joshua C. | Landis, Benjamin J. | Koegler, Sally | Hirsch, Brooke | Gianani, Roberto | Kim, Jeffrey | He, Ming-Xiao | Zhang, Bingqing | Su, Nan | Luo, Yuling | Ma, Xiao-Jun | Park, Emily | Kim, Dae Won | Copploa, Domenico | Kothari, Nishi | doo Chang, Young | Kim, Richard | Kim, Namyong | Lye, Melvin | Wan, Ee | Kim, Namyong | Lye, Melvin | Wan, Ee | Kim, Namyong | Lye, Melvin | Wan, Ee | Knaus, Hanna A. | Berglund, Sofia | Hackl, Hubert | Karp, Judith E. | Gojo, Ivana | Luznik, Leo | Hong, Henoch S. | Koch, Sven D. | Scheel, Birgit | Gnad-Vogt, 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Tracie | Sokol, Levi | Stein, Mark | Poplin, Elizabeth | Rodriguez-Rodriguez, Lorna | Silk, Ann | Chan, Nancy | Frankel, Melissa | Kane, Michael | Malhotra, Jyoti | Aisner, Joseph | Kaufman, Howard L. | Ali, Siraj | Ross, Jeffrey | White, Eileen | Bhanot, Gyan | Ganesan, Shridar | Monette, Anne | Bergeron, Derek | Amor, Amira Ben | Meunier, Liliane | Caron, Christine | Morou, Antigoni | Kaufmann, Daniel | Liberman, Moishe | Jurisica, Igor | Mes-Masson, Anne-Marie | Hamzaoui, Kamel | Lapointe, Rejean | Mongan, Ann | Ku, Yuan-Chieh | Tom, Warren | Sun, Yongming | Pankov, Alex | Looney, Tim | Au-Young, Janice | Hyland, Fiona | Conroy, Jeff | Morrison, Carl | Glenn, Sean | Burgher, Blake | Ji, He | Gardner, Mark | Mongan, Ann | Omilian, Angela R. | Conroy, Jeff | Bshara, Wiam | Angela, Omilian | Burgher, Blake | Ji, He | Glenn, Sean | Morrison, Carl | Mongan, Ann | Obeid, Joseph M. | Erdag, Gulsun | Smolkin, Mark E. | Deacon, Donna H. | Patterson, James W. | Chen, Lieping | Bullock, Timothy N. | Slingluff, Craig L. | Obeid, Joseph M. | Erdag, Gulsun | Deacon, Donna H. | Slingluff, Craig L. | Bullock, Timothy N. | Loffredo, John T. | Vuyyuru, Raja | Beyer, Sophie | Spires, Vanessa M. | Fox, Maxine | Ehrmann, Jon M. | Taylor, Katrina A. | Korman, Alan J. | Graziano, Robert F. | Page, David | Sanchez, Katherine | Ballesteros-Merino, Carmen | Martel, Maritza | Bifulco, Carlo | Urba, Walter | Fox, Bernard | Patel, Sapna P. | De Macedo, Mariana Petaccia | Qin, Yong | Reuben, Alex | Spencer, Christine | Guindani, Michele | Bassett, Roland | Wargo, Jennifer | Racolta, Adriana | Kelly, Brian | Jones, Tobin | Polaske, Nathan | Theiss, Noah | Robida, Mark | Meridew, Jeffrey | Habensus, Iva | Zhang, Liping | Pestic-Dragovich, Lidija | Tang, Lei | Sullivan, Ryan J. | Logan, Theodore | Khushalani, Nikhil | Margolin, Kim | Koon, Henry | Olencki, Thomas | Hutson, Thomas | Curti, Brendan | Roder, Joanna | Blackmon, Shauna | Roder, Heinrich | Stewart, John | Amin, Asim | Ernstoff, Marc S. | Clark, Joseph I. | Atkins, Michael B. | Kaufman, Howard L. | Sosman, Jeffrey | Weber, Jeffrey | McDermott, David F. | Weber, Jeffrey | Kluger, Harriet | Halaban, Ruth | Snzol, Mario | Roder, Heinrich | Roder, Joanna | Asmellash, Senait | Steingrimsson, Arni | Blackmon, Shauna | Sullivan, Ryan J. | Wang, Chichung | Roman, Kristin | Clement, Amanda | Downing, Sean | Hoyt, Clifford | Harder, Nathalie | Schmidt, Guenter | Schoenmeyer, Ralf | Brieu, Nicolas | Yigitsoy, Mehmet | Madonna, Gabriele | Botti, Gerardo | Grimaldi, Antonio | Ascierto, Paolo A. | Huss, Ralf | Athelogou, Maria | Hessel, Harald | Harder, Nathalie | Buchner, Alexander | Schmidt, Guenter | Stief, Christian | Huss, Ralf | Binnig, Gerd | Kirchner, Thomas | Sellappan, Shankar | Thyparambil, Sheeno | Schwartz, Sarit | Cecchi, Fabiola | Nguyen, Andrew | Vaske, Charles | Hembrough, Todd
Journal for Immunotherapy of Cancer  2016;4(Suppl 1):1-106.
doi:10.1186/s40425-016-0172-7
PMCID: PMC5123387
13.  Genetic architecture of the maize kernel row number revealed by combining QTL mapping using a high-density genetic map and bulked segregant RNA sequencing 
BMC Genomics  2016;17:915.
Background
The maize kernel row number (KRN) is a key component that contributes to grain yield and has high broad-sense heritability (H 2). Quantitative trait locus/loci (QTL) mapping using a high-density genetic map is a powerful approach to detecting loci that are responsible for traits of interest. Bulked segregant ribonucleic acid (RNA) sequencing (BSR-seq) is another rapid and cost-effective strategy to identify QTL. Combining QTL mapping using a high-density genetic map and BSR-seq may dissect comprehensively the genetic architecture underlying the maize KRN.
Results
A panel of 300 F2 individuals derived from inbred lines abe2 and B73 were genotyped using the specific-locus amplified fragment sequencing (SLAF-seq) method. A total of 4,579 high-quality polymorphic SLAF markers were obtained and used to construct a high-density genetic map with a total length of 2,123 centimorgan (cM) and an average distance between adjacent markers of 0.46 cM. Combining the genetic map and KRN of F2 individuals, four QTL (qKRN1, qKRN2, qKRN5, and qKRN8-1) were identified on chromosomes 1, 2, 5, and 8, respectively. The physical intervals of these four QTL ranged from 4.36 Mb for qKRN8-1 to 7.11 Mb for qKRN1 with an average value of 6.08 Mb. Based on high-throughput sequencing of two RNA pools bulked from leaves of plants with extremely high and low KRNs, two QTL were detected on chromosome 8 in the 10–25 Mb (BSR_QTL1) and 60–150 Mb (BSR_QTL2) intervals. According to the physical positions of these QTL, qKRN8-1 was included by BSR_QTL2. In addition, qKRN8-1 was validated using QTL mapping with a recombinant inbred lines population that was derived from inbred lines abe2 and B73.
Conclusions
In this study, we proved that combining QTL mapping using a high-density genetic map and BSR-seq is a powerful and cost-effective approach to comprehensively revealing genetic architecture underlying traits of interest. The QTL for the KRN detected in this study, especially qKRN8-1, can be used for performing fine mapping experiments and marker-assisted selection in maize breeding.
Electronic supplementary material
The online version of this article (doi:10.1186/s12864-016-3240-y) contains supplementary material, which is available to authorized users.
doi:10.1186/s12864-016-3240-y
PMCID: PMC5109822  PMID: 27842488
Maize; Kernel row number; Specific-locus amplified fragment sequencing; Bulked segregant RNA sequencing
14.  Anti-fibrotic action of pirfenidone in Dupuytren’s disease-derived fibroblasts 
Background
Dupuytren’s disease (DD) is a complex fibro-proliferative disorder of the hand that is often progressive and eventually can cause contractures of the affected fingers. Transforming growth factor beta (TGF-β1) has been implicated as a key stimulator of myofibroblast activity and fascial contraction in DD. Pirfenidone (PFD) is an active small molecule shown to inhibit TGF-β1-mediated action in other fibrotic disorders. This study investigates the efficacy of PFD in vitro in inhibiting TGF-β1-mediated cellular functions leading to Dupuytren’s fibrosis.
Methods
Fibroblasts harvested from (DD) and carpal tunnel (CT)- tissues were treated with or without TGF-β1 and/or PFD and were subjected to cell migration, cell proliferation and cell contraction assays. ELISA; western blots and real time RT-PCR assays were performed to determine the levels of fibronectin; p-Smad2/Smad3; alpha-smooth muscle actin (α-SMA), α2 chain of type I collagen and α1 chain of type III collagen respectively.
Results
Our results show that PFD effectively inhibits TGF-β1-induced cell migration, proliferation and cell contractile properties of both CT- and DD-derived fibroblasts. TGF-β1−induced α-SMA mRNA and protein levels were inhibited at the higher concentration of PFD (800 μg/ml). Interestingly, TGF-β1 induction of type I and type III collagens and fibronectin was inhibited by PFD in both CT- and DD- derived fibroblasts, but the effect was more prominent in DD cells. PFD down-regulated TGF-β1-induced phosphorylation of Smad2/Smad3, a key factor in the TGF-β1 signaling pathway.
Conclusion
Taken together these results suggest the PFD can potentially prevent TGF-β1−induced fibroblast to myofibroblast transformation and inhibit ECM production mainly Type I- and Type III- collagen and fibronectin in DD-derived fibroblasts. Further in-vivo studies with PFD may lead to a novel therapeutic application in preventing the progression or recurrence of Dupuytren’s disease.
doi:10.1186/s12891-016-1326-y
PMCID: PMC5106805  PMID: 27835939
Dupuytren’s contracture; Palmar fascia fibrosis; Carpal tunnel; Collagen; Alpha-SMA; Smad2/Smad3; Cell migration; Cell contraction
15.  Pulse oximetry could significantly enhance the early detection of critical congenital heart disease in neonatal intensive care units 
Acta Paediatrica (Oslo, Norway : 1992)  2016;105(11):e499-e505.
Abstract
Aim
Limited data have been available regarding critical congenital heart disease (CHD) screening in neonatal intensive care unit (NICUs). This study evaluated the feasibility of screening for CHD by adding pulse oximetry (POX) to clinical evaluation in a NICU in Shanghai, China.
Methods
We screened 4128 eligible consecutive NICU admissions using POX plus clinical evaluation. Infants with positive screening results were then evaluated with echocardiography. Those with negative screening results were put under observation, and they also underwent echocardiography if their oxygen saturation fell below 95% on room air during hospitalisation.
Results
This enhanced procedure detected 19 critical CHD cases, and seven of these diagnoses would have been delayed if POX had not been incorporated into the screening strategy. This means that the addition of POX increased the detection rate of critical CHD from 63.2 to 100%. The false‐positive rate of critical CHD screening using POX plus clinical evaluation was higher in NICU patients with high morbidity rates.
Conclusion
When pulse oximetry screening was added to clinical evaluation, it increased the number of critical CHD cases that were detected in our NICU. This method could provide a useful screening protocol for critical CHD cases.
doi:10.1111/apa.13553
PMCID: PMC5095792  PMID: 27540721
Clinical evaluation; Congenital heart disease; Neonatal intensive care unit; Neonatal screening; Pulse oximetry
16.  Dynamically sculpturing plasmonic vortices: from integer to fractional orbital angular momentum 
Scientific Reports  2016;6:36269.
As a fundamental tool for light-matter interactions, plasmonic vortex (PV) is extremely useful due to the unique near field property. However, it is a pity that, up to now, the orbital angular momentum (OAM) carried by PVs could not be dynamically and continuously tuned in practice as well as the properties of fractional PVs are still not well investigated. By comparing with two previously reported methods, it is suggested that our proposal of utilizing the propagation induced radial phase gradient of incident Laguerre-Gaussian (LG) beam is a promising candidate to sculpture PVs from integer to fractional OAM dynamically. Consequently, the preset OAM of PVs could have four composing parts: the incident spin and orbital angular momentum, the geometric contribution of chiral plasmonic structure, and the radial phase gradient dependent contribution. Moreover, an analytical expression for the fractional PV is derived as a linear superposition of infinite numbers of integer PVs described by Bessel function of the first kind. It is also shown that the actual mean OAM of a fractional PV would deviate from the preset value, which is similar with previous results for spatial fractional optical vortices.
doi:10.1038/srep36269
PMCID: PMC5095654  PMID: 27811986
17.  Decreased Expression of TMEM173 Predicts Poor Prognosis in Patients with Hepatocellular Carcinoma 
PLoS ONE  2016;11(11):e0165681.
Hepatocellular carcinoma (HCC) is one of the most lethal cancer types, and chronic infection with Hepatitis B Virus (HBV) is identified as the strongest risk factor for HCC. Transmembrane Protein 173 (TMEM173) is a pattern recognition receptor which functions as a major regulator of the innate immune response to viral and bacterial infections. However, the prognostic value of TMEM173 in HCC remains elusive. Thus, we aimed to evaluate the potential prognostic significance of TMEM173 expression in HCC patients following curative resection. Immunohistochemistry was used to detect TMEM173 expression in 96 HCC patients. We found that TMEM173 protein expression was remarkably decreased in tumor tissues compared to non-tumor tissues, and that TMEM173 staining intensity was inversely correlated with tumor size, tumor invasion TNM stage and overall survival (OS) in HCC patients. Multivariate analysis supported TMEM173 as an independent prognostic factor, and identified that combining TMEM173 expression with TNM stage showed better prognostic efficiency for OS in HCC patients. In summary, TMEM173 was discovered having an independent prognostic value and may serve as a potential immunotherapeutic target for HCC.
doi:10.1371/journal.pone.0165681
PMCID: PMC5096716  PMID: 27814372
18.  Neonatal mortality and morbidity among infants between 24 to 31 complete weeks: a multicenter survey in China from 2013 to 2014 
BMC Pediatrics  2016;16:174.
Background
The outcome of preterm infants has been varied in different hospitals and regions in developing countries. Regular clinical monitor are needed to know the effects of health care. This study aimed to describe the survival and morbidity rates of extreme to very preterm infants in 15 neonatal-intensive care hospitals in China.
Methods
Data were collected from January 1, 2013 to December 31, 2014 for preterm neonates with gestational age (GA) between 24 and 31 complete weeks born in hospitals from our collaborative study group. The primary outcomes were survival and major morbidities prior to hospital discharge. Major morbidities included bronchopulmonary dysplasia (BPD), intraventricular hemorrhage (IVH), necrotizing enterocolitis (NEC), retinopathy of prematurity (ROP), patent ductus arteriosus (PDA) and sepsis. Mutivariate logistic regression was used to analyze the risk factor influencing on the outcomes.
Results
The preterm birth rate was 9.9 % (13 701/138 240). The proportion of extreme to very preterm infants was 1.1 % and 11.8 % respectively. The survival rate prior to discharge was increased with increasing GA (0, 24 weeks; 28 %, 25 weeks; 84.8 %, 26 weeks; 83.5 %, 27 weeks; 87.4 %, 28 weeks; 90.7 %, 29 weeks; 93.9 %, 30 weeks; 96 %, 31 weeks). Rate of survival and without severe morbidity according to GA were 0 at 24 weeks, 8 % at 25 weeks, 60.6 % at 26 weeks; 53.2 % at 27 weeks; 62.3 % at 28 weeks; 67.9 % at 29 weeks; 79.1 % at 30 weeks, 85.8 % at 31 weeks respectively. Rate of antenatal steroid use was 56 %. The antenatal steroid use was lower in GA < 28 weeks infants than that in GA between 28 and 32 weeks (28–44.3 % vs 49.7–60.1 %, P < 0.05). Infants at the lowest GAs had a highest incidence of morbidities. Overall, 58.5 % had respiratory distress syndrome, 12.5 % bronchopulmonary dysplasia, 3.9 % necrotizing enterocolitis, 15.4 % intraventricular hemorrhage, 5.4 % retinopathy of prematurity, 28.4 % patent ductus arteriosus, and 9.7 % sepsis. Mortality and morbidity were influenced by gestational age (OR = 0.891, 95 % CI: 0.796–0.999, p = 0.0047 and OR = 0.666, 95 % CI: 0.645–0.688, p = 0.000 respectively), birth weight (OR = 0.520, 95 % CI: 0.420–0.643, p = 0.000 and OR = 0.921, 95 % CI: 0.851–0.997, p = 0.041 respectively), SGA (OR = 1.861, 95 % CI: 1.148–3.017, p = 0.012 and OR = 1.511, 95 % CI: 1.300–1.755, p = 0.000 respectively), Apgar score <7 at 5 min (OR = 1.947, 95 % CI: 1.269–2.987, p = 0.002 and OR = 2.262, 95 % CI: 1.950–2.624, p = 0.000 respectively). The survival rate was increased with more prenatal steroid use (OR = 1.615, 95 % CI: 1.233–1.901, p = 0.033).
Conclusion
Although most of the preterm infants with GAs ≥26 weeks survived, a high complication in survivors still can be observed. Rate of survival of GAs less than 26 weeks was still low, and quality improvement methods should be used to look into increasing the use of antenatal steroids in the very preterm births.
doi:10.1186/s12887-016-0716-5
PMCID: PMC5094017  PMID: 27809893
Preterm infants; Mortality; Morbidity; Outcome
19.  SUMOylation Regulates Growth Factor Independence 1 in Transcriptional Control and Hematopoiesis 
Molecular and Cellular Biology  2016;36(10):1438-1450.
Cell fate specification requires precise coordination of transcription factors and their regulators to achieve fidelity and flexibility in lineage allocation. The transcriptional repressor growth factor independence 1 (GFI1) is comprised of conserved Snail/Slug/Gfi1 (SNAG) and zinc finger motifs separated by a linker region poorly conserved with GFI1B, its closest homolog. Moreover, GFI1 and GFI1B coordinate distinct developmental fates in hematopoiesis, suggesting that their functional differences may derive from structures within their linkers. We show a binding interface between the GFI1 linker and the SP-RING domain of PIAS3, an E3-SUMO (small ubiquitin-related modifier) ligase. The PIAS3 binding region in GFI1 contains a conserved type I SUMOylation consensus element, centered on lysine-239 (K239). In silico prediction algorithms identify K239 as the only high-probability site for SUMO modification. We show that GFI1 is modified by SUMO at K239. SUMOylation-resistant derivatives of GFI1 fail to complement Gfi1 depletion phenotypes in zebrafish primitive erythropoiesis and granulocytic differentiation in cultured human cells. LSD1/CoREST recruitment and MYC repression by GFI1 are profoundly impaired for SUMOylation-resistant GFI1 derivatives, while enforced expression of MYC blocks granulocytic differentiation. These findings suggest that SUMOylation within the GFI1 linker favors LSD1/CoREST recruitment and MYC repression to govern hematopoietic differentiation.
doi:10.1128/MCB.01001-15
PMCID: PMC4859688  PMID: 26951200
20.  Articular Cartilage of the Human Knee Joint: In Vivo Multicomponent T2 Analysis at 3.0 T 
Radiology  2015;277(2):477-488.
The results of this study suggest that the fraction of the fast-relaxing water component may be more sensitive than single-component T2 for detection of cartilage degeneration in patients with osteoarthritis of the knee with greater diagnostic performance for distinguishing morphologically normal cartilage from morphologically degenerative cartilage at receiver operating characteristic curve analysis.
Purpose
To compare multicomponent T2 parameters of the articular cartilage of the knee joint measured by using multicomponent driven equilibrium single-shot observation of T1 and T2 (mcDESPOT) in asymptomatic volunteers and patients with osteoarthritis.
Materials and Methods
This prospective study was performed with institutional review board approval and with written informed consent from all subjects. The mcDESPOT sequence was performed in the knee joint of 13 asymptomatic volunteers and 14 patients with osteoarthritis of the knee. Single-component T2 (T2Single), T2 of the fast-relaxing water component (T2F) and of the slow-relaxing water component (T2S), and the fraction of the fast-relaxing water component (FF) of cartilage were measured. Wilcoxon rank-sum tests and multivariate linear regression models were used to compare mcDESPOT parameters between volunteers and patients with osteoarthritis. Receiver operating characteristic analysis was used to assess diagnostic performance with mcDESPOT parameters for distinguishing morphologically normal cartilage from morphologically degenerative cartilage identified at magnetic resonance imaging in eight cartilage subsections of the knee joint.
Results
Higher cartilage T2Single (P < .001), lower cartilage FF (P < .001), and similar cartilage T2F (P = .079) and T2S (P = .124) values were seen in patients with osteoarthritis compared with those in asymptomatic volunteers. Differences in T2Single and FF remained significant (P < .05) after consideration of age differences between groups of subjects. Diagnostic performance was higher with FF than with T2Single for distinguishing between normal and degenerative cartilage (P < .05), with greater areas under the curve at receiver operating characteristic analysis.
Conclusion
Patients with osteoarthritis of the knee had significantly higher cartilage T2Single and significantly lower cartilage FF than did asymptomatic volunteers, and receiver operating characteristic analysis results suggested that FF may allow greater diagnostic performance than that with T2Single for distinguishing between normal and degenerative cartilage.
© RSNA, 2015
Online supplemental material is available for this article.
doi:10.1148/radiol.2015142201
PMCID: PMC4627437  PMID: 26024307
21.  Predictors for Better Blood-Flow Restoration of Long-Segmental Below-the-Knee Chronic Total Occlusions after Endovascular Therapy in Diabetic Patients 
Korean Journal of Radiology  2016;17(6):874-881.
Objective
To prospectively investigate predictors for good restoration of blood flow of below-the-knee (BTK) chronic total occlusions (CTOs) after endovascular therapy in diabetes mellitus (DM) patients.
Materials and Methods
A total of 120 long-segmental (≥ 5 cm) BTK, CTOs in 81 patients who underwent recanalization were included in this study. After angioplasty, blood-flow restoration was assessed using modified thrombolysis in myocardial ischemia grades and classified as good flow (grade 3) and poor flow (grade 1/2). One hundred and six CTOs with successful recanalization were divided into a good flow group (GFG; n = 68) and poor flow group (PFG; n = 38). Multivariate logistic regression analyses were undertaken to determine independent predictors of blood-flow restoration. Receiver operating characteristic curves were constructed to determine the best cutoff value. The prevalence of target-lesion restenosis during follow-up was compared between two groups.
Results
Univariate analyses suggested that CTOs in GFG were characterized by lighter limb ischemia (p = 0.03), shorter course of ischemic symptoms (p < 0.01) and lesion length (p = 0.04), more frequent use of intraluminal angioplasty (p = 0.03), and higher runoff score (p < 0.01) than those in PFG. Multivariate regression analyses suggested that distal runoffs (p = 0.001; odds ratio [OR], 10.32; 95% confidence interval [CI]: 4.082–26.071) and lesion length (p < 0.001; OR, 1.26; 95% CI: 1.091–1.449) were independent predictors for good flow restoration. Kaplan-Meier analyses at 12 months showed a higher prevalence of non-restenosis in GFG (p < 0.01).
Conclusion
Distal runoffs and lesion length are independent predictors for good flow restoration for long-segmental BTK, CTOs in DM patients who receive endovascular therapy.
doi:10.3348/kjr.2016.17.6.874
PMCID: PMC5102915  PMID: 27833403
Chronic total occlusion; Extremity; Below the knee; Endovascular treatment; Blood flow restoration; Diabetes mellitus; DM
22.  Myocyte-specific enhancer factor 2C: a novel target gene of miR-214-3p in suppressing angiotensin II-induced cardiomyocyte hypertrophy 
Scientific Reports  2016;6:36146.
The role of microRNA-214-3p (miR-214-3p) in cardiac hypertrophy was not well illustrated. The present study aimed to investigate the expression and potential target of miR-214-3p in angiotensin II (Ang-II)-induced mouse cardiac hypertrophy. In mice with either Ang-II infusion or transverse aortic constriction (TAC) model, miR-214-3p expression was markedly decreased in the hypertrophic myocardium. Down-regulation of miR-214-3p was observed in the myocardium of patients with cardiac hypertrophy. Expression of miR-214-3p was upregulated in Ang-II-induced hypertrophic neonatal mouse ventricular cardiomyocytes. Cardiac hypertrophy was attenuated in Ang-II-infused mice by tail vein injection of miR-214-3p. Moreover, miR-214-3p inhibited the expression of atrial natriuretic peptide (ANP) and β-myosin heavy chain (MHC) in Ang-II-treated mouse cardiomyocytes in vitro. Myocyte-specific enhancer factor 2C (MEF2C), which was increased in Ang-II-induced hypertrophic mouse myocardium and cardiomyocytes, was identified as a target gene of miR-214-3p. Functionally, miR-214-3p mimic, consistent with MEF2C siRNA, inhibited cell size increase and protein expression of ANP and β-MHC in Ang-II-treated mouse cardiomyocytes. The NF-κB signal pathway was verified to mediate Ang-II-induced miR-214-3p expression in cardiomyocytes. Taken together, our results revealed that MEF2C is a novel target of miR-214-3p, and attenuation of miR-214-3p expression may contribute to MEF2Cexpressionin cardiac hypertrophy.
doi:10.1038/srep36146
PMCID: PMC5087095  PMID: 27796324
23.  Local Application of Probiotic Bacteria Prophylaxes against Sepsis and Death Resulting from Burn Wound Infection 
PLoS ONE  2016;11(10):e0165294.
Objective
To determine if local prophylactic application of probiotic bacteria to burn wounds will prevent death in a mouse model of burn wound sepsis.
Background
Infection remains the most common complication after burn injury and can result in sepsis and death, despite the use of topical and systemic antibiotics. Pseudomonas aeruginosa is a frequently implicated pathogen. Local application of probiotics directly to burn wounds is an attractive novel intervention that avoids the pitfalls of standard antibiotic therapies.
Methods
A burn-sepsis model was established using a sub-eschar injection of bioluminescent P. aeruginosa; infection was tracked using a charge-coupled camera. Full-thickness burn injuries were placed on the dorsums of adult mice; the injured sites were then treated with vehicle (burn wound control), probiotics (Lactobacillus plantarum only), pathogenic bacteria (Pseudomonas aeruginosa only), or probiotics plus pathogen (Lactobacillus plus Pseudomonas). Animals were monitored until death/moribundity or for one week, then sacrificed. Harvested tissues were subjected to imaging and molecular assays.
Results
Control and probiotic-only animals showed no mortality (100% survival) at one week. Pseudomonas-only animals showed > 90% mortality within 40 hours of infection. In contrast, animals treated with probiotics plus Pseudomonas showed less than 10% mortality. Use of bioluminescent Pseudomonas bacteria demonstrated that probiotic therapy inhibited septicemic accumulation of the pathogen in remote organs. In addition, probiotic therapy successfully suppressed the infection-dependent induction of TNF-α and interleukins 6 and 10 in the liver.
Conclusions
Local probiotic therapy shows great potential as a valuable adjunct in the management of complicated burn injury.
doi:10.1371/journal.pone.0165294
PMCID: PMC5079594  PMID: 27780258
24.  Genetic analysis of Upland cotton dynamic heterosis for boll number per plant at multiple developmental stages 
Scientific Reports  2016;6:35515.
Yield is an important breeding target. As important yield components, boll number per plant (BNP) shows dynamic character and strong heterosis in Upland cotton. However, the genetic basis underlying the dynamic heterosis is poorly understood. In this study, we conducted dynamic quantitative trait loci (QTL) analysis for BNP and heterosis at multiple developmental stages and environments using two recombinant inbred lines (RILs) and two corresponding backcross populations. By the single-locus analysis, 23 QTLs were identified at final maturity, while 99 QTLs were identified across other three developmental stages. A total of 48 conditional QTLs for BNP were identified for the adjacent stages. QTLs detected at later stage mainly existed in the partial dominance to dominance range and QTLs identified at early stage mostly showed effects with the dominance to overdominance range during plant development. By two-locus analysis, we observe that epistasis played an important role not only in the variation of the performance of the RIL population but also in the expression of heterosis in backcross population. Taken together, the present study reveals that the genetic basis of heterosis is dynamic and complicated, and it is involved in dynamic dominance effect, epistasis and QTL by environmental interactions.
doi:10.1038/srep35515
PMCID: PMC5066282  PMID: 27748451
25.  Controllable growth of vertically aligned graphene on C-face SiC 
Scientific Reports  2016;6:34814.
We investigated how to control the growth of vertically aligned graphene on C-face SiC by varying the processing conditions. It is found that, the growth rate scales with the annealing temperature and the graphene height is proportional to the annealing time. Temperature gradient and crystalline quality of the SiC substrates influence their vaporization. The partial vapor pressure is crucial as it can interfere with further vaporization. A growth mechanism is proposed in terms of physical vapor transport. The monolayer character of vertically aligned graphene is verified by Raman and X-ray absorption spectroscopy. With the processed samples, d0 magnetism is realized and negative magnetoresistance is observed after Cu implantation. We also prove that multiple carriers exist in vertically aligned graphene.
doi:10.1038/srep34814
PMCID: PMC5052588  PMID: 27708399

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