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Article ; Online: Discovery of novel and selective farnesoid X receptor antagonists through structure-based virtual screening, preliminary structure-activity relationship study, and biological evaluation.

Dou, Xiaodong / Huo, Tongyu / Liu, Yameng / Pang, Zichen / Su, Lingyu / Zhao, Xinyi / Peng, Xing / Liu, Zhenming / Zhang, Liangren / Jiao, Ning

European journal of medicinal chemistry

2024 Volume 269, Page(s) 116323

Abstract: Farnesoid X receptor (FXR) is a bile acids receptor and plays a crucial role in regulating bile acids, lipids, and glucose metabolism. Previous research suggests that inhibiting FXR activation can be beneficial in reducing cholesterol and low-density ... ...

Abstract	Farnesoid X receptor (FXR) is a bile acids receptor and plays a crucial role in regulating bile acids, lipids, and glucose metabolism. Previous research suggests that inhibiting FXR activation can be beneficial in reducing cholesterol and low-density lipoprotein cholesterol (LDL-C) levels, offering potential treatment options for metabolic syndrome with lipid disorders. Herein, we report p-acetylaminobenzene sulfonate derivatives as a novel scaffold of FXR antagonists by multistage screening. Among these derivatives, compound F44-A13 exhibited a half-maximal inhibitory concentration of 1.1 μM. Furthermore, compound F44-A13 demonstrated effective inhibition of FXR activation in cellular assays and exhibited high selectivity over eleven other nuclear receptors. Besides, compound F44-A13 significantly suppressed the regulation of FXR target genes Shp, Besp, and Cyp7a1, while reducing cholesterol levels in human hepatoma HepG2 cells. Pharmacological studies conducted on C57BL/6 mice further confirmed that compound F44-A13 had beneficial effects in reducing cholesterol, triglycerides, and LDL-C levels. These findings highlight that F44-A13 is a highly selective FXR antagonist that might serve as a useful molecule for further FXR studies as well as the development of FXR antagonists for the potential treatment of metabolic diseases with lipid disorders.
MeSH term(s)	Mice ; Animals ; Humans ; Cholesterol, LDL ; Mice, Inbred C57BL ; Structure-Activity Relationship ; Cholesterol/metabolism ; Bile Acids and Salts/pharmacology ; Liver/metabolism
Chemical Substances	Cholesterol, LDL ; Cholesterol (97C5T2UQ7J) ; Bile Acids and Salts
Language	English
Publishing date	2024-03-18
Publishing country	France
Document type	Journal Article
ZDB-ID	188597-2
ISSN	1768-3254 ; 0009-4374 ; 0223-5234
ISSN (online)	1768-3254
ISSN	0009-4374 ; 0223-5234
DOI	10.1016/j.ejmech.2024.116323
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Article ; Online: Differences in the phenotypes and transcriptomic signatures of chimeric antigen receptor T lymphocytes manufactured

Niu, Anna / Zou, Jintao / Hu, Xuan / Zhang, Zhang / Su, Lingyu / Wang, Jing / Lu, Xing / Zhang, Wei / Chen, Wei / Zhang, Xiaopeng

Frontiers in immunology

2023 Volume 14, Page(s) 1068625

Abstract: Chimeric antigen receptor (CAR)-T cell therapy is an innovative treatment for CD19-expressing lymphomas. CAR-T cells are primarily manufactured via lentivirus transfection or transposon electroporation. While anti-tumor efficacy comparisons between the ... ...

Abstract	Chimeric antigen receptor (CAR)-T cell therapy is an innovative treatment for CD19-expressing lymphomas. CAR-T cells are primarily manufactured via lentivirus transfection or transposon electroporation. While anti-tumor efficacy comparisons between the two methods have been conducted, there is a current dearth of studies investigating the phenotypes and transcriptome alterations induced in T cells by the two distinct manufacturing methods. Here, we established CAR-T signatures using fluorescent imaging, flow cytometry, and RNA-sequencing. A small fraction of CAR-T cells that were produced using the PiggyBac transposon (PB CAR-T cells) exhibited much higher expression of CAR than those produced using a lentivirus (Lenti CAR-T cells). PB and Lenti CAR-T cells contained more cytotoxic T cell subsets than control T cells, and Lenti CAR-T cells presented a more pronounced memory phenotype. RNA-sequencing further revealed vast disparities between the two CAR-T cell groups, with PB CAR-T cells exhibiting greater upregulation of cytokines, chemokines, and their receptors. Intriguingly, PB CAR-T cells singularly expressed IL-9 and fewer cytokine release syndrome-associated cytokines when activated by target cells. In addition, PB CAR-T cells exerted faster
MeSH term(s)	Receptors, Chimeric Antigen/genetics ; Receptors, Chimeric Antigen/metabolism ; Transcriptome ; Receptors, Antigen, T-Cell ; Transfection ; Electroporation ; T-Lymphocytes ; Cytokines/metabolism ; RNA/metabolism ; Phenotype
Chemical Substances	Receptors, Chimeric Antigen ; Receptors, Antigen, T-Cell ; Cytokines ; RNA (63231-63-0)
Language	English
Publishing date	2023-05-09
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2023.1068625
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Article ; Online: Discovery of 3-oxo-1,2,3,4-tetrahydropyrido[1,2-a]pyrazin derivatives as SARS-CoV-2 main protease inhibitors through virtual screening and biological evaluation.

Dou, Xiaodong / Sun, Qi / Liu, Yameng / Lu, Yangbin / Zhang, Caifang / Xu, Guofeng / Xu, Yue / Huo, Tongyu / Zhao, Xinyi / Su, Lingyu / Xing, Yihong / Lai, Luhua / Jiao, Ning

Bioorganic & medicinal chemistry letters

2023 Volume 97, Page(s) 129547

Abstract: The COVID-19 caused by SARS-CoV-2 has led to a global pandemic that continues to impact societies and economies worldwide. The main protease ( ... ...

Abstract	The COVID-19 caused by SARS-CoV-2 has led to a global pandemic that continues to impact societies and economies worldwide. The main protease (M
MeSH term(s)	Humans ; Antiviral Agents/pharmacology ; COVID-19/prevention & control ; Molecular Docking Simulation ; Molecular Dynamics Simulation ; Protease Inhibitors/pharmacology ; SARS-CoV-2/drug effects ; Viral Nonstructural Proteins ; Pyrazines/chemistry ; Pyrazines/pharmacology ; COVID-19 Drug Treatment
Chemical Substances	3C-like proteinase, SARS-CoV-2 (EC 3.4.22.-) ; Antiviral Agents ; Protease Inhibitors ; Viral Nonstructural Proteins ; Pyrazines
Language	English
Publishing date	2023-11-08
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1063195-1
ISSN	1464-3405 ; 0960-894X
ISSN (online)	1464-3405
ISSN	0960-894X
DOI	10.1016/j.bmcl.2023.129547
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Article ; Online: Association Between Toothbrushing and Behavioral Risk Factors of Non-communicable Diseases: A population Based Survey of 4500 adults in China.

Liu, Wenzhao / Su, Lingyu / Xie, Xudong / Xiang, Xuerong / Huang, Jiao / Ji, Ping

Scientific reports

2019 Volume 9, Issue 1, Page(s) 8498

Abstract: Non-communicable Disease (NCD) related behavioral risk factors (BRF) plays a crucial role in NCD prevention, as does oral hygiene behavior in oral health promotion. We examined the association between NCD BRF and toothbrushing using data from a ... ...

Abstract	Non-communicable Disease (NCD) related behavioral risk factors (BRF) plays a crucial role in NCD prevention, as does oral hygiene behavior in oral health promotion. We examined the association between NCD BRF and toothbrushing using data from a population-based survey, which recruited 4485 adults aged 18+ years, in Chongqing city, China. Prevalence of five NDC BRF and their clustering within individual were determined by toothbrushing frequency. Ordinal logistic regression examined the association between toothbrushing and BRF clustering. Prevalence of current smoking, insufficient intake of vegetable and fruit, and harmful use of alcohol increased significantly with toothbrushing frequency. Respondents who brushed teeth ≥2 times daily consumed more red meat than those with less frequent toothbrushing. Relative to those with no BRF, the adjusted cumulative odds ratio of brushing teeth less frequently was 2.1 (95% CI: 1.4-3.1) for respondents with 3+ BRF. The adjusted cumulative odds ratio was 1.5 (1.1-2.1) and 1.4 (1.0-1.8) for those who had two BRF and those who had one, respectively. Significant correlation between toothbrushing and NCD BRF implied that integrated intervention strategy involving the both may be beneficial in public health programs targeting at either oral health or NCDs, or both.
MeSH term(s)	Adult ; Behavior ; China/epidemiology ; Female ; Humans ; Logistic Models ; Male ; Middle Aged ; Noncommunicable Diseases/epidemiology ; Risk Factors ; Surveys and Questionnaires ; Toothbrushing/statistics & numerical data
Language	English
Publishing date	2019-06-11
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-019-44662-w
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Article: Anti-oral Squamous Cell Carcinoma Effects of a Potent TAZ Inhibitor AR-42.

Su, Lingyu / Wang, Si / Yuan, Ting / Xie, Xudong / Fu, Xiaoming / Ji, Ping / Zhong, Lei / Liu, Wenzhao

Journal of Cancer

2020 Volume 11, Issue 2, Page(s) 364–373

Abstract: Oral squamous cell carcinoma (OSCC) is one of the most common malignancies worldwide. Although great progress has been made in diagnosis and treatment strategies in recent years, the 5-year survival rate of OSCC patients is still disappointingly low. ... ...

Abstract	Oral squamous cell carcinoma (OSCC) is one of the most common malignancies worldwide. Although great progress has been made in diagnosis and treatment strategies in recent years, the 5-year survival rate of OSCC patients is still disappointingly low. Hence, there is still an unmet medical need for sufferers with OSCC. As a downstream effector of Hippo pathway, TAZ was up-regulated in multiple cancers including OSCC, and considered as an effective therapeutic target. In this study, we constructed a stable transfected cell line HEK293-TAZ to screen TAZ inhibitor using dual-luciferase reporter assay, and found a potential TAZ inhibitor AR-42. The results showed that AR-42 effectively suppressed the viability and proliferation of OSCC cells, and induced cellular apoptosis and cell cycle arrest in G2/M phase. Moreover, AR-42 potently inhibited cell invasion and the capacity of sphere-forming, as well as the expression of EMT and cancer stem cell related proteins in OSCC cells, exhibiting potential efficacy against OSCC metastasis and self-renewal of oral cancer stem cell. Further mechanism studies showed that AR-42 inhibited the total amount of TAZ and its paralog YAP mainly through blockade of TAZ/YAP transcription and promotion of TAZ/YAP protein degradation. Additionally, the inhibitory effect of AR-42 against TAZ, as well as its anti-OSCC activity could be also observed in SCC9 xenograft model. Taken together, AR-42 deserves to be further studied as a TAZ inhibitor, and is worthy to be further assessed as a potential drug candidate for OSCC treatment.
Language	English
Publishing date	2020-01-01
Publishing country	Australia
Document type	Journal Article
ZDB-ID	2573318-7
ISSN	1837-9664
ISSN	1837-9664
DOI	10.7150/jca.32436
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Article ; Online: Discovery of 2-(furan-2-ylmethylene)hydrazine-1-carbothioamide derivatives as novel inhibitors of SARS-CoV-2 main protease.

Dou, Xiaodong / Sun, Qi / Xu, Guofeng / Liu, Yameng / Zhang, Caifang / Wang, Bingding / Lu, Yangbin / Guo, Zheng / Su, Lingyu / Huo, Tongyu / Zhao, Xinyi / Wang, Chen / Yu, Zhongtian / Song, Song / Zhang, Liangren / Liu, Zhenming / Lai, Luhua / Jiao, Ning

European journal of medicinal chemistry

2022 Volume 238, Page(s) 114508

Abstract: The COVID-19 posed a serious threat to human life and health, and SARS-CoV-2 ... ...

Abstract	The COVID-19 posed a serious threat to human life and health, and SARS-CoV-2 M
MeSH term(s)	Antiviral Agents/chemistry ; Antiviral Agents/pharmacology ; COVID-19/drug therapy ; Coronavirus 3C Proteases/antagonists & inhibitors ; Coronavirus 3C Proteases/chemistry ; Coronavirus 3C Proteases/metabolism ; Drug Discovery/methods ; Furans/chemistry ; Furans/pharmacology ; Humans ; Hydrazines/pharmacology ; Molecular Docking Simulation ; Protease Inhibitors/chemistry ; Protease Inhibitors/pharmacology ; SARS-CoV-2/drug effects ; SARS-CoV-2/enzymology
Chemical Substances	Antiviral Agents ; Furans ; Hydrazines ; Protease Inhibitors ; 3C-like proteinase, SARS-CoV-2 (EC 3.4.22.-) ; Coronavirus 3C Proteases (EC 3.4.22.28)
Language	English
Publishing date	2022-06-03
Publishing country	France
Document type	Journal Article
ZDB-ID	188597-2
ISSN	1768-3254 ; 0009-4374 ; 0223-5234
ISSN (online)	1768-3254
ISSN	0009-4374 ; 0223-5234
DOI	10.1016/j.ejmech.2022.114508
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Article ; Online: pH responsive PEGylation through metal affinity for gene delivery mediated by histidine-grafted polyethylenimine.

Tseng, Wen-Chi / Su, Ling-Yu / Fang, Tsuei-Yun

Journal of biomedical materials research. Part B, Applied biomaterials

2012 Volume 101, Issue 2, Page(s) 375–386

Abstract: Polyethylene glycol (PEG) has been used to enhance the stability of a gene delivery system. The most commonly used approach is to add the PEG molecule by way of chemical conjugation. In this study, we prepared PEG-bearing nitrilotriacetic acid (ntaPEG) ... ...

Abstract	Polyethylene glycol (PEG) has been used to enhance the stability of a gene delivery system. The most commonly used approach is to add the PEG molecule by way of chemical conjugation. In this study, we prepared PEG-bearing nitrilotriacetic acid (ntaPEG) followed by chelation with either nickel or zinc ions. Polyethylenimine was grafted with histidine (hisPEI) and used as a primary gene carrier to form complexes with DNA. PEGylation was performed by incubating the complexes with chelated ntaPEG. It was noted that the coating of the chelated ntaPEG could provide a shielding effect against aggregation induced by bovine serum albumin and DNA release induced by heparin displacement, respectively. The coating was also found to improve cellular viability and maintain the transfection efficiency at a moderate level. The coated ntaPEG could dissociate from the complexes in an acidic condition of pH 4, suggesting that dePEGylation might occur in some acidic intracellular organelles, such as endosomes. This simple and effective PEGylation approach could be extended to other delivery systems to enhance the stability and to facilitate the dePEGylation process.
MeSH term(s)	Animals ; Biocompatible Materials/chemistry ; CHO Cells ; Cattle ; Chelating Agents/chemistry ; Coated Materials, Biocompatible/administration & dosage ; Coated Materials, Biocompatible/chemistry ; Cricetinae ; Cricetulus ; Gene Transfer Techniques ; Histidine/chemistry ; Hydrogen-Ion Concentration ; Materials Testing ; Nickel/chemistry ; Nitrilotriacetic Acid/chemistry ; Plasmids/administration & dosage ; Plasmids/genetics ; Polyethylene Glycols ; Polyethyleneimine ; Transfection ; Zinc/chemistry
Chemical Substances	Biocompatible Materials ; Chelating Agents ; Coated Materials, Biocompatible ; Polyethylene Glycols (3WJQ0SDW1A) ; Histidine (4QD397987E) ; Nickel (7OV03QG267) ; Polyethyleneimine (9002-98-6) ; Zinc (J41CSQ7QDS) ; Nitrilotriacetic Acid (KA90006V9D)
Language	English
Publishing date	2012-11-19
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2099992-6
ISSN	1552-4981 ; 1552-4973 ; 0021-9304
ISSN (online)	1552-4981
ISSN	1552-4973 ; 0021-9304
DOI	10.1002/jbm.b.32848
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Article: Experimental studies the burning process of gelled unsymmetrical dimethylhydrazine droplets under oxidant convective conditions

Feng, Songjiang / He, Bo / He, Haobo / Su, Lingyu / Hou, Zhiyong / Nie, Wansheng / Guo, Xihong

Fuel. 2013 Sept., v. 111

2013

Abstract: Gelled hypergolic propellants offer potential safety and performance improvements over conventional liquid and solid propellants. Understanding the combustion process of single gelled droplets is the first basic step to predict their behavior in the ... ...

Abstract	Gelled hypergolic propellants offer potential safety and performance improvements over conventional liquid and solid propellants. Understanding the combustion process of single gelled droplets is the first basic step to predict their behavior in the future combustion chambers. Experimental studies were performed to investigate the burning behavior of gelled unsymmetrical dimethylhydrazine (UDMH) droplets under oxidant convective conditions. The effects of oxidant convective conditions including velocity and temperature on the burning behavior were analyzed. The burning process was broken down into four stages: heating and swelling period, initial combustion period, violent combustion period, and stable and extinguished combustion period. Sometimes the droplet inside seemed to be porous or botryoidal. The microexplosion period lasted for a long time sometimes exceeding about 70% of the burning lifetime, and the phenomenon of gas jet combustion due to the burst steam from microexplosions was founded. The conversion of burning flame from a layered and enveloped flame structure to an escaped flame structure with increase in the convective velocity was observed. When the enveloped flame appeared, it was more helpful to the burning process, and the intensity of microexplosions and the burning rate constant were found to increase with the convective temperature. When the escaped flame appeared, it was disadvantageous to the burning process, and the intensity of microexplosions decreases with rise in convective velocity. Compared with the escaped flame, the intensity of microexplosions of the enveloped flame was lower, but the frequency was higher.
Keywords	burning ; combustion ; droplets ; heat ; oxidants ; steam ; temperature
Language	English
Dates of publication	2013-09
Size	p. 367-373.
Publishing place	Elsevier Ltd
Document type	Article
ISSN	0016-2361
DOI	10.1016/j.fuel.2013.03.071
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Using trehalose delivered by the intramuscular injection of plasmid DNA as an adjuvant for transgene expression.

Tang, Chien-Hsiang / Su, Ling-Yu / Tseng, Wen-Chi

The journal of gene medicine

2009 Volume 11, Issue 3, Page(s) 250–256

Abstract: Background: Intramuscular injection is a popular and effective approach to administer naked plasmid for transgene expression. The use of an adjuvant can provide a straightforward approach for enhancing transgene expression.: Methods: Expression ... ...

Abstract	Background: Intramuscular injection is a popular and effective approach to administer naked plasmid for transgene expression. The use of an adjuvant can provide a straightforward approach for enhancing transgene expression. Methods: Expression plasmid was formulated with various concentrations of trehalose for injection into the skeletal muscles of C57BL/6 mice. The effects of trehalose on gene dosage and the duration of transgene expression were assessed. The levels of transgene expression were indicated by levels of luciferase expression of the homogenized whole skeletal muscle or by histological X-gal staining of beta-galactosidase expression. Trehalose was also added to serum to examine the ability of protecting the DNA from degradation. Results: It was found that an optimal trehalose concentration of 10 mM will achieve a level of transgene expression that is seven-fold higher than in the absence of trehalose. When compared with other disaccharides, only the incorporation of trehalose can effectively enhance transgene expression. Trehalose is able to improve transgene expression by intramuscular injection at a low gene dosage as well as prolong the duration of transgene expression. Conclusions: Trehalose is an effective adjuvant for intramuscular administration of naked plasmid with respect to both enhanced levels and prolonged duration of transgene expression, most likely due to retarding plasmid degradation.
MeSH term(s)	Animals ; DNA/administration & dosage ; DNA/genetics ; DNA/metabolism ; Disaccharides/chemistry ; Female ; Gene Dosage/drug effects ; Gene Expression ; Gene Transfer Techniques ; Injections, Intramuscular ; Mice ; Mice, Inbred C57BL ; Muscle, Skeletal/cytology ; Muscle, Skeletal/drug effects ; Muscle, Skeletal/metabolism ; Plasmids/genetics ; Plasmids/metabolism ; Transgenes ; Trehalose/administration & dosage ; Trehalose/chemistry ; Trehalose/pharmacology
Chemical Substances	Disaccharides ; DNA (9007-49-2) ; Trehalose (B8WCK70T7I)
Language	English
Publishing date	2009-03
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1458024-x
ISSN	1521-2254 ; 1099-498X
ISSN (online)	1521-2254
ISSN	1099-498X
DOI	10.1002/jgm.1295
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Article ; Online: Toothbrushing, Blood Glucose and HbA1c: Findings from a Random Survey in Chinese Population.

Su, Lingyu / Liu, Wenzhao / Xie, Bingwu / Dou, Lei / Sun, Jun / Wan, Wenjuan / Fu, Xiaoming / Li, Guangyue / Huang, Jiao / Xu, Ling

Scientific reports

2016 Volume 6, Page(s) 28824

Abstract: Both diabetes and periodontal disease are prevalent in China. Poor oral hygiene practice is the major cause of periodontal disease. An association between oral hygiene practice and blood glucose level was reported in individuals with diabetes, but not in ...

Abstract	Both diabetes and periodontal disease are prevalent in China. Poor oral hygiene practice is the major cause of periodontal disease. An association between oral hygiene practice and blood glucose level was reported in individuals with diabetes, but not in the general population. We examined the association in a population-based random survey recruiting 2,105 adults without previously diagnosed diabetes in Chongqing city, China. Plasma glucose and hemoglobin A1c (HbA1c) were measured, and a 2-hour oral glucose tolerance test was conducted for each respondent. Self-reported toothbrushing frequency was used as a proxy for oral hygiene practice. In a linear model controlling for potential confounders (demographic characteristics, socio-economic status, lifestyle risk factors, BMI, dental visit frequency, etc.), urban residents who barely brushed their teeth had an increase of 0.50 (95% CI: 0.10-0.90) mmol/L in fasting plasma glucose, and an increase of 0.26% (0.04-0.47%) in HbA1c, relative to those brushing ≥twice daily; for rural residents, the effects were 0.26 (0.05-0.48) mmol/L in fasting plasma glucose and 0.20% (0.09-0.31%) in HbA1c. Individuals with better oral practice tended to have lower level of blood glucose and HbA1c. Establishing good oral health behavioral habits may be conducive to diabetes prevention and control in the general population.
MeSH term(s)	Adult ; Aged ; Blood Glucose/analysis ; Body Mass Index ; China ; Diabetes Mellitus ; Female ; Glucose Tolerance Test ; Glycated Hemoglobin A/metabolism ; Health Behavior ; Health Surveys ; Humans ; Life Style ; Linear Models ; Male ; Middle Aged ; Oral Hygiene ; Toothbrushing
Chemical Substances	Blood Glucose ; Glycated Hemoglobin A ; hemoglobin A1c protein, human
Language	English
Publishing date	2016--07
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/srep28824
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