Journal Home > Volume 11 , Issue 3
Food Science and Human Wellness 2022, 11(3): 587-597 https://doi.org/10.1016/j.fshw.2021.12.015
Review Article | Open Access | Issue | Published: 04 February 2022

Structure variety and its potential effects on biological activity of tea polysaccharides

Show Author's Information Ting Hua,  Peng Wua,  Jianfeng Zhana,  Weixin Wanga,  Junfeng Shena,  Meiyan Wangb( ),  Chi-Tang Hoc,  Shiming Lia( )
Hubei Key Laboratory of Economic Forest Germplasm Improvement and Resources Comprehensive Utilization, Huanggang Normal University, Huanggang 438000, China
School of Biotechnology and Food Science, Tianjin University of Commerce, Tianjin 300134, China
Department of Food Science, Rutgers University, NJ 08901, USA

Peer review under responsibility of KeAi Communications Co., Ltd.

Keywords:
Influencing factors, Relationship, Tea polysaccharides, Structure variety, Bioactivities
Cite this article:
Hu T, Wu P, Zhan J, et al. Structure variety and its potential effects on biological activity of tea polysaccharides. Food Science and Human Wellness, 2022, 11(3): 587-597. https://doi.org/10.1016/j.fshw.2021.12.015
Download citation
EndNote(RIS)
BibTeX

514

Views

31

Downloads

Citations

7

Crossref

6

WoS

8

Scopus

1

CSCD

Abstract Full text About this article

Tea polysaccharides (TPSs), one of the major bioactive ingredients in tea, have been widely studied due to their variety of biological activities, including antioxidant, cancer prevention, hypoglycemia, anti-fatigue, anti-coagulant, anti-obesity and immunomodulatory effect. The biological effectiveness of TPSs has direct relation with their structures such as monosaccharide composition, molecular weight, glycosidic linkages, conformation and others, which can be influenced by tea materials, processing methods, extraction and purification procedures among others. Comparing to the study of tea polyphenols, the exploration of TPSs in structural elucidation and biofunctionality is very preliminary. Yet several factors affecting the structural change of TPSs have been studied and identified. Consequently, the variation of some TPS biological activity brought by the change of TPS structures has been evaluated and preliminary correlation of structure activity relationship of TPSs has been performed. Therefore, this review aims to serve as a summary research report regarding the influencing factors on TPSs structures and consequential effects on the biological activities of TPSs. We hope to provide updated information and systematic references for future study and functional food development of TPSs.


menu
Abstract
Full text
Outline
About this article

Structure variety and its potential effects on biological activity of tea polysaccharides

Show Author's information Ting Hua, Peng Wua, Jianfeng Zhana, Weixin Wanga, Junfeng Shena, Meiyan Wangb( ), Chi-Tang Hoc, Shiming Lia( )
Hubei Key Laboratory of Economic Forest Germplasm Improvement and Resources Comprehensive Utilization, Huanggang Normal University, Huanggang 438000, China
School of Biotechnology and Food Science, Tianjin University of Commerce, Tianjin 300134, China
Department of Food Science, Rutgers University, NJ 08901, USA

Peer review under responsibility of KeAi Communications Co., Ltd.

Abstract

Tea polysaccharides (TPSs), one of the major bioactive ingredients in tea, have been widely studied due to their variety of biological activities, including antioxidant, cancer prevention, hypoglycemia, anti-fatigue, anti-coagulant, anti-obesity and immunomodulatory effect. The biological effectiveness of TPSs has direct relation with their structures such as monosaccharide composition, molecular weight, glycosidic linkages, conformation and others, which can be influenced by tea materials, processing methods, extraction and purification procedures among others. Comparing to the study of tea polyphenols, the exploration of TPSs in structural elucidation and biofunctionality is very preliminary. Yet several factors affecting the structural change of TPSs have been studied and identified. Consequently, the variation of some TPS biological activity brought by the change of TPS structures has been evaluated and preliminary correlation of structure activity relationship of TPSs has been performed. Therefore, this review aims to serve as a summary research report regarding the influencing factors on TPSs structures and consequential effects on the biological activities of TPSs. We hope to provide updated information and systematic references for future study and functional food development of TPSs.

Keywords: Influencing factors, Relationship, Tea polysaccharides, Structure variety, Bioactivities

References(66)

[1]

J.B. Xiao, H. Jiang, A review on the structure-function relationship aspect of polysaccharides from tea materials, Crit. Rev. Food Sci. Nutr. 55(7) (2015) 930-938. https://doi.org/10.1080/10408398.2012.678423.
DOI Google Scholar
[2]

Y. Gao, Y. Zhou, Q. Zhang, et al., Hydrothermal extraction, structural characterization, and inhibition HeLa cells proliferation of functional polysaccharides from Chinese tea Zhongcha 108, J. Funct. Foods. 39 (2017) 1-8. https://doi.org/10.1016/j.jff.2017.09.057.
DOI Google Scholar
[3]

G. Chen, Q. Yuan, M. Saeeduddin, et al., Recent advances in tea polysaccharides: extraction, purification, physicochemical characterization and bioactivities, Carbohydr. Polym. 153 (2016) 663-678. https://doi.org/10.1016/j.carbpol.2016.08.022.
DOI Google Scholar
[4]

C. Cabrera, R. Artacho, R. Giménez, Beneficial effects of green tea-a review, J. Am. Coll. Nutr. 25(2) (2006) 79-99. https://doi.org/10.1080/07315724.2006.10719518.
DOI Google Scholar
[5]

L. Zhang, C.T. Ho, J. Zhou, et al., Chemistry and biological activities of processed Camellia sinensis teas: a comprehensive review, Compr. Rev. Food Sci F. 18(5) (2019) 1474-1495. https://doi.org/10.1111/1541-4337.12479.
DOI Google Scholar
[6]
S. Nie, S.W. Cui, M. Xie, Chapter 7 - tea polysaccharide, in: S. Nie, S.W. Cui, M. Xie (Eds. ), Bioactive Polysaccharides, Academic Press 2018, pp. 349-394. https://doi.org/10.1016/B978-0-12-809418-1.00007-1.
[7]

C.T. Scoparo, L.M. Souza, N. Dartora, et al., Chemical characterization of heteropolysaccharides from green and black teas (Camellia sinensis) and their anti-ulcer effect, Int. J. Biol. Macromol. 86 (2016) 772-781. https://doi.org/10.1016/j.ijbiomac.2016.02.017.
DOI Google Scholar
[8]

H. Wang, S. Shi, B. Bao, et al., Structure characterization of an arabinogalactan from green tea and its anti-diabetic effect, Carbohydr. Polym. 124 (2015) 98-108. https://doi.org/10.1016/j.carbpol.2015.01.070.
DOI Google Scholar
[9]

Z. Peng, M. Xie, S. Nie, et al., Primary structure and configuration of tea polysaccharide, Science in China 47(5) (2004) 416-424. https://doi.org/10.1360/03yc0157.
DOI Google Scholar
[10]

Y. Wang, X. Wei, Z. Jin, Structure analysis of a neutral polysaccharide isolated from green tea, Food Res. Int. 42(5) (2009) 739-745. https://doi.org/10.1016/j.foodres.2009.03.011.
DOI Google Scholar
[11]

Y. Wang, X. Wei, Z. Jin, Structure analysis of an acidic polysaccharide isolated from green tea, Nat. Prod. Res. 23(7) (2009) 678-687. https://doi.org/10.1080/14786410902819178.
DOI Google Scholar
[12]

J. Zhu, Z. Chen, H. Zhou, et al., Effects of extraction methods on physicochemical properties and hypoglycemic activities of polysaccharides from coarse green tea, Glycoconj. J. 37(2) (2020) 241-250. https://doi.org/10.1007/s10719-019-09901-2.
DOI Google Scholar
[13]

W. Cai, L. Xie, Y. Chen, et al., Purification, characterization and anticoagulant activity of the polysaccharides from green tea, Carbohydr. Polym. 92(2) (2013) 1086-1090. https://doi.org/10.1016/j.carbpol.2012.10.057.
DOI Google Scholar
[14]

J. Yang, B. Chen, Y. Gu, Pharmacological evaluation of tea polysaccharides with antioxidant activity in gastric cancer mice, Carbohydr. Polym. 90(2) (2012) 943-947. https://doi.org/10.1016/j.carbpol.2012.06.024.
DOI Google Scholar
[15]

Y. Gu, Y. Qiu, X. Wei, et al., Characterization of selenium-containing polysaccharides isolated from selenium-enriched tea and its bioactivities, Food Chem. 316 (2020) 126371. https://doi.org/10.1016/j.foodchem.2020.126371.
DOI Google Scholar
[16]

L. Yang, S. Fu, X. Zhu, et al., Hyperbranched acidic polysaccharide from green tea, Biomacromolecules 11(12) (2010) 3395-3405. https://doi.org/10.1021/bm100902d.
DOI Google Scholar
[17]

X. Zhang, H. Chen, N. Zhang, et al., Extrusion treatment for improved physicochemical and antioxidant properties of high-molecular weight polysaccharides isolated from coarse tea, Food Res. Int. 53(2) (2013) 726-731. https://doi.org/10.1016/j.foodres.2012.08.011.
DOI Google Scholar
[18]

S. Li, H. Chen, J. Wang, et al., Involvement of the PI3K/Akt signal pathway in the hypoglycemic effects of tea polysaccharides on diabetic mice, Int. J. Biol. Macromol. 81 (2015) 967-974. https://doi.org/10.1016/j.ijbiomac.2015.09.037.
DOI Google Scholar
[19]

Y. Zhou, Q. Yao, T. Zhang, et al., Antibacterial activity and mechanism of green tea polysaccharide conjugates against Escherichia coli, Ind. Crop. Prod. 152 (2020) 112464. https://doi.org/10.1016/j.indcrop.2020.112464.
DOI Google Scholar
[20]

S. Nie, M. Xie, P. Zhou, et al., In vitro antioxidative and anticancer activities of tea glycoprotein in green tea, Eur. Food Res. Technol. 224(4) (2007) 437-442. https://doi.org/10.1007/s00217-006-0324-y.
DOI Google Scholar
[21]

A. Chi, H. Li, C. Kang, et al., Anti-fatigue activity of a novel polysaccharide conjugates from Ziyang green tea, Int. J. Biol. Macromol. 80 (2015) 566-572. https://doi.org/10.1016/j.ijbiomac.2015.06.055.
DOI Google Scholar
[22]

Y. Xu, M. Zhang, T. Wu, et al., The anti-obesity effect of green tea polysaccharides, polyphenols and caffeine in rats fed with a high-fat diet, Food Funct. 6 (2015) 297-304. https://doi.org/10.1039/c4fo00970c.
DOI Google Scholar
[23]

H. Wang, G. Wei, F. Liu, et al., Characterization of two homogalacturonan pectins with immunomodulatory activity from green tea, Int. J. Mol. Sci. 15 (2014) 9963-9978. https://doi.org/10.3390/ijms15069963.
DOI Google Scholar
[24]

H. Cao, Polysaccharides from Chinese tea: recent advance on bioactivity and function, Int. J. Biol. Macromol. 62 (2013) 76-79. https://doi.org/10.1016/j.ijbiomac.2013.08.033.
DOI Google Scholar
[25]

Z.Y. Zhao, L.T. Huangfu, L.L. Dong, et al., Functional groups and antioxidant activities of polysaccharides from five categories of tea, Ind. Crop. Prod. 58 (2014) 31-35. https://doi.org/10.1016/j.indcrop.2014.04.004.
DOI Google Scholar
[26]

Y. Wang, F. Mao, X. Wei, Characterization and antioxidant activities of polysaccharides from leaves, flowers and seeds of green tea, Carbohydr. Polym. 88(1) (2012) 146-153. https://doi.org/10.1016/j.carbpol.2011.11.083.
DOI Google Scholar
[27]

Y. Wang, Z. Yang, X. Wei, Antioxidant activities potential of tea polysaccharide fractions obtained by ultra filtration, Int. J. Biol. Macromol. 50(3) (2012) 558-564. https://doi.org/10.1016/j.ijbiomac.2011.12.028.
DOI Google Scholar
[28]

S.P. Nie, M.Y. Xie, A review on the isolation and structure of tea polysaccharides and their bioactivities, Food Hydrocoll. 25(2) (2011) 144-149. https://doi.org/10.1016/j.foodhyd.2010.04.010.
DOI Google Scholar
[29]

S. Nie, M. Xie, Z. Fu, et al., Study on the purification and chemical compositions of tea glycoprotein, Carbohydr. Polym. 71(4) (2008) 626-633. https://doi.org/10.1016/j.carbpol.2007.07.005.
DOI Google Scholar
[30]

L. Yin, S. Fu, R. Wu, et al., Chain conformation of an acidic polysaccharide from green tea and related mechanism of α-amylase inhibitory activity, Int. J. Biol. Macromol. 164 (2020) 1124-1132. https://doi.org/10.1016/j.ijbiomac.2020.07.125.
DOI Google Scholar
[31]

J. Zhu, Z. Chen, L. Chen, et al., Comparison and structural characterization of polysaccharides from natural and artificial Se-enriched green tea, Int. J. Biol. Macromol. 130 (2019) 388-398. https://doi.org/10.1016/j.ijbiomac.2019.02.102.
DOI Google Scholar
[32]

J. Xiao, J. Huo, H. Jiang, et al., Chemical compositions and bioactivities of crude polysaccharides from tea leaves beyond their useful date, Int. J. Biol. Macromol. 49(5) (2011) 1143-1151. https://doi.org/10.1016/j.ijbiomac.2011.09.013.
DOI Google Scholar
[33]

X. Chen, Z. Lin, Y. Ye, et al., Suppression of diabetes in non-obese diabetic (NOD) mice by oral administration of water-soluble and alkali-soluble polysaccharide conjugates prepared from green tea, Carbohydr. Polym. 82(1) (2010) 28-33. https://doi.org/10.1016/j.carbpol.2010.04.017.
DOI Google Scholar
[34]

H. Chen, Z. Qu, L. Fu, et al., Physicochemical properties and antioxidant capacity of 3 polysaccharides from green tea, oolong tea, and black tea, J. Food Sci. 74(6) (2009) C469-C474. https://doi.org/10.1111/j.1750-3841.2009.01231.x.
DOI Google Scholar
[35]

P. Xu, J. Wu, Y. Zhang, et al., Physicochemical characterization of puerh tea polysaccharides and their antioxidant and α-glycosidase inhibition, J. Funct. Foods 6 (2014) 545-554. https://doi.org/10.1016/j.jff.2013.11.021.
DOI Google Scholar
[36]

Y.F. Wang, J. Wang, J. Wu, et al., In vitro antioxidant activity and potential inhibitory action against α-glucosidase of polysaccharides from fruit peel of tea (Camellia sinensis L. ), J. Zhejiang Univ. SC. B. 15(2) (2014) 173-180. https://doi.org/10.1631/jzus.B1300186.
DOI Google Scholar
[37]

Y. Wang, Y. Liu, J. Huo, et al., Effect of different drying methods on chemical composition and bioactivity of tea polysaccharides, Int. J. Biol. Macromol. 62 (2013) 714-719. https://doi.org/10.1016/j.ijbiomac.2013.10.006.
DOI Google Scholar
[38]

X. Yang, M. Huang, C. Qin, et al., Structural characterization and evaluation of the antioxidant activities of polysaccharides extracted from Qingzhuan brick tea, Int. J. Biol. Macromol. 101 (2017) 768-775. https://doi.org/10.1016/j.ijbiomac.2017.03.189.
DOI Google Scholar
[39]

R. Xu, H. Ye, Y. Sun, et al., Preparation, preliminary characterization, antioxidant, hepatoprotective and antitumor activities of polysaccharides from the flower of tea plant (Camellia sinensis), Food Chem. Toxicol. 50(7) (2012) 2473-2480. https://doi.org/10.1016/j.fct.2011.10.047.
DOI Google Scholar
[40]

Y. Wang, S. Shao, P. Xu, et al., Fermentation process enhanced production and bioactivities of oolong tea polysaccharides, Food Res. Int. 46(1) (2012) 158-166. https://doi.org/10.1016/j.foodres.2011.11.027.
DOI Google Scholar
[41]

H. Chen, M. Zhang, Z. Qu, et al., Antioxidant activities of different fractions of polysaccharide conjugates from green tea (Camellia Sinensis), Food Chem. 106(2) (2008) 559-563. https://doi.org/10.1016/j.foodchem.2007.06.040.
DOI Google Scholar
[42]

X. Wei, Z. Yang, Y. Guo, et al., Composition and biological activity of tea polysaccharides obtained by water extraction and enzymatic extraction, Lat. Am. J. Pharm. 29(1) (2010) 117-121. https://doi.org/10.4196/kjpp.2010.14.1.51.
DOI Google Scholar
[43]

M. Monobe, K. Ema, F. Kato, et al., Immunostimulating activity of a crude polysaccharide derived from green tea (Camellia sinensis) extract, J. Agric. Food. Chem. 56(4) (2008) 1423-1427. https://doi.org/10.1021/jf073127h.
DOI Google Scholar
[44]

M. Monobe, K. Ema, Y. Tokuda, et al., Enhancement of the phagocytic activity of macrophage-like cells with a crude polysaccharide derived from green tea (Camellia sinensis) extract, Biosci. Biotechnol. Biochem. 74(6) (2010) 1306-1308. https://doi.org/10.1271/bbb.100087.
DOI Google Scholar
[45]

H. Quan, Q.Y. Yu, S. Jiang, et al., Structural characterization and antioxidant activities of 2 water-soluble polysaccharide fractions purified from tea (Camellia sinensis) flower, J. Food Sci. 76(3) (2011) C462-C471. https://doi.org/10.1111/j.1750-3841.2011.02063.x.
DOI Google Scholar
[46]

X. Chen, J. Xie, H. Wei, et al., Comparative analysis of physicochemical characteristics of green tea polysaccharide conjugates and its decolored fraction and their effect on HepG2 cell proliferation, Ind. Crop. Prod. 131 (2019) 243-249. https://doi.org/10.1016/j.indcrop.2019.01.061.
DOI Google Scholar
[47]

K. Yang, Z.Y. Gao, T.Q. Li, et al., Anti-tumor activity and the mechanism of a green tea (Camellia sinensis) polysaccharide on prostate cancer, Int. J. Biol. Macromol. 122 (2019) 95-103. https://doi.org/10.1016/j.ijbiomac.2018.10.101.
DOI Google Scholar
[48]

H.R. Park, D. Hwang, H.J. Suh, et al., Antitumor and antimetastatic activities of rhamnogalacturonan-II-type polysaccharide isolated from mature leaves of green tea via activation of macrophages and natural killer cells, Int. J. Biol. Macromol. 99 (2017) 179-186. https://doi.org/10.1016/j.ijbiomac.2017.02.043.
DOI Google Scholar
[49]

H. Wang, J. Chen, P. Ren, et al., Ultrasound irradiation alters the spatial structure and improves the antioxidant activity of the yellow tea polysaccharide, Ultrason. Sonochem. 70 (2021) 105355. https://doi.org/10.1016/j.ultsonch.2020.105355.
DOI Google Scholar
[50]

H. Qin, L. Huang, J. Teng, et al., Purification, characterization, and bioactivity of Liupao tea polysaccharides before and after fermentation, Food Chem. (2021) 129419. https://doi.org/10.1016/j.foodchem.2021.129419.
DOI Google Scholar
[51]

Z. Yu, Y.T. Shi, D.J. Ni, Effect of enzymatic modification green tea polysaccharide on immune function of the immunosuppressant mice, J. Tea Sci. 30 (2010) 567-572.
Google Scholar
[52]

D. Wang, C. Wang, G. Zhao, et al., Composition, characteristic and activity of rare earth element-bound polysaccharide from tea, Biosci. Biotechnol. Biochem. 65(9) (2001) 1987-1992. https://doi.org/10.1271/bbb.65.1987.
DOI Google Scholar
[53]

Y. Wang, Y. Peng, X. Wei, et al., Sulfation of tea polysaccharides: synthesis, characterization and hypoglycemic activity, Int. J. Biol. Macromol. 46(2) (2010) 270-274. https://doi.org/10.1016/j.ijbiomac.2009.12.007.
DOI Google Scholar
[54]

Y. Wang, Y. Li, Y. Liu, et al., Extraction, characterization and antioxidant activities of Se-enriched tea polysaccharides, Int. J. Biol. Macromol. 77 (2015) 76-84. https://doi.org/10.1016/j.ijbiomac.2015.02.052.
DOI Google Scholar
[55]

N. He, X. Shi, Y. Zhao, et al., Inhibitory effects and molecular mechanisms of selenium-containing tea polysaccharides on human breast cancer MCF-7 cells, J. Agric. Food. Chem. 61(3) (2013) 579-588. https://doi.org/10.1021/jf3036929.
DOI Google Scholar
[56]

Y. Wang, J. Chen, D. Zhang, et al., Tumoricidal effects of a selenium (Se)-polysaccharide from Ziyang green tea on human osteosarcoma U-2 OS cells, Carbohydr. Polym. 98(1) (2013) 1186-1190. https://doi.org/10.1016/j.carbpol.2013.07.022.
DOI Google Scholar
[57]

L. Cheng, L. Chen, Q. Yang, et al., Antitumor activity of Se-containing tea polysaccharides against sarcoma 180 and comparison with regular tea polysaccharides and Se-yeast, Int. J. Biol. Macromol. 120 (2018) 853-858. https://doi.org/10.1016/j.ijbiomac.2018.08.154.
DOI Google Scholar
[58]

J. Zhu, C. Yu, Z. Han, et al., Comparative analysis of existence form for selenium and structural characteristics in artificial selenium-enriched and synthetic selenized green tea polysaccharides, Int. J. Biol. Macromol. 154 (2020) 1408-1418. https://doi.org/10.1016/j.ijbiomac.2019.11.022.
DOI Google Scholar
[59]

M. Fan, X. Sun, Y. Qian, et al., Effects of metal ions in tea polysaccharides on their in vitro antioxidant activity and hypoglycemic activity, Int. J. Biol. Macromol. 113 (2018) 418-426. https://doi.org/10.1016/j.ijbiomac.2018.01.041.
DOI Google Scholar
[60]

N. Li, C. Wang, M.I. Georgiev, et al., Advances in dietary polysaccharides as anticancer agents: structure-activity relationship, Trends Food Sci. Technol. 111 (2021) 360-377. https://doi.org/10.1016/j.tifs.2021.03.008.
DOI Google Scholar
[61]

S.S. Ferreira, C.P. Passos, P. Madureira, et al., Structure–function relationships of immunostimulatory polysaccharides: a review, Carbohydr. Polym. 132 (2015) 378-396. https://doi.org/10.1016/j.carbpol.2015.05.079.
DOI Google Scholar
[62]

J. Qu, P. Huang, L. Zhang, et al., Hepatoprotective effect of plant polysaccharides from natural resources: a review of the mechanisms and structure-activity relationship, Int. J. Biol. Macromol. 161 (2020) 24-34. https://doi.org/10.1016/j.ijbiomac.2020.05.196.
DOI Google Scholar
[63]

Y. Zhang, S. Li, X. Wang, et al., Advances in lentinan: isolation, structure, chain conformation and bioactivities, Food Hydrocoll. 25(2) (2011) 196-206. https://doi.org/10.1016/j.foodhyd.2010.02.001.
DOI Google Scholar
[64]

N. Chen, H. Zhang, X. Zong, et al., Polysaccharides from Auricularia auricula: preparation, structural features and biological activities, Carbohydr. Polym. 247 (2020) 116750. https://doi.org/10.1016/j.carbpol.2020.116750.
DOI Google Scholar
[65]

T.D. Yea, S.Y. Lin-Shiau, L.F. Shyur, et al., Pu-erh tea polysaccharides decrease blood sugar by inhibition α-glucosidase activities in vitro and in mice, Food Funct. 6 (2015) 1539-1546. https://doi.org/10.1039/c4fo01025f.
DOI Google Scholar
[66]

Y. Wang, Z. Yang, X. Wei, Sugar compositions, α-glucosidase inhibitory and amylase inhibitory activities of polysaccharides from leaves and flowers of Camellia sinensis obtained by different extraction methods, Int. J. Biol. Macromol. 47(4) (2010) 534-539. https://doi.org/10.1016/j.ijbiomac.2010.07.007.
DOI Google Scholar
Publication history
Copyright
Acknowledgements
Rights and permissions

Publication history

Received: 25 January 2021
Revised: 17 April 2021
Accepted: 18 April 2021
Published: 04 February 2022
Issue date: May 2022

Copyright

© 2022 Beijing Academy of Food Sciences.

Acknowledgements

Acknowledgements

This work was supported by Hubei Science and Technology Plan Key Project (G2019ABA100), Assessment and Comprehensive Utilization of Characteristic Biological Resources in Dabie Mountains (4022019006), Natural Science Fund of Hubei Province (2019CFB395).

Rights and permissions

This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Return