Register      Login
Australian Journal of Chemistry Australian Journal of Chemistry Society
An international journal for chemical science
Shopping Cart: ( empty )
You are here: Home > Journals > CH > CH13485 > Fulltext
REVIEW
Contents Vol 67(1)

Polymer Complexation by Hydrogen Bonding at the Interface

Shuguang Yang A C , Songmei Ma A , Chunyan Wang A , Jian Xu B and Meifang Zhu A
+ Author Affiliations
- Author Affiliations

A State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, College of Material Science and Engineering, Donghua University, Shanghai 201620, China.

B Laboratory of Polymer Physics and Chemistry, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China.

C Corresponding author. Email: shgyang@dhu.edu.cn




Professor Shuguang Yang graduated from Wuhan University in 2002, and obtained his Ph.D. from the Institute of Chemistry, Chinese Academy of Sciences, in 2007. After one year as a research assistant in Peking University and two years as a research associate at the University of Akron, he joined Donghua University. His research activities include investigations of the hydrogen bonding dynamics of polymers, polymer interfacial complexation, polymer micellization, and interaction between polymers and colloidal particles.

Australian Journal of Chemistry 67(1) 11-21 https://doi.org/10.1071/CH13485
Submitted: 30 June 2013  Accepted: 3 October 2013   Published: 13 November 2013

Abstract

Polymer complexes can form in the bulk and at interfaces. Polymer complex formation in the bulk has been studied for a long time. The recently developed layer-by-layer assembly technique well realizes polymer complexation at interfaces. The layer-by-layer assembly of polymers based on Coulomb forces or hydrogen bonding is a repeated complexation process conducted at a surface. This paper reviews both single (once only) and repeatable interfacial complexation by hydrogen bonding, the available hydrogen bonding pairs for complexation, the thermodynamics and kinetics of complexation, and construction schemes.


References

[1]  E. A. Bekturov, L. A. Bimendina, Adv. Polym. Sci. 1981, 41, 99.
         | Crossref | GoogleScholarGoogle Scholar |

[2]  E. Tsuchida, K. Abe, Adv. Polym. Sci. 1982, 45, 1.
         | Crossref | GoogleScholarGoogle Scholar |

[3]  B. Philipp, H. Dautzenberg, K. J. Linov, J. Koetz, W. Dawydoff, Prog. Polym. Sci. 1989, 14, 91.
         | Crossref | GoogleScholarGoogle Scholar |

[4]  M. Jiang, M. Li, M. Xiang, H. Zhou, Adv. Polym. Sci. 1999, 146, 121.
         | Crossref | GoogleScholarGoogle Scholar |

[5]  E. Arunan, G. R. Desiraju, R. A. Klein, J. Sadlej, S. Scheiner, I. Alkorta, D. C. Clary, R. H. Crabtree, J. J. Dannenberg, P. Hobza, H. G. Kjaergaard, A. C. Legon, B. Mennucci, D. J. Nesbitt, Pure Appl. Chem. 2011, 83, 1619.
         | Crossref | GoogleScholarGoogle Scholar |

[6]  E. Arunan, G. R. Desiraju, R. A. Klein, J. Sadlej, S. Scheiner, I. Alkorta, D. C. Clary, R. H. Crabtree, J. J. Dannenberg, P. Hobza, H. G. Kjaergaard, A. C. Legon, B. Mennucci, D. J. Nesbitt, Pure Appl. Chem. 2011, 83, 1637.
         | Crossref | GoogleScholarGoogle Scholar |

[7]  L. Pauling, The Nature of the Chemical Bond 1960 (Cornell University Press: Ithaca, NY).

[8]  G. C. Pimentel, A. L. McClellan, The Hydrogen Bond 1960 (W. H. Freeman: San Francisco, CA).

[9]  S. N. Vinogradov, R. H. Linnell, Hydrogen Bonding 1971 (Van Nostrand-Reinhold: New York, NY).

[10]  G. A. Jeffrey, An Introduction to Hydrogen Bonding 1997 (Oxford University Press: Oxford).

[11]  P. Gilli, G. Gilli, The Nature of the Hydrogen Bond 2009 (Oxford University Press: Oxford).

[12]  P. A. Kollman, L. C. Allen, Chem. Rev. 1972, 72, 283.
         | Crossref | GoogleScholarGoogle Scholar |

[13]  J. C. MacDonald, G. M. Whitesides, Chem. Rev. 1994, 94, 2383.
         | Crossref | GoogleScholarGoogle Scholar |

[14]  I. Alkorta, I. Roza, J. Ekguero, Chem. Soc. Rev. 1998, 27, 163.
         | Crossref | GoogleScholarGoogle Scholar |

[15]  P. Hobza, Z. Havlas, Chem. Rev. 2000, 100, 4253.
         | Crossref | GoogleScholarGoogle Scholar | 11749346PubMed |

[16]  A. Dobry, Bull. Soc. Chim. Belg. 1948, 57, 280.
         | Crossref | GoogleScholarGoogle Scholar |

[17]  K. L. Smith, A. E. Winslow, D. E. Peterson, Ind. Eng. Chem. 1959, 51, 1361.
         | Crossref | GoogleScholarGoogle Scholar |

[18]  F. E. Bailey, R. D. Lundberg, R. W. Callard, J. Polym. Sci., Part A: Polym. Chem. 1964, 2, 845.

[19]  F. E. Bailey, J. V. Koleske, Poly(ethylene oxide) 1976 (Academic Press: New York, NY).

[20]  G. Decher, J. B. Schlenoff, Multillayer Thin Films 2003 (Wiley-VCH: Weinheim).

[21]  S. A. Sukhishvili, E. Kharlampieva, V. Izumrudov, Macromolecules 2006, 39, 8873.
         | Crossref | GoogleScholarGoogle Scholar |

[22]  G. Decher, J. D. Hong, Makromol. Chem. Macromol. Symp. 1991, 46, 321.

[23]  G. Decher, J. D. Hong, Ber. Bunsenges. Phys. Chem 1991, 95, 1430.
         | Crossref | GoogleScholarGoogle Scholar |

[24]  G. Decher, J. D. Hong, J. Schmitt, Thin Solid Films 1992, 210–211, 831.
         | Crossref | GoogleScholarGoogle Scholar |

[25]  G. Decher, Science 1997, 277, 1232.
         | Crossref | GoogleScholarGoogle Scholar |

[26]  G. Decher, M. Eckle, J. Schmitt, B. Struth, Curr. Opin. Colloid Interface Sci. 1998, 3, 32.
         | Crossref | GoogleScholarGoogle Scholar |

[27]  P. T. Hammond, Curr. Opin. Colloid Interface Sci. 1999, 4, 430.
         | Crossref | GoogleScholarGoogle Scholar |

[28]  P. Bertrand, A. Jonas, A. Laschewsky, R. Legras, Macromol. Rapid Commun. 2000, 21, 319.
         | Crossref | GoogleScholarGoogle Scholar |

[29]  M. Schonhoff, Curr. Opin. Colloid Interface Sci. 2003, 8, 86.
         | Crossref | GoogleScholarGoogle Scholar |

[30]  S. A. Sukhishvili, Curr. Opin. Colloid Interface Sci. 2005, 10, 37.
         | Crossref | GoogleScholarGoogle Scholar |

[31]  G. B. Sukhorukov, A. Fery, H. Mohwald, Prog. Polym. Sci. 2005, 30, 885.
         | Crossref | GoogleScholarGoogle Scholar |

[32]  P. T. Hammond, Adv. Mater. 2004, 16, 1271.
         | Crossref | GoogleScholarGoogle Scholar |

[33]  P. Lavalle, J.-C. Voegel, D. Vautier, B. Senger, P. Schaaf, V. Ball, Adv. Mater. 2011, 23, 1191.
         | Crossref | GoogleScholarGoogle Scholar | 21264957PubMed |

[34]  W. B. Stockton, M. F. Rubner, Macromolecules 1997, 30, 2717.
         | Crossref | GoogleScholarGoogle Scholar |

[35]  L. Wang, Z. Wang, X. Zhang, J. Shen, L. Chi, H. Fuchs, Macromol. Rapid Commun. 1997, 18, 509.
         | Crossref | GoogleScholarGoogle Scholar |

[36]  Y. Zhang, Y. Guan, S. Yang, J. Xu, C. C. Han, Adv. Mater. 2003, 15, 832.
         | Crossref | GoogleScholarGoogle Scholar |

[37]  E. Kharlampieva, V. Kozlovskaya, S. A. Sukhishvili, Adv. Mater. 2009, 21, 3053.
         | Crossref | GoogleScholarGoogle Scholar |

[38]  E. Kharlampieva, S. A. Sukhishvili, Polym. Rev. 2006, 46, 377.

[39]  J. F. Quinn, A. P. R. Johnston, G. K. Such, A. N. Zelikin, F. Caruso, Chem. Soc. Rev. 2007, 36, 707.
         | Crossref | GoogleScholarGoogle Scholar | 17471396PubMed |

[40]  G. K. Such, A. P. R. Johnston, F. Caruso, Chem. Soc. Rev. 2011, 40, 19.
         | Crossref | GoogleScholarGoogle Scholar | 20882254PubMed |

[41]  L. S. Roselin, M. S. Lin, P. H. Lin, Y. Chang, W. Y. Chen, Biotechnol. J. 2010, 5, 85.
         | Crossref | GoogleScholarGoogle Scholar | 19902461PubMed |

[42]  C. B. Bucur, Z. J. Sui, J. B. Schlenoff, J. Am. Chem. Soc. 2006, 128, 13690.
         | Crossref | GoogleScholarGoogle Scholar | 17044688PubMed |

[43]  Y. Osada, J. Polym. Sci., Polym. Chem. Ed. 1979, 17, 3485.

[44]  E. Tsuchida, Y. Osada, H. Ohno, J. Macromol. Sci. Part B: Phys. 1980, 17, 683.
         | Crossref | GoogleScholarGoogle Scholar |

[45]  H. Chen, H. Morawet, Macromolecules 1982, 15, 1445.
         | Crossref | GoogleScholarGoogle Scholar |

[46]  H. Chen, H. Morawet, Eur. Polym. J. 1983, 19, 923.
         | Crossref | GoogleScholarGoogle Scholar |

[47]  B. Bednár, H. Morawetz, Macromolecules 1984, 17, 1634.
         | Crossref | GoogleScholarGoogle Scholar |

[48]  T. Okubo, M. Suda, J. Colloid Interface Sci. 1999, 213, 565.
         | Crossref | GoogleScholarGoogle Scholar | 10222098PubMed |

[49]  H. Minami, Y. Mizuta, T. Suzuki, Langmuir 2013, 29, 554.
         | Crossref | GoogleScholarGoogle Scholar | 23244162PubMed |

[50]  W. Gao, Y. Bai, E. Chen, Z. Li, B. Han, W. Yang, Q. Zhou, Macromolecules 2006, 39, 4894.
         | Crossref | GoogleScholarGoogle Scholar |

[51]  Y. Bai, W. Gao, J. Yan, Y. Ma, D. Liang, Z. Li, B. Han, W. Yang, E. Chen, Polymer 2008, 49, 2099.
         | Crossref | GoogleScholarGoogle Scholar |

[52]  D. Xie, K. Xu, R. Bai, G. Zhang, J. Phys. Chem. B 2007, 111, 778.
         | Crossref | GoogleScholarGoogle Scholar | 17249821PubMed |

[53]  D. Xie, W. Bai, K. Xu, R. Bai, G. Zhang, J. Phys. Chem. B 2007, 111, 8034.
         | Crossref | GoogleScholarGoogle Scholar | 17583941PubMed |

[54]  C. Wang, S. Yang, X. Yu, J. X. Zheng, J. Ma, J. Xu, M. Zhu, Soft Matter 2012, 8, 10307.
         | Crossref | GoogleScholarGoogle Scholar |

[55]  S. Yang, X. Yu, L. Wang, Y. Tu, J. X. Zheng, J. Xu, R. M. Van Horn, S. Z. D. Cheng, Macromolecules 2010, 43, 3018.
         | Crossref | GoogleScholarGoogle Scholar |

[56]  J. Chen, W. Cao, Chem. Commun. 1999, 1711.
         | Crossref | GoogleScholarGoogle Scholar |

[57]  S. A. Sukhishvili, S. Granick, J. Am. Chem. Soc. 2000, 122, 9550.
         | Crossref | GoogleScholarGoogle Scholar |

[58]  S. A. Sukhishvili, S. Granick, Macromolecules 2002, 35, 301.
         | Crossref | GoogleScholarGoogle Scholar |

[59]  O. V. Khutoryanskaya, A. C. Williams, V. V. Khutoryanskiy, Macromolecules 2007, 40, 7707.
         | Crossref | GoogleScholarGoogle Scholar |

[60]  Y. Guan, Y. Zhang, T. Zhou, S. Zhou, Soft Matter 2009, 5, 842.
         | Crossref | GoogleScholarGoogle Scholar |

[61]  H. Zhang, Z. Wang, Y. Zhang, X. Zhang, Langmuir 2004, 20, 9366.
         | Crossref | GoogleScholarGoogle Scholar | 15461531PubMed |

[62]  T. Cao, J. Chen, C. Yang, W. Cao, New J. Chem. 2001, 25, 305.
         | Crossref | GoogleScholarGoogle Scholar |

[63]  Z. Yang, T. Cao, J. Chen, W. Cao, Eur. Polym. J. 2002, 38, 2077.
         | Crossref | GoogleScholarGoogle Scholar |

[64]  I. Erel-Unal, S. A. Sukhishvili, Macromolecules 2008, 41, 3962.
         | Crossref | GoogleScholarGoogle Scholar |

[65]  L. Zhou, M. Chen, L. Tian, Y. Guan, Y. Zhang, A. C. S. Appl, ACS Appl. Mater. Interfaces 2013, 5, 3541.
         | Crossref | GoogleScholarGoogle Scholar | 23547529PubMed |

[66]  L. Wang, S. Cui, Z. Wang, X. Zhang, M. Jiang, L. Chi, H. Fuchs, Langmuir 2000, 16, 10490.
         | Crossref | GoogleScholarGoogle Scholar |

[67]  H. Zhang, Y. Fu, D. Wang, L. Wang, Z. Wang, X. Zhang, Langmuir 2003, 19, 8497.
         | Crossref | GoogleScholarGoogle Scholar |

[68]  H. Zhong, J. Wang, X. Jia, Y. Li, Y. Qin, J. Chen, X. S. Zhao, W. Cao, M. Li, Y. Wei, Macromol. Rapid Commun. 2001, 22, 583.
         | Crossref | GoogleScholarGoogle Scholar |

[69]  I. Erel, Z. Zhu, A. Zhuk, S. A. Sukhishvili, J. Colloid Interface Sci. 2011, 355, 61.
         | Crossref | GoogleScholarGoogle Scholar | 21194703PubMed |

[70]  Z. Zhu, S. A. Sukhishvili, ACS Nano 2009, 3, 3595.
         | Crossref | GoogleScholarGoogle Scholar | 19795844PubMed |

[71]  S. Qin, D. Qin, W. T. Ford, J. E. Herrera, D. E. Resasco, Macromolecules 2004, 37, 9963.
         | Crossref | GoogleScholarGoogle Scholar |

[72]  E. Hao, T. Lian, Chem. Mater. 2000, 12, 3392.
         | Crossref | GoogleScholarGoogle Scholar |

[73]  E. Hao, T. Lian, Langmuir 2000, 16, 7879.
         | Crossref | GoogleScholarGoogle Scholar |

[74]  Y. Jiang, Y. Shen, P. Wu, J. Colloid, Interface Sci. 2008, 319, 398.

[75]  S. Yang, Y. Zhang, L. Wang, S. Hong, J. Xu, Y. Chen, C. Li, Langmuir 2006, 22, 338.
         | Crossref | GoogleScholarGoogle Scholar | 16378441PubMed |

[76]  F. Caruso, R. A. Caruso, H. Möhwald, Science 1998, 282, 1111.
         | Crossref | GoogleScholarGoogle Scholar | 9804547PubMed |

[77]  F. Caruso, Chem.–Eur. J. 2000, 6, 413.
         | Crossref | GoogleScholarGoogle Scholar | 10747405PubMed |

[78]  S. Yang, Y. Zhang, G. Yuan, X. Zhang, J. Xu, Macromolecules 2004, 37, 10059.
         | Crossref | GoogleScholarGoogle Scholar |

[79]  S. Y. Yang, D. Lee, R. E. Cohen, M. F. Rubner, Langmuir 2004, 20, 5978.
         | Crossref | GoogleScholarGoogle Scholar | 16459619PubMed |

[80]  V. Kozlovskaya, S. Ok, A. Sousa, M. Libera, S. A. Sukhishvili, Macromolecules 2003, 36, 8590.
         | Crossref | GoogleScholarGoogle Scholar |

[81]  V. Kozlovskaya, A. Shamaev, S. A. Sukhishvili, Soft Matter 2008, 4, 1499.
         | Crossref | GoogleScholarGoogle Scholar |

[82]  D. L. Elbert, C. B. Herbert, J. A. Hubbell, Langmuir 1999, 15, 5355.
         | Crossref | GoogleScholarGoogle Scholar |

[83]  C. Picart, J. Mutterer, L. Richert, Y. Luo, G. D. Prestwich, P. Schaaf, J. C. Voegel, Ph. Lavalle, Proc. Natl. Acad. Sci. USA 2002, 99, 12531.
         | Crossref | GoogleScholarGoogle Scholar | 12237412PubMed |

[84]  T. J. Halthur, U. M. Elofsson, Langmuir 2004, 20, 1739.
         | Crossref | GoogleScholarGoogle Scholar | 15801437PubMed |

[85]  P. Kujawa, P. Moraille, J. Sanchez, A. Badia, F. M. Winnik, J. Am. Chem. Soc. 2005, 127, 9224.
         | Crossref | GoogleScholarGoogle Scholar | 15969601PubMed |

[86]  F. Boulmedais, V. Ball, P. Schwinté, B. Frisch, P. Schaaf, J. C. Voegel, Langmuir 2003, 19, 440.
         | Crossref | GoogleScholarGoogle Scholar |

[87]  S. Yang, Hydrogen Bonding Layer-by-Layer Assembly Film: Fabrication, Application, and Some Fundamental Issues 2007, Ph.D. thesis, Chinese Academy of Sciences.

[88]  X. Liu, B. Dai, L. Zhou, J. Sun, J. Mater. Chem. 2009, 19, 497.
         | Crossref | GoogleScholarGoogle Scholar |

[89]  D. T. Haynie, E. Cho, P. Waduge, Langmuir 2011, 27, 5700.
         | Crossref | GoogleScholarGoogle Scholar | 21466156PubMed |

[90]  S. Yang, S. Tan, Y. Zhang, J. Xu, X. Zhang, Thin Solid Films 2008, 516, 4018.
         | Crossref | GoogleScholarGoogle Scholar |

[91]  J. B. Schlenoff, Langmuir 2009, 25, 14007.
         | Crossref | GoogleScholarGoogle Scholar | 19670891PubMed |

[92]  E. Kharlampieva, V. Kozlovskaya, J. F. Ankner, S. A. Sukhishvili, Langmuir 2008, 24, 11346.
         | Crossref | GoogleScholarGoogle Scholar | 18816021PubMed |

[93]  D. M. DeLongchamp, P. T. Hammond, Langmuir 2004, 20, 5403.
         | Crossref | GoogleScholarGoogle Scholar | 15986679PubMed |

[94]  S. Yang, Y. Zhang, J. Xu, Soft Matter 2007, 3, 463.
         | Crossref | GoogleScholarGoogle Scholar |

[95]  J. F. Quinn, F. Caruso, Langmuir 2004, 20, 20.
         | Crossref | GoogleScholarGoogle Scholar | 15744991PubMed |

[96]  J. Ma, S. Yang, Y. Li, X. Xu, J. Xu, Soft Matter 2011, 7, 9435.
         | Crossref | GoogleScholarGoogle Scholar |

[97]  Y. Guan, S. Yang, Y. Zhang, J. Xu, C. C. Han, N. A. Kotov, J. Phys. Chem. B 2006, 110, 13484.
         | Crossref | GoogleScholarGoogle Scholar | 16821874PubMed |

[98]  S. Yang, Y. Zhang, X. Zhang, Y. Guan, J. Xu, X. Zhang, ChemPhysChem 2007, 8, 418.
         | Crossref | GoogleScholarGoogle Scholar | 17183526PubMed |

[99]  S. T. Dubas, J. B. Schlenoff, Macromolecules 1999, 32, 8153.
         | Crossref | GoogleScholarGoogle Scholar |

[100]  L. Wang, Y. Fu, Z. Wang, Y. Fan, X. Zhang, Langmuir 1999, 15, 1360.
         | Crossref | GoogleScholarGoogle Scholar |

[101]  Y. Fu, S. Bai, S. Cui, D. Qiu, Z. Wang, X. Zhang, Macromolecules 2002, 35, 9451.
         | Crossref | GoogleScholarGoogle Scholar |

[102]  S. Bai, Z. Wang, X. Zhang, B. Wang, Langmuir 2004, 20, 11828.
         | Crossref | GoogleScholarGoogle Scholar | 15595820PubMed |

[103]  Y. Zhang, Z. Wang, Y. Zhang, X. Zhang, Langmuir 2004, 20, 9366.
         | Crossref | GoogleScholarGoogle Scholar | 15461531PubMed |

[104]  H. Ohno, K. Abe, E. Tsuchida, Makromol. Chem. 1978, 179, 755.
         | Crossref | GoogleScholarGoogle Scholar |

[105]  H. Ohno, A. Nii, E. Tsuchida, Makromol. Chem. 1980, 181, 1227.
         | Crossref | GoogleScholarGoogle Scholar |

[106]  D. E. Zhunuspayev, G. A. Mun, P. Hole, V. V. Khutoryanskiy, Langmuir 2008, 24, 13742.
         | Crossref | GoogleScholarGoogle Scholar | 18980359PubMed |

[107]  N. Nuraje, R. Asmatulu, R. E. Cohen, M. F. Rubner, Langmuir 2011, 27, 782.
         | Crossref | GoogleScholarGoogle Scholar | 21162522PubMed |

[108]  S. Yang, Y. Zhang, Y. Guan, S. Tan, X. Zhang, S. Cheng, J. Xu, Soft Matter 2006, 2, 699.
         | Crossref | GoogleScholarGoogle Scholar |

[109]  S. Yang, Y. Li, X. Li, Y. Li, X. Zhang, J. Xu, Thin Solid Films 2009, 517, 3024.
         | Crossref | GoogleScholarGoogle Scholar |

[110]  H. Lee, R. Mensire, R. E. Cohen, M. F. Rubner, Macromolecules 2012, 45, 347.
         | Crossref | GoogleScholarGoogle Scholar |

[111]  S. Y. Yang, M. F. Rubner, J. Am. Chem. Soc. 2002, 124, 2100.
         | Crossref | GoogleScholarGoogle Scholar | 11878948PubMed |

[112]  B. Wang, K. Ren, H. Chang, J. Wang, J. Jian, ACS Appl. Mater. Interfaces 2013, 5, 4136.
         | 23597281PubMed |

[113]  Z. Yang, T. Cao, J. Chen, W. Cao, Eur. Polym. J. 2002, 38, 2077.
         | Crossref | GoogleScholarGoogle Scholar |

[114]  T. Cao, J. Chen, C. Yang, W. Cao, New J. Chem. 2001, 25, 305.
         | Crossref | GoogleScholarGoogle Scholar |

[115]  Y. Zhang, S. Yang, Y. Guan, X. Miao, W. Cao, J. Xu, Thin Solid Films 2003, 437, 280.
         | Crossref | GoogleScholarGoogle Scholar |

[116]  J. F. Quinn, F. Caruso, Adv. Funct. Mater. 2006, 16, 1179.
         | Crossref | GoogleScholarGoogle Scholar |

[117]  A. N. Zelikin, Q. Li, F. Caruso, Angew. Chem. Int. Ed. 2006, 45, 7743.
         | Crossref | GoogleScholarGoogle Scholar |

[118]  A. N. Zelikin, J. F. Quinn, F. Caruso, Biomacromolecules 2006, 7, 27.
         | Crossref | GoogleScholarGoogle Scholar | 16398494PubMed |

[119]  C. R. Kinnane, G. K. Such, G. Antequera-Garcia, Y. Yan, S. J. Dodds, L. M. Liz-Marzan, F. Caruso, Biomacromolecules 2009, 10, 2839.
         | Crossref | GoogleScholarGoogle Scholar | 19719165PubMed |

[120]  C. J. Ochs, G. K. Such, Y. Yan, M. P. van Koeverden, F. Caruso, ACS Nano 2010, 4, 1653.
         | Crossref | GoogleScholarGoogle Scholar | 20201548PubMed |