反刍动物初乳microRNA组成和功能研究进展

doi:10.11843/j.issn.0366-6964.2025.01.007

Abstract

Abstract:

The colostrum of ruminants encompasses abundant bioactive components, of which microRNAs are kind of non-coding RNAs that can regulate gene expression at the post-transcriptional level and play important roles in regulating development of the mother's mammary gland and gastrointestinal tract of young ruminants. In recent years, studies on the profile and function of microRNAs derived from ruminant colostrum have attracted attention. In this review, the source, composition, influencing factors, and function of microRNA in ruminant colostrum as well as the limitations of current studies and future research directions were summarized, with an aim to provide theoretical support for the production of high-quality colostrum and improve integrated mother-neonate cultivation level.

Key words: ruminant, colostrum, microRNA, extracellular vesicles

CLC Number:

S823.91

SUN Tongyu, MA Tao. Research Progress on Composition and Function of Colostral MicroRNA in Ruminants[J]. Acta Veterinaria et Zootechnica Sinica, 2025, 56(1): 74-81.

Figures/Tables 3

Table 1

Top10 most abundant microRNA in colostrum samples collected from ruminant from different studies"

品种 Breed	胎次 Parity	相对丰度排名前10的microRNA Top 10 most abundant microRNA	MicroRNA数量 Amount of microRNA	初乳收集时间 Collection time of colostrum	文献 References
荷斯坦奶牛 Holstein	2~4胎次 Second to fourth parity	miR-148a-3p, miR-27b-3p, miR-let-7a-5p, miR-26a-5p	——	产后8 h内 Within 8 h after parturition	[17]^*
荷斯坦奶牛 Holstein	经产 Multi-parity	miR-30a, miR-148a, let-7a, miR-181a, let-7f, miR-26a, miR-22, miR-92a, miR-21, miR-30d	343	产后24 h内 Within 24 h postpartum	[3]
荷斯坦奶牛 Holstein	——	bta-let-7b, bta-miR-3596, bta-miR-99a-5p, bta-miR-148a, bta-miR-26a, bta-miR-26c, bta-let-7a-5p, bta-miR-30a-5p, bta-miR-21-5p, bta-miR-30d	299	产后1~2 d 1-2 postpartum days	[34]
东安纳托利亚红牛 Dogu Anadolu Kirmizisi (DAK)	——	bta-miR-21-5p, bta-miR-451, bta-miR-143, bta-miR-148a, bta-let-7i, bta-miR-320a, bta-miR-26a, bta-miR-26c, bta-miR-99a-5p, bta-miR-1	269	产后1~2 d 1-2 d postpartum	[34]
荷斯坦奶牛 Holstein	——	let-7a, let-7b, let-7c, let-7f, miR-15b, miR-20a, miR-24, miR-26a, miR-27b, miR-29b	100	产后3 d内 Within 3 d postpartum	[18]^*
安格斯牛、赫里福德牛、安格斯×赫里福德牛 Angus, Hereford, Angus× Hereford	初产经产混合 Mixed	let-7b, let-7a-5p, miR-30a-5p, miR-148a, miR-21-5p, miR-200a, miR-141, let-7f, miR-26a, miR-200c	389	——	[30]
荷斯坦奶牛 Holstein	——	bta-miR-26a, bta-miR-30a-5p, bta-miR181a, bta-let-7a-5p, bta-miR-22-3p, bta-miR-191, bta-miR-148a, bta-let-7f, bta-miR-27b, bta-miR-182	——	产后3 d内 Within 3 d postpartum	[29]
——	——	let-7b, miR-30a, let-7a, let-7c, miR-21, miR-103, miR-25, miR-320a, miR-107, miR-423-5p	230	产后7 d内 Within 7 d postpartum	[26]
瑞士褐牛 Brown Swiss cows	经产 Multi-parity	bta-miR-30a-5p, bta-miR-21-5p, bta-miR-148a, bta-miR-200a, bta-miR-200b, bta-miR-99a-5p, bta-miR-26a, bta-let-7f, bta-let-7g, bta-let-7a-5p	141	产后立即收集 Immediately after parturition	[27]
荷斯坦奶牛 Holstein	——	bta-mir-10, bta-mir-125b, bta-mir-150, bta-mir-223, bta-mir-24-1, bta-mir-93	——	产后1~2 d 1-2 d postpartum	[14]^*
——	——	miR-24, miR-30d, miR-93, miR-106a, miR-181a, miR-200a, miR-451	——	产后7 d内 Within 7 d postpartum	[22]^*
关中奶山羊 Guanzhong dairy goat	——	chi-miR-143-3p, chi-miR-30a-5p, chi-miR-148a-3p, chi-miR-10b-5p, chi-miR-26a-5p, chi-miR-181c-5p, chi-miR-27b-3p, chi-miR-146b-5p, chi-miR-21-5p, chi-let-7f-5p	568	产后2 d内 Within 2 d postpartum	[28]
萨能奶山羊 Saanen dairy goats	——	chi-miR-30a-5p, chi-miR-148a, chi-miR-22-3p, chi-miR-27b, chi-miR-378-3p, chi-miR-92a-3p, chi-miR-92b, chi-miR-21-5p, chi-miR-146b-5p, chi-miR-141	——	产后3 d内 Within 3 d postpartum	[29]
关中奶山羊 Guanzhong dairy goat	初产 Primiparous	miR-423-5p, miR-30a-5p, miR-26a-5p, miR-200b, miR-148a-3p, let-7g-5p, let-7f-5p, let-7c-5p, let-7b-5p, let-7a-5p	192	产后立即收集 Immediately after parturition	[45]

Table 1

Fig. 1

Fig. 2

References 54

1	LINEHAN K , ROSS R P , STANTON C . Bovine colostrum for veterinary and human health applications: a critical review[J]. Annu Rev Food Sci Technol, 2023, 14, 387- 410. doi: 10.1146/annurev-food-060721-014650
2	BAUMRUCKER C R , MACRINA A L , BRUCKMAIER R M . Colostrogenesis: role and mechanism of the bovine Fc receptor of the neonate (FcRn)[J]. J Mammary Gland Biol Neoplasia, 2021, 26 (4): 419- 453. doi: 10.1007/s10911-021-09506-2
3	YLIOJA C M , ROLF M M , MAMEDOVA L K , et al. Associations between body condition score at parturition and microRNA profile in colostrum of dairy cows as evaluated by paired mapping programs[J]. J Dairy Sci, 2019, 102 (12): 11609- 11621. doi: 10.3168/jds.2019-16675
4	CHEN X , BA Y , MA L J , et al. Characterization of microRNAs in serum: a novel class of biomarkers for diagnosis of cancer and other diseases[J]. Cell Res, 2008, 18 (10): 997- 1006. doi: 10.1038/cr.2008.282
5	LODISH H F , ZHOU B Y , LIU G , et al. Micromanagement of the immune system by microRNAs[J]. Nat Rev Immunol, 2008, 8 (2): 120- 130. doi: 10.1038/nri2252
6	LEE R C , AMBROS V . An extensive class of small RNAs in Caenorhabditis elegans[J]. Science, 2001, 294 (5543): 862- 864. doi: 10.1126/science.1065329
7	MOSS E G . MicroRNAs: hidden in the genome[J]. Curr Biol, 2002, 12 (4): R138- R140. doi: 10.1016/S0960-9822(02)00708-X
8	BUCHAN J R , PARKER R . The two faces of miRNA[J]. Science, 2007, 318 (5858): 1877- 1878. doi: 10.1126/science.1152623
9	ZOU Q P , LIANG Y , LUO H B , et al. miRNA-mediated RNAa by targeting enhancers[J]. Adv Exp Med Biol, 2017, 983, 113- 125.
10	YIN J Q , ZHAO R C , MORRIS K V . Profiling microRNA expression with microarrays[J]. Trends Biotechnol, 2008, 26 (2): 70- 76. doi: 10.1016/j.tibtech.2007.11.007
11	MEHTA J P . Sequencing small RNA: introduction and data analysis fundamentals[J]. Methods Mol Biol, 2014, 1182, 93- 103.
12	HUE D T , PETROVSKI K , CHEN T , et al. Analysis of immune-related microRNAs in cows and newborn calves[J]. J Dairy Sci, 2023, 106 (4): 2866- 2878. doi: 10.3168/jds.2022-22398
13	LI R , DUDEMAINE P L , ZHAO X , et al. Comparative analysis of the miRNome of bovine milk fat, whey and cells[J]. PLoS One, 2016, 11 (4): e0154129. doi: 10.1371/journal.pone.0154129
14	HATA T , MURAKAMI K , NAKATANI H , et al. Isolation of bovine milk-derived microvesicles carrying mRNAs and microRNAs[J]. Biochem Biophys Res Commun, 2010, 396 (2): 528- 533. doi: 10.1016/j.bbrc.2010.04.135
15	LI Z J , LAN X Y , GUO W J , et al. Comparative transcriptome profiling of dairy goat micrornas from dry period and peak lactation mammary gland tissues[J]. PLoS One, 2012, 7 (12): e52388. doi: 10.1371/journal.pone.0052388
16	ALSAWEED M , LAI C T , HARTMANN P E , et al. Human milk miRNAs primarily originate from the mammary gland resulting in unique miRNA profiles of fractionated milk[J]. Sci Rep, 2016, 6, 20680. doi: 10.1038/srep20680
17	CHANDLER T L , NEWMAN A , CHA J E , et al. Leukocytes, microRNA, and complement activity in raw, heat-treated, and frozen colostrum and their dynamics as colostrum transitions to mature milk in dairy cows[J]. J Dairy Sci, 2023, 106 (7): 4918- 4931. doi: 10.3168/jds.2022-22876
18	IZUMI H , KOSAKA N , SHIMIZU T , et al. Bovine milk contains microRNA and messenger RNA that are stable under degradative conditions[J]. J Dairy Sci, 2012, 95 (9): 4831- 4841. doi: 10.3168/jds.2012-5489
19	LI Z , LIU H Y , JIN X L , et al. Expression profiles of microRNAs from lactating and non-lactating bovine mammary glands and identification of miRNA related to lactation[J]. BMC Genomics, 2012, 13, 731. doi: 10.1186/1471-2164-13-731
20	KOSAKA N , IZUMI H , SEKINE K , et al. microRNA as a new immune-regulatory agent in breast milk[J]. Silence, 2010, 1 (1): 7. doi: 10.1186/1758-907X-1-7
21	VICKERS K C , PALMISANO B T , SHOUCRI B M , et al. MicroRNAs are transported in plasma and delivered to recipient cells by high-density lipoproteins[J]. Nat Cell Biol, 2011, 13 (4): 423- 433. doi: 10.1038/ncb2210
22	SUN Q , CHEN X , YU J X , et al. Immune modulatory function of abundant immune-related microRNAs in microvesicles from bovine colostrum[J]. Protein Cell, 2013, 4 (3): 197- 210. doi: 10.1007/s13238-013-2119-9
23	SIMONSEN J B . What are we looking at?Extracellular vesicles, lipoproteins, or both?[J]. Circ Res, 2017, 121 (8): 920- 922. doi: 10.1161/CIRCRESAHA.117.311767
24	GALLIER S , VOCKING K , POST J A , et al. A novel infant milk formula concept: mimicking the human milk fat globule structure[J]. Colloids Surf B: Biointerfaces, 2015, 136, 329- 339. doi: 10.1016/j.colsurfb.2015.09.024
25	丁军, 付子琳, 和俊豪, 等. 乳源外泌体研究进展[J]. 畜牧兽医学报, 2022, 53 (4): 1019- 1029. doi: 10.11843/j.issn.0366-6964.2022.04.003
	DING J , FU Z L , HE J H , et al. Research progress of milk-derived exosomes[J]. Acta Veterinaria et Zootechnica Sinica, 2022, 53 (4): 1019- 1029. doi: 10.11843/j.issn.0366-6964.2022.04.003
26	CHEN X , GAO C , LI H J , et al. Identification and characterization of microRNAs in raw milk during different periods of lactation, commercial fluid, and powdered milk products[J]. Cell Res, 2010, 20 (10): 1128- 1137. doi: 10.1038/cr.2010.80
27	KIRCHNER B , BUSCHMANN D , PAUL V , et al. Postprandial transfer of colostral extracellular vesicles and their protein and miRNA cargo in neonatal calves[J]. PLoS One, 2020, 15 (2): e0229606. doi: 10.1371/journal.pone.0229606
28	HOU J X , AN X P , SONG Y X , et al. Detection and comparison of microRNAs in the caprine mammary gland tissues of colostrum and common milk stages[J]. BMC Genet, 2017, 18 (1): 38. doi: 10.1186/s12863-017-0498-2
29	YUN B , KIM Y , PARK D J , et al. Comparative analysis of dietary exosome-derived microRNAs from human, bovine and caprine colostrum and mature milk[J]. J Anim Sci Technol, 2021, 63 (3): 593- 602. doi: 10.5187/jast.2021.e39
30	MA T , LI W , CHEN Y , et al. Assessment of microRNA profiles in small extracellular vesicles isolated from bovine colostrum with different immunoglobulin G concentrations[J]. JDS Commun, 2022, 3 (5): 328- 333. doi: 10.3168/jdsc.2022-0225
31	KAHN S , LIAO Y L , DU X G , et al. Exosomal micrornas in milk from mothers delivering preterm infants survive in vitro digestion and are taken up by human intestinal cells[J]. Mol Nutr Food Res, 2018, 62 (11): e1701050. doi: 10.1002/mnfr.201701050
32	QUAN S Y , NAN X M , WANG K , et al. Characterization of sheep milk extracellular vesicle-mirna by sequencing and comparison with cow milk[J]. Animals (Basel), 2020, 10 (2): 331.
33	GU Y R , LI M Z , WANG T , et al. Lactation-related microRNA expression profiles of porcine breast milk exosomes[J]. PLoS One, 2012, 7 (8): e43691. doi: 10.1371/journal.pone.0043691
34	ÖZDEMIR S . Identification and comparison of exosomal microRNAs in the milk and colostrum of two different cow breeds[J]. Gene, 2020, 743, 144609. doi: 10.1016/j.gene.2020.144609
35	QUAN S Y , NAN X M , WANG K , et al. Replacement of forage fiber with non-forage fiber sources in dairy cow diets changes milk extracellular vesicle-miRNA expression[J]. Food Funct, 2020, 11 (3): 2154- 2162. doi: 10.1039/C9FO03097B
36	ZHANG X L , CHENG Z X , WANG L X , et al. miR-21-3p centric regulatory network in dairy cow mammary epithelial cell proliferation[J]. J Agric Food Chem, 2019, 67 (40): 11137- 11147. doi: 10.1021/acs.jafc.9b04059
37	LI X H , JIANG P , YU H B , et al. miR-21-3p targets Elovl5 and regulates triglyceride production in mammary epithelial cells of cow[J]. DNA Cell Biol, 2019, 38 (4): 352- 357. doi: 10.1089/dna.2018.4409
38	LIAN S , GUO J R , NAN X M , et al. MicroRNA Bta-miR-181a regulates the biosynthesis of bovine milk fat by targeting ACSL1[J]. J Dairy Sci, 2016, 99 (5): 3916- 3924. doi: 10.3168/jds.2015-10484
39	HEINZ R E , RUDOLPH M C , RAMANATHAN P , et al. Constitutive expression of microRNA-150 in mammary epithelium suppresses secretory activation and impairs de novo lipogenesis[J]. Development, 2016, 143 (22): 4236- 4248. doi: 10.1242/dev.139642
40	SUN Y J , XIA H L , LU X B , et al. MicroRNA-141 participates in milk lipid metabolism by targeting SIRT1 in bovine mammary epithelial cells[J]. Anim Prod Sci, 2020, 60 (16): 1877- 1884. doi: 10.1071/AN19593
41	LIN X Z , LUO J , ZHANG L P , et al. miR-103 controls milk fat accumulation in goat (Capra hircus) mammary gland during lactation[J]. PLoS One, 2013, 8 (11): e79258. doi: 10.1371/journal.pone.0079258
42	CHEN Z , LUO J , SUN S , et al. miR-148a and miR-17-5p synergistically regulate milk TAG synthesis via PPARGC1A and PPARA in goat mammary epithelial cells[J]. RNA Biol, 2017, 14 (3): 326- 338. doi: 10.1080/15476286.2016.1276149
43	WANG X P , LUORENG Z M , ZAN L S , et al. Bovine miR-146a regulates inflammatory cytokines of bovine mammary epithelial cells via targeting the TRAF6 gene[J]. J Dairy Sci, 2017, 100 (9): 7648- 7658. doi: 10.3168/jds.2017-12630
44	ZHOU M , BARKEMA H W , GAO J , et al. MicroRNA miR-223 modulates NLRP3 and Keap1, mitigating lipopolysaccharide-induced inflammation and oxidative stress in bovine mammary epithelial cells and murine mammary glands[J]. Vet Res, 2023, 54 (1): 78. doi: 10.1186/s13567-023-01206-5
45	MA T , MENG Z , GHAFFARI M H , et al. Characterization and profiling of the microRNA in small extracellular vesicles isolated from goat milk samples collected during the first week postpartum[J]. JDS Commun, 2023, 4 (6): 507- 512. doi: 10.3168/jdsc.2022-0369
46	KHANAM A , NGU A , ZEMPLENI J . Bioavailability of orally administered small extracellular vesicles from bovine milk in C57BL/6J mice[J]. Int J Pharm, 2023, 639, 122974. doi: 10.1016/j.ijpharm.2023.122974
47	PECK B C E , SINCAVAGE J , FEINSTEIN S , et al. miR-30 family controls proliferation and differentiation of intestinal epithelial cell models by directing a broad gene expression program that includes Sox9 and the ubiquitin ligase pathway[J]. J Biol Chem, 2016, 291 (31): 15975- 15984. doi: 10.1074/jbc.M116.733733
48	DEY B K , GAGAN J , YAN Z , et al. miR-26a is required for skeletal muscle differentiation and regeneration in mice[J]. Genes Dev, 2012, 26 (19): 2180- 2191. doi: 10.1101/gad.198085.112
49	RIESS M , FUCHS N V , IDICA A , et al. Interferons induce expression of SAMHD1 in monocytes through down-regulation of miR-181a and miR-30a[J]. J Biol Chem, 2017, 292 (1): 264- 277. doi: 10.1074/jbc.M116.752584
50	ZHANG W , FU X H , XIE J S , et al. miR-26a attenuates colitis and colitis-associated cancer by targeting the multiple intestinal inflammatory pathways[J]. Mol Ther Nucleic Acids, 2021, 24, 264- 273. doi: 10.1016/j.omtn.2021.02.029
51	MUN D , KANG M K Y , SHIN M , et al. Alleviation of DSS-induced colitis via bovine colostrum-derived extracellular vesicles with microRNA let-7a-5p is mediated by regulating Akkermansia and β-hydroxybutyrate in gut environments[J]. Microbiol Spectr, 2023, 11 (6): e0012123. doi: 10.1128/spectrum.00121-23
52	GONZALEZ-MARTIN A , ADAMS B D , LAI M Y , et al. The microRNA miR-148a functions as a critical regulator of B cell tolerance and autoimmunity[J]. Nat Immunol, 2016, 17 (4): 433- 440. doi: 10.1038/ni.3385
53	TONG L J , ZHANG S T , LIU Q Q , et al. Milk-derived extracellular vesicles protect intestinal barrier integrity in the gut-liver axis[J]. Sci Adv, 2023, 9 (15): eade5041. doi: 10.1126/sciadv.ade5041
54	JOHNSTON D G W , WILLIAMS M A , THAISS C A , et al. Loss of MicroRNA-21 influences the gut microbiota, causing reduced susceptibility in a murine model of colitis[J]. J Crohns Colitis, 2018, 12 (7): 835- 848. doi: 10.1093/ecco-jcc/jjy038

[1]	Quanjun CHEN, Zuo WANG, Fachun WAN, Weijun SHEN. Functional Characteristics and Related Regulation of Glucose Sensing Receptors and Transporters in the Gastrointestinal Tract of Ruminants [J]. Acta Veterinaria et Zootechnica Sinica, 2024, 55(11): 4819-4828.
[2]	Helin LI, Yufen JIANG, Na CHENG, Yuchen HAN, Xiaoying HUO, Hongding SU, Yue CHANG, Yuzhu FANG, Pei WANG, Baoyu JIA, Hongjiang WEI, Wenmin CHENG. The Study of Regulatory Effect of Differentially Expressed microRNAs on the Npm2 Expression in Pig Oocytes [J]. Acta Veterinaria et Zootechnica Sinica, 2024, 55(11): 5035-5049.
[3]	Ruixue DENG, Chunrong PAN, Xueliang ZHU, Linjie HU, Yuefeng SUN, Qiaoying ZENG, Xuelian MENG. Suppressive Effect of Histone Deacetylase Inhibitor MGCD0103 on Peste Des Petits Rumants Virus Replication in vitro [J]. Acta Veterinaria et Zootechnica Sinica, 2024, 55(10): 4542-4552.
[4]	FAN Dingkun, ZHANG Jixian, FU Yuze, MA Tao, BI Yanliang, ZHANG Naifeng. Research Progress of Ruminant Microbial Culturomics [J]. Acta Veterinaria et Zootechnica Sinica, 2024, 55(1): 51-58.
[5]	MA Shujuan, XU Yijie, HE Ke, MA Ruifeng, ZHU Ying. Molecular Evolution and Expression Patterns of a Multigene Family of Toll-like Receptors in Ruminants [J]. Acta Veterinaria et Zootechnica Sinica, 2023, 54(9): 3722-3734.
[6]	YANG Yue, WANG Rui, GAN Yuan, HAO Fei, XIE Xing, ZHANG Lei, SHAO Guoqing, MENG Qingguo, CHEN Rong, FENG Zhixin. Purification and Identification of SIgA in Porcine Colostrum based on Tandem Affinity Chromatography [J]. Acta Veterinaria et Zootechnica Sinica, 2023, 54(9): 3884-3894.
[7]	YU Shixiong, WEI Lingyun, XU Tiantian, JIAO Jinzhen, JIANG Linshu, HE Zhixiong. Research Progress of Intestinal Microbial Colonization Pattern in Young Ruminants and Its Nutritional Regulation [J]. Acta Veterinaria et Zootechnica Sinica, 2023, 54(7): 2701-2707.
[8]	WANG Yu, GAO Yueyi, GAO Jinyuan, LIU Weijie, XU Huilin, XUE Qinghong. Establishment of Reverse Genetics System of Peste des petits Ruminants Virus Clone9 Strain [J]. Acta Veterinaria et Zootechnica Sinica, 2023, 54(7): 2956-2963.
[9]	ZHAO Wei, Mahmoud M. Abdelsattar, CHAI Jianmin, WANG Xin, DIAO Qiyu, ZHANG Naifeng. Research Progress of Rumen Microbiota Transplantation and Its Application [J]. Acta Veterinaria et Zootechnica Sinica, 2023, 54(5): 1792-1803.
[10]	DU Haidong, NA Renhua. Study on Gastrointestinal Epithelial Barrier Function and Interaction with Microorganisms in Ruminants [J]. Acta Veterinaria et Zootechnica Sinica, 2023, 54(5): 1804-1814.
[11]	FANG Yuan, HOU Qiaodi, XIANG Chaohui, ZHAO Hongyi, QI Xuefeng. Regulatory Effects of IFITM3 on Proliferation of Peste des Petits Ruminants Virus (PPRV) in Goat Endometrial Epithelial Cells [J]. Acta Veterinaria et Zootechnica Sinica, 2023, 54(5): 2200-2207.
[12]	WANG Lan, HE Mingyu, ZHANG Min, DING Juntao. MicroRNAs Regulate Antiviral Immunity and Viral Replication [J]. Acta Veterinaria et Zootechnica Sinica, 2023, 54(2): 463-472.
[13]	DU Haidong, NA Renhua. Research Progress on Physiological Metabolism and Microbial Changes of Ruminants During Gestation and Lactation and Their Effects on Offspring Development [J]. Acta Veterinaria et Zootechnica Sinica, 2023, 54(11): 4458-4467.
[14]	WANG Yiqun, LIU Zupei, LI Yating, ZHANG Haisen, LI Dan, JIN Yaping, CHEN Huatao. The Dairy Cow NR1D1 Gene’s Eukaryotic Expression Vector Construction, Expression Profile and Its Ovarian Localization [J]. Acta Veterinaria et Zootechnica Sinica, 2023, 54(1): 133-145.
[15]	PAN Chunrong, DENG Ruixue, HU Linjie, ZHU Xueliang, SUN Yuefeng, WANG Guirong, MENG Xuelian. Effect of Histone Deacetylase Inhibitors on Peste Des Petits Ruminants Virus Replication [J]. Acta Veterinaria et Zootechnica Sinica, 2022, 53(7): 2307-2316.

Research Progress on Composition and Function of Colostral MicroRNA in Ruminants

RichHTML

PDF (PC)

Knowledge

Abstract

Cite this article

share this article

Figures/Tables 3

References 54

Related Articles 15

Recommended Articles

Metrics

Comments