*4.8. Statistical Analysis*

All the transcriptome and metabolome samples were designed for three biological replicates. Statistical analyses were conducted using the SPSS 22.0 software (IBM, Chicago, IL, USA). An independent samples *t*-test was used for statistical evaluations between the control and treatment groups.

**Supplementary Materials:** Supplementary materials can be found at http://www.mdpi.com/1422-0067/21/2/564/s1. Figure S1: Overlapping analysis of the TIC in QC samples. The x-axis represents the retention time (min) of metabolite detection, and the y-axis represents the intensity of ion current (cps: count per second). (A) for ESI<sup>+</sup> mode; (B) for ESI− mode; Table S1: Total identified metabolites in the NM and M growth for six months; Table S2: Recovery test for each analyte; Table S3: Primer designed for qRT-PCR.

**Author Contributions:** Conceptualization, X.C. and Z.M.; Methodology, Y.Z. and Y.L.; Software, Y.Z.; Validation, Y.Z.; Resources, Z.M. and S.G.; Data curation, Y.Z., Y.L. and X.C.; Writing—Original draft preparation, Y.Z.; Writing—Review and editing, Z.M. and S.G.; Supervision, X.C.; Funding acquisition, S.G. and X.C. All authors have read and agreed to the published version of the manuscript.

**Funding:** This research was funded by the CAMS the Innovation Fund for Medical Sciences (CIFMS) (2017-I2M-3-013), the National Natural Science Foundation of China (81573526), and the Peking Union Medical College Discipline Construction Project (201920100901).

**Acknowledgments:** We thank Ruibin Hu from the Institute of Chemistry, Chinese Academy of Sciences for his help for data analysis and article logic structure; We thank Yung-I Lee from Biology Department, National Museum of Natural Science (Taiwan) for providing guidance for semi-thin section observation experiment.

**Conflicts of Interest:** The authors declare no conflict of interest.
