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Brain health is an important research direction of neuroscience. In addition to the effects of diseases, we cannot ignore the negative effect of aging on brain health. There have been many studies on brain aging, but only a few have used dynamic models to analyze differences in micro brain characteristics in healthy people. In this article, we use the relaxed mean-field model (rMFM) to study the effects of normal aging. Two main parameters of this model are the recurrent connection strength and subcortical input strength. The sensitivity of the rMFM to the initial values of the parameters has not been fully discussed in previous research. We examine this issue through repeated numerical experiments and obtain a reasonable initial parameter range for this model. Differences in recurrent connection strength and subcortical input strength due to aging have also not been studied previously. We use statistical methods to find the regions of interest (ROIs) exhibiting significant differences between young and old groups. Further, we carry out a difference analysis on the process of change of these ROIs on a more detailed timescale. We find that even with the same final results, the trends of change in these ROIs are different. This shows that to develop possible methods to prevent or delay brain damage due to aging, more attention needs to be paid to the trends of change of different ROIs, not just the final results.

Additional file 1: Table S1. Strains and plasmids used in this study. Table S2. Primers used in this study. Fig. S1. Predict the transmembrane domain of MenA in B. subtilis. Fig. S2. Colony PCR of the engineered strain BS011.Fig. S3. Fluorescence intensity curve of amplified pos5P. Note S1. Deducing the overall stoichiometry of glycerol conversion to DMK-7 in B. subtilis. Note S2. Abbreviations. Note S3. Supplementary sequence.

Additional file 1: Figure S1. Terpenoid backbone biosynthesis of E. meningoseptica sp. F2 based on KEGG pathway assignment. A-CoA acetyl coenzyme A; AA-CoA acetoacetyl-CoA; HMG-CoA hydroxymethylglutaryl-CoA; IPP isopentenyl diphosphate; DMAPP dimethylallyl diphosphate; GPP geranyl diphosphate; FPP farnesyl diphosphate; GGPP geranylgeranyl diphosphate; OPP octaprenyl diphosphate. Figure S2. Chromatography of MK-n (n = 4, 5, 6, 7, 8) by HPLC system. A The sample was extracted from monoculture system of E. meningoseptica, B the sample was extracted from coculture system of E. meningoseptica and E. coli. Figure S3. A The purification of GB1-OPPS. M: protein molecular weight marker; lane 1: The total cell lysate supernatant flows through the column. Lanes 2���6: wash fractions with 10, 15, 20, 25, 30 mM imidazole, respectively. Lanes 7���8: Elution fractions with 250 mM imidazole, respectively. B Purified GB1-EmOPPS proteins was confirmed by mass spectrometry. Figure S4. Enzymatic assay of EmOPPS in vivo and vitro. A, B LC-MS analysis of the GB1-EmOPPS products with farnesyl diphosphate (FPP) and isopentenyl diphosphate (IPP) as substrates after hydrolyzation. C, D J01 strains could accumulated MK-n (n = 6, 7, 8). LC-MS analysis of the production of this strains. A, C Horizontal graphs refer to result of HPLC and vertical graphs B, D refer to mass spectra. Figure S5. The comparison of the mass spectrum of the fermentation results of the J01, J02 strain with that of the MK-n (n = 4, 5, 6, 7) standard, A MK-4, MK-5, MK-6, and MK-7 standard, respectively, for MS analysis. B The mass spectrum results of monocultured E. coli producing MK-8 as a reference. Figure S6. Analysis and identification of mevalonolactone by GC-MS from fermentation supernatant. Figure S7. The monoculture of different E. coli strains as comparison. The error bars represent the standard error of at least three biological replicates. Statistical significance (p < 0.01) compared to the original strains. Figure S8. Visualization of different inocula by confocal laser scanning microscope. A E. meningoseptica. B E. coli. C, D E. meningoseptica and E. coli co-culture. Red circles surround the connected E. meningoseptica and E. coli cells in view. C Bright field; D fluorescence image merged image. Table S1. Masses and identities of LC/MS analyses results. Table S2. Oligonucleotide primers used in this study.