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Additional file 1: Figure S1. Effects of TNEA and its composing acupoints on the levels of APP/CTFs/Aβ in 5XFAD mice. (A) Representative Western blots showed the levels of full-length APP (FlAPP) and carboxy-terminal fragments (CTFs) in the prefrontal cortex (PFC) of mice from each group. (B) Data are quantified as mean ± SEM (male, n = 5-7). **p0.05) vs. 5xFAD group, analyzed by unpaired t-test or Mann–Whitney U test. (C) Representative Western blots showed the levels of Aβ in the hippocampus (HI) of mice from each group (n =3). The combined quantification data are shown in Fig. 1F. Figure S2. Activation of NLRP3 inflammasome in the hippocampus of 5xFAD mice. (A, C) Representative Western blots showed the levels of phosphorylated (p-)RELA (p65), NLRP3, CASP1 and IL1B in the hippocampi (HI) of 5xFAD mice at the age of 8 months (A) and 13 months (C). (B, D) Data are quantified as mean ± SEM (male, n = 6). *p0.05) vs. WT group, analyzed by unpaired t-test, unpaired t-test with Welch's correction, or Mann–Whitney U test. Figure S3. Negative controls for the IHC of ASC, NLRP3, SQSTM1 and CTSD. The slides from each group were stained with each 1st antibody at the same dilution as performed in Fig. 3 and 4, but without 2nd antibodies; or stained with 2nd antibodies at the same dilution as performed in Fig. 3 and 4, but without 1st antibodies. Images were visualized at the same settings as performed in Fig. 3 and 4. Scale bar: 100 μm. Figure S4. Effects of TNEA and its composing acupoints on TFEB activation in the prefrontal cortex of 5XFAD mice. (A) Representative Western blots showed the levels of phosphorylated (p-) TFEB (S142) in the prefrontal cortex (PFC) of mice from each group. (B) Data are quantified as mean ± SEM (male, n = 5-7). **p0.05) vs. 5xFAD group analyzed by unpaired t-test, unpaired t-test with Welch's correction, or Mann–Whitney U test. Figure S5. Effects of the composing acupoints of TNEA on TFE3 activation in the hippocampi of 5xFAD mice. (A) Representative Western blots showed the levels of cytosolic (Cyt) /nuclear (Nuc) levels of TFE3 in the hippocampi (HI) of mice from each group. GAPDH and H3F3A (H3 histone) were used as cytosolic and nuclear loading controls, respectively. (B) Data were quantified as mean ± SEM (male, n=5-7). *p0.05) vs. 5xFAD group analyzed by unpaired t-test. Figure S6. Unprocessed scans of all immunoblots.