Under M2 polarizing conditions (Fig. 7D–F, Supplemental Table S2, Data File S5C,D), 65–79*SE was predicted to exert an activation effect on several pro-inflammatory or pro-angiogenic upstream regulators, including Egr1, Irf3, Irf7, Epas1, Gli1 and NF-κB, and an inhibitory effect on anti-RA, anti-osteoclastogenic or anti-angiogenic upstream regulators, such as Tcf3 and Runx1 (Fig. 7D). Here, EPAS1 is linked to rheumatoid arthritis.