Early distinction of bipolar disorder (BD) from major depressive disorder (MDD) is difficult since no tools are available to estimate the risk of BD. Niu et al. have developed a nomogram centered on oxidative stress injury-related biomarkers, which could help in the individualized prediction of BD. In this cover, the scale, which is out-of-balance, represents BD, a disease that appears to consist of depressive episodes and manic episodes but is factually characterized by sustained unstable emotional states. The ice and fire at opposite ends of the scale represent the poles of bipolar disorder: ice represents the depressive phase, while fire represents the manic phase. Various stones represent the underlying mechanisms affecting the onset of BD, which also cause imbalance destroy and the scale (the onset of BD). See pages 979–991. (Cover designed by Drs Yuncheng Zhu, Zhiang Niu, Xiaohui Wu, and Yiru Fang).