The cover image illustrates the Lugou Bridge, which is one of the most famous scenic spots and the oldest existing stone arch bridge in Beijing. The stone lions carved above the stone guardrail are in different shapes, just like the heterogeneous fate choices of hemogenic endothelial cells on the way to become hematopoietic stem cells. See page 448–463 by Jun Xia et al. for details.

The artwork references history by depicting the concept of the Confucian “Doctrine of the Mean”. Tilting vessel, also known as yòu zuò zhī qì, is an ancient Chinese vessel that needs to be filled with an appropriate amount of water to maintain its upright position. Overfilling or underfilling the vessel can render it unstable. Likewise, CAR tonic signaling must be fine-tuned to ensure that it is neither too weak nor too robust, thereby optimizing CAR-T cell fitness. See page 341–354 by Jian Chen et al. for details.

The image shows a Chinese fairy tale, the “Blue Bird as a messenger”, wherein Blue Bird delivers messages for Xiwangmu (the Immortal Queen Mother). The Blue Bird is reminiscent of famsin, a novel gut-secreted hormone, which mediates communication between the intestine and other organs to promote metabolic adaptations to fasting and enhance animal survival when food is scarce. See page 273–287 by Aijun Long et al. for details.

A study revealed that SARS-CoV-2 generates Z-RNA during virus infection. The left-handed Z-RNA ignites ZBP1-RIPK3-MLKL necroptosis pathway. The RIPK3 scaffolding functionality additionally promotes chemokine production to magnify the inflammatory responses. These synergistically lead to SARS-CoV-2-triggered lung damage and COVID-19. See page 201–214 by Shufen Li et al. for details.

A study identified a novel APOE4-specific receptor LilrB3. A butterfly-like Cryo-EM structure of the complex reveals the details of how the immune “checkpoint” receptor LilrB3 recognizes APOE4. Upon binding, it will induce microglia cell into an Alzheimer Disease-associated status. See page 116–130 by Jiayao Zhou et al. for details.

The image tells a fable story, ‘dirty partner’. A wolf and a jackal often do evil things in collusion with each other. In KRAS-driven cancers, KRAS mutations are like wolves and RASON behaves like a jackal. KRAS mutations initiate tumour formation and promote tumour progression which are enhanced by RASON, a novel protein encoded by long non-coding RNA, LINC00673, and overexpressed in tumour to regulate RAS activity. Cover art is contributed by Chao Yan. See page 30–45 by Rongjie Cheng et al. for details.