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.