Treatment with mesenchymal stem cells (MSCs) can improve the outcomes of COVID-19 patients by restoring a harmonious homeostasis of the immune microenvironment disrupted by SARS-CoV-2 attack and promoting the immune system recovery. This process suggests a new interpretation to the story of “Moses divided the Red Sea” in the Exodus of the Bible: MSC therapy represents a promising new way in the treatment of COVID-19. See page 1244-1262 by Rongjia Zhu et al. for details.

The SARS-CoV-2 attacks host cells offensively via the respiratory system. In the asymptomatic subjects, the immune cells are active and finally kill the virus (right); whereas in the presymptomatic subjects, the immune cells are slack, the virus evades the attack of the immune system and amplifies quickly, and eventually causes the host to suffer from COVID-19 (left). The image is designed by Shanhe Yu and edited by Lehua Huang. See page 1148-1162 by Shanhe Yu et al. for details.

A SARS-CoV-2 virion (monster egg, inside of which is a monster representing viral RNA) touches host-cell plasma membrane (blue bending ground) producing tensile force (children’s pulling), which not only strengthens spike–ACE2 (children) recognition, but also accelerates the S1/S2 separation to boost viral fusion machinery. See page 1047-1060 by Wei Hu et al. for details.

The LD·ATTEC (the shining elixir) can harness autophagy (the self-eating circular dragons) to degrade lipid droplets. After taking the LD·ATTEC, the over-weighted beauty, Chang’e (left), became a slim goddess (right) and flew into the sky above the clouds. LD·ATTEC: autophagy-tethering compounds (ATTEC) targeting lipid-droplets (LD). See page 965–979 by Yuhua Fu et al. for details.

SARS-CoV-2 envelope protein (2-E) attacks host cells offensively via forming a type of cation channels on biological membranes. The newly identified channel blocker BE-33 exhibits excellent anti-viral activity in mice infection model. 2-E channel is a promising drug target against SARS-CoV-2.See page 847-860 by Bingqing Xia et al. for details.

The Monkey King is reminiscent of the embryonic skeletal stem and progenitor cells (eSSPCs) that localize in the perichondrial region of the developing long bones (mimicked by the Golden Cudgel), which self-renew and give rise to skeletal lineage cells as revealed by our single-cell transcriptomic and functional analyses. See page 742-757 by Jian He et al. for details.

When synthetic biology meets RNAi therapy. Programmable genetic circuits (multicolor circles) utilize the liver as tissue chassis and a biogenerator, which can continuously produce and assemble exosome-encapsulated siRNAs (orange balls with spikes) for targeted delivery to multiple organs. See page 631–648 by Zheng Fu et al. for details.

The cover depicts a newly built elevated highway (replicating DNA) that is damaged (mismatch). A worker (MutS-MutL complex) identifies the damage and communicates with the repair department (Exo1) to fix the problem. The columns (buildings) represent chromatin remodeling and DNA metabolic proteins. Designed by Yipin Wu.See page 542-553 by Janice Ortega et al. for details.

Paired Chinese knot, a symbol of unity and cooperation, represents the active state structure of human calcium-sensing receptor (CaSR), a dimeric class C GPCR responsible for maintaining Ca2+ homeostasis in the blood. Structural studies revealed that CaSR is cooperatively activated by calcium ions and L-Trp. See page 383-394 by Shenglong Ling et al. for details.

Buddha or evil, depends on a blinding flash. Neddylation can switch PTEN from a tumor suppressor (Buddha) to a tumor promoter (evil). See page 291-311 by Ping Xie et al. for details.

Formation of ER whorls by COPII machinery is a new type of UPR response. See page 141-156 by Fang Xu et al. for details.

Ca2+-induced (fallen leaves) and phosphatase-checked (shrimps) shuttling of CaMKII (lotuses) enlarges postsynaptic density assembly (larger cluster of fish) and induces structural long-term potentiation.