A schematic showing the underlying mechanisms of the inhibitory effects of Icariside II (ICS II) on cerebral ischemia/reperfusion (I/R)-induced apoptosis in rats. ICS II attenuates cerebral I/R-induced blood–brain barrier (BBB) dysfunction by inhibiting neuronal apoptosis in rats in a manner involving regulation of the MMP9/TIMP1 balance. See the article in pages 1547–1556.

In the current study, a simple, quick and efficient method was established to perform genome editing via CRISPR/Cas 9 system in induced pluripotent stem cells (iPSCs). With this method, genome edited cell line can be obtained within two weeks. This method can be easily applied to other cells too.

Cartoon depicting various representative molecules in the Ca2+ channel complex that regulate Ca2+ transfer at mitochondriaassociated ER membranes (MAMs). ER endoplasmic reticulum, IMM inner mitochondrial membrane, OMM outer mitochondrial membrane, MFN1/2 mitofusin 1/2, MCU mitochondrial calcium uniporter, NCLX Na+/Ca2+/Li+ permeable exchanger, VDAC1 voltage-dependent anion channel, IP3R inositol 1,4,5-triphosphate receptor, GRP75 chaperone 75 kDa glucose-regulated protein, FUNDC1 FUN14 domain containing 1, Sig-1R the sigma-1 receptor, PTPIP51 protein tyrosine phosphatase-interacting protein 51, and VAPB vesicle-associated membrane proteinassociated protein B.

Shuanghuanglian preparations and bioactive ingredients including baicalin and baicalein dose-dependently inhibited SARS-CoV-2 3CL protease and the replication of SARS-CoV-2 in cells. The crystal structure of SARS-CoV-2 3CL protease in complex with baicalein revealed a unique binding mode of this bioflavonoid as the first noncovalent, nonpeptidomimetic inhibitor of the protease.

The expression of FSHR in depression-related brain regions. a The CA1 region of the mouse hippocampus. b The CA3 region of mouse hippocampus. c The DG of the mouse hippocampus. d The cortex. e The nucleus accumbens. f The amygdala. g The prefrontal cortex. h The bed nucleus of the stria terminalis. i The lateral habenula. FSHR (red), NeuN (green, a marker of neurons), and DAPI (blue) immunofluorescence was detected under a fluorescence microscope. See the article in pages 1033–1040.

Nezha, who is the incarnation of lotus, is believed to be a demon slayer with magic power in Chinese mythology. We thus select Nezha for illustration of nanomedicine for cancer immunotherapy by regulating the tumor cells and the immune cells such as dendritic cells and T lymphocytes.

Schematic representation of possible mechanisms of aminoglycosides (AGs)-induced nephrotoxicity and ototoxicity. The schematic mainly includes three parts: (1) AGs are predominantly distributed in the mitochondria of renal tubular cells and inner ear hair cell-like cells; (2) AGs inhibit mitochondrial electron transport chain (ETC) complexes I, IV, and V; and (3) AGs inhibit the PGC-1α-NRF1-TFAM pathway, which may repress mitochondrial biosynthesis. See the article in pages 866-878.

Precision medicine based on molecular signatures of patients has shown increasing value in cancer treatment. This review summarized the common strategies of CRISPR-cas9 screening and the application of this screening in precision medicine including identification of new targets and biomarkers and elucidation of mechanisms leading to drug resistance.

Schematic illustration of cholinergic regulation in the striatum. ChIs exert influences on striatal function by regulating multiple targets (arrows). Activation of ChIs can reduce glutamatergic transmission to MSNs of both pathways via M2 and M4 mAChRs, trigger dopamine release from their terminals through nAChRs and generate feedback inhibition via M4 receptors. Although MSNs of both the direct and indirect pathways express M1 receptors, which increase the excitability of a neuron when activated, the direct pathway is inhibited by acetylcholine because of the high expression level of M4 receptors. See the article in pages 453–463.

Acetyl-CoA carboxylases (ACC1/ACC2) are important drug targets for NASH treatment. Gao et al developed WZ66, a novel inhibitor of ACCs that enables the decrease of de novo lipogenesis, the inactivation of Kupffer cells and hepatic stellate cells. WZ66 also altered the plasma lipids profile and gut microbiota composition.

A schema for the anti-neuroinflammation effect of isosibiricin, a natural coumarin compound from medicinal plant Murraya exotica. Isosibiricin inhibits microglia-mediated neuroinflammation by selectively targeting dopamine D1/2 receptor-dependent NLRP3/caspase-1 inflammasome pathway. See the article in pages 173–180.

Nicotine orchestrates activation of distinct repertoire of nicotinic acetylcholine receptor subtypes in midbrain GABAergic and dopaminergic neurons and striatal dopaminergic terminals, drives burst firing in dopaminergic neurons, and gates phasic release of dopamine in the striatum. These processes constitute the signaling pathway that conveys rewarding effects of nicotine. See the article in pages 1-9.