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The widely prescribed beta blocker carvedilol has strong antiarrhythmic effects on the heart, but the underlying mechanisms have been unclear. Qiang Zhou et al. now show that carvedilol, unlike other beta blockers, is also able to block proarrhythmogenic spontaneous calcium waves by directly inhibiting the calcium release channel RyR2. By generating new carvedilol analogs that inhibit RyR2 but not β-adrenergic receptors, the authors provide evidence that antiarrhythmic therapy might be optimized by combining agents that are individually selective for these two targets.

The cyclin-dependent kinase inhibitors p18 and p27 confer advantage to the propagation of haematopoietic stem cells (HSCs). In this manuscript, the authors demonstrate that p18 is a potent negative regulator of HSC self-renewal, and identify novel small molecules putatively inhibiting p18 that promote HSC growth in culture and mouse transplant assays.

Fluorescent sensors for small biomolecules are needed to shed insight into real-time cellular processes. Here the authors develop RealThiol, a sensor that can quantitatively monitor glutathione dynamics in living cells, and measure increased antioxidant capability of activated neurons and glutathione changes during ferroptosis.

Untethered capsules exhibit clinical promise for diagnosing and treating gastrointestinal diseases. Here, the authors develop small-scale magnetically driven capsules featuring a distinct magnetic soft valve, integrating multiple functional and motion modalities for biomedical applications.

Binning is an essential step in genome-resolved metagenomic analysis in which assembled contigs originating from the same source population are clustered. However it is challenging, especially for low abundance microbial species. Here the authors introduce a toolkit that integrates multiple prominent binning tools and AI for efficient and high-resolution recovery of non-redundant bins from short- and long-read metagenomic sequencing datasets.

The development of dental calculi involves bacteria in local mature biofilms converting the DNA in neutrophil extracellular traps from being degradable by the enzyme DNase I to being degradation resistant.

Two precursor additives improve the performance of tin-based perovskite solar cells, delivering a power conversion efficiency of 15.38% and maintaining 93% of the initial efficiency after 500 h of continuous illumination.

Xue-Jun Zhang and colleagues report genome-wide association analyses identifying six new susceptibility loci in the Chinese population.

Nanoparticles containing immiscible elements can be synthesized under certain experimental conditions.

The most up-to-date combination of results on the properties of the Higgs boson is reported, which indicate that its properties are consistent with the standard model predictions, within the precision achieved to date.

A ferroelectric material is used to switch the uniaxial magnetic anisotropy of an antiferromagnet, with implications for antiferromagnetic spintronics.

The molecular classification and tumour microenvironment in intrahepatic cholangiocarcinoma (iCCA) need further characterisation. Here, the authors perform single cell RNA-sequencing from 14 pairs of iCCA tumours and non-tumour liver tissues and propose S100P and SPP1 as markers for patient classification.

Layered heterostructures are promising photosensitive materials for advanced optoelectronics. Here, the authors introduce an interfacial coassembly method to construct large-scale perylene/grahene oxide (GO) heterobilayer for broadband photoreception and efficient neuromorphics.

Materials with Weyl cones and band gaps coexisting are desired due to their combination of Weyl cones and the tunable and controllable nature of semiconductor. Here, the authors find Weyl-related band structures and semiconducting gap of tellurium.

There is an ongoing need for diagnostic tools that can be used in remote areas. This protocol describes the preparation of a chip-based assay with a simple detector for the analysis of biomarkers in biofluids.

Liang, Yan, Long, Ji et al. find that the origin and dynamics of 5-hydroxymethylcytosine (5hmC) during early development are not conserved between humans and mice and that 5hmC contributes to the activation of human embryonic genes.

Visible-light photocatalysis has evolved as a powerful technique to enable controllable radical reactions and the exploration of new photocatalytic mode for product diversity is of great significance. Herein, the authors present a photo-induced chemoselective 1,2-diheteroarylation of unactivated alkenes utilizing halopyridines and quinolines.

An antimatter hypernucleus formed by an anti-lambda hadron, an antiproton and two antineutrons was observed through its two-body decay after production in ultrarelativistic heavy-ion collisions.

Here, the authors show that the gut commensal Parabacteroides distasonis alleviates insulin resistance via nicotinic acid-intestinal GPR109a axis activation, a process promoted by Dendrobium officinale polysaccharide.

Here, cryo-EM is used to identify an unreported fibril species derived from lab-cultured Bacillus amyloiquefaciens composed of the extracellular serine peptidase Vpr. Fibrillar Vpr is shown to be enzymatically active, suggesting the fibril form represents a strategy of enriching Vpr extracellular activity.

Controlling the kinetics and thermodynamics of electrochemical processes is essential to achieve high-performance multielectron reduction. Here, the authors report laser-induced copper bipyramids with abundant nanograins and controlled tip angles for enhanced multielectron CO₂ and nitrate reduction.

To avoid autoimmunity against the microbiome, plants use PHYTOSULFOKINE RECEPTOR 1-mediated regulation of salicylic acid signalling to tune the plant growth–defence balance in response to microbiota.

Salmonella Typhimurium establishes systemic infection by replicating in host macrophages. Here, Jiang et al. show that infected macrophages exhibit upregulated glycolysis and decreased serine synthesis, leading to accumulation of glycolytic intermediates that promote intracellular replication and virulence of S. Typhimurium.

It has been proposed that, during development, clonally related neurons migrate along the same radial glial fibre to form clusters of functionally similar cells; here, sister neurons in the same radial clone are shown to have similar orientation preferences in mice, providing support for this hypothesis.

A mild electrochemical exfoliation method has been developed to obtain large-size two-dimensional superconductor monolayers with high crystallinity and production yield, which enables the easy fabrication of twisted van der Waals heterostructures and printed films.

Xuejun Zhang and colleagues report a genome-wide association and replication studies for psoriasis, conducted in Chinese populations. They confirm previous associations in MHC and IL12B to psoriasis susceptibility, and report a new association within the LCE gene cluster at 1q21.

Primary open-angle glaucoma (POAG) is highly heritable, yet not well understood from a genetic perspective. Here, the authors perform a meta-analysis of genome-wide association studies in 34,179 POAG cases, identifying 44 previously unreported risk loci and mapping effects across multiple ethnicities.

Neutralizing antibodies are currently one versatile strategy to treat SARS-CoV-2 infection. Here, Li et al. characterize three monoclonal antibodies neutralizing authentic virus infection in vitro and in vivo by targeting the receptor binding domain as evidenced by Cryo-EM.

Mitochondria-associated ER membranes (MAMs) are involved in the regulation of many cellular functions. Here, the authors report that FUNDC1-dependent mitochondria-associated endoplasmic reticulum membranes play an essential role in the process of angiogenesis and neoangiogenesis.

In plants, RNA-directed DNA methylation (RdDM) is a de novo DNA methylation pathway that is responsible for transcriptional silencing of repetitive elements. Here, the authors characterized a new RdDM factor, RDM15, and show that it is required for RdDM-dependent DNA methylation and siRNA accumulation at a subset of RdDM target loci.

As studies continue sequencing with deeper coverage, computational processing of these profiles has become increasingly resource consuming. Here the authors designed an efficient computational method called Chromap to align and preprocess high throughput sequencing data from chromatin profiling techniques, including ChIP-seq, Hi-C, or scATAC-seq, with a major decrease in runtime.

Coronavirus main protease is essential for viral polyprotein processing and maturation. Here Fu et al. report efficient inhibition of SARS-CoV-2 replication using two inhibitors - Boceprevir and GC376 - targeting the active site of the main viral protease.

How the East Asian Summer Monsoon has changed over the Holocene has been debated, as some proxy records disagree with each other. Here, the authors suggest that monsoonal rainfall peaked in the early Holocene, while ecosystem responses peaked in the mid-Holocene, explaining the differences between records.

The extracellular matrix (ECM) can influence tumor growth and its response to therapy. Here, the authors develop a fibrinogen and thrombin based artificial ECM that can starve tumours and prevent dissemination of cancer cells.

The recent advances in accelerated polymerization of N-carboxyanhydrides (NCAs) enrich the toolbox to prepare well-defined polypeptide materials. Here the authors use crown ethers to catalyze the polymerization of NCA initiated by conventional primary amine initiators in solvents with low polarity and low hydrogen-bonding ability.

The mechanisms involved in regeneration of the spinal cord after injury are unclear. Here, the authors show that a subpopulation of intraspinal serotonergic neurons localized at the injury site stimulates axonal regrowth of interneurons via 5-HT1B receptor, resulting in recovery of function following SCI in zebrafish.

Research on permafrost microbial communities is crucial for predicting the response of permafrost ecosystems to climate change. Here, Kang et al. provide insights into the structure and functional potential of permafrost microbial communities by analyzing 16S rRNA gene sequence data and metagenomic data obtained from an ∼1000 km transect on the Tibetan Plateau.

Although the efficacy of chimaeric antigen receptor (CAR) T cell therapy has been demonstrated in relapsed/refractory diffuse large B-cell lymphoma (DLBCL), it has not been investigated in primary refractory DLBCL. In this phase I clinical trial, the authors report on the safety and efficacy of relmacabtagene autoleucel, a CD19-specific CAR T cell product, and demonstrate using single-cell RNA sequencing that cholesterol efflux from macrophages may impair CAR T cell responses in this context.

Selective electrochemical CO₂ reduction (CO₂RR) in strong acids remains challenging due to competition with the hydrogen evolution reaction. Now it is reported that peripheral functionalization of immobilized molecular complexes with quaternary ammonium groups can regulate the mass distribution surrounding the active sites, enabling selective CO₂RR in strong acids.

Comprehensive analyses of Cas9 proteins shed light on the evolution of the CRISPR–Cas9 system, and identify a pro-CRISPR accessory protein in bacteria that boosts CRISPR-mediated immunity by enhancing the DNA binding and cleavage activity of Cas9.

A hydrated lunar mineral, (NH₄)MgCl₃·6H₂O, is found in Chang’e-5 samples. The presence of abundant water and ammonium molecules on the Moon provides insight into the lunar degassing history and a potential resource for lunar habitation.

Shared neuroanatomical differential factors explain heterogeneous gray matter volume variations in five common psychiatric disorders. These factors are characterized by dissociable cognitive processes, molecular signatures, and connectome-informed epicenters.

Potential lead contamination risk and environmental vulnerability risk impose a significant obstacle for the commercialization of perovskite solar cells. Here, the authors create a biomimetic cage traps to mitigate lead leakage and establish a sustainable closed-loop lead management process.