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Cas12a represents the next generation of gene editing. Here, the authors present the generation and validation of a Cas12a transgenic mouse model. Additionally, the authors create whole-genome Cas12a knockout libraries, and demonstrate their utility across multiple in vitro and in vivo screens.

This Resource describes data, code and tools developed for the Human Reference Atlas and the Human BioMolecular Atlas Program for building and navigating a multiscale human atlas.

Ghergurovich, Xu and Wang et al. show that methionine synthase is important for tumour cell survival through the generation of tetrahydrofolate rather than methionine.

The efficiency and operating lifetimes of perovskite light-emitting diodes is improved by using a fluorinated triphenylphosphine oxide additive to control the cation diffusion during film deposition and passivate the surface.

The measurement of the total cross-section of proton–proton collisions is of fundamental importance for particle physics. Here, the first measurement of the inelastic cross-section is presented for proton–proton collisions at an energy of 7 teraelectronvolts using the ATLAS detector at the Large Hadron Collider.

The fast radio burst FRB 20200120E is shown to originate from a globular cluster in the galaxy M81, and may be a collapsed white dwarf or a merged compact binary star system.

Anti-human leukocyte antigen (HLA) antibodies are important mediators of alloresponses, but structural insights on antibody:HLA interaction are still lacking. Here the authors provide a 2.4 Å structure of antibody:HLA complex, and also analyse HLA features important for other HLA-interacting molecules, to enhance our understanding of alloimmunity.

Quantum electrodynamics predicts a rare process in which light is scattered by light. The ATLAS Collaboration reports signs of this elusive effect in the collisions of ultra-relativistic lead ions.

Schrodinger’s cat states constitute an important resource for quantum information processing, but present challenges in terms of scalabilty and controllability. Here, the authors exploit fast Kerr nonlinearity modulation to generate and store cat states in superconducting circuits in a more scalable way.

Analysis of the pulse profile of a fast radio burst showed sub-second periodicity, providing evidence for a neutron-star origin of the event and favouring emission arising from the magnetosphere.

Controllable synthesis of 1D metal halide perovskite nanocrystals is challenging due to their structural symmetry and ionic crystal nature. Now, a general platform of cylindrical unimolecular nanoreactors has been developed to craft a variety of 1D perovskite nanorods with tailored dimensions and compositions.

Chen et al. show that subtypes of immune cells in prenatal human brain promote angiogenesis in the germinal matrix. Conversely, in preterm infants, proinflammatory immune cells disrupt angiogenesis and promote germinal matrix hemorrhage.

A human–SARS-CoV-2 protein interaction map highlights cellular processes that are hijacked by the virus and that can be targeted by existing drugs, including inhibitors of mRNA translation and predicted regulators of the sigma receptors.

Pairs of microdisk lasers are one of the most common systems for studying optical PT-symmetry. Here, Lafalce, Zeng et al. study the influence of fabrication imperfections in a disk pair made from colloidal quantum dots and show that the resulting three modes also coalesce at an exceptional point.

Spermatogonial stem cells (SSCs) spontaneously convert to multipotent adult spermatogonial-derived stem cells (MASCs). Here, the authors reveal the dynamics of bivalent histone H3-lysine4 and -lysine27 methylation signatures at somatic gene promoters in SSCs and ESC-like promoter chromatin states in MASCs.

Halbrook et al. report two metabolic subgroups of pancreatic ductal adenocarcinoma cells defined by differential integrated stress response and asparagine production that permit symbiosis and phenformin resistance.

A framework for studying and engineering gene regulatory DNA sequences, based on deep neural sequence-to-expression models trained on large-scale libraries of random DNA, provides insight into the evolution, evolvability and fitness landscapes of regulatory DNA.

The DNA modification N⁶-methyladenine regulates gene expression during mouse trophoblast development by depositing at the boundaries of active chromatin and preventing its spread by antagonizing the chromatin organizer SATB1.

The mid-infrared technologies are essential to various applications but suffer from limited materials with suitable bandgap. Here the authors demonstrate that two-dimensional atomically thin PtSe₂ with variable bandgaps in the mid-infrared via layer and defect engineering is highly promising for mid-infrared optoelectronics.

Genome-wide association meta-analyses identify more than 350 loci associated with atrial fibrillation. A polygenic score derived from these results improves atrial fibrillation risk prediction compared to published clinical and polygenic scores.

Hydroxychloroquine and chloroquine have been investigated as a potential treatment for Covid-19 in several clinical trials. Here the authors report a meta-analysis of published and unpublished trials, and show that treatment with hydroxychloroquine for patients with Covid-19 was associated with increased mortality, and there was no benefit from chloroquine.

A single-cell transcriptomic analysis of 63 patients with colorectal cancer classifies tumor cells into two epithelial subtypes. An improved tumor classification based on epithelial subtype, microsatellite stability and fibrosis reveals differences in pathway activation and metastasis.

Electron filling causes a reduction of the chemical potential in (Sr_1−x La_x)₃Ir₂O₇, which suggests negative electronic compressibility. Studying the concomitant change of the bandgap provides insight into the physical mechanism behind this effect.

This bi-ancestral genome-wide association study of major depressive disorder (MDD) identified 178 risk variants. The results advance understanding of the biology of MDD and hint at new treatment possibilities.

The dynamics and durability of immune responses associated with protection against symptomatic infection in children offer insights to guide vaccination policies in pediatric populations.

Analysis of mitochondrial genomes (mtDNA) by using whole-genome sequencing data from 2,658 cancer samples across 38 cancer types identifies hypermutated mtDNA cases, frequent somatic nuclear transfer of mtDNA and high variability of mtDNA copy number in many cancers.

Electric-field-induced cracks are generally detrimental to functionality of ferroelectric ceramics. Liu et al. use an intermetallic alloy and ferroelectric oxide junction to mediate the reversible formation of cracks at nanoscales, resulting in colossal electroresistance modulation for memory applications.

High-performance engineered myosins robustly change speed or direction in response to an optical signal. In living cells, these motors localize to the tips of protrusions when illuminated and deliver molecular cargos.

Few-nanometre-thick flakes of trigonal and monoclinic Cr₅Te₈ can be grown using chemical vapour deposition, with the monoclinic phase exhibiting an anomalous Hall conductivity of 650 Ω^–1 cm^–1 and anomalous Hall angle of 5%.

Behavioural studies with deafened rats show that locus coeruleus activity and plasticity are key to rapid adaptation to and long-term hearing performance with cochlear implants.

Pneumocystis jirovecii is a fungus that can cause life-threatening pneumonia in immunocompromised patients. Here, the authors sequence the genomes of P. jirovecii and two other Pneumocystisspecies, and show the unexpected absence of chitin (a near universal fungal cell wall component).

Sequencing and genomic diversification of five allopolyploid cotton species provide insights into polyploid genome evolution and epigenetic landscapes for cotton improvement.

Tangram is a versatile tool for aligning single-cell and single-nucleus RNA-seq data to spatially resolved transcriptomics data using deep learning.

Detecting Alzheimer’s disease from blood samples is challenging because amyloid β blood levels are lower than the ELISA detection limit. Here the authors capture amyloid β bound to circulating exosomes on a plasmonic nanosensor, followed by enzymatic amplification to improve detection sensitivity.

Lipid nanoparticles can be optimized for the efficient delivery of therapeutic mRNAs to the lung via nebulization, as shown for the delivery of a therapeutic antibody in mice challenged with a lethal dose of the H1N1 influenza A virus.

Global sampling of microbial communities associated with wastewater treatment plants and application of ecological theory revealed a small, core bacterial community associated with performance and provides insights into the community dynamics in this environment.

The CRISPR–Cas nucleases Cas9 and Cpf1 have nickase activity, including in vivo in Saccharomyces cerevisiae, which could be explored for genome engineering.

Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory respiratory disease characterized by airflow limitation and infective exacerbations. Here, Chan et al. report the generation of nasopharyngeal and bronchial COPD organoids derived from adult stem cells and employ them in the study of host-pathogen interactions, including SARS-CoV-2 and Pseudomonas aeruginosa.

Brain imaging using the compact NanoLuc luciferase has been stymied by the lack of suitable substrates. Su et al. report a brain-optimized substrate, cephalofurimazine, and use it to perform non-invasive calcium imaging of neuronal activity.