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Yang et al. show that transcription–replication collisions lead to large tandem duplications, which are frequent in female-enriched, upper gastrointestinal tract and prostate cancers and are associated with poor survival and mutations in specific genes, such as CDK12.

Lentiviral massively parallel reporter assay (lentiMPRA) analysis of cardiac cis-regulatory elements characterizes the effects of noncoding de novo variants identified in congenital heart disease. EpiCard is a model for variant prioritization.

How lipopolysaccharide embedded in bacterial membranes is sensed by intracellular defense mechanisms has been puzzling. Randow and colleagues show that guanylate-binding proteins assemble on the surface of Gram-negative bacteria to initiate downstream pyroptosis.

Crystal sizes play a vital role in pushing up the efficiency of organometal halide perovskites based LEDs. Here Ban et al. incorporate a molecular additive to control the crystallite distribution and phase separation in the perovskite devices, resulting in high external quantum efficiency of 15.5%.

In this largest whole-exome sequencing study of epilepsies to date, the Epi25 Collaborative identified extremely rare variants that confer risk for diverse epilepsy subtypes, highlighting roles in synaptic transmission and neuronal excitability.

Genome-wide association meta-analyses identify 26 risk loci for epilepsy, including 19 loci specific to genetic generalized epilepsy. Prioritized candidate genes implicate synaptic processes and overlap with targets of antiseizure medications.

Using near-real-time daily carbon emission datasets from 48 cities in China, this paper explores post-COVID-19 during which Chinese cities experienced economic growth and reduced greenhouse gas emissions—a low-carbon recovery. Six low-carbon-recovery cities (mainly megacities) saved, on average, 1.2 times as many lives per 100,000 population than the 42 other cities.

Understanding how DNA double strand breaks (DSBs) form and are repaired in the genome depends on their accurate measurement. Here the authors describe INDUCE-seq; a DSB-detection method that simultaneously measures physiological and induced breaks throughout the genome.

A global network of researchers was formed to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity; this paper reports 13 genome-wide significant loci and potentially actionable mechanisms in response to infection.

Analysis of ground-sourced and satellite-derived models reveals a global forest carbon potential of 226 Gt outside agricultural and urban lands, with a difference of only 12% across these modelling approaches.

Lineage plasticity is increasingly recognized as an emergent resistance mechanism after treatment with androgen receptor signalling inhibitors. To understand determinants of resistance, the authors analyzed the transcriptomes of patient tumor biopsies before enzalutamide treatment and at progression and identified a gene expression program associated with lineage plasticity risk and poor outcomes.

In mouse brain, neurotensin released into the basolateral amygdala by neurons in the paraventricular nucleus of the thalamus assigns positive or negative valence during associative learning.

Large single crystals of charged 2D polymers are synthesized on a water surface, under kinetic control, by the irreversible Katritzky reaction. The crystals can act as an anion-selective membrane for osmotic energy generation.

Cryptochrome 1 (CRY1) is a transcriptional coregulator associated with the circadian clock. Here the authors reveal that CRY1 is hormone-regulated, stabilized by genomic insult, and promotes DNA repair and cell survival through temporal transcriptional regulation.

Continuous-flow biocatalysis with immobilized enzymes is a sustainable route for chemical synthesis, but inadequate biocatalytic efficiency caused by non-productive enzyme immobilization or enzyme-carrier mismatches presents a challenge for its application. Here, the authors report an approach for the fabrication of a high-performance enzymatic continuous-flow reactor via integrating scalable isoporous block copolymer membranes as carriers with an oriented one-step enzyme immobilization via a genetically fused material binding peptide.

Alternative stable states in forests have implications for the biosphere. Here, the authors combine forest biodiversity observations and simulations revealing that leaf types across temperate regions of the NH follow a bimodal distribution suggesting signatures of alternative forest states.

The field of perovskite light-emitting diodes witnesses rapid development in both device processing strategies and performances. Here Wang et al. develop high-quality perovskite-molecule composite thin films and achieve high quantum efficiency of 17.3% and half-lifetime of 100 h.

The BRAIN Initiative Cell Census Network has constructed a multimodal cell census and atlas of the mammalian primary motor cortex in a landmark effort towards understanding brain cell-type diversity, neural circuit organization and brain function.

Early stellarator designs suffered from high particle losses, an issue that can be addressed by optimization of the coils. Here the authors measure the magnetic field lines in the Wendelstein 7-X stellarator, confirming that the complicated design of the superconducting coils has been realized successfully.

The molecular mechanisms underlying androgen production in prostate cancer remain to be explored. Here, the authors reveal an epigenetic mark, K130Ac on H2A, following dual-phosphorylation on SREBP1 promoting de novo androgen synthesis to overcome the pharmacological inhibition of androgen synthesis.

A spatially resolved transcriptional atlas of the mid-gestational developing human brain has been created using laser-capture microdissection and microarray technology, providing a comprehensive reference resource which also enables new hypotheses about the nature of human brain evolution and the origins of neurodevelopmental disorders.

Global patterns of regional plant diversity are relatively well known, but whether they hold for local communities is debated. This study created multi-grain global maps of alpha diversity for vascular plants to provide a nuanced understanding of plant diversity hotspots and improve predictions of global change effects on biodiversity.

Immune checkpoint blockade is showing promise in cancer immune therapy, but many solid tumours are resistant. Authors here identify a pathway in T cells that leads to increased activity of C-terminal Src kinase, a negative regulator of T cell activity, thus disabling tumour infiltrating T cells and causing immune therapy resistance.

Georgakopoulos-Soares, Yizhar-Barnea, Mouratidis et al. identify neomers, short (16 base pair) DNA sequences that are absent in the genomes of healthy individuals but appear in tumors due to mutations. They show that neomers can accurately detect cancer from cell-free DNA and that neomers found in gene regulatory elements can alter regulatory activity.

Two newly designed co-adsorbed dye-sensitized solar cells that harvest light quantitatively across the entire visible domain are described, which offer promising applications as power supplies and battery replacements for low-power electronic devices.

Elevated expression of long noncoding RNA H19 is seen in clinical samples of neuroendocrine prostate cancer (PCa). Here the authors show H19 promotes plasticity from luminal to neuroendocrine by epigenetic reprogramming.

The changes that prostate cancer (PCa) induces in its microenvironment are not fully understood. Here the authors use single-cell RNA-seq and organoids to characterise how the microenvironment responds to PCa, and also identify tumour-associated epithelial cell states and club cells.

Combined use of a DNA-barcoded nucleosome library and a humanized yeast library allows the identification of histone globular domain mutations that affect histone exchange and nucleosome sliding processes, as well as cancer-associated gene pathways.

Davies et al. demonstrate that androgen receptor–targeted therapy induces lineage-plastic transcriptional reprogramming, which is mediated by EZH2 and favours stem cell and neuronal gene networks in treatment-resistant prostate cancer.

It remains a challenge to achieve a balance between performance and stability, as well as addressing the environmental impact of perovskite solar cells. Here, the authors propose a multimodal host-guest complexation strategy enabling these shortcomings to be addressed simultaneously.

In this disease mapping study, the authors estimate disability-adjusted life year rates for three of the major causes of mortality for children under five 43 countries in sub-Saharan Africa. They identify significant heterogeneity at the subnational level, highlighting the need for a targeted intervention approach.

Size and shape of the brain are, among others, influenced by the dimensions of the skull. Here, the authors report genome-wide association studies for head circumference and intracranial volume in children and adults and the identification of nine common or low-frequency variants associated with these traits.

The differentiation of prostate adenocarcinoma to neuroendocrine prostate cancer (CRPC-NE) is a mechanism of resistance to androgen deprivation therapy. Here the authors show that SWI/SNF chromatin-remodeling complex is deregulated in CRPC-NE and that the complex interacts with different lineage specific factors throughout prostate cancer transdifferentiation.

Neuroendocrine prostate cancer (NEPC) is characterized by loss of androgen receptor (AR) signaling during neuroendocrine transdifferentiation, resulting in resistance to AR-targeted therapy. Here they report ONECUT2 to drive NEPC tumorigenesis via regulation of hypoxia signaling and tumor hypoxia, and find hypoxia directed therapy to be effective in NEPC.

Using lineage tracing and molecular profiling, Abate-Shen and colleagues identify a Ras and Myc co-activation signature that predicts metastasis and castration resistance in localized prostate cancer.

In prostate cancer, investigating aberrant gene expression may shed light on disease etiology. Here, the authors imputed expression transcriptome-wide for 233,955 European ancestry men, discovering and replicating the associations between prostatic expression for select genes and prostate cancer risk, including the highly prevalent gene fusion partner TMPRSS2. The authors furthermore integrate diverse functional genomic datasets to interpret the epigenetic mechanisms by which the implicated risk variants and genes modulate disease risk.

SIRT7 is a protein deacetylase with important roles in rRNA synthesis, ribosome biogenesis and cell proliferation. Here the authors show a role of SIRT7 in rRNA maturation via deacetylation of U3-55k, a core component of the U3 snoRNP complex.

Some phages carry genes coding for anti-CRISPR (Acr) proteins that interfere with the activity of bacterial CRISPR-Cas systems. Here, Hynes et al. characterize a new Acr family from streptococcal phages and investigate its potential in genome-editing applications.

Polyaromatic hydrocarbons can be precisely manipulated to yield ever more complex and discrete graphene analogs, such as nanographenes. Here, the authors use azomethine ylide homocoupling to insert an antiaromatic pyrazine ring into the core of a nanographene, and characterize the molecule’s unique electronic character.

Christopher Newton-Cheh and colleagues report a genome-wide association study for blood pressure traits as part of the Global BPgen consortium. They report eight loci with replicated association to systolic and/or diastolic blood pressure, with each also showing association to hypertension.

A high-resolution X-ray diffraction study of chromium and niobium diselenide traces the evolution of the ordering wavevector in charge and spin density waves, respectively, as a function of temperature and applied pressure.

Polycomb group proteins are epigenetic gene silencers that are thought to exist in two biochemically distinct multiprotein complexes, termed PRC-1 and -2. Here, Cao et al.show that EED, a core component of PRC2, interacts with and functions as part of PRC1, thus coordinating the activities of both complexes.

In male mice with diet-induced obesity, deletion of insulin inhibitory receptor (inceptor) in the whole body, in the brain and in pancreatic β cells improves glucose homeostasis, underlining a role of inceptor in regulating glucose homeostasis in the brain and pancreas.

Cancer cells often have mutations in anticancer genes that make their survival dependent on other genes. The gene-editing approach CRISPR–Cas9 offers a way to identify such vulnerabilities.

Hand grip strength as a proxy of muscular fitness is a clinical predictor of mortality and morbidity. In a large-scale GWA study, the authors find 16 robustly associated genetic loci that highlight roles in muscle fibre structure and function, neuronal maintenance and nervous system signal transduction.