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Whole-genome sequencing data for 2,778 cancer samples from 2,658 unique donors across 38 cancer types is used to reconstruct the evolutionary history of cancer, revealing that driver mutations can precede diagnosis by several years to decades.

Some cancer patients first present with metastases where the location of the primary is unidentified; these are difficult to treat. In this study, using machine learning, the authors develop a method to determine the tissue of origin of a cancer based on whole sequencing data.

Many tumours exhibit hypoxia (low oxygen) and hypoxic tumours often respond poorly to therapy. Here, the authors quantify hypoxia in 1188 tumours from 27 cancer types, showing elevated hypoxia links to increased mutational load, directing evolutionary trajectories.

Multi-omics datasets pose major challenges to data interpretation and hypothesis generation owing to their high-dimensional molecular profiles. Here, the authors develop ActivePathways method, which uses data fusion techniques for integrative pathway analysis of multi-omics data and candidate gene discovery.

The characterization of 4,645 whole-genome and 19,184 exome sequences, covering most types of cancer, identifies 81 single-base substitution, doublet-base substitution and small-insertion-and-deletion mutational signatures, providing a systematic overview of the mutational processes that contribute to cancer development.

Northern China contains some of the world’s earliest farming societies. Here, authors use 55 ancient genomes to trace the genetic history of human migrations across northern China for the last 7500 years, and document genetic changes mirroring shifts in subsistence strategy.

Interstitials can substantially strengthen metals. Here the authors show a massive interstitial solid solution (MISS) approach enabling a model multicomponent alloy to achieve near-theoretical strength together with large deformability.

White matter hyperintensities are linked to cortical atrophy, a key feature in dementia. Here, the authors identify loci associated with cortical atrophy related to white matter hyperintensities, which involve vascular and neuronal processes.

Estimates from the Global Dietary Database indicated that 2.2 million new type 2 diabetes and 1.2 million new cardiovascular disease cases were attributable to sugar-sweetened beverages worldwide in 2020, with the highest burdens in sub-Saharan Africa, Latin America and the Caribbean.

A structural analysis focusing on plant immunity reveals how LRR-containing receptor-like proteins recognize pathogenic ligands and consequently become activated, with the data suggesting that these proteins target pathogens through two different mechanisms.

Whole-genome sequencing, transcriptome-wide association and fine-mapping analyses in over 7,000 individuals with critical COVID-19 are used to identify 16 independent variants that are associated with severe illness in COVID-19.

Current approaches to conditionally deplete target proteins require site-specific genetic engineering or have poor temporal control. Here the authors overcome these limitations by combining the AID system with nanobodies to reversibly degrade GFP-tagged proteins in living cells and zebrafish.

Cortex morphology varies with age, cognitive function, and in neurological and psychiatric diseases. Here the authors report 160 genome-wide significant associations with thickness, surface area and volume of the total cortex and 34 cortical regions from a GWAS meta-analysis in 22,824 adults.

Zooarchaeological and proteomic analyses of bones from Baishiya Karst Cave on the Tibetan Plateau identify a hominin rib specimen, and provide insight into the ways Denisovans interacted with their surrounding environment and made use of animal resources.

Recent estimates of sugar-sweetened beverages (SSBs) intake are generally unavailable. Here the authors show a global SSBs intake of 2.7 servings/week in 2018 in adults (range: 0.7 South Asia, 7.8 Latin America/Caribbean); intakes were higher among males, younger, more educated, and urban adults.

Literature produced inconsistent findings regarding the links between extreme weather events and climate policy support across regions, populations and events. This global study offers a holistic assessment of these relationships and highlights the role of subjective attribution.

Cognitive impairments are a key feature of psychopathology. Here, authors exploit the genetic overlap between cognitive dimensions and psychopathology to parse the biology of psychiatric illness and identify “meta-loci” genome segments characterized by specific patterns of overlap.

Topological semimetals with space-inversion and time-reversal symmetry breaking have attracted attention recently. Here, using a combination of experimental techniques and calculations, the authors demonstrate the tunability of the Weyl nodes via magnetism and pressure in the ferromagnetic Weyl semimetal CeAlSi.

Wolbachia are common obligate intracellular symbionts, yet their evolutionary relationships remain largely unknown. Here, the authors present a phylogenomic analysis of the group and show a possible single origin of the ubiquitous Wolbachialineages.

The authors report an Initial Upper Palaeolithic archaeological assemblage from China dating to 45,000 years ago that includes blade technology, tanged and hafted projectile points, long-distance obsidian transfer and the use of a perforated graphite disc.

What is the state of trust in scientists around the world? To answer this question, the authors surveyed 71,922 respondents in 68 countries and found that trust in scientists is moderately high.

A cultural assembly of traits at a 40,000-year-old archaeological site at Xiamabei, China supports a model of repeated early human expansions, cultural exchange and innovation in east Asia.

Van der Waals magnetic materials are characterized by strong magnetic interactions within each van der Waals layer, while the interaction between the layers is typically weaker. Here, Liu, Su, Gu and coauthors find a magnetic phase transition in the van der Waals magnet, NiI₂, under hydrostatic pressure, which they associate with the interlayer magnetic interaction.

By using liquid metal electrodes and selectively doped self-healing materials, the authors make devices with high performance, modular assembly, and application potential in wearable electronics.

A strategy for cooperation in repeated games, called cumulative reciprocity, is proposed. This strategy is robust with respect to errors, enforces fair outcomes, and evolves in environments that are usually hostile to cooperation.

Entanglement was observed in top–antitop quark events by the ATLAS experiment produced at the Large Hadron Collider at CERN using a proton–proton collision dataset with a centre-of-mass energy of √s  = 13 TeV and an integrated luminosity of 140 fb⁻¹.

Little is known about people’s preferred responses to norm violations across countries. Here, in a study of 57 countries, the authors highlight cultural similarities and differences in people’s perception of the appropriateness of norm violations.

A genome-wide association study of critically ill patients with COVID-19 identifies genetic signals that relate to important host antiviral defence mechanisms and mediators of inflammatory organ damage that may be targeted by repurposing drug treatments.

Thermal transistors can enable game changing applications in energy harvesting and heat routing. Here, the authors demonstrate reversible thermal modulation of nearly 10 times by ion intercalation in MoS₂ nanofilms. A new thermal microscopy technique allows operando imaging of Li ion segregation.

Neuropeptide Y signalling in the periphery contributes to the regulation of metabolic and energy homeostasis. Here the authors show that blocking Y1R signalling in peripheral tissues using the selective antagonist BIBO3304 ameliorates diet-induced obesity and improves whole-body glucose metabolism.

The future of the land carbon sink depends on the temperature response of ecosystem respiration. This Review explores observational and experimental evidence for a unimodal temperature response of respiration and the implications for carbon sequestration predictions.

Could similar ecological and biogeographic drivers explain the distributions of biological diversity and human cultural diversity? The authors explore ecological correlates of human language diversity, finding strong support for a role of high year-round productivity but less support for landscape features.

Stable carbon isotope analysis of mouse organs reveals no evidence for gut microbial essential amino acid provisioning after microbiome reconstitution as demonstrated by the nearly identical isotope patterns in germ-free and conventionalized mice.

Crowdsourcing analysis improves computational prediction of cytotoxic responses in humans.

The kagome superconductor CsV₃Sb₅ exhibits a charge density wave (CDW) as well as superconductivity (SC). Here, the authors find that the CDW transition temperature decreases with decreasing sample thickness to 72 K at 27 atomic layers, but then unexpectedly increases to 120 K at 5 layers, an opposite trend to SC.

Topological heterostructures are desired in metallic glasses to improve their mechanical properties. Here, the authors present an enthalpy-guided alloy design to introduce nanoscale chemical heterogeneity, producing a metallic glass with a large homogeneous plastic flow at room temperature.

Long-term consumption of a calorie-rich diet persistently activates brain microglia. Here, the authors show that microglial activity in mouse brains oscillates daily in conjunction with feeding, and that TNFα, secreted by activated microglia, induces mitochondrial stress in satiety-promoting POMC neurons.

Neutrophils release the serine proteases neutrophil elastase and cathepsin G, which have microbicidal activity and thereby contribute to the innate immune response. Steffen Massberg et al. now show that these neutrophil serine proteases, in association with extracellular nucleosomes, can also promote coagulation and thrombosis within large blood vessels. In a mouse model of systemic bacterial infection, these proteases spurred intravascular coagulation in the microcirculation of the liver, limiting bacterial tissue invasion. These findings point to a role for thrombosis in antimicrobial defense.

Analysis of peripheral mycobacteria-reactive CD4⁺ T cell receptor sequences from individuals infected with Mycobacterium tuberculosis shows a high degree of overlap between progressors and controllers, but points to some distinct clonotypes that are enriched in either group.

Here the authors show genome-wide chromatin changes and transcriptional reprogramming occur in response to heat stress in tomato, leading to the transient formation of promoter-enhancer contacts to drive the expression of heat-stress responsive genes. Furthermore, they show chromatin spatial reorganization requires HSFA1a, a transcription factor (TF) essential for heat stress tolerance in tomato.

During innate immune responses, plant cells secrete proteases into apoplastic spaces where they contribute to pathogen resistance. Here Wang et al. show that the Arabidopsis SAP1 and SAP2 proteases cleave the bacterial MucD protein to inhibit growth of Pseudomonas syringae.

The principle of Le Chatelier is a fundamental concept in textbooks, serving as a guiding principle for controlling chemical and catalytic systems. In this study, the authors present an oxygen electroreduction system based on a single zinc vacancy catalyst, which operates in a manner that extends “beyond” Le Chatelier’s principle.

Analyses of data from the UK Biobank reveal different urban living environments that are associated with affective, anxiety and emotional instability symptom groups and mediated by distinct neurological and genetic pathways in adults.

Early life experience contributes to behaviour in later life. Here the authors show in rats, that the infant brain, during a critical period, forms lasting memories of the spatial context of experiences; in adulthood, these memories involving medial prefrontal cortex improve spatial abilities in similar contexts.

Chips with 256 × 256 memristor arrays that were monolithically integrated on complementary metal–oxide–semiconductor (CMOS) circuits in a commercial foundry achieved 2,048 conductance levels in individual memristors.

It is unknown how endocardium growth is coordinated with that of the myocardium in the zebrafish. Here, the authors show that myocardial chamber volume expansion causes increased endocardial tissue tension, which in turn triggers Hippo signaling-mediated proliferation within the endocardium.