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Halogen-substituted silylium ions are compounds for which Lewis superacidity has been predicted, but their synthesis has proven challenging. Now a series of ionic halosilylium Lewis superacids have been prepared in the condensed phase, opening the door to their application in synthetic processes.

A new version of nanorate DNA sequencing, with an error rate lower than five errors per billion base pairs and compatible with whole-exome and targeted capture, enables epidemiological-scale studies of somatic mutation and selection and the generation of high-resolution selection maps across coding and non-coding sites for many genes.

Kaiser et al. characterize the disordered extracellular N-terminus of a peptide-activated G protein-coupled receptor. They combine biophysical, biochemical, and computational methods to uncover its role in the activation of G protein and arrestin pathways.

Small cell lung cancer cells form functional synapses with glutamatergic neurons, receiving synaptic transmissions and deriving a proliferative advantage from these interactions.

Tsering et al. show that in pants, HSP90 acts as a positive regulator of auxin transport by providing steady-state levels of ABCB transport capacity in an action that isorchestrated by its co-chaperone FKBP42/TWISTED DWARF1.

The quark structure of the f₀(980) hadron is still unknown after 50 years of its discovery. Here, the CMS Collaboration reports a measurement of the elliptic flow of the f₀(980) state in proton-lead collisions at a nucleon-nucleon centre-of-mass energy of 8.16 TeV, providing strong evidence that the state is an ordinary meson.

The accumulation of cytotoxic deoxysphingolipids causes retinopathies through unknown mechanisms. Here the authors use retinal organoids to show that photoreceptor toxicity is mediated by unfolded protein response signaling.

Cancer evolutionary dynamics are quantitatively inferred using a method, EVOFLUx, applied to fluctuating DNA methylation.

Using multi-ancestry genome-wide association study and fine-mapping, 298 loci and 36 credible genes are identified in the aetiology of bipolar disorder.

Magnetic excitations, or spinons, in a quasi-one-dimensional quantum magnet are investigated in an inelastic neutron-scattering experiment. The measurements confirm the existence of theoretically predicted higher-order spinons.

The authors highlight inconsistencies and divergencies in the literature reporting data on indirect calorimetry for studies on whole-body energy homeostasis, and propose harmonization of standards to facilitate data comparison and interpretation across different datasets.

This study used fine-mapping to analyze genetic regions associated with bipolar disorder, identifying specific risk genes and providing new insights into the biology of the condition that may guide future research and treatment approaches.

The advantage of living in cities compared with rural areas with respect to height and BMI in children and adolescents has generally become smaller globally from 1990 to 2020, except in sub-Saharan Africa.

Analysis of soundscape data from 139 globally distributed sites reveals that sounds of biological origin exhibit predictable rhythms depending on location and season, whereas sounds of anthropogenic origin are less predictable. Comparisons between paired urban–rural sites show that urban green spaces are noisier and dominated by sounds of technological origin.

Achieving phosphorus circularity is a key challenge to realizing sustainable phosphorus use, and recycling is a major route to accomplish this goal. This Review explores global barriers to phosphorus recycling and discusses approaches to overcome the technical, economic and societal challenges in attaining sustainable phosphorus management.

Melanie Bahlo and colleagues perform the first genome-wide association analysis for macular telangiectasia type 2. They identify three significant loci and report on a potential connection to the glycine/serine metabolism pathway.

Thermal bias may predict the impact of climate change. Looking at regional warming and marine bivalves, brachiopods, and gastropods in the early Jurassic, the authors find that species with cooler temperature preferences than local conditions were more likely to become extirpated or extinct.

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.

Stojanov et al. updated and internally validated a prediction model for the occurrence of post-operative shoulder stiffness following primary arthroscopic rotator cuff repair in Switzerland. Their findings support the development of further prediction models for an evidence-based and individualized decision-making in orthopedics.

Segmentation and classification of microstructures are required by quality control and materials development. The authors apply deep learning for the segmentation of complex phase steel microstructures, providing a bridge between experimental and computational methods for materials analysis.

CORNETO is a unified mathematical framework and software that integrates prior knowledge with omics data to jointly infer context-specific signalling, metabolic and protein networks across multiple samples, boosting interpretability and accuracy.

Keyl et al. present an explainable artificial intelligence model-based real-world data analysis from over 15,000 patients across 38 cancer types, identified key prognostic marker interactions, and confirmed these in an external lung cancer cohort.

Our ability to identify associations between behaviour and brain imaging is important for uncovering markers of cognition and disease. Here, the authors illustrate the importance of the reliability of behavioural measurements to accurately investigate brain-behaviour associations using machine learning.

The sensitive measurement of physical quantities offers a wide range of applications in fundamental and applied science. Cai et al. propose a hybrid technology combining colour centres in diamond and piezoactive layers to realize force, pressure and electric field sensors with nanoscale resolution.

Tracers are fluorescent protein ligands required for various displacement assays. Here, the authors announce a curated database named tracerDB, which will make essential tracer data, contributed by the worldwide research community, easily available and searchable.

Reduced glomerular filtration rate (eGFR) is a hallmark of chronic kidney disease. Here, Pattaro et al. conduct a meta-analysis to discover several new loci associated with variation in eGFR and find that genes associated with eGFR loci often encode proteins potentially related to kidney development.

Müller-Tidow and colleagues perform a randomized clinical trial and show that administration of convalescent plasma improves COVID-19 outcome in patients with cancer who are unable to generate an adequate immune response.

The LHCb experiment at CERN has observed significant asymmetries between the decay rates of the beauty baryon and its CP-conjugated antibaryon, thus demonstrating CP violation in baryon decays.

A deterministic correction of errors caused by qubit loss or leakage outside the computational space is demonstrated in a trapped-ion experiment by using a minimal instance of the topological surface code.

Brain insulin action regulates eating behavior and whole-body energy fluxes, however the impact of brain insulin resistance on long-term weight and body fat composition is unknown. Here, the authors show that high brain insulin sensitivity is linked to weight loss during lifestyle intervention and associates with a favorable body fat distribution.

Kinases regulate cellular processes, making their study essential for understanding cellular function and disease. Here, the authors evaluate methods to infer kinase activity from phosphoproteomics data and provide a toolkit to evaluate future methods.

The manufacturing process for GRIN lenses causes a symmetric birefringence variation which is considered a deficiency. Here, the authors show how this birefringence can generate vector vortex beams and form the basis of a Müller matrix polarimeter with potential for endoscopic label-free cancer diagnostics.

Meta-analyses in up to 1.3 million individuals identify 87 rare-variant associations with blood pressure traits. On average, rare variants exhibit effects ~8 times larger than the mean effects of common variants and implicate candidate causal genes at associated regions.

Understanding the immunological underpinnings of long-term survival in cancer is of high interest. Here, authors dissect the immune parameters of multiple myeloma long-term survivors following a single line of therapy longitudinally, and find sustained changes, including inflammation and impaired immune function.

In this phase 1 trial, patients with locally advanced or metastatic solid tumors were treated with the individualized mRNA neoantigen-specific immunotherapy (iNeST) autogene cevumeran alone or in combination with the anti-PD-L1 agent atezolizumab, showing long-lasting neoantigen-specific immune responses and preliminary clinical activity, supporting further development of this therapeutic approach.

Pepstatins are potent inhibitors of aspartic proteases, featuring two statine residues crucial for target binding, however, their biosynthesis is elusive. Here, the authors discover and characterize an unconventional gene cluster responsible for pepstatin biosynthesis, and characterize the role of PepI, an F₄₂₀H₂-dependent oxidoreductase catalysing the tandem reduction of β-keto pepstatin intermediates.

Different functional variants in ADH1B (and elsewhere) in Europeans and Africans strongly affect risk for alcohol dependence. Dependence only partly genetically correlates with consumption, with strong correlations to other psychiatric disorders.

Timothy Frayling, Joel Hirschhorn, Peter Visscher and colleagues report a meta-analysis of genome-wide association studies for adult height in 253,288 individuals. They identify 697 variants in 423 loci significantly associated with adult height and find that these variants cluster in pathways involved in growth and together explain one-fifth of the heritability for this trait.

Endothermy facilitated mammalian species radiation, but the events leading to sustained thermogenesis are not clear. Here, the authors report functional brown adipose tissue in a protoendothermic mammal, linking nonshivering thermogenesis directly to the roots of eutherian endothermic evolution.

Exome sequencing within a structured diagnostic process for rare diseases in Germany shows how facial image analysis and machine learning can guide variant prioritization and uncover many ultrarare diseases.

Monolayer graphene can support the quantum Hall effect up to room temperature. Here, the authors provide evidence that graphene encapsulated in hexagonal boron nitride realizes a novel transport regime where dissipation in the quantum Hall phase is mediated predominantly by electron-phonon scattering rather than disorder scattering.

Wood density is a key control on tree biomass, and understanding its spatial variation improves estimates of forest carbon stock. Sullivan et al. measure >900 forest plots to quantify wood density and produce high resolution maps of its variation across South American tropical forests.

The benefits and risks of nature to human health have been studied, however, robust empirical research on forest biodiversity and health outcomes is still lacking. Here the authors use a unique dataset from 164 European forest stands to explore the associations between forest types and well-being.