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Centennial-scale variations in methane carbon isotope ratios are attributed to changes in pyrogenic and biogenic sources that can be correlated with anthropogenic activities, such as varying levels of biomass burning during the period of the Roman empire and the Han dynasty, and changes in natural climate variability.

The impact of variants of uncertain significance (VUS) on protein function and cancer risk remain unclear. Here, the authors focus on the functional impact of VUS of the PALB2 gene and identify defects in DNA damage repair by homologous recombination associated with increased risk of breast cancer.

Amazonian fog samples contain viable microbes, suggesting fog plays a role microbial dispersal, colonization and nutrient cycling, according to analyses of fog samples from a tall tower observatory.

In a long-term follow-up of the FAME 2 trial, fractional flow reserve-guided percutaneous coronary intervention plus medical therapy in patients with stable coronary artery disease reduced cardiovascular events compared to medical therapy alone, primarily due to a decrease in urgent revascularization events.

Genomic analyses applied to 14 childhood- and adult-onset psychiatric disorders identifies five underlying genomic factors that explain the majority of the genetic variance of the individual disorders.

Including data from 1,047 patients across 19 inflammatory diseases, a new atlas presents a comprehensive model of inflammation in circulating immune cells.

Different agonists produce equilibria of at least four distinct active states of the G-protein-bound M2 muscarinic acetylcholine receptor, each with a different ability to activate G proteins.

Mapping of the neutrophil compartment using single-cell transcriptional data from multiple physiological and patological states reveals its organizational architecture and how cell state dynamics and trajectories vary during health, inflammation and cancer.

Accurate projections of heating and cooling needs are vital for planning energy use and achieving the sustainable development goals. A global dataset now maps global heating and cooling degree days, finding future hotspots, rising cooling demand and early shifts in energy needs with major global impacts.

AvrPm4 is a chimeric powdery mildew effector that is recognized by the wheat kinase fusion resistance protein Pm4. The pathogen can evade Pm4 recognition by expressing the suppressor SvrPm4, an RNase-like effector with multiple roles.

In a multicenter, randomized trial of patients with atrial fibrillation and a low risk of thromboembolic events, treatment with the anticoagulant rivaroxaban showed no benefit in reducing cognitive decline, stroke or transient ischemic attack when compared to placebo.

This study provides new insights into the role of endoglin (ENG) as a co-receptor in endothelial cells and addresses a gap-in-knowledge on how ENG could be involved in both TGF-β and BMP9 signalling. Such knowledge greatly facilitates therapeutic targeting of ENG-related pathways.

The B1.23.2 antibody binds HLA-B*44:05 at a site that overlaps the killer Ig-like receptor binding site. It blocks inhibitory receptor interactions, leads to NK cell activation and suppresses tumor growth in a humanized mouse model.

Fire hydrants can create stagnant zones in drinking water systems that degrade water quality. This study shows that stagnant water has much higher metal and microbial levels than flowing water, revealing distinct chemical and microbial shifts that may pose health risks.

Time-resolved serial femtosecond crystallography at X-ray free-electron lasers is a powerful approach for studying macromolecular dynamics, but its widespread use is limited by high sample consumption. Here, the authors introduce a segmented-droplet mix-and-inject strategy at the European XFEL that reduces sample consumption by up to 97% while preserving the data quality required for time-resolved structural studies of the enzyme NQO1.

Tree cover gains in the moist tropics (1982–2015) were 56% naturally regenerated forests and 27% managed tree systems, with forest type influencing carbon recovery. Effective forest restoration requires robust tracking of forest types established by restoration efforts.

The CMS Collaboration reports the measurement of the spin, parity, and charge conjugation properties of all-charm tetraquarks, exotic fleeting particles formed in proton–proton collisions at the Large Hadron Collider.

A newly published report reviews the techniques available for evaluating national performance in basic research and applies these techniques to solid state physics and genetics.

Current methods to generate haplotype-resolved assemblies for highly heterozygous genomes suffer from reference bias or may generate imbalanced haplomes. Here, the authors present the PhaseGrass workflow and demonstrate its application in assembling highly heterozygous genomes of Lolium perenne and L. multiflorum.

Programmable self-assembly can help construct complex nanostructures. Now a mathematical framework can identify if and how a particular structure can be assembled.

GRX-810, an oxide dispersion strengthened alloy, shows excellent structural performance above 1100°C and stability up to 1300 °C. Grain-size effects, additive manufacturing–induced anisotropy, and fine trigonal Y₂O₃ particles enhance creep resistance.

Channelized subsurface melting is an important process in the dynamics of ice shelves. Here the authors present observational data from Antarctic ice shelves and show that their basal melt is up to 50% higher than previously assumed.

Grosjean et al. present a network-aware, self-supervised learning approach for screening neuronal activity dynamics. They demonstrate its applicability across a range of neural interventions.

A key step in the evolution of the nitrogen-fixing root nodule symbiosis, occurring 100 million years ago, subjected the control of Nodule Inception (NIN) gene expression to a protein complex that regulated transcription much earlier in the arbuscular mycorrhiza symbiosis.

The ALICE Collaboration provides details on the microscopic mechanism that ends up creating antideuteron in high-energy proton–proton collisions at the Large Hadron Collider.

Here, the authors examine the mechanisms behind cheatgrass’s successful invasion of North American ecosystems. Their genetic analyses and common garden experiments demonstrate that multiple introductions and migrations facilitated cheatgrass local adaptation.

Translation initiation and elongation factors can be targets for cancer treatment. Here, the authors show that inhibiting translation elongation through eIF5A impairs mitochondrial function, slowing the proliferation of tumour cells.

The complement system depends on C3 cleavage that is critical to all three activation pathways, but currently structural data is lacking. Here authors present cryo-EM structures revealing a charge switch-over mechanism.

The cellular origin of soft-tissue cancers, such as synovial sarcoma (SyS), is unknown. Here, expression of the oncoprotein, SS18::SSX, in fibroblasts was sufficient to produce human-like SyS tumours, thereby identifying a cell of origin for SyS.

A detailed spatiotemporal roadmap of the human female and male reproductive tracts during key periods of sexual differentiation provides new cellular and molecular insights into how early axial gradients lead to specific cell lineages and tissue structures.

Zhang et al. characterize the mitochondrial inner membrane subdomain organizer (MISO) protein, which responds to inner mitochondrial membrane stress by inducing membrane subdomains promoting homeostatic fission and mtDNA degradation.

Here, as part of the Sherlock-Lung study, the authors profile the microbiomes of 940 lung cancers in never smokers finding no significant associations with demographic and clinical features, suggesting lung bacteria are unlikely to have a sizable role in lung cancer.

Wastewater-based surveillance tends to focus on specific pathogens. Here, the authors mapped the wastewater virome from 62 cities worldwide to identify over 2,500 viruses, revealing city-specific virome fingerprints and showing that wastewater metagenomics enables early detection of emerging viruses.

In this work, fragments identified by 19F-NMR are optimized into submicromolar binders of the MITF transcription factor. These results support direct targeting of bHLH-LZ DNA binding domains and provide a foundation for the development of new melanoma therapies.

Lung adenocarcinomas bearing the ID2 mutational signature display increased LINE-1 retrotransposon activity, which contributes to their fast evolutionary dynamics and aggressive phenotype.

Authors use data from Togo to model onchocerciasis infection trends and elimination probabilities. Both ivermectin and vector control led to marked prevalence decline. Some areas may reach elimination by 2030 but others need alternative strategies.

Laboratory automation, machine learning, and metabolic engineering may be combined to quickly and efficiently build productive microbial strains. Here the authors used these techniques in P. putida to boost isoprenol titers 5-fold over six DBTL cycles while sampling a reduced design space.

Npm1 promotes tumor formation via attenuating the integrated stress response and p53 activation in mouse WNT-driven intestinal and liver tumorigenesis.

Chronic tinnitus is often treated with cognitive-behavioural therapy, hearing aids, counselling, or sound therapy, but their combined benefit is unclear. Here, the authors show, in a multicentre randomised trial, that combination treatments improve tinnitus scores more than single therapies, though benefits appear compensatory rather than synergistic.

The effects of current protected areas on freshwater biodiversity are poorly understood. Here, the authors show that European protected areas have overall limited influence on changes in river biodiversity, underscoring the urgent need for improved effectiveness.

Human and rodent supragranular pyramidal neurons differ in HCN channel-related properties. Comparison across primates reveals robust HCN1 expression and HCN channel-dependent physiology, with cell type dependent differences in macaques versus humans.

In this work, the authors show that the essential Mycoplasma pneumoniae protein P116 enables cholesterol acquisition from lipoproteins and various cell types. An antibody against its C-terminal domain inhibits lipid acquisition, growth, and plaque binding, linking M. pneumoniae to atherosclerotic lipid-rich tissue.