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Men and women differ in their lipid biology. Here, the authors identify NCOA1 as a female-specific regulator that promotes the conversion of white fat into energy-burning fat, protecting women from obesity and metabolic disease by enhancing thermogenic activity in subcutaneous fat.

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.

Analysis combining multiple global tree databases reveals that whether a location is invaded by non-native tree species depends on anthropogenic factors, but the severity of the invasion depends on the native species diversity.

DOT1L slows transcription elongation and promotes RNAPII pausing, altering gene expression and creating conditions that enhance AID activity for antibody diversification but also facilitate off-target mutagenesis.

FLOWERING LOCUS M (FLM) is known as a repressor of Arabidopsis flowering. Here, the authors show that a single intronic substitution of FLM modulates leaf color and plant growth strategy along the leaf economics spectrum, as well as plays a role in plant adaptation.

Chronic stress disrupts the brain vasculature and contributes to mood disorders, but mechanisms of resilience remain unclear. Here, the authors show that enriched environments increase astrocytic Fgf2 to prevent stress-induced vascular alterations and depressive behavior with relevance to human depression.

Quantum error correction codes protect quantum information, but running algorithms also requires the ability to perform gates on logical qubits. A lattice surgery scheme for fault-tolerant gates has now been demonstrated in a quantum repetition code.

Humanity’s Last Exam, a multi-modal benchmark at the frontier of human knowledge, is designed to be an expert-level closed-ended academic benchmark with broad subject coverage.

cellSTAAR advances noncoding rare variant association analysis by integrating single-cell genomics data.

Chronic care manages long-term, progressive conditions, while acute care handles short-term ones. Here, authors show chronic conditions account for most of the global health burden, with 68% of DALYs and 93% of YLDs attributed to chronic care needs.

Kinematic measurements of the Perseus galaxy cluster reveal two drivers of gas motions: a small-scale driver in the inner core associated with black-hole feedback and a large-scale driver in the outer core powered by mergers.

Declining snow cover poses a substantial risk for many ski resorts that often counter this trend with snowmaking, leading to increasing emissions caused by ski tourism. Research now quantifies the risks of rising temperatures to the skiing industry at the pan-European level, together with the potential and emissions of snowmaking.

How landscapes are arranged affects soil pathogenic fungi worldwide. The authors reveal the global pattern and pronounced scale-dependency of landscape complexity and land-cover quantity on soil pathogenic fungal diversity.

Love and colleagues find an inhibitory function for CD3ζ ITAMs in response to low-affinity ligands, meaning that CD3ζ can perform a dual function in TCR signaling by playing a positive or negative role depending on the affinity of the TCR for its peptide ligand.

Current short-pulse-duration neutron sources suffer from a low repetition rate, hindering applications. Here, the authors demonstrate advancements of laser-wakefield based photoneutron generation at high repetition rates and conversion efficiencies, providing an alternative to traditional pitcher-catcher methods.

Large-scale sequencing and population genomic analyses reveal frequent transmission, a highly admixed global population structure and evidence of pervasive negative selection in Haemophilus influenzae.

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.

Single-agent maintenance PARP inhibition may represent an effective strategy for advanced/metastatic endometrial cancer treatment. Here this randomized phase IIb UTOLA trial evaluates the efficacy and safety of orally administered olaparib in female patients (n = 145) without progression following front-line platinum-based chemotherapy for advanced/metastatic endometrial cancer.

Meta-analysis of genome-wide association studies on Alzheimer’s disease and related dementias identifies new loci and enables generation of a new genetic risk score associated with the risk of future Alzheimer’s disease and dementia.

The authors reveal that the C-terminal tail anchors of BCL-2 family proteins control BH3 binding and cell survival by allosteric regulation at the mitochondrial membrane, involving BAX recruitment and complex disruption upon BH3 mimetic antagonism.

Borcoman and colleagues present the efficacy and safety results of the phase 2 PEVOsq basket trial investigating the combination of pembrolizumab with the epidrug vorinostat in patients with recurrent and/or metastatic squamous cell carcinoma.

Over the past 70 years, CERN’s accelerators and experiments have delivered some remarkable results and discoveries, owing to the efforts of generations of physicists. We asked seven of the new generation — all CERN Fellows, in the early stages of their career — to tell us about some of the milestone achievements in the history of their laboratory.

Adamopoulos, Rovas et al. show that high regional wall shear stress correlates with fibrosis and electrical scarring in the left atrium of patients with atrial fibrillation, providing insight into the development of fibrotic tissue.

The 2S–2P transitions in muonic helium-4 ions are measured using laser spectroscopy and used to obtain an α-particle charge-radius value five times more precise than that from electron scattering.

Large genome-wide meta-analysis of clinically diagnosed late-onset Alzheimer’s disease (LOAD) from 94,437 individuals identifies new LOAD risk loci and implicates Aβ formation, tau protein binding, immune response and lipid metabolism.

Whole-genome sequences and field experiments focusing on the global invasive forage crop, Trifolium repens, show high levels of genetic variation across continents and parallel signatures of selection in five haploblocks.

A region on chromosome 19p13 is associated with the risk of developing ovarian and breast cancer. Here, the authors genotyped SNPs in this region in thousands of breast and ovarian cancer patients and identified SNPs associated with three genes, which were analysed with functional studies.

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.

XRISM observations show the presence of odd-numbered elements chlorine and potassium in Cas A. These findings suggest that stellar activity plays an important role in cosmic chemical evolution, enriching space with elements vital for planets and life.

Analyses of 475 ancient horse genomes show modern horses emerged around 2200 bce, coinciding with sudden expansion across Eurasia, refuting the narrative of large horse herds accompanying earlier migrations of steppe peoples across Europe.

Genomic, transcriptomic and epigenetic analyses of malignant pleural mesothelioma identify molecular axes and specialized tumor profiles underlying intertumoral heterogeneity.

The non-coding RNA RNU4-2, which is highly expressed in the developing human brain, is identified as a syndromic neurodevelopmental disorder gene, and, using RNA sequencing, 5′ splice-site use is shown to be systematically disrupted in individuals with RNU4-2 variants.

A cross-ancestry meta-analysis of genome-wide association studies identifies association signals for stroke and its subtypes at 89 (61 new) independent loci, reveals putative causal genes, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as potential drug targets, and provides cross-ancestry integrative risk prediction.

Proactive personal, collective and generational actions are vital

The function of type 3 innate lymphoid cells (ILC3s) in cancer is still poorly understood. Bruchard et al. demonstrate that ILC3s are critical for the recruitment of T cells to the tumor microenvironment and thereby play important roles in antitumor responses.

Inventory data from more than 1 million trees across African, Amazonian and Southeast Asian tropical forests suggests that, despite their high diversity, just 1,053 species, representing a consistent ~2.2% of tropical tree species in each region, constitute half of Earth’s 800 billion tropical trees.

Quantum dots encapsulated in a gold nanoshell provide a hybrid plasmonic–fluorescent emitter with increased stability against high power excitation or drastic changes in the environment.