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Using ARPES, this work identifies dice-lattice flat bands in the electride material YCl. The authors show that anionic electrons act as lattice sites to create this rare electronic structure.

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.

Targeting neurons that regulate energy balance may offer new approaches for obesity treatment. Here, authors show that chemogenetic and pharmacological manipulation of GABAergic neurons in the DRN/vlPAG increases adaptive thermogenesis and reduces weight gain in mice fed a highfat diet.

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

APOBEC deaminases restrict retroviruses but can also mutate human DNA. Here, the authors show that cancerassociated APOBEC3s with low RNA binding, known to enter the nucleus, are selectively recognized by E3 ligases and degraded, eliminating harmful nuclear enzymes, and limiting genome mutation.

Plant traits drive ecosystem dynamics yet are challenging to map globally due to sparse measurements. Here, the authors combine crowdsourced biodiversity observations with Earth observation data to accurately map 31 plant traits at 1 km² resolution.

Affinity-proteomics platforms often yield poorly correlated measurements. Here, the authors show that protein-altering variants drive a portion of inter-platform inconsistency and that accounting for genetic variants can improve concordance of protein measures and phenotypic associations across ancestries.

High-resolution satellite data enables a unique verification of national methane emissions worldwide. Global estimates are 63 Tg a⁻¹ for oil-gas, 30% higher than the UNFCCC reports due to under-reporting by four largest emitters, and 33 Tg a⁻¹ for coal, consistent with previous estimates.

DNA methylation and gene expression data integration identify aging-related genes in blood that predict health outcomes, offering new insights into aging biology and potential therapeutic targets.

Researchers applied high resolution inversions of satellite methane observations to estimate methane emissions from 161 countries, finding that global anthropogenic emissions are 15% larger than Paris Agreement reporting.

Global Burden of Disease estimates show that between 1990 and 2023, the prevalence and burden of drug use disorders, inclusive of amphetamine, cannabis, cocaine and opioid use, have been increasing in high-income countries, particularly in the USA.

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.

Taveneau et al. leverage artificial-intelligence-driven protein design to create inhibitors that control RNA-targeting enzymes in cells, revealing a strategy to rapidly design off-switches for RNA-editing systems.

Estimates from the Global Burden of Disease study reveal declines in chronic respiratory disease mortality between 1990 and 2023—especially during the COVID-19 pandemic—but the burdens on people affected remain substantial.

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.

Integrating computational analyses of T cell exhaustion and mitochondrial fitness atlases with in vivo CRISPR screens has identified KLHL6 as a dual-negative regulator of both exhaustion differentiation and mitochondrial dysfunction, highlighting its potential as a target to enhance anti-tumour immunity.

TCR-engineered T cells have shown limited efficacy in part due to the absence of co-stimulation leading to limited accumulation in solid tumors. The authors here show engineering the CD8β coreceptor with an intracellular CD28 domain enhances cytokine production, persistence, and tumor control in vivo independent of tumor-associated co-stimulatory ligand encounter.

In this study, Kennedy et al. combine crystallography, biophysical measurements and biochemical assays to define a structural cycle for Werner syndrome helicase (WRN) and reveal how nucleotide binding and ssDNA engagement lead to conformational transitions.

A universal design strategy for nanograined metals aimed at utilizing oxygen nanoclustering to achieve the highly desired combination of high strength and large deformability that evades inverse Hall-Petch softening.

This study uses a multi-model intercomparison framework and a large-scale observational constraint based on a volcanic eruption and shows that climate models strongly underestimate how cloud cover responds to aerosols, leading to major uncertainties in climate projections.

Kang, Lazo de la Vega et al. introduce iCatalog, a precision oncology reporting tool developed to address the needs of a large multi-institutional pediatric study. iCatalog combines a database for patient, sample, and genomic data to enable clinical interpretation of patient-level tumor profiling results.

The extreme hot and dry conditions of 2023 reduced soil respiration and enhanced net forest carbon sequestration in Canada, offsetting wildfire emissions, according to satellite-based and in situ observations of CO₂ fluxes.

Here the authors provide an explanation for 95% of examined predicted loss of function variants found in disease-associated haploinsufficient genes in the Genome Aggregation Database (gnomAD), underscoring the power of the presented analysis to minimize false assignments of disease risk.

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.

Electron distributions exhibit velocity-space signatures indicative of the rapid energy released by magnetic reconnection explosions occurring in Earth’s magnetosphere and in plasmas throughout the universe. Here, the authors discover a smile-shaped signature in the electron gradient distribution associated with reconnection occurring at Earth’s dayside magnetopause boundary.

Epstein–Barr virus (EBV) is a widespread herpesvirus linked to cancer and autoimmune disease. The authors in this work design and characterize a stabilized prefusion form of gB, an essential viral fusion protein, advancing EBV vaccine and therapeutic development.

Exchange bias, where an adjacent antiferromagnet leads to an offset magnetization loop in a ferromagnet is a critical effect in magnetic memory devices. Here, Pellet-Mary et al introduce a “lateral exchange bias”, allowing control of the Neel vector in bilayer samples of CrSBr via laterally adjacent odd layered segments.

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.

CaBLAM is a bioluminescent genetically encoded calcium indicator that delivers high-contrast signals as shown in cell culture, in the in vivo mouse brain and in zebrafish larvae.

iGluSnFR4f and iGluSnFR4s are the latest generation of genetically encoded glutamate sensors. They are advantageous for detecting rapid dynamics and large population activity, respectively, as demonstrated in a variety of applications in the mouse brain.

The flagship paper of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium describes the generation of the integrative analyses of 2,658 cancer whole genomes and their matching normal tissues across 38 tumour types, the structures for international data sharing and standardized analyses, and the main scientific findings from across the consortium studies.

MultiSTAAR provides a general and flexible statistical framework for functionally informed multi-trait rare variant analysis of biobank-scale sequencing studies by jointly analyzing multiple traits and incorporating annotation information.

It is uncertain how much life expectancy of the Chinese population would improve under current and greater policy targets on lifestyle-based risk factors for chronic diseases and mortality behaviours. Here we report a simulation of how improvements in four risk factors, namely smoking, alcohol use, physical activity and diet, could affect mortality. We show that in the ideal scenario, that is, all people who currently smokers quit smoking, excessive alcohol userswas reduced to moderate intake, people under 65 increased moderate physical activity by one hour and those aged 65 and older increased by half an hour per day, and all participants ate 200 g more fresh fruits and 50 g more fish/seafood per day, life expectancy at age 30 would increase by 4.83 and 5.39 years for men and women, respectively. In a more moderate risk reduction scenario referred to as the practical scenario, where improvements in each lifestyle factor were approximately halved, the gains in life expectancy at age 30 could be half those of the ideal scenario. However, the validity of these estimates in practise may be influenced by population-wide adherence to lifestyle recommendations. Our findings suggest that the current policy targets set by the Healthy China Initiative could be adjusted dynamically, and a greater increase in life expectancy would be achieved.

A meta-analysis of genome-wide association studies of type 2 diabetes (T2D) identifies more than 600 T2D-associated loci; integrating physiological trait and single-cell chromatin accessibility data at these loci sheds light on heterogeneity within the T2D phenotype.

Rare loss-of-function mutations in SETD1A are associated with schizophrenia, but how SETD1A haploinsufficiency leads to disease phenotypes remains unknown. Here, authors show that SETD1A regulates genes at common schizophrenia risk loci regulating genomic stability and synaptic function.

Hodgkin Reed Sternberg (HRS) cells and their surrounding microenvironment in Hodgkin lymphoma remain poorly characterized. Here, the authors perform genome-wide transcriptional profiling with spatial and single-cell resolution to explore the cellular and molecular composition of the Hodgkin lymphoma microenvironment and used machine learning to identify IL13 as a potential HRS cell survival factor.

An analysis of 2,954 genomes from 38 cancer subtypes identified 19,166 retrotransposition events in 35% of samples. Aberrant LINE-1 retrotranspositions can lead to the deletion of tumor-suppressor genes as well as the amplification of oncogenes.

Understanding deregulation of biological pathways in cancer can provide insight into disease etiology and potential therapies. Here, as part of the PanCancer Analysis of Whole Genomes (PCAWG) consortium, the authors present pathway and network analysis of 2583 whole cancer genomes from 27 tumour types.

Understanding the mechanisms underlying the survival of drug tolerant persister cells following chemotherapy remains elusive. Here, multi-omics analysis and experimental approaches show that the germ-cell-specific H3K4 methyltransferase PRDM9 promotes metabolic rewiring in glioblastoma stem cells.

Analyses of 2,658 whole genomes across 38 types of cancer identify the contribution of non-coding point mutations and structural variants to driving cancer.

Chen et al. show that PEX39 cooperates with PEX7 in the peroxisomal import of proteins containing a PTS2 site and uncover an (R/K)PWE motif in PEX39 and PEX13 that binds to PEX7 and facilitates the import of PTS2-containing proteins.

Long COVID has heterogeneous presentation and clinical trajectories are not well defined. Here, the authors define trajectories using data from a prospective cohort study in the United States involving symptom questionnaires from acute infection up to 15 months.

In this study the authors consider the structural variants (SVs) present within cancer cases of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. They report hundreds of genes, including known cancer-associated genes for which the nearby presence of a SV breakpoint is associated with altered expression.

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.

Here, the authors report an exome-wide association study for multi-organ imaging traits by leveraging recent bioinformatic tools such as AlphaMissense. The identified signals elucidate the genetic effects from rare variants on human organs and their connections to complex diseases

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.