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Insulin signaling plays a crucial role in coordinating skeletal development with whole‑body energy metabolism. Here, the authors use phosphoproteomics to show insulin-signaling rewiring in aged, insulin-resistant bone and identify defective phosphorylation of AFF4 as a key mechanism for regulating gene-specific transcriptional activation.

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.

Here the authors report asperigimycins, fungal ribosomally synthesized and post-translationally modified peptides with a heptacyclic scaffold. After chemically modifying them for nanomolar anticancer activity, CRISPR screening identifies SLC46A3 as a key transporter for their uptake in cells.

Cardiac tissue remodeling in heart failure is driven by interactions between multiple cell types, but existing studies have not fully captured these coordinated responses. Here, the authors show that integrating bulk and single-cell transcriptomics across 1,524 individuals reveals robust multicellular programs that link fibroblast activation to cardiomyocyte stress and recovery.

Twin propagation involves three-dimensional normal, forward and lateral motion of twin interfaces with respect to the twinning shear direction. Here, the authors combine electron microscopy and atomistic simulations to study the until now unknown lateral structure of tensile deformation twins in magnesium.

Thermal lepton pairs are ideal probes for the temperature of quark-gluon plasma. Here, the STAR Collaboration uses thermal electron-positron pair production to measure quark-gluon plasma average temperature at different stages of the evolution.

Low-carbon lifestyles could reduce global carbon footprints by 10.4 gigatons CO₂e by targeting the top 23.7% of emitting households. This study quantifies 21 low-carbon expenditures while noting potential rebound effects that may offset carbon savings.

An understanding of the molecular mechanisms promoting the generation of immunoregulatory and tumour-promoting monocytes and macrophages is key to breaking the cycle of tumour myelopoiesis and developing more effective myeloid-targeting therapies.

Analysis of cancer genome sequencing data has enabled the discovery of driver mutations. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium the authors present DriverPower, a software package that identifies coding and non-coding driver mutations within cancer whole genomes via consideration of mutational burden and functional impact evidence.

A new artificial intelligence model, DeepSeek-R1, is introduced, demonstrating that the reasoning abilities of large language models can be incentivized through pure reinforcement learning, removing the need for human-annotated demonstrations.

PROTAC development has surged in popularity, however our ability to characterize PROTAC specificity in living cells has lagged behind. Here, the authors develop ProtacID, a flexible proximity-dependent biotinylation (BioID)-based approach to identify PROTAC-protein interactions in living cells.

Patagia—the mammalian gliding membrane—repeatedly originated through a process of convergent genomic evolution, whereby the regulation of Emx2 was altered by distinct cis-regulatory elements in independently evolved species.

The role Tibetan Plateau uplift played in Asian inland aridification remains unclear due to a paucity of accurately dated records. Here, the authors present a continuous aeolian sequence for the period >51–39 Ma, analysis of which indicates that aridification was driven by global climatic forcing rather than uplift.

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.

Molecular-beam epitaxy is famous for creating heterostructures with atomic-layer precision. Here, the authors show that rather than following the stoichiometry suggested by the crystal structure of a layered oxide, the desired layering is obtained utilizing deliberate non-stoichiometric growth conditions.

Nie et al. describe a mechanism underlying the degradation of the histone methyltransferase NSD2 through the recruitment of FBXO22 E3 ligase, providing a chemical probe for NSD2 function study and targeted protein degradation.

There’s an emerging body of evidence to show how biological sex impacts cancer incidence, treatment and underlying biology. Here, using a large pan-cancer dataset, the authors further highlight how sex differences shape the cancer genome.

Ensemble forecasts from a dynamical model suggest that fluctuations in atmospheric angular momentum and the length of day can be predicted over a year in advance, thereby providing a source of long-range climate predictability.

With the generation of large pan-cancer whole-exome and whole-genome sequencing projects, a question remains about how comparable these datasets are. Here, using The Cancer Genome Atlas samples analysed as part of the Pan-Cancer Analysis of Whole Genomes project, the authors explore the concordance of mutations called by whole exome sequencing and whole genome sequencing techniques.

Organometallic perovskite solar cells exhibit good efficiency but their photostability is still relatively poorly understood and controlled. Here the authors show that photo-degradation arises from the formation of light-activated meta-stable trap states, is reversible, and can be frozen at 0 °C.

Imaging deformation twins in three dimensions is difficult and they are usually viewed as two-dimensional ellipsoids. Here, the authors statistically analyze more than two hundred deformation twins in magnesium observed in three different views and show lateral twin expansion is faster than forward propagation.

Integrative analyses of transcriptome and whole-genome sequencing data for 1,188 tumours across 27 types of cancer are used to provide a comprehensive catalogue of RNA-level alterations in cancer.

A pan-cancer genomic analysis reports the effects of structural variations on chromatin domains (TADs). Most TAD disruptions do not result in appreciable changes in expression of nearby genes.

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.

The study of lattice vibrations coupled to electronic excitations may provide an avenue for exploring exotic physical phenomena. Here, Xuet al. observe a Fano resonance in the Weyl semimetal TaAs, revealing evidence for a strong coupling between phonons and Weyl fermions.

The semileptonic decay channels of the Λc baryon can give important insights into weak interaction, but decay into a neutron, positron and electron neutrino has not been reported so far, due to difficulties in the final products’ identification. Here, the BESIII Collaboration reports its observation in e+e- collision data, exploiting machine-learning-based identification techniques.

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.

The collective-flow-assisted nuclear shape-imaging method images the nuclear global shape by colliding them at ultrarelativistic speeds and analysing the collective response of outgoing debris.

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.

Whole-genome sequencing data from more than 2,500 cancers of 38 tumour types reveal 16 signatures that can be used to classify somatic structural variants, highlighting the diversity of genomic rearrangements in cancer.

Closed-loop optogenetic stimulation with excitatory opsins enables the precise manipulation of neural dynamics in brain slices from transgenic mice and in anaesthetized non-human primates.

The authors present SVclone, a computational method for inferring the cancer cell fraction of structural variants from whole-genome sequencing data.

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.

Cancers evolve as they progress under differing selective pressures. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, the authors present the method TrackSig the estimates evolutionary trajectories of somatic mutational processes from single bulk tumour data.

The stability issue of perovskite-based solar cells is in part due to electrode corrosion. Here, Brinkmannet al. develop an impermeable bilayered electron-extraction layer between the active layer and the electrode, suppressing decomposition of the perovskite and preventing corrosion from the inside.

Astrocytes adopt diverse states in response to brain injuries. Here, the authors develop a platform for spatially resolved, single-cell transcriptomics and proteomics, called tDISCO (tissue-digital microfluidic isolation of single cells for -Omics) to uncover the spatial boundaries of molecularly distinct reactive astrocyte populations in stroke.

Rifaximin use, particularly in patients with liver cirrhosis, may be compromising the clinical use of daptomycin.

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.

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 T cell response to SARS-CoV-2 is detected by a PCR assay on whole blood.

Viral pathogen load in cancer genomes is estimated through analysis of sequencing data from 2,656 tumors across 35 cancer types using multiple pathogen-detection pipelines, identifying viruses in 382 genomic and 68 transcriptome datasets.

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.

Targeting TBK1 is an effective strategy to overcome resistance to cancer immunotherapy.

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.