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Capturing RNA-protein interactions is vital for understanding cellular regulation but remains technically challenging. Here, the authors develop CuCLIP-seq, a sensitive, chemical-crosslinking method that accurately identifies diverse RNA substrates, including low-abundance targets.

Electron microscopy and spectroscopy, together with electronic structure calculations, are used to show that orbital ordering of ions at grain boundaries can facilitate the stabilization of ferroelectric phases.

SLC15A4 is essential for TLR7/8/9-mediated immune responses through a conformation-dependent interaction with TASL. Here, the authors identify two conformation-selective antibodies that differentially target distinct structural states of human SLC15A4.

The ABC transporter ABCC1 confers resistance to anticancer drugs and mediates physiological functions by exporting diverse substrates. Here, authors determine ten cryo-EM structures of ABCC1 in distinct functional states, providing systematic insights into its substrate recognition diversity and transport dynamics.

Dual-mode ferroelectric transistors enable hardware-efficient analogue operations for generative-adversarial-network-inspired image processing in medical imaging applications.

SLC19A1 is crucial for transporting folates, antifolates and cyclic dinucleotides. Here authors determined outward-open structures of hSLC19A1 with and without bound substrates, revealing detailed mechanisms of substrate recognition and conformational changes during transport.

Here, Zhang et al. succeed in creating a heavily distorted oxygen deficient film of lanthanum cobaltite. The new phase of LaCoO_2.5 has several unique properties, most notably, a Curie temperature of 284 K, significantly larger than the films from which it was derived.

Nanometer-wide lateral heterostructures between 2D semiconductors are still rare. Here the authors report the valley-selective hole state transmission between ferroelectric SnTe monolayers separated by a PbTe barrier with the width of merely 2 nm.

Neuromorphic vision hardware calls for all-in-one integration of photodetection and computing. Huo et al. report an optoelectronic synapse based on a ReS₂ channel integrated to a metal–ferroelectric–metal–insulator–semiconductor architecture, showing ultra-low dark current and high photoresponsivity.

Two cyclic dinucleotide molecules bind within the cavity of human SLC19A1 as a compact dual-molecule unit, whereas folate and antifolate bind to SLC19A1 as a monomer and occupy a distinct pocket of the cavity.

The defense-associated sirtuin 2 (DSR2) system protects bacteria from phages by depleting NAD⁺. Here, authors elucidate the molecular mechanisms underlying DSR2 assembly, activation, and inhibition, providing important insights into bacterial anti-phage defense.

In a multicenter, open-label, randomized phase 2 trial, neoadjuvant chemoradiation with PD-1 blockade elicited a pathological complete response rate superior to that with neoadjuvant chemoradiation alone in patients with locally advanced rectal cancer.

Li et al. uncover a lysosomal surveillance response whereby intestinal lumen deacidification induces a transcriptional programme that boosts lysosomal activity and improves protein aggregate clearance in multiple worm disease models, extending healthspan.

Tian et al. reveal that rich temporal dynamics within individual brain regions form stable individual-specific ‘barcodes’, advancing generalizable brain-wide association studies beyond traditional connectivity measures.

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.

Transistor-type optoelectronic sensors combine photodetection with gate-tunable transistor architectures, enabling programmable and multifunctional sensing beyond conventional devices. This Review outlines their operating principles and architectures, and highlights opportunities for intelligent, next-generation optoelectronic sensing.

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.

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.

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.

In somatic cells the mechanisms maintaining the chromosome ends are normally inactivated; however, cancer cells can re-activate these pathways to support continuous growth. Here, the authors characterize the telomeric landscapes across tumour types and identify genomic alterations associated with different telomere maintenance mechanisms.

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.

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.

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.

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.

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 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.

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.

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.

Some cancer patients first present with metastases where the location of the primary is unidentified; these are difficult to treat. In this study, using machine learning, the authors develop a method to determine the tissue of origin of a cancer based on whole sequencing data.

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

Many tumours exhibit hypoxia (low oxygen) and hypoxic tumours often respond poorly to therapy. Here, the authors quantify hypoxia in 1188 tumours from 27 cancer types, showing elevated hypoxia links to increased mutational load, directing evolutionary trajectories.

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 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.

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.

Ferroelectric phase stability is a pivotal challenge for fluorite-structure ferroelectrics. Using electron microscopy, a ferroelastically protected reversible polar-to-non-polar phase transition in ZrO₂ is observed and the critical strain state to break the reversibility is measured.

A hybrid epoxy–acrylate resin is reported for the digital light processing 3D printing of bioinspired metamaterial structures with precisely patterned hard and soft domains.

Flow-based generative models enable Boltzmann sampling but are computationally limited in high-dimensional systems due to costly Jacobian evaluations. The authors introduce a stochastic flow perturbation method that achieves unbiased and significantly faster Boltzmann sampling, outperforming the Hutchinson estimator in both accuracy and efficiency.

Methods for transition-metal-catalysed enantioselective C(sp³)–S bond construction are underdeveloped. Now, by taking advantage of the biomimetic radical homolytic substitution manifold, the copper-catalysed enantioconvergent C(sp³)–S cross-coupling of racemic secondary and tertiary alkyl halides with highly transformable sulfur nucleophiles has been realized. This reaction provides access to an array of α-chiral alkyl organosulfur compounds.

A transfer technique that embeds a van der Waals interface of interest in a high-adhesion matrix can decouple the properties of the functional interface from the forces required for its fabrication, providing single-step material-to-device integration.

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.

Reconfigurable transistors are important for creating compact and efficient neuromorphic computing networks. Here, authors present an antiferroelectric transistor utilizing synergic polarization switching and charge trapping dynamics to perform multiple neuromorphic functions.

While Bell inequalities have been violated several times—mostly in photonic systems—their violations within particle physics experiments are less explored. Here, the BESIII Collaboration showcases Bell-violating nonlocal correlations between entangled hyperon pairs.

Favoured cathodes for batteries should include abundant and redox-active elements, such as manganese. Here the authors report a Na_0.6Li_0.2Mn_0.8O₂ cathode design featuring a unique layer stacking sequence that provides topological protection to oxygen redox to overcome the performance fading.

How the position of conspecifics is represented in the brain is not fully understood. Here authors show that the position of conspecifics is represented relative to self-position in the hippocampus of female mice, which is modulated by context and identity and improved through learning.