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PCBP2 is elevated in AD and forms condensates that sequester mitochondrial proteins and RBPs, disrupting mitochondrial function and the NMD of BACE1 mRNA, alongside amyloid deposition. The small molecule, CN-0928 mitigates AD pathology by inhibiting PCBP2 condensation.

This study shows that the tropical meridional surface temperature gradient remains stable across a wide range of climates from extremely cold to extremely hot. This robust feature is maintained by solar radiation and tropical dynamics and provides a fundamental law to study climate change.

This work uncovers why traditional methods underestimate active site density in fuel cell catalysts. The researchers developed a novel in-situ acid-assisted method coupled with infrared spectroscopy to accurately quantify sites and elucidate their structure, validated across multiple catalysts.

Metallic materials suffer severe strength degradation at elevated temperatures. The authors report exceptional high-temperature strength in an additive manufactured aluminum alloy with a thermally stable nanoscale eutectic cellular network.

In a prespecified interim analysis of the randomized, double-blind phase 3 COMPASSION-15 trial, patients with advanced HER2-negative gastric/GEJ cancer treated with the anti-PD-L1/CTLA-4 bispecific Ab cadonilimab plus chemotherapy showed significantly improved overall survival compared with patients treated with placebo plus chemotherapy as first-line treatment.

Lipid nanoparticles are the gold standard for mRNA delivery but suffer from low loading capacity. Here, the authors report on the use of manganese ions to form mRNA rich cores within lipid nanoparticles which increased mRNA loading, reducing the lipid needed and increasing transfection and immune response in vivo.

The partial oxidation of methane to value-added C₁ chemicals is a promising approach for natural gas utilization. Here the authors report a catalyst-free oxidation method via mechanical stirring and ultrasonic cavitation.

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.

The authors study the effects of heterovalent doping on superconducting bilayer nickelate thin films.

In the phase 2 trial NEOSUMMIT-01, perioperative treatment of patients with locally advanced gastric or gastro-esophageal junction adenocarcinoma with anti-PD-1 and SOX/XELOX versus SOX/XELOX alone improved pathological complete response or near-complete response rate.

Theories of Cenozoic mountain uplift and associated global cooling assume that eroded mountain sediments are stored in marine basins. Here, based on detailed provenance data, Nie et al. show that Northeast Tibetan sediments are in fact stored inland, in the Chinese Loess Plateau and Mu Us desert.

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 authors report a study increasing hydrogen peroxide electrosynthesis kinetics over a Ni(OH)₂/CNT material. They show that the catalyst enhances H₂O dissociation and proton transfer in neutral media.

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.

In this Perspective, members of the Aging Biomarker Consortium outline the X-Age Project, an Aging Biomarker Consortium plan for building standardized aging clocks in China. The authors discuss the project roadmap and its aims of decoding aging heterogeneity, detecting accelerated aging early and evaluating geroprotective interventions.

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.

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

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 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.

Two types of skyrmion-like polar nanodomain are observed in oxide bilayers transferred onto silicon, and these nanodomains, with distinct resistive behaviour, can be converted to each other under an external electric field.

A selective shielding strategy achieves the differentiation and quantification of distinct plasmonic photocatalytic mechanisms including hot carrier-driven photochemistry, resonant field-mediated energy transfers, and thermal contributions.

A-kinase anchoring protein 1 (AKAP1) promotes the assembly of signalosomes on the mitochondrial outer membrane and act as a central hub for mitochondrial signalling. Here, the authors show that AKAP1 protects against MASLD progression by inhibiting mitochondrial GPAT1 activity and subsequent lysophosphatidic acid production.

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.

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.

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.

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.

Senescent melanocytes of skin nevi drive hyperactivation of hair growth through the signalling factor SPP1.

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.

In situ mechanical testing and simulations unveil a reversible shuffle twinning mechanism enabled by bond switching, which gives rise to anisotropic tensile superelasticity in GeSe ceramics.

The inner ear is highly organized, with distinct domains being located across the Line of Polarity Reversal (LPR). Here they show that Emx2 establishes the LPR and bidirectional selectivity of otolith organs, and that loss of the LPR in mice affects swimming and balance.

Worldwide, the number of only-child families is increasing. This research examines how growing up without siblings affects adult brain structure, function and connectivity, cognition, personality and mental health.

This study reveals how the North Atlantic Oscillation emerged and evolved over 160 million years, highlighting the role of continental drift, land-ocean contrast, and orography in shaping modern atmospheric variability.

DNA 5-hydroxymethylcytosine (5hmC) modification is associated with gene transcription and used as a mark of mammalian development. Here the authors report a comprehensive 5hmC tissue map and analysis of 5hmC genomic distributions in 19 human tissues derived from 10 organ systems, thus providing insights into the role of 5hmC in tissue-specific development.

cell–cell communication (CCC) is crucial for understanding biological processes. Here, authors present DeepTalk, which combines single-cell RNA sequencing and spatial transcriptomics data to infer cell–cell communication at single-cell resolution, revealing intricate intercellular dynamics within tissues.

Primary biliary cholangitis is an autoimmune liver disease. Here, the authors show that variants in interleukin genes which potentially deregulate their expression are associated with this condition, and suggest that the IL21 signalling pathway may have a role in disease aetiology.

Type I PRMT inhibition elicits potent antitumor activity associated with increased interferon response and intron-retained dsRNA accumulation, suggesting its potential combination with immune checkpoint inhibitors for cancer treatment.

Freestanding perovskite oxides pave the way to novel flexural properties. Here, the authors observe the nanoscale strain gradient induced flexoelectric polarization with an unusual flexo-expansion/shrinkage effect in freestanding ferroelectric oxide.