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Base editors (BEs) enable precise base substitutions but are limited by their large size. Here, the authors engineer a split BE system utilizing coiled-coil heterodimers (CC-BE) and demonstrate that CC-BEs maintain or even enhance efficiency, enabling gene therapy applications via dual AAV.

T-cell engager (TCE)-based immunotherapy requires further development in solid tumors due to limited T cell penetration, immunosuppressive tumor microenvironment and toxicity. The authors here develop a glypican-3 targeting mRNA TCE (MTS105) which manifests superior T cell activation and tumor regression hepatocellular carcinoma mice model comparing to conventional TCE, and safety with cynomolgus monkey studies.

Identifying jets originating from heavy quarks plays a fundamental role in hadronic collider experiments. In this work, the ATLAS Collaboration describes and tests a transformer-based neural network architecture for jet flavour tagging based on low-level input and physics-inspired constraints.

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.

Major depressive disorder has been linked to peripheral immune dysfunction. Here, the authors identify elevated stem cell-like memory CD8⁺ T cells in patients and in a murine stress model show migration to the intestine via PPBP-CXCR2 and suggest gut CD8 cells modulate tyrosine metabolizing bacteria and homovanillic acid potentiating neuroinflammation and depressive phenotype.

In this attempt at xenotransplantation of a lung from a genetically modified pig into a brain-dead recipient, although the grafted lung initially maintained viability and functionality, antibody-mediated rejection rapidly occurred, contributing to xenograft damage.

Shroom3 genetic variants increase Shroom3 levels and promote kidney fibrosis but reduce proteinuria, complicating Shroom3 targeting for precision medicine. Here, the authors show increased fibrosis mediated by Shroom3–Rock signaling and blocking this interaction genetically or with new compounds reduces tubular Rock activation and fibrosis.

Here, a draft sequence of the giant panda genome is assembled using next-generation sequencing technology alone. Genome analysis reveals a low divergence rate in comparison with dog and human genomes and insights into panda-specific traits; for example, the giant panda's bamboo diet may be more dependent on its gut microbiome than its own genetic composition.

A DNA matrix material potentiates humoral response through multiple administration routes, generating neutralizing antibodies and conferring robust protection against infection.

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 influenza virus neuraminidase has been well documented, yet the functions of mammalian neuraminidases remain less explored. Here, the authors show that neuraminidase 1 promotes renal fibrosis development by interacting with ALK5 to activate SMAD2/3.

Understanding the impact of the solid electrolyte interphase (SEI) on lithium deposition is crucial for developing high-energy lithium metal batteries. Here, authors elucidate the multi-scale effects of the SEI on lithium deposition behavior based on the established SEI-omics framework.

This Review provides a holistic view of sustainable gas, liquid and solid insulating materials, focusing on substitution, benign degradation, recycling, reuse and resource conversion to support net zero power systems.

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.

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 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.

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.

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.

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.

Immune check point therapies have not been successful for prostate cancers, but the underlying mechanisms are unclear. Here the authors show that a transcription factor, YY1, may promote the SUMOylation and stability of HIF-1α to suppress anti-tumor immunity, while targeting YY1 helps improve tumor control, in mouse prostate cancer models.

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.

Here, the authors combine structural, binding, mutational in vitro and in vivo assays to characterize neutralizing antibodies derived from IGHV3-53/3-66 against SARS-CoV-2, finding one antibody, named P5A-3C8, to exhibit protective efficacy in a golden Syrian hamster model of infection while showing the emergence of mutations at position 417 of the Spike protein that confer resistance.

The H9N2 avian influenza viruses (AIVs) remain dominant in live poultry markets in China, and H9N2 AIVs with HA-Q226L, PB2-V/K627 and NP-N52 mutations can be transmitted between guinea pigs and between ferrets via direct contact and respiratory droplet.

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.

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.

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.

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

Multiple genetic loci are associated with lung cancer risk, but the underlying genetic mechanisms remain poorly understood. Here, the authors perform single-cell RNA-seq and ATAC-seq analyses of lung cells from ever- and never-smokers; they report candidate cis-regulatory elements that colocalise with candidate causal variants in lung cancer risk loci and potential susceptibility genes.

Global land cover conversions increased carbon uptake during 1982 to 2019, with newly established forests in the Northern Hemisphere driving gains that counterbalanced emissions from tropical deforestation.

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.

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.

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.

Proton exchange membrane water electrolysis promises green hydrogen production but safety risks in industrial operations remain unexplored. Here, the authors identify water-starvation as the cause of water electrolysis stack deflagration and establish safety precautions for industrial scale-up.

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.

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.

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.

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.

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.

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.

The microglia–neuron interactions contributing to neuronal hyperexcitability are unclear. Here, the authors show how GABA and C3 signaling coordinate microglial engulfment of inhibitory synapses, driving excitatory–inhibitory imbalance and neuronal hyperexcitability in epilepsy.

Analysis of mitochondrial genomes (mtDNA) by using whole-genome sequencing data from 2,658 cancer samples across 38 cancer types identifies hypermutated mtDNA cases, frequent somatic nuclear transfer of mtDNA and high variability of mtDNA copy number in many cancers.

During electrocatalytic nitrate reduction, cobalt-based catalysts degrade fast due to the combined effect of nitrate oxidation and electric-field reduction. Here, the authors develop a Co6Ni4 heterostructured catalyst to prevent high valence Co accumulation and achieve efficient ammonia synthesis.

Zi-Jiang Chen and colleagues report a genome-wide association analysis for polycystic ovary syndrome (PCOS) in Han Chinese. They identify eight new susceptibility loci for PCOS in this population.