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A mouse ovarian cancer model MEPP with Pten/Trp53 loss, engineered using the EPI-SauriCas9 system, provides a platform for dissecting ovarian cancer biology and accelerating drug discovery.

The mechanisms underlying the limited response to immune checkpoint blockade (ICB) in most patients remain elusive. This study identifies GBP2 as a key enhancer of T cell-mediated ferroptosis and ICB efficacy through phase separation and STAT1 activation.

Environmental Li pollution and health problems have been becoming an important concern worldwide. Here, the authors show that Li exposure causes trophoblast cell ferroptosis and thus induces unexplained miscarriage through a non-canonical MBOAT1 pathway.

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.

The quality of immune response to SARS-CoV-2 is thought to wane over time, but it is unclear how long it can persist. Here the authors show persistent immune responses in a large number of patients over the course of a 1-year follow-up from the time of recovery from COVID-19.

Robust Cu single-atom catalysts show promise for CO₂ electroreduction but face stability challenges. Here, the authors report a self-healing Cu single-atom catalyst that maintains high performance and stability for CO₂-to-CH₄ conversion at industrial current densities.

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

Fan et al. show that cTAGE5 is essential for adipogenesis and adipose tissue development. Mechanistically, cTAGE5 promotes pro-insulin receptor processing, which mediates actin cytoskeleton remodeling and lipolysis during the adipocyte differentiation.

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.

Lu et al. characterize cis-regulatory element dynamics at different stages of colorectal cancer progression and identify a functional variant associated with increased colorectal cancer risk because of selective transcription factor binding.

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.

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.

In the multicenter phase 2 OptiTROP-Lung01 trial in patients with treatment-naive advanced non-small-cell lung cancers, the antibody–drug conjugate sacituzumab tirumotecan with anti-PD-L1 tagitanlimab was safe and showed encouraging clinical efficacy.

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 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.

Here, the authors performed plasma proteomics and metabolomics analysis and identify the vinculin (VCL) pathway as a key mediator of lung exudation in SARS-CoV-2 infections, particularly associated with Omicron infection. In a mouse model of infection inhibition of VCL leads to reduced lung pathology.

In the OptiTROP-Breast01 phase 3 trial, patients with metastatic triple-negative breast cancer who received the TROP2-targeted antibody–drug conjugate sacituzumab tirumotecan experienced longer progression-free survival than patients treated with chemotherapy.

Bioisosteric design has become an essential approach during drug molecule discovery process. Here, the authors describe a strategy for defluorinative couplings of propellanes, enabling the synthesis of aryl difluoromethyl bicyclopentanes as benzophenone-type bioisosteres.

Changes of left ventricular structure are used to predict morbidity and mortality in cardiovascular diseases. Here the authors conducted a study using advanced deep learning technology to analyze left ventricular regional wall thickness (LVRWT) in a large population, identifying 72 significant genetic loci linked to LVRWT traits.

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.

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.

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.

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.

Chemical analyses show permafrost soils on the Tibetan Plateau contain large amounts of halogenated organic chemicals that could be remobilized in a changing climate.

A Gobi Desert megalake system reconstruction enables a quantitative estimate of East Asian Monsoon climate for the last two interglacials and provides insights into dust flux variations across East Asia and northern Pacific

A Fusarium graminearum effector is found to target wheat fumarylacetoacetate hydrolase for 26S proteasomal degradation. The hydrolase enhances resistance to Fusarium head blight by regulating defense genes and amino acid metabolism, offering a genetic target for wheat improvement.

Interpreting bone metastases (BMs) from computed tomography (CT) images remains challenging. Here, the authors develop an AI-based Bone Lesion Detection System - BLDS - and validate it in a cohort of 2,518 patients across five hospitals, showing highly sensitive and accurate performance for BM detection from CT scans.

Rapid temperature flips between hot and cold extremes will become more frequent, more intense, and more rapid globally by the end of the twenty-first century, which is exacerbated in world’s breadbasket regions and low-income countries.

In this study, authors identified neutralizing antibodies by isolating B cells from SARS-CoV-2 Delta infected patients and detect altered structural features, likely introduced by somatic hypermutation, that are involved in epitope binding and increase neutralization breadth against virus variants.

SARS-CoV-2 breakthrough infections in vaccinated individuals are a public health concern. Here, the authors analyse the clinical characteristics and profile immune alterations among vaccinated and non-vaccinated residents with Delta SARS-CoV-2 infection in Guangzhou.

The effect of zingerone on postmenopausal osteoporosis, as modelled in mouse, was assessed The authors combine single-cell transcriptomics and bulk metabolomics to investigate cardiac myxoma. They identify Subtype 1 marked by MAPK/WNT/EGFR pathway activation and Subtype 2, characterized by ribosomal and oxidative phosphorylation signatures

There is increasing evidence that treatment of hepatitis B with interferon alpha can be beneficial. Here, Wang et al, present a type 1 interferon receptor humanized mouse model and characterize it as a platform in which to study interferon function in vivo.

The role of cations in the CO₂ electroreduction is crucial, but elusive. Here, the authors combine electrokinetic on a well-defined single-atom catalyst with grand canonical potential kinetics simulations to provide an in-depth study of the interaction of K ⁺ -ions with adsorbed CO₂⁻.

Identifying causal relations or causal networks among molecules/genes is of great importance but challenging. By introducing a causal inference algorithm based on cross-validated predictability (CVP), the research demonstrates high accuracy and robustness in predicting causal networks independent of time-series data and directed acyclic graph (DAG)

Indigenous and crossbred bovines produce less methane and consume nitrogen more efficiently than improved bovines, according to a meta-analysis combined with measurements of methane emissions from yaks in China.

Population growth in the coming decades will lead to increasing land conversion to urban areas. Here, the authors use spatially explicit projections of global urban expansion to analyze its effects on habitat changes, and terrestrial mammals, birds and amphibians under the main shared socioeconomic pathways.

Here, the authors apply the Activity-by-Contact (ABC) model to infer enhancer-gene regulation and the effect of associated variants across multiple cancer types, integrating genetic and multi-omics data. Then, they explore the mechanisms associated with ABC regulatory variants in colorectal cancer.

Two sequence-verified, clonal, publicly available collections of human open reading frames are reported. One collection is in a lentiviral vector for expression in mammalian cells; the other is in the Gateway vector system.