Search

Fan et al. describe DF-003, an alpha-kinase 1 (ALPK1) inhibitor that targets the root cause of the rare genetic disease ROSAH syndrome, demonstrating the ability of DF-003 to inhibit ocular inflammatory pathology in ROSAH model mice.

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.

Assessing failure pressure is critical in determining pipeline integrity. In this study, based on the unified yield criterion, authors propose a limit state equation for steel pipes under various loads which can be converted into a series of failure pressure evaluation models for pipeline with different yield criteria.

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.

On-chip mode-division multiplexing has many challenges including crosstalk, losses, and footprint.  Here the authors use a nanohole metastructure to create multiplexed bends and crossings for photonic data communications circuit routing with high density that combats these challenges.

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.

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.

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.

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.

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.

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.

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 use of biomarkers of ageing is crucial for investigating age-related processes. This Review discusses biomarkers of ageing and of ageing-associated physiological changes, at the cellular, tissue and organism levels in humans and non-human primates.

Nanotwinning strategies are widely recognized for their ability to substantially enhance the mechanical properties of materials. Here diamond with both penetrating and interlocked twins was synthesized, yielding a hardness of 276 GPa, which can be explained by diamond models that feature diverse twin configurations and dimensions.

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 physiological significance of low fatty acid synthesis in adipocytes remains unclear. Here, the authors show a protective role of this phenomenon by demonstrating that overproduction of fatty acids increases ROS production and results in adipocyte necroptosis and lipodystrophy.

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.

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.

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.

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.

Tea contains catechins such as (−)-epigallocatechin gallate (EGCG) which have antioxidant activity and potential health benefits. Here the authors characterise two enzymes that produce O-methylated EGCG, a modified form found in some tea cultivars that has improved bioavailability.

SARS-CoV-2 variants with immune escape capability highlight the need for the development of cross-neutralising vaccines and regimens. Here, the authors assess the immunogenicity and safety of NVSI-06-08, that integrates antigens from multiple SARS-CoV-2 strains into a single immunogen, as a heterologous booster in adults previously vaccinated with the inactivated vaccine.

Here the authors show an AI-powered assessment system (AIHFLevel, www.hf-ai-survival.com) empowering healthcare professionals for continuous risk monitoring and prognosis assessment of patients who have advanced heart failure with renal dysfunction.

Recently, the asymmetric bifunctionalization of alkenes has received much attention but the development of enantioselective alkoxyalkenylation has posed a considerable challenge and has lagged largely behind. Here, the authors report a palladium-catalyzed enantioselective alkoxyalkenylation reaction, using a range of primary, secondary, and tertiary γ-hydroxyalkenes with alkenyl halides.

Here the authors show that lithium carbonate can revitalize tumor-reactive CD8⁺T cells by shunting cytosolic lactic acid into the mitochondria for oxidation, indicating that lithium ions might be applied as a cancer immunotherapy.

The Chinese Liver Cancer Atlas project depicts a panoramic genomic landscape of hepatocellular carcinoma, covering candidate coding and non-coding drivers, mutational signatures, extrachromosomal circular DNA, subclonal catastrophic events and detailed evolutionary history.

This study describes experiments with ultracold lithium Fermi gases in which many-body pairing leads to the emergence of a pseudogap, and it confirms theoretical predictions relevant to cuprate superconductivity.

By growing a topological insulator on top of a high-temperature superconducting substrate it is possible to induce superconductivity in the surface states of the topological insulator. Moreover, the pairing symmetry of the induced superconductivity is s-wave, unlike the d-wave symmetry of the substrate.

The mechanistic functions of neutrophils in skin inflammation are not fully understood. Here the authors use human psoriasis samples and a mouse model of skin inflammation to study neutrophils and find a CXCR4^hi population of NET-forming, phagocytic neutrophils whose induction depends on the transcription factor CREB1.

Cancer can be associated with alterations in innate immunity. Gao et al. demonstrate that these alterations arise from immunomodulatory exosomes released by tumors, which then dampen the production of type I interferons by macrophages.

Bacterial allosteric transcription factors can sense and respond to a variety of small molecules. Here the authors present CaT-SMelor which uses Cas12a and allosteric transcription factors to detect small molecules in the nanomolar range.

The power conversion efficiencies of thick-film perovskite solar cells lag behind those with nanometre film thickness. Here, the authors rule out the restrictions of carrier lifetime on device performance and reveal the critical role of lattice strain in micron-scale thick perovskite films.

Aberrant activation of TGF-β signalling promotes cancer metastasis but the initial steps of this activation are unclear. Here Xieet al. show that FAF1 regulates the surface levels of TGF-β type II receptor thus influencing the persistence of the signalling and breast cancer metastasis.

An additive manufacturing strategy is used to produce dual-phase nanolamellar high-entropy alloys that show a combination of enhanced high yield strength and high tensile ductility.