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Enantioselective dicarbofunctionalization of alkenes is a powerful strategy for constructing functionalized sp³-rich molecules. Here, the authors report a palladium-catalyzed asymmetric migratory process that enables highly selective 1,3- and 1,4- diarylation of unactivated trisubstituted alkenes.

In this study, the authors show that citrulline accumulation exacerbates Fusarium wilt and that enhancing the soil’s citrulline-degrading function, particularly via the arcB gene, significantly reduces disease in continuous cucurbitaceous cropping systems.

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.

A ligand-restricted strategy is developed to realize the synthesis of dual-atom catalysts with high pairing ratio and tunable atomic distances.

Laser plasma instabilities are the main factors contributing to degradation of hohlraum performance in inertial confinement fusion experiments. Here, the authors show asymmetric backscattering within the same laser cone at the SG-100kJ laser facility, unveiling the role of crossed-beam energy transfer and laser polarization.

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 64-plex fluorescence imaging of RNA in tissues is achieved in one imaging cycle

Upstream pathways regulating Brg1 stability and their role in carcinogenesis are unknown. Here they show Brg1 to be phosphorylated by CK1δ to promote its ubiquitination by SCF^FBW7 (FBW7), Brg1 stabilization to promote gastric cancer metastasis, and suggest targeting Brg1 in FBW7 compromised gastric cancer.

Wang and colleagues show that an AI-assisted designed peptide obstructs GSDMD pores and inhibits IL-1β and IL-18 release and pyroptosis.

The Dark sectioning algorithm removes the background and provides single-frame optical sectioning in fluorescence microscopy. It offers improved quantitative analysis and deep-tissue segmentation accuracy and is compatible to diverse modalities.

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.

Xu et al. identify the MondoA–TXNIP signalling axis as a regulator of antitumour immune surveillance in response to lactic acid in the tumour microenvironment.

The mechanisms underlying the invasiveness and aggressiveness of pituitary neuroendocrine tumours (PitNETs) remain poorly understood. Here, the authors perform single-cell RNA sequencing and spatial transcriptomics to characterise the tumour microenvironment of PitNETs and identify potential therapeutic targets.

N-degron pathways play an important role in maintaining protein homeostasis. Here, Li et al. demonstrates an additional non-Ac/N-degron pathway, in which N-terminal non-acetylated small residue degrons (Ser, Ala, or Cys) are recognized by CRL2^ZER1/ZYG11B and targeted for protein degradation.

Extracellular vesicles are naturally occurring nanoparticles that are gaining ground as delivery modalities for therapeutics. Here, the authors conducted a large-scale screening programme to identify potential scaffold proteins for cargo loading into extracellular vesicles.

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 authors propose a targeted doping strategy that enables copper atoms to occupy specific positions within the material’s crystal structure, avoiding the unwanted defects typically introduced by conventional methods.

The bacterium Lacticaseibacillus paracasei is used in the food industry and as a probiotic. Here, the authors use multi-omics and high-throughput chromosome conformation capture analyses to investigate the roles of a type of DNA methylation (N6-methyladenine modification) in this organism.

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.

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.

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.

Gastrointestinal stromal tumours (GISTs) are clinically heterogeneous, with varying degrees of aggressiveness. Here, the authors describe the genomic and transcriptomic landscape of 117 GISTs from 105 patients; they find four molecular subtypes as well as recurrent inactivating YLPM1 mutations in high-risk/metastatic GIST.

The methyltransferase complex of METTL3-METTL14-WTAP is responsible for m⁶A modification on RNA. Here the authors report that METTL14 arginine 255 (R255) is methylated by PRMT1 and this modification increases interaction of METTL3/METTL14 interaction with WTAP and substrate RNA, promoting m⁶A methylation activity of the complex.

Modulation of regulatory T cells (Treg) in the tumour environment is a potential avenue to bolster anti-tumor immunity. Here Liu et al show that perturbation of the negative feedback loop involving STAT1- IFITM3 influences anti-tumor immunity, and that IFITM3 or STAT1 deficiency resulting in the fragility of tumor-infiltrating Treg cells.

Histone modification recognition is an important mechanism for gene expression regulation in cancer. Here, the authors identify YEATS2 as a histone H3K27ac reader, regulating a transcriptional program essential for tumorigenesis in human non-small cell lung cancer.

Bacteria have been exploited as a potential bio-factory for the synthesis of nanoparticles. Here the authors report the generation of gold nanoparticles from Escherichia coli and show their application for eliciting hyperthermia and anti-tumor immune responses in preclinical cancer models.

In a cluster-randomized trial performed in 48 residential elderly care facilities in China, use of a low-sodium salt substitute instead of regular salt decreased blood pressure and cardiovascular events, whereas an alternative strategy of restricting salt consumption was not successful and did not have these beneficial effects.

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.

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.

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.

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.

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.

Shengyue Wang and colleagues report the draft genome sequence and transcriptome analysis for Echinococcus granulosus, a parasitic helminth and cause of human hydatid disease. Their comparative genomic analysis identifies genes acquired by E. granulosus that are associated with host immune response, parasite survival and growth.

The polycomb group protein BMI1 is highly expressed in prostate cancer. Here, the authors demonstrate that BMI1 directly interacts with AR leading to increased AR signaling independently of PRC1 complex and that targeting BMI1 inhibits tumor growth of castration-resistant prostate cancer tumors.

Alpha-fetoprotein producing gastric carcinomas (AFPGC) are rare and aggressive. Here, the authors profile AFPGC tumours using whole exome sequencing, and find amplifications in CCNE1 and ERBB2 that are associated with poor outcomes but are potential therapeutic targets, as shown in patient-derived xenografts.

Esophageal squamous-cell carcinomas (ESCC) have poor prognosis, and detailed molecular profiles are necessary to identify prognostic markers. Here the authors analyse 60 ESCC patient samples using scRNA-seq, TCR-seq and genomics; they find mucosal immunity markers associated with survival and immunosuppressive microenvironments.

The authors show that the lncRNA-derived microprotein SMIMP, which is shown to promote tumor formation, regulates cohesin core subunit binding to cis-regulatory elements and alters the expression of tumor-suppressive cell cycle regulators.