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Type 3 innate lymphoid cells (ILC3) are involved in maintaining gut immune homeostasis. Here the authors identify a circular RNA, circKcnt2, to be induced in ILC3s from inflamed gut, yet circKcnt2 deletion aggravates mouse experimental colitis, thereby implicating circKcnt2 as a potential feedback regulator of ILC3 activation and gut immunity.

A synthetic protein quality control system (ProQC) uses RNA hybridization to enhance translation of full-length proteins in coupled transcription–translation systems to optimize production of biosynthetic enzymes for metabolic engineering efforts.

How RNA polymerase II subunits enter the nucleus is not well understood. Here, the authors show that Transport and Golgi organization protein 6, TANGO6, recruits RNA polymerase II subunit B2, RPB2, to the ER membrane in a retrograde manner and transports it to the nucleus with the aid of importins.

Tagging tumour cells with microbial antigens using a tumour-specific replicating virus activates memory T cells for treating solid tumours in mouse models.

Heterostructures of segmented semiconductor materials are difficult to produce by sequential epitaxial nucleation. Here, the authors report on the spontaneous formation of 1D heterostructures with numerous fluorescent stripe patterns following an assembly strategy based on Plateau-Rayleigh instability.

Broad-spectrum vaccines have been proposed as a tool for rapid response to emerging infectious disease threats and are in pre-clinical development. Here, the authors use mathematical modelling to assess the potential impacts of broadly protective sarbecovirus vaccines for a hypothetical “SARS-X” outbreak.

In fetal liver, the structure of the differentiated haemapoietic progenitor cell population is established directly from precursor cells, independently of haemapoietic stem cells.

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.

Gene implication methods (GIMs) are crucial tools for analyzing genome-wide association studies, but are often ambiguous. We present the LocusCompare2 platform to incorporate six popular GIMs and hundreds of quantitative trait loci datasets, enabling validation across several GIMs and window settings to improve accuracy and reproducibility.

Single-cell RNA sequencing of bone marrow innate lymphoid cell (ILC) precursors reveals that PD-1 marks a committed ILC progenitor and that ILC2 development requires Bcl11b and IL-25R expression; activated ILCs can also be depleted by a PD-1 antibody.

Impaired Aβ clearance in late-onset Alzheimer’s disease (AD) affects progression. Here, the authors show that CD14 + CD16+ monocytes carry Aβ in peripheral circulation and CSF in AD, suggesting a role in Aβ clearance.

Here the authors provide an explanation for 95% of examined predicted loss of function variants found in disease-associated haploinsufficient genes in the Genome Aggregation Database (gnomAD), underscoring the power of the presented analysis to minimize false assignments of disease risk.

Phosphatase of regenerating liver 3 (PRL3) is usually found intracellularly, and is over-expressed in cancer cells. Here the authors show that PRL-3 is also detectable on cell surface, and can be recognized by PRL3-zumab to recruit immune cells into tumor to promote anti-tumor immunity, thereby implicating PRL-3 as a potential tumor antigen.

Florfenicol treatment substantially increased the abundance and mobility of antibiotic resistance genes (ARGs) in the common carp gut microbiome. The resistome and mobilome profiles failed to return to baseline after the mandated withdrawal time, indicating that this period is insufficient to mitigate the risk of ARG transmission to consumers.

The chemotherapeutic efficacy of prodrug is limited by its cancer-targeting ability. Here this group reports an engineered commensal Lactobacillus plantarum strain with anticancer prodrugs loading on the surface for nasopharyngeal carcinoma cell-targeting and growth inhibition.

SN16X is upregulated in mouse hypertrophic hearts and accelerates AngII-induced cardiac hypertrophy via enhancing EGFR recycling and transactivation.

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.

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.

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.

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.

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.

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

Innate lymphoid cells (ILC) are important regulators of mucosal immunity, but how their development and homeostasis are modulated is still unclear. Here the authors show that the differentiation of group 3 ILCs is controlled by the glutamylation of IL-7Rα and the induction of transcription factor Sall3.

PEGylated black phosphorus nanosheets boost mitochondrial oxidative phosphorylation, thereby modulating the survival and immune evasion in tumour cells, and further promoting the activation of immune regulation.

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 feasibility of satellite-assisted quantum communication is demonstrated by a field test on the ground. To supress noise due to sunlight the wavelength of 1,550 nm is chosen, and spectrum and spatial filtering technology developed.

Cerebral malaria (CM) is a severe complication of Plasmodium falciparum infection. Here the authors show that methylene blue treatment reverses brainstem damage in rhesus macaque CM and identify neutrophil-linked genes as potential biomarkers for severe and fatal P. falciparum infection.

Synaptic vesicle protein SV2A is a target for antiseizure drugs. Here cryo-EM structures of human SV2A in its apo state or with antiseizure medications reveal the conformational changes upon ligand binding and an allosteric site that modulates ligand engagement to the orthosteric site.

The role of structural variants (SVs) in Mycobacterium tuberculosis has been understudied. In this study, the authors leverage 859 high-quality, diverse, long-read assemblies to construct pangenome reference graphs (PRGs).

Large language models (LLMs) are emerging as powerful tools in healthcare, with a growing role in global health, particularly in low- and middle-income countries. This Perspective examines the current progress, challenges and prospects of LLMs in addressing health system disparities and supporting achievement of the Sustainable Development Goals.

This study shows that trigonometric gradient microstructures in 3D-printed single crystals can be used to program mechanical properties and overcome the strength-ductility trade-off, offering new design strategies for high-temperature materials.

A meta-analysis of genome-wide association studies of type 2 diabetes (T2D) identifies more than 600 T2D-associated loci; integrating physiological trait and single-cell chromatin accessibility data at these loci sheds light on heterogeneity within the T2D phenotype.

Low-metallicity molecular clouds in the Milky Way and nearby galaxies exhibit a strong deficiency in turbulent support against their self-gravity, suggesting that the magnetic field may play a dominant role in supporting clouds under such conditions.

Here, the authors show that mechanical loading promotes subchondral bone osteocytes to secrete extracellular vesicles containing miR-23b-3p, which accelerates osteoarthritis progression by inhibiting mitophagy and disrupting cartilage metabolism.

Genome-wide association studies (GWAS) have improved our understanding of the genetic basis of lung adenocarcinoma but known susceptibility variants explain only a small fraction of the familial risk. Here, the authors perform a two-stage GWAS and report 12 novel genetic loci associated with lung adenocarcinoma in East Asians.

Immune checkpoint blockade is an effective therapy in melanoma, but response is highly variable between patients. Here, the authors show that Inducing co-stimulatory immune checkpoint CD137L expression in melanoma cells enhances T cell-mediated anti-tumor immunity.

Chan et al. report that 3′ UTR splicing is widespread and enhanced across different cancer types and is associated with more advanced tumour progression.