Search

This study defines tissue- and sex-specific N- and O-glycoproteomes of adult Schistosoma mansoni, uncovers novel and HexA-modified glycans, shows glycosylation is essential for parasite survival, and reveals vaccine candidates as glycoproteins.

Engineered mucus-tethering bispecific nanobodies neutralize and entrap viruses to enhance mucosal immunity, preventing influenza infection and limiting SARS-CoV-2 transmission.

Patients with primary mitochondrial disease manifesting cardiomyopathy are twice as likely to die compared to those without cardiomyopathy. Here, the authors show that a modest increase in cardiac mitochondrial energetics via gene therapy can significantly improve cardiac function and is effective in treating mitochondrial cardiomyopathy.

Researchers identified a unique “latch bulge” in yeast mitofusin Fzo1. This fungi-specific structure allows Fzo1 to dimerize and remain locked after catalyzing GTP hydrolysis, enabling efficient mitochondrial fusion with minimal energy consumption.

In this Resource paper the authors provide a multiomic single-cell atlas of mouse eosinophil heterogeneity across various organs and use fate-mapping methods to look at the dynamics of residency.

Challenges in simplicity and accessibility limit the current widespread applicability of neuromuscular models. Here, the authors present a readily fabricated, organised human motor assembloids-on-a-chip approach for neuromuscular research and hypoxia disease modelling.

Polygenic scores for body mass index and obesity constructed using data from 5 million people with different ancestries were associated with distinct weight gain trajectories from early childhood to adulthood.

Wang, Xiao and colleagues develop and validate organ-specific proteomic aging clocks across large population cohorts in the UK, the USA and China, which show strong performance in tracking organ aging and predicting the risk of morbidity and mortality.

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.

A lipid nanoparticle is used to deliver mRNA to hematopoietic stem cells in macaques.

A genome-wide association meta-analysis study of blood lipid levels in roughly 1.6 million individuals demonstrates the gain of power attained when diverse ancestries are included to improve fine-mapping and polygenic score generation, with gains in locus discovery related to sample size.

An avialan species from the Zhenghe Fauna—a collection of vertebrate fossils from the Late Jurassic of China—had an unusual combination of features, including very long hindlimbs, suggesting that it had a terrestrial or wading lifestyle.

While the ligand coordination microenvironment surrounding catalytic centres influences reactivity, dynamic oxygen reconstruction during water oxidation electrocatalysis complicates structure-based mechanistic insights. Now the in situ formation of lattice O–O ligands has been shown to activate Fe centres in metal oxides and hydroxides, thereby enhancing their oxygen evolution reaction activity.

Understanding the local microenvironment is crucial yet challenging for catalyst design. Here, the authors demonstrate that the nanoconfined environment of carbon nanotubes enriches CO and induces structural deformation in cobalt phthalocyanine, thereby promoting CO₂ electroreduction to methanol.

Here, the authors identify key DNA methylation sites associated with incident acute coronary syndrome (ACS), improving ACS prediction and highlighting potential biomarkers and therapeutic targets for ACS.

Temperature-adaptive elastic conductive fibers are crucial for developing electronic textiles, though balancing elasticity, conductivity and adaptivity is challenging. Here the authors design an elastic conductive fiber utilizing thermoplastic polyurethane, silver flakes, and liquid metal microspheres incorporated into wearable electronics.

Detecting small molecules is pivotal across many fields. Here, authors leverage a split crRNA mode to construct spatially blocked split CRISPR-Cas12a system. This approach establishes a low-background, highly sensitive platform for small molecule detection.

Air-water interface and preferential orientation problems are crucial challenges in cryo-EM specimen preparation. Here, the authors utilize graphene-coated EM grids functionalized by salts with various electrostatic properties, successfully overcoming preferred orientation.

Guided bone regeneration (GBR) membranes are used to treat bone defects, but face challenges in regulating the immune microenvironment. Here, Yang et al. report a Janus collagen-based barrier membrane that modulates the osteoimmune microenvironment to effectively promote bone regeneration.

Upon nutrient stress in hepatocellular carcinoma, the glycolytic enzyme PFKL facilitates mitochondria tethering to lipid droplets to engage lipid mobilization and ensure nutrient supply.

Angiotensin II is known to cause renal inflammation and fibrosis. Here Lu et al. show that levels of circulating miR-103a-3p are elevated in hypertensive nephropathy patients and in an animal model of angiotensin II-induced renal dysfunction, and that miR-103a-3p suppresses SNRK expression leading to the activation of the pro-inflammatory NF-κB pathway in glomerular endothelial cells.

Porphyrins are produced at scale through metabolic engineering and optimization of CPIII purification.

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.

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 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.

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.

Tao et al. show that epidermal growth factor receptor and insulin-like growth factor 1 receptor activation enhances thymidine kinase 1 expression through ERK phosphorylation and deubiquitylation mediated by ubiquitin carboxyl-terminal hydrolase 9X, thus enhancing enzyme activity-dependent DNA synthesis and enzyme activity-independent glycolysis.

The authors present the full-length structure of the polymerase (L protein) from the severe fever with thrombocytopenia syndrome virus (SFTSV)—a segmented, negative-stranded RNA virus. The structure reveals important details with implications for the understanding of viral transcription and replication, and provides information on the organization of the polymerase core domain, entrance and exit tunnels, as well as the cap-binding and endonuclease domains.

This paper shows that the uniformity of vitreous ice thickness relies on the surface flatness of the supporting film, and presents a method to use ultraflat graphene as the support for cryo-EM specimen preparation.

Here, the authors design a nanoprobe for in vivo imaging of electronic transfer, consisting of a ferrocene-DNA polymer to transfer electrons to luminescent nanoparticles, changing their optical signal. Using this probe, they map activation of EGFR signalling during tumour treatment.