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Hexokinase detachment from the outer mitochondrial membrane is shown to support aerobic glycolysis in cancer cells. Differential localization of the HK1 isoform to the outer mitochondrial membrane, compared to the HK2 isoform, explains the conditional essentiality of HK2 in cancer cells cultured in physiologic media.

CDK4/6 inhibitors are promising treatments for ER+ breast cancer, however resistance remains a challenge. Here, the authors analyse the NeoPalANA cohort and indicate that a 33 gene signature was predictive of response to neoadjuvant anastrozole and palbociclib.

This study provides new insights into the role of endoglin (ENG) as a co-receptor in endothelial cells and addresses a gap-in-knowledge on how ENG could be involved in both TGF-β and BMP9 signalling. Such knowledge greatly facilitates therapeutic targeting of ENG-related pathways.

Transcriptomic and proteomic analyses of cells and matrix along the fibrotic trajectory in mouse lung identified PI16 as an anti-fibrotic factor with potential for therapeutic application in humans.

Pcm1 bridges centrosome asymmetry and polarized endosome trafficking to regulate radial glia progenitor fate decisions, balancing self-renewal and differentiation in zebrafish and human cortical organoids.

Genomic analyses applied to 14 childhood- and adult-onset psychiatric disorders identifies five underlying genomic factors that explain the majority of the genetic variance of the individual disorders.

Here authors report that mutations in the neurodevelopmental risk gene ZMYND11 disrupt human cortical neuron development by altering chromatin regulation and RNA splicing.

Alterations in lipid metabolism and circulating lipid species have been reported in patients with acute critical illness. Here the authors show that selective rise in systemic phosphatidylethanolamine levels is a common feature of critical illness that associates with worse clinical outcomes.

The balance between radial progenitors and intermediate precursors to generate upper-layer neurons during the development and evolution of the cerebral cortex is mediated by members of the tuberous sclerosis complex.

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.

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.

PetaKit5D offers versatile processing workflows for light sheet microscopy data including performant image input/output, geometric transformations, deconvolution and stitching. The software is efficient and scalable to petabyte-size datasets.

A high-resolution update of Antarctic bed topography using mass conservation reveals broad stabilizing ridges for glaciers flowing across the Transantarctic Mountains, and stabilizing slopes beneath Moscow University, Totten and Lambert glacier system.

Extensive measurements of the emissions of methane, nitrous oxide and ammonia from wastewater treatment facilities in the USA present higher values than are currently stated in national inventories. The results of this analysis show that greenhouse gas and nitrogenous emissions from the wastewater sector are often overlooked and that their impact on climate should be reassessed.

An artificial intelligence hardware approach that uses the adaptive reservoir computation of biological neural networks in a brain organoid can perform tasks such as speech recognition and nonlinear equation prediction.

Whether and under what circumstances chemical bonds could be imaged via force microscopy is a controversial topic. Here authors develop a particular combination of model surface, imaging procedures and simulation approach and discuss possible indications of chemical contrast in imaging data they obtain.

This paper presents TDAC-seq, a targeted chromatin-accessibility-profiling method using cytidine deaminases and long-read sequencing, to resolve the effects of CRISPR edits on single chromatin fibers.

Genome-wide association and fine-mapping analyses in ancestrally diverse populations implicate candidate causal genes and mechanisms underlying type 2 diabetes. Trans-ancestry genetic risk scores enhance transferability across populations.

Genome-wide analyses identify 30 independent loci associated with obsessive–compulsive disorder, highlighting genetic overlap with other psychiatric disorders and implicating putative effector genes and cell types contributing to its etiology.

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.

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.

Analyses of genome and exome sequencing data identify rare coding and structural variants associated with atrial fibrillation and highlight genetic links between atrial fibrillation and cardiomyopathies.

A diverse collection of potent neutralizing antibodies against the SARS-CoV-2 spike protein have been isolated from five patients with severe COVID-19 and high serum neutralization titres.

Single-nucleus and spatial, whole-transcriptome profiling of 43 pancreatic adenocarcinomas provides a refined molecular and cellular classification, highlighting a new neoadjuvant treatment-associated neural-like progenitor tumor cell state.

Sajti and colleagues identify TREM2 as a critical factor in myeloid cells in response to hyperoxia-induced lung injury in neonates, finding that TREM2 deficiency protects mice from bronchopulmonary dysplasia.

Meng et al. develop the adeno-associated virus 9-based therapy CM-YAP^on to transiently and inducibly express YAP in the heart. In mice, CM-YAP^on promoted cardiomyocyte cell cycle reentry and reprogrammed the cardiac microenvironment. The CM-YAP^on gene therapy improved cardiac function after myocardial infarction (MI) and conferred cardioprotection before MI.

In preclinical studies, the FDA approved TSP-1 antagonist gabapentin has been shown to disrupt neuronal-glioma interactions, slowing glioblastoma progression. Here, authors report a retrospective cohort study demonstrating a survival benefit associated with gabapentin in patients with newly diagnosed glioblastoma.

A large genome-wide association study of more than 5 million individuals reveals that 12,111 single-nucleotide polymorphisms account for nearly all the heritability of height attributable to common genetic variants.

The authors summarize the data produced by phase III of the Encyclopedia of DNA Elements (ENCODE) project, a resource for better understanding of the human and mouse genomes.

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

Protein-based nanobiosensors with two epistatically interacting synthetic allosteric regulatory systems result in YES gate protein switches with large dynamic ranges and fast response times. These biosensors enable construction of rapid diagnostic tests compatible with clinical chemistry analysers.

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.

A dataset of the genomes of 363 species from the Bird 10,000 Genomes Project shows increased power to detect shared and lineage-specific variation, demonstrating the importance of phylogenetically diverse taxon sampling in whole-genome sequencing.

Federated learning can be used to train medical AI models on sensitive personal data while preserving important privacy properties; however, the sensitive nature of the data makes it difficult to evaluate approaches reproducibly on real data. The MedPerf project presented by Karargyris et al. provides the tools and infrastructure to distribute models to healthcare facilities, such that they can be trained and evaluated in realistic settings.

Osteoclasts are derived from circulating myeloid cells to mediate bone repair, maintenance and remodeling. Here, the authors show that the lung also recruits and reprograms monocytes and alveolar macrophages into osteoclast-like cells to clear pathogenic particles from the airspace.

A high-bandwidth neuromotor interface offers performant out-of-the-box generalization across people.

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.

Spatial molecular imaging analysis of human pancreatic adenocarcinomas describes multicellular neighborhoods in the tumor microenvironment. Ligand–receptor analysis using optimal transport-based SCOTIA identifies interleukin-6 as a mediator of chemoresistance.

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.

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.

Ghorani et al. use a multiomics approach to characterize the effect of tumour mutational burden on the differentiation of CD4 and CD8 T cell subpopulations in non-small cell lung cancer.

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 collapse of tropical forests during the Permian–Triassic Mass Extinction weakened carbon sequestration, sustaining high CO2 and extreme global warmth for millions of years: an example of a runaway feedback in Earth’s climate-carbon system.

Introducing spin–orbit coupling by substrate proximity effect leads to an enhancement of superconducting phases in rhombohedral trilayer graphene.

A cell-based phenotypic screen identifying inhibitors of Notch signaling led to the discovery of NVS-ZP7-4, which blocks the activity of the zinc transporter SLC39a7 (ZIP7) and induces cell death through an ER stress mechanism.

This Consensus Statement presents the standards for technical reporting in environmental and host-associated microbiome studies (STREAMS) guidelines.

A method that allows for the detection of mosaic chromosomal alterations from blood whole-genome sequencing data highlights ancestry-specific differences in the distribution of common and rare germline susceptibility variants.

Transcriptomic and proteomic analyses show that high levels of the extracellular-matrix protein osteopontin are associated with the attenuated foreign-body response elicited by breast silicone implants wrapped with acellular dermal matrix.