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The Cancer Genome Atlas Research Network report integrated genomic and molecular analyses of 164 squamous cell carcinomas and adenocarcinomas of the oesophagus; they find genomic and molecular features that differentiate squamous and adenocarcinomas of the oesophagus, and strong similarities between oesophageal adenocarcinomas and the chromosomally unstable variant of gastric adenocarcinoma, suggesting that gastroesophageal adenocarcinoma is a single disease entity.

Ellis and colleagues show that combination of EZH2 inhibition and anti-PD-1 can increase antitumor immune responses in typically ‘immune cold’ prostate cancer, by increasing EZH2-regulated dsRNA–STING–ISG response signaling.

Here, the authors characterize the gut microbiome fermentation properties and therapeutic potential of chemically diverse synthetic glycans (SGs), showing they promote specific shifts in taxonomic and metabolite profiles, and exhibit therapeutic benefits in mouse models of colonic inflammation, together implying SGs as a potential avenue to treat disease by modulating the composition and metabolites produced by the gut microbiome.

Genetic susceptibility loci for oropharyngeal cancer have been reported but these studies have not always examined human papillomavirus (HPV) status. Here, the authors perform genome-wide analysis taking into account HPV16 serology status and report two independent loci in the HLA region, suggesting the protective role of HLA variants against HPV infection.

A randomized phase 2 study recently showed that the addition of ATR inhibitor berzosertib to gemcitabine improved PFS compared to gemcitabine alone in patients with ovarian cancer. In this preplanned exploratory study, the authors demonstrate that a genomic biomarker of replication-stress is associated with outcome to gemcitabine alone and may predict which patients benefit from addition of the ATR inhibitor berzosertib.

Photothermal Fischer-Tropsch synthesis represents a promising strategy for converting CO into value-added chemicals. Here the authors report a Ru₁Co single atom alloy catalyst for CO photo-hydrogenation to C₅₊ liquid fuels at ambient pressure, and confirm the role of Ru single atoms in promoting CO activation and C-C coupling whilst suppressing CH_x* over-hydrogenation.

Learning to predict reward is thought to be driven by dopaminergic prediction errors, which reflect discrepancies between actual and expected value. Here the authors show that learning to predict neutral events is also driven by prediction errors and that such value-neutral associative learning is also likely mediated by dopaminergic error signals.

Behaviour requires knowledge of cues and outcomes. Here the authors use neuromodulation of lateral orbitofrontal cortex and neuroimaging of error-related midbrain activity to reveal the neurocomputational mechanisms underlying reward identity learning.

Chromatin architecture is a key regulator of transcriptional processes, however current methods to investigate it have technical limitations. Here, the authors describe a novel chromatin capture technique, CATCH, which can be used to identify and characterize complex genomic interaction networks.

Sequences of synthetic polymers are generally heterogeneous and dictate many of their physiochemical properties, but are challenging to determine. Now an imaging method, termed CREATS (coupled reaction approach toward super-resolution imaging), can count, localize and identify each monomer of single polymer chains during (co)polymerization.

Fernando Rivadeneira and colleagues in the Genetic Factors for Osteoporosis Consortium report a large-scale meta-analysis identifying new loci associated with bone mineral density (BMD) and risk of fracture. Thirty-two new loci are found to be associated with BMD, and 6 loci confer higher risk for low-trauma bone fracture.

Using large-scale mobility data from diverse cities around the globe, a simple and robust scaling law that captures the temporal and spatial range of population movement is revealed.

Solid organ transplant recipients are at increased risk of infectious disease and have unique molecular pathophysiology. Here the authors use host-microbe profiling to assess SARS-CoV-2 infection and immunity in solid organ transplant recipients, showing enhanced viral abundance, impaired clearance, and increased expression of innate immunity genes.

mRNA-1273, an mRNA vaccine that encodes a stabilized prefusion-state severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein, elicits robust immune responses and protects mice against replication of SARS-CoV-2 in the upper and lower airways.

The systemic immune features that distinguish COVID-19 from common infections remain incompletely elucidated. Here McClain et al. compare RNA sequencing in peripheral blood between subjects with SARS-CoV-2 and other respiratory infections and demonstrate dysregulated immune responses in COVID-19 with both heterogeneous and conserved components.

With non-small cell lung cancer (NSCLC) being the leading cause of cancer deaths worldwide, the development of targeted therapies remains crucial. Here, the generation and multi-omics characterization of 137 NSCLC patient-derived xenografts provides a resource for potential classifications and targets.

The role of IgG glycosylation in the immune response has been studied, but less is known about IgM glycosylation. Here the authors characterize glycosylation of SARS-CoV-2 spike specific IgM and show that it correlates with COVID-19 severity and affects complement deposition.

Luis Pérez-Jurado, Stephen Chanock and colleagues detect clonal chromosomal abnormalities in peripheral blood or buccal samples from individuals in the general population. They show that the frequency of such events increases with age and is associated with elevated risk of developing subsequent hematological cancers.

Cell therapy requires sufficient amounts of therapeutic cells to be delivered to the injured tissue. Here the authors use magnetic iron nanoparticles conjugated with antibodies that bind therapeutic cells and cardiomyocytes to treat myocardial ischemia/reperfusion injury in rats and show that targeting to the heart is enhanced upon local application of a magnetic field.

Lung adenocarcinoma (ADC) and squamous cell carcinoma (SCC) are the two major subtypes of lung cancer. Here the authors integrate omic data sets, including gene copy number, mRNA expression and proteomics, to identify subtype-specific molecular signatures and candidate drivers linked to ADC and SCC.

This study presents the assembly and analysis of the genome sequence of a female domestic Duroc pig and a comparison with the genomes of wild and domestic pigs from Europe and Asia; the results shed light on the evolutionary relationship between European and Asian wild boars.

We carried out genomic and ecological analyses of all eight extant baobab species, providing insights into their evolutionary history and recommendations for conservation efforts.

Gestational duration depends on both maternal and fetal genetic influences. Here, the authors perform a fetal genome-wide association meta-analysis and find that a locus on 2q13 is associated with pregnancy duration and further show that the lead SNP rs7594852 changes the binding properties of transcriptional repressor HIC1.

Oxygen in shallow shelf waters rose linearly with atmospheric oxygen in the Neoproterozoic era, potentially driving the first radiation of marine animals, but widespread ocean oxygenation came later, according to reconstructions of oxygen levels and marine productivity.

An in vivo approach to identify proteins whose enrichment near cardiac Ca_V1.2 channels changes upon β-adrenergic stimulation finds the G protein Rad, which is phosphorylated by protein kinase A, thereby relieving channel inhibition by Rad and causing an increased Ca²⁺ current.

Covalent organic frameworks (COFs) represent an emerging class of organic photocatalysts but it remains challenging to gain insight into photocatalytic active sites and reaction mechanisms. Herein, the authors construct a family of isoreticular crystalline hydrazide-based COF photocatalysts, with the optoelectronic properties and local pore characteristics of the COFs modulated using different linkers

Papa et al. show that phosphorylation by PKA of four residues in Rad, a calcium channel inhibitor, is required to mediate the β-adrenergic-induced increase in calcium current and contractile force. Additionally, Rad-phosphosite-mutant mice showed reduced basal heart rate and contractility. Conversely, expression of mutant calcium channel unable to bind wild-type or phosphosite-mutant Rad was sufficient to enhance basal calcium influx and contractility, independently of β-adrenergic stimulation.

A genome-wide association study for lung cancer finds that genetic sequences in the nicotinic acetylcholine receptor subunit gene cluster contribute susceptibility. Interestingly, this susceptibility is not related to smoking status or frequency, and seems to come from a change in an amino acid in the receptor itself.

Joyce, Pascual et al. identify luminal progenitors as likely cells-of-origin in BRCA2-mutant breast cancer, exhibiting dysregulated proteostasis and translation, which may be therapeutically targeted via mTORC1 inhibition.

Insulin therapies for patients with diabetes have challenges, including diminished hepatic preference of insulin action compared with endogenous insulin. Here the authors characterize insulin dimers that function as insulin receptor partial agonists, and exhibit hepatic and adipose tissue preference of insulin action and metabolic benefits in preclinical models.

Light-driven catalytic conversion of CO₂ to fuels and chemicals presents a way to reduce reliance on fossil fuels, but new strategies are needed to improve performance. Here the authors find that greenhouse effects can be exploited in photothermal catalysts to enhance their ability to produce methane and carbon monoxide.

Evaluating the short-term exposure to wildfire-specific fine particulate matter (PM_2.5) showed greater risks of hospitalization for all major respiratory diseases than non-wildfire PM_2.5. When developing air quality guidelines, it is also important to consider that PM_2.5 from varying sources can have different health effects, which require targeted health and environmental policy approaches.

Visvader and colleagues report that in the mouse mammary gland, EGF and mTOR signalling induce expression of the anti-apoptotic Bcl2 family member Mcl-1 and show that this is required for the survival of milk-producing mammary epithelial cells.

CO₂ electroreduction in acidic electrolytes avoids carbon loss but entails the issue of salt formation arising from the addition of metal cations, thereby limiting operational stability. Now copper is decorated with immobilized cationic ionomers, achieving stable CO₂ reduction towards multi-carbon products in metal cation-free acidic electrolytes.

To date, treatment strategies for heart failure have focused on the symptomatic stage of disease, often after irreversible remodeling and functional impairment have occurred. Early identification of cardiac dysfunction would allow implementation of early intervention strategies to delay the progression or to prevent the onset of heart failure altogether. This Review highlights the utility of a staged approach for patients with predisposing risk factors, which uses serological biomarkers followed by noninvasive imaging techniques.

The main function of the mammary gland is to produce milk to sustain offspring. Here, the authors show that secretory alveolar cells in the lactating gland in several species are binucleated, which increases milk production, and that binucleation is regulated by Aurora kinase-A and Polo-like kinase-1.

The chromosome 15q25.1 locus is a leading susceptibility region for lung cancer. Here, the authors interrogate three GWAS cohorts with 42,901 individuals to investigate potential pathological pathways such as gated channel activity and neuroactive ligand receptor interaction in lung cancer etiology.

The optical properties of certain metals can be reversibly switched by hydrogen loading but challenges remain to achieve electrical and reversible control. Here, the authors report a nanoscale proton switch that allows for electrical control of optical properties through electrochemical hydrogen gating.

Dawson et al. characterize a macrophage population associated with mammary ducts that are long lived, derive from embryonic precursors and have multiple roles in pregnancy, lactation, involution and cancer.

The role of impaired lung function in lung cancer etiology is complex due to the relation of cigarette smoking to both conditions. Here, supported by Mendelian randomization analysis the authors find a link between pulmonary function impairment and lung cancer risk beyond smoking, implicating immune-related pathways

The basis for associations between lung cancer and major histocompatibility complex genes is not completely understood. Here the authors further consider genetic variation within the MHC region in lung cancer patients and identify independent associations within HLA genes that explain MHC lung cancer associations in Europeans and Asian populations.

Whole-genome sequencing analysis of individuals with primary immunodeficiency identifies new candidate disease-associated genes and shows how the interplay between genetic variants can explain the variable penetrance and complexity of the disease.

Alzheimer’s disease has been associated with increased structural brain aging. Here the authors describe a model that predicts brain aging from resting state functional connectivity data, and demonstrate this is accelerated in individuals with pre-clinical familial Alzheimer’s disease.

Sequencing the nuclear genomes of Guillardia theta and Bigelowiella natans, transitional forms in the endosymbiotic acquisition of photosynthesis by engulfment of certain eukaryotic algae, reveals unprecedented alternative splicing for a single-celled organism (B. natans) and extensive genetic and biochemical mosaicism, shedding light on why nucleomorphs persist in these species but not other algae.