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Adenosine is an immunosuppressive metabolite known to limit anti-tumor immune responses. Here the authors report the characterization of an adenosine A2A receptor (A2AR) eGFP reporter mouse, providing immunological insights into the biology of A2AR expression in the context of anti-tumor immunity.

Rich and colleagues identify that lymphatic endothelial-like cells in glioblastoma drive the growth of cancer stem cells via CCL21–CCR7 signaling, inducing KAT5 to acetylate HMGSC1, which enhances its protein stability and cholesterol synthesis.

A deep learning model trained on raw pixel data in hundreds of thousands of echocardiographic videos for the prediction of one-year all-cause mortality outperforms clinical scores and improves predictions by cardiologists.

An integrated analysis of de novo and inherited coding variants in 42,607 individuals with autism spectrum disorder identifies 60 risk genes of which five have not previously been associated with neurodevelopmental disorders.

The main protease, a key enzyme of SARS-CoV-2, can protect itself from oxidative damage. Here, Reinke, Schubert, and colleagues used XFEL radiation to image the enzyme, revealing the disulfide and NOS/SONOS bonds that form in response to oxygen.

Large-scale sequence-based analyses identify novel risk variants and susceptibility genes for Crohn’s disease, and implicate mesenchymal cell-mediated intestinal homeostasis in disease etiology.

Lymphoplasmacytic lymphoma is a B-cell low-grade lymphoma with no approved standard therapy. Here the authors report a non-randomized phase 1 clinical trial performing early intervention with personalized neoantigen vaccines in asymptomatic patients and associating clinical efficacy with successful perturbation of the tumor immune microenvironment.

Accurate classification of genetic variants is critical for research and patient care. Here, the authors report that population-based associations between rare variants and quantitative endophenotypes for monogenic diseases can provide support for variant pathogenicity.

Ribosomes have evolved to polymerize L-α-amino acids into proteins comprising a peptide backbone. Here, a pyridazinone backbone is formed using ribosomes in vitro, producing a variety of sequence-defined alternating block-copolymers.

High-resolution subnational mapping of child growth failure indicators for 105 low- and middle-income countries between 2000 and 2017 shows that, despite considerable progress, substantial geographical inequalities still exist in some countries.

As part of the first anniversary issue of Nature Chemical Engineering, we present a collection of opinions from 40 researchers within the field on what they think are the most exciting opportunities that lie ahead for their respective topics.

A phase 1/2a study shows that human neural progenitor cells modified to release the growth factor GDNF are safely transplanted into the spinal cord of patients with ALS, with cell survival and GDNF production for over 3 years.

Bhattacharjee and Schaeffer et al. map exclusive breastfeeding (EBF) in 94 low- and middle-income countries (LMICs), finding increased EBF practice and reduced subnational variation across the majority of LMICs from 2000 to 2018. However, only six LMICs will meet WHO’s target of ≥70% EBF by 2030 nationally, and only three will achieve this in all districts.

Post-acute sequelae of SARS-CoV-2 (PASC) is still not well understood. Here the authors provide patient reported outcomes from 590 hospitalized COVID-19 patients and show association of PASC with higher respiratory SARS-CoV-2 load and circulating antibody titers, and in some an elevation in circulating fibroblast growth factor 21.

The 3CL protease of SARS-CoV-2 is inhibited by PF-00835231 in vitro. Here, the authors show that the prodrug PF-07304814 has broad spectrum activity, inhibiting SARS-CoV and SARS-CoV-2 in mice and its ADME and safety profile support clinical development.

Insights on the mechanistic differences between artificial metalloenzymes (ArMs) with non-native metal centres and the free cofactor or natural enzymes are scarce. Now, a detailed mechanistic analysis of a cyclopropanation reaction catalysed by such an ArM is provided, revealing intriguing differences to the natural system.

Bacteriophage repressor proteins downregulate viral lytic gene expression. Herein, the authors present the X-ray crystal structure of a monomeric repressor that binds an asymmetric DNA sequence using two independent domains.

Analysing data from 39 grassland biodiversity experiments, the authors uncover the direct and indirect contributions to ecosystem stability of taxonomic, phylogenetic and functional trait diversity.

Distinct monocyte subsets associate with different outcomes of SIV vaccines.

Apicomplexan parasites share complex cell pellicular structures that isolates the cytosol from most of the plasma membrane. Koreny et al show that, as an early adaptation to this barrier, dedicated stable endocytic structures occur at select sites in these cells. In Toxoplasma, plasma membrane homeostasis is particularly dependent on endocytosis.

B cells need at least two signals to terminally differentiate into antibody-secreting cells. Pierce and colleagues show that persistent exposure to antigen in the absence of T cell help or ‘pathogen pattern motifs’ leads to B cell death via a calcium-dependent ‘metabolic timer’.

Screening of a library of bile acid metabolites revealed two derivatives of lithocholic acid that act as regulators of T helper cells that express IL-17a and regulatory T cells, thus influencing host immune responses.

Analysis of genomic data from 25 distantly related plant species shows signatures of selection on the same gene families and functions that repeatedly contributed to local adaptation to climate.

The genomic landscape of brain metastasis (BM) in patients with non-small cell lung cancer (NSCLC) remains to be explored. Here, the authors analyse a cohort of 233 patients with BM including 47 primary tumour, 42 extracranial metastatic matched samples and reveal distinct mutational patterns.

Here, using animal models, Deodhar et al. single parenteral dose of dolutegravir (DTG) prodrug nanocrystals sustains drug protein-adjusted 90% inhibitory concentration for up to a year, without injection site reactions or systemic toxicities.

It is unclear why different antibiotics vary in their ability to shorten treatment of tuberculosis. Here, the authors show that a measure based on ribosomal RNA synthesis in Mycobacterium tuberculosis correlates with treatment shortening in culture, in mice and in human studies.

A genetic study identifies hundreds of loci associated with risk tolerance and risky behaviors, finds evidence of substantial shared genetic influences across these phenotypes, and implicates genes involved in neurotransmission.

Sexual dimorphism in genetic vulnerability to schizophrenia, systemic lupus erythematosus and Sjögren’s syndrome is linked to differential protein abundance from alleles of complement component 4.

Poor antitumor response of pancreatic cancer to immunotherapies is a major barrier to effective disease management. Herein we show that pancreatic cancers overexpress vasoactive intestinal peptide, and pharmacological inhibition of its signaling significantly enhances responsiveness of pancreatic ductal adenocarcinoma to immune checkpoint therapy, thus improving overall survival in mouse models.

An oncometabolite produced by tumor cells acts as a paracrine immunosuppressant dampening antitumor T cell responses in glioma.

Analyses of the relationships between temperature, moisture and seven key plant functional traits across the tundra and over time show that community height increased with warming across all sites, whereas other traits lagged behind predicted rates of change.

Here authors show that machine learning derives the degree of background retinal pigmentation with more nuance than self-described ethnicity. Retinal pigment scores are associated with genes linked to melanin and may improve algorithmic fairness.

Psychedelic alkaloids served as lead structures for the development of tabernanthalog, a non-hallucinogenic and non-toxic analogue that reduces alcohol- and heroin-seeking behaviour and produces antidepressant-like effects in rodents.

By performing experiments under upper tropospheric conditions, nitric acid, sulfuric acid and ammonia can form particles synergistically, at rates orders of magnitude faster than any two of the three components.

Many genetic variants have been associated with human traits, but the mechanism is often unknown. Here, the authors integrate local and distal genetic associations with multi-omics datasets to provide a roadmap to understand the underlying mechanisms of GWAS variants on complex traits.

Ceramides are signalling molecules that regulate several physiological functions including insulin sensitivity. Here the authors report a selective ceramide synthase 1 inhibitor that counteracts lipid accumulation within the muscle and adiposity by increasing fatty acid oxidation but without affecting insulin sensitivity in mice fed with an obesogenic diet.

Clinical multi-omics data are integrated and analyzed using a generative deep-learning model.

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.

Human tumours with mutations in LKB1 and Kras have a specific hypermetabolic state associated with increased DNA methylation, pointing to potential metabolic and epigenetic vulnerabilities of specific tumours.

Mutagenesis of 23 ultraconserved enhancers and examination of their activities in transgenic mouse reporter assays show that overall their regulatory properties are robust to mutation. Manipulation of endogenous loci in mice corroborates reporter assay data.

High-throughput screening and longitudinal scRNA-seq of a 3D alveolar organoid model reveals that reduction of TGF-β1-induced fibroblast activation and concurrent AHR activation promotes AT1 cell regeneration in a lung fibrosis model.