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Experiments and computer simulations show that Janus ellipsoids can self-assemble into self-limiting fibres that have shape-memory properties and can be actuated by applying an external electric field.

Tuning of mechanical properties of single composition hydrogel materials and application in integrated devices remains challenging. Here, the authors introduce a macromolecule conformational shaping strategy that enables mechanical programming of polymorphic hydrogel fibre-based devices.

Type I IFN is vital for antiviral defense. Here, the authors use TurboID-based proximity labeling to comprehensively map the protein landscapes surrounding core IFN signaling members. Among factors uncovered, PJA2 emerged as a negative regulator of IFN signaling that ubiquitinates the Janus kinases.

This Primer by Guttman-Yassky and colleagues reviews the epidemiology, pathophysiology, diagnosis and treatment of alopecia areata. This Primer also discusses the quality of life issues faced by patients and future research avenues.

The assembly of microscopic particles into macroscopic structures may allow the fabrication of complex materials, but general strategies to provide a wide variety of structures are lacking. Khalilet al. develop a colloidal assembly system, which can be tuned to provide over 20 different pre-programmed structures.

A hydrogel serving as a high-capacity drug depot and combining a dissipative tough matrix on one side and a tendon-adhesive surface on the other side boosts tissue healing in rat models of tendon rupture.

Chemical proteomics identified covalent ligands targeting an isoform-restricted allosteric cysteine in JAK1. The compounds inhibit JAK1-dependent signaling in immune cells with unprecedented selectivity.

Small intestinal neuroendocrine tumours (siNETs) are rare bowel tumors generally considered to be a single entity. Here, the authors perform a multiomics analysis of siNETs and reveal four distinct molecular groups with clinical relevance, including groups linked to differentiation patterns, immunity, and mesenchymal properties.

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.

Oligodendrocytes are vulnerable to chemical toxicity during development. However, few environmental chemicals have been identified as potential hazards. Here, the authors discover chemicals in common household products as harmful to oligodendrocyte development.

Bendelac, McDonald and colleagues show that the NK cell-committed precursor in the mouse bone marrow expresses the transcription factor Eomes.

This Review discusses latest advances in the field of cutaneous lupus, including the improved understanding of disease pathogenesis and emerging targeted therapies.

Analysis of soundscape data from 139 globally distributed sites reveals that sounds of biological origin exhibit predictable rhythms depending on location and season, whereas sounds of anthropogenic origin are less predictable. Comparisons between paired urban–rural sites show that urban green spaces are noisier and dominated by sounds of technological origin.

Characterization of DCAF16-based BRD4 molecular glue degraders revealed a trans-labeling mechanism termed ‘template-assisted covalent modification’, which opens a new path for proximity-driven pharmacology.

Substrate channeling can improve biosynthetic efficiency and has been implicated in the reactions of fusicoccadiene synthase. Here, the authors analyze this bifunctional enzyme complex by cryoEM, cross-linking MS and integrative modeling, providing structural insights into how substrate channeling is achieved.

Schrank et al. report the design and characterization of an antibody–toxin conjugate targeting CD47, promoting anti-tumor immunity in preclinical cancer models.

Astrocytes have important roles in disease. However, modulation of their reactive state is challenging. Here the authors present a phenotypic in vitro screening platform they can leverage to identify chemical compounds able to modulate astrocyte reactivity in vitro and in vivo.

Meningitis is a severe form of invasive pneumococcal disease (IPD). To study the contribution of bacterial genomic variation, here Li et al. perform whole genome sequencing of pneumococcal isolates from IPD patients and identify an association for higher risk of meningitis with a pbp1bA641C variant

Active matter can spontaneously form complex patterns and assemblies via a one-way energy flow from the environment into the system. Here, the authors demonstrate that a two-way coupling, where active particles act back on the environment can give rise to novel superstructures, named as active droploids.

Rifaximin use, particularly in patients with liver cirrhosis, may be compromising the clinical use of daptomycin.

Phenotypic screens in organoids and primary cells are scaled up using perturbation pooling.

Chimeric antigen receptor T cell efficacy is enhanced with an interleukin 2-recruiting molecule.

The cytokine IL-6 controls the survival, proliferation and effector functions of lymphocytes. Jones and colleagues show that activation of CD4⁺ T cells leads to suppression of STAT1 activation by tyrosine phosphatases and changes the effector characteristics of memory CD4⁺ T cells in response to IL-6.

Dimethyl fumarate (DMF) is an anti-inflammatory drug proposed as a treatment for COVID19. Here the results are reported from a randomised trial testing DMF treatment in 713 patients hospitalised with COVID-19. DMF was not associated with any improvement in day 5 outcomes.

In this DREAM challenge, 75 methods for the identification of disease-relevant modules from molecular networks are compared and validated with GWAS data. The authors provide practical guidelines for users and establish benchmarks for network analysis.

Here, Goode et al. build a T-cell eQTL map from primary sclerosing cholangitis and ulcerative colitis patients. Integrating eQTL and GWAS, they nominate effector genes at six genetic risk loci for primary sclerosing cholangitis.

Metabolic liver disease is highly prevalent in subjects with obesity and involves inflammation, insulin resistance, and fibrosis, leading to cirrhosis. Here, the authors show the IFNγ-IL12 axis in regulating intercellular crosstalk in the liver and playing a major role in the pathogenesis of metabolic liver disease.

In a phase 1 trial followed by translational analyses, patients with acute myeloid leukemia (AML) treated with chimeric antigen receptor (CAR) T cell therapy targeting CD123 experienced high levels of cytokine release syndrome and short-lived clinical responses, probably due to CAR T cell-derived cytokines increasing the viability of AML blasts and antigen persistence.

Analysis of mitochondrial genomes (mtDNA) by using whole-genome sequencing data from 2,658 cancer samples across 38 cancer types identifies hypermutated mtDNA cases, frequent somatic nuclear transfer of mtDNA and high variability of mtDNA copy number in many cancers.

Urinary albumin-to-creatinine ratio (UCAR) is associated with various clinical outcomes such as kidney disease and cardiovascular disease. Here, the authors report genome-wide meta-analysis in over 500,000 individuals and find 68 UACR loci, followed by statistical fine-mapping, gene prioritization and experimental validation in flies.

During tumorigenesis, liposarcoma has been reported to develop a dependence on serine metabolism but it is unclear how this high energetic demand is met. Here, the authors identify a crosstalk mechanism between tumor and distant muscle cells wherein liposarcoma cell-derived IL-6 drives muscle cell release of serine, in turn accelerating tumor growth.

An inhibitor of Aurora kinase promotes megakaryocytic differentiation of cells from patients with primary myelofibrosis and shows antifibrotic effects in mouse models of this disease.

Unbiased large scale screening of small molecules for drug discovery in psychiatric disease is technically challenging and financially costly. Here, Readhead and colleagues integrate in silico and in vitro approaches to design and conduct transcriptomic drug screening in schizophrenia patient-derived neural cells, in order to survey novel pathologies and points of intervention.

In this Review, Minkoff and tenOever examine the relationship between SARS-CoV-2 biology and innate immunity, and they explore how antagonism and dysregulation of host innate immune defences contribute to COVID-19 disease severity.

Nipah virus (NiV) can be transmitted from bats and other animals to humans, causing severe encephalitis and respiratory disease. Here, Satterfield et al.show that the W protein of NiV modulates the host immune response and determines disease course in a ferret model of infection.

Functional characterization of the regulatory landscape of the adjacent costimulatory genes CD28, CTLA4 and ICOS in primary human T cell subsets identifies context-dependent programs controlling this locus critical for immune homeostasis.

Grockowiak et al. explore bone marrow niche heterogeneity in myeloproliferative neoplasms, polycytemia vera and essential thrombocytemia and find JAK2-mutated hematopoietic stem cells occupying distinct niches affecting cell growth and therapy response.

Vancomycin-resistant Enterococcus faecium is an important healthcare-associated pathogen and genomic analyses could inform targeted interventions. Here, the authors optimise an analysis pipeline for identification of putative transmission events using core genome multilocus sequence type clustering and split kmer analysis.

Organoid models of intestinal stem cell differentiation into Paneth cells allow for the identification, via high-throughput phenotypic screening, of biological targets and small molecules regulating the composition of intestinal epithelium.

Here the authors deliver aerosolized human monoclonal antibodies to SARS-CoV-2-infected rhesus macaques and show that the treatment significantly reduces viral RNA and infectious virus in the respiratory tracts, limits lung pathology, and decreases inflammatory cytokines.

Detection of primary aldosteronism, the most common form of secondary arterial hypertension, is essential for targeted management and prevention of cardiovascular complications. Here, the authors identify genetic loci associated with primary aldosteronism, suggesting new mechanisms of disease.

Analysis of lower respiratory tract microbiome of mechanically ventilated COVID-19 patients rules out a role for secondary respiratory infections as drivers of increased mortality.

The advantage of living in cities compared with rural areas with respect to height and BMI in children and adolescents has generally become smaller globally from 1990 to 2020, except in sub-Saharan Africa.

BRCA2 plays important roles in cell physiology by promoting DNA replication and DNA double-strand breaks repair. Here the authors, reveal the impact of BRCA2 depletion on the cell transcriptional program with activation of the innate immune response that is potentiated by PARP inhibitor treatments.

Barlesi and colleagues describe the determinants of severe COVID-19 outcomes in patients with cancer managed at the Gustave Roussy Cancer Centre.

Response to PD-1 checkpoint blockade is unpredictable in lung cancer patients. Here authors show in human lung and mouse tumour models that low or absent α_V integrin expression leads to better tumour growth control by anti-PD-1 via reduced TGF-β activation and hence increased infiltration of anti-tumour CD8⁺ T cells.

This Review discusses the molecular processes and clonal evolution that lead to myelodysplastic syndrome (MDS) and secondary acute myeloid leukaemia, highlighting the ways in which these insights are shaping the clinical management of MDS.

Multi-ancestry genome-wide association analyses identify new risk loci for Parkinson’s disease, and fine-mapping and co-localization analyses implicate candidate genes whose expression is associated with disease susceptibility.

A ‘bottom-up’ approach for calculating the rate of organic carbon burial in the global ocean shows larger variability than has been previously estimated, suggesting that the organic carbon cycle acted as positive feedback of past global warming.