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An analysis of 24,202 critical cases of COVID-19 identifies potentially druggable targets in inflammatory signalling (JAK1), monocyte–macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).

A global network of researchers was formed to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity; this paper reports 13 genome-wide significant loci and potentially actionable mechanisms in response to infection.

A simple and versatile strategy is established to facilitate molecular recognition by extending electron catalysis for use in supramolecular non-covalent chemistry.

Structural variants (SVs) in human genomes contribute diversity and diseases. Here, the authors use a multi-platform strategy to generate haplotype-resolved SVs for three human parent–child trios.

In this study, Jirsaraie et al. analyze data from the Adolescent Brain Cognitive Developmental study and use machine learning to predict both current and future psychological symptoms and to determine rates of change in symptom severity over time.

Whole-genome sequencing, transcriptome-wide association and fine-mapping analyses in over 7,000 individuals with critical COVID-19 are used to identify 16 independent variants that are associated with severe illness in COVID-19.

The supercooling parameter, P, was found to be the best indicator of grain morphology of metallic alloys produced with high solidification velocities. This provides guidance for the design of new alloys for use with additive manufacturing.

A long-period radio transient with coincident radio and X-ray emission and observational properties unlike any known Galactic object has been observed by the Australian Square Kilometre Array Pathfinder.

Acetylcholine–α9 nAChR signaling regulates thymic negative selection.

An integrated data and sample repository for clinical, cellular and multi-omics research from diverse spaceflight missions known as Space Omics and Medical Atlas (SOMA) is presented.

Trees come in all shapes and size, but what drives this incredible variation in tree form remains poorly understood. Using a global dataset, the authors show that a combination of climate, competition, disturbance and evolutionary history shape the crown architecture of the world’s trees and thereby constrain the 3D structure of woody ecosystems.

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.

The molecular mechanisms underlying the function of different cellular states in glioblastoma stem cells (GSCs) remain poorly understood. Here, the authors perform integrated single cell and bulk analysis of GSCs and identify potential therapeutic targets.

Proteins are promising molecular materials for next-generation electronic devices. Here, the authors fabricated printable digital logic circuits comprising resistors and diodes from self-assembled photosystem I complexes that enable pulse modulation.

Achieved high thermoelectric figure of merit (ZT) in organic thermoelectric materials remains a challenge due to their low packing order and poor host/dopant miscibility. Here, the authors report side chain-engineered n-doped fullerene derivatives with record ZT >0.3 for organic thermoelectrics.

Analysis of rare protein-truncating, damaging missense and copy number variants from exome sequencing of 63,237 individuals identifies 72 genes associated with autism spectrum disorder.

Developing broad antiviral drugs against dengue is challenging due to genetic diversity. Here, the authors generate PROTACs targeting the dengue virus envelope protein demonstrating improved potency and broadened activity against other mosquito-borne flaviviruses as compared to the parental inhibitors.

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.

In this phase 1 trial, patients with locally advanced or metastatic solid tumors were treated with the individualized mRNA neoantigen-specific immunotherapy (iNeST) autogene cevumeran alone or in combination with the anti-PD-L1 agent atezolizumab, showing long-lasting neoantigen-specific immune responses and preliminary clinical activity, supporting further development of this therapeutic approach.

Peptide-based therapeutics are promising therapeutic modalities, however, their prevalent drawback is poor circulation half-life in vivo. Here, the authors report the selection of albumin-binding macrocyclic peptides from genetically encoded libraries of peptides modified by perfluoroaryl-cysteine chemistry, with decafluoro-diphenylsulfone.

It is not clear how agricultural intensification affects spatially coupled ecosystems. Here, the authors use long-term datasets on managed grasslands coupled with unmanaged wetlands showing that grassland intensification affects ecosystem service multifunctionality of spatially coupled wetlands

Analysis of ancient human DNA from the Swahili coast reveals that predominantly African female ancestors and Asian male ancestors formed families after around ad 1000 and lived in elite communities in coastal stone towns.

Chemisorbed molecules combining glycol-ether moieties and fullerenes are shown to form uniform and air-stable self-assembled bilayers on coinage metals, and are amenable to versatile functionalization by in-place exchange of the top layer.

Here the authors report spaceflight secretome profiles by integrating plasma proteome, metabolome, and extracellular vesicles/particles proteome from the SpaceX Inspiration4 crew, which showed differences in coagulation, oxidative stress, and brain-enriched proteins.

Longitudinal multi-omics reveals shifts to the human microbiome across multiple body sites and the associated immune responses during short-term spaceflight.

Enhancers for endodermal organs are primed at the chromatin level prior to lineage induction by FOXA pioneer transcription factors; how pervasive this is, is not well known. Here the authors show that only a small subset of organ-specific enhancers are bound and primed by FOXA prior to lineage induction, whereas the majority do not undergo chromatin priming and engage FOXA upon lineage induction.

An orally bioavailable small-molecule active-site inhibitor of the phosphatases PTPN2 and PTPN1, ABBV-CLS-484, demonstrates immunotherapeutic efficacy in mouse models of cancer resistant to PD-1 blockade.

A trans-ancestry genome-wide association study of serum urate levels identifies 183 loci influencing this trait. Enrichment analyses, fine-mapping and colocalization with gene expression in 47 tissues implicate the kidney and liver as key target organs and prioritize potential causal genes.

Theories of change have been a staple of sustainability research, but how to connect such overarching concepts to actionable items can be a struggle. This study uses coastal wetlands to demonstrate a potential framework for integrating indicators of conservation enabling conditions into theories of change.

Tunnelling currents through molecular junctions are affected by quantum interference effects, but understanding the factors leading to them remains a challenge. Here the authors show that through-space conjugation in self-assembled monolayers leads to conformation-dependent quantum interference that suppresses conductivity.

Chiral domain walls in magnetic films can be electrically controlled, which makes them attractive for applications, but domain walls in ultrathin films are normally non-chiral. Here, the authors observe chiral domain walls in ultrathin Fe/Ni bilayers that are stabilized by the magnetic anisotropy.

Ferroptosis is a lipid-peroxide-driven cell death with promising therapeutic applications. Although peroxidation of various subcellular membranes can initiate ferroptosis, the authors found that the endoplasmic reticulum is an essential site.

A genome-wide association study of critically ill patients with COVID-19 identifies genetic signals that relate to important host antiviral defence mechanisms and mediators of inflammatory organ damage that may be targeted by repurposing drug treatments.

Across 24 countries, Hoogeveen et al. found that gobbledegook coming from a scientist was considered more credible than when coming from a spiritual guru. This ‘Einstein effect’ was less pronounced for religious individuals.

The ability to print arbitrary colors and shapes in all three dimensions at microscopic length scales is still lacking. Here, the authors introduce a means to produce three-dimensionally-printed photonic crystals with a periodicity as small as 280 nm, achieving sub-100-nm features with a full range of colors.

Myoepithelial cells prevent tumour growth and invasion in DCIS. Here, the authors show that p63 and TCF7 cooperate to regulate a transcription factor network for the maintenance of normal myoepithelial function and altered expression of these genes perturb myoepithelial function in DCIS to promote invasive progression.

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.

Eusocial caste systems have evolved independently multiple times. Here, Warner et al. investigate the amount of shared vs. lineage-specific genes involved in the evolution of caste in pharaoh ants and honey bees by comparing transcriptomes across tissues, developmental stages, and castes.

The Somatic Mosaicism across Human Tissues Network aims to create a reference catalogue of somatic mosaicism across different tissues and cells within individuals.

This study presents an analysis of reported happiness following spending decisions of an endowment of 10,000 USD. Participants in high vs low-income countries differed regarding what spending decisions contributed more to happiness.

Brillouin lasing with 0.7 Hz fundamental linewidth is observed by optically exciting a monolithic bus–ring Si₃N₄ waveguide resonator. The Brillouin laser is applied to an optical gyroscope and a low phase-noise photonic microwave oscillator.

CREST-seq allows functional screening of cis-regulatory elements through the use of sgRNA pairs to introduce tiled deletions in regions of interest. The analysis of a 2-megabase target region shows that promoters can act as distal enhancers for unrelated genes.

A new computational method allows key developmental checkpoints and important parameters of population dynamics to be inferred from single-cell RNA-sequencing time series data.

The Impact of Genomic Variation on Function Consortium is combining single-cell mapping, genomic perturbations and predictive modelling to investigate relationships between human genomic variation, genome function and phenotypes and will provide an open resource to the community.

In an inter-laboratory study, the authors compare the accuracy and performance of three optical density calibration protocols (colloidal silica, serial dilution of silica microspheres, and colony-forming unit (CFU) assay). They demonstrate that serial dilution of silica microspheres is the best of these tested protocols, allowing precise and robust calibration that is easily assessed for quality control and can also evaluate the effective linear range of an instrument.