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The disordered molecular aggregation of non-fullerene acceptors in nonhalogenated solvents limits the performance of organic solar cells. Here, the authors apply an ultrasound field to induce J aggregation of molecules, achieving maximum efficiency of 20.41% for o-xylene-processed ternary devices.

Kozai, Fernandez-Martinez et al. use high-speed atomic force microscopy to study the permeability barrier of yeast nuclear pore complexes. They show that karyopherins remodel a central plug that shapes barrier dynamics and disorder within the pore.

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.

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).

Tumour evolution and heterogeneity in high grade serous ovarian cancer (HGSOC) remains poorly characterised. Here, the authors investigate the genomic landscape of HGSOC and reveal two distinct evolutionary trajectories associated with clinical outcomes.

Nabbi et. al. analyze immunohistochemistry, comprehensive genomic profiling, RNA-sequencing, and TCR-sequencing data from 66 pediatric patients with cancer from a phase 1–2 clinical trial (iMATRIX-atezo) to nominate biomarkers associated with response to immunotherapy in pediatric cancer.

BMP signaling is important for multiple process, including craniofacial development, but relatively little is known about how BMP ligands are secreted. Here they show that embryonic palate mesenchyme cells undergo transient changes in intracellular calcium and that depolarization of these cells induces BMP4 release, suggesting that ion channels are a node in BMP4 signaling.

Integration of mathematical modeling, ecological analyses of patient biopsies, and neoantigen heterogeneity suggests recruitment of immunosuppressive cells is key to initializing transformation from adenoma to carcinoma in human colorectal cancer.

Triple negative breast cancer is a deadly form of breast cancer with limited therapeutic options. Here the authors show the efficacy of GLUT1 pharmacological inhibition against a subset of tumors expressing RB1, thereby identifying RB1 protein level as a biomarker of sensitivity to anti-GLUT1 therapy.

As synthetic biology expands, creating “drag-and-drop” regulatory tools that can achieve diverse regulatory outcomes are paramount. In this work, the Carbon Storage Regulatory Network of Escherichia coli is rewired to create synthetic post-transcriptional genetic circuits that leverage the native interactions and are composed to achieve complex bacterial computation.

HLA peptidomic analysis identifies recurrent intracellular bacteria-derived peptides presented on HLA-I and HLA-II molecules in melanoma tumours, revealing how bacteria can modulate immune functions and responses to cancer therapies.

This paper reports integrative molecular analyses of urothelial bladder carcinoma at the DNA, RNA, and protein levels performed as part of The Cancer Genome Atlas project; recurrent mutations were found in 32 genes, including those involved in cell-cycle regulation, chromatin regulation and kinase signalling pathways; chromatin regulatory genes were more frequently mutated in urothelial carcinoma than in any other common cancer studied so far.

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.

Analysis of data on six stable crops, capturing two-thirds of global crop calories, allows estimation of agricultural impacts and the potential of global producer adaptations to reduce output losses owing to climate change.

The thymus supports T cell immunity by providing the environment for thymocyte differentiation. Here the authors profile human thymic stroma at the single cell level, identifying ionocytes as a new medullary population and defining tissue specific antigen expression in multiple stromal cell types.

Efforts to identify microbial signatures of response to immune checkpoint blockade suggest that strain-level associations may be cancer type agnostic but cancer therapy specific.

T-cell receptor peptide vaccines may hold promise as future therapy for multiple sclerosis (pages 1109–1115).

The spatial organization of a tumor affects how it grows and responds to treatment. Here, the authors present VALIS, a software to align sets of whole slide images (WSI) with state-of-the-art accuracy, enabling spatial studies of the tumor ecology.

Using a quantum annealing processor to study three-dimensional spin glasses demonstrates an accurate large-scale quantum simulation of critical dynamics and a scaling advantage over analogous classical methods for energy optimization.

A nanoscale superconducting sensor used to map the magnetic fringe fields in twisted bilayers of MoTe₂ shows the formation of fractional Chern insulator states at zero magnetic field.

A study establishes a scalable approach to engineer and characterize a many-body-localized discrete time crystal phase on a superconducting quantum processor.

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.

X-ray crystallography, cryo-electron microscopy, structural modelling, biochemistry, cell biology, and evolutionary analysis enable characterization of ORF2p, the reverse transcriptase of the ancient ‘parasitic’ LINE-1 retrotransposon that has written around one-third of the human genome.

Shifts in species’ migration timing as a result of climate change can result in mismatched temporal overlap with their critical resources. Here the authors show that the magnitude and direction of shifts in juvenile Pacific salmon migration timing vary among species and populations, resulting in variable mismatch with marine productivity, which has implications for climate change vulnerability.

Dual-rail encodings of quantum information can be used to detect loss errors, allowing these errors to be treated as erasures. The measurement of dual-rail states with error detection has now been demonstrated in superconducting cavities.

Stig Bojesen, Georgia Chenevix-Trench, Alison Dunning and colleagues report common variants at the TERT-CLPTM1L locus associated with mean telomere length measured in whole blood. They also identify associations at this locus to breast or ovarian cancer susceptibility and report functional studies in breast and ovarian cancer tissue and cell lines.

Gelareh Zadeh, Kenneth Aldape and colleagues present an integrative genomic analysis of schwannomas. In addition to finding recurrent mutations in ARID1A, ARID1B and DDR1, they identify a recurrent SH3PXD2A-HTRA1 fusion that confers increased proliferation, invasion and in vivo transformation, and is associated with sensitivity to MEK inhibition.

Chronic neuropathic pain is associated with K⁺ channel downregulation in primary sensory neurons. The authors show that G9a, a histone-modifying enzyme, is required for transcriptional repression of K⁺ channel–associated gene families caused by nerve injury. G9a in primary sensory neurons is a key epigenetic regulator involved in acute-to-chronic pain transition.

Lineage tracing of human stem cells is achieved by measuring fluctuating DNA methylation.

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.

Artificial Intelligence (AI) has the potential of assisting the study and diagnosis of veterinary cancers. Here, the authors build a cancer digital pathology atlas encompassing multiple animal species and demonstrate an AI approach for comparative pathology, which yields insights about immune response and morphological similarities.

The Cancer Genome Atlas presents an integrative genome-wide analysis of genetic alterations in 279 head and neck squamous cell carcinomas (HNSCCs), which are classified by human papillomavirus (HPV) status; alterations in EGFR, FGFR, PIK3CA and cyclin-dependent kinases are shown to represent candidate targets for therapeutic intervention in most HNSCCs.

A new specific, small-molecule activator of the PI3Kα isoform (UCL-TRO-1938) identified through high-throughput screening can transiently activate PI3K signalling and biological responses in cells and tissues, with potential therapeutic applications in tissue protection and regeneration.

By methylating the phosphate groups of PtdIns(3,4,5)P₃ researchers can load this lipid more efficiently into a mass spectrometer and thus this lipid can be quantified in the presence of an internal synthetic standard.

Alterations in proteins within nuclear compartments often lead to changes in chromosomal architecture. Here, using acute targeted protein degradation, the authors reveal that the nuclear complex protein Matrin3 directly mediates differentiation through stabilizing chromatin loop domain interactions.

Three key axes of variation of ecosystem functional changes and their underlying causes are identified from a dataset of surface gas exchange measurements across major terrestrial biomes and climate zones.

The function of B cells in peripheral blood and secondary lymphoid organs has long been appreciated but whether and how they contribute to tissue immune homeostasis is lesser known. Non-lymphoid organs harbour tissue-resident B cells that include a substantial population of B-1 cells and promote homeostatic anti-inflammatory macrophage polarization via IL-10, with profound effects on bacterial clearance during local infection.