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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.

Using a cryogenic 300-mm wafer prober, a new approach for the testing of hundreds of industry-manufactured spin qubit devices at 1.6 K provides high-volume data on performance, allowing optimization of the complementary metal–oxide–semiconductor (CMOS)-compatible fabrication process.

Oral vaccination is a potential option to elicit systemic and mucosal immunity against HIV. Here, Jones et al. show that oral vaccination with a modified needle-free injector induces protective immunity against SHIV in non-human primates and is superior to topical application of vaccines to oral tissues.

Human pluripotent cells (hPSCs) in standard culture are similar to mouse epiblast cells, but heterogeneity within hPSC cultures complicates comparisons. Here the authors show that a subpopulation of hPSCs enriched for self-renewal capacity have distinct cell cycle, metabolic, DNA methylation, and ATAC-seq profiles.

The clinical detection of fluorescent protoporphyrin IX during glioma-resection surgery can be improved via a microscope that pairs stimulated Raman histology and two-photon excitation fluorescence microscopy.

Delivering genes to and across the brain vasculature efficiently and specifically across species remains challenging. Here, the authors show that endothelial-specific AAVs with serotype flexibility enable redosing and transform the brain vasculature into an in vivo biofactory in genetically diverse rodents. In primates, these vectors cross the blood-brain-barrier and show broad tropism.

Methylation profiling of single cells in high throughput achieves read-alignment rates approaching bulk cell population studies.

Intrinsically disordered proteins that form amyloid fibrils are hard to target with traditional therapeutic approaches. Here, the authors report on an oligoquinoline derivative that binds the human islet amyloid polypeptide, stabilising an alpha-helical structure that reduces its cellular toxicity.

Understanding the dynamics of light-induced carriers is vital for employing two-dimensional materials in optoelectronic applications. Here, the authors use a sub diffraction-limit optical technique to reveal the excitonic properties of monolayer molybdenum disulfide at the nanoscale.

Here the authors present an HIV-1 vaccine strategy that combines Env stabilization, nanoparticle display, and glycan trimming, which improves neutralizing antibody responses, frequency of vaccine responders, and germinal center reactions in animal models.

Amino acid changes in a newly identified spike epitope enabled the Delta variant to evade a population antibody response.

In an analysis of long-term safety events in 783 patients treated with T cell therapy in 38 trials, 2.3% of patients developed second primary malignancies, and vector integration analyses revealed no pathological insertions.

The expression of fibroblast growth factor in aged muscle fibre, the muscle stem cell niche, is shown to cause satellite cells to lose the capacity for self-renewal, and is thus an age-dependent change that directly influences stem cell quiescence and function.

Biochemical and genetics studies identify CRL4^AMBRA1 as the ubiquitin ligase that has a key role in regulating the stability of D-type cyclins during cell-cycle progression.

Homotrimeric DARPin molecules neutralize SARS-CoV-2 variants of concern by targeting a critical ACE2-binding interface.

Ibogaine is a natural substance that interrupts opioid addiction but has cardiac risks. This article introduces novel ibogaine analogs that show reduced cardiac risk and enhanced neuroplasticity and therapeutic-like effects in models of opioid use disorder.

Post birth the gastrointestinal tract undergoes development including the establishment of the microbiome, establishment of tolerance and maturation of the epithelium. Here the authors show a histone demethylase LSD1 is required for postnatal intestinal epithelium maturation and how this impacts local immune cell composition and gut homeostasis.

Antigen-specific CD8⁺ T cells can be imaged by immunoPET with the help of synTacs, MHC-based tools that bind to relevant T-cell receptors.

Loss-of-function variants in thyroid hormone transporter MCT8 cause a neurodevelopmental and metabolic disorder. Here the authors identify genotype-phenotype relationships, advance insights in MCT8 (dys)function and create a pathogenicity-severity variant classifier.

Longitudinal clinical and multi-omics data from 108 healthy individuals are analyzed to identify putative biomarkers and diagnostics of early disease states.

Wang et al. show how glucose sensing via O-GlcNAcylation drives the assembly of a glycolytic metabolon on the mitochondrial surface to couple metabolic efficiency with neuronal activity.

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.

Efficient transmission of SARS-CoV-2 among infected ferrets requires a functional furin cleavage site in the SARS-CoV-2 spike protein.

Manipulation of spins in the solid state is a promising avenue for quantum information and field sensing applications. Bennett et al. demonstrate voltage tunability of single-spin states in a quantum dot as a step towards universal control of a single spin with a single electrical gate.

Hailong, an anti-phage defence system, synthesizes an oligodeoxyadenylate signal that blocks effector activity in the absence of phage infection but is degraded by phage-encoded DNA exonucleases, leading to protective growth arrest of infected cells.

Tumours acquire new vasculature through angiogenesis or through alternative pathways including the less understood vasculogenesis mimicry. Here the authors identify a vasculogenic mimicry-competent subpopulation of melanoma cells that expresses the vascular cell adhesion molecule PECAM1, but not VEGFR-2.

Analysis of ground-sourced and satellite-derived models reveals a global forest carbon potential of 226 Gt outside agricultural and urban lands, with a difference of only 12% across these modelling approaches.

Segal and colleagues identify a population of immature neutrophils as having regenerative properties on injured neurons and being capable of inducing axon regeneration. These findings suggest potential strategies for restoring lost neurological functions in central nervous system disorders.

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.

Factors limiting CNS remyelination with age are poorly understood. Here the authors show that aged Treg lose capacity to support CNS remyelination in mice, which can be restored in a young environment.

Human antibodies cross-reactive for several viruses within the Ebolavirus genus have been identified. Here the authors present the crystal structure of such a neutralizing monoclonal antibody (mAb) targeting the stalk of Bundibugyo virus glycoprotein and show that mAb binding may interfere with trimeric bundle assembly and/or the viral membrane.

Here, the authors use electrostatic gates to trap interlayer excitons (IE) in MoSe₂/WSe₂ heterobilayers. They observe an exponential broadening of the IE emission linewidth that signals the IE ionization threshold.

A small molecule identified from high-throughput screening and optimization specifically stabilizes a disease-linked CLRN1 protein, delivering it to its site of action at the plasma membrane and preserving hearing in a new mouse model for Usher syndrome type III.

Wiita and colleagues use cross-linking mass spectrometry and glycoprotein surface capture to identify an activated conformation of integrin β₂ present on AML cells and develop CAR T cells that target this conformation antigen in preclinical models.

Photoselective sequencing combines targeted illumination and photocaged fragment libraries to enable the spatial analysis of genomic sequence and chromatin accessibility profiles with subcellular resolution in the context of complex tissues.

A class of compounds with a dual mechanism of action—direct targeting of IspH and stimulation of cytotoxic γδ T cells to enhance pathogen clearance—are active against multidrug-resistant bacteria.

Golub and colleagues identify the phosphate exporter XPR1 as a therapeutic vulnerability in ovarian and uterine cancers, and show that phosphate efflux inhibition reduces tumor cell viability through accumulation of intracellular phosphate.

The authors describe an integrated atlas of the diverse cell types in the mouse primary motor cortex.

A longitudinal study of an individual patient developing neutralizing antibodies against HIV-1 (targeting the V1V2 region of gp120) reveals how such neutralizing antibodies develop and evolve over time, providing important insights relevant to vaccine development.

Studies have shown that placental aneuploidy is correlated with adverse pregnancy outcomes, though few causative data are available. Here they show that chromosomal instability is an inherent feature of trophoblasts and normal human placentas, without functional compromise, and provide mechanisms for how this damage is tolerated.

An analysis of over 2,000 genomes from Human Microbiome Project metagenomic data led to the identification of several extended- and narrow-spectrum antibiotics against clinical multidrug-resistant pathogens, including methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococci.