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Aged hematopoietic stem cells (HSC) are characterised by reduced regenerative potential and a loss of quiescence. Here, the authors show nicotinamide riboside treatment shrinks the age-enlarged stem cell pool and shifts aged HSC functionally, metabolically and molecularly towards the young state.

Soft tissue trauma can result in aberrant osteochondral differentiation of local mesenchymal progenitor cells. Here the authors show that, in mice, soft tissue trauma results in NGF expression by perivascular cells, which leads to axonal invasion and drives abnormal osteochondral differentiation, and show that this process can be prevented by inhibition of NGF signaling.

Using time-controlled CRISPR screens, the authors identify AKIRIN2 as a factor involved in the nuclear import of the proteasome.

Integrative single-cell RNA sequencing and immunological profiling reveal that older adults have reduced antigen-specific cellular and humoral responses accompanied by increased cytokine storm and myeloid cell recruiting factors in response to acute SARS-CoV-2 infection.

A short isoform of the SARS-CoV-2 host receptor ACE2, expressed in human nasal and bronchial respiratory epithelia, is upregulated in response to interferon treatment and rhinovirus infection, but not SARS-CoV-2 infection.

Mass spectrometric profiling of a glycan library reveals that sialylated glycans, especially sialic acid-containing gangliosides, interact with the RBD of the SARS-CoV-2 spike protein and are involved in ACE2-dependent viral infection.

Foliar application of different forms of nanoscale copper to plant seedlings induces material-specific biochemical and molecular changes in root tissue that stimulate plant defence against soybean sudden death syndrome.

Microglia, the brain’s immune cells, suppress neuronal activity in response to synaptic ATP release and alter behavioural responses in mice.

Directed evolution of the ribosome is challenging because the requirement of cell viability limits the mutations that can be made. Here the authors develop a platform for in vitro ribosome synthesis and evolution (RISE) to overcome these constraints.

Using mouse and human plasma, Carver et al. identify factors that are altered with age and test which are reverted by a panel of genetic and pharmacological senolytic interventions in aged mice. They identify IL-23R as a senescence-associated, age-increased circulating biomarker.

Whole-genome sequencing and phenotype data sharing are introduced in a national health system to streamline diagnosis and to discover coding and non-coding variants that cause rare diseases.

HIV vaccine development will be facilitated by having animal models that are predictive for translation to humans. Here, the authors use two nonhuman primate models to compare the effects of natural infection and different adjuvants on antigen persistence, diversity and humoral immunity.

The impact of the DART spacecraft on the asteroid Dimorphos is reported and reconstructed, demonstrating that kinetic impactor technology is a viable technique to potentially defend Earth from asteroids.

The source of where definitive hematopoietic stem cells (dHSCs) develop in the mouse embyro has been much debated. Here, the authors identify that dHSCs arise from the intra-embyronic region by using murine embryonic explant transplantation but not from the yolk sac.

Inhibition of immune cell–derived acetylcholine synthesis or of its signaling via CHRNA2 in beige adipocytes reduces thermogenesis and exacerbates diet-induced obesity, suggesting a new mode of immuno–fat communication in energy metabolism.

Nematode bacterial symbionts were evolved in vitro to resist insect-sequestered plant toxins to improve the insect-killing efficacy of their nematode host.

The authors develop a noninvasive stimulation protocol to restore neural synchronization patterns and improve working memory in older humans, contributing to groundwork for future drug-free therapeutics targeting age-related cognitive decline.

Pulmonary arterial hypertension is a severe lung disease characterised by progressive vascular remodelling. Here, the authors show that reduced signalling of flow-activated transcription factor KLF2 is a common feature of human PAH and that KLF2-regulated exosomal miRNAs have a therapeutic effect.

The molecular mechanisms that drive irreversible acute liver failure remain poorly characterized. Here, the authors show that the recently discovered platelet receptor CLEC-2 (C-type lectin-like receptor) perpetuates and worsens liver damage during acute liver injury by blocking restorative neutrophil driven inflammation.

The potential links between infections and neurodegenerative disorders are unclear. Here, Wu et al. present a mouse model of low-grade candidemia characterized by highly localized cerebritis, accumulation of amyloid precursor protein and beta peptides, and mild memory impairment that resolves with fungal clearance.

Lowered synaptic density is believed to occur in major depressive disorder and PTSD, possibly as an effect of stress. Here, the authors use positron emission tomography (PET) to measure levels of the synaptic marker SV2A and show that SV2A density is lower in those with more severe symptoms of depression.

Castaño et al. show that primary breast tumours drive an IL-1β -mediated inflammatory response that inhibits cellular plasticity and metastatic colonization of metastasis-initiating cells.

The role of innate T cell subsets in the pathogenesis of spondyloarthritis (SpA) is not well understood. Here, the authors examine the role of invariant natural killer T (iNKT) and γδ-T cells in SpA and show that disease-derived iNKT and γδ-T cells have unique and Th17-skewed phenotype and gene expression profiles within inflamed joints.

Mast cells within the tumor microenvironment have controversial roles. Here, the authors show, using genetic mouse models, that in gastric cancer, mast cells at the periphery of the tumors are activated via cancer cell produced-IL33 and promote tumorigenesis by recruiting macrophages within the tumors.

The severity of ulcerative colitis, and response to treatment, is highly variable. Here, the authors examine rectal gene expression signatures and faecal microbiomes of children and adults with the disease and provide new insights in to pathogenesis.

A wealth of critical minerals has driven widespread artisanal mining in the Congo Basin, bringing with it the risk of deforestation. Statistical analysis of remote-sensing data reveals that mining-associated deforestation is dominated by indirect factors, land-use change to support mining communities, rather than the direct impacts of the onset of mining.

Decellularized whole porcine livers revascularized with human endothelial cells and implanted heterotopically into immunosuppressed pigs whose spleens had been removed can sustain perfusion for up to 15 days.

Humans understand actions by making inferences about the person's intentions. Comparing humans with chimpanzees, this study shows that humans refer to the actors' faces more than chimpanzees do when observing goal-directed actions, indicating that humans view actions by integrating information from the actor.

Pumas are experiencing increased isolation as human persecution and habitat loss fragment the populations of this once widespread species. Here, the authors estimate the genomic consequences of this isolation by analyzing the genomes of ten pumas from across North and South America.

The olfactory bulb (OB) is involved in odour processing, but exactly how is unclear. Tatti et al.identify a population of VGluT3-expressing neurons within the OB that suppresses spontaneous and odour-evoked firing of OB output neurons via direct connections with OB output neurons and juxtaglomerular cells.

SLAP is an adaptor protein that negatively regulates receptor signalling, but its involvement in cancer has not been described. In this study, Naudin et al. demonstrate that SLAP negatively regulates the receptor EphA2 in a Src-dependent manner and is reduced in expression in colorectal cancer.

Synaptic inhibition in the olfactory bulb (OB) is believed to play a role in odour processing. Here, the authors use a Pcdh21-driven Cre-line to disrupt KCC2 expression in OB mitral cells and find altered synaptic connectivity along with disrupted separation of odour-induced activity patterns.

T cell activation upon TCR signaling can lead to development of effector and memory cells. Roychoudhuri and colleagues show that the transcription factor BACH2 promotes memory CD8⁺ T cell generation by blocking access to genomic regulatory sites recognized by AP-1.