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Here they demonstrate a therapeutic intervention elevating levels of CYP450-derived lipids to control the expansion of intermediate monocytes in tissue and peripheral blood, presenting a first in class therapeutic approach for treating chronic inflammatory disease.

Muscularis macrophages, housekeepers of enteric nervous system integrity and intestinal homeostasis, modulate α-synuclein pathology and neurodegeneration in models of Parkinson’s disease, and understanding the accompanying mechanisms could pave the way for early-stage biomarkers.

Engineered mucus-tethering bispecific nanobodies neutralize and entrap viruses to enhance mucosal immunity, preventing influenza infection and limiting SARS-CoV-2 transmission.

Walmsley and colleagues report that systemic hypoxia induces persistent loss of histone H3K4me3 marks and epigenetic reprogramming in neutrophil progenitors, resulting in long-term impairment of subsequent neutrophil effector functions.

Addressing how the nitrogen-induced changes in plant diversity differ from those in soil organisms is critical. This global meta-analysis suggests that nitrogen enrichment has stronger negative effects on plant diversity but modest to negligible effects on soil bacterial and fungal diversity.

Highly pathogenic avian influenza A H5N1 clade 2.3.4.4b virus has caused outbreaks in dairy cattle and cases in humans in the United States. Here, the authors assess levels of pre-existing cross-reactive antibodies to the epidemic virus strain in human serum samples collected in the United States.

Birth season has been associated with differences in epigenetic, developmental and health outcomes, but associations to developing metabolome are unclear. Here the authors report a secondary exploratory analysis of The Early Life Interventions for Childhood growth and development in Tanzania (ELICIT) trial showing that in rural Tanzania, an infant’s birth season shapes their metabolism up to 18 months of life, linked to rainfall, food insecurity and breastmilk composition.

Modulating mitochondrial NAD⁺ levels by changing the expression of the mitochondrial NAD⁺ transporter, SLC25A51, Mukherjee et al. demonstrate that mitochondrial, rather than cytosolic or nuclear, NAD⁺ levels are a key determinant of the rate of liver regeneration.

Parity induces an accumulation of CD8⁺ T cells, including cells with a tissue-resident-memory-like phenotype within human normal breast tissue, offering long-term protection against triple-negative breast cancer.

In Caenorhabditis tropicalis, three toxin–antidote elements arose via gene duplication from the essential tRNA-synthetase subunit FARS-3. The ancestral antidote probably acquired affinity for FARS-3, enabling presuppression of toxicity and allowing otherwise deleterious mutant alleles to evolve into selfish genes.

LEVA is a label-free immobilization method for studying surface-bound extracellular vesicles.

Yong et al. highlight how sampling conditions affect metabolic profile in renal cancer, showing that prolonged ischemic exposure disrupts tissue metabolome stability and masks important phenotypes, such as suppressed gluconeogenesis.

Spatial transcriptomics reveals distinct microglial mechanisms driving amyloid-β clearance in both passively and actively immunized patients with Alzheimer’s disease.

Analyses of genome and exome sequencing data identify rare coding and structural variants associated with atrial fibrillation and highlight genetic links between atrial fibrillation and cardiomyopathies.

Patients with inflammatory bowel disease (IBD) have increased risk for venous thromboembolism, but mechanistic insight is still lacking. Using both mouse experimental colitis models and IBD patient biopsies, here the authors implicate increased tissue factor activity on colitogenic T cells as a potential link.

Community-based conservation efforts for ecosystems can have manifold effects beyond the direct areas being managed. This study finds that, deep in the Amazon, communities effectively protected an area 36 times larger than the area they were guarding, but also had to bear all of the costs.

A purpose-built implantable system based on biomimetic epidural electrical stimulation of the spinal cord reduces the severity of hypotensive complications in people with spinal cord injury and improves quality of life.

Our understanding of variation in monocyte context-specific splicing and transcript usage is limited. Here, the authors find genetic variants that affect gene splicing in monocytes in specific contexts, including several diseases, and in response to stimulants.

Initial exposure to lipopolysaccharide (LPS) induces endotoxin tolerance, which reduces immunological reactions to LPS; here it is shown that primary LPS challenge is controlled by AhR, TDO2 and IL-10, whereas sustained effects require AhR, IDO1 and TGF-β, allowing for disease tolerance with reduced immunopathology in infections.

Convergent selection between crops can help to identify genetic variants with important roles in adaptation as a source of diversity for the improvement of cultivated species through the concept of inter-crop translational research for breeding.

Motile and non-motile cilia have distinct functions and protein complexes associated with them. Here, the authors show the conserved protein CFAP20 is important for both motile and non-motile cilia and is distinct from other ciliopathy-associated domains or macromolecular complexes.

This Viewpoint attempts to counter the arguments presented by Cravedi et al. in this issue of Nature Clinical Practice Nephrology. Although β-cell islet transplantation is not yet a widely viable treatment for type 1 diabetes, AM James Shapiro argues that the procedure's shortcomings are not insurmountable and that now is not the time for a moratorium on clinical research. Enhancing the mass of the initial islet engraftment, which would alleviate many of the present challenges, could be achieved in ongoing trials, and remarkable progress with xenotransplantation and human embryonic stem cells foreshadows the possibility of a renewable islet cell source.

Insufficient oxygen limits the efficacy of cell encapsulation therapies for type 1 diabetes. Here, the authors develop an implantable system that continuously generates oxygen to support high-density islet cell survival and function, enabling diabetes reversal in rats without immunosuppression.

Many individual genetic risk loci associate with multiple diseases, but the molecular basis of these loci often remains unclear. Here, the authors provide a framework to reveal the genetic cross-disease associations at the PROCR vascular disease locus.

Localized intrathecal administration of KCC2-expressing AAV9s enhances functional recovery in cervical models of traumatic contusive-compression spinal cord injury by restoring balanced excitatory/inhibitory neurotransmission.

High pathogenicity avian influenza virus has a wide host range and has been detected across a large geographic area. Here, the authors present evidence of spread to the Antarctic and sub-Antarctic regions, with signs of clinical infection and positive virus detection in birds and elephant seals.

How changes in brain blood vessels lead to a chronic reduction in blood flow and, consequently, to vascular dementia is poorly understood. Here, the authors show that venous endothelial dysfunction driven by EPAS1 promotes abnormal vascular remodeling and contributes to cognitive decline.

Neuromodulators that activate Gq-coupled receptors exert powerful control over brain function. Here, the authors develop a fluorescence lifetime sensor capable of imaging protein kinase C activity—a major effector of the Gq pathway—at cellular resolution in vivo.

Immunogenomic analyses of advanced high-grade serous ovarian cancer samples before and after neoadjuvant chemotherapy show that the tumor–immune microenvironment is intrinsically heterogeneous and that chemotherapy induces local immune activation.

Astrocytes are important players in ischemic stroke. Here, the authors use single nuclei transcriptomics to characterise marmoset astrocytes following brain injury. At functional level, they show that NogoAexpressing astrocytes limit macrophage infiltration.