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Desmoplastic stroma is a hallmark of aggressive colorectal cancer. Matrix cancer-associated fibroblasts derived THBS2 establishes a fibrotic, immune-exclusionary barrier that limits CD8⁺ T cell infiltration, while its inhibition restores CXCR3-mediated T cell recruitment and enhances response to immune checkpoint blockade.

A vesicular nanoreactor has increased crosslinks between the constituent polyions for longer blood circulation, and is shown to sensitize solid tumours to asparagine starvation therapy.

Poor access to suitable light-sheet microscopes remains a big obstacle for many end-users in biomedical research. Here, the authors present descSPIM, a low-cost, low-expertise light-sheet microscope for routine 3D imaging of cleared samples.

Mitochondria with mutations in their DNA from cancer cells can be transferred to T cells in the tumour microenvironment, which leads to T cell dysfunction and impaired antitumour immunity.

XBB is the first recombinant, globally dominant variant of SARS-CoV-2. Here, the authors examine the variant’s origins and virological properties, showing it is the first example of SARS-CoV-2 improving its fitness through recombination.

The intestinal mucosa presents a complex immune environment requiring a fine balance of immune activity against pathogenic, benign or self antigens. Here the authors show that gut CD4⁻CD8αβ⁻TCRαβ⁺ T (double-negative T/DNT) cells express MHC-II, serve as antigen-presenting cells, and tolerize gut CD4 T cells to help maintain gut immune homeostasis.

Membrane potentials in living cells can function as electrical signals. Here, the authors report that spermatozoa utilize their electrical signals during the maturing stage to create appropriate membrane lipids environment that is important for sperm motility.

XBB.1.5 of SARS-CoV-2 is a descendant of XBB.1 and has mutations in spike and ORF8, making it more infectious to humans. Here, the authors examined in detail the differences in virological properties of the two variants.

Glycoprotein-2 (GP-2) can protect the intestinal epithelial barrier from bacteria and is associated with protection against Crohn’s disease. Here, the authors show pancreatic GP-2 is the source of the intestine’s luminal GP-2 that binds bacteria and prevents them from attaching to the epithelium, also limiting pathology in a DSS colitis mouse model.

Here, the authors develop a cell-permeable chemical catalyst that acetylates histone H2BK120 in leukemia cells, attenuates NELFE chromatin binding, reprograms transcription, and reduces the tumorigenic potential of leukemia cells in mice.

Allogenic induced pluripotent stem cell-derived cardiomyocytes transplanted directly into infarcted cynomolgus monkey hearts show electrical coupling with host cardiomyocytes improve cardiac contractile function after mild immunosuppression.

This prospective study conducted in a phase 3 trial has shown that pre-treatment serum VEGF-A was a negative biomarker for PFS in patients with advanced NSCLC treated with a combination of an anti-angiogenic agent and a PD-1 axis inhibitor.

It is unclear how a single oncogenic cell primes tumorigenesis. Here the authors visualised this behaviour using a zebrafish larval skin as a model and show that RasG12V oncogenic cell is eliminated through oncogene-senescence while a gain of function mutation in p53 alters this behaviour from tumour suppressive to tumour promoting.

Monoclonal antibodies conjugated with multiple polymer chains functionalized to target glucose transporter 1 and detaching in the reductive tumour microenvironment augment the potency and safety of checkpoint blockade therapy for glioblastoma.

VMAT2 regulates neurotransmitter uptake into synaptic vesicles. Here, the authors determined the cryo-EM structures of VMAT2, providing a structural basis for understanding VMAT2- mediated vesicular transport of neurotransmitters.

Recent Omicron SARS-CoV-2 subvariants independently acquire 5 key Spike mutations. Here, the authors evaluate the evolutionary importance of the 5 mutations and characterize the virological properties of variant BQ.1.1 harboring all 5 mutations.

Lipidated Atg8 affects membrane morphology via two aromatic membrane-facing residues that are important for autophagy in budding yeast and mammalian cells.

Histamine receptor H₄R is implicated in chronic inflammatory diseases, such as asthma, arthritis, and atopic dermatitis. Here, the authors determined the first cryo-EM structure of the histamine H4 receptor, providing valuable structural insights for the design of drugs targeting H4R in chronic inflammatory diseases.

In a rat model of short bowel syndrome, transplantation of small intestinal organoids into the colon partially restores intestinal function and improves survival—a proof of principle that organoid transplantation might have therapeutic benefit.

The naked mole-rat exhibits an exceptional resistance to cancer. Here, the authors show that induced pluripotent stem cells derived from the naked mole-rat lack teratoma-forming tumorigenicity due to a naked mole-rat-specific ARF-dependent tumour-suppression mechanism.

Cortical excitatory/inhibitory (E/I) imbalance is a feature of autism spectrum disorder (ASD). Here, the authors show that FoxG1 regulates the formation of cortical GABAergic circuits affecting social behaviour during a specific postnatal time window in mouse models of ASD.

Tissue-resident memory T cells (T_RM cells) are important for the localized protection of specific body compartments. Nakayama and colleagues identify heterogeneity in lung T_RM cells, with one subset driving fibrosis and inflammation and another reining in pathology in response to fungal challenge.

Mutations in Ftkn cause Fukuyama muscular dystrophy, and heart failure is the main cause of death in thes patients. Here the authors show that acute elimination of Fktn in adult mice causes early mortality, and this is associated with myocyte dysfunction, with disorganised Golg-microtubule networks, and that the pathology can be ameliorated with colchicine treatment.

A comprehensive analysis of the central nervous system in aging mice implicates senescent microglia and commensal bacteria as modulators of neuroinflammatory phenotypes.

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Neuropathic pain hypersensitivity is known to undergo diurnal variations, although the underlying mechanisms are not clear. Using a sciatic nerve-injury mouse model, the authors find such diurnal changes are mediated by glucocorticoid induced enhancement of ATP release from astrocytes via pannexin-1 hemichannels.

Autism spectrum disorder (ASD) is manifested by subtle but significant changes in the brain. Here, Yahata and colleagues devise a novel machine learning algorithm and develop a reliable ASD classifier based on brain functional connectivity, with which they quantitatively measure neuroimaging dimensions between ASD and other mental disorders.

While a majority of histones are replaced by protamines during spermatogenesis, a small amount is retained in mammalian spermatozoa. Here the authors develop a method to purify histones from replacement-completed sperm (HRCS), completely solubilize histones from cross-linked HRCS without MNase digestion, and map histone-binding sites in these cells.

Tanaka et al investigate the mechanism by which psoriasis-like dermatitis may occur following PD-1 antibody treatment for melanoma. They find that PD-1 loss in CD8 T-cells accelerates dermatitis in a manner depending on IL-6 signaling, suggesting IL-6 as a potential therapeutic target.

Regulatory T cells proliferate robustly in gut lymphoid tissues. Hase et al. show that this proliferation requires their expression of the epigenetic regulator Uhrf1, which is increased in response to IL-2 produced by effector T cells.

The authors investigate the in vivo function of microRNA-124a by specifically disrupting Rncr3, the dominant source of miR-124a in mice. Their results suggest that miR-124a is important for maturation and survival of dentate gyrus neurons and retinal cones and acts by repressing Lhx2 translation.