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An inherently explainable AI trained on 1,015 expert-annotated prostate tissue images achieved strong Gleason pattern segmentation while providing interpretable outputs and addressing interobserver variability in pathology.

Autoimmune encephalitis (AIE) may involve neuron-specific cytotoxic T cells, but evidence is still lacking. Here the authors use induced pluripotent stem cells from patients with AIE and single cell RNA-sequencing of ex vivo CD8 T cells to find neuron-specific, KIR⁺CD8⁺ T cells with altered transcriptome that potentially contribute to AIE etiology.

The transcription factor ATF6 causes an enrichment in long-chain fatty acids in the colonic epithelium, which leads to changes in the gut microbiota and contributes to the development of colorectal cancer in humans and mice, thereby linking endoplasmic reticulum stress responses to lipid metabolism and tumorigenesis.

Non-antibiotic drugs from a wide range of therapeutic classes can alter the ability of gut commensals to resist invasion by enteropathogens, a previously underappreciated side effect of such drugs.

P. Poduval et al. theoretically study the nonzero-temperature vestigial phases of a 2D model exhibiting both triplet superconductivity and magnetism. They show that this model allows for a unique superconducting state in which the condensate consists of entities with three electrons and one hole, with properties similar to those seen in experiments on moiré systems.

In individuals who have achieved natural control of HIV-1 without drug treatment, intact proviral sequences are integrated into genomic regions that are not permissive to active viral transcription, indicating deep latency of the virus.

Reduced glomerular filtration rate (eGFR) is a hallmark of chronic kidney disease. Here, Pattaro et al. conduct a meta-analysis to discover several new loci associated with variation in eGFR and find that genes associated with eGFR loci often encode proteins potentially related to kidney development.

Plasma extracellular vesicles contain quantifiable amounts of TDP-43 and full-length tau, allowing the accurate assessment of pathology in frontotemporal dementia, frontotemporal dementia spectrum disorders and amyotrophic lateral sclerosis.

Medin promotes the formation of vascular aggregates with amyloid-β in mouse models and in human patients with Alzheimer’s disease, and is associated with vascular defects and cognitive decline.

Blockade of lymphotoxin β-receptor (LTβR) signalling restores WNT signalling and epithelial repair in a model of chronic obstructive pulmonary disease.

Therapeutic interference with the immune response after myocardial infarction holds the potential to close a clinically relevant gap. Here, the authors show that inhibition of a cardiomyocyte-specific ADAM10 / CX3CL1 axis improves post infarction survival and cardiac function by attenuating neutrophil-mediated myocardial damage.

Cellular nuisance compounds are a burden in chemical biology and drug screening. Here the authors profile prototypical cytotoxic and nuisance compounds using the cell painting assay to systematically characterise cellular morphologies associated with compound-dependent cellular injury and nuisance activity.

Patricia Munroe, Christopher Newton-Cheh, Andrew Morris and colleagues perform association studies in over 340,000 individuals of European ancestry and identify 66 loci, of which 17 are novel, involved in blood pressure regulation. The risk SNPs are enriched for cis-regulatory elements, particularly in vascular endothelial cells.

A cryo-electron tomography study reports the structure of thick myosin filaments of mouse cardiac muscle in the relaxed state in situ and the MyBP-C links that connect them with the surrounding thin actin filaments.

Majorana fermions, which are their own antiparticles, are expected to exist in topological superconductors. A study using superconducting leads in contact with a quantum well reveals the presence of supercurrents along one-dimensional sample edges of a quantum spin Hall state. These edge supercurrents are topological.

The mechanisms governing the ontogeny and maturation of the mucosal immune system during the postnatal period are not well understood. Here the authors characterize the homing kinetic, anatomical distribution and maturation of early intestinal CD4 T cells and provide insights into active T-cell suppression during the postnatal period.

Peripheral stimuli can induce acute immune training and tolerance in the brain and lead to long-lasting epigenetic reprogramming of microglia; these changes alter pathology in mouse models of stroke and Alzheimer’s pathology .

Cachexia manifests in cancer, chronic inflammation and infections. Bergthaler and colleagues show that CD8⁺ T cells mediate infection-associated cachexia in a manner dependent on T cell–intrinsic type I IFN signaling and antigen recognition.

FR171456 is a bioactive chemical produced by some microorganisms. Here, the authors identify the enzyme NSDHL of the sterol synthesis pathway as the molecular target of FR171456, rendering it the first compound to specifically target this class of enzyme in yeast and mammalian cells.

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.

In addition to having direct anti-cancer effects, the cardiac glycoside ouabain is shown to kill a broad range of senescent cells, thus suggesting that cardiac glycosides represent a novel class of senolytics.

The mouse cancer model 'Multi-Hit' allows for the evaluation of oncogene cooperativities in tumor development based on stochastic Cre-recombination events. Cells with cooperating oncogenes are positively selected and give rise to tumors. The approach is used to study Ras downstream effector pathways in tumorigenesis.

Genomes and phenotypes of interspecific yeast hybrids isolated from breweries reveal hybridization between Saccharomyces species followed by adaptation to specific beer styles.

Early-life stress, acting through corticotrophin-releasing hormone (CRH) and its receptor CRHR1, can have long-lasting effects on animals' behavior. Nectin-3 is a cell adhesion molecule whose heterodimeric interaction with presynaptic nectin-1 organizes the postsynaptic afadin–actin–N-cadherin complex to shape synaptic structure and function. Here, the authors show that structural synaptic adaptation and cognitive dysfunction in adulthood following early-life stress are dependent on CRH signaling acting through Nectin-3.

A mass spectrometric analysis of plasma tau species identifies phosphorylated tau peptides p-tau217, p-tau231 and p-tau205 with distinct correlations with amyloid and tau pathologies and emergences along the AD continuum.

A systematic review of evidence, across the key pillars of prevention, diagnosis, treatment and prognosis, outlines milestones that need to be met to enable the broad clinical implementation of precision medicine in diabetes care.

Combined analysis of proton-proton collision data from the Large Hadron Collider at CERN by the CMS and LHCb collaborations leads to the observation of the extremely rare decay of the strange B meson into muons; the result is compatible with the standard model of particle physics, and does not show any signs of new physics, such as supersymmetry.

Misra, Wagner et al. systematically review if strategies to subclassify type 2 diabetes (T2D) are associated with high quality evidence and patient outcomes. Cluster-based stratification yields T2D subtypes that associate with outcomes, suggesting subclassification could have future clinical use.