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The anterior cingulate cortex encodes affective pain behaviours modulated by opioids; targeting opioid-sensitive neurons through a new chemogenetic gene therapy replicates the analgesic effects of morphine, providing precise chronic pain relief without affecting sensory detection.

Cancer immunotherapy benefits from antibody-lectin chimeras that block glyco-immune checkpoints.

Massively parallel reporter assay in primary human CD4⁺ T cells and bulk and single-cell CRISPR-interference screens identify candidate causal variants linked to autoimmune disease risk that modulate T cell gene expression and proliferation.

Cocaine chemogenetics in rats is a selective approach for countering drug reinforcement by clamping dopamine release in the presence of cocaine.

Most patients with metastatic melanoma still develop primary or acquired resistance to immune checkpoint inhibition (ICI). Here the authors report the results of a phase II trial of cryoablation and ICI in patients with unresectable melanoma progressing on ICI.

In an updated report on 70 laboratory-confirmed highly pathogenic avian influenza A H5N1 cases in the USA between March 2024 and May 2025, the absence of human-to-human transmission to date was confirmed, with no known mutations of resistance to neuroaminidase inhibitors.

A connectome of the right optic lobe from a male fruitfly is presented together with an extensive collection of genetic drivers matched to a comprehensive neuron-type catalogue.

Alzheimer’s disease has been associated with increased structural brain aging. Here the authors describe a model that predicts brain aging from resting state functional connectivity data, and demonstrate this is accelerated in individuals with pre-clinical familial Alzheimer’s disease.

A consensus cell type atlas for the fly brain provides both an intellectual framework and open-source toolchains for brain-scale comparative connectomics.

This study finds that sST2 is a disease-causing factor for Alzheimer’s disease. Higher sST2 levels impair microglial Aβ clearance in APOE4⁺ female individuals. A genetic variant, rs1921622, is associated with a reduction in sST2 level and protects against AD in APOE4⁺ female individuals.

The BIN1 SNP rs744373 is associated with higher CSF tau and phosphorylated tau levels. Here the authors show, using PET imaging, that this SNP is associated with tau accumulation in the brain as well as impaired memory in older individuals without dementia.

Brain-iron elevation is implicated in Alzheimer’s disease (AD), but the impact of the metal on disease outcomes has not been analysed in a longitudinal study. Here, the authors examine the association between the levels of ferritin, an iron storage protein, in the cerebrospinal fluid (CSF) of AD patients and show that CSF ferritin levels predict AD outcomes.

This Perspective discusses using long-term ecological research networks to advance our understanding of fundamental evolutionary processes and evolutionary responses to global change.

An analysis of 24,202 critical cases of COVID-19 identifies potentially druggable targets in inflammatory signalling (JAK1), monocyte–macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).

Progressive diseases tend to be heterogeneous in their underlying aetiology mechanism, disease manifestation, and disease time course. Here, Young and colleagues devise a computational method to account for both phenotypic heterogeneity and temporal heterogeneity, and demonstrate it using two neurodegenerative disease cohorts.

Whether Alzheimer’s disease originates in basal forebrain or entorhinal cortex remains highly debated. Here the authors use structural magnetic resonance data from a longitudinal sample of participants stratified by cerebrospinal biomarker and clinical diagnosis to show that tissue volume changes appear earlier in the basal forebrain than in the entorhinal cortex.

Late-onset Alzheimer's disease (LOAD) is a complex multi-factorial disorder. Here, the authors perform a data-driven analysis of LOAD progression, including multimodal brain imaging, plasma and CSF biomarkers, and find vascular dysfunction is among the earliest and strongest altered events.

The interplay between amyloid and tau pathology in Alzheimer’s disease is still not well understood. Here, the authors show that amyloid-related increased in soluble p-tau is related to subsequent accumulation of tau aggregates and cognitive decline in early stage of the disease.

Zika and Dengue virus non-structural protein 5 can antagonise STAT2 modulating the host response and this interaction is involved in determining tropism. Here the authors show mammals independently evolved resistance to flavivirus NS5 multiple times, involving complex genetic changes in STAT2 which balance viral defence whilst maintaining STAT2’s critical functions.

Neuroendocrine differentiation of epithelial tumor cells can contribute to cancer cell resistance and survival. Here, the authors show that dysregulated c-Myc promotes neuroendocrine differentiation in pancreatic ductal adenocarcinoma, leading to poor survival and chemoresistance.

Tau accumulation is associated with disease progression in Alzheimer’s disease. Here the authors use resting state fMRI and tau-PET to demonstrate that baseline connectivity in Alzheimer's disease is associated with tau spreading.

Alzheimer’s disease is heterogeneous in its neuroimaging and clinical phenotypes. Here the authors present a semi-supervised deep learning method, Smile-GAN, to show four neurodegenerative patterns and two progression pathways providing prognostic and clinical information.

Several studies show that APOE-ε4 coding variants are associated with Alzheimer’s disease (AD) risk. Here, Zhou et al. perform fine-mapping of the APOE region and find AD risk haplotypes with non-coding variants in the PVRL2 and APOC1 regions that are associated with relevant endophenotypes.

Cleared-tissue axially swept light-sheet microscopy (ctASLM) enables high-speed, refraction index-independent imaging of live, cleared and expanded samples with isotropic, submicron resolution.

A diverse intestinal microbiota is required for mice to undergo extinction-related neuronal plasticity and normal fear extinction learning.

The KL-VS haplotype of the Klotho gene has been associated with reduced risk of Alzheimer’s disease and dementia. Here the authors show an association between the KL-VS haplotype and amyloid-dependent tau accumulation using PET data.

Systematic characterization of longitudinal tau variability in human Alzheimer’s disease using an unbiased subtyping algorithm reveals four trajectories of tau deposition with distinct clinical features.

In Alzheimer’s disease (AD) tau and neurodegeneration have complex regional relationships. Here, the authors show neuronal hypometabolism discordant with tau burden defines functional resilience or susceptibility to Alzheimer’s pathology via limbic/cortical axes. Susceptible groups have faster cognitive decline and evidence of non-Alzheimer’s pathologies.

In Arabidopsis thaliana, a genetic network that controls the phosphate stress response also influences the structure of the root microbiome community, even under non-stress phosphate conditions.

The tau protein is theorized to spread transneuronally in Alzheimers disease, though this theory remains unproven in humans. Our simulations of epidemic-like protein spreading across human brain networks support this theory, and suggest the spreading dynamics are modified by β-amyloid

Sun et al. report human lifespan changes in the brain’s functional connectome in 33,250 individuals, which highlights critical growth milestones and distinct maturation patterns and offers a normative reference for development, aging and diseases.

The helicase Ded1p associates with the pre-initiation complex and influences translation from near-cognate initiation codons by controlling the levels of mRNA secondary structure in 5′ untranslated regions.

Here the authors report new human fossils from Tam Pà Ling cave, Laos, consisting of a cranial and a tibial fragment, dated to 68–86 thousand years ago. This find confirms that Homo sapiens were present in Southeast Asia by this time and the shape of the fossils indicates they may have descended from non-local populations.

Precise control of stereocilia length by auditory hair cells is vital for normal hearing. Drummond et al. follow in real-time the incorporation of actin into these structures and show that while the actin core is remarkably stable, and actin polymerization is limited to their distal tips.

The GREGoR consortium provides foundational resources and substrates for the future of rare disease genomics.

Type 1 regulatory T cells control autoinflammatory diseases. In two linked papers, groups led by Kuchroo and Quintana demonstrate the role of the aryl hydrocarbon receptor in the differentiation of these cells.

Conserved microbiome features across clinical and geographical variations may enable microbiome-based predictions of outcomes in CD19-targeted CAR-T cell immunotherapy

Computational search identifies dynobactin A which is a systemically active, natural-product peptide antibiotic that kills Gram-negative bacteria.

Alterations in lipid metabolism and circulating lipid species have been reported in patients with acute critical illness. Here the authors show that selective rise in systemic phosphatidylethanolamine levels is a common feature of critical illness that associates with worse clinical outcomes.

Understanding how RNA structure influences its function has been hampered by a lack of approaches that can accurately quantify RNA structure in vivo; here, RNA structure is revealed on a global scale and with nucleotide-level resolution, showing that there is less structure within cells than expected from in vitro and in silico analyses.

Data from more than 200 million observations of plants, animals and fungi provide support for the concept that terrestrial biodiversity patterns reflect distinct ecoregions.

Neuropilin-1 (Nrp1) on regulatory T (T_reg) cells is shown to interact with semaphorin-4a (Sema4a) to promote a program of T_reg-cell stability and survival, in part through PTEN-mediated modulation of Akt signalling; Nrp1-deficient T_reg cells can maintain immune homeostasis but fail to suppress in inflammatory sites, such as tumours, providing an attractive immunotherapeutic target for the treatment of cancers.

In multiple sclerosis and experimental autoimmune encephalomyelitis, astrocytes produce lactosylceramide, a glycolipid that promotes astrocyte and microglial activation and immune cell infiltration into the CNS.

Single-cell transcriptomic profiling of fetal liver, skin, kidney and yolk sac reveals the differentiation trajectories of human haematopoietic stem cells and multipotent progenitors, which are validated to produce an integrated map of fetal liver haematopoiesis.

Comparative genomic analysis of 3,837 bacterial genomes, including new sequences from 484 root-associated isolates, identifies plant-associated gene clusters and plant-mimicking domains.

FlyWire presents a neuronal wiring diagram of the whole fly brain with annotations for cell types, classes, nerves, hemilineages and predicted neurotransmitters, with data products and an open ecosystem to facilitate exploration and browsing.

Tissue remodelling events create gaps in the basement membrane and have been previously accounted for by the degradation or reduced synthesis of basement membrane components. Live-cell imaging shows that basement membrane sliding enlarges the opening of the uterus during Caenorhabditis elegans development and that integrins-based adhesion negatively regulates sliding.

DMS-MaPseq enables genome-wide and target-specific RNA secondary structure probing of even rare or heterogeneously structured RNAs in vivo and was used to study structure involved in translation regulation as well as nascent transcripts.