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A pan-genome can reduce bias in genetic diversity analysis inherent in using a single reference genome. Here, the authors assemble genomes of 10 diverse apple accessions, conduct pan-genome analysis together with three existing genomes, and reveal the role of mitogen-activated protein kinase homolog MMK2 in fruit coloration.

Disruption of dendritic cell (DC) interstitial motility in the tumour microenvironment promotes immune evasion, and enhancement of DC interstitial motility offers a route for DC-centric immunotherapy.

Developing multi-cancer early detection (MCED) tests based on cfDNA or protein markers holds great promise for effective cancer screening. Here, the authors show a sensitive, non-invasive pan-cancer detection method that concurrently detects the oncofetal chondroitin sulfate (ofCS) glycans and its protein backbone in plasma.

Tong et al. describe a super pangenome assembled from long-read sequences of 545 wild and domesticated silkworms. Naturally selected (diapause, aposemantic coloration) or artificially selected (silk yield and fineness) sets of genes are delineated.

Alternative polyadenylation (APA) can play a key role in cancer initiation and progression. Here, the authors conducted a comprehensive pan-cancer APA TWAS analysis and discovered a distinct class of APA-mediated cancer susceptibility genes across 22 cancer types.

The immunomodulatory functions of mast cells (MCs) within the tumor microenvironment are elusive. Here, the authors present a transcriptomic characterization of LUAD-infiltrating MCs and identify a proinflammatory subset that contributes to the activation of cytotoxic MAIT cells by secreting IL-18 via NRLP3 activation and pyroptosis, ultimately boosting anti-tumor immunity.

c-Myc and p53 operate in a negative feedback manner to maintain cellular homeostasis. Here, the authors report a long noncoding RNA, MILIP as a downstream target of c-Myc and that MILIP represses p53 to support tumorigenicity.

Analysis of multiple tumor types, cancer cell lines and adult tissues identifies tumor-specific transposable-element-chimeric transcripts. Mass spectrometry data confirm that many are translated and subsequently located on the extracellular surface of cancer cells, highlighting potential immunogenic therapies.

Dysregulated R-loops can compromise genome stability, leading to pathological consequences. Li et al. demonstrate that R-loop-induced poly(ADP-ribose) polymerase 1 activation orchestrates exonuclease 3′–5′ ___domain-containing 2-mediated R-loop resolution, thereby safeguarding genomic integrity.

Researchers revealed a 3.6 Å cryo-EM structure showing how HIV-1 Vif hijacks the host’s CUL5 E3 ligase to degrade APOBEC3H, a viral defense protein. The findings shed light on HIV’s immune evasion and suggest potential antiviral targets.

Genomic amplification of chromosome 3q often encodes proteins that contribute to cancer development. Here the authors identify a non-coding product of the 3q region, the lncRNA PLANE that promotes tumorigenesis through the deregulation of transcriptional corepressor NCOR2 pre-mRNA splicing.

Gut microbiota-derived succinate promotes CitC succinyltransferase-dependent succinylation of PurR to alleviate T3SS repression and promote virulence in enterohaemorrhagic Escherichia coli and Citrobacter rodentium.

Immune lymphocyte estimation from nucleotide sequencing (ImmuneLENS) infers B cell and T cell fractions from whole-genome sequencing data. Applied to the 100,000 Genomes Project datasets, circulating T cell fraction provides sex-dependent and prognostic insights in patients.

Chronic care manages long-term, progressive conditions, while acute care handles short-term ones. Here, authors show chronic conditions account for most of the global health burden, with 68% of DALYs and 93% of YLDs attributed to chronic care needs.

Dendritic cells play pivotal roles in the immune response to viral infection but are targeted by flaviviruses resulting in evasion of the host response. Here the authors show Zika but not Dengue virus limits the NF-κB response in monocyte derived dendritic cells diminishing their ability to activate T cells.

Wang, Wang, Pan and colleagues uncover a C864–C869 disulfide linkage stimulated by viral RNA that drives RIG-I activation, phase separation and stimulates downstream innate immune signalling.

It is challenging to purify and prepare large amount of methacrylated proteins from cells. Here, the authors develop genetic code expansion technology to site-specifically incorporate ε-N-Methacryllysine into proteins and identify the post-translational modification ε-N-methyl-ε-N-methacrylation.

Liu et al. developed a platform to identify transcription factors (TFs) that turn stem cells into desired cell types. They discovered six key TFs that produce microglia efficiently, enhancing cell differentiation methods.

In a post-hoc analysis of circulating tumor DNA (ctDNA) features from patients with metastatic prostate cancer treated with [¹⁷⁷Lu]Lu–PSMA-617 or cabazitaxel in the randomized phase 2 TheraP trial, low ctDNA levels at baseline were predictive of clinical benefit from [¹⁷⁷Lu]Lu–PSMA-617, and PTEN or ATM alterations were identified as potential biomarkers of response.

Jiang and colleagues identify ETV7 as a transcriptional node that skews CD8⁺ T cell transcriptional profiles toward exhaustion, consequently limiting antiviral and antitumor efficacy, and show that it can be targeted in CAR T cells to enhance efficacy.

Frequencies for motor kinematics are encoded by the cerebellum through population tuning of firing probabilities, which leads to cerebellar oscillations and corresponding motions.

Profiling nuclear N⁶-methyladenosine (m⁶A) modifications revealed enrichment of m⁶A on nuclear RNAs derived from chromosome pericentromeric γ satellite DNA II (GSATII), which regulates GSATII transcription and influences chromosome segregation during mitosis.

Here the authors unveil the essential role of MCL-1 for adult hair follicle regeneration and inhibition of proliferation stress-induced apoptosis in mice. They also identify a P53/MCL-1/BAK axis balancing proliferation and death of activated hair follicle stem cells to ensure proper hair growth.

Cell-type-resolved spatial proteomics of the skin from patients with toxic epidermal necrolysis reveals that it is driven by JAK/STAT signaling, leading to successful treatment of this potentially fatal condition in patients using JAK inhibitors.

Xue et al. report self-powered photoelectrochemical photodetectors based on CuOx decorated AlGaN nanowires with staggered energy band structure. High-energy photons can be absorbed by CuOx to trigger the multiexciton generation effect, enabling an external quantum efficiency of 131.5% at 255 nm.

The cross-population Sum of Single Effects (SuSiEx) model is a robust and computationally efficient method for conducting multi-ancestry fine-mapping of genome-wide association signals, producing smaller credible sets and capturing population-specific causal variants.

This study presents an oral CRISPR–Cas9 delivery system that precisely disrupts the TRAP1 gene in colorectal cancer, enhancing chemo-immunotherapy with robust antitumour effects.

Huang et al. show that ADAM9 loss upregulates PAI-1, promoting its interaction with KRAS and resulting in selective lysosomal degradation of KRAS. They also identify a small-molecule inhibitor of ADAM9 with therapeutic benefits in the context of PDAC.

Kdm2a demethylates H3K36me2 to mediate fast-to-slow-twitch myofiber transition and reshape skeletal muscle metabolic flexibility under metabolic stress conditions.

Circulating tumor cells (CTCs) are clinically useful for detecting and monitoring cancer, but they are rare in blood. Here, the authors use a highthroughput microfluidic device to massively enrich CTCs from leukapheresis products to uncover single cell molecular features in prostate and other cancers.

Here the author reveal that histone crotonylation (including H3K9cr) exert a role in kidney fibrosis, where ACSS2 represents a potential target to slow fibrotic kidney disease progression.

The authors provide insights into the role of neuronal CCL2 expression, which is triggered with hyperglycaemia and modulates anxiety disorders under conditions of diabetes.

Overcoming the suppressive tumor microenvironment (TME) is crucial to improving the efficacy of cancer therapy. Here the authors show that, in mouse cancer models, administration of exogenous IL-16 establishes a Th1-dominant TME via regulation of glutamine catabolism and triggers a Th1 cell-macrophage crosstalk, enhancing anti-tumor immune responses and the efficacy of immunotherapy.

The function of rare non-coding variants remains challenging to decipher. Here, the authors developed MapUTR to uncover 10,524 functional rare 3’ UTR variants regulating mRNA abundance, many of which reside in cancer driver genes.

Observations of optical flares from AT2022tsd (the ‘Tasmanian Devil’) show that they have durations on the timescale of minutes, occur over a period of months, are highly energetic, are probably nonthermal and have supernova luminosities.