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While therapies targeting type I BRAF mutations have been developed, there are limited options for those with type II and III mutations. Here, the authors identify a subset of BRAF-mutant non-small cell lung cancer patients and characterise the pan-RAF inhibitor exarafenib, demonstrating efficacy in preclinical models and investigating subsequent resistance mechanisms.

Treatment failure exists in Induction chemotherapy followed by concurrent chemoradiotherapy (CCRT) for locoregionally advanced nasopharyngeal carcinoma (LA-NPC) patients. Here this group reports a phase 2 randomized trial evaluating the efficacy and safety of adding nimotuzumab, to CCRT on 246 patients with untreated, non-keratinising, stage II–IVA LA-NPC.

Development of the pangenome-informed genome assembly (PIGA) workflow enabled the generation of 1,116 diploid genome assemblies (55 de novo and 1,061 pangenome-informed), representing an extensive resource of medically relevant genic variations.

The role of long non-coding RNAs (lncRNAs) in regulating cancer progression remains to be explored. Here, the authors identify an antisense lncRNA in the IGF1R locus (IGF1RAS1) which strongly interacts with super enhancers and modulates MYC expression in metastatic prostate cancer.

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.

Global Burden of Disease analysis found that in 2023, suboptimal diet was estimated to be responsible for 4 million deaths and 97 million morbidity burdens from ischemic heart disease.

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.

The COMPASSION16 trial showed survival benefits of cadonilimab plus standard therapy in advanced cervical cancer. Here, subgroup analysis confirms consistent progression-free and overall survival improvements across diverse patient profiles.

Dong and colleagues report that blockade of T cell-expressed cytotoxic and regulatory T cell molecule results in selective mitigation of immune-related toxicities without affecting antitumor efficacy of immune checkpoint inhibitors.

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.

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.

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.

Covert mortality nodavirus, a pathogen previously known to cause important losses in shrimp aquaculture, is identified as being a potential causative agent of an emerging and severe ocular disease in humans, specifically presenting as persistent ocular hypertensive viral anterior uveitis.

Wound biomarker monitoring faces challenges in both sensitivity and stability. Here, authors present soft wireless bioelectronic device, using self-confined tetrahedral DNA circuits, that enhance detection limits, resists biofouling, and enables stable and real-time monitoring of diabetic wound healing.

This study reports a self-driven nanoemulsification mechanism via surfactant-flux-induced interfacial instability, enabling the rapid, scalable production of highly uniform nanocarriers, such as nanodroplets, micelles, vesicles and polymeric nanoparticles, under mild conditions.

Increased glycolysis in pancreatic cancer promotes immune escape by altering the tumor microenvironment. Here, the authors show that lactate-driven histone lactylation via PCAF increases CXCL1 expression, recruiting neutrophils and enabling immunosuppression, and PCAF inhibition improves anti-PD-1 therapy in pancreatic cancer mouse models.

The Taiwan Precision Medicine Initiative (TPMI) has built a cohort of more than half a million individuals with Han Chinese ancestry, providing a rich resource of genetic and medical data for this group.

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.

Wang, Zheng, Qian, Pan, Tian et al. characterize the crosstalk between peritumoural visceral adipose tissue and colorectal tumour microenvironment and report an immune escape mechanism, which may be potentially targeted for improved immunotherapy.

Neurovascular interaction is critical for normal brain vascular development. Here, the authors show that neuronal NMDARs regulate brain vascular development via VEGF-induced global Ca2+ activities of endothelial tip cells.

Delirium presents a major challenge in intensive care and postoperative settings; however, the pathophysiology is poorly understood. In this Perspective, Nedergaard and colleagues examine the evidence for impaired glymphatic flow as a central mechanism in the development of delirium and discuss potential strategies to mitigate delirium risk.

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.

The catalytic oxidation of 5-hydroxymethylfurfural to 2,5-furandicarboxylic acid is a crucial step in the production of bio-based plastics, yet it is hindered by sluggish multi-electron transfer kinetics. Here, the authors address this challenge by introducing a Mn–O–Co electron bridge within spinel CoMn₂O₄ to facilitate and accelerate electron transfer.

Concurrent chemoradiotherapy (CCRT) has remained the standard treatment for unresectable locally advanced esophageal squamous cell carcinoma. This study presents findings from a single-arm, phase 2 clinical trial assessing the efficacy and safety of immune checkpoint blockade before CCRT.

The use of membranes for the separation of complex amino acid mixtures is energy efficient but relies on achieving precise molecular recognition. Here, the authors report on a homochiral covalent organic framework membrane for the enantioseparation and fractionation of amino acids.

The role of TGFβ in cancer is paradoxical and context-dependent. Here, the authors discover that a preserved, DLD-mediated metabolic suppression by TGFβ undermines anti-TGFβ therapy, promoting gastric cancer growth.

Talin has been believed to be indispensable for integrin activation. Here, the authors show that the curvature-sensing protein FCHo2, not talin, enables inside-out activation of integrin ɑvβ5 in curved adhesions formed at curved membranes.

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.

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.

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.

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.

Mechanism of CD8 T cell dysfunction in tumor microenvironment requires continuous investigation. The authors here show that Lypd6b expression is increased in CD8 T cells of colorectal cancer tissue and its absence inhibits MC38 or CMT-93 tumor growth associated with upregulated glycolysis and reduced oxidative phosphorylation.

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.

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.