Osteoclasts intercept meningeal lymphatic paths for dural metastasis.

September 30, 2026| Source: Nature

Dural metastasis (DM)-a devastating complication of advanced malignancies such as breast and lung cancers-is defined by tumour cell infiltration into the dura mater and presents unique clinical challenges distinct from brain metastasis 1,2 . Our study unveils a, to our knowledge, previously unrecognized role of meningeal lymphatic dysfunction in DM pathophysiology, providing a new conceptual framework for this unique form of metastatic disease. Distinctive cranial erosion patterns, identified through clinical imaging, set DM apart from other metastases. Using a new mouse DM model, we discovered significant impairments in meningeal lymphatic drainage associated with tumour progression. Through single-cell RNA sequencing analysis, we characterized the tumour micro-environmental landscape of DM, highlighting the predominant immunosuppressive tactics driven by cancer-related osteoclasts (OCs). Notably, large OCs localize specifically at the skull-tumour interface, whereas smaller OCs permeate intratumoral regions. We found that these OCs disrupted lymphatic paths significantly, and targeting them therapeutically led to restoration of meningeal lymphatic structure and function in DM, thereby augmenting anti-tumour immune responses. Mechanistically, we demonstrated that OC-derived angiopoietin-2 contributes to the dysregulation of meningeal lymphatic drainage in the DM model. Our findings suggest a new therapeutic approach to restore meningeal lymphatic function through selective OC targeting, offering promising avenues for enhancing anti-tumour immunity and improving clinical outcomes in patients with DM.

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The honey bee stinger: An unusual pump with collapsible double pistons.

Most stinging animals deliver venom by contracting muscles around a venom reservoir, but honey bees employ a fundamentally different strategy. The stingers of worker bees have the unique ability to autotomize, separating from the body, to continue to sting independently. Despite more than a century of anatomical descriptions, the mechanics of venom pumping have remained unresolved due to the challenges of observing them in action. We recorded high-speed videos of active, autotomized stingers, co

Health & MedicineOctober 20, 2026

Chronic cigarette smoke exposure induces distinct stem cell states driving genetic driver-specific non-small cell lung cancer subtypes.

Cigarette smoke-induced chronic inflammation (CI) potentiates development of non-small cell lung cancer (NSCLC) by mediating genetic and epigenetic events. Using normal lung organoids (LOs), we define how chronic cigarette smoke condensate (CSC) exposure drives two separate stem cell populations to evolve premalignant states harboring progressive epigenetic and linked transcriptomic abnormalities in the absence of major driver mutations. These dynamics facilitate evolution of an immune evasive s

Health & MedicineOctober 20, 2026

Cell identity competes with surface tension to determine stromal organization in tumor spheroids beyond the CAF shell paradigm.

Cancer-associated fibroblasts (CAFs) are often found forming a peripheral stromal barrier around tumors. Here, this paradigm is challenged using microfabricated 3D cancer-CAF spheroid models combined with quantitative magnetic force tensiometry. A surface tension atlas is established for eight cancer cell lines, three CAF populations, and heterotypic tumor-CAF assemblies, spanning nearly two orders of magnitude. Surface tension is first shown to govern spheroid morphology and modulate drug respo

Health & MedicineOctober 15, 2026

A phenome-wide structural variant map from 467,152 UK Biobank genomes.

Structural variants (SVs) are large (>50 base pairs) genomic rearrangements that can significantly influence human phenotypes, yet their contribution to health and disease remains undercharacterized. We conducted a phenome-wide association study (PheWAS) of 1.6 million SVs identified in whole-genome sequencing data from 467,152 UK Biobank participants, across 13,322 binary, 2,018 quantitative, and 2,923 plasma protein traits. Of these, 82.25% of SVs were outside the detectable range of prior

Health & MedicineOctober 15, 2026

Mitochondria-targeted tetraoxanes initiate lipid peroxidation to drive ferroptosis and tumor suppression.

Ferroptosis is implicated as a vulnerability in multiple cancers, yet approaches for effectively inducing ferroptosis in vivo are limited. Bypassing conventional strategies targeting the antiferroptotic glutathione peroxidase 4 (GPX4) and ferroptosis suppressor protein 1 (FSP1) proteins, we designed metabolic initiators of lipid peroxidation (MILPOs) and developed the compounds WMK-1/2, which contain tetraoxane radical-generating and mitochondria-targeting groups, as de novo ferroptosis inducers