BackgroundThrombosis is a common complication in paroxysmal nocturnal haemoglobinuria (PNH) patients, but primary prevention remains controversial. Identifying high‐risk individuals could enable risk‐stratified prophylactic anticoagulation strategies.MethodsWe analyzed clinical data from PNH patients with or without thrombosis, including MUC4 mutation status and serum complement C5b‐9 levels. Complement deposition assays and a murine lower limb deep vein thrombosis model were used to investigate the role of MUC4 mutation in thrombotic risk and explore the underlying mechanism involving terminal complement activation in PNH patients. Therapeutic interventions with low molecular weight heparin (LMWH) were tested in vivo.ResultsWe found that PNH patients with MUC4 mutations have a higher incidence of thrombotic events (TEs) and MUC4 mutation is an independent risk factor for TE in PNH patients. Additionally, PNH patients with acute thrombosis had elevated serum complement C5b‐9 levels, and complement deposition experiments further confirmed the abnormal activation and excessive deposition of C5b‐9 as the basis for the thrombotic tendency in PNH patients. By constructing a mouse model of lower limb deep vein thrombosis, we confirmed the thrombotic tendency in a PNH mouse model and that MUC4 deficiency further promoted the thrombotic phenotype of the mice. Moreover, we found that MUC4 knockdown promoted the deposition of C5b‐9 on the cell surface, indicating that a lack of MUC4 expression facilitates the deposition of C5b‐9. Finally, in vivo drug administration experiments demonstrated that prophylactic anticoagulation with LMWH significantly reduced both the incidence of thrombosis and thrombus length in murine models.ConclusionMUC4 mutations promote the thrombotic phenotype in PNH patients by increasing the deposition of terminal complement. In PNH patients with concomitant MUC4 mutations, the risk of TEs is further elevated. The potential role of early complement inhibitor therapy in reducing this heightened thrombotic risk, as well as the value of prophylactic LMWH therapy as a potential option for patients who are unable to receive complement inhibitor treatment, warrants further study and prospective validation.Key pointsMUC4 gene mutation increases the deposition of abnormally activated terminal complement in patients with PNH, thereby promoting the thrombotic phenotype in these patients. Consequently, the risk of thrombosis is further elevated in PNH patients with concurrent MUC4 mutations.In patients with PNH who have concurrent MUC4 mutations, the potential role of early complement inhibitor therapy in reducing thrombosis risk, as well as the value of prophylactic LMWH therapy as a potential alternative for those who are unable to receive complement inhibitor treatment, may warrant further study and prospective validation.

Angiogenesis, driven by the vascular endothelial growth factor (VEGF)/VEGFR signalling axis under hypoxic conditions, is one of the hallmarks of ovarian cancer (OC), contributing to tumour progression, metastatic dissemination and immune evasion. Hypoxia-induced angiogenic signalling sustains tumour growth and shapes an immunosuppressive tumour microenvironment, while homologous recombination deficiency (HRD) has been associated with increased tumour hypoxia and pro-angiogenic signalling. Conversely, VEGF pathway inhibition may exacerbate DNA damage and modulate immune cell trafficking, providing a strong biological rationale for synergy between anti-angiogenic agents, PARP inhibitors (PARPi), and immune checkpoint inhibitors. Bevacizumab, a humanised monoclonal antibody targeting VEGF-A, represents a pivotal therapeutic agent in OC management by inhibiting tumour angiogenesis and inducing transient vascular normalisation. Its clinical efficacy has been demonstrated as maintenance therapy in the first-line setting, alone or in combination with PARPi for HRD-positive disease, and in the recurrent setting both in platinum-sensitive and platinum-resistant disease. Despite these benefits, variability in patient response highlights the unmet need for validated predictive biomarkers. Circulating, tissue-based and molecular biomarkers have been investigated, including angiogenic factors (Tie2/Ang1 axis, interleukin-6 [IL-6] and chitinase-3-like protein [YKL-40]), VEGF-A isoforms, microvessel density, EGFR/ADAM17 signalling, angiomiRs and transcriptional subtypes with mesenchymal and proliferative phenotypes showing greater sensitivity to anti-angiogenic strategies. Although HRD status holds prognostic relevance and selected microRNAs show emerging potential, no biomarker has yet been validated to predict benefit from bevacizumab in clinical practice. Translational analyses from the MITO16A/MaNGO OV-2 program, highlight challenges such as assay standardisation, multiplicity correction and external validation, while identifying tumour immune infiltration patterns, TP53 mutation classes and composite HRD assessments as areas of further investigation. In conclusion, bevacizumab remains an integral component of OC treatment. Future progress will depend on biomarker-driven, prospectively designed clinical trials and the integration of multi-omic data and machine learning approaches to enable precision application of anti-angiogenic strategies, maximising clinical benefit while minimising toxicity.

BackgroundIn colorectal cancer (CRC), innate lymphoid cells (ILCs) play a vital role in preserving and modulating immune homeostasis within the intestinal environment. However, the origins and diverse functions of ILCs in CRC remain poorly understood, making it difficult to clarify how these cells contribute to disease progression and influence therapeutic efficacy.MethodsSingle‐cell RNA sequencing (scRNA‐seq) generated an atlas of ILCs from multiple tissues (bone marrow, blood, and intestine), revealing their origins, heterogeneity, and plasticity. Spatial transcriptomics (ST) and immunofluorescence (IF) defined their specific cellular neighbourhoods within the tumour microenvironment. In vitro co‐culture assays were performed to validate the regulatory role of ILC2s in B cell maturation. Bulk RNA sequencing and flow cytometry were employed to assess the survival and therapeutic response potential of ILCs.ResultsIntestinal ILCs have two distinct origins: ILC3‐CD83 cells derived from the fetal gut, which persist into adulthood; and ILC2 and ILC3‐S100A4 cells that might originate from the bone marrow and migrate through the circulation to colonise intestinal tissues. The tissue‐resident ILC3 subsets exhibited diverse functional roles in CRC. Specifically, trajectory analysis showed that ILC3s differentiated into either stress‐responsive ILC3‐HSPA1B cells or cytotoxic ILC1/NK cells in CRC. Additionally, by using spatial transcriptomics analysis combined with functional assays, we found that bone marrow‐derived ILC2s preferentially localise in tertiary lymphoid structures (TLSs), where they likely support B cell maturation. Notably, higher ILC2 abundance correlated with better clinical outcomes and greater therapeutic benefit.ConclusionsThis study reveals the distinct origins and functional heterogeneity of intestinal ILC subsets in CRC. The enrichment of bone marrow‐derived ILC2s in TLSs, where they likely support B cell maturation, is associated with improved prognosis and favourable immunotherapy response, which may serve as biomarkers for survival and therapeutic efficacy in CRC.

This study investigates the impact of sleep restriction (SR) on flap viability and its underlying mechanisms. It reveals that SR triggers clock rhythmic ferroptosis, which leads to impaired skin barrier function and increased flap necrosis. A retrospective analysis of sleep quality in 344 patients undergoing flap surgery proved that SR is a risk factor for flap necrosis. Further research demonstrated that SR increases the level of ferroptosis, disrupts the circadian rhythm of ferroptosis and exacerbates flap damage in human and murine models. In order to address this clinical issue, the use of melatonin (MT)-preconditioned bone marrow mesenchymal stromal cells-derived exosomes (MEXOs) was found to enhance the therapeutic efficacy of flap repair by mitigating clock rhythmic ferroptosis. Mechanistically, MT increased m6A modification to stabilise and enhance the translation of ubiquitin-specific protease 4 (USP4) mRNA within MEXOs. USP4 delivered by MEXOs directly interacted with and deubiquitinated ARNTL, a core circadian regulator, stabilising its protein levels and suppressing ferroptosis in flap. These findings identify SR-induced clock rhythmic ferroptosis as a critical pathological driver of flap failure and propose a novel exosome-based strategy targeting the USP4-ARNTL axis to enhance skin barrier integrity and flap survival, offering translational potential for clinical reconstructive surgery. This study identifies SR-induced clock rhythmic ferroptosis as a pivotal pathological process in flap necrosis. We reveal a potential therapeutic mechanism in which USP4-enriched MEXOs can effectively repair SR-induced flap necrosis. USP4-enriched MEXOs represent a novel therapy for SR-induced flap necrosis by stabilizing ARNTL to inhibit clock rhythmic ferroptosis.

BackgroundKey biological processes underlying health and disease‐including electron transfer, redox regulation, and radical‐mediated signaling‐are fundamentally governed by quantum‐mechanical principles. These processes are central to mitochondrial function, metabolism, and cellular signaling, yet their biomedical implications have remained difficult to address using classical computational approaches.RationaleRecent advances in quantum computing, quantum sensing, and quantum machine learning enable direct simulation and measurement of quantum phenomena in biologically relevant systems. Hybrid quantum‐classical algorithms, such as the Variational Quantum Eigensolver and Quantum Phase Estimation, now provide first‐principles access to redox potentials, electronic couplings, and spin‐dependent reactions that are directly linked to disease mechanisms. These developments establish the foundation for quantum biomedicine as a translational framework bridging molecular physics and clinical medicine.ContentThis review synthesizes current progress in the application of quantum technologies to biomedicine, emphasizing translational relevance. We discuss quantum‐informed modeling of cancer metabolism and redox rewiring, protein misfolding in neurodegenerative diseases, immune and inflammatory signaling, infectious disease mechanisms, and drug discovery. We further propose a Quantum‐Experimental‐Clinical (QEC) pipeline that integrates quantum simulations with experimental validation and multi‐omics clinical data, enabling mechanistic interpretation of disease phenotypes and identification of redox‐ and spin‐sensitive therapeutic targets.ConclusionQuantum biomedicine introduces a new mechanistic layer that links electronic‐scale processes to clinical phenotypes. While current implementations are constrained by NISQ‐era hardware, rapid advances in quantum algorithms and sensing technologies position quantum approaches as emerging tools in precision and translational medicine. Strategic integration of quantum methods with experimental and clinical workflows may accelerate biomarker discovery and therapeutic development.Key pointsQuantum biomedicine redefines life as a dynamic equilibrium sustained by quantum coherence, tunnelling and redox resonance.Hybrid quantum–classical algorithms, such as VQE and QPE, enable first‐principles modelling of redox and spin‐dependent reactions with near‐experimental accuracy.NISQ‐era hardware supports proof‐of‐concept simulations of electron tunnelling and radical‐pair dynamics, bridging computation with measurable biophysics.Integration of quantum simulations with spectroscopy and cryo‐EM establishes a quantum–experimental–clinical (QEC) pipeline linking theory, experiment and medicine.Ethical, educational and governance frameworks are essential for equitable, transparent and sustainable implementation of quantum health technologies.

Triple‐negative breast cancer (TNBC), marked by profound immunosuppressive complexity, poses a critical challenge in therapy due to the absence of hormone receptors in its phenotype, making it unavailable for conventional therapies. The stimulator of interferon genes (STING) pathway is emerging as critical pathway translating the immunogenic ‘cold’ TNBC tumour into ‘hot’ one, thereby improving the responsiveness to immune checkpoint blockade (ICB). However, the clinical translation is still hindered by insufficient cytosolic delivery, rapid systemic degradation and tumour microenvironment‐induced metabolic inactivation. This review outlines the recent advances in STING‐mediated nanoparticle delivery with special emphasis on biomimetic, Trojan horse logic gate, manganese‐based and redox‐responsive stimuli delivery systems. Mechanistically, it integrates immune activation by ferroptosis, cuproptosis and mitochondrial DNA disruption. They synergise the amplification of type 1 interferon with dendritic cell maturation, potentiating antitumour immunogenesis. Notably, the combination with ICBs will further amplify the therapeutic potential of nanoparticles. Convergence of immunology and targeted therapies with nanoparticles opens new array for TNBC treatment. The review visualizes the clinical translation of mind maps into clinical reality, activating the innate immunity.HighlightsSTING activation converts immunologically cold TNBC into ICB‐responsive hot tumors.Nanoparticles overcome poor delivery, degradation, and TME‐driven STING inactivation.Biomimetic and stimuli‐responsive systems enhance type I IFN and DC maturation.Synergy with ICBs boosts innate immunity and antitumor immunogenesis.