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Integrative transcriptomic, spatial and functional-genomic analysis identifies a UFMylation-related vascular-stromal program and prioritizes WWTR1 in glioblastoma.

Glioblastoma (GBM) contains spatially organized stress-adaptive and vascular niches. Because transcript abundance does not measure UFM1 conjugation, we asked whether a UFMylation-related transcriptional axis identifies a reproducible tissue program and alters candidate prioritization. In 518 unique primary TCGA-GBM tumors profiled on the Affymetrix HT Human Genome U133A array, weighted gene co-expression network analysis of 8,000 variable genes yielded 12 modules. The 278-gene green module ranked first across nine prespecified traits (mean |r|=0.637). Direct overlap comprised 1/3 measurable UFMylation-core, 5/19 ER-stress/UPR, and 2/15 proteostasis genes; after excluding overlapping genes, correlations with the green eigengene remained significant (r = 0.373, 0.831, 0.639, and 0.699 for UFMylation-core, ER-stress/UPR, proteostasis, and composite scores, respectively). The green score was associated with overall survival per standard-deviation increase (HR 1.17, 95% CI 1.07-1.28), although clinical adjustment attenuated the estimate. In a 10-sample single-cell dataset, sample-level scores were higher in pericytes and endothelial cells than in malignant cells. Donor-aware IvyGAP analysis supported regional organization, whereas one Visium section showed stronger concordance with ER-stress/UPR and mesenchymal scores than with the UFMylation-core score. CellChat indicated pathway-selective rather than global remodeling of inferred vascular communication. Layer ablation moved WWTR1 from rank 48 using WGCNA alone to rank 4 overall and rank 1 among non-common-essential genes after cross-platform integration. These findings define an ER-stress/mesenchymal-weighted, UFMylation-related vascular-stromal transcriptional association and nominate WWTR1 for experimental testing.

Humans

Genomic Analysis of CTX-M-15-Producing E. coli Colonizing a Rescued Capuchin Monkey.

Illegal wild animal trade and possession represents a threat to One Health due to the pathogens exchange between wild animals and humans. We report the detection and genomic characterization of a multidrug-resistant (MDR) Escherichia coli strain (MP02) colonizing a capuchin monkey (Sapajus sp.) rescued from illegal possession. MP02 exhibited ExPEC-related genes, harbored an IncHI2-ST1 plasmid composed of quinolones, aminoglycosides, and sulfonamides resistance genes, besides the extended-spectrum β-lactamase (ESBL)-encoding gene blaCTX-M-15 located in a conserved Tn3-like transposon. To the author's knowledge, this is the first report and genomic analysis of a MDR bacterium isolated from an illegally traded non-human primate.

antibiotic resistance

A nationwide survey of pregnant women on their experience with fetal ultrasound examination in Japan.

PURPOSE: Fetal ultrasound examination (FUSE) is a prenatal screening test that can detect fetal structural abnormalities before birth. The purpose of this study was to clarify how pregnant women perceive FUSE and what they expect from it. METHODS: A questionnaire survey comprising 21 questions was conducted using the "Baby Plus" application for pregnant women. The response period was from November 8 to November 30, 2023. The participants were women who were at least 20 weeks of gestation and postpartum mothers within 3 months of delivery. Statistical analyses were performed using the chi-square test. RESULTS: Responses were received from 1,100 women. Sixty-six percent of the women recognized the differences between FUSE and routine ultrasonography. Forty-nine percent had undergone or planned to undergo FUSE, and 87% of those had received an explanation about the test. Many women expressed a desire for detailed explanations about the examination itself. Although less common, some women indicated that they did not wish to undergo fetal ultrasound examinations or learn about fetal abnormalities. Approximately 70% of women reported that they would consider termination of pregnancy if fetal abnormalities were detected. CONCLUSION: There may be a mismatch between pregnant women's expectations regarding FUSE and the way it is currently provided, including the timing of the examination and the explanations given. To help reduce this mismatch and support informed decision-making among pregnant women, greater standardization of FUSE practices and individualized explanations may be beneficial.

Fetal ultrasound examination

Silicon-mediated alleviation of mercury toxicity requires coordinated regulation of antioxidant defense, metal homeostasis, and nodule function in mung bean.

Mercury (Hg) contamination and accumulation in agricultural soil represent a major hazardous environmental concern, posing serious threats to living organisms, including plants. Silicon (Si) has been widely recognized to mitigate heavy metal (loid) toxicity; however, the underlying mechanism of Si-mediated mitigation of Hg-stress in mung bean remains unclear. In this study, we addressed this research gap by thoroughly examining the potential effects of Si supplementation on Hg-stressed mung bean plants, with particular emphasis on investigating the possible effects of Si on plant biomass, nodulation traits, antioxidant defense, and expression of metal-transporter and detoxification genes. Our findings demonstrated that Hg stress significantly impaired plant growth by inducing oxidative stress and reducing biological nitrogen fixation efficiency whereas Si application significantly alleviated the Hg-induced toxicity. Specifically, Si increased shoot dry biomass by +113% (2.13-fold), root dry biomass by +60% (1.60-fold), nodule number by +152% (2.52-fold), and nodule dry weight by +273% (3.73-fold) under Hg stress compared to Hg treated plants only. Furthermore, Si enhanced antioxidant defense system, restricted the uptake and accumulation of Hg in different plant tissues, and regulated the expression of genes related to metal transport and detoxification, contributing to improved nodulation and nitrogen fixation under Hg stress. Overall, our findings demonstrate that Si application mitigates the Hg-induced toxicity in mung bean plants by enhancing antioxidant defense, improving nitrogen fixation, regulation of genes involved in metal transport and detoxification, and limiting Hg accumulation.

Vigna radiata

CRISPR-Enabled functional genomics in hPSCs-derived neural models for autism spectrum disorder.

Autism Spectrum Disorder (ASD) is a genetically heterogeneous neurodevelopmental condition in which hundreds of individually rare risk variants converge on a small number of shared biological pathways, including synaptic scaffolding, chromatin remodeling, excitation-inhibition balance, and cellular energy metabolism. Translating this genetic heterogeneity into mechanistic insight requires experimental systems capable of interrogating individual gene functions in human-relevant neural contexts at scale. CRISPR-enabled functional genomics in human pluripotent stem cell (hPSC)-derived neural models, spanning neural progenitors, cortical and inhibitory neurons, astrocytes, microglia, and brain organoids, provides precisely this capability. By integrating pooled perturbation screens with multimodal readouts including single-cell and spatial transcriptomics, chromatin accessibility profiling, proximity labeling proteomics, multi-electrode array electrophysiology, and metabolic flux analysis, these platforms enable systematic, causal mapping of ASD gene function at system resolution. Early applications have already revealed convergent mechanisms: BAF complex disruption expands the ventral progenitor pool and biases its fate toward oligodendrocyte and interneuron lineages; ADNP loss impairs microglial synaptic pruning through altered endocytic trafficking; and mTOR pathway dysregulation in PTEN- and TSC2-perturbed models links genetic risk directly to metabolic and mitochondrial dysfunction. Computational frameworks including MIMOSCA and SCEPTRE enable causal network reconstruction and pseudotime inference from these datasets, moving the field from gene lists toward pathway-level models of ASD pathobiology. Translational applications leverage isogenic iPSC panels and variant-level base and prime editing to stratify ASD variants by functional impact, informing gene therapy design for haploinsufficient targets such as CHD8 and SCN2A via AAV or antisense oligonucleotide delivery. Remaining challenges, including model developmental immaturity, batch variability, and the difficulty of modeling polygenic risk, are addressed by a roadmap integrating spatial perturbomics, AI-driven causal inference, and population-scale standardized biobanks. This review synthesizes the current state of CRISPR-based functional genomics in human stem cell neural models as a coherent experimental framework for converting ASD genetic associations into mechanistic understanding and therapeutic opportunity.

Humans

Collateral sensitivity-harnessing microbial vulnerabilities as a solution to antimicrobial resistance.

Bacteria exhibit an evolutionary trade-off through their development of collateral sensitivity (CS) which allows them to resist one antibiotic while becoming more vulnerable to another. This vulnerability offers a compelling therapeutic opportunity by selecting against resistant isolates. Laboratory evolution studies, genome sequencing, deep mutagenesis and use of artificial intelligence and machine learning can design the bespoke strategy against multi-drug-resistant bacteria. This review discusses about recent studies that are rationally designed to harness this evolutionary trade-off for the development of alternative antimicrobial strategies. The translational barriers to the clinical implementation of CS are addressed and evidence-based design principles for optimization of CS-guided therapy are discussed.

Bacteria

Integrated analysis of VEGFA rs833061 (- 460T > C) promoter polymorphism and serum YKL-40 levels in bladder cancer: evidence of a genotype-phenotype association.

BACKGROUND: Angiogenesis plays a central role in bladder cancer progression. VEGFA regulates angiogenesis, whereas YKL-40 is a pro-angiogenic biomarker. The relationship between VEGFA polymorphism and circulating YKL-40 remains unclear. METHODS AND RESULTS: A hospital-based case-control study involving 120 bladder cancer patients and 120 age- and sex-matched healthy controls was conducted. VEGFA rs833061 genotyping was performed using ARMS-PCR and confirmed by Sanger sequencing. Serum YKL-40 concentrations were measured by ELISA. Multivariable binary logistic regression analysis adjusted for age, sex, and smoking status demonstrated that the CT and TT genotypes remained independently associated with an increased risk of bladder cancer. Serum YKL-40 concentrations were significantly elevated in patients and increased progressively with tumor stage. TT genotype carriers exhibited the highest serum YKL-40 levels. CONCLUSIONS: After adjustment for age, sex, and smoking status, the VEGFA rs833061 polymorphism remained independently associated with bladder cancer susceptibility and circulating YKL-40 concentrations. These findings provide preliminary evidence of a genotype-phenotype relationship; however, validation in larger multicentre cohorts is required.

Humans

Retrotransposable element derepression distinguishes DNMT3A-mutant from TET2-mutant clonal haematopoiesis.

Clonal haematopoiesis (CH) is driven by somatic mutations in haematopoietic stem cells that generate clonal populations detectable in peripheral blood and is present in 10-20% of individuals over the age of 65. Mutations in DNMT3A and TET2 are the most common drivers and have been linked to inflammatory phenotypes and increased risk of haematologic and cardiovascular disease. However, the cell-intrinsic mechanisms connecting these mutations to inflammatory signalling remain incompletely understood. Because retrotransposable elements (RTEs) are epigenetically regulated and can activate innate immune pathways when derepressed, we hypothesised that RTE reactivation may represent a mutation-specific mechanism linking clonal haematopoiesis driver mutations to inflammatory pathways. We analysed RTE expression and clonal burden in peripheral blood mononuclear cell (PBMC) samples from 56 individuals with CH and 12 non-CH controls using integrated genomic and transcriptomic approaches, with complementary validation by TARGET-seq across haematopoietic lineages. High variant allele frequency (VAF; > 10%) DNMT3A-mutant clones exhibited widespread derepression of RTEs, particularly LINE and LTR families, whereas TET2-mutant clones showed a trend towards reduced RTE expression relative to controls. Transcriptomic analyses revealed that DNMT3A high-variant allele frequency clones with elevated RTE expression were enriched for inflammatory signalling pathways, including TNF-α/NF-κB signalling, interferon responses, and senescence-associated signatures. In contrast, TET2-mutant clones lacked these RTE-associated inflammatory signatures and instead showed enrichment of oxidative phosphorylation, reactive oxygen species signalling, and a mechanistic target of rapamycin complex 1 pathway. These findings were reproduced in an independent cohort. Collectively, our results highlight mutation-specific inflammatory mechanisms in clonal haematopoiesis and provide a foundation for future functional and preclinical studies to determine whether modulation of RTE activity can influence the inflammatory phenotype of DNMT3A-mutant CH and represent a potential therapeutic strategy.

DNMT3A

Recent Advances in Surveillance Strategies for Nasopharyngeal Carcinoma.

PURPOSE OF REVIEW: Nasopharyngeal carcinoma (NPC) is a malignant tumor characterized by a distinct geographical distribution. Effective surveillance is crucial for the early detection of recurrence or metastasis and for improving patient prognosis.This review systematically examines current NPC follow-up protocols and recent developments to inform individualized precision surveillance. RECENT FINDINGS: This review focuses on two main aspects. 1) We compare and analyze current major NPC follow-up guidelines, with key discussions covering follow-up frequency, imaging modalities (including magnetic resonance imaging [MRI] and positron emission tomography [PET]), plasma Epstein-Barr virus DNA (EBV-DNA) monitoring, and functional assessments. 2)We elaborate on the application prospects and research progress of genomics, radiomics, and artificial intelligence in NPC surveillance. Studies suggest that risk-stratified, individualized follow-up strategies, such as those based on conditional survival models, can enhance the cost-effectiveness of surveillance. Additionally, emerging technologies, including radiomics and artificial intelligence, show promise for improving recurrence risk assessment, prognostic stratification, and individualized surveillance in NPC. Concurrently, advances in genomics and radiomics offer new opportunities for predicting complications and guiding treatment adjustments. Future efforts should focus on integrating multidisciplinary expertise to develop dynamic monitoring systems that enable precise follow-up and ultimately improve patient survival outcomes.

Humans

Synthesis of Padina boergesenii-Derived Zinc Oxide Nanoparticles and their Therapeutic Potential Against Oral Squamous Cell Carcinoma: A Transcriptomic and in Vitro Evaluation.

Cancer remains a major health challenge, with oral squamous cell carcinoma (OSCC) being an high aggressive subtype of head and neck squamous cell carcinoma that lacks effective therapeutic options. Current study integrates the synthesis of zinc oxide nanoparticles (ZnO-NPs) from the marine brown algae Padina boergesenii with the OSCC gene expression profile to evaluate their potential therapeutic effects against OSCC. Herein, the ZnO-NPs from Padina boergesenii were prepared through the green synthesis method. The obtained ZnO-NPs were characterized through spectroscopic methods, the UV spectrophotometer shows maximum absorbance at 372 nm, FT-IR presents Zn-O functional band at 516 cm- 1, HR-TEM confirms average particle size of 55.70 nm and the Zetasizer shows zeta potential of + 12.9 mV, indicating colloidal stability. The cytotoxicity assay with ZnO-NPs against oral cancer cell lines exhibited a reduction in cell viability at IC₅₀ value of 20 µg/mL. Meanwhile, the transcriptome analysis of OSCC highlights that MYC, STAT3, BRCA1, and AKT1 are the OSCC therapeutic targets involved in proliferation, immune evasion, genomic instability, and cancer signalling pathways. Further, qRT-PCR based gene expression analysis demonstrates significant down-regulation of these targets upon ZnO-NPs treatment in KB cell lines. Overall, this study emphasizes the anticancer potential of Padina boergesenii-derived ZnO-NPs that could effectively modulate the therapeutic targets and may benefit the treatment of OSCC cancer.

Cytotoxicity

Early-Onset Colorectal Cancer: Clinical and Molecular Features with Emerging Insights from Comprehensive Genomic Profiling.

Early‑onset colorectal cancer (EOCRC), defined as colorectal cancer (CRC) diagnosed before 50 years of age, is increasing globally. Colorectal cancer is currently the third most commonly diagnosed cancer and the second leading cause of cancer-related death worldwide, with GLOBOCAN 2024 estimating approximately 2.04 million new cases and 917,895 deaths in 2024. Recent studies indicate a sustained rise in EOCRC incidence across multiple regions and birth cohorts, with the greatest increases observed among younger adults. Although hereditary cancer syndromes account for 20-25% of EOCRC cases, most occur in the absence of known genetic predispositions or established risk factors. Emerging evidence implicates the gut microbiome as a potential contributor to EOCRC, with distinct microbial signatures differentiating it from late‑onset colorectal cancer (LOCRC) diagnosed after 50 years of age. This review synthesizes current evidence on clinical, molecular, and diagnostic features distinguishing EOCRC from LOCRC, including differences in anatomical distribution, histopathology, genomic and epigenetic alterations, microbiome composition, and immune landscape, and discusses their implications for personalised screening and therapeutic strategies. We performed a retrospective secondary analysis of comprehensive genomic and immune profiling data from 1737 patients with colorectal cancer tested between June 2021 and June 2023. The analysis showed that tumours arising in patients with EOCRC had lower tumour mutational burden than tumours diagnosed as LOCRC, whereas other immune-related biomarkers, including tumour immunogenicity score, did not remain significantly different after correction for multiple testing. Despite these emerging biological differences, current screening strategies remain largely dependent on an age threshold of 50 years, and EOCRC is not addressed by age‑specific treatment approaches. We therefore review the translational potential of emerging biomarkers, including microbial signatures and liquid biopsy approaches, and propose a framework for integrating molecular profiling into clinical practice. Finally, we highlight the unmet need for coordinated efforts to improve screening in younger populations, address fertility preservation considerations, and ensure adequate psychosocial support for patients with EOCRC.

Early-onset colorectal cancer

Microbial diversity: the essential foundation for life on our planet.

The biological basis of life on Earth is microbial diversity that ensures human health, agricultural productivity, ecological balance, and ecosystem functioning. Microorganisms enable ecosystem restoration through bioremediation, maintain soil fertility, support plant growth, manage vital biogeochemical cycles, and contribute to climate resilience. Precision probiotics, postbiotics, faecal microbiota transplantation, and personalized microbiome medicine are the examples of emerging microbiome-based therapies that offer promising therapeutic opportunities. In humans, the gut microbial community is essential for immune regulation, metabolism, and disease prevention. In terrestrial ecological systems, interactions between plants, fungi, bacteria, and other soil microorganisms improve carbon sequestration, nutrient cycling, stress resilience, and sustainable agricultural productivity in the given effects of climate change. Emerging uses in agriculture, environmental restoration, and medicine are made possible by advancements in multi-omic techniques, synthetic microbial genomes, microbiome engineering, and artificial intelligence. Considering these developments, issues with ecological complexity, long-term validation, standardization, and field scale application still exist. Therefore, preserving microbial diversity is important for conserving ecological resilience and strengthening the One Health framework, which highlights the mutual dependance of health of animal, human, plant, and environment. This review summarizes what has been discovered about ecological and biomedical relevance of microbiome, identifies important research gaps, highlighting emerging technologies, and evaluates potential future directions for using microbiome to support planetary sustainability.

Bioremediation

3D chromatin remodeling during domestication defines novel targets for crop improvement.

Three-dimensional (3D) genome folding shapes gene regulation, yet the genetic underpinnings linking 3D genome evolution to phenotypic innovation during domestication remain elusive. Using population-scale Hi-C profiling of 34 semi-wild and 267 cultivated allotetraploid cottons, we generated a pan-3D genome atlas capturing extensive diversity in topologically associating domains (TADs) and chromatin loops. Chromatin interactome-wide association studies identified 105 TAD reconfigurations and 58 loop rewirings that were established as the 3D chromatin basis of fiber quality, boosting heritability estimates for fiber strength by 16% and fiber length by 20%. We reveal that domestication selection within sequence-defined sweeps fixed 57% of 3D conformation signatures, thereby decoupling sequence-level from chromatin-level selection and shifting the subgenome expression balance of 39 homoeologs in cultivated cotton. Sequence-based modeling and mutational analyses identified the C2H2 zinc-finger protein YY1 as a conserved mediator of 3D genome organization. This study provides a resource for redefining precision-breeding paradigms by harnessing cryptic 3D chromatin targets.

3D genome

Plasma proteins are integral to cross-tissue gene regulatory networks implicated in cardiometabolic disorders and coronary artery disease.

The plasma proteome has demonstrated promise for identifying diagnostic markers for cardiometabolic disorders (CMDs) and coronary artery disease (CAD). However, identifying the organ of origin for these biomarkers is critical for establishing biological relevance. We performed a multi-omic integrative analysis across multiple tissues from the STARNET study by profiling 974 plasma proteins in 532 CAD patients, integrating RNA sequencing (RNA-seq) data from the arterial wall, major metabolic organs, and blood. We identified 144 cis-protein quantitative trait loci in plasma, colocalizing with tissue cis-expression quantitative trait loci. Additionally, by mapping tissue mRNA "seed genes," we traced 262 plasma proteins to their source organs, primarily the liver. Crucially, we found that 851 plasma proteins are associated with the activity of cross-tissue gene regulatory networks (GRNs), including GRNs implicated in CMD and CAD development. Our findings demonstrate that plasma proteins are integral components of GRNs, with potential for developing reliable diagnostics and precise therapeutic targets. A record of this paper's transparent peer review process is included in the supplemental information.

cardiometabolic disorders

Pathway-driven target prioritisation in drug discovery.

Genome-scale association studies and functional screens routinely implicate hundreds of candidate genes per disease, yet only a few will be clinically validated as drug targets. Choosing which to pursue is a central drug-discovery decision that depends on interpreting each candidate in its biological context. Curated pathway databases provide this context, while enrichment analysis applies it at scale, turning gene-level signals from genome-wide association, transcriptomic, proteomic and CRISPR studies into mechanistic hypotheses for prioritisation. This review examines how pathway-based methods inform target prioritisation, the databases and tools available for this purpose, and why pathway co-membership should be viewed as a starting point for validation rather than as evidence of causal involvement.

CRISPR

Post-colonial human admixture and natural selection: disentangling signals in complex demographic contexts.

Natural selection and admixture are defining population genetic features of modern human populations, yet their interaction has only recently emerged as a major focus in human evolutionary genomics. While the influence of natural selection on population structure and trait diversity is well established, the ways in which selective pressures operate after admixture have historically received far less attention. In this review, we synthesise the latest progress in understanding post-admixture selection and highlight case studies that illustrate how novel environments, pathogen exposure, dietary shifts and socio-historical transformations have driven genomic adaptation. We conclude by identifying key gaps that remain in the field with the aim of motivating future research and facilitating new insights into how admixture and selection jointly shape human diversity.

Journal Article

MicroRNA-driven regulatory networks in aphid ecological adaptation: integrating stress tolerance, dispersal plasticity, and population expansion.

Aphids (Hemiptera: Aphididae) are important agricultural pests and exhibit strong ecological adaptability, allowing them to persist under stress, disperse to new habitats, and rapidly increase population size. Recent advances in functional genomics have identified microRNAs (miRNAs) as key post-transcriptional regulators involved in these processes, yet their roles have remained fragmented across studies. Here, we synthesize current evidence into a "three-stage framework", encompassing population maintenance under stress, dispersal to new habitats, and population expansion upon establishment. We highlight how miRNAs regulate detoxification pathways (e.g., P450s, UGTs, ABC transporters), mediate interactions with host plants and symbionts, and integrate hormonal signaling networks including insulin, juvenile hormone, and ecdysteroid pathways. This framework identifies candidate miRNAs, target genes, and signaling pathways that may recur across different ecological contexts, including stress responses, dispersal-related plasticity, and reproductive regulation. However, direct evidence demonstrating that candidate shared miRNA regulators coordinate multiple life-history stages remains limited and requires further experimental validation. We critically evaluate the strength of functional evidence, distinguishing experimentally validated miRNA-target interactions from prediction- or expression-based associations. Finally, we discuss emerging applications of miRNA-based pest control, including artificial miRNAs, RNAi technologies, and nanocarrier delivery systems. By linking molecular mechanisms with ecological outcomes, this review provides a synthesis and highlights miRNAs as important regulators of aphid adaptation and candidate targets for sustainable management strategies.

Aphids

Evaluation of a rapid-release mitomycin C-loaded porous microcapsule formulation (MitoCap) in a human urothelium-tumour model.

Intravesical mitomycin C (MMC) is limited by short bladder exposure and incomplete delivery to residual tumour tissue. We developed MitoCap, a porous MMC-loaded microcapsule formulation, and evaluated its formulation properties and antitumour performance in a human three-dimensional urothelium-tumour model (3D-UHU-TU). Microcapsules were produced by electrohydrodynamic atomisation using 2% or 5% poly(lactic-co-glycolic acid) (PLGA). Compared with 5% PLGA, the 2% formulation generated smaller microcapsules (2.90 ± 0.30 versus 4.03 ± 0.81 µm), greater apparent surface porosity and faster MMC release, with approximately 60% released within 15 min. The 2% formulation achieved an MMC loading capacity of 4.99 ± 0.16% (w/w), corresponding to 95.78 ± 3.09% recovery relative to the theoretical loading, and was selected for biological evaluation. The 3D-UHU-TU model integrates RT112 or T24 bladder cancer spheroids into a differentiated, urine-tolerant human urothelium, enabling tumour and urothelial responses to be assessed within the same construct. FITC-loaded microcapsules increased fluorescent model cargo signal within tumour regions compared with equivalent free FITC. Following 1 h apical exposure and 72 h recovery, MitoCap increased tumour-associated cleaved caspase-3 and tumour cell death relative to dose-matched free MMC. Tumour cell death increased from 62.3 ± 7.9% to 94.2 ± 1.3% in RT112 models and from 36.6 ± 4.7% to 52.8 ± 4.8% in T24 models, without increasing urothelial cell death relative to dose-matched free MMC. These findings support MitoCap as a rapid-release intravesical MMC formulation and demonstrate the value of compartment-resolved human urothelium-tumour models for evaluating local drug delivery.

Bladder cancer