Distracted driving is a critical global concern and a major factor in numerous road collisions. To mitigate these issues, this article introduces a novel model, LiteDriveNet, a resource-efficient 16-layer convolutional neural network with a compact size of 1.71 MB, designed for precise image identification and behavioral analysis. The architecture incorporates multi-scale receptive blending, progressive feature enhancement, and hierarchical feature aggregation to achieve robust feature extraction. To assess the model performance, a dataset named DistractedDrivingSet_v1 is also proposed, comprising 6075 outdoor images across 8 distinctive classes, captured under real-world lighting conditions such as sunlight and shadows. LiteDriveNet's efficacy was further verified using two publicly available benchmark datasets, the State Farm Distracted Driver Detection (SFD3) dataset and the American University in Cairo (AUC) version 2. Experimental findings show that LiteDriveNet consistently surpasses both accuracy and computational efficiency compared to existing state-of-the-art, lightweight, and neural architecture search-based (NAS) models. LiteDriveNet achieves average validation accuracy improvements of 16.53% on DistractedDrivingSet_v1, 6.70% on SFD3, 10.91% on AUCv2 Camera1, and 28.97% on AUCv2 Camera2. An ablation study also proves that LiteDriveNet is an eminent lightweight model for distracted driver recognition, as it is highly suitable for real-time environments compared to state-of-the-art techniques.
Driving requires complex visuospatial, cognitive and physical abilities, with vision being a key determinant of safety. Progressive eye diseases, diabetes and neurological conditions can impair visual acuity (VA) and visual fields (VF), increasing motor vehicle accident risk. With an ageing population, vision-related driving impairment is expected to rise. This article summarises Australian driving standard guidelines and provides a practical framework for general practitioners to assess, monitor and refer drivers with visual conditions that may affect fitness to drive. VA and VF primarily determine visual fitness to drive, with specific thresholds for private and commercial licences. Understanding variable state-based reporting laws and initiating early, well-documented conversations about driving retirement can help maintain driver safety and autonomy while supporting community wellbeing.
A major challenge in developing effective photocatalysts lies in engineering the efficient coupling of one-electron photochemistry with the multi-electron requirements of chemical transformations. Here we demonstrate biohybrid assemblies that achieve this key performance requirement by storing photoenergized electrons on multiple heme cofactors within the MtrC enzyme which catalyzes azo dye reduction. The biohybrid assemblies were created by site-selective labeling of MtrC with a Ru(II) (bipyridine)3 photosensitizer dye. Photocatalytic azo dye reduction and decoloration occurred when these assemblies were irradiated in the presence of a sacrificial electron donor. Our Ru(II) (bipyridine)3-MtrC biohybrid assemblies operate in a manner analogous to Ru(II) (bipyridine)3-sensitized TiO2 in the sense that photoenergized electrons accumulate in the MtrC heme chain rather than in the TiO2 conduction band prior to driving reductive chemical transformations. We anticipate that decoration of the photosensitized MtrC protein with electrocatalysts (natural or synthetic) will enable the Ru(II) (bipyridine)3-MtrC assemblies to drive a wide range of light-driven reductive transformations. Thus, MtrC provides a natural alternative to TiO2 materials for which the production and disposal present significant environmental and energy impacts.
The escalating atmospheric CO2 concentration, exceeding 430 ppm since the pre-industrial era, presents a critical threat to global climate stability. Moving beyond mere carbon capture, this review synthesizes cutting-edge advancements in technology-driven CO2 fixation, focusing on microbial conversion systems. It begins by examining inherent limitations of natural pathways like the Calvin-Benson-Bassham cycle, constrained by low energy efficiency (<1%) and enzymatic inefficiencies of RuBisCO. The discussion then progresses to engineering native pathways and de novo design of synthetic routes (e.g., rGly, CETCH, THETA cycles), which demonstrate superior thermodynamic and kinetic properties for efficient carbon conversion. CRISPR-Cas systems' revolutionary impact, overcoming genetic barriers in carbon-fixing microorganisms. These tools enable precise metabolic rewiring and conversion of heterotrophic chassis into synthetic autotrophs. Furthermore, the convergence of microbiology with electrochemistry and materials science is detailed, highlighting innovative platforms like microbial electrosynthesis and semi-artificial photosynthetic systems. These biohybrid technologies create synergistic interfaces where microbes utilize electrons from electrodes or artificial materials to drive efficient CO2 reduction into multicarbon compounds, addressing critical energy supply challenges. The review analyzes the transition from natural pathway optimization to custom artificial system construction, underscoring a paradigm shift from isolated improvements to deeply integrated approaches. This new paradigm fuses metabolic engineering, synthetic biology, electrochemistry, and nanomaterials, guided by AI-aided design and modeling. The conclusion emphasizes that seamless integration of microbial capabilities, advanced materials, and artificial intelligence is pivotal for advancing CO2 fixation toward precision, high efficiency, and carbon negativity, laying the essential foundation for sustainable carbon-negative biomanufacturing and contributing meaningfully to global carbon neutrality goals.
Pulmonary fibrosis (PF) remains a lethal progressive disease with poorly defined molecular drivers. Epithelial dysfunction and metabolic reprogramming contribute to PF, but the mechanistic link between these processes remains unclear. Here, we identify a Kat5-STAT6 epigenetic-metabolic axis that governs fibrotic progression. Kat5 directly acetylates STAT6 at lysine 636 (K636), thereby suppressing STAT6 dimerization, phosphorylation and nuclear translocation. In fibrotic lungs, STAT6 acetylation at K636 is reduced, leading to its hyperactivation. Activated STAT6 drives transcription of pro-glycolytic enzyme hexokinase 2 (HK2), promoting metabolic reprogramming in alveolar type II (ATII) cells and extracellular matrix deposition. ATII cell-specific restoration of Kat5 rescues STAT6 acetylation, normalizes its activity and ameliorates fibrosis in vivo. Mechanistically, Kat5-mediated STAT6 acetylation functions as a biochemical brake that limits cooperation with profibrotic mediators such as tissue plasminogen activator (tPA). These findings redefine STAT6 regulation, highlight an acetylation-phosphorylation checkpoint controlling fibrogenesis, and suggest that Kat5 enhancers or STAT6 acetylation mimetics may represent potential therapeutic strategies for chronic lung disease.
Neurotropic alphavirus infection is characterized by neuronal injury and sustained neuroinflammation, yet the viral determinants linking membrane perturbation to host inflammatory damage remain poorly defined. Here, we show that the Western equine encephalitis virus (WEEV) 6K protein functions as an ER-localized viroporin, displaying stable single-channel activity with broad cation permeability. Consistent with its ion channel activity, 6K expression perturbs intracellular Ca²⁺ store homeostasis and is associated with cellular injury phenotypes. Mechanistically, 6K predominantly engages MLKL-mediated necroptosis, identifying programmed necrotic signaling as a principal pathway underlying 6K-driven injury under these conditions. Importantly, genetic deletion or pharmacological inhibition of MLKL significantly attenuates 6K-associated cellular damage and inflammatory release, establishing MLKL-dependent execution as a key modifiable node in viroporin-induced host injury. We further identify HYH09-D4 as a protective small molecule that dampens MLKL activation and limits tissue damage associated with 6K expression. Together, these findings define WEEV 6K as a host-facing viroporin that links ionic dysregulation to MLKL-dependent necroptosis and suggest that targeting MLKL may represent a broadly applicable strategy to mitigate host injury driven by 6K-encoding alphaviruses.
Bound states in the continuum (BIC) leverage symmetry-protected resonant modes for exceptional light confinement, yet their leaky modes are almost underutilized. Meanwhile, multiple quantum well (MQW) structures face limited optical absorption due to strict transition selection rules. We demonstrate the regulation of the leaky mode of quasi-BIC (QBIC) by analyzing MQW-vertical field coupling, revealing that increasing asymmetric parameters enhances the transverse leakage of wave vector and optical field nonlinearly. This drives a nonlinear photoresponse as increasing asymmetry parameter, while linear scenario with incident angle and external bias voltage. We then develop an optoelectrical fusion neuromorphic processor, implementing QBIC-MQWs into an artificial neural network for machine vision applications. Graphical abstract. This work presents a proof-of-concept BIC-MQW device, in which the photocurrent characteristics are leveraged to realize image processing functionalities.
Kirsten rat sarcoma viral oncogene (KRAS) G12C inhibitors have demonstrated clinical efficacy against KRAS G12C-mutant non-small cell lung cancer (NSCLC); however, intrinsic and acquired resistance limit their therapeutic potential. Therefore, combination strategies are needed to address these limitations. While various combination regimens are currently being tested in clinical trials, treatments tailored to specific biomarkers remain underexplored. In this study, intrinsic and acquired KRAS G12C inhibitor-resistant tumor cells were established using patient-derived xenograft (PDX) and mouse models. We identified that tumor cell-autocrine amphiregulin (AREG)-mediated epidermal growth factor receptor (EGFR) phosphorylation plays a pivotal role in both intrinsic and acquired resistance to KRAS inhibitors. Notably, the same resistance mechanism was observed in central nervous system metastatic recurrence in a leptomeningeal carcinomatosis mouse model. RNAscope in situ hybridization detected AREG mRNA in tumor tissues and may serve as a diagnostic tool for assessing AREG expression. Furthermore, combining KRAS inhibitors with EGFR tyrosine kinase inhibitors suppressed tumor growth, effectively overcoming resistance. Notably, high AREG mRNA expression was observed in three of nine tumor samples from patients harboring the KRAS G12C mutation, including two patients who exhibited a poor response to sotorasib and one patient who achieved a partial response. In conclusion, AREG-mediated EGFR activation is a key driver of resistance to KRAS inhibitors in patients with KRAS G12C-mutant NSCLC. Combining EGFR and KRAS inhibition represents a promising strategy to overcome therapeutic resistance and may enhance and prolong clinical benefit in patients.
Although biohybrid robots offer the potential for soft, adaptive actuation by harnessing living muscle, practical operation in cell culture environments is often limited by the requirement of immersed leads or cumbersome stimulation equipment. Here, we present a thin, miniaturized, wireless bioelectronic stimulator that can electrically drive biohybrid robots while maintaining stability in aqueous cell culture media. Built on a 50-µm liquid crystal polymer (LCP) substrate, the device integrates a planar receiving coil, interconnects, a diode-based rectifier, and a tank capacitor. This enables the device to convert an approximately 4.9-MHz radio-frequency (RF) input into pulsed direct current (DC), which is delivered through integrated stimulation electrodes. The stimulator has a footprint of ~ 32 mm² and a total thickness and mass of ~ 100 μm and ~ 7 mg, respectively. We integrated the stimulator with a nanopatterned carbon nanotube (CNT)/gelatin hydrogel fin seeded with human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) to generate propulsion through fin flapping. By optimizing the thickness of the polydimethylsiloxane (PDMS) encapsulation layer, the density was tuned, and the robot remained freely floating and retained shape integrity during operation. This produced autonomous forward locomotion of 74.8 ± 16.4 μm s- 1. The stimulator generated distance-dependent output voltage pulses and enabled external pacing/modulation under the tested conditions, without a marked loss of cardiomyocyte attachment or α-actinin-positive sarcomeric organization. Together, these results provide a proof-of-concept compact, media-compatible, wireless bioelectronic interface toward closed-system biohybrid robotics.
Pulmonary ischemia-reperfusion (I/R) injury is a life-threatening complication of thoracic surgery with limited therapeutic options. While ferroptosis contributes significantly to lung damage, its transcriptional regulation remains poorly understood. Murine pulmonary I/R models and hypoxia/reoxygenation (H/R)-treated lung epithelial cells were integrated to explore the molecular mechanisms underlying ferroptosis. Transcriptomics, proximity-dependent biotin labeling using a promiscuous biotin ligase (TurboID), chromatin immunoprecipitation (ChIP), co-immunoprecipitation (co-IP), luciferase reporter assays, and functional rescue assays were employed to delineate the FosB proto-oncogene, activator protein-1 (AP-1) transcription factor subunit (FOSB)-histone deacetylase 6 (HDAC6)-hepcidin antimicrobial peptide (HAMP) axis. Molecular markers were assessed by reverse transcription-quantitative polymerase chain reaction (RT-qPCR), immunoblotting, and biochemical kits. I/R injury upregulated FOSB expression in lung tissues, correlating with alterations in ferroptosis markers, including reduced expression of glutathione peroxidase 4 (GPX4) and solute carrier family 7 member 11 (SLC7A11), concomitant with elevated expression of acyl-coenzyme A synthetase long-chain family member 4 (ACSL4), accumulation of ferrous iron (Fe2+), and increased levels of reactive oxygen species (ROS). FOSB directly bound the HAMP promoter at -600/-300 bp, inducing hepcidin expression. HDAC6 physically interacted with FOSB and enhanced its promoter occupancy, amplifying hepcidin production. HAMP overexpression reversed FOSB knockdown-mediated protection against ferroptosis in vitro. The FOSB-HDAC6 complex transcriptionally activates HAMP to drive hepcidin-mediated iron overload and ferroptosis in pulmonary I/R injury, revealing a targetable axis for lung protection.
ATP-competitive kinase inhibitors represent one of the largest classes of targeted anti-cancer drugs. While their primary mechanism is to block catalytic activity, they can also trigger paradoxical phenotypic effects that cannot be explained by catalytic inhibition alone. These observations point to a hidden layer of drug action that modulates non-catalytic kinase functions via changes in kinase conformation and protein-protein interactions (PPIs). Here, we developed a multimodal proteomics approach combining limited proteolysis coupled mass spectrometry on affinity-purified samples (AP-LiP-MS), AP-MS, and proximity labeling-MS to map inhibitor-induced conformation and PPI changes. We show that inhibitor binding causes structural rearrangements in the autoinhibitory domains (AIDs) of all tested kinases, consistent with a transition to an open, active-like kinase conformation. These structural shifts drive distinct kinase-protein interaction changes that control non-catalytic functions: sequestration of AMPK by inhibited CAMKK2 blocks phosphorylation by other kinases, CHEK1 inhibition causes dissociation from the mitochondrial protein CLPB and leads to mitochondrial fragmentation, and structural changes in inhibited PRKCA trigger rapid relocalization to cell junctions. Thus, we identify the ATP-binding site as a major organizing center of kinase conformation and interaction. Our work suggests that these on-target, off-mechanism effects are likely to occur in other kinases as well, and provides the analytical framework to systematically characterize a frequently overlooked phenomenon highly relevant for understanding drug side effects to guide the development of novel therapeutics.
The tumor microenvironment is a critical regulator of cancer progression. Histone lactylation, a novel post-translational modification, has emerged as a key player in various tumors and is closely linked to macrophage polarization within the immune tumor microenvironment. Here, we delineated the signaling axis through which histone lactylation, specifically H3K18la, orchestrates crosstalk between intrahepatic cholangiocarcinoma cells and the tumor microenvironment (TME). Cleavage Under Target and Tagmentation analysis revealed an enrichment of H3K18la at the promoter of the N6-methyladenosine reader protein insulin-like growth factor-2 mRNA-binding protein 3 (IGF2BP3), enhancing its transcription. IGF2BP3 stabilizes the mRNA of the key factor secreted phosphoprotein 1 (SPP1), thereby promoting its secretion. Single-cell RNA sequencing indicated that tumor-derived SPP1 promoted intrahepatic cholangiocarcinoma (iCCA) progression by acting on macrophages via the SPP1/CD44 axis, inducing M2 polarization and migration to shape an immunosuppressive tumor microenvironment. Furthermore, using clinically relevant patient-derived organoids, xenograft models, and immunocompetent mouse models, we demonstrated that a glycolysis inhibitor synergizes with the first-line chemotherapeutic agent gemcitabine, significantly enhancing its therapeutic efficacy. These findings deliver a new exploration and important supplement of metabolic reprogramming, epigenetic regulation, and tumor immune microenvironment, and provide a new strategy for improving clinical efficacy of gemcitabine in iCCA by inhibiting histone lactylation. Histone lactylation is a recently identified post-translational modification implicated in diverse oncogenic processes, particularly macrophage polarization, yet its role in intrahepatic cholangiocarcinoma (iCCA) remains poorly defined. By integrating single-cell sequencing, CUT&Tag profiling, three-dimensional organoid culture, and conventional in vitro and in vivo models, this study delineates a previously unrecognized signaling axis through which H3K18la governs crosstalk between iCCA cells and macrophages. We demonstrate that H3K18la targets insulin-like growth factor-2 mRNA-binding protein 3 (IGF2BP3), enhancing the stabilization and secretion of secreted phosphoprotein 1 (SPP1), which engages CD44 on macrophages to drive their M2 polarization and facilitate tumor progression. Notably, pharmacological inhibition of histone lactylation combined with standard chemotherapy achieved significantly greater anti-tumor efficacy than monotherapy alone. These findings establish H3K18la as a central regulator of macrophage polarization in iCCA, thereby highlighting this modification as a promising therapeutic target.
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We generated two mouse models, p21+/Tert and p21+/TertCi, expressing either telomerase reverse transcriptase (Tert) or a catalytically inactive variant under the control of the p21 promoter. By 18-20 mo of age, ∼15% of mice from both genotypes developed liver tumors with histopathological features resembling human hepatocellular carcinoma (HCC). Whole-exome sequencing identified activating Ctnnb1 mutations and recurrent PP1 subunit alterations in p21+/Tert tumors, whereas p21+/TertCi tumors harbored activating HrasGln61Lys mutations associated with elevated C > A transversions. Both models exhibited chromosomal aberrations commonly observed in human HCC. Transcriptomic analyses revealed that β-catenin-activated tumors recapitulated gene expression signatures of human HCC, whereas MAPK-mutated tumors showed profiles consistent with MAPK/ERK pathway activation. All HCCs suppressed the gluconeogenic genes Fbp1 and AldoB, but diverged into two distinct groups based on their glycolytic and NRF2 target gene expression profiles. Spatial profiling further revealed reduced HNF4α-positive hepatocytes across tumors, independent of HNF4α transcription, and markedly diminished immune cell infiltration, particularly in β-catenin-activated tumors. Collectively, these findings uncover telomere-independent functions of Tert and identify molecular and metabolic features with potential relevance for predicting immunotherapy response.
Microplastic (MP) pollution is a growing global concern due to its ubiquity in aquatic ecosystems and its potential to act as a vector for environmental contaminants. Although laboratory studies have examined how photoaging alters the adsorptive behavior of MPs, their findings remain fragmented and often contradictory. Here, we conducted a systematic review and a three-level random-effects meta-analysis to quantitatively assess the impact of photoaging on the adsorption capacity of MPs. A total of 30 studies met the inclusion criteria, yielding 256 control-treatment comparisons. Extracted data included adsorption capacity (mean ± SD), polymer type, crystallinity, contaminant class, and experimental conditions, which were evaluated as potential moderators. Overall, photoaging exhibited a marginally positive effect on adsorption capacity, although results varied substantially across studies. Polymer-related properties, particularly type and hydrophobicity, emerged as stronger predictors of adsorption outcomes than environmental or operational variables, whereas crystallinity showed no significant effect. Among environmental moderators, only pH significantly influenced adsorption, with higher effects under acidic conditions. In contrast, salinity, temperature, and contaminant class showed no consistent moderating role. Notably, the type of microplastic was a stronger determinant than either contaminant concentration or chemical class, underscoring the central role of polymer-specific features in determining adsorption behavior after photoaging. More hydrophobic polymers, especially PE, PS, and PVC displayed greater increases in adsorption capacity after photoaging than hydrophilic ones. These findings suggest that the physicochemical nature of MPs, especially polymer type and hydrophobicity, plays a more decisive role in shaping adsorption patterns after photoaging than external conditions or contaminant characteristics. By identifying the key sources of variability across studies, our findings provide a robust evidence base to refine environmental risk assessments and to guide future research priorities.
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Cold tumors, defined by an immunosuppressive microenvironment and metabolic stress, including glutamine deficiency, frequently exhibit resistance to therapeutic interventions. This study examined the role of glutathione peroxidase 1 (GPX1) in mediating resistance to cuproptosis and ferroptosis during glutamine deprivation. Through integrated multi-omics analyses, CRISPR-mediated gene editing, and functional assays in cold tumor cell lines, we identified GPX1 as a key regulator of redox homeostasis and a protector against cuproptosis. Upstream, glutamine deprivation induced the SLC7A11 upregulation, which enhanced GPX1-mediated resistance through the maintenance of pyrimidine metabolism. Downstream, GPX1 knockout mediated cross-sensitization to ferroptosis by altering the Fenton reaction, thereby exacerbating cell death. In vivo experiments confirmed that GPX1 knockout restored sensitivity to cuproptosis inducers and improved the efficacy of PD-L1 blockade. Collectively, these findings position GPX1 as a central metabolic checkpoint in cold tumors and highlight the SLC7A11-UMPs-GPX1 axis as a promising therapeutic target for overcoming treatment resistance and enhancing immunotherapy response.
Vasculogenic mimicry (VM), a novel endothelial-independent blood perfusion pathway, is linked to advanced stage and poor prognosis in esophageal squamous cell carcinoma (ESCC). In this study, by integrating single-cell RNA sequencing and transcriptomic data and employing a machine learning framework incorporating 117 algorithmic combinations, we constructed a robust 4-VM-related gene prognostic model for ESCC. Consensus clustering further stratified patients into two subtypes. The high-risk subtype (C2) was characterized by unfavorable prognosis, activated stroma, enrichment of M2 macrophages, and multidrug resistance. As the core regulatory hub of this model, SAP18 was markedly upregulated in ESCC tissues and showed positive correlations with aggressive clinicopathological features. Mechanistically, SAP18 binds to PIK3CB, activating the AKT/mTOR signaling cascade and upregulating HIF-1α, thereby conferring VM-forming capability to epithelial-derived tumor cells. Both in vitro and in vivo experiments confirmed that knockdown of SAP18 significantly suppressed malignant phenotypes in ESCC. Pharmacological intervention using the highly selective AKT inhibitor MK-2206 effectively abolished VM network formation and profoundly inhibited tumor growth. Our integrated multi-omics and functional analyses decipher the molecular architecture of VM in ESCC, nominating SAP18 as a precise prognostic biomarker and therapeutic target, and providing a foundation for individualized VM-targeted strategies in ESCC management.
Melanoma is the most aggressive form of skin cancer due to its high metastatic potential and resistance to therapy. Current treatment strategies include surgical resection for localized disease, as well as targeted therapy with MAPK inhibitors and immunotherapy for advanced stages. However, therapeutic resistance and disease relapse remain major clinical challenges. Activating mutations in components of the mitogen-activated protein kinase (MAPK) pathway, particularly in BRAF and NRAS, are among the most frequent oncogenic events in melanoma, driving tumor initiation and progression through sustained ERK signaling. Mitochondria are dynamic organelles whose morphology is regulated by the balance between fission and fusion. In melanoma cells, MAPK-dependent signaling has been implicated in the regulation of key components of the mitochondrial dynamics machinery, thereby reshaping the mitochondrial network. These structural alterations have functional consequences for cellular metabolism, contributing to metabolic plasticity and enabling tumor cells to switch between glycolytic and oxidative metabolic states in response to environmental stimuli and therapeutic pressures. In this review, we discuss current evidence linking oncogenic MAPK signaling to the control of mitochondrial dynamics in melanoma and examine how these processes contribute to metabolic reprogramming. We further explore how mitochondrial remodeling influences therapeutic response and resistance, particularly in the context of MAPK pathway inhibition. Finally, we highlight mitochondrial dynamics as key regulators of metabolic plasticity and as promising therapeutic targets to improve treatment response in melanoma.
Acute myeloid leukemia (AML) is a biologically heterogeneous hematologic malignancy, and racial disparities in outcomes remain incompletely characterized. This retrospective study analyzed 677 patients diagnosed with AML at Moffitt Cancer Center (2014-2024) to evaluate the impact of race on genomic profiles and clinical outcomes. The cohort comprised 18.6% Black, 19.1% Hispanic, and 62.3% White patients. While ELN 2022 risk groups and most driver mutations were similarly distributed, Black patients exhibited a higher frequency of KRAS mutations (p < 0.05). With a median follow-up of 3.3 years, median overall survival (OS) was 2.2 years for White, 1.5 years for Black, and 2.4 years for Hispanic patients (p = 0.045). Notably, no survival differences existed within favorable or adverse ELN risk categories; however, Black patients with intermediate-risk disease experienced significantly inferior OS compared to White (p = 0.02) and Hispanic patients (p = 0.003). Among those receiving intensive induction, Black patients had significantly worse OS (p ≤ 0.001), while Hispanic patients treated with lower-intensity regimens demonstrated inferior OS compared to White patients (p = 0.01). In multivariable analysis, race was not an independent predictor of OS. Survival was independently driven by prior myeloid malignancy, ELN risk, allogeneic HCT, and mutations in TP53 and IDH2. Regarding race-specific molecular drivers, TP53 and IDH2 mutations were associated with OS in White patients, TP53 in Black patients, and IDH1 in Hispanic patients. These findings suggest that while racial disparities exist in specific clinical subgroups, they are primarily driven by distinct molecular profiles, cytogenetic heterogeneity, and patient-specific clinical factors rather than race alone.