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HyCARD-Net: A Synergistic Hybrid Intelligence Framework for Cardiovascular Disease Diagnosis

arXiv:2601.17767v1 Announce Type: new Abstract: Cardiovascular disease (CVD) remains the foremost cause of mortality worldwide, underscoring the urgent need for intelligent and data-driven diagnostic tools. Traditional predictive models often struggle to generalize across heterogeneous datasets and complex physiological patterns. To address this, we propose a hybrid ensemble framework that integrates deep learning architectures, Convolutional Neural Networks (CNN) and Long Short-Term Memory (LSTM), with classical machine learning algorithms, including K-Nearest Neighbor (KNN) and Extreme Gradient Boosting (XGB), using an ensemble voting mechanism. This approach combines the representational power of deep networks with the interpretability and efficiency of traditional models. Experiments on two publicly available Kaggle datasets demonstrate that the proposed model achieves superior performance, reaching 82.30 percent accuracy on Dataset I and 97.10 percent on Dataset II, with consistent gains in precision, recall, and F1-score. These findings underscore the robustness and clinical potential of hybrid AI frameworks for predicting cardiovascular disease and facilitating early intervention. Furthermore, this study directly supports the United Nations Sustainable Development Goal 3 (Good Health and Well-being) by promoting early diagnosis, prevention, and management of non-communicable diseases through innovative, data-driven healthcare solutions.

Coronary Artery Segmentation and Vessel-Type Classification in X-Ray Angiography

arXiv:2601.17429v1 Announce Type: cross Abstract: X-ray coronary angiography (XCA) is the clinical reference standard for assessing coronary artery disease, yet quantitative analysis is limited by the difficulty of robust vessel segmentation in routine data. Low contrast, motion, foreshortening, overlap, and catheter confounding degrade segmentation and contribute to domain shift across centers. Reliable segmentation, together with vessel-type labeling, enables vessel-specific coronary analytics and downstream measurements that depend on anatomical localization. From 670 cine sequences (407 subjects), we select a best frame near peak opacification using a low-intensity histogram criterion and apply joint super-resolution and enhancement. We benchmark classical Meijering, Frangi, and Sato vesselness filters under per-image oracle tuning, a single global mean setting, and per-image parameter prediction via Support Vector Regression (SVR). Neural baselines include U-Net, FPN, and a Swin Transformer, trained with coronary-only and merged coronary+catheter supervision. A second stage assigns vessel identity (LAD, LCX, RCA). External evaluation uses the public DCA1 cohort. SVR per-image tuning improves Dice over global means for all classical filters (e.g., Frangi: 0.759 vs. 0.741). Among deep models, FPN attains 0.914+/-0.007 Dice (coronary-only), and merged coronary+catheter labels further improve to 0.931+/-0.006. On DCA1 as a strict external test, Dice drops to 0.798 (coronary-only) and 0.814 (merged), while light in-domain fine-tuning recovers to 0.881+/-0.014 and 0.882+/-0.015. Vessel-type labeling achieves 98.5% accuracy (Dice 0.844) for RCA, 95.4% (0.786) for LAD, and 96.2% (0.794) for LCX. Learned per-image tuning strengthens classical pipelines, while high-resolution FPN models and merged-label supervision improve stability and external transfer with modest adaptation.

"Rebuilding" Statistics in the Age of AI: A Town Hall Discussion on Culture, Infrastructure, and Training

arXiv:2601.17510v1 Announce Type: cross Abstract: This article presents the full, original record of the 2024 Joint Statistical Meetings (JSM) town hall, "Statistics in the Age of AI," which convened leading statisticians to discuss how the field is evolving in response to advances in artificial intelligence, foundation models, large-scale empirical modeling, and data-intensive infrastructures. The town hall was structured around open panel discussion and extensive audience Q&A, with the aim of eliciting candid, experience-driven perspectives rather than formal presentations or prepared statements. This document preserves the extended exchanges among panelists and audience members, with minimal editorial intervention, and organizes the conversation around five recurring questions concerning disciplinary culture and practices, data curation and "data work," engagement with modern empirical modeling, training for large-scale AI applications, and partnerships with key AI stakeholders. By providing an archival record of this discussion, the preprint aims to support transparency, community reflection, and ongoing dialogue about the evolving role of statistics in the data- and AI-centric future.

GenAI-Net: A Generative AI Framework for Automated Biomolecular Network Design

arXiv:2601.17582v1 Announce Type: cross Abstract: Biomolecular networks underpin emerging technologies in synthetic biology-from robust biomanufacturing and metabolic engineering to smart therapeutics and cell-based diagnostics-and also provide a mechanistic language for understanding complex dynamics in natural and ecological systems. Yet designing chemical reaction networks (CRNs) that implement a desired dynamical function remains largely manual: while a proposed network can be checked by simulation, the reverse problem of discovering a network from a behavioral specification is difficult, requiring substantial human insight to navigate a vast space of topologies and kinetic parameters with nonlinear and possibly stochastic dynamics. Here we introduce GenAI-Net, a generative AI framework that automates CRN design by coupling an agent that proposes reactions to simulation-based evaluation defined by a user-specified objective. GenAI-Net efficiently produces novel, topologically diverse solutions across multiple design tasks, including dose responses, complex logic gates, classifiers, oscillators, and robust perfect adaptation in deterministic and stochastic settings (including noise reduction). By turning specifications into families of circuit candidates and reusable motifs, GenAI-Net provides a general route to programmable biomolecular circuit design and accelerates the translation from desired function to implementable mechanisms.

From Specialist to Generalist: Unlocking SAM's Learning Potential on Unlabeled Medical Images

arXiv:2601.17934v1 Announce Type: cross Abstract: Foundation models like the Segment Anything Model (SAM) show strong generalization, yet adapting them to medical images remains difficult due to domain shift, scarce labels, and the inability of Parameter-Efficient Fine-Tuning (PEFT) to exploit unlabeled data. While conventional models like U-Net excel in semi-supervised medical learning, their potential to assist a PEFT SAM has been largely overlooked. We introduce SC-SAM, a specialist-generalist framework where U-Net provides point-based prompts and pseudo-labels to guide SAM's adaptation, while SAM serves as a powerful generalist supervisor to regularize U-Net. This reciprocal guidance forms a bidirectional co-training loop that allows both models to effectively exploit the unlabeled data. Across prostate MRI and polyp segmentation benchmarks, our method achieves state-of-the-art results, outperforming other existing semi-supervised SAM variants and even medical foundation models like MedSAM, highlighting the value of specialist-generalist cooperation for label-efficient medical image segmentation. Our code is available at https://github.com/vnlvi2k3/SC-SAM.

The Limits of AI Data Transparency Policy: Three Disclosure Fallacies

arXiv:2601.18127v1 Announce Type: cross Abstract: Data transparency has emerged as a rallying cry for addressing concerns about AI: data quality, privacy, and copyright chief among them. Yet while these calls are crucial for accountability, current transparency policies often fall short of their intended aims. Similar to nutrition facts for food, policies aimed at nutrition facts for AI currently suffer from a limited consideration of research on effective disclosures. We offer an institutional perspective and identify three common fallacies in policy implementations of data disclosures for AI. First, many data transparency proposals exhibit a specification gap between the stated goals of data transparency and the actual disclosures necessary to achieve such goals. Second, reform attempts exhibit an enforcement gap between required disclosures on paper and enforcement to ensure compliance in fact. Third, policy proposals manifest an impact gap between disclosed information and meaningful changes in developer practices and public understanding. Informed by the social science on transparency, our analysis identifies affirmative paths for transparency that are effective rather than merely symbolic.

Unheard in the Digital Age: Rethinking AI Bias and Speech Diversity

arXiv:2601.18641v1 Announce Type: cross Abstract: Speech remains one of the most visible yet overlooked vectors of inclusion and exclusion in contemporary society. While fluency is often equated with credibility and competence, individuals with atypical speech patterns are routinely marginalized. Given the current state of the debate, this article focuses on the structural biases that shape perceptions of atypical speech and are now being encoded into artificial intelligence. Automated speech recognition (ASR) systems and voice interfaces, trained predominantly on standardized speech, routinely fail to recognize or respond to diverse voices, compounding digital exclusion. As AI technologies increasingly mediate access to opportunity, the study calls for inclusive technological design, anti-bias training to minimize the impact of discriminatory algorithmic decisions, and enforceable policy reform that explicitly recognize speech diversity as a matter of equity, not merely accessibility. Drawing on interdisciplinary research, the article advocates for a cultural and institutional shift in how we value voice, urging co-created solutions that elevate the rights, representation, and realities of atypical speakers in the digital age. Ultimately, the article reframes speech inclusion as a matter of equity (not accommodation) and advocates for co-created AI systems that reflect the full spectrum of human voices.

Learning temporal embeddings from electronic health records of chronic kidney disease patients

arXiv:2601.18675v1 Announce Type: cross Abstract: We investigate whether temporal embedding models trained on longitudinal electronic health records can learn clinically meaningful representations without compromising predictive performance, and how architectural choices affect embedding quality. Model-guided medicine requires representations that capture disease dynamics while remaining transparent and task agnostic, whereas most clinical prediction models are optimised for a single task. Representation learning facilitates learning embeddings that generalise across downstream tasks, and recurrent architectures are well-suited for modelling temporal structure in observational clinical data. Using the MIMIC-IV dataset, we study patients with chronic kidney disease (CKD) and compare three recurrent architectures: a vanilla LSTM, an attention-augmented LSTM, and a time-aware LSTM (T-LSTM). All models are trained both as embedding models and as direct end-to-end predictors. Embedding quality is evaluated via CKD stage clustering and in-ICU mortality prediction. The T-LSTM produces more structured embeddings, achieving a lower Davies-Bouldin Index (DBI = 9.91) and higher CKD stage classification accuracy (0.74) than the vanilla LSTM (DBI = 15.85, accuracy = 0.63) and attention-augmented LSTM (DBI = 20.72, accuracy = 0.67). For in-ICU mortality prediction, embedding models consistently outperform end-to-end predictors, improving accuracy from 0.72-0.75 to 0.82-0.83, which indicates that learning embeddings as an intermediate step is more effective than direct end-to-end learning.

Trust, Don't Trust, or Flip: Robust Preference-Based Reinforcement Learning with Multi-Expert Feedback

arXiv:2601.18751v1 Announce Type: cross Abstract: Preference-based reinforcement learning (PBRL) offers a promising alternative to explicit reward engineering by learning from pairwise trajectory comparisons. However, real-world preference data often comes from heterogeneous annotators with varying reliability; some accurate, some noisy, and some systematically adversarial. Existing PBRL methods either treat all feedback equally or attempt to filter out unreliable sources, but both approaches fail when faced with adversarial annotators who systematically provide incorrect preferences. We introduce TriTrust-PBRL (TTP), a unified framework that jointly learns a shared reward model and expert-specific trust parameters from multi-expert preference feedback. The key insight is that trust parameters naturally evolve during gradient-based optimization to be positive (trust), near zero (ignore), or negative (flip), enabling the model to automatically invert adversarial preferences and recover useful signal rather than merely discarding corrupted feedback. We provide theoretical analysis establishing identifiability guarantees and detailed gradient analysis that explains how expert separation emerges naturally during training without explicit supervision. Empirically, we evaluate TTP on four diverse domains spanning manipulation tasks (MetaWorld) and locomotion (DM Control) under various corruption scenarios. TTP achieves state-of-the-art robustness, maintaining near-oracle performance under adversarial corruption while standard PBRL methods fail catastrophically. Notably, TTP outperforms existing baselines by successfully learning from mixed expert pools containing both reliable and adversarial annotators, all while requiring no expert features beyond identification indices and integrating seamlessly with existing PBRL pipelines.

Computational Phenomenology of Borderline Personality Disorder: A Comparative Evaluation of LLM-Simulated Expert Personas and Human Clinical Experts

arXiv:2508.19008v2 Announce Type: replace Abstract: Building on a human-led thematic analysis of life-story interviews with inpatients with Borderline Personality Disorder, this study examines the capacity of large language models (OpenAI's GPT, Google's Gemini, and Anthropic's Claude) to support qualitative clinical analysis. The models were evaluated through a mixed procedure. Study A involved blinded and non-blinded expert judges in phenomenology and clinical psychology. Assessments included semantic congruence, Jaccard coefficients for overlap of outputs, multidimensional validity ratings of credibility, coherence, and the substantiveness of results, and their grounding in qualitative data. In Study B, neural methods were used to embed the theme descriptions created by humans and the models in a two-dimensional vector space to provide a computational measure of the difference between human and model semantics and linguistic style. In Study C, complementary non-expert evaluations were conducted to examine the influence of thematic verbosity on the perception of human authorship and content validity. Results of all three studies revealed variable overlap with the human analysis, with models being partly indistinguishable from, and also identifying themes originally omitted by, human researchers. The findings highlight both the variability and potential of AI-augmented thematic qualitative analysis to mitigate human interpretative bias and enhance sensitivity.

MEDIC: Comprehensive Evaluation of Leading Indicators for LLM Safety and Utility in Clinical Applications

arXiv:2409.07314v2 Announce Type: replace-cross Abstract: While Large Language Models (LLMs) achieve superhuman performance on standardized medical licensing exams, these static benchmarks have become saturated and increasingly disconnected from the functional requirements of clinical workflows. To bridge the gap between theoretical capability and verified utility, we introduce MEDIC, a comprehensive evaluation framework establishing leading indicators across various clinical dimensions. Beyond standard question-answering, we assess operational capabilities using deterministic execution protocols and a novel Cross-Examination Framework (CEF), which quantifies information fidelity and hallucination rates without reliance on reference texts. Our evaluation across a heterogeneous task suite exposes critical performance trade-offs: we identify a significant knowledge-execution gap, where proficiency in static retrieval does not predict success in operational tasks such as clinical calculation or SQL generation. Furthermore, we observe a divergence between passive safety (refusal) and active safety (error detection), revealing that models fine-tuned for high refusal rates often fail to reliably audit clinical documentation for factual accuracy. These findings demonstrate that no single architecture dominates across all dimensions, highlighting the necessity of a portfolio approach to clinical model deployment. As part of this investigation, we released a public leaderboard on Hugging Face.\footnote{https://huggingface.co/spaces/m42-health/MEDIC-Benchmark}

Pretrain Value, Not Reward: Decoupled Value Policy Optimization

arXiv:2502.16944v2 Announce Type: replace-cross Abstract: In this paper, we explore how directly pretraining a value model simplifies and stabilizes reinforcement learning from human feedback (RLHF). In reinforcement learning, value estimation is the key to policy optimization, distinct from reward supervision. The value function predicts the \emph{return-to-go} of a partial answer, that is, how promising the partial answer is if it were continued to completion. In RLHF, however, the standard pipeline first pretrains a reward model and then learns a value function online, even though no new reward signals are available once preference data is collected. This makes critic learning redundant, as the process of training a reward model and then deriving a value model is informationally equivalent to directly pretraining a value model. Importantly, this requires no additional supervision, and our value model is trained on exactly the same data used for reward modeling. Building on this insight, we introduce \emph{Decoupled Value Policy Optimization} (DVPO), a framework that pretrains a \emph{Global Value Model} (GVM) offline and freezes it as a universal critic for policy learning. The GVM provides stable, fine-grained credit assignment without critic drift or trajectory sampling. Experiments across MT-Bench, Alpaca-Eval, and Arena-Hard demonstrate that DVPO matches or surpasses state-of-the-art RLHF methods. These results highlight RLHF can be reframed as policy-only optimization guided by a single pretrained value model.

A Comprehensive Survey of Mixture-of-Experts: Algorithms, Theory, and Applications

arXiv:2503.07137v4 Announce Type: replace-cross Abstract: Artificial intelligence (AI) has achieved astonishing successes in many domains, especially with the recent breakthroughs in the development of foundational large models. These large models, leveraging their extensive training data, provide versatile solutions for a wide range of downstream tasks. However, as modern datasets become increasingly diverse and complex, the development of large AI models faces two major challenges: (1) the enormous consumption of computational resources and deployment difficulties, and (2) the difficulty in fitting heterogeneous and complex data, which limits the usability of the models. Mixture of Experts (MoE) models has recently attracted much attention in addressing these challenges, by dynamically selecting and activating the most relevant sub-models to process input data. It has been shown that MoEs can significantly improve model performance and efficiency with fewer resources, particularly excelling in handling large-scale, multimodal data. Given the tremendous potential MoE has demonstrated across various domains, it is urgent to provide a comprehensive summary of recent advancements of MoEs in many important fields. Existing surveys on MoE have their limitations, e.g., being outdated or lacking discussion on certain key areas, and we aim to address these gaps. In this paper, we first introduce the basic design of MoE, including gating functions, expert networks, routing mechanisms, training strategies, and system design. We then explore the algorithm design of MoE in important machine learning paradigms such as continual learning, meta-learning, multi-task learning, and reinforcement learning. Additionally, we summarize theoretical studies aimed at understanding MoE and review its applications in computer vision and natural language processing. Finally, we discuss promising future research directions.

Multimodal Cancer Modeling in the Age of Foundation Model Embeddings

arXiv:2505.07683v4 Announce Type: replace-cross Abstract: The Cancer Genome Atlas (TCGA) has enabled novel discoveries and served as a large-scale reference dataset in cancer through its harmonized genomics, clinical, and imaging data. Numerous prior studies have developed bespoke deep learning models over TCGA for tasks such as cancer survival prediction. A modern paradigm in biomedical deep learning is the development of foundation models (FMs) to derive feature embeddings agnostic to a specific modeling task. Biomedical text especially has seen growing development of FMs. While TCGA contains free-text data as pathology reports, these have been historically underutilized. Here, we investigate the ability to train classical machine learning models over multimodal, zero-shot FM embeddings of cancer data. We demonstrate the ease and additive effect of multimodal fusion, outperforming unimodal models. Further, we show the benefit of including pathology report text and rigorously evaluate the effect of model-based text summarization and hallucination. Overall, we propose an embedding-centric approach to multimodal cancer modeling.

uPVC-Net: A Universal Premature Ventricular Contraction Detection Deep Learning Algorithm

arXiv:2506.11238v2 Announce Type: replace-cross Abstract: Introduction: Premature Ventricular Contractions (PVCs) are common cardiac arrhythmias originating from the ventricles. Accurate detection remains challenging due to variability in electrocardiogram (ECG) waveforms caused by differences in lead placement, recording conditions, and population demographics. Methods: We developed uPVC-Net, a universal deep learning model to detect PVCs from any single-lead ECG recordings. The model is developed on four independent ECG datasets comprising a total of 8.3 million beats collected from Holter monitors and a modern wearable ECG patch. uPVC-Net employs a custom architecture and a multi-source, multi-lead training strategy. For each experiment, one dataset is held out to evaluate out-of-distribution (OOD) generalization. Results: uPVC-Net achieved an AUC between 97.8% and 99.1% on the held-out datasets. Notably, performance on wearable single-lead ECG data reached an AUC of 99.1%. Conclusion: uPVC-Net exhibits strong generalization across diverse lead configurations and populations, highlighting its potential for robust, real-world clinical deployment.

On the Fundamental Limits of LLMs at Scale

arXiv:2511.12869v2 Announce Type: replace-cross Abstract: Large Language Models (LLMs) have benefited enormously from scaling, yet these gains are bounded by five fundamental limitations: (1) hallucination, (2) context compression, (3) reasoning degradation, (4) retrieval fragility, and (5) multimodal misalignment. While existing surveys describe these phenomena empirically, they lack a rigorous theoretical synthesis connecting them to the foundational limits of computation, information, and learning. This work closes that gap by presenting a unified, proof-informed framework that formalizes the innate theoretical ceilings of LLM scaling. First, computability and uncomputability imply an irreducible residue of error: for any computably enumerable model family, diagonalization guarantees inputs on which some model must fail, and undecidable queries (e.g., halting-style tasks) induce infinite failure sets for all computable predictors. Second, information-theoretic and statistical constraints bound attainable accuracy even on decidable tasks, finite description length enforces compression error, and long-tail factual knowledge requires prohibitive sample complexity. Third, geometric and computational effects compress long contexts far below their nominal size due to positional under-training, encoding attenuation, and softmax crowding. We further show how likelihood-based training favors pattern completion over inference, how retrieval under token limits suffers from semantic drift and coupling noise, and how multimodal scaling inherits shallow cross-modal alignment. Across sections, we pair theorems and empirical evidence to outline where scaling helps, where it saturates, and where it cannot progress, providing both theoretical foundations and practical mitigation paths like bounded-oracle retrieval, positional curricula, and sparse or hierarchical attention.

Empowering LLMs for Structure-Based Drug Design via Exploration-Augmented Latent Inference

arXiv:2601.15333v2 Announce Type: replace-cross Abstract: Large Language Models (LLMs) possess strong representation and reasoning capabilities, but their application to structure-based drug design (SBDD) is limited by insufficient understanding of protein structures and unpredictable molecular generation. To address these challenges, we propose Exploration-Augmented Latent Inference for LLMs (ELILLM), a framework that reinterprets the LLM generation process as an encoding, latent space exploration, and decoding workflow. ELILLM explicitly explores portions of the design problem beyond the model's current knowledge while using a decoding module to handle familiar regions, generating chemically valid and synthetically reasonable molecules. In our implementation, Bayesian optimization guides the systematic exploration of latent embeddings, and a position-aware surrogate model efficiently predicts binding affinity distributions to inform the search. Knowledge-guided decoding further reduces randomness and effectively imposes chemical validity constraints. We demonstrate ELILLM on the CrossDocked2020 benchmark, showing strong controlled exploration and high binding affinity scores compared with seven baseline methods. These results demonstrate that ELILLM can effectively enhance LLMs capabilities for SBDD.

Multimodal digital biopsy for preoperative prediction of occult peritoneal metastasis in gastric cancer

npj Digital Medicine, Published online: 26 January 2026; doi:10.1038/s41746-025-02268-9

Multimodal digital biopsy for preoperative prediction of occult peritoneal metastasis in gastric cancer

Feasibility, Acceptability, and Perspectives Regarding the Use of Activity Tracking Wearable Devices Among Home Health Aides: Mixed Methods Study

Background: Home health aides and attendants (HHAs) provide in-home care to the growing population of older adults who want to age in place. Despite their vital role in patient care, HHAs are an underserved and vulnerable population of health care professionals who often experience poor health themselves. Activity tracking devices offer a promising way to improve HHAs’ health-related awareness and promote health behavior change, particularly regarding physical activity and sleep quality, 2 areas in which the workforce struggles. Objective: This study aimed to understand how feasible it is for HHAs to use activity tracking devices and assess their perceptions of such devices for improving their health. Specifically, we conducted (1) a field study to assess the use, feasibility, and acceptability of these devices among HHAs and (2) a qualitative study to understand HHAs’ perspectives on and reactions to activity trackers on and off the job. Methods: We partnered with the 1199 Service Employees International Union Training and Employment Fund to conduct a field study with home care agency–employed HHAs working in New York City, New York. Participants wore activity tracking devices for 4 weeks that collected data on physical activity and sleep. The HHAs were subsequently interviewed on their experiences with and attitudes toward the devices and asked to reflect on personalized visualizations of their data to prompt them to think aloud. Quantitative data were analyzed using descriptive statistics. Qualitative data were analyzed using grounded theory. Results: A total of 17 HHAs participated; their mean age was 48.7 (SD 12.2) years, 15 (88%) were women, 11 (65%) identified as Black, 5 (29%) identified as Hispanic or Latinx, and they had worked as HHAs for a mean of 11.7 (SD 7.5) years. In total, 94% (n=16) of the HHAs wore their activity trackers for the full 28-day study period. Participants took a mean of 10,230 (SD 3586) daily steps during the study period and slept for a mean of 6.27 (SD 0.58) hours per night. Overall, 4 key themes emerged: (1) activity tracking devices enhanced participants’ health awareness by providing empirical data for self-reflection; (2) this increased awareness led to positive behavior changes, including setting and achieving health-related goals; (3) HHAs believed that these devices could improve not only their own health but also that of their patients through positive behavior changes; and (4) despite this optimism, participants emphasized that their ability to modify sleep and activity patterns was constrained by social and occupational determinants, with sleep improvements being particularly challenging. Conclusions: Our findings suggest that appropriately designed personal tracking interventions could offer a promising approach to supporting positive health-related changes in this historically overlooked workforce, potentially improving their well-being and the quality of care they provide to their patients.

Multi-Omics and Functional Analyses Identify let-7b-3p as a Negative Regulator of EMT in Lung Adenocarcinoma

J Biochem Mol Toxicol. 2026 Feb;40(2):e70700. doi: 10.1002/jbt.70700.

ABSTRACT

Lung adenocarcinoma (LUAD) is the most common subtype of non-small cell lung cancer (NSCLC), and its malignant progression involves complex molecular mechanisms. While microRNAs (miRNAs) play a crucial regulatory role in LUAD development, their specific mechanisms remain unclear. This study used bioinformatics analysis to identify key miRNA-mRNA interaction axes in LUAD, revealing that let-7b-3p was significantly downregulated. Functional analyses demonstrated that let-7b-3p regulates LUAD cell proliferation, migration, and invasion by targeting High Mobility Group AT-Hook 2 (HMGA2) and Lin-28 Homolog A (LIN28A). Dual-luciferase reporter assays confirmed that let-7b-3p directly binds to HMGA2 and LIN28A, suppressing their expression. Furthermore, Western blot and immunofluorescence (IF) assays showed that let-7b-3p inhibits the Wnt/TGF-β signaling pathway and epithelial-mesenchymal transition (EMT) via the HMGA2-LIN28A axis. In vivo, experiments using a nude mouse model further demonstrated that let-7b-3p overexpression significantly suppressed LUAD tumor growth and lung metastasis while reducing the expression of EMT-related molecules. Importantly, this study is the first to reveal the inhibitory role of let-7b-3p in LUAD through the HMGA2-LIN28A axis in regulating the Wnt/TGF-β signaling pathway and EMT. These findings highlight the originality of this work and underscore the potential clinical translational value of targeting let-7b-3p or the HMGA2-LIN28A axis as novel therapeutic strategies for LUAD.

PMID:41586577 | DOI:10.1002/jbt.70700

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