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FCGR2B (+) Macrophages as a Critical Node Linking Ferroptosis and Immunosuppression: A Multiomics Framework for Prognosis and Therapy in High-Grade Serous Ovarian Cancer

Hum Mutat. 2026 Apr 6;2026:8027584. doi: 10.1155/humu/8027584. eCollection 2026.

ABSTRACT

BACKGROUND: High-grade serous ovarian cancer (HGSOC) is characterized by a complex tumor microenvironment and poor prognosis, yet the roles of specific tumor-associated macrophages (TAMs) subpopulations in driving disease progression remain elusive.

METHODS: This study evaluated the prognostic relevance of FCGR2B in HGSOC. Single-cell RNA sequencing identified FCGR2B + TAMs as a distinct macrophage subpopulation with unique transcriptional features. Integrative analyses combining single-cell and bulk differentially expressed genes, macrophage-associated modules, and ferroptosis-related gene sets identified 26 candidate prognostic genes, from which a four-gene signature (CRYAB, PLAUR, EREG, and C5AR1) was derived to construct the prognostic risk model. The model was validated in an independent cohort. Immune infiltration, single-cell trajectory, copy number variation, and drug-gene associations were analyzed to explore the molecular and therapeutic implications of risk stratification.

RESULTS: HGSOC patients classified as high risk exhibited poorer survival outcomes, increased infiltration of M2-like macrophages, elevated expression of immune checkpoints, and enrichment of immune- and ferroptosis-related pathways. Trajectory and copy number variation analyses revealed stage-specific gene expression patterns and amplification-associated regulation. Drug-gene association analyses further suggested that high-risk patients may be more responsive to targeted therapies and proteasome inhibitors, whereas low-risk patients may benefit from conventional chemotherapy.

CONCLUSION: FCGR2B + TAMs are closely linked to HGSOC progression, and the proposed prognostic model based on FCGR2B + TAMs provides predictive value and potential therapeutic insights for patient stratification.

PMID:41953398 | PMC:PMC13054137 | DOI:10.1155/humu/8027584

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Unmasking FCGR2B as a high-grade serous ovarian cancer specific marker of immune suppression and tumor progression through multi-omics mining

Transl Oncol. 2026 Apr 3;67:102748. doi: 10.1016/j.tranon.2026.102748. Online ahead of print.

ABSTRACT

BACKGROUND: Epithelial ovarian cancer (EOC) encompasses five major histological subtypes with marked genetic, immunological, and clinical heterogeneity. While genome-wide association studies (GWAS) have identified subtype-specific risk loci, a critical gap remains in understanding how plasma proteins influence immune-cell traits and contribute to EOC pathogenesis.

METHODS: We integrated subtype-stratified GWAS data from two EOC cohorts with plasma proteomics and immune-cell traits to construct protein-immune-EOC regulatory landscapes using a three-stage Mendelian randomization framework. Single-cell RNA-seq and multiplex immunofluorescence were employed to delineate the cellular distribution and spatial context of causal proteins. Subsequent analyses characterized immune infiltration, macrophage polarization, and clinicopathological associations. Drug-gene correlations were used to identify potential therapeutic targets, and transcriptomic analyses were applied to delineate the underlying transcriptional landscape.

RESULTS: We identified 20 subtype-specific protein-immune-EOC regulatory axes, with FCGR2B emerging as a causal plasma protein in immune regulation and high-grade serous ovarian cancer (HGSOC) progression. FCGR2B was highly expressed in tumor-associated macrophages and was associated with an M2-like polarization phenotype. Functional characterization revealed that FCGR2B was associated with shorter progression-free survival and an immunosuppressive tumor microenvironment. Transcriptomic analyses revealed altered NF-ΞΊB signaling upon FCGR2B knockdown, and drug-response data suggested a potential association between high FCGR2B expression and sensitivity to NF-ΞΊB inhibitors.

CONCLUSIONS: These findings delineate subtype-specific genetically informed protein-immune regulatory landscapes in EOC and identify FCGR2B as a key immunoregulatory and prognostic biomarker in HGSOC, suggesting FCGR2B as a potential therapeutic vulnerability that warrants further investigation.

PMID:41934917 | DOI:10.1016/j.tranon.2026.102748

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LLM-Meta-SR: In-Context Learning for Evolving Selection Operators in Symbolic Regression

arXiv:2505.18602v3 Announce Type: replace-cross Abstract: Large language models (LLMs) have revolutionized algorithm development, yet their application in symbolic regression, where algorithms automatically discover symbolic expressions from data, remains limited. In this paper, we propose a meta-learning framework that enables LLMs to automatically design selection operators for evolutionary symbolic regression algorithms. We first identify two key limitations in existing LLM-based algorithm evolution techniques: lack of semantic guidance and code bloat. The absence of semantic awareness can lead to ineffective exchange of useful code components, while bloat results in unnecessarily complex components; both can hinder evolutionary learning progress or reduce the interpretability of the designed algorithm. To address these issues, we enhance the LLM-based evolution framework for meta-symbolic regression with two key innovations: a complementary, semantics-aware selection operator and bloat control. Additionally, we embed domain knowledge into the prompt, enabling the LLM to generate more effective and contextually relevant selection operators. Our experimental results on symbolic regression benchmarks show that LLMs can devise selection operators that outperform nine expert-designed baselines, achieving state-of-the-art performance. Moreover, the evolved operator can further improve a state-of-the-art symbolic regression algorithm, achieving the best performance among 28 symbolic regression and other machine learning algorithms across 116 regression datasets. This demonstrates that LLMs can exceed expert-level algorithm design for symbolic regression.
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Maximizing carrier extraction in hybrid back-contact silicon solar cells

Nature, Published online: 10 March 2026; doi:10.1038/s41586-026-10351-8

Maximizing carrier extraction in hybrid back-contact silicon solar cells
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Contextualized Privacy Defense for LLM Agents

arXiv:2603.02983v1 Announce Type: cross Abstract: LLM agents increasingly act on users' personal information, yet existing privacy defenses remain limited in both design and adaptability. Most prior approaches rely on static or passive defenses, such as prompting and guarding. These paradigms are insufficient for supporting contextual, proactive privacy decisions in multi-step agent execution. We propose Contextualized Defense Instructing (CDI), a new privacy defense paradigm in which an instructor model generates step-specific, context-aware privacy guidance during execution, proactively shaping actions rather than merely constraining or vetoing them. Crucially, CDI is paired with an experience-driven optimization framework that trains the instructor via reinforcement learning (RL), where we convert failure trajectories with privacy violations into learning environments. We formalize baseline defenses and CDI as distinct intervention points in a canonical agent loop, and compare their privacy-helpfulness trade-offs within a unified simulation framework. Results show that our CDI consistently achieves a better balance between privacy preservation (94.2%) and helpfulness (80.6%) than baselines, with superior robustness to adversarial conditions and generalization.
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LaDiR: Latent Diffusion Enhances LLMs for Text Reasoning

arXiv:2510.04573v5 Announce Type: replace-cross Abstract: Large Language Models (LLMs) demonstrate their reasoning ability through chain-of-thought (CoT) generation. However, LLM's autoregressive decoding may limit the ability to revisit and refine earlier tokens in a holistic manner, which can also lead to inefficient exploration for diverse solutions. In this paper, we propose LaDiR (Latent Diffusion Reasoner), a novel reasoning framework that unifies the expressiveness of continuous latent representation with the iterative refinement capabilities of latent diffusion models for an existing LLM. We first construct a structured latent reasoning space using a Variational Autoencoder (VAE) that encodes text reasoning steps into blocks of thought tokens, preserving semantic information and interpretability while offering compact but expressive representations. Subsequently, we utilize a latent diffusion model that learns to denoise a block of latent thought tokens with a blockwise bidirectional attention mask, enabling longer horizon and iterative refinement with adaptive test-time compute. This design allows efficient parallel generation of diverse reasoning trajectories, allowing the model to plan and revise the reasoning process holistically. We conduct evaluations on a suite of mathematical reasoning and planning benchmarks. Empirical results show that LaDiR consistently improves accuracy, diversity, and interpretability over existing autoregressive, diffusion-based, and latent reasoning methods, revealing a new paradigm for text reasoning with latent diffusion.
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