Normal view
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cs.AI, q-bio.NC updates on arXiv.org
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Beyond Static Vision: Scene Dynamic Field Unlocks Intuitive Physics Understanding in Multi-modal Large Language Models
arXiv:2604.03302v1 Announce Type: cross Abstract: While Multimodal Large Language Models (MLLMs) have demonstrated impressive capabilities in image and video understanding, their ability to comprehend the physical world has become an increasingly important research focus. Despite their improvements, current MLLMs struggle significantly with high-level physics reasoning. In this work, we investigate the first step of physical reasoning, i.e., intuitive physics understanding, revealing substantia
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cs.AI, q-bio.NC updates on arXiv.org
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DP-OPD: Differentially Private On-Policy Distillation for Language Models
arXiv:2604.04461v1 Announce Type: cross Abstract: Large language models (LLMs) are increasingly adapted to proprietary and domain-specific corpora that contain sensitive information, creating a tension between formal privacy guarantees and efficient deployment through model compression. Differential privacy (DP), typically enforced via DP-SGD, provides record-level protection but often incurs substantial utility loss in autoregressive generation, where optimization noise can amplify exposure bi
DP-OPD: Differentially Private On-Policy Distillation for Language Models
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cs.AI, q-bio.NC updates on arXiv.org
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Parallel Universes, Parallel Languages: A Comprehensive Study on LLM-based Multilingual Counterfactual Example Generation
arXiv:2601.00263v2 Announce Type: replace-cross Abstract: Counterfactuals refer to minimally edited inputs that cause a model's prediction to change, serving as a promising approach to explaining the model's behavior. Large language models (LLMs) excel at generating English counterfactuals and demonstrate multilingual proficiency. However, their effectiveness in generating multilingual counterfactuals remains unclear. To this end, we conduct a comprehensive study on multilingual counterfactuals
Parallel Universes, Parallel Languages: A Comprehensive Study on LLM-based Multilingual Counterfactual Example Generation
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(Multiomics OR Omics) AND (Lung OR gastric OR Hepatocellular)
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Decoding macrophage heterogeneity in the pulmonary fibrosis lung cancer transition
Front Immunol. 2026 Mar 20;17:1787094. doi: 10.3389/fimmu.2026.1787094. eCollection 2026.ABSTRACTPulmonary fibrosis (PF) significantly increases the risk of lung cancer (LC), but the mechanisms underlying this transition remain unclear. This overview positions macrophage heterogeneity as a central node within the PF-LC continuum. First, we describe important subpopulations of profibrotic and pro-tumor macrophages, including SPP1+, MERTK+, TREM2+, and MARCO+ cells, using high-resolution spatial a
Decoding macrophage heterogeneity in the pulmonary fibrosis lung cancer transition
Front Immunol. 2026 Mar 20;17:1787094. doi: 10.3389/fimmu.2026.1787094. eCollection 2026.
ABSTRACT
Pulmonary fibrosis (PF) significantly increases the risk of lung cancer (LC), but the mechanisms underlying this transition remain unclear. This overview positions macrophage heterogeneity as a central node within the PF-LC continuum. First, we describe important subpopulations of profibrotic and pro-tumor macrophages, including SPP1+, MERTK+, TREM2+, and MARCO+ cells, using high-resolution spatial and single-cell omics technologies. Next, we analyze the fundamental mechanisms that determine their function: the fibrotic microenvironment (e.g., extracellular matrix stiffness, hypoxia) induces profound metabolic reprogramming (e.g., Warburg effect, lipid peroxidation) and stabilizes epigenetic memory (e.g., DNA methylation, histone modifications), locking them into a pathogenic state. This reprogramming occurs through two main pathways: (1) metabolic reprogramming, characterized by aerobic glycolytic conversion and dysregulated lipid metabolism, which stimulates both pathogenic functions and suppression of T cell activity; (2) Epigenetic modifications, including stabilized alterations in DNA methylation, histone modifications, and superactivator patterns, which maintain cells in a tumor-promoting phenotype. As central nodes of communication, these macrophages interact pathologically with fibroblasts and epithelial cells through secreted factors and extracellular vesicles, forming self-reinforcing feedback loops that promote disease progression. We are studying the crucial role of new technologies, particularly multi-omic spatial models and high-precision organoids, in fostering mechanistic discoveries. These discoveries pave the way for new macrophage-focused therapeutic strategies, including the precise stratification of patients using biomarkers from liquid biopsies (such as soluble SPP1 and MARCO) and the development of targeted drug delivery systems for the selective modulation of macrophage function, thus establishing a new paradigm for therapeutic interventions in pulmonary fibrosis with concomitant lung cancer.
PMID:41939908 | PMC:PMC13046558 | DOI:10.3389/fimmu.2026.1787094
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Omics In Lung
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Decoding macrophage heterogeneity in the pulmonary fibrosis lung cancer transition
Front Immunol. 2026 Mar 20;17:1787094. doi: 10.3389/fimmu.2026.1787094. eCollection 2026.ABSTRACTPulmonary fibrosis (PF) significantly increases the risk of lung cancer (LC), but the mechanisms underlying this transition remain unclear. This overview positions macrophage heterogeneity as a central node within the PF-LC continuum. First, we describe important subpopulations of profibrotic and pro-tumor macrophages, including SPP1+, MERTK+, TREM2+, and MARCO+ cells, using high-resolution spatial a
Decoding macrophage heterogeneity in the pulmonary fibrosis lung cancer transition
Front Immunol. 2026 Mar 20;17:1787094. doi: 10.3389/fimmu.2026.1787094. eCollection 2026.
ABSTRACT
Pulmonary fibrosis (PF) significantly increases the risk of lung cancer (LC), but the mechanisms underlying this transition remain unclear. This overview positions macrophage heterogeneity as a central node within the PF-LC continuum. First, we describe important subpopulations of profibrotic and pro-tumor macrophages, including SPP1+, MERTK+, TREM2+, and MARCO+ cells, using high-resolution spatial and single-cell omics technologies. Next, we analyze the fundamental mechanisms that determine their function: the fibrotic microenvironment (e.g., extracellular matrix stiffness, hypoxia) induces profound metabolic reprogramming (e.g., Warburg effect, lipid peroxidation) and stabilizes epigenetic memory (e.g., DNA methylation, histone modifications), locking them into a pathogenic state. This reprogramming occurs through two main pathways: (1) metabolic reprogramming, characterized by aerobic glycolytic conversion and dysregulated lipid metabolism, which stimulates both pathogenic functions and suppression of T cell activity; (2) Epigenetic modifications, including stabilized alterations in DNA methylation, histone modifications, and superactivator patterns, which maintain cells in a tumor-promoting phenotype. As central nodes of communication, these macrophages interact pathologically with fibroblasts and epithelial cells through secreted factors and extracellular vesicles, forming self-reinforcing feedback loops that promote disease progression. We are studying the crucial role of new technologies, particularly multi-omic spatial models and high-precision organoids, in fostering mechanistic discoveries. These discoveries pave the way for new macrophage-focused therapeutic strategies, including the precise stratification of patients using biomarkers from liquid biopsies (such as soluble SPP1 and MARCO) and the development of targeted drug delivery systems for the selective modulation of macrophage function, thus establishing a new paradigm for therapeutic interventions in pulmonary fibrosis with concomitant lung cancer.
PMID:41939908 | PMC:PMC13046558 | DOI:10.3389/fimmu.2026.1787094
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Cell
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Functional RNA splitting drove the evolutionary emergence of type V CRISPR-Cas systems from transposons
(Cell 188, 6283–6300.e1–e10; October 30, 2025)
Functional RNA splitting drove the evolutionary emergence of type V CRISPR-Cas systems from transposons
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Cell
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Restoring circadian rhythms in the hypothalamic paraventricular nucleus reverses aging biomarkers and extends lifespan in male mice
Enhancing circadian amplitude in mouse hypothalamic paraventricular nucleus neurons by 3′-deoxyadenosine treatment alleviates age-related pathologies and extends lifespan.
Restoring circadian rhythms in the hypothalamic paraventricular nucleus reverses aging biomarkers and extends lifespan in male mice
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Nature - Issue - nature.com science feeds
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Structure of the mouse cytoplasmic lattice
Nature, Published online: 31 March 2026; doi:10.1038/s41586-026-10442-6Structure of the mouse cytoplasmic lattice
Structure of the mouse cytoplasmic lattice
Nature, Published online: 31 March 2026; doi:10.1038/s41586-026-10442-6
Structure of the mouse cytoplasmic lattice-
(Multiomics OR Omics) AND (Lung OR gastric OR Hepatocellular)
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Multi-Omics Characterization of Lactate-Associated Molecular Subtypes in Lung Cancer Suggests a Role for DKK1 in Lactate-Linked Migration, Invasion, and Lactylation Programs
Cancers (Basel). 2026 Feb 25;18(5):735. doi: 10.3390/cancers18050735.ABSTRACTBACKGROUND: Lactate accumulation is increasingly recognized as a feature of tumor metabolic reprogramming that can coincide with immune dysregulation and aggressive phenotypes. The prognostic and immunologic relevance of lactate-associated heterogeneity in lung cancer remains to be clarified.METHODS: We curated lactate-related genes and identified prognostic candidates in lung cancer cohorts. Consensus clustering was ap
Multi-Omics Characterization of Lactate-Associated Molecular Subtypes in Lung Cancer Suggests a Role for DKK1 in Lactate-Linked Migration, Invasion, and Lactylation Programs
Cancers (Basel). 2026 Feb 25;18(5):735. doi: 10.3390/cancers18050735.
ABSTRACT
BACKGROUND: Lactate accumulation is increasingly recognized as a feature of tumor metabolic reprogramming that can coincide with immune dysregulation and aggressive phenotypes. The prognostic and immunologic relevance of lactate-associated heterogeneity in lung cancer remains to be clarified.
METHODS: We curated lactate-related genes and identified prognostic candidates in lung cancer cohorts. Consensus clustering was applied to define lactate-associated molecular subtypes, followed by characterization of survival and tumor microenvironment features. A LASSO-based gene signature was developed to generate an individual-level risk score and an integrated nomogram. Multi-omics analyses were used to evaluate concordance between transcriptomic and proteomic alterations. Single-cell transcriptomic data were analyzed to explore cellular heterogeneity in lactate-related programs. In vitro assays evaluated the response of candidate genes to lactate exposure and assessed cell migration and invasion under proliferation-inhibited conditions after genetic perturbation.
RESULTS: Two lactate-associated molecular subtypes were identified with distinct overall survival and divergent immune microenvironment features. Subtype 1 was associated with better outcomes and a more immune-inflamed profile, whereas Subtype 2 was associated with poorer outcomes and a myeloid-enriched, immunosuppressive contexture. Pathway analyses indicated subtype-associated differences in extracellular matrix-related processes and apoptosis-associated signaling. We developed an 11-gene prognostic signature and nomogram that stratified patients by risk across TCGA and GEO cohorts. Multi-omics integration highlighted ANLN, FGA, and DKK1 as consistently dysregulated at both transcript and protein levels. Among these candidates, DKK1 showed lactate-responsive induction in vitro. DKK1 perturbation altered lactate-enhanced migratory and invasive phenotypes and was accompanied by changes in intracellular lactate levels and global protein lactylation, supporting a potential feedforward relationship between lactate exposure, DKK1 expression, and lactylation.
CONCLUSIONS: This study characterizes lactate-associated molecular heterogeneity in lung cancer and provides a lactate-related subtype framework and prognostic risk model for patient stratification. The findings nominate DKK1 as a lactate-responsive candidate linked to migration/invasion phenotypes and lactate/lactylation changes in vitro.
PMID:41827671 | PMC:PMC12985219 | DOI:10.3390/cancers18050735
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Omics In Lung
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Multi-Omics Characterization of Lactate-Associated Molecular Subtypes in Lung Cancer Suggests a Role for DKK1 in Lactate-Linked Migration, Invasion, and Lactylation Programs
Cancers (Basel). 2026 Feb 25;18(5):735. doi: 10.3390/cancers18050735.ABSTRACTBACKGROUND: Lactate accumulation is increasingly recognized as a feature of tumor metabolic reprogramming that can coincide with immune dysregulation and aggressive phenotypes. The prognostic and immunologic relevance of lactate-associated heterogeneity in lung cancer remains to be clarified.METHODS: We curated lactate-related genes and identified prognostic candidates in lung cancer cohorts. Consensus clustering was ap
Multi-Omics Characterization of Lactate-Associated Molecular Subtypes in Lung Cancer Suggests a Role for DKK1 in Lactate-Linked Migration, Invasion, and Lactylation Programs
Cancers (Basel). 2026 Feb 25;18(5):735. doi: 10.3390/cancers18050735.
ABSTRACT
BACKGROUND: Lactate accumulation is increasingly recognized as a feature of tumor metabolic reprogramming that can coincide with immune dysregulation and aggressive phenotypes. The prognostic and immunologic relevance of lactate-associated heterogeneity in lung cancer remains to be clarified.
METHODS: We curated lactate-related genes and identified prognostic candidates in lung cancer cohorts. Consensus clustering was applied to define lactate-associated molecular subtypes, followed by characterization of survival and tumor microenvironment features. A LASSO-based gene signature was developed to generate an individual-level risk score and an integrated nomogram. Multi-omics analyses were used to evaluate concordance between transcriptomic and proteomic alterations. Single-cell transcriptomic data were analyzed to explore cellular heterogeneity in lactate-related programs. In vitro assays evaluated the response of candidate genes to lactate exposure and assessed cell migration and invasion under proliferation-inhibited conditions after genetic perturbation.
RESULTS: Two lactate-associated molecular subtypes were identified with distinct overall survival and divergent immune microenvironment features. Subtype 1 was associated with better outcomes and a more immune-inflamed profile, whereas Subtype 2 was associated with poorer outcomes and a myeloid-enriched, immunosuppressive contexture. Pathway analyses indicated subtype-associated differences in extracellular matrix-related processes and apoptosis-associated signaling. We developed an 11-gene prognostic signature and nomogram that stratified patients by risk across TCGA and GEO cohorts. Multi-omics integration highlighted ANLN, FGA, and DKK1 as consistently dysregulated at both transcript and protein levels. Among these candidates, DKK1 showed lactate-responsive induction in vitro. DKK1 perturbation altered lactate-enhanced migratory and invasive phenotypes and was accompanied by changes in intracellular lactate levels and global protein lactylation, supporting a potential feedforward relationship between lactate exposure, DKK1 expression, and lactylation.
CONCLUSIONS: This study characterizes lactate-associated molecular heterogeneity in lung cancer and provides a lactate-related subtype framework and prognostic risk model for patient stratification. The findings nominate DKK1 as a lactate-responsive candidate linked to migration/invasion phenotypes and lactate/lactylation changes in vitro.
PMID:41827671 | PMC:PMC12985219 | DOI:10.3390/cancers18050735
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Omics in Gastric
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Multi-omics investigation of benzo[a]pyrene in gastric cancer: comprehensive network toxicology, machine learning and molecular docking approaches
Mol Divers. 2026 Mar 12. doi: 10.1007/s11030-026-11508-3. Online ahead of print.ABSTRACTGastric cancer (GC) risk is shaped by environmental exposures such as benzo[a]pyrene (BaP). Here, we systematically identified BaP-toxicological targets and dissected their contribution to GC development. BaP-related targets were independently predicted with stringent filters from ChEMBL, Similarity Ensemble Approach (SEA) and PharmMapper databases, while GC-related targets were mined from the Comparative Tox
Multi-omics investigation of benzo[a]pyrene in gastric cancer: comprehensive network toxicology, machine learning and molecular docking approaches
Mol Divers. 2026 Mar 12. doi: 10.1007/s11030-026-11508-3. Online ahead of print.
ABSTRACT
Gastric cancer (GC) risk is shaped by environmental exposures such as benzo[a]pyrene (BaP). Here, we systematically identified BaP-toxicological targets and dissected their contribution to GC development. BaP-related targets were independently predicted with stringent filters from ChEMBL, Similarity Ensemble Approach (SEA) and PharmMapper databases, while GC-related targets were mined from the Comparative Toxicogenomics Database (CTD), GeneCards and OMIM databases. Overlapping targets were subjected to protein-protein interaction (PPI) network construction, functional enrichment analysis and molecular docking. We then integrated multi-omics data using ten clustering algorithms to identify the consensus GC subtypes, which were subsequently employed 101 machine learning combinations to develop a consensus benzo[a]pyrene-related signature (CBRS) for GC patients. As a result, we identified seven hub toxicological targets: ALB, HSP90AA1, ESR1, INS, TP53, TNF, and EGFR, underscoring their potential central roles in BaP-driven GC pathogenesis. These targets are enriched in the MAPK, Lipid and atherosclerosis, and PI3K-Akt signaling pathway. The BaP-toxicological classifiers and the CBRS prognostic model could provide useful support for risk stratification and inform personalized therapeutic strategies for GC patients. Molecular docking results suggest that BaP exhibits relatively strong binding affinity with these key toxicological targets, potentially implicating their involvement in BaP-induced gastric cancer toxicity. Therefore, this study integrates multi-dimensional omics data with advanced machine learning algorithms to establish a comprehensive analytical framework for the toxicological effects of between BaP and GC, which transcends the limitations of traditional analyses and offers unprecedented insights and evidence chains for elucidating the pathogenesis of GC.
PMID:41817952 | DOI:10.1007/s11030-026-11508-3
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Cell Death Discovery nature.com science feeds
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CSF1R T567M mutation induces microglial dysfunction and synaptic impairment in patient iPSC-derived cerebral organoids of CSF1R-related disorder
Cell Death Discovery, Published online: 12 March 2026; doi:10.1038/s41420-026-02995-2CSF1R T567M mutation induces microglial dysfunction and synaptic impairment in patient iPSC-derived cerebral organoids of CSF1R-related disorder
CSF1R T567M mutation induces microglial dysfunction and synaptic impairment in patient iPSC-derived cerebral organoids of CSF1R-related disorder
Cell Death Discovery, Published online: 12 March 2026; doi:10.1038/s41420-026-02995-2
CSF1R T567M mutation induces microglial dysfunction and synaptic impairment in patient iPSC-derived cerebral organoids of CSF1R-related disorder-
Omics in Hepatocellular
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Regulatory mechanisms of ALKBH5/CIITA axis in the synergistic modulation of hepatocellular carcinoma radiotherapy and immunotherapy
Genes Immun. 2026 Mar 10. doi: 10.1038/s41435-026-00382-6. Online ahead of print.ABSTRACTThe prognosis for hepatocellular carcinoma remains grim. Combining radiotherapy with immune checkpoint blockade (ICB) has shown potential to enhance therapeutic outcomes, yet there is a pressing need for further advancements. Our previous research demonstrated that this combined approach suppresses ALKBH5 gene expression and increases m6A modification levels in hepatocellular carcinoma tissues. High-throughp
Regulatory mechanisms of ALKBH5/CIITA axis in the synergistic modulation of hepatocellular carcinoma radiotherapy and immunotherapy
Genes Immun. 2026 Mar 10. doi: 10.1038/s41435-026-00382-6. Online ahead of print.
ABSTRACT
The prognosis for hepatocellular carcinoma remains grim. Combining radiotherapy with immune checkpoint blockade (ICB) has shown potential to enhance therapeutic outcomes, yet there is a pressing need for further advancements. Our previous research demonstrated that this combined approach suppresses ALKBH5 gene expression and increases m6A modification levels in hepatocellular carcinoma tissues. High-throughput sequencing and detailed molecular analysis revealed that inhibiting ALKBH5 amplifies CIITA m6A modifications post-therapy. This modulation triggers MHC II molecule expression in tumors, facilitating the presentation of tumor-associated antigens to CD4 + T lymphocytes and the recruitment of CD8 + T cells for an anti-tumor immune response. Building on these findings, we engineered a CIITA vector with a specific site mutation to confirm that the regulation of CIITA by the combined radiotherapy and immunotherapy is mediated through m6A methylation. Consequently, we established a comprehensive network involving ALKBH5, CIITA, MHC II, and CD4+ and CD8 + T cells. To elucidate the role and underlying molecular mechanisms of this combined therapy in reshaping the tumor immune microenvironment for hepatocellular carcinoma, we employed multi-omics approaches across in vitro, animal model, and clinical multi-dimensional studies, offering novel insights for enhancing treatment efficacy.
PMID:41807814 | DOI:10.1038/s41435-026-00382-6
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Oncogene - Issue - nature.com science feeds
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Dexamethasone promotes neutrophil ROS-mediated tumor killing through the glucocorticoid receptor
Oncogene, Published online: 06 March 2026; doi:10.1038/s41388-026-03708-wDexamethasone promotes neutrophil ROS-mediated tumor killing through the glucocorticoid receptor
Dexamethasone promotes neutrophil ROS-mediated tumor killing through the glucocorticoid receptor
Oncogene, Published online: 06 March 2026; doi:10.1038/s41388-026-03708-w
Dexamethasone promotes neutrophil ROS-mediated tumor killing through the glucocorticoid receptor-
cs.AI, q-bio.NC updates on arXiv.org
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LifeBench: A Benchmark for Long-Horizon Multi-Source Memory
arXiv:2603.03781v1 Announce Type: new Abstract: Long-term memory is fundamental for personalized agents capable of accumulating knowledge, reasoning over user experiences, and adapting across time. However, existing memory benchmarks primarily target declarative memory, specifically semantic and episodic types, where all information is explicitly presented in dialogues. In contrast, real-world actions are also governed by non-declarative memory, including habitual and procedural types, and need
LifeBench: A Benchmark for Long-Horizon Multi-Source Memory
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cs.AI, q-bio.NC updates on arXiv.org
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StegaFFD: Privacy-Preserving Face Forgery Detection via Fine-Grained Steganographic Domain Lifting
arXiv:2603.02886v1 Announce Type: cross Abstract: Most existing Face Forgery Detection (FFD) models assume access to raw face images. In practice, under a client-server framework, private facial data may be intercepted during transmission or leaked by untrusted servers. Previous privacy protection approaches, such as anonymization, encryption, or distortion, partly mitigate leakage but often introduce severe semantic distortion, making images appear obviously protected. This alerts attackers, p
StegaFFD: Privacy-Preserving Face Forgery Detection via Fine-Grained Steganographic Domain Lifting
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cs.AI, q-bio.NC updates on arXiv.org
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Dynamic Manifold Hopfield Networks for Context-Dependent Associative Memory
arXiv:2506.01303v3 Announce Type: replace-cross Abstract: Neural population activity in cortical and hippocampal circuits can be flexibly reorganized by context, suggesting that cognition relies on dynamic manifolds rather than static representations. However, how such dynamic organization can be realized mechanistically within a unified dynamical system remains unclear. Continuous Hopfield networks provide a classical attractor framework in which neural dynamics follow gradient descent on a fi
Dynamic Manifold Hopfield Networks for Context-Dependent Associative Memory
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cs.AI, q-bio.NC updates on arXiv.org
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DMTrack: Spatio-Temporal Multimodal Tracking via Dual-Adapter
arXiv:2508.01592v2 Announce Type: replace-cross Abstract: In this paper, we explore adapter tuning and introduce a novel dual-adapter architecture for spatio-temporal multimodal tracking, dubbed DMTrack. The key of our DMTrack lies in two simple yet effective modules, including a spatio-temporal modality adapter (STMA) and a progressive modality complementary adapter (PMCA) module. The former, applied to each modality alone, aims to adjust spatio-temporal features extracted from a frozen backbo
DMTrack: Spatio-Temporal Multimodal Tracking via Dual-Adapter
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cs.AI, q-bio.NC updates on arXiv.org
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QIME: Constructing Interpretable Medical Text Embeddings via Ontology-Grounded Questions
arXiv:2603.01690v2 Announce Type: replace-cross Abstract: While dense biomedical embeddings achieve strong performance, their black-box nature limits their utility in clinical decision-making. Recent question-based interpretable embeddings represent text as binary answers to natural-language questions, but these approaches often rely on heuristic or surface-level contrastive signals and overlook specialized domain knowledge. We propose QIME, an ontology-grounded framework for constructing inter
QIME: Constructing Interpretable Medical Text Embeddings via Ontology-Grounded Questions
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cs.AI, q-bio.NC updates on arXiv.org
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Reshaping MOFs text mining with a dynamic multi-agents framework of large language model
arXiv:2504.18880v4 Announce Type: replace Abstract: Accurately identifying the synthesis conditions of metal-organic frameworks (MOFs) is essential for guiding experimental design, yet remains challenging because relevant information in the literature is often scattered, inconsistent, and difficult to interpret. We present MOFh6, a large language model driven system that reads raw articles or crystal codes and converts them into standardized synthesis tables. It links related descriptions acros