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InRTL: Effective Intra-Inter Interaction Learning for Relational Tables

arXiv:2609.12712v1 Announce Type: cross Abstract: Relational table learning has recently emerged as an important research direction for modeling multiple tables connected through primary key-foreign key (PK-FK) relationships. Despite recent advances, a principled modeling framework tailored to this task remains underexplored. In this paper, we propose Intra-Inter Relational Table Learning (InRTL), a unified framework that explicitly models dependencies both within and across relational tables. Specifically, InRTL formalizes two complementary interaction patterns: intra-table interactions, describing associations among rows within the same table, and inter-table interactions, describing dependencies between rows across PK-FK-linked tables. To model these dependencies, we develop a column-aware table encoder to generate initial row representations, followed by Transformer-based self-attention and cross-attention modules for intra-table and inter-table learning, respectively. To further improve scalability, InRTL incorporates linearized attention and heterogeneous graph neural networks to simplify the self-attention and cross-attention operations. Extensive experiments on ten datasets covering 24 real-world tasks demonstrate the effectiveness of our approach. Code is available at https://github.com/W1nterFloW/InRTL.

SimSkill: A Self-Evolving LLM Agent for Skill and Knowledge Accumulation in Traffic Simulation

arXiv:2609.03753v3 Announce Type: replace Abstract: Cumulative culture enables humans to preserve, reuse, and extend knowledge and skills across experiences and generations. Inspired by this principle, we introduce \textit{SimSkill}, a self-evolving agent built around the Simulation of Urban MObility (SUMO) traffic simulator. SimSkill continually identifies capability gaps, generates and solves environment-grounded tasks, verifies solutions through an action--critic loop, and consolidates experience into episodic, procedural, and semantic memory. Through autonomous exploration, it builds a library of reusable skills and knowledge spanning major stages of the traffic-simulation workflow. We evaluate SimSkill on two held-out benchmarks across three backbone LLMs, with each result independently verified. It improves verified success by up to 25 percentage points, and ablations show complementary contributions from procedural and semantic memory. Its benefits remain backbone- and budget-dependent, as memory does not improve every model or uniformly reduce inference cost. More broadly, SimSkill illustrates a natural-language-centered design paradigm for LLM-based agent systems. Its high-level control logic, operating principles, and accumulated knowledge are expressed in natural language, while an LLM integrates them with executable tools and code to realize precise and reproducible execution. All code and experimental data are publicly available at https://github.com/qiliuchn/SimSkill-V1.

MMSDH facilitates ACSL4 propionylation to counteract ferroptosis upon hypoxia and impairs PDAC chemotherapy efficacy

Nature Cancer, Published online: 11 September 2026; doi:10.1038/s43018-026-01236-w

Zheng et al. describe how hypoxia-induced methylmalonate semialdehyde dehydrogenase lactylation promotes acyl-CoA synthetase long-chain family member 4 propionylation and degradation, thereby suppressing ferroptosis induced by chemotherapy, and develop a blocking peptide that increased chemotherapy efficacy in pancreatic ductal adenocarcinoma.

The landscape of peripheral blood RNA modifications and its clinical implications for diagnosis of hepatocellular carcinoma

Cell Commun Signal. 2026 Sep 11;24(1):488. doi: 10.1186/s12964-026-03206-2.

ABSTRACT

BACKGROUND: While over 170 RNA modifications have been identified and implicated in various cancers, their role in hepatocellular carcinoma (HCC) progression is increasingly recognized. Despite this established relevance in tumor biology, the landscape of RNA modifications in the peripheral blood of HCC patients-and their potential diagnostic utility-remains largely unexplored.

METHODS: Peripheral blood samples from patients with HCC, liver cirrhosis (LC), and normal healthy (NH) controls were collected. The abundances of 55 RNA modifications were quantified using liquid chromatography-tandem mass spectrometry (LC-MS/MS) to assess their diagnostic potential for HCC, particularly at early stages. Correlations among these modifications and their associations with clinical parameters were analyzed. Simultaneously, differentially expressed genes, including those encoding RNA-modifying enzymes, were screened in peripheral blood. The biological relevance of the identified signatures was subsequently validated using in vitro co-culture and in vivo syngeneic HCC mouse models.

RESULTS: Compared to the combined non-HCC group (NH and LC), the abundances of 11 RNA modifications were significantly altered in both overall and stage I HCC groups, with N2,N2-dimethylguanosine (m2,2G) emerging as a key component exhibiting the most pronounced dysregulation. A diagnostic model centered on an m2,2G-based modification panel achieved area under the curves (AUCs) of 0.901 and 0.891 for detecting HCC and stage I HCC, respectively, demonstrating promising diagnostic potential. Notably, the incorporation of two upregulated genes in peripheral blood-IFI27 and CCR2-significantly enhanced the model's performance, yielding improved AUCs of 0.972 and 0.968, respectively. Further analysis revealed distinct correlation patterns among RNA modifications, as well as between RNA modifications and clinical laboratory parameters, exhibiting both shared and HCC-specific features that suggest systemic reprogramming of RNA modification network in HCC. This biological relevance was confirmed by elevated m2,2G abundances in human lymphocytes co-cultured with HCC cells and blood from a syngeneic HCC mouse model.

CONCLUSIONS: This study systematically profiled peripheral blood RNA modifications and provided preliminary evidence supporting their potential as diagnostic biomarkers for HCC. By integrating key modifications (m2,2G, m2,2,7G, m6,6A) with two mRNA markers (IFI27 and CCR2), we developed a multi-omics signature that demonstrated promising diagnostic performance, particularly for early-stage HCC.

PMID:42732057 | PMC:PMC13570552 | DOI:10.1186/s12964-026-03206-2

The landscape of peripheral blood RNA modifications and its clinical implications for diagnosis of hepatocellular carcinoma

Cell Commun Signal. 2026 Sep 11;24(1):488. doi: 10.1186/s12964-026-03206-2.

ABSTRACT

BACKGROUND: While over 170 RNA modifications have been identified and implicated in various cancers, their role in hepatocellular carcinoma (HCC) progression is increasingly recognized. Despite this established relevance in tumor biology, the landscape of RNA modifications in the peripheral blood of HCC patients-and their potential diagnostic utility-remains largely unexplored.

METHODS: Peripheral blood samples from patients with HCC, liver cirrhosis (LC), and normal healthy (NH) controls were collected. The abundances of 55 RNA modifications were quantified using liquid chromatography-tandem mass spectrometry (LC-MS/MS) to assess their diagnostic potential for HCC, particularly at early stages. Correlations among these modifications and their associations with clinical parameters were analyzed. Simultaneously, differentially expressed genes, including those encoding RNA-modifying enzymes, were screened in peripheral blood. The biological relevance of the identified signatures was subsequently validated using in vitro co-culture and in vivo syngeneic HCC mouse models.

RESULTS: Compared to the combined non-HCC group (NH and LC), the abundances of 11 RNA modifications were significantly altered in both overall and stage I HCC groups, with N2,N2-dimethylguanosine (m2,2G) emerging as a key component exhibiting the most pronounced dysregulation. A diagnostic model centered on an m2,2G-based modification panel achieved area under the curves (AUCs) of 0.901 and 0.891 for detecting HCC and stage I HCC, respectively, demonstrating promising diagnostic potential. Notably, the incorporation of two upregulated genes in peripheral blood-IFI27 and CCR2-significantly enhanced the model's performance, yielding improved AUCs of 0.972 and 0.968, respectively. Further analysis revealed distinct correlation patterns among RNA modifications, as well as between RNA modifications and clinical laboratory parameters, exhibiting both shared and HCC-specific features that suggest systemic reprogramming of RNA modification network in HCC. This biological relevance was confirmed by elevated m2,2G abundances in human lymphocytes co-cultured with HCC cells and blood from a syngeneic HCC mouse model.

CONCLUSIONS: This study systematically profiled peripheral blood RNA modifications and provided preliminary evidence supporting their potential as diagnostic biomarkers for HCC. By integrating key modifications (m2,2G, m2,2,7G, m6,6A) with two mRNA markers (IFI27 and CCR2), we developed a multi-omics signature that demonstrated promising diagnostic performance, particularly for early-stage HCC.

PMID:42732057 | PMC:PMC13570552 | DOI:10.1186/s12964-026-03206-2

Joint impact of pathological burden and cognitive resilience on Alzheimer’s disease risk

Nature Medicine, Published online: 11 September 2026; doi:10.1038/s41591-026-04635-9

A 15-year cohort study shows that Alzheimer’s dementia risk is jointly shaped by Alzheimer’s pathology and cognitive resilience, with high resilience linked to lower risk, even under greater pathology.

Intranasal delivery of a vasoactive intestinal peptide-based circRNA vaccine induces systemic and mucosal immunity against RSV in mice

A vasoactive intestinal peptide (VIP)-based protein carrier self-assembles with respiratory syncytial virus circular RNA vaccines for intranasal delivery, inducing systemic antibodies, mucosal IgA, and Th1-biased protection in mice. This platform offers a protein-guided strategy for respiratory mucosal RNA vaccination and broadens the application of VIP in vaccine delivery.

The redox architecture of gestational diabetes mellitus: from cellular stress engine to epigenetic and mitochondrial rewiring

Free Radic Biol Med. 2026 Sep 9;256:441-460. doi: 10.1016/j.freeradbiomed.2026.09.006. Online ahead of print.

ABSTRACT

Gestational diabetes mellitus (GDM) is a common pregnancy complication with a rising global prevalence, posing serious short-term and long-term health threats to both mothers and offspring. This review repositions GDM as a systemic disorder in which oxidative stress acts as a proposed mechanistic hub, linking upstream risk factors to downstream pathophysiology. We first examine how "upstream" factors-including genetic susceptibility, pre-conception status, and environmental exposures-converge to promote a state of pathological redox imbalance. We then examine key mechanistic pathways through which oxidative stress is thought to contribute to systemic insulin resistance and pancreatic β-cell failure, highlighting novel pathways involving intercellular communication via tunneling nanotubes and exosomes. Furthermore, we explore the downstream cascade, where oxidative stress may program maternal accelerated biological aging and multi-organ offspring disease trajectories through nuclear epigenetic programming and mitochondrial dysfunction programming, leaving what has been termed a persistent "metabolic memory". Consequently, this review evaluates emerging strategies that target oxidative stress for early prediction and precision intervention. Early prediction models based on direct redox biomarkers and multi-omics signatures hold potential to shift diagnosis from late-gestation oral glucose tolerance test (OGTT) to first-trimester risk stratification. Current supporting evidence draws from human epidemiological associations, ex vivo placental analyses, and experimental models. However, direct causal and interventional validation in pregnant women remains limited. Integrating targeted redox risk stratification and precision interventions into a life-course clinical framework may help interrupt the intergenerational transmission of metabolic disease initiated by GDM.

PMID:42716407 | DOI:10.1016/j.freeradbiomed.2026.09.006

Targeting peripheral 5-HT2AR enhances antitumor immunity in colorectal cancer

By selectively targeting peripheral 5-HT2AR without inducing psychedelic effects, a non-brain-penetrant agonist boosts antitumor CD8+ T cell immunity and improves immunotherapy responses in preclinical models of colorectal cancer.

Multiomic characterization of malignant pulmonary nodules and development of a methylation-based diagnostic Model

J Transl Med. 2026 Jun 8;24(1):776. doi: 10.1186/s12967-026-08382-w.

ABSTRACT

BACKGROUND: The molecular distinction between benign and malignant pulmonary nodules remains a significant diagnostic challenge. While genomic drivers are well studied, multiomic integration of the epigenetic-transcriptional landscape and its translation into noninvasive tools are lacking.

METHODS: We performed a multiomic characterization (genomic, epigenomic, and transcriptomic) of 158 pulmonary nodules. Unsupervised factor analysis integrated these layers to identify core regulatory axes. A 9-gene cell-free DNA (cfDNA) methylation classifier was developed and validated in blood and tissue cohorts.

RESULTS: Genomic profiling revealed EGFR mutations (exclusive to malignant nodules) and MYC amplification as fundamental initiators of malignancy. Multiomic factor analysis (Factor 1) revealed profound genetic‒epigenetic synergy, in which these alterations dictate a permissive methylome, leading to aberrant epigenetic programming of chromatin accessibility, as well as epigenetic-transcriptional effects: hypomethylation at the promoters of cell cycle genes that augments their expression, and hypermethylation at immune related pathways gene loci that silences their transcription. This effect orchestrates formation of proproliferative (E2F target/G2M checkpoint) and "immune-cold" malignant phenotype, characterized by elevated Treg/CD8+ ratios and fibroblast recruitment. Notably, we observed a gradual accumulation of methylation aberrations along the premalignant-to-invasive continuum (adenocarcinoma in situ [AIS]→minimally invasive adenocarcinoma [MIA]→adenocarcinoma [ADC]), identifying progressive epigenetic dysregulation as a hallmark of tumor aggressiveness. Global methylome remodeling drives ADC progression through hypermethylation-mediated silencing of tumor suppressors (RASA3 and PPARG) and hypomethylation-activated oncogenic axes, specifically the GDF15 axis, which independently predict poor survival in patients with lung ADC in the TCGA cohort. We translated these tissue-derived insights into a 9-gene cfDNA methylation classifier, which achieved exceptional diagnostic accuracy across independent cohorts (training AUC = 1.00; test AUC = 0.93; tissue AUC = 0.96). Rooted in the biological "ground truth" of tissue dysregulation, this classifier functions specifically as a functional readout of the core cell cycle and proliferative pathways, offering a robust, noninvasive tool for the biology-informed risk assessment of pulmonary nodules.

CONCLUSIONS: This study delineates an epigenetic-transcriptional regulatory network that drives nodule malignancy. Our findings provide a robust theoretical foundation and a high-performance liquid biopsy tool for the precise, noninvasive diagnosis of pulmonary nodules.

PMID:42260586 | PMC:PMC13274191 | DOI:10.1186/s12967-026-08382-w

When Does Multi-Agent RL Improve LLM Workflows? Workflow, Scale, and Policy-Sharing Tradeoffs

arXiv:2605.24202v1 Announce Type: new Abstract: Multi-agent LLM workflows route inference through specialized roles to lift end-task accuracy, but jointly training those roles with reinforcement learning is unstable in ways that are poorly understood. We study when end-to-end RL training of multi-agent LLM workflows improves over their base models, comparing Shared-Policy training, where all roles update one policy, with Isolated-Policy training, where each role has its own parameters. Our experimental matrix spans Eval-Opt, Voting, and Orch-Workers workflows, math and code tasks, and three model scales (0.6B, 1.7B, 4B). We find that multi-agent RL usually improves over base models, but gains depend jointly on workflow, task, and scale, not on policy sharing alone. Isolated-Policy tends to reach higher peak accuracy yet more often falls off a terminal accuracy cliff, while Shared-Policy training does not eliminate failure; it redistributes failure into qualitatively different patterns. We then explain the strongest of these patterns through role-level gradient dynamics induced by workflow topology and policy routing: under Isolated-Policy, parallel same-role agents on shared prompts amplify per-role gradients and drive terminal degradation in Voting and Orch-Workers workflows; under Shared-Policy, asymmetric per-step gradient mass causes the shared policy to be captured by the dominant role, producing different failure signatures by task and workflow. Together, the empirical map and its underlying mechanisms show that policy sharing routes training pressure through different channels rather than offering uniform stability, making it a design choice with workflow- and task-conditional tradeoffs.

STREAM: A Data-Centric Framework for Mining High-Value Task-Oriented Dialogues from Streaming Media

arXiv:2605.25162v1 Announce Type: cross Abstract: Large language models for vertical domains are bottlenecked by the scarcity of complex, domain-specific task-oriented dialogues. Existing data acquisition pipelines face a persistent trilemma: expert annotation is expensive, real-world service conversations are constrained by privacy and commercial restrictions, and static corpora quickly become temporally stale. We propose Stream, a data-centric framework that leverages publicly available streaming media (live streams and short videos) to synthesize high-value service dialogues at scale. Stream mines authentic interaction signals from noisy streams and synthesizes conversations by integrating role-grounded persona construction with Conversational Blueprint construction; it further adopts retrieval-augmented generation (RAG) to support knowledge-aware responses. Based on Stream, we release StreamDial, a large-scale multi-domain dataset covering Automotive, Restaurant, and Hotel. StreamDial contains 87,498 dialogue sessions and 1,497,320 turns in total, with an average of 17.11 turns per session and a comparable scale across domains. Each session is organized as a structured quadruplet $\langle P_u, P_a, B, H \rangle$ that pairs dialogue history with explicit user/agent personas and a Conversational Blueprint, capturing realistic service behaviors such as requirement mining, constraint conflicts, negotiation, and recovery. Evaluations with automatic judges and downstream tasks show that StreamDial improves intrinsic dialogue quality over strong baselines, and models trained with StreamDial improve Dialogue State Tracking across backbones; we further report a completed human-evaluation set and encouraging multilingual transfer on Qwen3-8B under a controlled training budget. The data is released in https://github.com/hitxueliang/DialogDataSetBySTREAM.

AutoResearchClaw: Self-Reinforcing Autonomous Research with Human-AI Collaboration

arXiv:2605.20025v2 Announce Type: replace Abstract: Automating scientific discovery requires more than generating papers from ideas. Real research is iterative: hypotheses are challenged from multiple perspectives, experiments fail and inform the next attempt, and lessons accumulate across cycles. Existing autonomous research systems often model this process as a linear pipeline: they rely on single-agent reasoning, stop when execution fails, and do not carry experience across runs. We present AutoResearchClaw, a multi-agent autonomous research pipeline built on five mechanisms: structured multi-agent debate for hypothesis generation and result analysis, a self-healing executor with a \textsc{Pivot}/\textsc{Refine} decision loop that transforms failures into information, verifiable result reporting that prevents fabricated numbers and hallucinated citations, human-in-the-loop collaboration with seven intervention modes spanning full autonomy to step-by-step oversight, and cross-run evolution that converts past mistakes into future safeguards. On ARC-Bench, a 25-topic experiment-stage benchmark, AutoResearchClaw outperforms AI Scientist v2 by 54.7%. A human-in-the-loop ablation across seven intervention modes reveals that precise, targeted collaboration at high-leverage decision points consistently outperforms both full autonomy and exhaustive step-by-step oversight. We position AutoResearchClaw as a research amplifier that augments rather than replaces human scientific judgment. Code is available at https://github.com/aiming-lab/AutoResearchClaw.

BacktestBench: Benchmarking Large Language Models for Automated Quantitative Strategy Backtesting

arXiv:2605.17937v2 Announce Type: replace-cross Abstract: Quantitative backtesting is essential for evaluating trading strategies but remains hampered by high technical barriers and limited scalability. While Large Language Models (LLMs) offer a transformative path to automate this complex, interdisciplinary workflow through advanced code generation, tool usage, and agentic planning, the practical realization is significantly challenged by the current lack of a large-scale benchmark dedicated to automated quantitative backtesting, which hinders progress in this field. To bridge this critical gap, we introduce BacktestBench, the first large-scale benchmark for automated quantitative backtesting. Built from over 6 million real market records, it comprises 18,246 meticulously annotated question-answering pairs across four task categories: metrics calculation, ticker selection, strategy selection, and parameter confirmation. We also propose AutoBacktest, a robust multi-agent baseline that translates natural language strategies into reproducible backtests by coordinating a Summarizer for semantic factor extraction, a Retriever for validated SQL generation, and a Coder for Python backtesting implementation. Our evaluation on 23 mainstream LLMs, complemented by targeted ablations, identifies key factors that influence end-to-end performance and highlights the importance of grounded verification and standardized indicator representations.

A pathogen lncRNA secreted into rice sequesters a host miRNA for virulence

Nature, Published online: 20 May 2026; doi:10.1038/s41586-026-10572-x

A fungal long non-coding RNA from Magnaporthe oryzae translocates into rice cells to sequester a host microRNA that normally represses PKR1, a negative immunity regulator, thereby facilitating infection and revealing a widespread RNA-based pathogen–host interaction mechanism.

Spatial transcriptomic-metabolic features of tumor foci and tumor capsule in microvascular invasion with hepatocellular carcinoma: A spatial multi-omics study

PLoS Med. 2026 May 15;23(5):e1004703. doi: 10.1371/journal.pmed.1004703. eCollection 2026 May.

ABSTRACT

BACKGROUND: Microvascular invasion (MVI) is closely related to the recurrence and metastasis of hepatocellular carcinoma (HCC), but the underlying cellular mechanism remains largely elusive. This study aims to elucidate the regional cellular discrepancy between MVI-positive (MVI+) and MVI-negative (MVI-) HCC by integrating Spatial transcriptomics (ST) and spatial metabolomics (SM).

METHODS AND FINDINGS: ST and SM were performed on six tissue samples from four patients (including 2 MVI+, 2 MVI-, and 2 paratumor tissues), with the integration of 79 public single-cell RNA sequencing datasets of HCC. Patient identity was used as a covariate in the linear equation for regional differentially expressed gene analysis with the ST data. Clinical validation was conducted through multiplex immunofluorescence staining in 79 patients, together with external validation in the cancer genome atlas (TCGA)-liver hepatocellular carcinoma (LIHC) cohort (n = 299) and an independent microarray dataset (n = 62). For cell-type-specific metabolic profiling, spatial transcriptomic-metabolic registration was performed. The functional roles of key metabolites were further validated in vitro using inflammatory cancer-associated fibroblasts (iCAFs) derived from hepatic stellate cells (HSCs) and primary CAFs through co-culture models and various functional assays assessing cell proliferation, migration, and invasion. In the tumor lesion, a malignant STMN1+HMGN2+GPC3+ cell subtype enriched in MVI+ HCC was identified, which exhibited enhanced proliferative activity and was associated with poor prognosis. This finding was further confirmed in a local cohort of 79 patients, where multiplex immunofluorescence staining for the three genes (STMN1, HMGN2, and GPC3) showed significantly higher expression in the MVI+ group than in the MVI- group (p = 0.046). Integrated SM analysis further revealed that this cell population underwent metabolic reprogramming characterized by suppressed glycerolipid metabolism. In the tumor capsule, iCAFs-related genes were downregulated in MVI+ cases, and iCAFs were located distally from the tumor boundary. Spatial metabolite mapping showed a strong correlation between taurine and iCAFs, and functional assays demonstrated that taurine promotes HCC proliferation and migration by suppressing iCAF activity. One limitation of this study is the small sample size of spatial omics data, which hinders a more complete molecular functional analysis of the STMN1+HMGN2+GPC3+ cell subtype and iCAFs in MVI+ HCC. Larger-scale ST cohorts are required to further validate and expand the findings of this study.

CONCLUSIONS: This integrative spatial atlas proposes a hypothesis that there exists a highly proliferative and metabolically reprogrammed malignant cell subtype in the tumor lesion of MVI+ HCC, and that taurine in the tumor capsule modulates iCAF activity to influence tumor progression. The exploratory results provide mechanistic insights into MVI-related HCC progression and offer potential avenues for targeted therapeutic intervention of MVI+ HCC.

PMID:42139279 | PMC:PMC13178920 | DOI:10.1371/journal.pmed.1004703

Integrated radiopathomics nomogram for predicting angiogenic microvascular patterns in NSCLC: a dual-center validation study

Ann Med. 2026 Dec;58(1):2654291. doi: 10.1080/07853890.2026.2654291. Epub 2026 Apr 17.

ABSTRACT

BACKGROUND: To develop and validate an integrated radiopathomics nomogram combining multiphase CT images, H&E-stained slides, and clinicopathological variables for predicting microvascular patterns (MVPs) in non-small cell lung cancer (NSCLC).

METHODS: We retrospectively included consecutive surgically resected NSCLC patients from two centers (n = 258). Patients from center 1 were randomly divided into training and internal validation cohorts, while patients from center 2 formed external validation cohort. CD34-immunohistochemistry was used as the reference standard for MVPs to classify patients into non-angiogenic alveolar (NAA) and non-NAA groups. Radiomics and pathomics features were extracted to construct single-phase radiomics, combined radiomics, and pathomics models. Rad-score and Path-score were derived from combined radiomics and pathomics models, respectively. Rad-score, Path-score, and clinicopathological independent predictors were integrated to develop a nomogram. Model performance was assessed by area under the curve (AUC), calibration curve, decision curve analysis (DCA), and DeLong test.

RESULTS: On multivariable analysis, histological grade was an independent predictor of NAA MVP. Combined radiomics model for predicting MVPs achieved AUCs of 0.863, 0.856, and 0.849 in training, internal validation, and external validation cohorts, showing better performance than single-phase models. Pathomics model yielded AUCs of 0.878, 0.860, and 0.833, however, its specificity markedly decreased in validation cohorts. Nomogram model achieved the superior performance across all cohorts, with AUCs of 0.911, 0.903, and 0.901, outperforming single-modality models (DeLong test: all p < 0.05).

CONCLUSION: The nomogram demonstrated high accuracy and robustness in predicting MVPs in NSCLC, offering a promising tool for characterizing the tumor microenvironment and supporting individualized treatment.

PMID:41992828 | DOI:10.1080/07853890.2026.2654291

Pan-neurodegeneration proteomics reveals disease subtypes and molecular signatures

A pan-neurodegeneration atlas built from multilayer, deep proteomics of 2,279 brain samples across 6 major diseases integrates whole proteome, detergent-insoluble proteome, and posttranslational modifications to enable intra- and inter-disease comparisons to reveal disease-specific subtypes and dysregulated pathways, while identifying shared changes such as GPNMB upregulation and NPTX2 downregulation.

Characterization and regulatory mechanism evaluation of C8orf33 in hepatocellular carcinoma through multiomics profiling

Discov Oncol. 2026 Apr 11. doi: 10.1007/s12672-026-04951-z. Online ahead of print.

ABSTRACT

BACKGROUND: Hepatocellular carcinoma (HCC) is a major cause of cancer-related mortality. Chromosome 8 open reading frame 33 (C8orf33) has been noted as a potential oncogenic factor in several cancers, but its biological roles and regulatory mechanism in HCC microenvironment remain unknown.

METHODS: We integrated bulk RNA sequencing, single-cell RNA sequencing (scRNA-seq), and spatial transcriptomics (ST) to characterize the expression landscape of C8orf33. We then performed C8orf33 loss-of-function studies in HCC cell lines, including in vitro phenotypic assays and subcutaneous xenografts.

RESULTS: C8orf33 was broadly overexpressed and associated with unfavorable prognosis across multiple Cancers. In HCC, higher C8orf33 aligned with advanced stage and shorter overall survival. C8orf33 knockdown reduced proliferation and migration, impaired tumorigenic capacity, and increased apoptosis. ScRNA-seq analyses identified a malignant population of Epi3 with high C8orf33 expression. Cell-cell communication analysis suggested that C8orf33-high Epi3 state was associated with an enriched MIF-CD74/CXCR4/CD44 signaling program toward macrophage populations with M2-like features. ST analyses further confirmed the colocalization of C8orf33 with malignant features in tumor cores. In Huh7 cells, C8orf33 knockdown was accompanied by reduced mRNA and protein levels of MIF and its receptor components. Consistently, xenografts derived from C8orf33-silenced cells showed lower expression of these MIF-axis components and reduced infiltration of CD163 and CD206-positive macrophages.

CONCLUSION: These results support a tumor-promoting association of C8orf33 in HCC and suggest a potential link to macrophage-associated immunomodulatory features, nominating C8orf33 as a candidate biomarker and therapeutic target.

PMID:41965457 | DOI:10.1007/s12672-026-04951-z

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