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Kernel-Complexity Edge Sanitization for Training-Free Defense against Structural Graph Attacks
Skin-innervating glutamatergic neurons modulate aging
FrontierOR: Benchmarking LLMs' Capacity for Efficient Algorithm Design in Large-Scale Optimization
Iterative Refinement Neural Operators are Learned Fixed-Point Solvers: A Principled Approach to Spectral Bias Mitigation
NSR-Boost: A Neuro-Symbolic Residual Boosting Framework for Industrial Legacy Models
SkillOpt: Executive Strategy for Self-Evolving Agent Skills
Forest carbon protocols underestimate climate-driven carbon loss risks
Nature, Published online: 20 May 2026; doi:10.1038/s41586-026-10571-y
The buffer pool designed to compensate for unintended carbon losses from the largest forest climate mitigation programme in the United States is too small when considering the impact of future climate change scenarios.Stromal ACTA2 Counteracts TCDD-Induced Hepatocarcinogenesis via Suppression of the PI3K-AKT-mTOR Pathway
J Hepatocell Carcinoma. 2026 May 10;13:586916. doi: 10.2147/JHC.S586916. eCollection 2026.
ABSTRACT
PURPOSE: 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a persistent environmental pollutant that promotes hepatocellular carcinoma (HCC) through non-genotoxic mechanisms. However, stromal regulatory factors that counteract its tumor-promoting effects remain poorly defined. This study aimed to elucidate the role of actin alpha-2 (ACTA2) in TCDD-associated hepatocarcinogenesis.
METHODS: An integrative strategy combining network toxicology, Mendelian randomization, multi-omics and single-cell analyses, molecular docking and molecular dynamics simulations, along with in vitro experiments, was employed to investigate the functional role of ACTA2.
RESULTS: ACTA2 was identified as a stromal-associated factor linked to reduced HCC risk and improved patient survival. Single-cell and multi-omics analyses revealed that ACTA2 is predominantly expressed in hepatic stellate cells and fibroblast-like populations, reflecting tumor microenvironment composition rather than tumor cell-intrinsic expression. Functional enrichment analyses indicated that ACTA2 is associated with extracellular matrix remodeling and PI3K-AKT signaling. Molecular simulations demonstrated stable binding of TCDD to ACTA2 (ΔG_bind ≈ -7.05 kcal/mol), suggesting potential structural perturbation. In vitro experiments showed that TCDD downregulated ACTA2 expression, promoted proliferation of LX-2 and cancer-associated fibroblasts (CAFs), and activated PI3K-AKT-mTOR signaling, whereas ACTA2 overexpression attenuated these effects.
CONCLUSION: ACTA2 acts as a context-dependent stromal regulator that modulates PI3K-AKT-mTOR signaling in TCDD-induced hepatocarcinogenesis. These findings highlight the importance of stromal remodeling in environmental carcinogenesis and suggest ACTA2 as a potential biomarker and therapeutic target in dioxin-associated HCC.
PMID:42148320 | PMC:PMC13175077 | DOI:10.2147/JHC.S586916
Refined immune-based molecular subtypes of gastric cancer: Integrating mismatch repair status and tumor microenvironment for enhanced immunotherapy prediction
Chin J Cancer Res. 2026 Apr 30;38(2):234-251. doi: 10.21147/j.issn.1000-9604.2026.02.09.
ABSTRACT
OBJECTIVE: Gastric cancer (GC) is heterogeneous, and current mismatch repair (MMR)-based classifications incompletely predict response to immune checkpoint inhibitors (ICIs).
METHODS: RNA sequencing (RNA-seq) and immune infiltration profiles from 189 resected GC were used to derive four refined immune-MMR subtypes (R1-R4) by integrating MMR status, survival, and tumor microenvironment (TME) features. Multi-omics profiling and pathway analysis defined subtype biology. External transcriptomic cohorts and an ICI-treated cohort were classified with Nearest Template Prediction (NTP). Immune response-associated genes were identified from responder vs. non-responder comparisons within the ICI-sensitive subtype and validated by multiplex immunohistochemistry (mIHC).
RESULTS: R1 showed the best prognosis and highest immunotherapy response with objective response rate (ORR) 54.5%, while R4 had the worst prognosis. R2 represented an immune-unresponsive deficient mismatch repair (dMMR) subset, and R3 captured an immune-active proficient mismatch repair (pMMR) subgroup with moderate therapy sensitivity. Multi-omics integration revealed subtype-specific pathways (e.g., ECM remodeling in R1, metabolic reprogramming in R2). Reclassification of pMMR tumors based on transcriptional similarity to R1 identified a New R3 subset with enhanced immune features and higher ICI response. Eight immune response-associated genes (e.g., CXCL10, CXCL11, ELN, GAD1, IL32, MT1E, OR2I1P, SLC3A1) were identified and validated by mIHC for predictive relevance.
CONCLUSIONS: This immune-based molecular framework refines risk stratification beyond conventional MMR categories, identifies ICI-sensitive subsets among both dMMR and pMMR tumors, and proposes candidate biomarkers for patient selection.
PMID:42147371 | PMC:PMC13171420 | DOI:10.21147/j.issn.1000-9604.2026.02.09
SortedRL: Accelerating RL Training for LLMs through Online Length-Aware Scheduling
FCMBench: The First Large-scale Financial Credit Multimodal Benchmark for Real-world Applications
Ferroptosis of smooth muscle cells in vascular diseases: from basic principles to clinical translation
Cell Death Discovery, Published online: 09 March 2026; doi:10.1038/s41420-026-02950-1
Ferroptosis of smooth muscle cells in vascular diseases: from basic principles to clinical translation