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Systems pharmacology approaches decipher the anti-cancer efficacy of ethnopharmacological agents in hepatocellular carcinoma
Sci Rep. 2025 Dec 17;15(1):43996. doi: 10.1038/s41598-025-27744-w.
ABSTRACT
Hepatocellular carcinoma (HCC) poses a significant global health burden with limited therapeutic efficacy. Chinese herbal medicines (CHMs) offer multi-target potential, yet their systematic screening and mechanistic elucidation remain challenging. We established a high-throughput multi-omics platform integrating transcriptomics, proteomics, and deep learning (autoencoder and multiple kernel learning) to screen 187 medicinal plants. Five CHMs candidates were identified and shown to modulate hub genes (e.g., AKR1B10, HMGCR, THBS1) and key pathways (TNF/IL-17/MAPK, apoptosis, ferroptosis). Proteomic validation and functional assays confirmed their roles in suppressing proliferation, migration, and inducing apoptosis in HCC cells. This study provides a robust, data-driven pipeline for natural anti-HCC drug discovery, linking specific hub genes to CHM efficacy and offering novel insights into precision ethnopharmacology.
PMID:41408124 | DOI:10.1038/s41598-025-27744-w
ClinicalTrialsHub: Bridging Registries and Literature for Comprehensive Clinical Trial Access
Genomic Next-Token Predictors are In-Context Learners
Stereo-seq V2: Spatial mapping of total RNA on FFPE sections with high resolution
PaperArena: An Evaluation Benchmark for Tool-Augmented Agentic Reasoning on Scientific Literature
Annotation Guidelines-Based Knowledge Augmentation: Towards Enhancing Large Language Models for Educational Text Classification
Liquid Biopsy in CRC Management: Early Detection, Minimal Residual Disease, and Therapy Optimization-Clinical Evidence and Challenges
Diagn Cytopathol. 2025 Nov;53(11):580-591. doi: 10.1002/dc.70009. Epub 2025 Sep 4.
ABSTRACT
Colorectal cancer (CRC) is a major global health burden, ranking among the leading causes of cancer-related deaths. Despite improvements in screening and treatment, challenges such as late-stage diagnosis, high recurrence rates, and therapy resistance continue to impede optimal outcomes. Liquid biopsy, a minimally invasive technique that analyzes tumor-derived components in bodily fluids-including circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), and extracellular vesicles (EVs)-is emerging as a powerful tool to transform CRC management across the disease continuum. This review provides a comprehensive overview of liquid biopsy's current and emerging applications in CRC. We examine its role in early detection, where sensitive ctDNA-based assays and epigenetic biomarkers have demonstrated the ability to identify CRC at asymptomatic or early stages, potentially improving screening uptake and compliance. Furthermore, we explore how liquid biopsy enables dynamic monitoring of treatment response and clonal evolution, facilitating the timely identification of resistance mutations and supporting personalized therapy adjustments. Innovations in multi-omics integration, artificial intelligence, and ultra-sensitive sequencing technologies are also discussed as pivotal advancements that enhance the clinical utility of liquid biopsy. Despite significant progress, the widespread adoption of liquid biopsy faces several hurdles, including assay standardization, sensitivity for low-shedding tumors, regulatory approval, and cost-effectiveness. Continued research, validation in large prospective trials, and harmonization of testing protocols are essential to overcome these challenges. Ultimately, liquid biopsy holds the potential to become a cornerstone of precision oncology in CRC, enabling earlier intervention, more tailored treatment strategies, and improved patient outcomes.
PMID:40905096 | DOI:10.1002/dc.70009
Stereo-seq V2: Spatial mapping of total RNA on FFPE sections with high resolution
Cell. 2025 Aug 22:S0092-8674(25)00922-5. doi: 10.1016/j.cell.2025.08.008. Online ahead of print.
ABSTRACT
Performing total RNA profiling on formalin-fixed, paraffin-embedded (FFPE) samples, the predominant sample conservation method in clinical practice, remains challenging for current spatial transcriptomics techniques. Here, we introduce Stereo-seq V2, which employs random primers to capture and sequence RNAs in situ on FFPE sections and provides single-cell resolution. The random-priming-based strategy offers unbiased transcript capturing and uniform gene body coverage, which increase the sensitivity to marker genes, the efficiency of non-polyadenylation (poly(A)) RNA profiling, and immune repertoire coverage. We demonstrated the robust performance of Stereo-seq V2 on clinical FFPE samples using triple-negative breast cancer (TNBC) sections and identified tumor-specific alternative splicing events. In a Mycobacterium tuberculosis (Mtb)-infected mouse model, we monitored gene expression dynamics of host and pathogen transcriptomes simultaneously by utilizing Stereo-seq V2. We also assembled immune repertoires and identified Mtb-specific BCR clones, which could also be observed in human tuberculous lung samples. These results highlight Stereo-seq V2's potential in biomedical research and personalized medicine.
PMID:40882628 | DOI:10.1016/j.cell.2025.08.008
Pre-rRNA spatial distribution and functional organization of the nucleolus
Nature, Published online: 23 July 2025; doi:10.1038/s41586-025-09412-1
Pre-rRNA spatial distribution and functional organization of the nucleolusSpatiotemporal control of necroptotic cell death and plasma membrane recruitment using engineered MLKL domains
Cell Death Discovery, Published online: 29 November 2022; doi:10.1038/s41420-022-01258-0
Spatiotemporal control of necroptotic cell death and plasma membrane recruitment using engineered MLKL domains