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PPGFlowECG: Latent Rectified Flow with Cross-Modal Encoding for PPG-Guided ECG Generation and Cardiovascular Disease Detection
AI-generated data contamination erodes pathological variability and diagnostic reliability
SciEvalKit: An Open-source Evaluation Toolkit for Scientific General Intelligence
Senescence-driven molecular subtyping in pancreatic cancer: a multi-omics framework for precision medicine
BMC Cancer. 2025 Dec 15. doi: 10.1186/s12885-025-15341-z. Online ahead of print.
NO ABSTRACT
PMID:41398222 | DOI:10.1186/s12885-025-15341-z
Causal relationship of immune cell characteristics in hepatocellular carcinoma: A multi-omics analysis based on Mendelian randomization
Medicine (Baltimore). 2025 Dec 5;104(49):e45942. doi: 10.1097/MD.0000000000045942.
ABSTRACT
The tumor immune microenvironment of hepatocellular carcinoma (HCC) is complex, yet the causal relationship between immune cell subpopulations and HCC risk remains incompletely elucidated. This study aims to systematically evaluate the causal association between immune cell subpopulations and HCC using Mendelian randomization (MR) analysis, and to validate the biological mechanisms underlying these associations through multi-omics data. Bidirectional two-sample MR analysis was performed to examine causal relationships between 731 immune cell subpopulations and HCC. Inverse-variance weighting (IVW) served as the primary analysis method, with robustness validation through Bayesian weighted MR (BWMR) and machine learning algorithms. Therefore, for significantly associated immune subpopulations, independent analyses of gene expression, prognosis, and tumor immune microenvironment were conducted using HCC data from the Cancer Genome Atlas (TCGA) LIHC cohort. MR analysis and validation identified 21 immune cell subpopulations with significant causal associations to HCC risk. Among these, 12 were identified as risk factors, and 9 as protective factors. Validation in the TCGA cohort revealed that risk-associated immune subpopulations were predominantly enriched for markers of T cell exhaustion and immunosuppressive microenvironments, whereas protective subpopulations likely represented a distinct regulatory B cell subset whose function was associated with the anti-inflammatory factor interleukin-10. This study genetically confirms that specific immune cell functional subpopulations constitute causal risk factors for HCC. These subpopulations exert their effects by shaping distinct tumor immune microenvironments. These findings provide novel mechanisms for understanding the immunopathogenesis of HCC and identify potential targets for developing novel immune intervention strategies.
PMID:41366997 | DOI:10.1097/MD.0000000000045942
AI Application in Anti-Money Laundering for Sustainable and Transparent Financial Systems
A Definition of AGI
SciAgent: A Unified Multi-Agent System for Generalistic Scientific Reasoning
SciAgent: A Unified Multi-Agent System for Generalistic Scientific Reasoning
A Definition of AGI
VaultGemma: A Differentially Private Gemma Model
Targeting spermine metabolism to overcome immunotherapy resistance in pancreatic cancer
Nat Commun. 2025 Aug 22;16(1):7827. doi: 10.1038/s41467-025-63146-2.
ABSTRACT
While dysregulation of polyamine metabolism is frequently observed in cancer, it is unknown how polyamines alter the tumor microenvironment (TME) and contribute to therapeutic resistance. Analysis of polyamines in the plasma of pancreatic cancer patients reveals that spermine levels are significantly elevated and correlate with poor prognosis. Using a multi-omics approach, we identify Serpinb9 as a vulnerability in spermine metabolism in pancreatic cancer. Serpinb9, a serine protease inhibitor, directly interacts with spermine synthase (SMS), impeding its lysosome-mediated degradation and thereby augmenting spermine production and secretion. Mechanistically, the accumulation of spermine in the TME alters the metabolic landscape of immune cells, promoting CD8+ T cell dysfunction and pro-tumor polarization of macrophages, thus creating an immunosuppressive microenvironment. Small peptides that disrupt the Serpinb9-SMS interaction significantly enhance the efficacy of immune checkpoint blockade therapy. Together, our findings suggest that targeting spermine metabolism is a promising strategy to improve pancreatic cancer immunotherapy.
PMID:40846845 | PMC:PMC12373741 | DOI:10.1038/s41467-025-63146-2
Integrative single-cell multi-omics profiling of human pancreatic islets identifies T1D-associated genes and regulatory signals
Cell Rep. 2025 Jul 29;44(8):116065. doi: 10.1016/j.celrep.2025.116065. Online ahead of print.
ABSTRACT
Genome-wide association studies (GWASs) have identified over 100 signals associated with type 1 diabetes (T1D). However, it has been challenging to translate any given T1D GWAS signal into mechanistic insights, such as causal variants, their target genes, and the specific cell types involved. Here, we present a comprehensive multi-omic integrative analysis of single-cell/nucleus resolution profiles of gene expression and chromatin accessibility in human pancreatic islets under baseline and T1D-stimulating conditions. We nominate effector cell types for all T1D GWAS signals and the regulatory elements and genes for three independent T1D signals acting through β cells at the DLK1/MEG3, RASGRP1, and TOX loci. Subsequently, we validated the functional impact of these genes and regulatory regions using isogenic human embryonic stem cells (hESCs). We found that loss of RASGRP1 or DLK1, as well as disruption of their corresponding regulatory regions, led to increased β cell apoptosis. Furthermore, β cells derived from isogenic hESCs carrying the T1D risk allele of rs3783355 associated with DLK1 showed elevated β cell death. Through additional RNA sequencing (RNA-seq) and assay for transposase-accessible chromatin using sequencing (ATAC-seq) analyses, we identified five genes upregulated in both RASGRP1-/- and DLK1-/- β-like cells, four of which are near T1D GWAS signals. This integrative approach combining single-cell multi-omics, GWASs, and isogenic human pluripotent stem cell (hPSC)-derived β-like cells illuminates cell type context, genes, single nucleotide polymorphisms (SNPs), and regulatory elements underlying T1D-associated signals, providing insights into the biological functions and molecular mechanisms involved.
PMID:40737125 | DOI:10.1016/j.celrep.2025.116065
A deep learning framework for <em>in silico</em> screening of anticancer drugs at the single-cell level
Natl Sci Rev. 2024 Dec 10;12(2):nwae451. doi: 10.1093/nsr/nwae451. eCollection 2025 Feb.
ABSTRACT
Tumor heterogeneity plays a pivotal role in tumor progression and resistance to clinical treatment. Single-cell RNA sequencing (scRNA-seq) enables us to explore heterogeneity within a cell population and identify rare cell types, thereby improving our design of targeted therapeutic strategies. Here, we use a pan-cancer and pan-tissue single-cell transcriptional landscape to reveal heterogeneous expression patterns within malignant cells, precancerous cells, as well as cancer-associated stromal and endothelial cells. We introduce a deep learning framework named Shennong for in silico screening of anticancer drugs for targeting each of the landscape cell clusters. Utilizing Shennong, we could predict individual cell responses to pharmacologic compounds, evaluate drug candidates' tissue damaging effects, and investigate their corresponding action mechanisms. Prioritized compounds in Shennong's prediction results include FDA-approved drugs currently undergoing clinical trials for new indications, as well as drug candidates reporting anti-tumor activity. Furthermore, the tissue damaging effect prediction aligns with documented injuries and terminated discovery events. This robust and explainable framework has the potential to accelerate the drug discovery process and enhance the accuracy and efficiency of drug screening.
PMID:39872221 | PMC:PMC11771446 | DOI:10.1093/nsr/nwae451
Targeting MFAP5 in cancer-associated fibroblasts sensitizes pancreatic cancer to PD-L1-based immunochemotherapy via remodeling the matrix
Oncogene, Published online: 08 May 2023; doi:10.1038/s41388-023-02711-9
Targeting MFAP5 in cancer-associated fibroblasts sensitizes pancreatic cancer to PD-L1-based immunochemotherapy via remodeling the matrix