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Improving early cancer detection has the potential to substantially reduce cancer-related mortality. Cell-free methylated DNA immunoprecipitation and high-throughput sequencing (cfMeDIP–seq) is a highly sensitive assay capable of detecting early-stage tumors. We report accurate classification of patients across all stages of renal cell carcinoma (RCC) in plasma (area under the receiver operating characteristic (AUROC) curve of 0.99) and demonstrate the validity of this assay to identify patients with RCC using urine cell-free DNA (cfDNA; AUROC of 0.86). A cell-free DNA-methylation sequencing assay accurately identifies renal cell carcinoma using plasma and urine samples.

Previous studies have shown that the main function of VASP is to regulate the cytoskeleton and play an important role in promoting tumor cell metastasis. In this study, we first reveal that VASP is located in the nucleus of breast cancer cells and elucidate a Wnt/β-catenin/VASP positive feedback loop. We identify that VASP is a target gene of Wnt/β-catenin signaling pathway, and activation of Wnt/β-catenin signaling pathway can significantly upregulate VASP protein expression, while upregulated VASP protein can in turn promote translocation of β-catenin and DVL3 proteins into the nucleus. In the nucleus, VASP, DVL3, β-catenin, and TCF4 can form VASP/DVL3/β-catenin/TCF4 protein complex, activating Wnt/β-catenin signaling pathway, and promoting the expression of target genes VASP, c-myc, and cyclin D1. Thus, our study reveals that there is a Wnt/β-catenin/VASP malignant positive feedback loop in breast cancer, which promotes the proliferation and migration of breast cancer cells, and breaking this positive feedback loop may provide new strategy for breast cancer treatment.

Lymph node metastasis is the major adverse feature for recurrence and death of thyroid cancer patients. To identify lncRNAs involved in thyroid cancer metastasis, we systemically screened differentially expressed lncRNAs in lymph node metastasis, thyroid cancer, and normal tissues via RNAseq. We found that lncRNA SLC26A4-AS1 was continuously, significantly down-regulated in normal tissues, thyroid cancer, and lymph node metastasis specimens. Low SLC26A4-AS1 levels in tissues were significantly associated with poor prognosis of thyroid cancer patients. LncRNA SLC26A4-AS1 markedly inhibited migration, invasion, and metastasis capability of cancer cells in vitro and in vivo. Intriguingly, SLC26A4-AS1 could simultaneously interact with DDX5 and the E3 ligase TRIM25, which promoting DDX5 degradation through the ubiquitin-proteasome pathway. In particular, SLC26A4-AS1 inhibited expression of multiple DNA double-strand breaks (DSBs) repair genes, especially genes coding proteins in the MRE11/RAS50/NBS1 (MRN) complex. Enhanced interaction between DDX5 and transcriptional factor E2F1 due to silencing of SLC26A4-AS1 promoted binding of the DDX5–E2F1 complex at promoters of the MRN genes and, thus, stimulate the MRN/ATM dependent DSB signaling and thyroid cancer metastasis. Our study uncovered new insights into the biology driving thyroid cancer metastasis and highlights potentials of lncRNAs as future therapeutic targets again cancer metastasis.

Epigenetic processes govern prostate cancer (PCa) biology, as evidenced by the dependency of PCa cells on the androgen receptor (AR), a prostate master transcription factor. We generated 268 epigenomic datasets spanning two state transitions—from normal prostate epithelium to localized PCa to metastases—in specimens derived from human tissue. We discovered that reprogrammed AR sites in metastatic PCa are not created de novo; rather, they are prepopulated by the transcription factors FOXA1 and HOXB13 in normal prostate epithelium. Reprogrammed regulatory elements commissioned in metastatic disease hijack latent developmental programs, accessing sites that are implicated in prostate organogenesis. Analysis of reactivated regulatory elements enabled the identification and functional validation of previously unknown metastasis-specific enhancers at HOXB13 , FOXA1 and NKX3-1 . Finally, we observed that prostate lineage-specific regulatory elements were strongly associated with PCa risk heritability and somatic mutation density. Examining prostate biology through an epigenomic lens is fundamental for understanding the mechanisms underlying tumor progression. Analyses of epigenomic datasets spanning transitions from normal prostate epithelium to localized prostate cancer to metastases show that latent developmental programs are reactivated in metastatic disease and that prostate lineage-specific regulatory elements are strongly enriched for prostate cancer risk heritability.

With the exponential growth in the quantity and complexity of malware, traditional detection methods face severe challenges. This paper proposes GCSA-ResNet, a novel deep learning model that significantly enhances malware detection performance by integrating the Global Channel-Spatial Attention (GCSA) module with ResNet-50. The core innovation lies in the GCSA module, which for the first time collaboratively designs channel attention, channel shuffling, and spatial attention mechanisms to simultaneously capture local texture features and global dependency relationships in visualized malware images. Compared with existing attention models such as SE and CBAM, GCSA strengthens cross-channel information interaction through channel shuffling operations and employs spatial attention with a 7 × 7 convolutional kernel to more effectively model long-range spatial correlations. Experiments on the Malimg and Microsoft BIG 2015 datasets demonstrate that GCSA-ResNet achieves over 98.50% accuracy, representing a performance improvement of more than 0.5% compared to baseline models. Quantitative results show that the model maintains stable performance in precision, recall, and F1-score, while reducing false positive rates by 40–50%. These advancements effectively address the limitations of existing methods in feature degradation and cross-family misclassification.

With the rapid development of the internet, phishing attacks have become more diverse, making phishing website detection a key focus in cybersecurity. While machine learning and deep learning have led to various phishing URL detection methods, many remain incomplete, limiting accuracy. This paper proposes CSPPC-BiLSTM, a malicious URL detection model based on BiLSTM (Bidirectional Long Short-Term Memory, BiLSTM). The model processes URL character sequences through an embedding layer and captures contextual information via BiLSTM. By integrating CBAM (Convolutional Block Attention Module, CBAM), it applies channel and spatial attention to highlight key features and transforms URL sequence features into a spatial matrix. The SPP (Spatial Pyramid Pooling, SPP) module enables multi-scale pooling. Finally, a fully connected layer fuses features, and dropout regularization enhances robustness. Compared to CharBiLSTM, CSPPC-BiLSTM significantly improves detection accuracy. Evaluated on two datasets, Grambedding (balanced) and Mendeley AK Singh 2020 phish (imbalanced)—and compared with six baselines, it demonstrates strong generalization and accuracy. Ablation experiments confirm the critical role of CBAM and SPP in boosting performance.

Sarcomatoid and rhabdoid (S/R) renal cell carcinoma (RCC) are highly aggressive tumors with limited molecular and clinical characterization. Emerging evidence suggests immune checkpoint inhibitors (ICI) are particularly effective for these tumors, although the biological basis for this property is largely unknown. Here, we evaluate multiple clinical trial and real-world cohorts of S/R RCC to characterize their molecular features, clinical outcomes, and immunologic characteristics. We find that S/R RCC tumors harbor distinctive molecular features that may account for their aggressive behavior, including BAP1 mutations, CDKN2A deletions, and increased expression of MYC transcriptional programs. We show that these tumors are highly responsive to ICI and that they exhibit an immune-inflamed phenotype characterized by immune activation, increased cytotoxic immune infiltration, upregulation of antigen presentation machinery genes, and PD-L1 expression. Our findings build on prior work and shed light on the molecular drivers of aggressivity and responsiveness to ICI of S/R RCC. Sarcomatoid and rhabdoid tumours are highly aggressive forms of renal cell carcinoma that are also responsive to immunotherapy. In this study, the authors perform a comprehensive molecular characterization of these tumours discovering an enrichment of specific alterations and an inflamed phenotype.

Over the past decade, organoids have emerged as a prevalent and promising research tool, mirroring the physiological architecture of the human body. However, as the field advances, the traditional use of animal or tumor-derived extracellular matrix (ECM) as scaffolds has become increasingly inadequate. This shift has led to a focus on developing synthetic scaffolds, particularly hydrogels, that more accurately mimic three-dimensional (3D) tissue structures and dynamics in vitro. The ECM–cell interaction is crucial for organoid growth, necessitating hydrogels that meet organoid-specific requirements through modifiable physical and compositional properties. Advanced composite hydrogels have been engineered to more effectively replicate in vivo conditions, offering a more accurate representation of human organs compared to traditional matrices. This review explores the evolution and current uses of decellularized ECM scaffolds, emphasizing the application of decellularized ECM hydrogels in organoid culture. It also explores the fabrication of composite hydrogels and the prospects for their future use in organoid systems.

The role of long noncoding RNA (lncRNA) HOX transcript antisense RNA (HOTAIR) and its functional single nucleotide polymorphisms (SNPs) in papillary thyroid carcinoma (PTC) is still largely unclear. Therefore, we investigated the involvement of lncRNA HOTAIR and its three haplotype-tagging SNPs (htSNPs) in PTC. There was higher expression of HOTAIR in PTC tissues compared to normal tissues. A series of gain-loss assays demonstrated that HOTAIR acts as a PTC oncogene via promoting tumorigenic properties of PTC cells. Additionally, the functional HOTAIR rs920778 genetic variant was a PTC susceptibility SNP. Subjects with the HOTAIR rs920778 TT genotype had an odds ratio (OR) of 1.88, 1.25 and 1.61 ( P  = 6.0 × 10 −6 , P  = 0.028 and P  = 3.2 × 10 −5 ) for developing PTC in Shandong, Jiangsu and Jilin case-control sets compared with subjects with the CC genotype. This statistically significant associations were only found between the rs920778 genetic polymorphism and PTC risk in females but not in males. The allele-specific regulation on HOTAIR expression by the rs920778 SNP was confirmed both in vitro and in vivo . Our results demonstrate that functional SNPs influencing lncRNA regulation may explain a part of PTC genetic basis.

Chondral defects are challenging to repair because of the poor self-healing capacity of articular cartilage. The aim of this study was to compare and investigate the cartilage regeneration of stromal vascular fraction (SVF) cells and adipose-derived stem cells (ASCs) co-cultured with chondrocytes seeding on scaffolds composed of polyhydroxybutyrate (PHB)/poly-(hydroxybutyrate-co-hydroxyhexanoate) (PHBHHx). In this study, the cellular morphologies and proliferation capabilities on scaffolds were evaluated. Next, scaffolds with 1:1 co-culture of ASCs/SVF and chondrocytes were implanted into the full-thickness cartilage defects in rabbit knee for 10 weeks. Cells seeded on the scaffolds showed better adhesion, migration, and proliferation in vitro. Importantly, implantation with scaffolds with SVF and chondrocytes revealed more desirable in vivo healing outcomes. Our results illustrate a one-step surgical procedure for the regeneration of focal cartilage defects using a mixture of SVF from adipose tissue and uncultured chondrocytes.