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Abstract Background Assay of Transposase Accessible Chromatin Sequencing (ATAC-seq) is a high-throughput sequencing technique that detects open chromatin regions across the genome. These regions are critical in facilitating transcription factor binding and subsequent gene expression. Herein, we utilized ATAC-seq to identify key molecular targets regulating the development and progression of hepatocellular carcinoma (HCC) and elucidate the underlying mechanisms. Methods We first compared chromatin accessibility profiles between HCC and normal tissues. Subsequently, RNA-seq data was employed to identify differentially expressed genes (DEGs). Integrating ATAC-seq and RNA-seq data allowed the identification of transcription factors and their putative target genes associated with differentially accessible regions (DARs). Finally, functional experiments were conducted to investigate the effects of the identified regulatory factors and corresponding targets on HCC cell proliferation and migration. Results Enrichment analysis of DARs between HCC and adjacent normal tissues revealed distinct signaling pathways and regulatory factors. Upregulated DARs in HCC were enriched in genes related to the MAPK and FoxO signaling pathways and associated with transcription factor families like ETS and AP-1. Conversely, downregulated DARs were associated with the TGF-β, cAMP, and p53 signaling pathways and the CTCF family. Integration of the datasets revealed a positive correlation between specific DARs and DEGs. Notably, PRPF3 emerged as a gene associated with DARs in HCC, and functional assays demonstrated its ability to promote HCC cell proliferation and migration. To the best of our knowledge, this is the first report highlighting the oncogenic role of PRPF3 in HCC. Furthermore, ZNF93 expression positively correlated with PRPF3, and ChIP-seq data indicated its potential role as a transcription factor regulating PRPF3 by binding to its promoter region. Conclusion This study provides a comprehensive analysis of the epigenetic landscape in HCC, encompassing both chromatin accessibility and the transcriptome. Our findings reveal that ZNF93 promotes the proliferation and motility of HCC cells through transcriptional regulation of a novel oncogene, PRPF3.

Abstract Background/Aims Gastric cancer (GC) ranks among the prevalent types of cancer, and its progression is influenced by the tumor microenvironment (TME). A comprehensive comprehension of the TME associated with GC has the potential to unveil therapeutic targets of significance. Methods The complexity and heterogeneity of TME interactions were revealed through our investigation using an integrated analysis of single-cell and bulk-tissue sequencing data. Results We constructed a single-cell transcriptomic atlas of 150,913 cells isolated from GC patients. Our analysis revealed the intricate nature and heterogeneity of the GC TME and the metabolic properties of major cell types. Furthermore, two cell subtypes, LOX+ Fibroblasts and M2 Macrophages, were enriched in tumor tissue and related to the outcome of GC patients. In addition, LOX+ Fibroblasts were significantly associated with M2 macrophages. immunofluorescence double labeling indicated LOX+ Fibroblasts and M2 Macrophages were tightly localized in GC tissue. The two cell subpopulations strongly interacted in a hypoxic microenvironment, yielding an immunosuppressive phenotype. Our findings further suggest that LOX+ Fibroblasts may act as a trigger for inducing the differentiation of monocytes into M2 Macrophages via the IL6-IL6R signaling pathway. Conclusions Our study revealed the intricate and interdependent communication network between the fibroblast and macrophage subpopulations, which could offer valuable insights for targeted manipulation of the tumor microenvironment.

Abstract Background The tumor microenvironment (TME) exerts profound effects on tumor progression and therapeutic efficacy. In hepatocellular carcinoma (HCC), the TME is enriched with cancer-associated fibroblasts (CAFs), which secrete a plethora of cytokines, chemokines, and growth factors that facilitate tumor cell proliferation and invasion. However, the intricate architecture of the TME in HCC, as well as the mechanisms driving interactions between tumor cells and CAFs, remains largely enigmatic. Methods We analyzed 10 spatial transcriptomics and 12 single-cell transcriptomics samples sourced from public databases, complemented by 20 tumor tissue samples from liver cancer patients obtained in a clinical setting. Results Our findings reveal that tumor cells exhibiting high levels of SPP1 are preferentially localized adjacent to hepatic stellate cells (HSCs). The SPP1 secreted by these tumor cells interacts with the CD44 receptor on HSCs, thereby activating the PI3K/AKT signaling pathway, which promotes the differentiation of HSCs into CAFs. Notably, blockade of the CD44 receptor effectively abrogates this interaction. Furthermore, in vivo studies demonstrate that silencing SPP1 expression in tumor cells significantly impairs HSC differentiation into CAFs, leading to a reduction in tumor volume and collagen deposition within the tumor stroma. Conclusions This study delineates the SPP1-CD44 signaling axis as a pivotal mechanism underpinning the interaction between tumor cells and CAFs. Targeting this pathway holds potential to mitigate liver fibrosis and offers novel therapeutic perspectives for liver cancer management.

Objectivesto construct a prediction model for clinically significant prostate cancer (csPCa) based on prostate-specific antigen (PSA) levels, digital rectal examination (DRE), and transrectal ultrasonography (TRUS).MethodsWe retrospectively analysed 1196 Asian patients who underwent transrectal ultrasound-guided biopsy (TRUSB) between June 2000 and February 2023. Patients were randomly divided into a training set of 837 cases (70%) and a validation set of 359 patients (30%). A csPCa risk prediction model was established using the logistic regression. The performance of the model was examined based on calibration curves, receiver operating characteristic (ROC) curves, decision curve analysis (DCA), and clinical impact curves (CIC).ResultsSerum PSA levels, age, DRE results, prostatic shape, prostatic border and hypoechoic area were associated with pathological outcomes. The area under the ROC curve of the training set was 0.890 (95%CI: 0.865-0.816). The optimal cut-off value was 0.279. The calibration curves indicated good calibration, and the DCA and CIC results demonstrated good clinical utility. Significantly, the prediction model has higher negative predictive value (89.8%) and positive predictive value (68.0%) compared with MRI. Subsequently, we developed an online calculator (https://jiwentong0.shinyapps.io/dynnomapp/) with six variables for biopsy optimization.ConclusionThis study incorporated the results of three traditional diagnostic methods to establish a cost-effective and highly accurate model for predicting csPCa before biopsy. With this model, we aim to provide a non-invasive and cost-effective tool for csPCa detection in Asia and other underdeveloped areas.

Since ELL-associated factor 2 (EAF2) was identified in 1997 as an androgen response gene, it has been of medical and scientific interest. Early studies demonstrated the tumor-suppressing function of EAF2 in the prostate. Sequencing studies indicated an association between EAF2 and several other malignant diseases and multiple physiological processes, such as transcription, apoptosis, embryogenesis, and DNA repair. Further understanding of EAF2 will provide new opportunities and therapeutic approaches for cancers, especially prostate cancer. This narrative review summarizes the existing knowledge of EAF2 and outlines its potential significance. To our knowledge, this is the first review of the role of this novel tumor suppressor gene and its possible functions.

Abstract Filamentous fungi produce polysaccharide-degrading enzymes, which is controlled by poorly understood transcriptional circuits. Here we show that a circuit comprising RsrC-RsrA-RsrB (Rsr: production of raw-starch-degrading enzyme regulator) that positively regulates production of raw starch-degrading enzymes in Penicillium oxalicum. Transcription factor (TF) RsrA is essential for biosynthesis of raw starch-degrading enzymes. RsrB and RsrC containing Zn2Cys6- and C2H2-zinc finger domains, act downstream and upstream of RsrA, respectively. RsrA activates rsrB transcription, and three nucleotides (G-286, G-287 and G-292) of rsrB promoter region are required for RsrA, in terms of TF, for binding. RsrB165−271 binds to DNA sequence 5’-TCGATCAGGCACGCC-3’ in the promoter region of the gene encoding key raw-starch-degrading enzyme PoxGA15A. RsrC specifically binds rsrA promoter, but not amylase genes, to positively regulate the expression of rsrA and the production of raw starch-degrading enzymes. These findings expand complex regulatory network of fungal raw starch-degrading enzyme biosynthesis.

Heavy metal pollution such as cadmium and arsenic in water seriously threatens human health and safety, and the removal of Cd/As combined pollution is more difficult. In this work, the performance of mechanically activated calcite composite FeSO4 to remove Cd/As combined pollution was investigated by Cd/As combined pollution removal test in water. It was found that mechanically activated calcite can significantly improve the removal efficiency of Cd/As combined pollution in water. The results showed that the removal rate of Cd and As can reach 99% in 30 min by activated calcite composite FeSO4. The removal mechanism of Cd/As combined pollution in water by activated calcite and FeSO4 was studied by SEM-EDS, XPS, and XRD. The results showed that the crystallinity and dissolution activity of calcite were changed by mechanical activation, and the hydrolysis of calcite to produce CO32- and OH- was enhanced. OH- promoted the formation of a stable iron oxide bound precipitate of FeSO4 with arsenic, and CO32- binded with cadmium to form a stable precipitate of cadmium carbonate.

Radiation therapy is a common treatment modality for patients with malignant tumors of the head and neck, chest and axilla. However, radiotherapy inevitably causes damage to normal tissues at the irradiated site, among which damage to the brachial plexus nerve(BP) is a serious adverse effect in patients receiving radiation therapy in the scapular or axillary regions, with clinical manifestations including abnormal sensation, neuropathic pain, and dyskinesia, etc. These adverse effects seriously reduce the living quality of patients and pose obstacles to their prognosis. Therefore, it is important to elucidate the mechanism of radiation induced brachial plexus injury (RIBP) which remains unclear. Current studies have shown that the pathways of radiation-induced BP injury can be divided into two categories: direct injury and indirect injury, and the indirect injury is closely related to the inflammatory response, microvascular damage, cytokine production and other factors causing radiation-induced fibrosis. In this review, we summarize the underlying mechanisms of RIBP occurrence and possible effective methods to prevent and treat RIBP.

Abstract Fish are vital in river ecosystems; however, traditional investigations of fish usually cause ecological damage. Extracting DNA from aquatic environments and identifying DNA sequences offer an alternative, noninvasive approach for detecting fish species. In this study, the effects of environmental DNA (eDNA), coupled with PCR and next‐generation sequencing, and electrofishing for identifying fish community composition and diversity were compared. In three subtropical rivers of southern China, fish specimens and eDNA in water were collected along the longitudinal (upstream–downstream) gradient of the rivers. Both fish population parameters, including species abundance and biomass, and eDNA OTU richness grouped 38 sampling sites into eight spatial zones with significant differences in local fish community composition. Compared with order‐/family‐level grouping, genus‐/species‐level grouping could more accurately reveal the differences between upstream zones I−III, midstream zones IV−V, and downstream zones VI–VIII. From the headwaters to the estuary, two environmental gradients significantly influenced the longitudinal distribution of the fish species, including the first gradient composed of habitat and physical water parameters and the second gradient composed of chemical water parameters. The high regression coefficient of alpha diversity between eDNA and electrofishing methods as well as the accurate identification of dominant, alien, and biomarker species in each spatial zone indicated that eDNA could characterize fish community attributes at a level similar to that of traditional approaches. Overall, our results demonstrated that eDNA metabarcoding can be used as an effective tool for revealing fish composition and diversity, which is important for using the eDNA technique in aquatic field monitoring.