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Background: Pancreatic ductal adenocarcinoma (PDAC) is frequently diagnosed in advanced stages, necessitating pancreaticoduodenectomy (PD) as a primary therapeutic approach. However, PD surgery can engender intricate complications. Thus, understanding the factors influencing postoperative complications documented in electronic medical records and their impact on survival rates is crucial for improving overall patient outcomes. Methods: A total of 749 patients were divided into two groups: 598 (79.84%) chose the RPD (Robotic pancreaticoduodenectomy) procedure and 151 (20.16%) chose the LPD (Laparoscopic pancreaticoduodenectomy) procedure. We used correlation analysis, survival analysis, and decision tree models to find the similarities and differences about postoperative complications and prognostic survival. Results: Pancreatic cancer, known for its aggressiveness, often requires pancreaticoduodenectomy as an effective treatment. In predictive models, both BMI and surgery duration weigh heavily. Lower BMI correlates with longer survival, while patients with heart disease and diabetes have lower survival rates. Complications like delayed gastric emptying, pancreatic fistula, and infection are closely linked post-surgery, prompting conjectures about their causal mechanisms. Interestingly, we found no significant correlation between nasogastric tube removal timing and delayed gastric emptying, suggesting its prompt removal post-decompression. Conclusion: This study aimed to explore predictive factors for postoperative complications and survival in PD patients. Effective predictive models enable early identification of high-risk individuals, allowing timely interventions. Higher BMI, heart disease, or diabetes significantly reduce survival rates in pancreatic cancer patients post-PD. Additionally, there's no significant correlation between DGE incidence and postoperative extubation time, necessitating further investigation into its interaction with pancreatic fistula and infection. [ABSTRACT FROM AUTHOR]

Topologically associating domains (TADs), megabase-scale features of chromatin spatial architecture, are organized in a domain-within-domain TAD hierarchy. Within TADs, the inner and smaller subTADs not only manifest cellto-cell variability, but also precisely regulate transcription and differentiation. Although over 20 TAD callers are able to detect TAD, their usability in biomedicine is confined by a disagreement of outputs and a limit in understanding TAD hierarchy. We compare 13 computational tools across various conditions and develop a metric to evaluate the similarity of TAD hierarchy. Although outputs of TAD hierarchy at each level vary among callers, data resolutions, sequencing depths, and matrices normalization, they are more consistent when they have a higher similarity of larger TADs. We present comprehensive benchmarking of TAD hierarchy callers and operational guidance to researchers of life science researchers. Moreover, by simulating the mixing of different types of cells, we confirm that TAD hierarchy is generated not simply from stacking Hi-C heatmaps of heterogeneous cells. Finally, we propose an air conditioner model to decipher the role of TAD hierarchy in transcription. [ABSTRACT FROM AUTHOR]

Pancreatic ductal adenocarcinoma (PDAC) is one of the leading causes of cancer-related death. Therefore, we intend to explore novel strategies against PDAC. The exosomes-based biomimetic nanoparticle is an appealing candidate served as a drug carrier in cancer treatment, due to its inherit abilities. In the present study, we designed dasatinib-loaded hybrid exosomes by fusing human pancreatic cancer cells derived exosomes with dasatinib-loaded liposomes, followed by characterization for particle size (119.9 ± 6.10 nm) and zeta potential (-11.45 ± 2.24 mV). Major protein analysis from western blot techniques reveal the presence of exosome marker proteins CD9 and CD81. PEGylated hybrid exosomes showed pH-sensitive drug release in acidic condition, benefiting drug delivery to acidic cancer environment. Dasatinib-loaded hybrid exosomes exhibited significantly higher uptake rates and cytotoxicity to parent PDAC cells by two-sample t-test or by one-way ANOVA analysis of variance, as compared to free drug or liposomal formulations. The results from our computational analysis demonstrated that the drug-likeness, ADMET, and protein-ligand binding affinity of dasatinib are verified successfully. Cancer derived hybrid exosomes may serve as a potential therapeutic candidate for pancreatic cancer treatment. [ABSTRACT FROM AUTHOR]

Background: The hierarchical three-dimensional (3D) architectures of chromatin play an important role in fundamental biological processes, such as cell differentiation, cellular senescence, and transcriptional regulation. Aberrant chromatin 3D structural alterations often present in human diseases and even cancers, but their underlying mechanisms remain unclear. Results: 3D chromatin structures (chromatin compartment A/B, topologically associated domains, and enhancerpromoter interactions) play key roles in cancer development, metastasis, and drug resistance. Bioinformatics techniques based on machine learning and deep learning have shown great potential in the study of 3D cancer genome. Conclusion: Current advances in the study of the 3D cancer genome have expanded our understanding of the mechanisms underlying tumorigenesis and development. It will provide new insights into precise diagnosis and personalized treatment for cancers. [ABSTRACT FROM AUTHOR]

Transcription factors (TFs) and microRNAs (miRNAs) are well-characterized transacting essential players in gene expression regulation. Growing evidence indicates that TFs and miRNAs can work cooperatively, and their dysregulation has been associated with many diseases including cancer. A unified picture of regulatory interactions of these regulators and their joint target genes would shed light on cancer studies. Although online resources developed to support probing of TF-gene and miRNA-gene interactions are available, online applications for miRNA-TF co-regulatory analysis, especially with a focus on cancers, are lacking. In light of this, we developed a web tool, namely CMTCN (freely available at http://www.cbportal.org/CMTCN), which constructs miRNA-TF co-regulatory networks and conducts comprehensive analyses within the context of particular cancer types. With its user-friendly provision of topological and functional analyses, CMTCN promises to be a reliable and indispensable web tool for biomedical studies. [ABSTRACT FROM AUTHOR]

Motivation: Transcription factor binding sites (TFBSs) are clustered in the human genome, forming the TFBS-clustered regions that regulate gene transcription, which requires dynamic chromatin configurations between promoters and distal regulatory elements. Here, we propose a regulatory model called spatially adjacent TFBS-clustered regions (SATs), in which TFBS-clustered regions are connected by spatial proximity as identified by high-resolution Hi-C data. Results: TFBS-clustered regions forming SATs appeared less frequently in gene promoters than did isolated TFBS-clustered regions, whereas SATs as a whole appeared more frequently. These observations indicate that multiple distal TFBS-clustered regions combined to form SATs to regulate genes. Further examination confirmed that a substantial portion of genes regulated by SATs were located between the paired TFBS-clustered regions instead of the downstream. We reconstructed the chromosomal conformation of the H1 human embryonic stem cell line using the ShRec3D algorithm and proposed the SAT regulatory model. [ABSTRACT FROM AUTHOR]

Chromatin insulators are DNA elements that regulate the level of gene expression either by preventing gene silencing through the maintenance of heterochromatin boundaries or by preventing gene activation by blocking interactions between enhancers and promoters. CCCTC-binding factor (CTCF), a ubiquitously expressed 11-zinc-finger DNA-binding protein, is the only protein implicated in the establishment of insulators in vertebrates. While CTCF has been implicated in diverse regulatory functions, CTCF has only been studied in a limited number of cell types across human genome. Thus, it is not clear whether the identified cell type-specific differences in CTCF-binding sites are functionally significant. Here, we identify and characterize cell type-specific and ubiquitous CTCF-binding sites in the human genome across 38 cell types designated by the Encyclopedia of DNA Elements (ENCODE) consortium. These cell type-specific and ubiquitous CTCFbinding sites show uniquely versatile transcriptional functions and characteristic chromatin features. In addition, we confirm the insulator barrier function of CTCF-binding and explore the novel function of CTCF in DNA replication. These results represent a critical step toward the comprehensive and systematic understanding of CTCF-dependent insulators and their versatile roles in the human genome. [ABSTRACT FROM AUTHOR]

Background: Perfluorododecanoic acid (PFDoA) is a perfluorinated carboxylic chemical (PFC) that has broad applications and distribution in the environment. While many studies have focused on hepatotoxicity, immunotoxicity, and reproductive toxicity of PFCAs, few have investigated renal toxicity. Methodology/Principal Findings: Here, we used comparative proteomic and metabonomic technologies to provide a global perspective on renal response to PFDoA. Male rats were exposed to 0, 0.05, 0.2, and 0.5 mg/kg/day of PFDoA for 110 days. After 2-D DIGE and MALDI TOF/TOF analysis, 79 differentially expressed proteins between the control and the PFDoA treated rats (0.2 and 0.5 mg-dosed groups) were successfully identified. These proteins were mainly involved in amino acid metabolism, the tricarboxylic acid cycle, gluconeogenesis, glycolysis, electron transport, and stress response. Nuclear magnetic resonance-based metabonomic analysis showed an increase in pyruvate, lactate, acetate, choline, and a variety of amino acids in the highest dose group. Furthermore, the profiles of free amino acids in the PFDoA treated groups were investigated quantitatively by high-coverage quantitative iTRAQ-LC MS/MS, which showed levels of sarcosine, asparagine, histidine, 1-methylhistidine, Ile, Leu, Val, Trp, Tyr, Phe, Cys, and Met increased markedly in the 0.5 mg dosed group, while homocitrulline, a-aminoadipic acid, b-alanine, and cystathionine decreased. Conclusion/Significance: These observations provide evidence that disorders in glucose and amino acid metabolism may contribute to PFDoA nephrotoxicity. Additionally, &agr;2u globulin may play an important role in protecting the kidneys from PFDoA toxicity. [ABSTRACT FROM AUTHOR]