3D printed VEGF-CPO biomaterial scaffold to promote subcutaneous vascularization and survival of transplanted islets for the treatment of diabetes.

Diabetes is a complex metabolic disease and islet transplantation is a promising approach for the treatment of diabetes. Unfortunately, the transplanted islets at the subcutaneous site are also affected by various adverse factors such as poor vascularization and hypoxia. In this study, we utilize biocompatible copolymers l-lactide and D,l-lactide to manufacture a biomaterial scaffold with a mesh-like structure via 3D printing technology, providing a material foundation for encapsulating pancreatic islet cells. The scaffold maintains the sustained release of vascular endothelial growth factor (VEGF) and a slow release of oxygen from calcium peroxide (CPO), thereby regulating the microenvironment for islet survival. This helps to improve insufficient subcutaneous vascularization and reduce islet death due to hypoxia post-transplantation. By pre-implanting VEGF-CPO scaffolds subcutaneously into diabetic rats, a sufficiently vascularized site is formed, thereby ensuring early survival of transplanted islets. In a word, the VEGF-CPO scaffold shows good biocompatibility both in vitro and in vivo, avoids the adverse effects on the implanted islets, and displays promising clinical transformation prospects.

Liquid biopsy techniques and pancreatic cancer: diagnosis, monitoring, and evaluation.

Pancreatic cancer (PC) is one of the most common malignancies. Surgical resection is a potential curative approach for PC, but most patients are unsuitable for operations when at the time of diagnosis. Even with surgery, some patients may still experience tumour metastasis during the operation or shortly after surgery, as precise prognosis evaluation is not always possible. If patients miss the opportunity for surgery and resort to chemotherapy, they may face the challenging issue of chemotherapy resistance. In recent years, liquid biopsy has shown promising prospects in disease diagnosis, treatment monitoring, and prognosis assessment. As a noninvasive detection method, liquid biopsy offers advantages over traditional diagnostic procedures, such as tissue biopsy, in terms of both cost-effectiveness and convenience. The information provided by liquid biopsy helps clinical practitioners understand the molecular mechanisms underlying tumour occurrence and development, enabling the formulation of more precise and personalized treatment decisions for each patient. This review introduces molecular biomarkers and detection methods in liquid biopsy for PC, including circulating tumour cells (CTCs), circulating tumour DNA (ctDNA), noncoding RNAs (ncRNAs), and extracellular vesicles (EVs) or exosomes. Additionally, we summarize the applications of liquid biopsy in the early diagnosis, treatment response, resistance assessment, and prognostic evaluation of PC.

Comprehensive analysis of expression signature and immune microenvironment signature of biomarker Endothelin Receptor Type A in stomach adenocarcinoma.

Background: EDNRA (Endothelin Receptor Type A) is closely associated with tumor progression in many tumor types. However, the functional mechanism of EDNRA in stomach adenocarcinoma (STAD) remains to be elucidated. Methods: ENDRA expression levels in STAD were assessed. A Receiver Operating Characteristic (ROC) curve was constructed to measure the diagnostic value of EDNRA. The correlation between ENDRA expression levels and patient clinical-pathological characteristics was analyzed. The survival and prognostic significance were validated using Kaplan-Meier and Cox regression and confirmed by the immunohistochemistry cohorts. Differentially expressed genes of EDNRA in STAD were determined, and EDNRA related functional enrichment and biological pathways involved in STAD were obtained by Gene-Set Enrichment Analysis (GSEA). The correlation between EDNRA expression in STAD and immune cell infiltration was assessed using the CIBERSORT and Spearman correlation analysis, and the correlation between EDNRA and TMB, MSI, IC50, and immune checkpoints was examined. Results: EDNRA expression was significantly higher in STAD than in normal tissues (P < 0.001) and associated with worse overall survival (OS). EDNRA expression was significantly associated with T stage, histological type, histologic grade, and TP53 status. Cox regression analysis revealed that primary therapy outcome, age, tumor status, and EDNRA were independent prognostic factors for OS. Multivariate analysis revealed that EDNRA expression, tumor status, age, and primary therapy outcome influenced patient prognosis. GSEA was significantly enriched in several pathways and biological processes, which include Immunoregulatory, Hedgehog, WNT, PI3K-AKT.NK cells, Tem, macrophages, and mast cells were substantially positively correlated with EDNRA expression in the STAD microenvironment. Notably, high EDNRA expression may promote M2 macrophages to block PD-1-mediated immunotherapy and induce immunosuppression. In addition, patients with high expression of EDNRA might be resistant to the treatment of several anti-tumor drugs. Conclusion: Our results suggest that EDNRA was closely related to clinicopathologic characteristics, poor prognosis, and promoted macrophage differentiation and synergistic role in immunosuppression.

Identification of Novel Biomarkers With Diagnostic Value and Immune Infiltration in Burn Injury.

Burn injury is an intractable problem in the field of surgery where screening relevant target genes and exploring pathological mechanisms through bioinformatic methods has become a necessity. Herein, we integrated three burn injury mRNA microarray datasets from the Gene Expression Omnibus database to analyze the hub differentially expressed genes (DEGs) between burn injury patient samples and healthy human samples; we conducted multiple functional enrichment analyses and constructed the protein-protein interaction (PPI) network. Finally, we evaluated the immune infiltration in the burn injury microenvironment. A total of 84 intersection DEGs (32 upregulated and 52 downregulated) were screened in burn injury patients via integrated analyses. Upregulated genes were primarily enriched in regulation of T cell activation, regulation of response to DNA damage stimulus, positive regulation of innate immune response, positive regulation of defense response. We also identified 10 hub genes from the PPI network (CCNB2, MYO10, TTK, POLQ, VASP, TIMP1, CDK16, MMP1, ZYX, and PKMYT1). Next, we found that 22 immune cells were substantially changed during the burn injury by CIBERSORT. In addition, we verified that VASP and POLQ are two novel diagnostic markers in burn processes with high diagnostic efficacy via immunohistochemistry. In summary, we identified several key genes involved in burn injury and provided a favorable basis for elucidating the molecular mechanisms of burn injury through comprehensive bioinformatic analysis.

Molecular Characteristics, Oncogenic Roles, and Relevant Immune and Pharmacogenomic Features of EVA1B in Colorectal Cancer.

OBJECTIVE: EVA1B, a protein coding gene, is a critical paralog of EVA1A gene. Herein, our study was conducted to investigate the role of EVA1B in colorectal cancer (CRC) progression and prognosis. METHODS: Pan-cancer analysis was conducted to analyze expression, genetic and epigenetic alterations, and immunological characteristics of EVA1B. Especially, immunological characteristics and mutational landscape were compared between high and low EVA1B expression groups in the combined TCGA-COAD and TCGA-READ datasets. Through random survival forest analysis, an EVA1B-derived genomic model was developed, and its prognostic value was verified in the external datasets (GSE14333, GSE39582, and GSE87211). Drug sensitivity was compared between high- and low-risk subpopulations. A nomogram was conducted through integrating independent factors. RESULTS: EVA1B expression presented a remarkable upregulation in most cancer types, especially CRC. EVA1B expression was significantly correlated to DNA methyltransferases, DNA mismatch repair genes, m6A regulators, TMB, and MSI across pan-cancer. High EVA1B expression indicated an undesirable CRC patients' prognosis. Additionally, its upregulation was correlated to enhanced immune cell infiltration, increased stromal and immune activation, and elevated activities of cancer immunity cycle. Higher frequencies of amplification and deletion were investigated in high EVA1B expression subpopulation. Following verification, the EVA1B-derived genomic model reliably predicted patients' prognosis and drug responses. The nomogram (age, stage, EVA1B-derived risk score) was conducted to quantify an individual's survival probability. Furthermore, our experimental validation based on immunohistochemistry indicated that EVA1B overexpression is correlated with CRC tumorigenesis and poor outcomes in our CRC patients' cohort. CONCLUSION: Collectively, our findings provided valuable resource for guiding the mechanisms and therapeutic analysis of EVA1B in CRC.

Identification and Validation of a Novel 2-LncRNAs Signature Associated with m6A Regulation in Colorectal Cancer.

Colorectal cancer (CRC) is one of the most common tumors in the digestive system, and it is urgent to identify a new biomarker for the diagnosis and treatment of CRC. N6-methyladenosine (m6A) is an abundant mRNA modification and is almost involved in every aspect of physiological processes. In this study, we constructed a novel m6A-related 2-lncRNAs signature that can predict the prognosis of CRC. We obtained m6A-related lncRNAs and identified prognostic lncRNAs through univariate Cox regression analysis and least absolute shrinkage and selection operator (LASSO) analysis, then constructed a prognostic model based on the risk score, and we also verified the stability of the model. In addition, differential expression analysis between the high- and low-risk subgroups was performed. A total of 1,894 m6A-related lncRNAs were screened from various sources. Using univariate Cox regression analysis and survival analysis, two lncRNAs (AL135999.1 and AL049840.4) were identified (P < 0.05), and the coefficients of lncRNAs were calculated by LASSO. The high-risk group had worse clinical outcomes and overall survival (OS) than the low-risk group, and the risk score can serve as an independent prognostic factor in CRC. In addition, different stages of CRC also showed a different level of risk score. Finally, we found that two lncRNAs were differentially expressed (P < 0.01) in CRC patients, and AL135999.1 may be relevant to m6A modification mediated by methyltransferase-like 3 (METTL3) in CRC. In summary, we constructed a reliable 2-lncRNAs signature based on the risk score, and we identified two m6A-related prognostic lncRNAs, AL135999.1 and AL049840.4. The novel 2-lncRNAs signature plays an essential role in predicting the prognosis of CRC.

Assessing Tetrahedral Lattice Parameters for Engineering Applications Through Finite Element Analysis.

Minimizing weight while maintaining strength in components is a continuous struggle within manufacturing industries, especially in aerospace. This study explores how controlling the dimensions of the geometric parameters of a lattice yields ideal mechanical properties for aerospace-related applications. A previously developed Bubble-mesh based computational method was used to generate a novel type of tetrahedral lattice that allows for the manipulation of three geometric parameters: cell size/density, strut diameter, and strut intersection rounding. Topology optimization and lattice generation within components are typical methods used to decrease weight while maintaining strength. Although these are robust optimization methods, each have their faults. Highly topology-optimized components may fail under unexpected loads, and lattice generation within commercial software is often limited in its ability to create ideal lattices with controlled geometric parameters, resulting in lattices with repeating unit cells. In this study, we used finite element methods (FEM)-based compression tests on latticed cubes with various parameter combinations to determine the best balance of lattice parameters. The results showed that strut diameter and strut intersection rounding were the best parameters to control to maintain strength and reduce weight. This understanding of the lattice structures was then applied to two aerospace components: a jet engine bracket and an airplane bearing bracket. By applying tetrahedral lattices with specified strut diameters and strut intersection rounding, the weight of the jet engine bracket was reduced by 51.8%, and the airplane bearing bracket was reduced by 20.5%.