Synthesis of Asp-based lactam cyclic peptides using an amide-bonded diaminodiacid to prevent aspartimide formation.

Asp-based lactam cyclic peptides are considered promising drug candidates. However, using Fmoc solid-phase peptide synthesis (Fmoc-SPPS) for these peptides also causes aspartimide formation, resulting in low yields or even failure to obtain the target peptides. Here, we developed a diaminodiacid containing an amide bond as a ß-carboxyl-protecting group for Asp to avoid aspartimide formation. The practicality of this diaminodiacid has been illustrated by the synthesis of lactam cyclic peptide cyclo[Lys9,Asp13] KIIIA7-14 and 1Y.

Cell-Permeable Ubiquitin and Histone Tools for Studying Post-translational Modifications.

Protein post-translational modifications (PTMs) regulate nearly all biological processes in eukaryotic cells, and synthetic PTM protein tools are widely used to detect the activity of the related enzymes and identify the interacting proteins in cell lysates. Recently, the study of these enzymes and the interacting proteome has been accomplished in live cells using cell-permeable PTM protein tools. In this concept, we will introduce cell penetrating techniques, the syntheses of cell-permeable PTM protein tools, and offer some future perspective.

Research on the application and effect of flipped-classroom combined with TBL teaching model in WeChat-platform-based biochemical teaching under the trend of COVID-19.

BACKGROUND: Biochemistry is a core subject in clinical medical education. The traditional classroom teaching model led by teachers is often limited to the knowledge transfer of teachers and the passive acceptance of students. It lacks interactive and efficient teaching methods and is not enough to meet the learning needs and educational goals of modern students. The combination of WeChat public platform, flipped classroom and TBL teaching model is closer to the needs of real life and workplace, helping students to cultivate comprehensive literacy and the ability to solve practical problems. At the same time, this teaching model has yet to be used in biochemistry courses. OBJECTIVE: To explore the influence of the mixed teaching model of flipped classroom and combining TBL based on WeChat public platform upon undergraduates in biochemistry. METHODS: Using the mixed research method of quasi-experimental research design and descriptive qualitative research, 68 students were selected into the traditional and the blended teaching groups. Among them, the blended teaching group adopts the blended teaching model of flipped classroom combined with TBL based on the WeChat platform to learn biochemical courses. In this study, an independent sample t-test was intended to analyze the differences in final scores, a chi-square test was served to analyze the differences in satisfaction questionnaires, and thematic analysis was used to analyze semi-structured interview data. RESULTS: Compared with the traditional teaching model, the mixed teaching model significantly improved students' final exam scores (P < 0.05). The teaching satisfaction of the mixed teaching group was also higher than that of the traditional teaching group with statistical significance (P < 0.05). The results of the interviews with eight students were summarized into three topics: (1) Stimulating interest in learning; (2) Improving the ability of autonomous learning; (3) Recommendations for improvement. CONCLUSIONS: The combination of the WeChat platform and flipped classroom with TBL has a positive effect on improving medical students' autonomous learning ability and problem-solving ability. The research shows that the teaching mode of flipped classroom combined with TBL based on the WeChat platform is effective and feasible.

Formulation and Physicochemical and Biological Characterization of Etoposide-Loaded Submicron Emulsions with Biosurfactant of Sophorolipids.

Etoposide (ETO), a traditional anticancer chemotherapeutic agent, is commercialized in oral soft gelatin capsules and non-aqueous parenteral solutions form. Novel formulation application and new excipients exploration are needed to improve the water-solubility and comfort of the drug administration. In the present study, novel etoposide-loaded submicron emulsions (ESE) with the biosurfactants of acidic sophorolipid (ASL) and lactonic sophorolipid (LSL) instead of the chemical surfactant of Tween-80 were prepared and characterized. Firstly, parameters of medium-chain triglyceride: long-chain triglyceride (MCT:LCT), lecithin concentration, homogenization pressure and cycle, and type and concentration of surfactants were investigated to optimize the formation of ESEs. Then the physicochemical properties, antitumor activity, stability, and security of ESEs were compared. The results showed that ASL performed the best properties and activities than Tween-80 and LSL in ESE formation. ASL-ESE showed higher drug loading capacity, slower release rate, and significantly increased antitumor activity against ovarian cancer cell line A2780 via apoptosis than Tween-ESE and commercial ETO injection. Besides, both ASL-ESE and Tween-ESE caused no hemolysis, and the safe dose of ASL was 2.14-fold that of Tween-80 in the hemolysis test, making ASL more reliable for drug delivery applications. Furthermore, ASL-ESE exhibited equivalent long-term and autoclaving stability to Tween-ESE. These results thus suggested the excellent competences of ASL in ESE formation, efficacy enhancement, and safety improvement.

Investigating the Involvement of Cytoskeletal Proteins MreB and FtsZ in the Origin of Legume-Rhizobial Symbiosis.

Rhizobia are rod-shaped bacteria that form nitrogen-fixing root nodules on leguminous plants; however, they don't carry MreB, a key determinant of rod-like cell shape. Here, we introduced an actin-like mreB homolog from a pseudomonad into Mesorhizobium huakuii 7653R (a microsymbiont of Astragalus sinicus L.) and examined the molecular, cellular, and symbiotic phenotypes of the resultant mutant. Exogenous mreB caused an enlarged cell size and slower growth in laboratory medium. However, the mutant formed small, ineffective nodules on A. sinicus (Nod+ Fix-), and rhizobial cells in the infection zone were unable to differentiate into bacteroids. RNA sequencing analysis also revealed minor effects of mreB on global gene expression in free-living cells but larger effects for cells grown in planta. Differentially expressed nodule-specific genes include cell cycle regulators such as the tubulin-like ftsZ1 and ftsZ2. Unlike the ubiquitous FtsZ1, an FtsZ2 homolog was commonly found in Rhizobium, Sinorhizobium, and Mesorhizobium spp. but not in closely related nonsymbiotic species. Bacterial two-hybrid analysis revealed that MreB interacts with FtsZ1 and FtsZ2, which are targeted by the host-derived nodule-specific cysteine-rich peptides. Significantly, MreB mutation D283A disrupted the protein-protein interactions and restored the aforementioned phenotypic defects caused by MreB in M. huakuii. Together, our data indicate that MreB is detrimental for modern rhizobia and its interaction with FtsZ1 and FtsZ2 causes the symbiotic process to cease at the late stage of bacteroid differentiation. These findings led to a hypothesis that loss of mreB in the common ancestor of members of Rhizobiales and subsequent acquisition of ftsZ2 are critical evolutionary steps leading to legume-rhizobial symbiosis.[Formula: see text] Copyright © 2021 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

Chemical synthesis of disulfide surrogate peptides by using beta-carbon dimethyl modified diaminodiacids.

The replacement of disulfide bridges with metabolically stable isosteres is a promising strategy to improve the stability of disulfide-rich polypeptides towards reducing agents and isomerases. A diaminodiacid-based strategy is one of the most effective methods to construct disulfide bond mimics, but modified diaminodiacids have not been developed till now. Inspired by the fact that alkylation of disulfide bonds can regulate the activity of polypeptides, herein, we report the first example of thioether bridged diaminodiacids incorporating Cys Cß dimethyl modification, obtained by penicillamine (Pen)-based thiol alkylation. The utility of these new diaminodiacids was demonstrated by the synthesis of disulfide surrogates of oxytocin containing a short-span disulfide bond and of KIIIA with large-span disulfide bonds. This new type of synthetic bridge further extends the diaminodiacid toolbox to facilitate the study of the structure-activity relationship of disulfide-rich peptides.

In-situ reactive heat breaking cell wall by SO3 hydration: innovative cell-wall breaking technique to enhance extraction of cinnamaldehyde from cinnamon.

Cinnamaldehyde (CA) is one of the major active pharmaceutical ingredient of cinnamon bark. Hydrodistillation (HD) is usually used in CA extraction, however, the extraction yield is lower. The cell wall is a key factor limiting the extraction of essential oils. In-situ reactive heat breaking cell wall (RHB) could destroy the cell wall, which was conducive to the diffusion of CA. The aim of this work was to examine the effect of RHB pretreatment to HD extraction. Response surface methodology (RSM) was used to optimize RHB pretreatment parameters, and Box-Behnken Design (BBD) method was performed to evaluate the effects of different operating parameters. The maximum yield was increased to 3.31 ± 0.11% (w/w) from 2.08 ± 0.042% (w/w) after RSM optimization. Scanning electron microscopic (SEM) analysis showed that RHB destroyed and disrupted the cell wall of cinnamon bark. The GC analysis demonstrated that the purity of cinnamaldehyde was improved and no new components were presented in the extraction product from the cinnamon via RHB pretreatment. In conclusion, RHB is an effective pretreatment method for the CA extraction, and also may be used in the other herbal medicine extraction.

P(NMe2)3 mediated cyclopropanation of α-methylene-ß-lactams for rapid syntheses of spirocyclopropyl ß-lactams.

An expedient cyclopropanation of α-methylene-ß-lactams with α-ketoesters mediated by P(NMe2)3 has been developed. This reaction enables rapid access to a series of functionalized spirocyclopropyl ß-lactams in good yields from bench-stable starting materials under mild conditions. The experimental results indicated that the C3-substituent of the α-methylene-ß-lactam not only significantly impacted the reaction efficiency and stereochemistry but also played a pivotal role in determining the chemoselectivity of the reaction.

Sophorolipid biosynthesis and production from diverse hydrophilic and hydrophobic carbon substrates.

Sophorolipids (SLs), mainly synthesized by yeasts, were a sort of biosurfactant with the highest fermentation level at present. In recent years, SLs have drawn extensive attention for their excellent physiochemical properties and physiological activities. Besides, issues such as economics, sustainability, and use of renewable resources also stimulate the shift from chemical surfactants towards green or microbial-derived biosurfactants. SLs' large-scale production and application were restricted by the relatively high production costs. Currently, waste streams from agriculture, food and oil refining industries, etc., have been exploited as low-cost renewable substrates for SL production. Advanced cultivation method, uncommonly used substrates, and new genetically modified SL-producing mutants were also designed and applied to improve the productivity or the special properties of SLs. In this review, a systematic and detailed description of primary and secondary metabolism pathways involved in SL biosynthesis was summarized firstly. Furthermore, based on the pathways of SL biosynthesis from different carbon substrates, we reviewed the current knowledge and advances in the exploration of cost-effective and infrequently used hydrophilic and hydrophobic substrates for large or specialized SL production.

Mutant breeding of Starmerella bombicola by atmospheric and room-temperature plasma (ARTP) for improved production of specific or total sophorolipids.

To enhance specific or total sophorolipids (SLs) production by Starmerella bombicola for specific application, mutant library consisting of 106 mutants from 7 batches was constructed via atmospheric and room-temperature plasma (ARTP). When compared to the wild strain, 11, 36 and 12 mutants performed increases over 30% in lactonic, acidic or total SLs production. Genetic stability investigation showed that 8, 7, and 4 mutants could maintain the improved SLs production capacity. Mutants of A6-9 and A2-8 were selected out for enhanced specific SLs and total SLs production in fed-batch cultivation in flask. Without optimization, A6-9 obtained the highest reported lactonic SLs production of 51.95 g/l and A2-8 performed comparable acidic and total SLs production of 68.75 g/l and 100.33 g/l with all the reported stains. The structural composition of the obtained SLs was analyzed by HPLC and LC/MS, and the results confirmed the enhancement of SLs and certain SL components. These mutants would be important in industrial applications because the production and purification costs of SLs could be greatly reduced. Besides, the acquisition of these mutants also provided materials for the investigation of regulation mechanism of SLs biosynthesis for further genetic engineering of S. bombicola. Furthermore, critical micelle concentration (CMC), minimum surface tension (STmin) and hydrophilic-lipophilic balance (HLB) of the SLs obtained from the wild and mutant strains were also examined and compared. These results demonstrated the feasibility of obtaining SLs with different properties from different strains and the high efficiency of mutation breeding of S. bombicola by ARTP.

GATA binding protein 3 is correlated with leptin regulation of PPARγ1 in hepatic stellate cells.

Accumulating evidence reveals that hormone leptin, mainly produced by adipocyte, plays a unique role in promotion of liver fibrosis. Hepatic stellate cell (HSC) activation is a key step in liver fibrosis and peroxisome-proliferator activated receptor γ (PPARγ) exerts a crucial role in inhibition of HSC activation. Our previous researches demonstrated that leptin reduced PPARγ1 (a major subtype of PPARγ in HSCs) expression through GATA binding protein 2 (GATA2) binding to a site around -2323 in PPARγ1 promoter. The present researches aimed to examine the effect of GATA3 on leptin-induced inhibition of PPARγ1 and elucidate the relationship between GATA3 and GATA2. Gene expressions were analysed by real-time PCR, western blot, luciferase assay and immunostaining. C57BL/6J ob/ob mouse model of thioacetamide-induced liver injury was used in vivo. Results demonstrate that leptin significantly induces GATA3 expression in HSCs by multiple signalling pathways including NADPH oxidase pathway. There exist crosstalks between NADPH oxidase pathway and the other pathways. GATA3 can bind to GATA2-binding site in PPARγ1 promoter and interacts with GATA2, contributing to leptin inhibition of PPARγ1 expression in HSCs. These data demonstrated novel molecular events for leptin inhibition of PPARγ1 expression in HSCs and thus might have potential implications for clarifying the detailed mechanisms underlying liver fibrosis in diseases in which circulating leptin levels are elevated such as non-alcoholic steatohepatitis in obese patients.

Inactivated Sendai virus induces apoptosis and autophagy via the PI3K/Akt/mTOR/p70S6K pathway in human non-small cell lung cancer cells.

Inactivated Sendai virus (HVJ-E) has shown potential anticancer efficacy in various cancer cells. However, the ability of HVJ-E to regulate cancer cell survival and death remains largely unknown. In the present study we first found that HVJ-E exhibited cytotoxic effects in the non-small cell lung cancer cell (NSCLC) line A549 and cisplatin-resistant A549 cells (A549/DDP). The suppression of cell viability was due to both the activation of caspases and the JNK and p38 MAPK signaling pathways in A549 and A549/DDP human lung cancer cells. In addition, we demonstrated that HVJ-E could induce autophagy in NSCLC cells via the PI3K/Akt/mTOR/p70S6K signaling pathway for the first time. Inhibiting autophagy in A549/DDP cells and inducing autophagy in A549 cells enhanced HVJ-E-induced apoptosis. These findings provide a molecular basis of HVJ-E-mediated cell death and support the notion that combination treatment with autophagy modulators is an effective strategy to augment the cytotoxic effects of HVJ-E in NSCLC cells.

Multi-omics analysis reveals the unique landscape of DLD in the breast cancer tumor microenvironment and its implications for immune-related prognosis.

Background: Cuproptosis, i.e., copper-induced programmed cell death, has potential implications in cancer therapy. However, the impact of the cuproptosis-related gene (CRG) dihydrolipoyl dehydrogenase (DLD) on breast cancer (BC) prognosis remains underexplored. Methods: We employed real-time quantitative PCR and multiplexed immunostaining techniques to quantify DLD expression in both BC and the adjacent non-cancerous tissues. Immunofluorescence analysis was employed to assess the influence of DLD on immune cells and immunological checkpoints in the BC microenvironment. DLD knockdown experiments were conducted in BC cell lines MDA-MB-468 and SK-BR-3, with knockdown efficiency validated via western blot. Subsequently, we performed the cell counting kit-8 (CCK-8) assay, clone formation assay, Transwell migration assay, and invasion assay. To construct a prognostic model, we employed a Lasso-Cox regression analysis of immune-related genes associated with DLD. Additionally, we established a competing endogenous RNA network based on CRGs to evaluate potential regulatory pathways. Results: Compared to the adjacent tissues, BC tissues exhibited markedly elevated DLD expression levels. In vitro experiments demonstrated that DLD knockdown effectively inhibited BC cell migration, invasion, and proliferation. DLD exhibited positive correlations with CD68+ macrophages and PD-L1 in the tumor, as well as with macrophages and CD4+ T cells in the stroma. Tumor regions with high DLD expression were enriched in PD-L1 and macrophages, while stromal regions with high DLD expression contained CD4+ T cells and macrophages. The AUC values for 1-, 3-, and 5-year overall survival in TCGA-BRCA training set were 0.67, 0.66, and 0.66, respectively. A nomogram with a C-index of 0.715 indicated that risk score, tumor stage, and age could serve as independent prognostic factors for BC. Conclusion: Our findings underscore the significant predictive significance of DLD in BC and its influence on the tumor microenvironment. DLD represents a promising diagnostic and prognostic marker for BC, offering novel avenues for the identification of therapeutic targets and the enhancement of immunotherapy in BC.

Application effect evaluation of hybrid biochemistry teaching model based on WeChat platform under the trend of COVID-19.

With WeChat platform as the carrier, we explored the effect of online and offline mixed teaching mode applied to Biochemistry teaching. One hundred and eighty-three students from the 4-year nursing major of Xinglin College of Nantong University in 2018 and 2019 were used as the observation group, using online and offline hybrid teaching methods, and 221 students majoring in 4-year nursing from Xinglin College of Nantong University in 2016 and 2017 were the control group, where the traditional classroom teaching method was adopted. The usual stage scores and final scores of the observation group were significantly higher than those of the control group (P < .01). The micro-lecture videos, animations, and periodic assessment methods of the WeChat platform under "Internet+" can greatly stimulate students' interest in learning, thereby significantly improving academic performance and autonomous learning ability.

Machine learning- and WGCNA-mediated double analysis based on genes associated with disulfidptosis, cuproptosis and ferroptosis for the construction and validation of the prognostic model for breast cancer.

BACKGROUND: Disulfidptosis, a recently discovered cellular death mechanism, has not been extensively studied in relation to breast cancer (BC). Specifically, no previous research has integrated disulfidptosis-related genes (DRGs), cuproptosis-related genes (CRGs), and ferroptosis-related genes (FRGs) to construct a prognostic signature for BC. METHODS: DRGs, CRGs and FRGs with prognostic potential were identified through Cox regression analysis. A predictive model was constructed by intersecting the core genes obtained from unsupervised cluster analysis and weighted correlation network analysis (WGCNA). Differences in chemotherapy drug sensitivity, immune checkpoint levels were analyzed according to different risk score groups. The expression of the core disulfidptosis gene, SLC7A11, was analyzed using immunofluorescence. RESULTS: Single-cell RNA sequencing analysis revealed differential expression of DRGs in the BC tumor microenvironment. We developed a prognostic model, consisting of six genes, based on machine learning which included unsupervised cluster analysis and Lasso-Cox analysis. An internal training set and a validation set, both derived from the Cancer Genome Atlas-Breast Cancer (TCGA-BRCA) database, GSE20685 and GSE42568 as external validation sets all verified the model's validity. The low-risk group exhibited increased sensitivity to paclitaxel. Additionally, the high-risk group demonstrated significantly higher expression of tumor mutation burden and microsatellite instability compared to the low-risk group. A nomogram confirmed that the risk score can be an independent risk factor for BC. Notably, our findings highlighted the impact of SLC7A11 on the BC tumor microenvironment. Immunofluorescence analysis revealed significantly higher expression of SLC7A11 in BC tissues compared to paracancerous tissues. CONCLUSION: Multiplex analysis based on DRGs, CRGs and FRGs correlated strongly with BC, providing new insights for developing clinical prognostic tools and designing immunotherapy regimens for BC patients.

p38 mitogen-activated protein kinase and liver X receptor-α mediate the leptin effect on sterol regulatory element binding protein-1c expression in hepatic stellate cells.

Leptin, a key hormone in regulating energy homeostasis, is mainly produced by adipocytes. Cogent evidence indicates a unique role of leptin in the promotion of liver fibrosis. Hepatic stellate cell (HSC) activation is a pivotal step in the process of liver fibrosis. Sterol regulatory element binding protein (SREBP)-1c, a critical transcription factor for lipid synthesis and adipocyte differentiation, functions as a key transcription factor in inhibition of HSC activation. SREBP-1c is highly expressed in quiescent HSCs and downregulated upon HSC activation. The aim of this study is to examine the effect of leptin on SREBP-1c gene expression in HSCs in vitro and in vivo and elucidate the underlying mechanisms. The results of the present study demonstrated that leptin strongly inhibited SREBP-1c expression in HSCs in vivo and in vitro. p38 MAPK was involved in leptin regulation of SREBP-1c expression in cultured HSCs. Leptin-induced activation of p38 MAPK led to the decreases in liver X receptor (LXR)-α protein level, activity and its binding to the SREBP-1c promoter, which caused the downregulation of SREBP-1c expression. Moreover, leptin inhibition of SREBP-1c expression via p38 MAPK increased the expression of alpha1(I) collagen in HSCs. Our results might provide new insights into the mechanisms of the unique role of leptin in the development of liver fibrosis and might have potential implications for clarifying the molecular mechanisms underlying liver fibrosis in diseases in which circulating leptin levels are elevated such as nonalcoholic steatohepatitis, type 2 diabetes mellitus and alcoholic cirrhosis.

Novel and highly effective chemoenzymatic synthesis of (2R)-2-[4-(4-cyano-2-fluorophenoxy)phenoxy]butylpropanoate based on lipase mediated transesterification.

(2R)-2-[4-(4-Cyano-2-fluorophenoxy)phenoxy]butylpropanoate (cyhalofop-butyl, CyB) was synthesized by a chemoenzymatic route involving enantioselective transesterification with Candida antarctica lipase B (Novozym 435). The optimum organic solvent, acyl donor, a ( w ), reaction temperature and shaking rate for the transesterification were acetonitrile, n-butanol, 0.11, 45°C and 200 rpm, respectively. Under the optimum conditions, the maximum substrate conversion and the enantiomeric purity of the product were 96.9 and >99%, respectively. The total yield and enantiomeric purity of CyB by this chemoenzymatic synthesis were 60.4 and >99%, respectively; 15.3 and 21% higher than that of the traditional way (45 and 78%).

MicroRNA-21 as a potential biomarker for detecting esophageal carcinoma in Asian populations: a meta-analysis.

Background: MicroRNA-21 (miR-21) is significantly expressed in a variety of cancers and could be used as a tumor biomarker. However, the results are varied, and no studies on the diagnostic usefulness of miR-21 in Asian esophageal cancer (EC) patients have been published. This meta-analysis was aimed at exploring whether miR-21 can be used as a diagnostic marker and assessing its effectiveness. Methods: The relevant literature was identified in six main databases: Ovid MEDLINE, PsycINFO, PubMed MEDLINE, Embase, Web of Science, and the Cochrane Library. Two researchers independently selected the literature based on the inclusion and exclusion criteria, extracted data, and evaluated the risk of bias. The meta-analysis was carried out using Review Manager 5.4, Meta-Disc 1.4 and STATA 15.1 software. In the end, 987 patients from 12 different studies were included. Quality evaluation of diagnostic accuracy studies 2 (QUADAS-2) was used to examine the risk of bias. Results: The pooled sensitivity (SEN) was 0.72 (95% CI [0.69-0.75]), the pooled specificity (SPE) was 0.78 (95% CI [0.75-0.81]), the pooled positive likelihood ratio (PLR) was 2.87 (95% CI [2.28-3.59]), the pooled negative likelihood ratio (NLR) was 0.36 (95% CI [0.31-0.43]), the pooled diagnostic odds ratio (DOR) was 10.00 (95% CI [7.73-12.95]), and the area under the curve 0.82 (95% CI [0.79-0.85]). A Deeks' funnel plot shows that there was no publication bias (P = 0.99). Conclusion: Our findings suggest miR-21 might be the potential biomarker for detecting EC in Asian populations, with a good diagnostic value.

Effect of the whole seamless connection of nursing from WeChat interactive platform on stigma and quality of life in patients with urinary system cancer.

Objective: To evaluate the effects of intervention by "whole seamless connection of nursing from WeChat interactive platform" on stigma and quality of life of the patients with urinary system cancer. Methods: Overall, 80 patients with urinary cancer were randomly divided (40 cases per group) into control and observation groups. Routine nursing was provided to the control group, whereas positive psychological intervention was provided to the intervention group through a "whole seamless connection of nursing from the WeChat interactive platform" in addition to routine nursing. The Chinese version of social impact and cancer patients' quality of life scales were used to evaluate the effects before and after the intervention. Results: After the intervention, the total score for stigma was significantly lower (p < 0.01), while that of quality of life was higher (p < 0.05) in the observation group relative to the control group. Conclusions: The whole seamless connection of nursing from the WeChat interactive platform could reduce stigma and improve the quality of life of patients with urinary cancer.

Developing and validating a survival prediction model based on blood exosomal ceRNA network in patients with PAAD.

BACKGROUND: Among the most lethal cancers, pancreatic adenocarcinoma (PAAD) is an essential component of digestive system malignancies that still lacks effective diagnosis and treatment methods. As exosomes and competing endogenous RNA (ceRNA) regulatory networks in tumors go deeper, we expect to construct a ceRNA regulatory network derived from blood exosomes of PAAD patients by bioinformatics methods and develop a survival prediction model based on it. METHODS: Blood exosome sequencing data of PAAD patients and normal controls were downloaded from the exoRbase database, and the expression profiles of exosomal mRNA, lncRNA, and circRNA were differentially analyzed by R. The related mRNA, circRNA, lncRNA, and their corresponding miRNA prediction data were imported into Cytoscape software to visualize the ceRNA network. Then, we conducted GO and KEGG enrichment analysis of mRNA in the ceRNA network. Genes that express differently in pancreatic cancer tissues compared with normal tissues and associate with survival (P < 0.05) were determined as Hub genes by GEPIA. We identified optimal prognosis-related differentially expressed mRNAs (DEmRNAs) and generated a risk score model by performing univariate and multivariate Cox regression analyses. RESULTS: 205 DEmRNAs, 118 differentially expressed lncRNAs (DElncRNAs), and 98 differentially expressed circRNAs (DEcircRNAs) were screened out. We constructed the ceRNA network, and a total of 26 mRNA nodes, 7 lncRNA nodes, 6 circRNA nodes, and 16 miRNA nodes were identified. KEGG enrichment analysis showed that the DEmRNAs in the regulatory network were mainly enriched in Human papillomavirus infection, PI3K-Akt signaling pathway, Osteoclast differentiation, and ECM-receptor interaction. Next, six hub genes (S100A14, KRT8, KRT19, MAL2, MYO5B, PSCA) were determined through GEPIA. They all showed significantly increased expression in cancer tissues compared with control groups, and their high expression pointed to adverse survival. Two optimal prognostic-related DEmRNAs, MYO5B (HR = 1.41, P < 0.05) and PSCA (HR = 1.10, P < 0.05) were included to construct the survival prediction model. CONCLUSION: In this study, we successfully constructed a ceRNA regulatory network in blood exosomes from PAAD patients and developed a two-gene survival prediction model that provided new targets which shall aid in diagnosing and treating PAAD.