Perfluoro-1-butanesulfonic acid etching strategy for dendrite suppression in aqueous zinc metal batteries.

Perfluoro-1-butanesulfonic acid (PFBS) was used to etch on the surface of a zinc anode to introduce a 3D C4F9O3S-Zn interface layer with unique fluorine groups (Zn@PFBS) to inhibit the formation of dendrites. The C-F chains in the Zn@PFBS coating enhance the anode hydrophobicity of the zinc metal, which not only suppresses the HER of the surface of the zinc metal, but also strengthens the corrosion resistance of the zinc metal. Meanwhile, -SO3 - in the coating enhanced the binding energy with Zn2+, which acted as a nucleation site on the surface of the zinc anode to induce the uniform deposition of Zn2+ and inhibited the disordered growth of zinc dendrites. As a result, the symmetric battery assembled with the Zn@PFBS anode achieved a stable cycling of 6200 cycles at 5 mA cm-2 to 1 mA h cm-2. Meanwhile, the Zn@PFBS anode exhibited a higher cycling performance with a capacity retention rate of 78.6% after 1000 cycles in a Zn@PFBS//Na5V12O32 (NVO) full cell.

TAGLN2 targeted control of ARPC5-mediated activation of the MEK/ERK signaling pathway influences the proliferation, invasion, and metastasis of pancreatic cancer cells.

PURPOSE: Pcancreatic cancer (PC) is a common tumor of the digestive tract with an insidious onset and high malignancy potential. Currently, surgery is the only effective treatment modality. Therefore, it is crucial to discover new targeted therapeutic modalities. We studied whether transgelin 2 (TAGLN2) targeted control of actin-related protein 2/3 complex subunit 5 (ARPC5)-mediated activation of the MEK/ERK signaling pathway to Influences the proliferation, invasion, and metastasis of pancreatic cancer cells. METHODS: The effects of TAGLN2 overexpression and knockdown on the proliferative viability and invasive metastatic ability of pancreatic cancer cells were verified through in vitro and in vivo assays via constructing a stable lentiviral transfection of human pancreatic cancer cell lines PANC-1 and SW1990. Bioinformatics analysis was used to predict the relationship between TAGLN2 and ARPC5. These findings were subsequently verified through protein profiling, immunofluorescence (IF), and coimmunoprecipitation (CO-IP) assays. In vitro experiments were also conducted to confirm the effect of TAGLN2 modulation on ARPC5 expression, which subsequently affects the proliferation and invasive metastatic ability of pancreatic cancer cells. The study analyzed the relationship between TAGLN2 and the MEK/ERK signaling pathway through bioinformatics and in vitro experiments with the MEK signaling pathway inhibitor U0126. RESULTS: TAGLN2 is expressed at high levels in pancreatic cancer cell lines, and its expression is positively correlated with poor prognosis of pancreatic cancer. ARPC5 is a direct target of TAGLN2 and is associated with the MEK/ERK signaling pathway. In vivo and ex vivo experiments confirmed that overexpression of TAGLN2 promoted the proliferation, invasion, and metastasis of pancreatic cancer cells, and silencing ARPC5 reversed these effect. CONCLUSION: Our research revealed that TAGLN2 protein binds to ARPC5 protein and contributes to increased ARPC5 expression and activation of the MEK/ERK signaling pathway. This activation promotes pancreatic cancer cell growth, infiltration, and spread. Hence, TAGLN2 is a potential viable therapeutic target in pancreatic cancer and represents a novel therapeutic approach.

Unveiling the role of PYGB in pancreatic cancer: a novel diagnostic biomarker and gene therapy target.

PURPOSE: Pancreatic cancer (PC) is a highly malignant tumor that poses a severe threat to human health. Brain glycogen phosphorylase (PYGB) breaks down glycogen and provides an energy source for tumor cells. Although PYGB has been reported in several tumors, its role in PC remains unclear. METHODS: We constructed a risk diagnostic model of PC-related genes by WGCNA and LASSO regression and found PYGB, an essential gene in PC. Then, we explored the pro-carcinogenic role of PYGB in PC by in vivo and in vitro experiments. RESULTS: We found that PYGB, SCL2A1, and SLC16A3 had a significant effect on the diagnosis and prognosis of PC, but PYGB had the most significant effect on the prognosis. Pan-cancer analysis showed that PYGB was highly expressed in most of the tumors but had the highest correlation with PC. In TCGA and GEO databases, we found that PYGB was highly expressed in PC tissues and correlated with PC's prognostic and pathological features. Through in vivo and in vitro experiments, we found that high expression of PYGB promoted the proliferation, invasion, and metastasis of PC cells. Through enrichment analysis, we found that PYGB is associated with several key cell biological processes and signaling pathways. In experiments, we validated that the MAPK/ERK pathway is involved in the pro-tumorigenic mechanism of PYGB in PC. CONCLUSION: Our results suggest that PYGB promotes PC cell proliferation, invasion, and metastasis, leading to poor patient prognosis. PYGB gene may be a novel diagnostic biomarker and gene therapy target for PC.

PELI1: key players in the oncogenic characteristics of pancreatic Cancer.

BACKGROUND: Pancreatic cancer (PC) is a highly malignant gastrointestinal tumor, which is characterized by difficulties in early diagnosis, early metastasis, limited therapeutic response and a grim prognosis. Therefore, it is imperative to explore potential therapeutic targets for PC. Currently, although the involvement of the Pellino E3 Ubiquitin Protein Ligase 1 (PELI1) in the human growth of some malignant tumors has been demonstrated, its association with PC remains uncertain. METHODS: Bioinformatics, qRT-PCR, Western blot and IHC were used to detect the expression of PELI1 in pancreas or PC tissues and cells at mRNA and protein levels. The effects of PELI1 on the proliferation and metastatic ability of pancreatic cancer in vitro and in vivo were investigated using CCK8, cloning formation, EdU, flow cytometry, IHC, Transwell assay, wound healing, nude mice subcutaneous tumorigenesis and intrasplenic injection to construct a liver metastasis model. The interactions of PELI1 with proteins as well as the main functions and pathways were investigated by protein profiling, Co-IP, GST-pull down, Immunofluorescence techniques, immunohistochemical co-localization and enrichment analysis. The rescue experiment verified the above experimental results. RESULTS: The mRNA and protein expression levels of PELI1 in PC tissues were upregulated and were associated with poor prognosis of patients, in vitro and in vivo experiments confirmed that PELI1 can affect the proliferation and metastatic ability of PC cells. Co-IP, GST-pull down, and other experiments found that PELI1 interacted with Ribosomal Protein S3 (RPS3) through the FHA structural domain and promoted the polyubiquitination of RPS3 in the K48 chain, thereby activates the PI3K/Akt/GSK3ß signaling pathway. Moreover, ubiquitinated degradation of RPS3 further reduces Tumor Protein P53 (p53) protein stability and increases p53 degradation by MDM2 Proto-Oncogene (MDM2). CONCLUSION: PELI1 is overexpressed in PC, which increased ubiquitination of RPS3 proteins and activates the PI3K/Akt/GSK3ß signaling pathway, as well as reduces the protective effect of RPS3 on p53 and promotes the degradation of the p53 protein, which facilitates the progression of PC and leads to a poor prognosis for patients. Therefore, PELI1 is a potential target for the treatment of PC.

A study on the role of Taxifolin in inducing apoptosis of pancreatic cancer cells: screening results using weighted gene co-expression network analysis.

Pancreatic adenocarcinoma (PAAD) is a frequent malignant tumor in the pancreas. The incomplete understanding of cancer etiology and pathogenesis, as well as the limitations in early detection and diagnostic methods, have created an urgent need for the discovery of new therapeutic targets and drugs to control this disease. As a result, the current therapeutic options are limited. In this study, the weighted gene co-expression network analysis (WGCNA) method was employed to identify key genes associated with the progression and prognosis of pancreatic adenocarcinoma (PAAD) patients in the Gene Expression Profiling Interactive Analysis (GEPIA) database. To identify small molecule drugs with potential in the treatment of pancreatic adenocarcinoma (PAAD), we compared key genes to the reference dataset in the CMAP database. First, we analyzed the antitumor properties of small molecule drugs using cell counting kit-8 (CCK-8), AO/EB and Transwell assays. Subsequently, we integrated network pharmacology with molecular docking to explore the potential mechanisms of the identified molecules' anti-tumor effects. Our findings indicated that the progression and prognosis of PAAD patients in pancreatic cancer were associated with 11 genes, namely, DKK1, S100A2, CDA, KRT6A, ITGA3, GPR87, IL20RB, ZBED2, PMEPA1, CST6, and MUC16. These genes were filtered based on their therapeutic potential through comparing them with the reference dataset in the CMAP database. Taxifolin, a natural small molecule drug with the potential for treating PAAD, was screened by comparing it with the reference dataset in the CMAP database. Cell-based experiments have validated the potential of Taxifolin to facilitate apoptosis in pancreatic cancer cells while restraining their invasion and metastasis. This outcome is believed to be achieved via the HIF-1 signaling pathway. In conclusion, this study provided a theoretical basis for screening genes related to the progression of pancreatic cancer and discovered potentially active small molecule drugs. The experimental results confirm that Taxifolin has the ability to promote apoptosis in pancreatic cancer cells.

Dilemma of Low-Cost Filter Paper as Separator: Toughen Its Wet Strength for Robust Aqueous Zinc-Ion Batteries.

The industrialization of aqueous zinc-ion batteries (AZIBs) is hampered by poor-performance separators. Filter paper (FP), with mature production processes and low prices, has potential as a separator. However, its swelling and decline of mechanical durability in aqueous environments make it easily punctured by dendrites. In response, wet strength promotion is proposed to toughen FP for robust AZIBs, termed wet-strengthened FP (WSFP). Due to the self-cross-linking network formed on cellulose fibers, water molecules are prevented from easily permeating and disrupting the hydrogen bonds between cellulose molecules. Moreover, the positively charged network can anchor SO42-, thus increasing the Zn2+ transference number and facilitating uniform zinc deposition. Surprisingly, the half and full cells with the WSFP separator present much more stable cycling than untreated FP and glass fiber (GF) separators. These results suggest that robust and low-cost WSFP separators provide a new avenue for the development of high-performance AZIBs with potential for commercialization.

Strong Replaces Weak: Design of H-Bond Interactions Enables Cryogenic Aqueous Zn Metal Batteries.

Despite the numerous advantages of aqueous Zn batteries, their practical application under cryogenic conditions is hindered by the freezing of the electrolyte because the abundance of hydrogen bonds (H-bonds) between H2O molecules drives the aqueous system to transform to an orderly frozen structure. Here, a design of H-bond interactions based on the guiding ideology of "strong replaces weak" is proposed. The strong H-bonds formed between introduced eutectic components and water molecules break down the weak H-bonds in the original water molecule network, which contributes to an ultralow freezing point and a high ionic conductivity of 1.7 mS cm-1 at -40 °C. Based on multiperspective theoretical simulations and tailor-made in situ cooling Raman characterizations, it has been demonstrated that substituting weak H-bonds with strong H-bonds facilitates the structural reshaping of Zn2+ solvation and remodeling of the H-bond network in the electrolyte. Endowed with this advantage, reversible and stable Zn plating/stripping behaviors could be realized at -40 °C, and the full cells display a high discharge capacity (200 mA h g-1) at -40 °C with ∼75% capacity retention after 1000 cycles. This study will expand the design philosophy of antifreezing aqueous electrolytes and provide a perspective to promote the adoption of Zn metal batteries for cryogenic environment large-scale energy storage.

Trapping High-Activity Water in Nature-Inspired Plant-Derived Separator to Realize Ultrastable Interfacial Chemistry of Zn Anode.

Side reactions caused by highly active water molecules, including severe corrosion, hydrogen evolution, and dendrite growth, are impediments to the advancement of aqueous zinc ion batteries (ZIBs). Here, inspired by the pivotal role of plant fibers to prevent dehydration in nature, we designed a unique water-retaining plant fiber (WRPF) separator with strong hygroscopic ability to adsorb and trap water molecules. Elaborated theoretical and experimental characterizations prove that high-activity water could be sequestered by a WRPF separator, alleviating water-induced side reactions and accelerating the desolvation of hydrate Zn2+. Prominently, reversible Zn plating and stripping could be realized in Zn//Cu batteries. Even with elevated cathodic mass loading (21.94 mg cm-2), the Zn//VS2 full cell delivers high areal capacity 3.3 mAh cm-2 and well-maintained stability. The present study offers a versatile design strategy for separators using nature-inspired materials, aiming to address the challenging issue of "water" and achieve ultrastable interfacial chemistry of Zn anode.

Assessing the predictability of the H3K27M status in diffuse glioma patients using frequency importance analysis on chemical exchange saturation transfer MRI.

BACKGROUND AND OBJECTIVES: In diffuse glioma patients, Lys-27-Met mutations in histone 3 genes (H3K27M) are associated with an aggravated prognosis and further decreased overall survival. By using frequency importance analysis on chemical exchange saturation transfer (CEST) MRI, this study aimed to assess the predictability of the H3K27M status in diffuse glioma patients. METHODS: Twenty-two patients diagnosed with diffuse glioma, with a known H3K27M status, were included in the present study. All patients underwent CEST MRI scans. The previously proposed frequency importance analysis was performed to determine the relative contribution of the amide and aliphatic protons for the differentiation between normal tissues and tumors. For this comparison, the conventional MTRasym analysis of amide protons at 3.5 ppm, i.e., the amide proton transfer-weighted (APTw) signal, was employed. Statistical analysis was performed using the Mann-Whitney U test, and the receiver operating characteristic (ROC) and area under the curve (AUC) analyses. RESULTS: The mean and 90th percentile of the ΔAPTw intensities, amide and aliphatic frequency importance values revealed statistically significant differences between the wildtype and the H3K27M-altered patient groups (p < 0.05). For the prediction of the H3K27M status, amide frequency importance achieved highest AUCs of 0.97, with a specificity of 0.93. In contrast, the ΔAPTw intensities and aliphatic frequency importance showed relatively lower AUCs (<0.35) in predicting the H3K27M status. CONCLUSIONS: Amide frequency importance exhibited satisfactory performance in the prediction of the H3K27M status. As such, it may be considered as a non-invasive MRI biomarker for the diagnosis of diffuse gliomas.

Analysis and validation of the potential of the MYO1E gene in pancreatic adenocarcinoma based on a bioinformatics approach.

Pancreatic adenocarcinoma (PAAD) is a common digestive cancer, and its prognosis is poor. Myosin 1E (MYO1E) is a class I myosin family member whose expression and function have not been reported in PAAD. In the present study, bioinformatics analysis was used to explore the expression levels of MYO1E in PAAD and its prognostic value, and the immunological role of MYO1E in PAAD was analyzed. The study revealed that a variety of malignancies have substantially increased MYO1E expression. Further investigation demonstrated that PAAD tissues exhibited greater levels of MYO1E mRNA and protein expression than normal tissues. High MYO1E expression is associated with poor prognosis in patients with PAAD. MYO1E expression was also associated with pathological stage in patients with PAAD. Functional enrichment analysis demonstrated that MYO1E was linked to multiple tumor-related mechanisms in PAAD. The pancreatic adenocarcinoma tumor microenvironment (TME) was analyzed and it was revealed that MYO1E expression was positively associated with tumor immune cell infiltration. In addition, MYO1E was closely associated with some tumor chemokines/receptors and immune checkpoints. In vitro experiments revealed that the suppression of MYO1E expression could inhibit pancreatic adenocarcinoma cell proliferation, invasion and migration. Through preliminary analysis, the present study evaluated the potential function of MYO1E in PAAD and its function in TME, and MYO1E may become a potential biomarker for PAAD.

FBXO28 promotes proliferation, invasion, and metastasis of pancreatic cancer cells through regulation of SMARCC2 ubiquitination.

The E3 ligase F-box only protein 28 (FBXO28) belongs to the F-box family of proteins that play a critical role in tumor development. However, the potential function of FBXO28 in pancreatic cancer (PC) and its molecular mechanism remain unclear. In this study, we examined FBXO28 expression in PC and its biological role and explored the mechanism of FBXO28-mediated proliferation, invasion, and metastasis of PC cells. Compared with paracancerous tissues and human normal pancreatic ductal epithelial cells, FBXO28 was highly expressed in PC tissues and cell lines. High expression of FBXO28 was negatively correlated with the survival prognosis of patients with PC. Functional assays indicated that FBXO28 promoted PC cell proliferation, invasion, and metastasis in vitro and in vivo. Furthermore, immunoprecipitation-mass spectrometry was used to identify SMARCC2 as the target of FBXO28; upregulation of SMARCC2 can reverse the effect of overexpression of FBXO28 on promoting the proliferation, invasion, and metastasis of PC cells. Mechanistically, FBXO28 inhibited SMARCC2 expression in post-translation by increasing SMARCC2 ubiquitination and protein degradation. In conclusion, FBXO28 has a potential role in PC, possibly promoting PC progression through SMARCC2 ubiquitination. Thus, FBXO28 might be a potential treatment target in PC.

The deubiquitinating enzyme MINDY2 promotes pancreatic cancer proliferation and metastasis by stabilizing ACTN4 expression and activating the PI3K/AKT/mTOR signaling pathway.

The pathogenic mechanisms of pancreatic cancer (PC) are still not fully understood. Ubiquitination modifications have a crucial role in tumorigenesis and progression. Yet, the role of MINDY2, a member of the motif interacting with Ub-containing novel DUB family (MINDY), as a newly identified deubiquitinating enzyme, in PC is still unclear. In this study, we found that MINDY2 expression is elevated in PC tissue (clinical samples) and was associated with poor prognosis. We also found that MINDY2 is associated with pro-carcinogenic factors such as epithelial-mesenchymal transition (EMT), inflammatory response, and angiogenesis; the ROC curve suggested that MINDY2 has a high diagnostic value in PC. Immunological correlation analysis suggested that MINDY2 is deeply involved in immune cell infiltration in PC and is associated with immune checkpoint-related genes. In vivo and in vitro experiments further suggested that elevated MINDY2 promotes PC proliferation, invasive metastasis, and EMT. Meanwhile, actinin alpha 4 (ACTN4) was identified as a MINDY2-interacting protein by mass spectrometry and other experiments, and ACTN4 protein levels were significantly correlated with MINDY2 expression. The ubiquitination assay confirmed that MINDY2 stabilizes the ACTN4 protein level by deubiquitination. The pro-oncogenic effect of MINDY2 was significantly inhibited by silencing ACTN4. Bioinformatics Analysis and Western blot experiments further confirmed that MINDY2 stabilizes ACTN4 through deubiquitination and thus activates the PI3K/AKT/mTOR signaling pathway. In conclusion, we identified the oncogenic role and mechanism of MINDY2 in PC, suggesting that MINDY2 is a viable candidate gene for PC and may be a therapeutic target and critical prognostic indicator.

A Survey on the Integration of Blockchains and Databases.

The success of blockchain technology in cryptocurrencies reveals its potential in the data management field. Recently, there is a trend in the database community to integrate blockchains and traditional databases to obtain security, efficiency, and privacy from the two distinctive but related systems. In this survey, we discuss the use of blockchain technology in the data management field and focus on the fusion system of blockchains and databases. We first classify existing blockchain-related data management technologies by their locations on the blockchain-database spectrum. Based on the taxonomy, we discuss three types of fusion systems and analyze their design spaces and trade-offs. Then, by further investigating the typical systems and techniques of each type of fusion system and comparing the solutions, we provide insights of each fusion model. Finally, we outline the unsolved challenges and promising directions in this field and believe that fusion systems will take a more important role in data management tasks. We hope this survey can help both academia and industry to better understand the advantages and limitations of blockchain-related data management systems and develop fusion systems that meet various requirements in practice.

Sustained-Compensated Interfacial Zincophilic Sites to Assist High-Capacity Aqueous Zn Metal Batteries.

Aqueous Zn metal batteries have attracted extensive attention due to their intrinsic advantages. However, zinc ions tend to deposit irregularly, seriously depleting the capacity and stability of the battery. The construction of zincophilic sites can effectively regulate the nucleation and growth of Zn, but there is a defect that these sites will be covered with gradual failure after long-term cycling. Here, in combination with the sustained-compensated strategy, interfacial zincophilic sites are continuously constructed, thus effectively avoiding the threat of dendrites and improving the electrochemical performance. Impressively, at 10 mA cm-2 and 5 mAh cm-2, the protected Zn metal exhibits excellent cycling stability over 2000 cycles in the Zn//Zn battery. Moreover, even the cathode mass loading is considerably high (35 mg cm-2), and the Zn//NVO full cell significantly outperforms with high areal capacity (up to 4 mAh cm-2). This novel strategy provides a direction for the development of high-capacity aqueous batteries.

Bone Marrow-Derived Mesenchymal Stem Cells Transplantation Attenuates Renal Fibrosis Following Acute Kidney Injury in Rats by Diminishing Pericyte-Myofibroblast Transition and Extracellular Matrix Augment.

BACKGROUND: Renal fibrosis is a common chronic outcome of acute kidney injury (AKI). Pericyte-myofibroblasts transition and production of abundant extracellular matrix are the important pathologic basis. This study investigated the effect of bone marrow-derived mesenchymal stem cells (BMSCs) transplantation on the AKI kidney fibrosis and the possible mechanisms. METHODS: By constructing the animal and cell model of AKI pericyte injury, the therapeutic effect of BMSCs on pericyte-myofibroblasts transition was detected. The production and accumulation of extracellular matrix, including collagen I, collagen III, and fibronectin were also tested. The mechanism was revealed by means of analysis of signal pathway. RESULTS: After AKI insult, many myofibroblasts emerged in the renal interstitium together with a large amount of extracellular matrix components. The BMSCs transplantation significantly decreased the number of myofibroblasts trans-differentiated from pericytes in the AKI model. The changes of vascular endothelial growth factor subtypes and Ang-I/AngII secreted by pericytes were also significantly reduced after BMSCs co-culture. At the same time, extracellular matrix components, including collagen I, collagen III, and fibronectin, decreased significantly. Transplantation treatment alleviated the fibrosis score. The transforming growth factor ß (TGF-ß) concentration decreased as well as the levels of Smad2/3 and p-Smad2/3 with the presence of BMSCs therapy. CONCLUSIONS: Bone marrow-derived mesenchymal stem cells transplantation diminished pericyte-myofibroblast transition and extracellular matrix augment after AKI by regulating the TGF-ß/Smad2/3 signaling pathway. It may be used as a novel therapeutic method for retarding renal fibrosis, which is worthy of further study.

Identification and validation of a potential key gene SGOL1 for poor prognosis in hepatocellular carcinoma based on a bioinformatics approach.

Objective: Hepatocellular carcinoma (HCC) is one of the most prevalent types of cancer worldwide. Shugoshin 1 (SGOL1) plays a crucial role in cell mitosis and its aberrant expression level in human tumors has shown to promote chromosomal instability (CIN) and accelerate tumor growth. SGOL1 expression level in HCC cells and tissues, whether it has an influence on HCC patients' prognosis, and its mechanism of action have not yet been studied. Methods: We carried out the bioinformatics analysis of SGOL1 expression level and survival analysis in 8 different malignancies, including HCC. In addition, we analyzed SGOL1 expression level in HCC tissues, as well as HCC patients' clinical features, enrichment analysis of SGOL1 function and mechanism of action in HCC and tumor immune cells. The effects of SGOL1 expression level and cell viability on HCC were confirmed by in vitro cytological assays. Results: It was found that SGOL1 mRNA expression level was significantly higher in several tumor tissues, including HCC, than in corresponding normal tissues, and the elevated SGOL1 expression level was strongly associated with HCC patients' poor prognosis. It was also revealed that SGOL1 expression level in HCC tissue was positively correlated with disease stage, tumor grade, and tumor size, and the results of multivariate logistic regression analysis showed that SGOL1 was one of the independent influential factors of the prognosis of HCC. Enrichment analysis revealed that SGOL1 expression level in HCC tissue was mainly associated with tumor proliferation, cell cycle, and other factors. The results of the immune infiltration analysis indicated that SGOL1 expression level was associated with immune cell infiltration and immune checkpoints in HCC. In vitro experiments demonstrated the high SGOL1 expression level in HCC tissues and cells, and silencing of SGOL1 resulted in altered cell cycle markers and decreased proliferation, invasion, and migration of HCC cells. Conclusion: The findings revealed that SGOL1 is highly expressed in HCC tissues, it is a biomarker of a poor prognosis, which may be related to immune cell infiltration in HCC, and may enhance the proliferation, invasion, and migration of HCC cells. The results may provide new insights into targeted treatment of HCC and improve HCC patients' prognosis.

FOXD1 facilitates pancreatic cancer cell proliferation, invasion, and metastasis by regulating GLUT1-mediated aerobic glycolysis.

Although FOXD1 has been found to be involved in the malignant processes of several types of cancers, its role in pancreatic cancer (PC) is not well understood. This study aimed to investigate the expression and function of FOXD1 in PC. We found that FOXD1 mRNA and protein expression were upregulated in PC tissues compared with non-tumor tissues, and high expression level of FOXD1 was associated with an adverse prognostic index of PC. The results of in vitro and in vivo assays indicate that overexpression of FOXD1 promotes aerobic glycolysis and the capacity of PC cells to proliferate, invade, and metastasize, whereas FOXD1 knockdown inhibits these functions. The results of mechanistic experiments suggest that FOXD1 can not only directly promote SLC2A1 transcription but also inhibit the degradation of SLC2A1 through the RNA-induced silencing complex. As a result, FOXD1 enhances GLUT1 expression and ultimately facilitates PC cell proliferation, invasion, and metastasis by regulating aerobic glycolysis. Taken together, FOXD1 is suggested to be a potential therapeutic target for PC.

Exosome-derived FGD5-AS1 promotes tumor-associated macrophage M2 polarization-mediated pancreatic cancer cell proliferation and metastasis.

Inflammatory molecules and exosomes are crucial for signal transduction between tumor-associated macrophages and tumor cells. IL-6, a key inflammatory molecule secreted by M2 macrophages after polarization, can mediate malignant progression of pancreatic cancer (PC). However, the functions and mechanisms of IL-6 and tumor-derived exosomes in tumor-associated macrophages and PC remain unclear. Transcriptome chip and quantitative reverse transcription PCR experiments indicated that FGD5-AS1 induced IL-6 and high FGD5-AS1 expression correlated with the poor prognosis in PC patients. RNA pulldown, mass spectrometry, and dual luciferase reporter assays were used to identify the mechanism of exosomal FGD5-AS1 in promoting PC progression and M2 macrophage polarization. FGD5-AS1 exerted cancer-promoting functions when co-cultured with M2 macrophages. PC-derived exosomal FGD5-AS1 stimulated M2 macrophage polarization by activating STAT3/NF-κB pathway. FGD5-AS1 interacts with p300, resulting in STAT3 acetylation, thus promoting nuclear localization and transcriptional activity of STAT3/NF-κB. These data indicated that PC cells generate FGD5-AS1-rich exosomes, which cause M2 macrophage polarization to promote the malignant behaviors of PC cells. Targeting exosomal FGD5-AS1 may provide a potential diagnosis and treatment strategy for PC.

CAV2 Regulates Mir-4723/Wnt7A Signalling Axis through Endocytosis and Epithelial-Mesenchymal Transition to Promote Proliferation, Invasion, and Metastasis of Pancreatic Cancer Cells.

Background: Pancreatic cancer is one of the most aggressive malignancies globally, with no improvement in the cure rates yet.Caveolin-2 (CAV2) has been repeatedly reported to play an important role in cellular transport and signalling and in exhibiting a pro-oncogenic response in a variety of tumours, although its specific action mechanisms in pancreatic cancer are not well documented. MiRNA is recognized as a therapeutic target for a variety of tumours, making it an important regulator of the Wnt/ß-catenin signalling pathway. MiR-4723/Wnt7A constitutes an oncogenic signalling axis in pancreatic cancer by targeting and inhibiting Wnt7A through the activation of MiR4723, but its molecular action mechanism remains unexplored. Therefore, in the present study, we investigated the effect of CAV2 on the MiR-4723/Wnt7A pathway and its action mechanism. Methods: We employed TCGA, the GEO database for bioinformatics analysis, cell proliferation assay, wound healing assay, Transwell assay, colony-forming assay, qRT-PCR, and Western blotting to validate the cancer-promoting role of CAV2 in pancreatic cancer and to determine its potential target WNT7A. We then explored CAV2 as a positive regulator of the Wnt7A/ß-catenin pathway through immunofluorescence assay, qRT-PCR, and Western blotting. Database analyses, CCK-8 and qRT-PCR revealed that MiR-4723 is an oncogene in pancreatic cancer. Luciferase assay and qRT-PCR revealed that MiR-4723 is a negative regulator of the Wnt7A/ß-catenin pathway. To investigate the mechanism of CAV2 action on MiR-4723/Wnt7A, we detected the gene expression of CAV2 through qRT-PCR after MiR-4723 overexpression. Several genes related to endocytosis and epithelial-mesenchymal transition (EMT) were subsequently analysed through immunofluorescence, Western blotting, and qRT-PCR. Results: Overexpression of CAV2 promotes invasion, migration, cloning and metastasis of pancreatic cancer cells. Overexpression of MiR-4723 inhibits CAV2 expression. Here, we are the first to demonstrate that CAV2 exerts a pro-carcinogenic effect on pancreatic cancer through the activation of the Wnt7A/ß-catenin signalling pathway. Conclusion: CAV2 can regulate the MiR-4723/Wnt7A signalling axis in pancreatic cancer cell lines by inhibiting endocytosis and promoting EMT, thereby fulfilling the mechanism pro-carcinogenic effects.