Interfacial Rivet to Fill Structural Defects: A Spacer Engineering Gift for 3D Solar Cells.

The combination of 2D and 3D perovskites to passivate surfaces or interfaces with a high concentration of defects shows great promise for improving the efficiency of perovskite solar cells (PSCs). Constructing high-quality perovskite film systems by precisely modulating 2D perovskites with good morphologies and growth sites on 3D perovskite films remains a formidable challenge due to the complexity of spacer-engineered surface reactions. In this study, phase-pure 2D (HA)2(MA)n-1PbnI3n+1 perovskites with a controlled number of layers (n) are separated on a large scale and exploited as interface rivets to optimize 3D perovskite films, resulting in tunable film structural defects and grain boundaries. The optimized PSCs system benefits from a reduction in non-radiative recombination, resulting in improved optical performance, higher mobility, and lower trap density. The corresponding device achieves a champion power conversion efficiency (PCE) of more than 25%, especially for voltage (VOC) and fill factor (FF). The quality and uniformity of the perovskite films are further confirmed using large-area devices with an active area of 14 cm2, which exhibits a PCE of more than 21.24%. The high-quality thin-film system based on the 2D perovskites presented herein provides a new perspective for improving the efficiency and stability of PSCs.

Development of machine learning prognostic models for overall survival of prostate cancer patients with lymph node-positive.

Prostate cancer (PCa) patients with lymph node involvement (LNI) constitute a single-risk group with varied prognoses. Existing studies on this group have focused solely on those who underwent prostatectomy (RP), using statistical models to predict prognosis. This study aimed to develop an easily accessible individual survival prediction tool based on multiple machine learning (ML) algorithms to predict survival probability for PCa patients with LNI. A total of 3280 PCa patients with LNI were identified from the Surveillance, Epidemiology, and End Results (SEER) database, covering the years 2000-2019. The primary endpoint was overall survival (OS). Gradient Boosting Survival Analysis (GBSA), Random Survival Forest (RSF), and Extra Survival Trees (EST) were used to develop prognosis models, which were compared to Cox regression. Discrimination was evaluated using the time-dependent areas under the receiver operating characteristic curve (time-dependent AUC) and the concordance index (c-index). Calibration was assessed using the time-dependent Brier score (time-dependent BS) and the integrated Brier score (IBS). Moreover, the beeswarm summary plot in SHAP (SHapley Additive exPlanations) was used to display the contribution of variables to the results. The 3280 patients were randomly split into a training cohort (n = 2624) and a validation cohort (n = 656). Nine variables including age at diagnosis, race, marital status, clinical T stage, prostate-specific antigen (PSA) level at diagnosis, Gleason Score (GS), number of positive lymph nodes, radical prostatectomy (RP), and radiotherapy (RT) were used to develop models. The mean time-dependent AUC for GBSA, RSF, and EST was 0.782 (95% confidence interval [CI] 0.779-0.783), 0.779 (95% CI 0.776-0.780), and 0.781 (95% CI 0.778-0.782), respectively, which were higher than the Cox regression model of 0.770 (95% CI 0.769-0.773). Additionally, all models demonstrated almost similar calibration, with low IBS. A web-based prediction tool was developed using the best-performing GBSA, which is accessible at https://pengzihexjtu-pca-n1.streamlit.app/ . ML algorithms showed better performance compared with Cox regression and we developed a web-based tool, which may help to guide patient treatment and follow-up.

Synthesis of robust underwater glues from common proteins via unfolding-aggregating strategy.

Underwater adhesive proteins secreted by organisms greatly inspires the development of underwater glue. However, except for specific proteins such as mussel adhesive protein, barnacle cement proteins, curli protein and their related recombinant proteins, it is believed that abundant common proteins cannot be converted into underwater glue. Here, we demonstrate that unfolded common proteins exhibit high affinity to surfaces and strong internal cohesion via amyloid-like aggregation in water. Using bovine serum albumin (BSA) as a model protein, we obtain a stable unfolded protein by cleaving the disulfide bonds and maintaining the unfolded state by means of stabilizing agents such as trifluoroethanol (TFE) and urea. The diffusion of stabilizing agents into water exposes the hydrophobic residues of an unfolded protein and initiates aggregation of the unfolded protein into a solid block. A robust and stable underwater glue can thus be prepared from tens of common proteins. This strategy deciphers a general code in common proteins to construct robust underwater glue from abundant biomass.

Rectifying disorder of extracellular matrix to suppress urethral stricture by protein nanofilm-controlled drug delivery from urinary catheter.

Urethral stricture secondary to urethral injury, afflicting both patients and urologists, is initiated by excessive deposition of extracellular matrix in the submucosal and periurethral tissues. Although various anti-fibrotic drugs have been applied to urethral stricture by irrigation or submucosal injection, their clinical feasibility and effectiveness are limited. Here, to target the pathological state of the extracellular matrix, we design a protein-based nanofilm-controlled drug delivery system and assemble it on the catheter. This approach, which integrates excellent anti-biofilm properties with stable and controlled drug delivery for tens of days in one step, ensures optimal efficacy and negligible side effects while preventing biofilm-related infections. In a rabbit model of urethral injury, the anti-fibrotic catheter maintains extracellular matrix homeostasis by reducing fibroblast-derived collagen production and enhancing metalloproteinase 1-induced collagen degradation, resulting in a greater improvement in lumen stenosis than other topical therapies for urethral stricture prevention. Such facilely fabricated biocompatible coating with antibacterial contamination and sustained-drug-release functionality could not only benefit populations at high risk of urethral stricture but also serve as an advanced paradigm for a range of biomedical applications.

Amyloid-Mediated Nanoarchitectonics with Biomimetic Mineralization of Polyetheretherketone for Enhanced Osseointegration.

Polyetheretherketone (PEEK), a widely used implant material, has attracted the attention of scientific researchers because of its bone-matched elastic modulus, radiolucency, and chemical resistance. However, the bioinert chemical properties of PEEK do not promote bone apposition once implanted. In this study, using a phase-transitioned lysozyme (PTL) nanofilm as a sandwiched layer, a robust hydroxyapatite (HAp) coating on PEEK (HAp@PTL@PEEK) is constructed. The PTL nanofilm shows strong adhesion to the PEEK surface and induces biomimetic mineralization to form a compact HAp coating on PEEK in simulated body fluids. This HAp coating not only shares a higher adhesion strength and better stability but can also be applied to implants with complex 3D structures. HAp@PTL@PEEK showed significantly enhanced osteogenic capacity when cultured with rat bone marrow mesenchymal stem cells by promoting initial cell adhesion, proliferation, and osteogenic differentiation in vitro. In vivo evaluations utilizing models of femoral condyle defects and skull defects confirm that the HAp coating substantially augments bone remodeling and osseointegration ability. Compared with the traditional method, our modified method is simpler, more environmentally friendly, and uses less hazardous components. Furthermore, the obtained HAp coating shares a higher adhesion strength to PEEK and a better osteogenic capacity. The study offers a novel method to improve the osseointegration of PEEK-based implants in biointerfaces and tissue engineering.

[Corrigendum] MicroRNA­218 inhibits tumor angiogenesis of human renal cell carcinoma by targeting GAB2.

Subsequently to the publication of the above article, the authors have realized that the cell migration and tube formation assay data portrayed in Figs. 2 and 4 in their paper were published with some inadvertent errors. Specifically, the photograph selected for the ACHN-SFM group was accidentally misused for the 769P/LV-miR-218 group in Fig. 2F. Secondly, the photograph for the 786O/LV­NC group in Fig. 2F was accidentally misused as the image for the 786O/shNC group in Fig. 4E; and thirdly, the photograph selected for the ACHN/shNC group in Fig. 4C was inadvertently misused for the ACHN/shNC group in Fig. 4D. These errors arose inadvertently as a consequence of the authors' mishandling their data; however, the authors were able to retrieve their original data, and have been able to reassemble these figures to show the data as was originally intended. The revised versions of Figs. 2 and 4, featuring the corrected data panels for the 769P/LV­miR­218 group in Fig. 2F, the ACHN/shNC group in Fig. 4D and the 786O/shNC group in Fig. 4E, are shown on the next two pages. The revised data shown for these Figures do not affect the overall conclusions reported in the paper. All the authors agree with the publication of this corrigendum. The authors are grateful to the Editor of Oncology Reports for allowing them the opportunity to publish this corrigendum, and apologize to the readership for any inconvenience caused. [Oncology Reports 44: 1961­1970, 2020; DOI: 10.3892/or.2020.7759].

Corrigendum: A New Prognostic Risk Score: Based on the Analysis of Autophagy-Related Genes and Renal Cell Carcinoma.

[This corrects the article DOI: 10.3389/fgene.2021.820154.].

Abnormal expression and the significant prognostic value of aquaporins in clear cell renal cell carcinoma.

Aquaporins (AQPs) are a kind of transmembrane proteins that exist in various organs of the human body. AQPs play an important role in regulating water transport, lipid metabolism and glycolysis of cells. Clear cell renal cell carcinoma (ccRCC) is a common malignant tumor of the kidney, and the prognosis is worse than other types of renal cell cancer (RCC). The impact of AQPs on the prognosis of ccRCC and the potential relationship between AQPs and the occurrence and development of ccRCC are demanded to be investigated. In this study, we first explored the expression pattern of AQPs by using Oncomine, UALCAN, and HPA databases. Secondly, we constructed protein-protein interaction (PPI) network and performed function enrichment analysis through STRING, GeneMANIA, and Metascape. Then a comprehensive analysis of the genetic mutant frequency of AQPs in ccRCC was carried out using the cBioPortal database. In addition, we also analyzed the main enriched biological functions of AQPs and the correlation with seven main immune cells. Finally, we confirmed the prognostic value of AQPs throughGEPIA and Cox regression analysis. We found that the mRNA expression levels of AQP0/8/9/10 were up-regulated in patients with ccRCC, while those of AQP1/2/3/4/5/6/7/11 showed the opposite. Among them, the expression differences of AQP1/2/3/4/5/6/7/8/9/11 were statistically significant. The differences in protein expression levels of AQP1/2/3/4/5/6 in ccRCC and normal renal tissues were consistent with the change trends of mRNA. The biological functions of AQPs were mainly concentrated in water transport, homeostasis maintenance, glycerol transport, and intracellular movement of sugar transporters. The high mRNA expression levels of AQP0/8/9 were significantly correlated with worse overall survival (OS), while those of AQP1/4/7 were correlated with better OS. AQP0/1/4/9 were prognostic-related factors, and AQP1/9 were independent prognostic factors. In general, this research has investigated the values of AQPs in ccRCC, which could become new survival markers for ccRCC targeted therapy.

Correction: Tumor-suppressive microRNA-218 inhibits tumor angiogenesis via targeting the mTOR component RICTOR in prostate cancer.

[This corrects the article DOI: 10.18632/oncotarget.14131.].

Prognostic value of circulating tumor cells and immune-inflammatory cells in patients with renal cell carcinoma.

PURPOSE: The relationships among circulating tumor cells (CTCs), inflammatory cells, and platelets in patients with renal cell carcinoma (RCC) are not transparent. We evaluated the correlations among CTCs, blood inflammatory cells, and platelets in patients with RCC and their prognostic value for metastasis-free survival. METHODS: CTC and typical tumor cell chip data were collected and analyzed by the GEO database. The baseline data, survival data, CTCs data, and blood test results were statistically analyzed. RESULTS: Bioinformatics analysis showed that the function of the differentially expressed genes between CTCs and normal tumor cells mainly involved platelets and immune inflammation. A total of 82 patients whose follow-up time was 3 to 68 months were included in the analysis. Clinical data of the patients confirmed that there is a correlation between platelets and mesenchymal CTCs. Simultaneously, there was a correlation between immune inflammatory cells and platelets. The univariate Cox proportional hazards model indicated that staging, mesenchymal CTCs, and the monocyte-to-neutrophil ratio (MNR) had prognostic value. The multivariate Cox proportional hazards model indicated that staging and the MNR had prognostic value and high accuracy. CONCLUSIONS: Bioinformatics analysis showed that CTCs were related to platelets and immune-inflammatory cells. Furthermore, the clinical data confirmed that platelets were correlated with mesenchymal CTCs and immune-inflammatory cells in the blood. By using mesenchymal CTCs, the MNR, or staging respectively, it is possible to predict the risk of postoperative metastasis in RCC patients. As a compound prognostic factor, staging, and the MNR can provide more convenient and accurate condition monitoring.

The prognostic value of circulating tumour cells (CTCs) and CTC white blood cell clusters in patients with renal cell carcinoma.

PURPOSE: Circulating tumour cell (CTC) and CTC-white blood cell (CTC-WBC) clusters are related to the prognosis of tumour patients. However, the relationship between CTC-WBC clusters and prognosis in renal cell carcinoma (RCC) patients is not clear. We evaluated the prognostic value of CTC-WBC clusters using metastasis-free survival (MFS) and overall survival (OS) in patients with RCC. MATERIALS AND METHODS: The baseline, survival, and CTC data of patients with RCC were statistically analysed by R. RESULTS: The Cox risk proportional regression model suggests that the total CTCs, pathology type, and CTC-WBC clusters can be used as prognostic indicators for the MFS of RCC patients. Total CTCs and solid tumour diameter can be used as prognostic indicators for the OS of RCC patients. Using Kaplan-Meier survival analysis, we found that patients with total CTCs, pathology, and CTC-WBC clusters greater than the cut-off value had a worse MFS, and patients with total CTCs greater than the cut-off value had a worse OS. CONCLUSION: The analysis of the clinical sample data in patients with RCC shows that CTC-WBC clusters play an important role in monitoring the prognosis of RCC. Among them, total CTCs, pathology, and CTC-WBC clusters were combined as prognostic factors for the MFS of RCC patients. Total CTCs and solid tumour diameter can be combined as prognostic factors for the OS of RCC patients. These prognostic factors provide more convenient and accurate condition monitoring for renal cancer patients and can be used to actively improve the prognosis of patients.

A New Prognostic Risk Score: Based on the Analysis of Autophagy-Related Genes and Renal Cell Carcinoma.

Introduction: Clear cell renal cell carcinoma (ccRCC) patients suffer from its high recurrence and metastasis rate, and a new prognostic risk score to predict individuals with high possibility of recurrence or metastasis is in urgent need. Autophagy has been found to have a dual influence on tumorigenesis. In this study we aim to analyze autophagy related genes (ATGs) and ccRCC patients and find a new prognostic risk score. Method: Analyzing differential expression genes (DEGs) in TCGA-KIRC dataset, and took intersection with ATGs. Through lasso, univariate, and multivariate cox regression, DEGs were chosen, and the coefficients and expression levels of them were components constructing the formula of risk score. We analyzed mRNA expression of DEGs in tumor and normal tissue in ONCOMINE database and TCGA-KIRC dataset. The Human Protein Atlas (HPA) was used to analyze protein levels of DEGs. The protein-protein interaction (PPI) network was examined in STRING and visualized in cytoscape. Functional enrichment analysis was performed in RStudio. To prove the ability and practicibility of risk score, we analyzed univariate and multivariate cox regression, Kaplan-Meier curve (K-M curve), risk factor association diagram, receiver operating characteristic curve (ROC curve) of survival and nomogram, and the performance of nomogram was evaluated by calibration curve. Then we further explored functional enrichment related to risk groups through Gene Set Enrichment Analysis (GSEA), weighted gene co-expression network analysis (WGCNA), and Metascape database. At last, we investigated immune cell infiltration of DEGs and two risk groups through TIMER database and "Cibersort" algorithm. Result: We identified 7 DEGs (BIRC5, CAPS, CLDN7, CLVS1, GMIP, IFI16, and TCIRG1) as components of construction of risk score. All 7 DEGs were differently expressed in ccRCC and normal tissue according to ONCOMINE database and TCGA-KIRC dataset. Functional enrichment analysis indicated DEGs, and their most associated genes were shown to be abundant in autophagy-related pathways and played roles in tumorigenesis and progression processes. A serious analysis proved that this risk score is independent from the risk signature of ccRCC patients. Conclusion: The risk score constructed by 7 DEGs had the ability of predicting prognosis of ccRCC patients and was conducive to the identification of novel prognostic molecular markers. However, further experiment is still needed to verify its ability and practicability.

FOXM1-Dependent Transcriptional Regulation of EZH2 Induces Proliferation and Progression in Prostate Cancer.

BACKGROUND: Prostate cancer is one of the most commonly diagnosed cancers and one of the most common causes of cancer-related deaths among men worldwide. Patients who are diagnosed with localized prostate cancer and treated with radical prostatectomy often respond well to therapy. The current standard therapy for prostate cancer involves maximal surgical resection, followed by radiotherapy and chemotherapy. Clarifying the molecular mechanism of tumor proliferation and recurrence becomes more and more important for clinical therapies of prostate cancer. METHODS: Quantitative Real-Time PCR and Western-blot were used in the detection of mRNA and protein expression. Lentivirus infection was used to overexpress or knockdown the target gene. Flow cytometry analysis was performed to test protein expression and apoptosis level. Immunohistochemistry was used to identify protein expression in tissue. Statistical differences between the two groups are evaluated by two-tailed t-tests. The comparison among multiple groups is performed by one-way Analysis of Variance (ANOVA) followed by Dunnett's posttest. The statistical significance of the Kaplan-Meier survival plot is determined by log-rank analysis. RESULTS: In this study, we identified that FOXM1 expression was significantly enriched in prostate cancer compared with normal tissue. Additionally, FOXM1 was functionally required for tumor proliferation and its expression was associated with poor prognosis in prostate cancer patients. Mechanically, FOXM1-dependent regulation of EZH2 is essential for proliferation and progression in prostate cancer. CONCLUSION: Taken together, our data suggest that oncogenic transcription factor FoxM1 is up-regulated in prostate cancer, suggesting that the growth of cancer cells may depend on FOXM1 activity. FOXM1 may serve as a clinical prognostic factor and a therapeutic target for prostate cancer.

Identification of key genes and functions of circulating tumor cells in multiple cancers through bioinformatic analysis.

BACKGROUND: Circulating tumor cells (CTCs) play a key role in cancer progression, especially metastasis, due to the rarity and heterogeneity of CTCs, fewer researches have been conducted on them at the molecular level. However, through the Gene Expression Omnibus (GEO) database, this kind of minority researches can be well integrated, the gene expression differences between CTCs and primary tumors can be identified, and molecular targets for CTCs can be found. METHODS: We analyzed 7 sets of gene chips (GSE82198, GSE99394, GSE31023, GSE65505, GSE67982, GSE76250, GSE50746) obtained by GEO. Analysis of differentially expressed genes (DEGs) between CTCs and corresponding primary tumors by NetworkAnalyst. Metascape tool for Gene Ontology (GO) / Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of differential genes and visual display. Cytoscape performs protein-protein interaction (PPI) analysis and obtains the hub genes. Renal cancer patients' clinical specimens to verify the correctness of enrichment results. Prognostic analysis of hub genes in kidney cancer patients using the Kaplan-Meier plotter survival analysis tool. RESULTS: We obtained a total of 589 DEGs. The GO / KEGG enrichment results indicate that the DEGs are mainly concentrated in cell adhesion, epithelial-mesenchymal transition (EMT), and apoptosis. Renal cancer clinical specimens suggest that CTCs have epithelial and mesenchymal types. At the same time, PSMC2 can be used as a poor prognostic indicator for renal cancer patients. CONCLUSIONS: In summary, our study suggests that compared with primary tumors, CTCs mainly change cell adhesion, EMT, and apoptosis. PSMC2 can be used as a poor prognostic factor.

MicroRNA­218 inhibits tumor angiogenesis of human renal cell carcinoma by targeting GAB2.

Renal cell carcinoma (RCC) is one of the most common malignant cancers in the adult urinary system worldwide. Tumor angiogenesis is a critical process during cancer progression, as it modulates carcinogenesis and metastasis. In recent years, microRNA­218 (miR­218) has been confirmed to play a crucial role in tumor suppression. However, the role of miR­218 in RCC angiogenesis remains unclear. In the present study, it was found that the expression of miR­218 was decreased in RCC tumor tissues and cell lines as detected by real­time PCR analysis. Tube formation assays and migration assays also confirmed that miR­218 inhibited the interaction between RCC cells and vascular endothelial cells by suppressing proangiogenic factor vascular endothelial growth factor A (VEGFA) in RCC cells. miR­218 also repressed the subcutaneous tumorigenesis of RCC cells in nude mice, and the corneal angiogenesis in rabbit eyes. The underlying molecular mechanism was elucidated; miR­218 targets GRB2­associated binding protein 2 (GAB2), thereby inhibiting the PI3K/AKT/mTOR/VEGFA pathway. These results provide new insights into the mechanism of RCC carcinogenesis and progression, suggesting that miRNA­218 may be a therapeutic target for the treatment of RCC.

The Value of Prostate-Specific Antigen-Related Indexes and Imaging Screening in the Diagnosis of Prostate Cancer.

OBJECTIVE: The aim of this study was to explore the value of the prostate-specific antigen (PSA) levels, the ratio of free PSA to total PSA (fPSA/TPSA), the PSA density (PSAD), digital rectal examination (DRE), transrectal prostate ultrasound (TRUS), and multiparameter MRI (MP-MRI) in the differential diagnosis of benign prostatic hyperplasia (BPH) and prostate cancer (PCa). METHODS: From February 2016 to September 2019, data from 620 patients who underwent systematic transrectal ultrasound-guided prostate biopsy (STURS-PB) in our hospital were retrospectively collected, including the PSA levels, the fPSA/TPSA ratio, the PSAD, DRE, TRUS, MP-MRI, prostate volume, and other clinical data. RESULTS: Among the 620 patients, 249 patients were in the PCa group, and 371 patients in the BPH group. The positive puncture rate was 40.16%. The positive predictive values of DRE, TRUS, mpMRI, and TPSA levels for PCa were 39.91%, 39.38%, 64.14%, and 41.57%, respectively; the sensitivity of these parameters was 37.35%, 51.41%, 74.69%, and 57.43%, respectively; and the specificity of these parameters was 62.26%, 46.90%, 71.97%, and 45.82%, respectively. When the TPSA concentration was in the range of 4-20 ng/mL, the positive puncture rate of STURS-PB was 23.18%, with a high rate of misdiagnosis. When the TPSA concentration was in the range of 4-20 ng/mL, the fPSA/TPSA ratio was 0.15, the PSAD was 0.16, the comprehensive evaluation of PCa was optimal (the sensitivity of these parameters was 88.85% and 84.09%, respectively; the specificity was 80.17% and 67.29%, respectively; the positive predictive value was 57.41% and 51.39%, respectively). When the TPSA concentration >4 ng/mL, the fPSA/TPSA ratio ≤0.15 and the PSAD ≥0.16, the sensitivity, specificity, and correctness index of the PCa and BPH diagnosis were 80.54%, 82.75%, and 67.07%, respectively. CONCLUSION: When using DRE, TRUS, and MP-MRI to screen for PCa, MP-MRI has a relatively high sensitivity and specificity. Using these three thresholds (TPSA >4 ng/mL combined with an fPSA/TPSA ratio ≤0.15 and a PSAD ≥0.16) is significantly better than using TPSA levels alone for the differential diagnosis of PCa and BPH.

GRB2-associated binding protein 2 regulates multiple pathways associated with the development of prostate cancer.

The development of prostate cancer is complicated and involves a number of tumor-associated gene expression level abnormalities. Gene chip technology is a high-throughput method that can detect gene expression levels in different tissues and cells on a large scale. In the present study, gene chip technology was used to screen differentially expressed genes in PC-3 human prostate cancer cells following GRB-associated binding protein 2 (GAB2) gene knockdown, and the corresponding biological information was analyzed to investigate the role of GAB2 in prostate cancer. The PC-3 human prostate cancer cell GAB2 gene was knocked out and gene chip hybridization and bioinformatics methods were used to analyze the classical pathway and predict upstream regulatory molecules, disease and function associations and genetic interaction networks. According to the screening conditions |fold change|>1 and P<0.05, 1,242 differential genes were screened; 665 genes were upregulated, and 577 genes were downregulated. Ingenuity Pathway Analysis software demonstrated that GAB2 regulates pathways, such as the superpathway of cholesterol biosynthesis and p53 signaling in cells, and serves a role in diseases and functions such as 'non-melanoma solid tumors', 'viral infections' and 'morbidity or mortality'. In the occurrence and development of prostate cancer, factors such as the activation of genes involved in the proliferative cycle, abnormalities in metabolism-associated enzyme gene activities and viral infection play key roles. The present study provides novel research directions and therapeutic targets for prostate cancer.

Amyloid-like protein aggregates combining antifouling with antibacterial activity.

Infections related to implanted medical devices have placed a heavy burden on public health and require feasible solutions. In this study, a simple approach is reported to fabricate an antifouling and antibacterial dual-functional coating. One-step aqueous supramolecular assembly of bovine serum albumin (BSA) is employed to immobilize ε-polylysine (ε-PL) and form a coating (PTB@ε-PL). Based on amyloid-like protein aggregation through the rapid reduction of the intramolecular disulfide bonds of BSA by tris(2-carboxyethyl) phosphine, a dense PTB@ε-PL nanofilm with controllable thickness and ε-PL loading density can be covered on virtually arbitrary material surfaces by simple aqueous dipping. In vitro and in vivo experiments show that this coating not only exhibits effective antibacterial activity against Gram-positive/Gram-negative bacteria, but also imparts excellent antifouling property to the surface. As a pure biopolymer coating, the PTB@ε-PL nanofilm shows negligible cytotoxicity and hemolysis. In addition, due to the various functional groups exposed on the surface of the nanofilm, the coating shows excellent interfacial bonding stability and can maintain bactericidal and antifouling properties under harsh conditions including ultrasound, autoclaving, organic solvents, and physiological body fluids.

The miR-218/GAB2 axis regulates proliferation, invasion and EMT via the PI3K/AKT/GSK-3ß pathway in prostate cancer.

Altered expression of microRNA (miRNA) is associated with the occurrence and metastasis of various tumors. We previously found that miR-218 inhibits tumor angiogenesis through the RICTOR/VEGFA axis in prostate cancer (PCa). In this study, we determined that miR-218 also had a negative effect on cell growth, migration, and invasion ability in PCa. Our data showed that miR-218 bound to the Grb2-associated binding protein 2 (GAB2) 3'-UTR region and inhibited GAB2 expression. As a novel downstream target of miR-218, GAB2 has been reported to be involved in the occurrence and development of various human tumors, but its role in the progression and metastasis of PCa has not been addressed. We demonstrated for the first time that the expression of GAB2 in the PCa cell lines was increased, while knocking down GAB2 significantly inhibited cell growth, metastatic ability and EMT process in PCa. In addition, the recovery of GAB2 could reverse the changes in the biological function of PCa cells caused by the ectopic expression of miR-218. Mechanistically, miR-218-mediated GAB2 transcriptional suppression significantly inhibited the activity of the PI3K/AKT/GSK-3ß pathway, whose abnormal activation was found to be related to the malignant progression of PCa. Taken together, our findings suggest that the miR-218/GAB2 axis may become a novel prognostic indicator and potential therapeutic target in PCa.