Morphology tailoring and temperature sensitivity control of waist cross-linked micelles and evaluation of their application as intelligent drug carriers

A novel type of waist cross-linked micelle (WCM) was developed as an intelligent drug carrier via the self-assembly guiding free radical polymerization of an amphiphilic oligomer: octadecyl, polyethylene glycol butenedioates (O-B-EGs). By changing the concentration of O-B-EG reaction solution, WCMs with monolayer, compound and vesicle-like morphologies were obtained. These WCMs showed controllable temperature responsive properties. DLS and UV-vis analyses indicate that the critical temperatures at which WCMs show an abrupt change in particle size evidently increases with the increase in the molecular weight of the PEG chains. Direct switching of the release of pyrene in WCMs is also realized by a slight change of temperature. Pyrene is released rapidly at the temperatures around the critical temperature of the WCMs, but a further increase in temperature shuts down the release of pyrene. More importantly, these WCMs exhibit reversible and rapid pyrene releasing-absorbing behavior. We suggest that these excellent properties endow WCMs with great potential in drug encapsulation and controlled releaseNational Natural Science Foundation of China [50873082, 30700020]; Research Fund for the Doctoral Program of Higher Education [20070384047]; Scientific and Technical Project of Fujian Province of China [2009J1009

Empirical Analysis of the Driving Factors of China’s ‘Land Finance’ Mechanism Using Soft Budget Constraint Theory and the PLS-SEM Model

“Land finance„ refers to the key fiscal strategy in which local governments in China generate revenue through land grant premiums and land tax revenues. A burgeoning body of literature has focused on the driving factors of China’s land finance from different aspects including fiscal decentralization, revenue decentralization, competition among local governments, land marketization, infrastructure development, and economic development. However, little research has provided a comprehensive perspective integrating social, economic and institutional aspects to investigate the driving forces of these unique and profound issues in China. This study aims to investigate the driving factors and working mechanism of land finance. A theoretical and empirical model was proposed using soft budget constraint theory and least squares structural equation modeling (PLS-SEM). The panel data of 35 Chinese major cities were assessed between 2006 and 2015. The empirical results contend the following: (1) the land transfer and fiscal systems provide the key impetus for land financing because the land transfer system forms a stable modality, and the fiscal system is an important incentive for land financing; (2) the effects of the economic development and political system are insignificant; and (3) the political and land systems significantly influence economic development. Our contributions focus on two aspects. Firstly, a comprehensive framework of factors germane to land finance is constructed. Secondly, a new research methodology for land use study is proposed. To the best of our knowledge, the current study is the first to employ the PLS-SEM method to delineate and verify the influence paths between multiple driving factors and land finance in different cities. Hence, research reliability can be improved

SMG9 is a novel prognostic-related biomarker in glioma correlating with ferroptosis and immune infiltrates

Background: Glioma is the most frequent type of malignancy that may damage the brain with high morbidity and mortality rates and patients' prognoses are still dismal. Ferroptosis, a newly uncovered mode of programmed cell death, may be triggered to destroy glioma cells. Nevertheless, the significance of ferroptosis-related genes (FRGs) in predicting prognosis in glioma individuals is still a mystery. Methods: The CGGA (The Chinese Glioma Atlas), GEO (Gene Expression Omnibus), and TCGA (The Cancer Genome Atlas) databases were all searched to obtain the glioma expression dataset. First, TCGA was searched to identify differentially expressed genes (DEGs). This was followed by a machine learning algorithm-based screening of the glioma's most relevant genes. Additionally, these genes were subjected to Gene Ontology (GO) and KEGG (Kyoto Encyclopedia of Genes and Genomes) functional enrichment analyses. The chosen biological markers were then submitted to single-cell, immune function, and gene set enrichment analysis (GSEA). In addition, we performed functional enrichment and Mfuzz expression profile clustering on the most promising biological markers to delve deeper into their regulatory mechanisms and assess their clinical diagnostic capacities. Results: We identified 4444 DEGs via differential analysis and 564 FRGs from the FerrDb database. The two were subjected to intersection analysis, which led to the discovery of 143 overlapping genes. After that, glioma biological markers were identified in fourteen genes by the use of machine learning methods. In terms of its use for clinical diagnosis, SMG9 stands out as the most significant among these biomarkers. Conclusion: In light of these findings, the identification of SMG9 as a new biological marker has the potential to provide information on the mechanism of action and the effect of the immune milieu in glioma. The promise of SMG9 in glioma prognosis prediction warrants more study

Expression pattern and prognostic value of key regulators for N7-methylguanosine RNA modification in prostate cancer

Alterations in the regulators of RNA methylation modifications, such as N7-methylguanosine (m7G), have been implicated in a variety of diseases. Therefore, the analysis and identification of disease-related m7G modification regulators will accelerate advances in understanding disease pathogenesis. However, the implications of alterations in the regulators of m7G modifications remain poorly understood in prostate adenocarcinoma. In the present study, we analyze the expression patterns of 29 m7G RNA modification regulators in prostate adenocarcinoma using The Cancer Genome Atlas (TCGA) and perform consistent clustering analysis of differentially expressed genes (DEGs). We find that 18 m7G-related genes are differentially expressed in tumor and normal tissues. In different cluster subgroups, DEGs are mainly enriched in tumorigenesis and tumor development. Furthermore, immune analyses demonstrate that patients in cluster 1 have significantly higher scores for stromal and immune cells, such as B cells, T cells, and macrophages. Then, a TCGA-related risk model is developed and successfully validated using a Gene Expression Omnibus external dataset. Two genes ( EIF4A1 and NCBP2) are determined to be prognostically significant. Most importantly, we construct tissue microarrays from 26 tumor specimens and 20 normal specimens, and further confirm that EIF4A1 and NCBP2 are associated with tumor progression and Gleason score. Therefore, we conclude that the m7G RNA methylation regulators may be involved in the poor prognosis of patients with prostate adenocarcinoma. The results of this study may provide support for exploring the underlying molecular mechanisms of m7G regulators, especially EIF4A1 and NCBP2

MACC1 down-regulation inhibits proliferation and tumourigenicity of nasopharyngeal carcinoma cells through Akt/β-catenin signaling pathway.

The present study was aimed at investigating the expression of metastasis-associated in colon cancer 1 (MACC1) in nasopharyngeal carcinoma (NPC), its relationship with β-catenin, Met expression and the clinicopathological features of NPC, and its roles in carcinogenesis of NPC. Our results showed that MACC1 expression was higher in NPC cells and tissues than that in normal nasopharyngeal cells and chronic inflammation of the nasopharynx tissues, respectively. MACC1 expression was closely related to the clinical stage (p = 0.005) and the N classification (p<0.05) of NPC. Significant correlations between MACC1 expression and Met expression (p = 0.003), MACC1 expression and β-catenin abnormal expression (p = 0.033) were found in NPC tissues. MACC1 knockdown dramatically inhibited cellular proliferation, migration, invasion, and colony formation, but induced apoptosis in NPC cells compared with the control group. Furthermore, MACC1 down-regulation inhibited phosphorylated-Akt (Ser473) and β-catenin expression in NPC cells, but phosphorylated-Erk1/2 expression was not altered. Further study showed that phosphotidylinsitol-3-kinase inhibitor downregulated β-catenin and Met expression in NPC cells. There was a significant relationship between MACC1 expression and phosphorylated-Akt expression (p = 0.03), β-catenin abnormal expression and phosphorylated-Akt expression (p = 0.012) in NPC tissue, respectively. In addition, Epstein Barr virus-encoded oncogene latent membrane protein 1 upregulated MACC1 expression in NPC cells. Our results firstly suggest that MACC1 plays an important role in carcinogenesis of NPC through Akt/β-catenin signaling pathway. Targeting MACC1 may be a novel therapeutic strategy for NPC

Microarray-based analysis and clinical validation identify ubiquitin-conjugating enzyme E2E1 (UBE2E1) as a prognostic factor in acute myeloid leukemia

Abstract Background Previous research suggested that single gene expression might be correlated with acute myeloid leukemia (AML) survival. Therefore, we conducted a systematical analysis for AML prognostic gene expressions. Methods We performed a microarray-based analysis for correlations between gene expression and adult AML overall survival (OS) using datasets GSE12417 and GSE8970. Positive findings were validated in an independent cohort of 50 newly diagnosed, non-acute promyelocytic leukemia (APL) AML patients by quantitative RT-PCR and survival analysis. Results Microarray-based analysis suggested that expression of eight genes was each associated with 1-year and 3-year AML OS in both GSE12417 and GSE8970 datasets (p < 0.05). Next, we validated our findings in an independent cohort of AML samples collected in our hospital. We found that ubiquitin-conjugating enzyme E2E1 (UBE2E1) expression was adversely correlated with AML survival (p = 0.04). Multivariable analysis showed that UBE2E1 high patients had a significant shorter OS and shorter progression-free survival after adjusting other known prognostic factors (p = 0.03). At last, we found that UBE2E1 expression was negatively correlated with patients’ response to induction chemotherapy (p < 0.05). Conclusions In summary, we demonstrated that UBE2E1 expression was a novel prognostic factor in adult, non-APL AML patients