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Background: Hepatocellular carcinoma (HCC) has a hidden onset and high malignancy. Its high metastasis, high recurrence, and short survival time have always been a difficult and hot spot in clinical practice. Our previous study revealed that myc-associated zinc finger protein (MAZ) is highly upregulated in HCC tissues and may promote the proliferation and metastasis of HCC cells by inducing the epithelial-mesenchymal transformation (EMT) process. However, the specific regulatory mechanism by which MAZ functions as an oncogene in HCC has still not been fully elucidated. Methods: Immunohistochemical staining and bioinformatics analyses were conducted to measure the expression of MAZ, key m6A enzymes, and ZEB1 in HCC tissues. RNA sequencing (RNA-seq) of MAZ knockdown HCC cells and human mRNA m6A sequencing (m6A-seq) of HCC tissues were intersected to screen the downstream targets for both MAZ and m6A methylation. The correlations between MAZ and its targets were analyzed by dual-luciferase assays and cell rescue experiments. Results: Here, we report for the first time that MAZ is involved in m6A methylation of HCC by targeting the transcriptional regulation of key m6A enzymes. MAZ expression was significantly correlated with the expression of key m6A enzymes in HCC tissues and cell lines. Moreover, MAZ could bind to the promoters of key m6A enzymes, and multivariate Cox regression analysis suggested that MAZ and METTL3 expression were independent risk factors for the survival of HCC patients. Through RNA-seq and m6A-seq, we screened out EMT regulators ZEB1 and TRIM50 as the downstream targets for both MAZ and m6A methylation. Mechanistically, m6A sites with high confidence in ZEB1 and TRIM50 mRNA were identified by SRAMP, and there were significant relationships between ZEB1 and METTL3 in HCC tissues and cells. A nomogram model was established to better display the combined effect of MAZ, METTL3, and ZEB1 on HCC prognosis. Conclusions: Our study revealed a promising clinical application of MAZ, METTL3, and ZEB1 in HCC prognosis, further suggesting that MAZ can be used as a potential molecular biomarker for HCC diagnosis and prognosis. [ABSTRACT FROM AUTHOR]

CKLF Like Marvel Transmembrane Domain Containing 1 (CMTM1) plays a role in breast cancer and lung cancer, but studies on the occurrence and development of CMTM1 in hepatocellular carcinoma (HCC) have not been reported.

We aim to investigate the expression and clinical significance of the tubulin gamma complex-associated protein 4 (TUBGCP4) in hepatocellular carcinoma (HCC). The mRNA expression of TUBGCP4 in HCC tissues was analyzed using The Cancer Genome Atlas (TCGA) database. Paired HCC and adjacent nontumor tissues were obtained from HCC patients to measure the protein expression of TUBGCP4 by immunohistochemistry (IHC) and to analyze the relationship between TUBGCP4 protein expression and the clinicopathological characteristics and the prognosis of HCC patients. We found that TUBGCP4 mRNA expression was upregulated in HCC tissues from TCGA database. IHC analysis showed that TUBGCP4 was positively expressed in 61.25% (49/80) of HCC tissues and 77.5% (62/80) of adjacent nontumor tissues. The Chi-square analysis indicated that the positive rate of TUBGCP4 expression between HCC tissues and the adjacent nontumor tissues was statistically different (P < 0.05). Furthermore, we found that TUBGCP4 protein expression was correlated with carbohydrate antigen (CA-199) levels of HCC patients (P < 0.05). Further, survival analysis showed that the overall survival time and tumor-free survival time in the TUBGCP4 positive group were significantly higher than those of the negative group (P < 0.05), indicating that the positive expression of TUBGCP4 was related to a better prognosis of HCC patients. COX model showed that TUBGCP4 was an independent prognostic factor for HCC patients. Our study indicates that TUBGCP4 protein expression is downregulated in HCC tissues and has a relationship with the prognosis of HCC patients. [ABSTRACT FROM AUTHOR]

As an important transcription factor that is widely expressed in most tissues of the human body, Myc‐associated zinc finger protein (MAZ) has been reported highly expressed in many malignant tumors and thought to be a promising therapeutic target for cancer treatment. In this review, we aim to offer a comprehensive understanding of MAZ regulation in malignant tumors. The carboxy terminal of MAZ protein contains six C2H2 zinc fingers, and its regulation of transcription is based on the interaction between the GC‐rich DNA binding sites of target genes and its carboxy‐terminal zinc finger motifs. MAZ protein has been found to activate or inhibit the transcriptional initiation process of many target genes, as well as play an important role in the transcriptional termination process of some target genes, so MAZ poses dual regulatory functions in the initiation and termination process of gene transcription. Through the transcriptional regulation of c‐myc and Ras gene family, MAZ poses an important role in the occurrence and development of breast cancer, pancreatic cancer, prostate cancer, glioblastoma, neuroblastoma, and other malignant tumors. Our review shows a vital role of MAZ in many malignant tumors and provides novel insight for cancer diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Aims: The aim of this study was to examine the RNA and protein expression levels and clinical significance of the pore membrane protein 121 kDa (POM121) in lung cancer. Materials and Methods: Paired lung cancer and adjacent nontumor tissues were obtained from lung cancer patients to measure the expression of POM121 by quantitative reverse transcription–polymerase chain reaction and immunohistochemistry. Patient clinical and pathological data were collected to analyze their relationships with POM121 protein expression levels by chi-square test and log-rank test, respectively. Results:POM121 mRNA and protein expression were both upregulated in lung cancer tissues. POM121 protein expression was observed in 48.00% (36/75) of lung cancer tissues and 25.33% (19/75) of adjacent nontumor tissues. A chi-square analysis indicated that this difference was statistically significant (p < 0.05). Furthermore, we found that POM121 protein expression was correlated with gender, tumor node metastasis stage, and lymphatic metastasis (p < 0.05). In addition, we found a significant relationship among POM121 expression, gender, and metastasis based on a multivariate logistic regression analysis. A Kaplan–Meier survival analysis indicated that lung cancer patients with POM121 expression had a poorer prognosis than those without POM121 expression (p < 0.05). Conclusion: POM121 protein expression is associated with lung cancer metastasis and is a potential prognostic biomarker for lung cancer patients. [ABSTRACT FROM AUTHOR]

The purpose of this study was to investigate the expression and clinical significance of N6-methyladenosine demethylase FTO in thyroid cancer. Bioinformatic analysis showed that FTO expression was downregulated in thyroid cancer tissues and correlated with lymph node metastasis in thyroid cancer patients. We conducted experimental verification by collecting Asian samples. The results of quantitative reverse transcription-PCR showed that the mRNA expression of FTO in the blood of 30 thyroid cancer patients was lower than that of the control population. At the same time, we found that FTO expression was negative in tissues of 16/56 (28.57%) thyroid cancer cases and 4/40 (10.00%) nontumor thyroid cases through the immunohistochemical method, indicating a lower FTO expression in thyroid cancer tissues than nontumor thyroid tissues (p < 0.05). In addition, the protein expression of FTO was significantly related to the tumor grade and lymph node metastasis in thyroid cancer patients (p < 0.05), but not to other clinicopathological features. Multivariate logistic regression analysis showed that FTO expression was an independent risk factor for tumor grade. Survival analysis showed no significant difference in the disease-free survival time of thyroid cancer patients between high expression and low expression groups of FTO. Furthermore, bioinformatic analysis found that promoter DNA methylation and copy number variation might cause downregulated FTO and then affect TP53 pathways in thyroid cancer. We found that FTO expression was downregulated in thyroid cancer tissues and related to the progression of thyroid cancer, suggesting a tumor suppressor role of FTO in thyroid cancer. [ABSTRACT FROM AUTHOR]

Background: Our recent study identified that human chemokine-like factor (CKLF)-like MARVEL transmembrane domain-containing family member 2 (CMTM2) was deregulated in hepatocellular carcinoma (HCC) tissues and posed as a potential tumor suppressor. However, the mechanism of CMTM2 in HCC occurrence and development has not been well elaborated. Materials and Methods: The expression of CMTM2 was knocked-down by RNA interruption in Huh-7 and SMMC7721 cells. Cell proliferation ability was detected by CCK8 test and colony formation assay. The cell invasion and migration were measured by wound healing and Transwell assay. Results: We found that the cell proliferation was significantly increased by interruption of CMTM2 expression, both in Huh-7 and SMMC7721 cells. Moreover, down-regulated CMTM2 could promote the invasion and migration ability of HCC cells through inducing the epithelial-mesenchymal transition (EMT) process. We further discovered that both the expression of CMTM2 and the EMT-associated marker E-cadherin were decreased in the same thirty cases of HCC tissues compared with the corresponding adjacent non-tumor tissues. Pearson correlation test showed that there was a significantly positive correlation between CMTM2 and E-cadherin in HCC tissues (P< 0.05). Conclusion: Based on the results of cell model and HCC tissues, our study suggests that down-regulated CMTM2 promotes HCC metastasis through inducing the EMT process. [ABSTRACT FROM AUTHOR]

Although the Chinese government at all levels has increasingly embraced Public-Private Partnership (PPP) as their preferred approach to deliver large-scale infrastructure since 2014, residual value risk (RVR) has been ignored in PPP practice. To systematically explore the critical risk factors (CRFs) responsible for measuring RVR in highway PPP projects, this paper proposes and refines a conceptual model composed of two risk dimensions (four risk categories) and 29 indicators through process-based viewpoint. Through literature review and expert interview, a structured questionnaire was developed to collect responses with rich working experience in construction industry or highway PPP projects. The refined measurement model with 21 CRFs was validated through mean value analysis (MVA) and confirmatory factor analysis (CFA) performed by SPSS 23.0 and AMOS 23.0, respectively. The findings indicate that 21 CRFs are significant in influencing RVR of highway PPP projects. Moreover, RVR from system dimension is mainly concentrating on institutional environment, macroeconomy, and relationship aspects, whereas financing in preconstruction, quality in construction, and market demand in operation are the most significant CRFs in nonsystem dimension. Furthermore, there is an accumulative exposure of RVR during the project process, especially in preconstruction and operation. This paper sheds light on the significance of lifecycle management on RVR and provides a practical approach for measuring RVR and implementing sustainable practice in highway or other transportation PPP projects. [ABSTRACT FROM AUTHOR]

Depression is a serious psychiatric illness that causes great inconvenience to the lives of elderly individuals. However, the diagnosis of depression is somewhat subjective. Nontargeted gas chromatography (GC)/liquid chromatography (LC)–mass spectrometry (MS) was used to study the plasma metabolic profile and identify objective markers for depression and metabolic pathway variation. We recruited 379 Chinese community-dwelling individuals aged ≥ 65. Plasma samples were collected and detected by GC/LC‒MS. Orthogonal partial least squares discriminant analysis and a heatmap were utilized to distinguish the metabolites. Receiver operating characteristic curves were constructed to evaluate the diagnostic value of these differential metabolites. Additionally, metabolic pathway enrichment was performed to reveal metabolic pathway variation. According to our standard, 49 people were included in the depression cohort (DC), and 49 people age- and sex-matched individuals were included in the non-depression cohort (NDC). 64 metabolites identified via GC‒MS and 73 metabolites identified via LC‒MS had significant contributions to the differentiation between the DC and NDC, with VIP values > 1 and p values < 0.05. Three substances were detected by both methods: hypoxanthine, phytosphingosine, and xanthine. Furthermore, 1-(sn-glycero-3-phospho)-1D-myo-inositol had the largest area under the curve (AUC) value (AUC = 0.842). The purine metabolic pathway is the most important change in metabolic pathways. These findings show that there were differences in plasma metabolites between the depression cohort and the non-depression cohort. These identified differential metabolites may be markers of depression and can be used to study the changes in depression metabolic pathways. [ABSTRACT FROM AUTHOR]

In order to explore the causal relationship between the level of urban digital construction and urban economic growth, this paper takes 280 cities in China as the research object and constructs a comprehensive indicator evaluation system covering digital infrastructure, overall economic level, innovation development level, digital industry development status, and ecological environment conditions. Using the entropy method to weigh various indicators, this paper has obtained the evaluation results of the digital construction level of each city from 2011 to 2021. Furthermore, a panel data regression model is used to empirically analyze the impact of urban digital construction level on urban economic growth. The results show that for every 1% increase in the level of urban digital construction, the GDP will increase by 0.974. Through the above research, we hope to further enrich the theoretical and empirical research in the field of the digital economy, provide a scientific and reasonable method for quantitatively evaluating the level of urban digital construction, and provide decision-making references for improving the level of urban digital construction and promoting sustainable urban development. [ABSTRACT FROM AUTHOR]

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The futures contracts were introduced to act as hedging instruments and ensure the price discovery (referred to as PD hereafter) mechanism for the underlying securities. If the price movement of a futures contract leads the price movement of the underlying securities in the spot market, this confirms the existence of price discovery in the market. This study undertakes an in-depth analysis of past research in order to find research trends and directions for the future in the field of price discovery. The bibliometric analysis technique is used to analyse the existing literature. The study considers the 1431 documents collected from the Scopus database for the period of 1982–2021 to conduct the descriptive and network analysis of search results. The study identifies three key clusters, i.e., the foundation of the price discovery process (Cluster 1), the econometric tools and techniques to assess the price discovery process (Cluster 2), and price discovery under different market conditions and constraints (Cluster 3). After an in-depth content analysis of these clusters, the study provides suggestions for future research in the field of price discovery. The study is the first of its type to conduct an in-depth analysis of the literature of price discovery since inception, and provides directions for future research in the field. [ABSTRACT FROM AUTHOR]

Smart cities are purported to produce vast amounts of data of immense value, both commercially and from a governance perspective. The control and stewardship of this smart city data remains controversial, with concerns for the role of the individual smart citizens and the control they exercise over the data they generate. Elinor Ostrom's Nobel prize winning work on long-lasting and sustainable commons has been suggested as a solution, whereby the commons management principles would be applied to smart city data. This paper seeks to identify the current applications of Ostrom's commons to smart city data in literature, as well as explore their legal implications. Particularly, what legal challenges may arise from the smart city data commons, and how they could be addressed through legislative frameworks. The article aims to identify and highlight these legal challenges and thereby provide a legal perspective on the concept of smart city data commons. [ABSTRACT FROM AUTHOR]

In this paper, the mesoscale damage properties of concrete and mortar were studied experimentally under Brazilian disc splitting tensile tests combining X-ray computed tomography (CT) and digital image correlation (DIC) technology. Considering the factors of water/cement ratios and loading rates, the influence of meso components on the macro tensile properties and failure modes of concrete were studied. The experimental results and analysis indicate that the following: (1) the existence of coarse aggregate makes the tensile strength of concrete lower than that of mortar and reduces the sensitivity of tensile strength to the loading rates; (2) the failure modes of mortar and concrete Brazilian discs differ in the crack initiation positions and localization phenomena. Under high loading rates, the local failure plays a critical role in the strength improvement of concrete; (3) for concrete, interface failure and mortar failure are the main failure modes under low loading rates, whereas aggregate failure gradually becomes the main failure mode with increasing loading rates. The decrease in water/cement ratios improves the strength of the mortar matrix and interfacial bonding performance, leading to more serious aggregate damage and higher strength. [ABSTRACT FROM AUTHOR]

The concept of smart public governance (SPG) is gaining attention among researchers, policymakers, and practitioners around the world, especially in response to the modernisation of public administration through emerging technologies in both local (smart city) and national (smart government) levels. Spurred by the noticeable lack of understanding of the SPG concept, the paper aims to comprehensively examine the SPG research by considering the characteristic differences between the smart city and smart government concepts. Bibliometric analysis is based on the Scopus database, containing 775 documents published in the last two decades and facilitated by several established and innovative bibliometric approaches. The results reveal the growth of SPG research over time. Despite the smart city concept being the dominant focus in the SPG research, the smart government concept has been becoming more relevant in recent years, as indicated by some prominent documents published in reputable journals like Government Information Quarterly. Moreover, Anglo-Saxon countries are chiefly engaged in SPG research. However, New Zealand and South Korea are identified as countries with a stronger focus on the smart government concept. The results show the smart city concept is connected with several smart-related initiatives (e.g., smart transportation, smart living, smart energy, etc.), while the smart government concept is primarily associated with smart (de)regulation and smart grid. The findings may add to the understanding of the future development of SPG research, on both local and national levels. [ABSTRACT FROM AUTHOR]

An external direct current (DC) was introduced to counteract the thermoelectric magnetic effect during the directional solidification of Sn-10 wt pct Bi alloy under a 0.5 T transverse static magnetic field. The results show that the single-side Bi segregation induced by the thermoelectric magnetic effect gradually becomes weakened, disappeared, and then reversed with the increasing current density of the external DC. Therefore, a new method for counteracting the thermoelectric magnetic effect during materials processing under the magnetic field was proposed. In order to verify this method, the absolute thermoelectric power of Sn-10 wt pct Bi alloy and the internal thermoelectric current under the experimental conditions were measured and calculated, respectively. A 2D numerical simulation was established to simulate the evolution of the solid-liquid interface morphology, flow field, and composition segregation with the increasing current density of the external DC during directional solidification under a transverse static magnetic field. The present study not only facilitates the understanding of the effects of the forced flows on the directionally solidified microstructures and composition segregation, but also provides a new way for eliminating segregation and obtaining the higher-quality solidification structure by using the electromagnetic compounding technique. [ABSTRACT FROM AUTHOR]