Adrenal tumors are common, but adrenocortical carcinomas (ACCs) are a rare and challenging form of cancer to diagnose and manage.This study aimed to explore the critical role of mitochondrial quality ...in maintaining cellular function and the implications of the abnormal expression of mitochondrial metabolism-related proteins observed in ACC patients. We focused on identifying the connection between mitochondrial quality and the development of ACC at molecular and genomic levels.
We compared mitochondrial quality-related genes (MQRGs) across ACC subtypes using overall survival (OS) and disease-free survival (DFS) as evaluation indicators. Furthermore, a novel MQRG score was developed to predict clinical prognosis and guide immunotherapy responses accurately.
The majority of MQRGs were upregulated in the ACC samples, correlating to poor prognosis. The MQRG score was confirmed as an independent prognostic factor for ACC, with the high-risk MQRG score group showing a significantly shorter overall survival period.
Multilayer alterations in MQRGs are associated with patient prognosis and immune cell infiltration characteristics. This comprehensive analysis of MQRGs can contribute to a deeper understanding of potential differences in ACC patients' tumor microenvironment. This can influence clinical decision-making and advanced prognosis prediction, thereby offering new insights into personalized treatments in ACC.
Although the tumor mutation burden (TMB) was reported as a biomarker for immunotherapy of various cancers, whether it can effectively predict the survival prognosis in breast cancer patients remains ...unclear. In this study, the prognostic value of TMB and its correlation with immune infiltration were explored by using multigroup studies.
The somatic mutation data of 986 breast cancer patients were obtained from TCGA database. Breast cancer patients were divided into a low-TMB group and a high-TMB group according to the quartile of TMB scores. The differentially expressed genes (DEGs) were identified by the "limma" R program. The CIBERSORT algorithm was utilized to estimate the immune cell fraction of each sample. The TIMER database was utilized to evaluate the association between CNVs of immune genes and tumor immune cell infiltration and the prognostic value of the immune cells in breast cancer.
In breast cancer, TP53, PIK3CA, TTN, CDH1 and other genes were the most important mutated genes. Higher survival rate of patients was found in the low-TMB group. Among the top 10 DEGs, three of them belong to the KRT gene family. GSEA enrichment analysis showed that MAPK, Hedgehog, mTOR, TGF-bate and GnRH signaling pathways were enriched in the low-TMB group. The infiltration levels of the most of immune cells were higher in the low-TMB group (P < 0.01). Higher expression of CCL18 and TRGC1 was correlated with poor prognosis. Breast cancer patients with CCL18 copy number variations, especially arm-level gains, showed significantly decreased immune cell infiltration. In the low B cell infiltration group, the survival prognosis of breast cancer patients was poor.
TMB is a potential prognosis marker in breast cancer. Immune-related gene CCL18 and TRGC1 are biomarkers of poor prognosis while immune (B cell) infiltration is a biomarker of good prognosis.
To study the value of plasma miRNA23-a and miRNA-451 as potential biomarkers for early diagnosis of non-small cell lung cancer (NSCLC).
Fifty patients with NSCLC and 50 healthy control subjects were ...recruited for testing the plasma levels of miRNA23-a and miRNA-451 and their expression levels in the tumor tissues using qRT-PCR. The correlations of the plasma levels of miRNA23-a and miRNA-451 with their expressions in the tumor tissues were analyzed. The diagnostic power of CEA, miRNA23-a and miRNA-451 for NSCLC was evaluated using the receiver-operating characteristics (ROC) curves and the area under the ROC curves (AUC). In the NSCLC cell line A549, we tested the effect of inhibition of miRNA-23a and miRNA-451 on the expression levels of SPRY2 and MIF mRNA using qRT-PCR.
The expression levels of miRNA-23a and miRNA-451 in NSCLC tissues was significantly associated with smoking, tumor size, lymph node metastasis and TNM stage (
< 0.05). Compared with those in the control group, miRNA-23a level was significant
BACKGROUND Lung adenocarcinoma currently accounts for the highest cancer-related mortality rate worldwide. MiR-21-5p has a vital role in various types of cancers. We have analyzed the miR-21-5p ...expression level, prognosis, and associated molecular pathways in lung adenocarcinoma with multiple bioinformatics databases. MATERIAL AND METHODS The Cancer Genome Atlas (TCGA) database was employed to fetch the miR-21-5p expression profile in multiple tumors. We used the UALCAN platform to assess the differential regulation of the miR-21-5p in healthy tissue and lung adenocarcinoma. Also, the survival prognosis of the miR-21-5p in each stage of lung adenocarcinoma was done by the Kaplan-Meier database. The STARBASE and UALCAN databases were employed to predict the miR-21-5p target genes, and the levels of target genes and their prognostic value were analyzed. RESULTS MiR-21-5p was overexpressed in the majority of human cancers. MiR-21-5p demonstrated escalated expression in the lung adenocarcinoma tissue in contrast to the normal tissue (P<0.05). Poor prognosis was witnessed in the miR-21-5p high expression group as compared to the low expression group (hazard ratio HR= 1.59, P<0.05). PDZD2 was predicted as a miR-21-5p potential target. We found a negative correlation between PDZD2 and miR-21-5p (r=-0.255, P<0.05). PDZD2 was downregulated in lung adenocarcinoma (P<0.05). Overexpression of PDZD2 was associated with a better prognosis of survival in lung adenocarcinoma patients (HR=0.45, P<0.05). CONCLUSIONS MiR-21-5p exhibits the potential to act as a biomarker for the survival prognosis of lung adenocarcinoma. It might be responsible for the onset and progression of lung adenocarcinoma through PDZD2 regulation.
Non-small cell lung cancer (NSCLC) is a common malignancy with a high morbidity and mortality rate worldwide, but the driver genes and signaling pathways involved are largely unclear. Herein, our ...study aimed to identify significant genes with poor outcome and underlying mechanisms in NSCLC using bioinformatics analyses.
Gene expression profiles (GSE33532, GSE19188, GSE102287, GSE27262), including 319 NSCLC and 232 adjacent lung tissues, were downloaded from the GEO database. Differentially expressed genes (DEGs) were identified by the GEO2R online tool. Functional and pathway enrichment analyses were performed via the DAVID database. The protein-protein interactions (PPIs) of these DEGs were constructed by the STRING website and visualized by the Cytoscape software platform. The expression of hub genes in NSCLC was validated through the GEPIA database. Kaplan-Meier plotter was used to analyse the survival rate with multivariate Cox regression. The expression of protein tyrosine kinase 2 (PTK2) in NSCLC and adjacent lung tissues was evaluated on the UALCAN database platform.
A total of 225 significant DEGs were obtained between NSCLC and adjacent lung tissues, containing 52 upregulated genes and 173 downregulated genes. The DEGs were clustered based on functions and signaling pathways that may be closely associated with NSCLC occurrence. A total of 174 DEGs were identified from the PPI network complex. Top 10 hub genes were selected by CytoHubba plugin. As independent predictors, seven genes (
) were associated with poor prognosis in NSCLC via multivariate Cox regression (P<0.01). Four genes (
) were found to be significantly enriched in the focal adhesion pathway (P=1.04E-04) and to be upstream regulators of PTK2. PTK2 was upregulated in NSCLC and associated with poor survival prognosis in lung squamous cell carcinoma (LUSC).
Taken together, the important genes and pathways in NSCLC were identified by using integrated bioinformatics analysis. PTK2 could be a key gene associated with the biological process of NSCLC formation and progression and a potential therapeutic target for NSCLC treatment.
Predicting the concentration distribution of solute transport in vegetated flows is significant for associated environmental applications in water resources. While a semianalytical study has been ...made for the steady dispersion with a continuous release (Rubol et al., 2016, https://doi.org/10.1002/2016WR018907), an in‐depth analytical investigation has yet to be performed for the more complicated case of transient dispersion due to an instantaneous release. In regard to the pioneering benchmark observation (Murphy et al., 2007, https://doi.org/10.1029/2006WR005229) of transient solute dispersion in a submerged vegetated flow for an instantaneous source release at the top of the canopy, an extensive analytical effort is paid in this work to derive the time‐dependent basic properties and to investigate the temporal evolution of concentration distribution. Obtained large‐time asymptotic dispersivities agree well with available experimental results (Murphy et al., 2007, https://doi.org/10.1029/2006WR005229), with higher significance (
R2=0.87,
n=24) for correlation between analytical results and experimental data. Analytical solutions covering effects of dispersivity, skewness, and kurtosis of detailed concentration distribution are compared satisfactorily with numerical results obtained by the random displacement method. The findings illuminate the applicability of this analytical approach in environmental risk assessment and water quality management.
Key Points
An analytical study is performed for transient solute dispersion in wetland flows with submerged vegetation
Basic time‐dependent properties including dispersivity are derived with asymptotic values consistent with available experimental data
Temporal evolution of concentration distribution is revealed agreeing well with numerical results by the random displacement method
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•Transport process of point source on water surface in a channel flow is revealed.•The complete two-dimensional concentration distribution is presented.•The effect of bed absorption on the dispersion ...process is thoroughly discussed.
Studying solute dispersion in channel flows is of significance for environmental and industrial applications. Two-dimensional concentration distribution for a most typical case of a point source release on the free water surface in a channel flow with bed absorption is presented by means of Chatwin’s long-time asymptotic technique. Five basic characteristics of Taylor dispersion and vertical mean concentration distribution with skewness and kurtosis modifications are also analyzed. The results reveal that bed absorption affects both the longitudinal and vertical concentration distributions and causes the contaminant cloud to concentrate in the upper layer. Additionally, the cross-sectional concentration distribution shows an asymptotic Gaussian distribution at large time which is unaffected by the bed absorption. The vertical concentration distribution is found to be nonuniform even at large time. The obtained results are essential for practical implements with strict environmental standards.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
•The effect of bed absorption causes contaminant to concentrate more in upper layer.•With bed absorption environmental dispersivity is reduced in a shallow channel.•Skewness of the cross-sectional ...mean concentration distribution is presented.•Length and duration of the influenced region are reduced with bed absorption.
Predicting the evolution of concentration distribution for contaminant transport in wetland flows has a wide range of ecological applications. To account for the ecological effect such as substrate absorption, the influence of bed absorption on the dispersion process of contaminant transport in a wetland channel with rectangular cross-section is analytically investigated in this study by the technique of long-time asymptotic expansion. The combined effects of bed absorption, free-water-surface-effect and the bank-sidewall-effect are demonstrated, by parameter analysis in terms of the bed absorption coefficient and the aspect ratio of the channel section. The studied cases illustrate that bed absorption decreases the total mass of the contaminant cloud retained in the flow and causes the contaminant cloud to concentrate more in the upper layer. The mean advection velocity of the contaminant cloud increases as the intensity of bed absorption amplifies. Environmental dispersivity is augmented with bed absorption in a deep wetland channel, which is inverse in a shallow channel. The effect of bed absorption weakens the positive skewness of the cross-sectional mean concentration distribution when the wetland channel approaches square, while strengthens the negative skewness of the cross-sectional mean concentration distribution when the channel is relatively shallow. Moreover, the cross-sectional mean concentration decays faster under the effect of bed absorption. For applications, the critical length and duration of the influenced region are presented with bed absorption.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Objective
Alzheimer’s disease (AD) is a socially significant neurodegenerative disorder among the elderly worldwide. An increasing number of studies have revealed that as a non-pharmacological ...intervention, exercise can prevent and treat AD. However, information regarding the research status of this field remains minimal. Therefore, this study aimed to analyze trends and topics in exercise and AD research by using a bibliometric method.
Methods
We systematically searched the Web of Science Core Collection for published papers on exercise and AD. The retrieved data regarding institutions, journals, countries, authors, journal distribution, and keywords were analyzed using CiteSpace software. Meanwhile, the co-occurrence of keywords was constructed.
Results
A total of 1,104 papers were ultimately included in accordance with our specified inclusion criteria. The data showed that the number of published papers on exercise and AD is increasing each year, with papers published in 64 countries/regions and 396 academic journals. The Journal of Alzheimer’s Disease published the most papers (73 publications). Journals are concentrated in the fields of neuroscience and geriatrics gerontology. The University of Kansas and the United States are the major institution and country, respectively. The cited keywords show that oxidative stress, amyloid beta, and physical exercise are the research hotspots in recent years. After analysis, the neuroprotective effect of exercise was identified as the development trend in this field.
Conclusions
Based on a bibliometric analysis, the number of publications on exercise and AD has been increasing rapidly, especially in the past 10 years. “Amyloid beta,” “oxidative stress,” and “exercise program” trigger the most interest among researchers in this field. The study of exercise program and mechanism of exercise in AD is still the focus of future research.
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