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  • 1
    Online Resource
    Online Resource
    Bioinformatics Prediction and Experimental Verification Identify CAB39L as a Diagnostic and Prognostic Biomarker of Kidney Renal Clear Cell Carcinoma
    MDPI AG ; 2023
    In:  Medicina Vol. 59, No. 4 ( 2023-04-06), p. 716-
    Details
    In: Medicina, MDPI AG, Vol. 59, No. 4 ( 2023-04-06), p. 716-
    Abstract: Background and Objectives: Calcium-binding protein 39-like (CAB39L) has been reported to be downregulated and possessed diagnostic and prognostic values in several types of cancer. However, the clinical value and mechanism of CAB39L in kidney renal clear cell carcinoma (KIRC) remain unclear. Materials and Methods: Bioinformatics analysis was conducted using different databases including TCGA, UALCAN, GEPIA, LinkedOmics, STRING, and TIMER. One-way variance analysis and t-test were chosen to investigate the statistical differences of CAB39L expression in KIRC tissues with different clinical characteristics. The receiver operating characteristic (ROC) curve was chosen to assess the discriminatory capacity of CAB39L. Kaplan–Meier curves were employed for assessing the influence of CAB39L on the progression-free survival (PFS), disease-specific survival (DSS), and overall survival (OS) of KIRC patients. The independent prognostic significance of clinical parameters for OS such as CAB39L expression in KIRC patients was estimated by Cox analysis. A series of in vitro functional experiments and Western blot (WB) and immunohistochemistry (IHC) were used to validate the relative protein expression and function of CAB39L. Results: The mRNA and protein levels of CAB39L were relatively downregulated in KIRC samples. Meanwhile, hypermethylation of the CAB39L promoter region was possibly associated with its low expression in KIRC. The ROC curve showed that the mRNA expression of CAB39L had a strong diagnostic value for both early and late KIRC. Kaplan–Meier survival curves indicated that a higher mRNA level of CAB39L predicted good PFS, DSS, and OS. The mRNA expression of CAB39L was an independent prognostic factor (hazard ratio = 0.6, p = 0.034) identified by multivariate Cox regression analysis. The Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analysis exhibited that CAB39L was mainly associated with substance and energy metabolism. Finally, overexpression of CAB39L impaired the proliferation and metastasis of KIRC cells in vitro. Conclusions: CAB39L possesses prognostic and diagnostic capacity in KIRC.
    Type of Medium: Online Resource
    ISSN: 1648-9144
    URL: Article
    DOI: 10.3390/medicina59040716
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2088820-X
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  • 2
    Online Resource
    Online Resource
    Activation of cGAS-STING Signal to Inhibit the Proliferation of Bladder Cancer: The Immune Effect of Cisplatin
    MDPI AG ; 2022
    In:  Cells Vol. 11, No. 19 ( 2022-09-27), p. 3011-
    Details
    In: Cells, MDPI AG, Vol. 11, No. 19 ( 2022-09-27), p. 3011-
    Abstract: Cisplatin is commonly used in neoadjuvant, adjuvant, and systemic therapy for advanced bladder cancer, but its immune-related mechanism is still unclear. Exploration of the immune effects of cisplatin in bladder cancer would complement the comprehensive mechanism of cisplatin and provide the basis for combination therapy of cisplatin and immunotherapy in bladder cancer. We confirmed the immune effects of cisplatin on T24 and TCCSUP bladder cancer cell lines in vitro and explored the important function of these immune effects in the bladder cancer microenvironment in a mice tumor model. We found cisplatin induced immune response in bladder cancer by RNA sequencing and validated that cGAS-STING signal was deeply involved in this response. Cisplatin induced cGAS-STING signal inhibited the proliferation of bladder cancer and increased the infiltration percentages of CD8+ T cells and dendritic cells in a transplantation mice tumor model. Accumulation of dsDNA and the release of chromatin bound cGAS are important to activate downstream STING. Our findings indicated a cisplatin-related immune effect in bladder cancer, and cisplatin combined with immunotherapy might have a synergistic effect for bladder cancer therapy.
    Type of Medium: Online Resource
    ISSN: 2073-4409
    URL: Article
    DOI: 10.3390/cells11193011
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2661518-6
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  • 3
    Online Resource
    Online Resource
    SAA1 Has Potential as a Prognostic Biomarker Correlated with Cell Proliferation, Migration, and an Indicator for Immune Infiltration of Tumor Microenvironment in Clear Cell Renal Cell Carcinoma
    MDPI AG ; 2023
    In:  International Journal of Molecular Sciences Vol. 24, No. 8 ( 2023-04-19), p. 7505-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 24, No. 8 ( 2023-04-19), p. 7505-
    Abstract: The tumor microenvironment (TME) plays an important part in the initiation and development of clear cell renal cell carcinoma (ccRCC). However, an understanding of the immune infiltration in TME is still unknown. Our study aims to explore the correlation between the TME and the clinical features, as well as the prognosis of ccRCC. In the present study, ESTIMATE and CIBERSORT computational methods were applied to calculate the proportion of tumor-infiltrating immune cells (TICs) and the amount of immune and stromal fractions in the ccRCC form The Cancer Genome Atlas (TCGA) database. Then, we sought to find out those immune cell types and genes which may play a significant role and validated them in the GEO database. Furthermore, an immunohistochemical analysis of our external validation dataset was used to detect SAA1 and PDL1 expression in the ccRCC cancer tissues and corresponding normal tissues. Statistical analysis was performed to study the relationship between SAA1 and clinical characteristics, as well as PDL1 expression. Furthermore, a ccRCC cell model with SAA1 knockdown was constructed, which was used for cell proliferation and the migration test. The intersection analysis of the univariate COX and PPI analysis were performed to imply Serum Amyloid A1 (SAA1) as a predictive factor. The expression of SAA1 was significantly negatively correlated to OS and positively correlated to the clinical TMN stage system. The genes in the high-expression SAA1 group were basically enriched in immune-related activities. The proportion of mast cells resting was negatively correlated with SAA1 expression, indicating that SAA1 may be involved in the maintenance of the immune status for the TME. Moreover, the PDL1 expression was positively related to the SAA1 expression and negatively correlated with the patients’ prognosis. Further experiments revealed that the knockdown of SAA1 inhibited ccRCC development through suppressing cell proliferation and migration. SAA1 may be a novel marker for the prognosis prediction of ccRCC patients and may play a vital role in the TME by mast cell resting and PDL1 expression. SAA1 has the potential to become a therapeutic target and indicator for immune target therapy in ccRCC treatment.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms24087505
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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  • 4
    Online Resource
    Online Resource
    Cryogenic Transport Characteristics of P-Type Gate-All-Around Silicon Nanowire MOSFETs
    MDPI AG ; 2021
    In:  Nanomaterials Vol. 11, No. 2 ( 2021-01-26), p. 309-
    Details
    In: Nanomaterials, MDPI AG, Vol. 11, No. 2 ( 2021-01-26), p. 309-
    Abstract: A 16-nm-Lg p-type Gate-all-around (GAA) silicon nanowire (Si NW) metal oxide semiconductor field effect transistor (MOSFET) was fabricated based on the mainstream bulk fin field-effect transistor (FinFET) technology. The temperature dependence of electrical characteristics for normal MOSFET as well as the quantum transport at cryogenic has been investigated systematically. We demonstrate a good gate-control ability and body effect immunity at cryogenic for the GAA Si NW MOSFETs and observe the transport of two-fold degenerate hole sub-bands in the nanowire (110) channel direction sub-band structure experimentally. In addition, the pronounced ballistic transport characteristics were demonstrated in the GAA Si NW MOSFET. Due to the existence of spacers for the typical MOSFET, the quantum interference was also successfully achieved at lower bias.
    Type of Medium: Online Resource
    ISSN: 2079-4991
    URL: Article
    DOI: 10.3390/nano11020309
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2662255-5
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  • 5
    Online Resource
    Online Resource
    A Novel Methylation Marker NRN1 plus TERT and FGFR3 Mutation Using Urine Sediment Enables the Detection of Urothelial Bladder Carcinoma
    MDPI AG ; 2023
    In:  Cancers Vol. 15, No. 3 ( 2023-01-19), p. 615-
    Details
    In: Cancers, MDPI AG, Vol. 15, No. 3 ( 2023-01-19), p. 615-
    Abstract: Background: Aberrant DNA methylation is an early event during tumorigenesis. In the present study, we aimed to construct a methylation diagnostic tool using urine sediment for the detection of urothelial bladder carcinoma, and improved the diagnostic performance of the model by incorporating single-nucleotide polymorphism (SNP) sites. Methods: A three-stage analysis was carried out to construct the model and evaluate the diagnostic performance. In stage I, two small cohorts from Xiangya hospital were recruited to validate and identify the detailed regions of collected methylation biomarkers. In stage II, proof-of-concept study cohorts from the Hunan multicenter were recruited to construct a diagnostic tool. In stage III, a blinded cohort comprising suspicious UBC patients was recruited from Beijing single center to further test the robustness of the model. Results: In stage I, single NRN1 exhibited the highest AUC compared with six other biomarkers and the Random Forest model. At the best cutoff value of 5.16, a single NRN1 biomarker gave a diagnosis with a sensitivity of 0.93 and a specificity of 0.97. In stage II, the Random Forest algorithm was applied to construct a diagnostic tool, consisting of NRN1, TERT C228T and FGFR3 p.S249C. The tool exhibited AUC values of 0.953, 0.946 and 0.951 in training, test and all cohorts. At the best cutoff value, the model resulted in a sensitivity of 0.871 and a specificity of 0.947. In stage III, the diagnostic tool achieved a good discrimination in the external validation cohort, with an overall AUC of 0.935, sensitivity of 0.864 and specificity of 0.895. Additionally, the model exhibited a superior sensitivity and comparable specificity compared with conventional cytology and FISH. Conclusions: The diagnostic tool exhibited a highly specific and robust performance. It may be used as a replaceable approach for the detection of UBC.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers15030615
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2527080-1
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  • 6
    Online Resource
    Online Resource
    Urine Cellular DNA Point Mutation and Methylation for Identifying Upper Tract Urinary Carcinoma
    MDPI AG ; 2022
    In:  Cancers Vol. 14, No. 14 ( 2022-07-21), p. 3537-
    Details
    In: Cancers, MDPI AG, Vol. 14, No. 14 ( 2022-07-21), p. 3537-
    Abstract: Background: To improve the selection of patients for ureteroscopy, avoid excessive testing and reduce costs, we aimed to develop and validate a diagnostic urine assay for upper tract urinary carcinoma (UTUC). Methods: In this cohort study we recruited 402 patients from six Hunan hospitals who underwent ureteroscopy for hematuria, including 95 patients with UTUC and 307 patients with non-UTUC findings. Midstream morning urine samples were collected before ureteroscopy and surgery. DNA was extracted and qPCR was used to analyze mutations in TERT and FGFR3 and the methylation of NRN1. In the training set, the random forest algorithm was used to build an optimal panel. Lastly, the Beijing cohort (n = 76) was used to validate the panel. Results: The panel combining the methylation with mutation markers led to an AUC of 0.958 (95% CI: 0.933–0.975) with a sensitivity of 91.58% and a specificity of 94.79%. The panel presented a favorable diagnostic value for UTUC vs. other malignant tumors (AUC = 0.920) and UTUC vs. benign disease (AUC = 0.975). Furthermore, combining the panel with age revealed satisfactory results, with 93.68% sensitivity, 94.44% specificity, AUC = 0.970 and NPV = 98.6%. In the external validation process, the model showed an AUC of 0.971, a sensitivity of 95.83% and a specificity of 92.31, respectively. Conclusions: A novel diagnostic model for analyzing hematuria patients for the risk of UTUC was developed, which could lead to a reduction in the need for invasive examinations. Combining NRN1 methylation and gene mutation (FGFR3 and TERT) with age resulted in a validated accurate prediction model.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers14143537
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
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  • 7
    Online Resource
    Online Resource
    Role of Intestinal Microbes in Chronic Liver Diseases
    MDPI AG ; 2022
    In:  International Journal of Molecular Sciences Vol. 23, No. 20 ( 2022-10-21), p. 12661-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 23, No. 20 ( 2022-10-21), p. 12661-
    Abstract: With the recent availability and upgrading of many emerging intestinal microbes sequencing technologies, our research on intestinal microbes is changing rapidly. A variety of investigations have found that intestinal microbes are essential for immune system regulation and energy metabolism homeostasis, which impacts many critical organs. The liver is the first organ to be traversed by the intestinal portal vein, and there is a strong bidirectional link between the liver and intestine. Many intestinal factors, such as intestinal microbes, bacterial composition, and intestinal bacterial metabolites, are deeply involved in liver homeostasis. Intestinal microbial dysbiosis and increased intestinal permeability are associated with the pathogenesis of many chronic liver diseases, such as alcoholic fatty liver disease (AFLD), non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), chronic hepatitis B (CHB), chronic hepatitis C (CHC), autoimmune liver disease (AIH) and the development of hepatocellular carcinoma (HCC). Intestinal permeability and dysbacteriosis often lead to Lipopolysaccharide (LPS) and metabolites entering in serum. Then, Toll-like receptors activation in the liver induces the exposure of the intestine and liver to many small molecules with pro-inflammatory properties. And all of these eventually result in various liver diseases. In this paper, we have discussed the current evidence on the role of various intestinal microbes in different chronic liver diseases. As well as potential new therapeutic approaches are proposed in this review, such as antibiotics, probiotics, and prebiotics, which may have an improvement in liver diseases.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms232012661
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2019364-6
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  • 8
    Online Resource
    Online Resource
    RNA-Seq Transcriptome Analysis of Rice Primary Roots Reveals the Role of Flavonoids in Regulating the Rice Primary Root Growth
    MDPI AG ; 2019
    In:  Genes Vol. 10, No. 3 ( 2019-03-13), p. 213-
    Details
    In: Genes, MDPI AG, Vol. 10, No. 3 ( 2019-03-13), p. 213-
    Abstract: Flavonoids play important roles in root development and in its tropic responses, whereas the flavonoids-mediated changes of the global transcription levels during root growth remain unclear. Here, the global transcription changes in quercetin-treated rice primary roots were analyzed. Quercetin treatment significantly induced the inhibition of root growth and the reduction of H2O2 and O2− levels. In addition, the RNA-seq analysis revealed that there are 1243 differentially expressed genes (DEGs) identified in quercetin-treated roots, including 1032 up-regulated and 211 down-regulated genes. A gene ontology (GO) enrichment analysis showed that the enriched GO terms are mainly associated with the cell wall organization, response to oxidative stress, and response to hormone stimulus. The Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment pathway analysis showed that the enriched DEGs are involved in phenylpropanoid biosynthesis, glutathione metabolism, and plant hormone signal transduction. Moreover, the quercetin treatment led to an increase of the antioxidant enzyme activities of catalase (CAT), peroxidase (POD), and superoxide dismutase (SOD) in rice roots. Also, the quercetin treatment altered the DR5:GUS expression pattern in the root tips. All of these data indicated that the flavonoids-mediated transcription changes of genes are related to the genes involved in cell wall remodeling, redox homeostasis, and auxin signaling, leading to a reduced cell division in the meristem zone and cell elongation in the elongation zone of roots.
    Type of Medium: Online Resource
    ISSN: 2073-4425
    URL: Article
    DOI: 10.3390/genes10030213
    Language: English
    Publisher: MDPI AG
    Publication Date: 2019
    detail.hit.zdb_id: 2527218-4
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  • 9
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    Genomic Prediction across Structured Hybrid Populations and Environments in Maize
    MDPI AG ; 2021
    In:  Plants Vol. 10, No. 6 ( 2021-06-09), p. 1174-
    Details
    In: Plants, MDPI AG, Vol. 10, No. 6 ( 2021-06-09), p. 1174-
    Abstract: Genomic prediction (GP) across different populations and environments should be enhanced to increase the efficiency of crop breeding. In this study, four populations were constructed and genotyped with DNA chips containing 55,000 SNPs. These populations were testcrossed to a common tester, generating four hybrid populations. Yields of the four hybrid populations were evaluated in three environments. We demonstrated by using real data that the prediction accuracies of GP across structured hybrid populations were lower than those of within-population GP. Including relatives of the validation population in the training population could increase the prediction accuracies of GP across structured hybrid populations drastically. G × E models (including main and genotype-by-environment effect) had better performance than single environment (within environment) and across environment (including only main effect) GP models in the structured hybrid population, especially in the environment where yields had higher heritability. GP by implementing G × E models in two cross-validation schemes indicated that, to increase the prediction accuracy of a new hybrid line, it would be better to field-test the hybrid line in at least one environment. Our results would be helpful for designing training population and planning field testing in hybrid breeding.
    Type of Medium: Online Resource
    ISSN: 2223-7747
    URL: Article
    DOI: 10.3390/plants10061174
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2704341-1
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  • 10
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    Optimization of Structure and Electrical Characteristics for Four-Layer Vertically-Stacked Horizontal Gate-All-Around Si Nanosheets Devices
    MDPI AG ; 2021
    In:  Nanomaterials Vol. 11, No. 3 ( 2021-03-05), p. 646-
    Details
    In: Nanomaterials, MDPI AG, Vol. 11, No. 3 ( 2021-03-05), p. 646-
    Abstract: In this paper, the optimizations of vertically-stacked horizontal gate-all-around (GAA) Si nanosheet (NS) transistors on bulk Si substrate are systemically investigated. The release process of NS channels was firstly optimized to achieve uniform device structures. An over 100:1 selective wet-etch ratio of GeSi to Si layer was achieved for GeSi/Si stacks samples with different GeSi thickness (5 nm, 10 nm, and 20 nm) or annealing temperatures (≤900 °C). Furthermore, the influence of ground-plane (GP) doping in Si sub-fin region to improve electrical characteristics of devices was carefully investigated by experiment and simulations. The subthreshold characteristics of n-type devices were greatly improved with the increase of GP doping doses. However, the p-type devices initially were improved and then deteriorated with the increase of GP doping doses, and they demonstrated the best electrical characteristics with the GP doping concentrations of about 1 × 1018 cm−3, which was also confirmed by technical computer aided design (TCAD) simulation results. Finally, 4 stacked GAA Si NS channels with 6 nm in thickness and 30 nm in width were firstly fabricated on bulk substrate, and the performance of the stacked GAA Si NS devices achieved a larger ION/IOFF ratio (3.15 × 105) and smaller values of Subthreshold swings (SSs) (71.2 (N)/78.7 (P) mV/dec) and drain-induced barrier lowering (DIBLs) (9 (N)/22 (P) mV/V) by the optimization of suppression of parasitic channels and device’s structure.
    Type of Medium: Online Resource
    ISSN: 2079-4991
    URL: Article
    DOI: 10.3390/nano11030646
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2662255-5
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