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Genomic Analysis Reveals Novel Specific Metastatic Mutations in Chinese Clear Cell Renal Cell Carcinoma
Clear cell renal cell carcinoma (ccRCC) accounts for more than 75% of renal cell carcinoma. Nearly 25% of ccRCC patients were diagnosed with metastasis. Though the genomic profile of ccRCC has been widely studied, the difference between localized and metastatic ccRCC was not clarified. Primary tumor samples and matched whole blood were collected from 106 sporadic patients diagnosed with renal clear cell carcinoma at Qilu Hospital of Shandong University from January 2017 to November 2019, and 17 of them were diagnosed with metastasis. A hybridization capture-based next-generation sequencing of 618 cancer-related genes was performed to investigate the somatic and germline variants, tumor mutation burden (TMB), and microsatellite instability (MSI). Five genes with significantly different prevalence were identified in the metastatic group, especially TOP1 (17.65% vs. 0%) and SNCAIP (17.65% vs. 0%). The altered frequency of PBRM1 (0% vs. 27%) and BAP1 (24% vs. 10%) differed between the metastatic and nonmetastatic groups, which may relate to the prognosis. Of these 106 patients, 42 patients (39.62%) had at least one alteration in DNA damage repair (DDR) genes, including 58.82% of metastatic ccRCC patients and 35.96% of ccRCC patients without metastasis. Ten pathogenic or likely pathogenic (P/LP) variants were identified in 11 sporadic clear cell renal cell carcinoma patients (10.38%), including rarely reported ATM (n=1), MUTYH (n=1), NBN (n=1), RAD51D (n=1), and BRCA2 (n=1). No significant difference in the ratio of P/LP variant carriers or TMB was identified between the metastatic and nonmetastatic groups. We found a unique genomic feature of Chinese metastatic ccRCC patients with a higher prevalence of alterations in DDR, TOP1, and SNCAIP. Further investigated studies and drug development are needed in the future.
Individual- and Community-Level Determinants for Complete Vaccination among Children Aged 12-23 Months in Ethiopia: A Multilevel Analysis
Background. Childhood vaccination continues to increase dramatically. In spite of the success of immunization programs to date, millions of children continued to die each year, and sub-Saharan Africa (SSA) accounted for the world’s highest neonatal deaths. Childhood vaccination was designed as one of the most effective ways to reduce child mortalities from fatal vaccine-preventable diseases. Therefore, this study is aimed at investigating the individual- and community-level determinants of childhood complete vaccination in Ethiopia. Methods. A secondary data analysis was done based on the 2016 Ethiopian Demographic and Health Survey (EDHS). A total weighted sample of 1,984 children aged 12-23 months was included for analysis. Considering the hierarchical nature of EDHS data, a two-level multilevel analysis for assessing individual- and community-level determinants of childhood complete vaccination was done. The intraclass correlation coefficient (ICC), Median Odds Ratio (MOR), Proportional Change in Variance (PCV), and deviance (-2LL) were used for model comparison and for checking model fitness. Variables with value < 0.2 in the bivariable multilevel analysis were considered for the multivariable multilevel analysis. In the multivariable multilevel logistic regression analysis, the Adjusted Odds Ratio (AOR) with 95% Confidence Interval (CI) was reported to declare significant determinants of complete childhood vaccination. Results. Overall complete vaccination status among children aged 12-23 months was 39% (95% CI: 36.8, 41.2). In the multilevel analysis, secondary or above educated mothers (; 95% CI: 1.41, 4.36), richest wealth status (; 95% CI: 1.16, 4.32), ≥four ANC visits (; 95% CI: 1.90-4.02), employed mothers (; 95% CI: 1.26, 2.18), urban residence (; 95% CI: 1.00, 3.51), and children in city administration (; 9% CI: 1.53, 4.62) were positively associated with vaccination status. On the other hand, children with a female household head (; 95% CI: 0.48, 0.96) were negatively associated. Conclusion. Overall, childhood full vaccination status was low compared with the WHO targets. Maternal education, wealth status, ANC visit, maternal occupation, residence, region, and sex of household head were significant predictors of childhood complete vaccination. As a result, it is better to design a compensation mechanism to the costs associated with childhood vaccination for the poor households and strengthen awareness creation for rural residents to improve the access, utilization, and continuum of vaccination service.
Chloroplast Genome Sequences and Comparative Analyses of Combretaceae Mangroves with Related Species
In the Combretaceae family, only two species of Lumnitzera and one species of Laguncularia belong to mangroves. Among them, Lumnitzera littorea (Jack) Voigt. is an endangered mangrove plant in China for the limited occurrence and seed abortion. In contrast, Lumnitzera racemosa Willd. is known as the most widespread mangrove plant in China. Laguncularia racemosa C. F. Gaertn., an exotic mangrove in China, has the fast growth and high adaptation ability. To better understand the phylogenetic positions of these mangroves in Combretaceae and in Myrtales and to provide information for studies on evolutionary adaptation for intertidal habitat, the complete chloroplast (cp) genomes of Lu. racemosa and La. racemosa were sequenced. Furthermore, we present here the results from the assembly and annotation of the two cp genomes, which were further subjected to the comparative analysis with Lu. littorea cp genomes we published before and other eleven closely related species within Myrtales. The chloroplast genomes of the three Combretaceae mangrove species: Lu. littorea, Lu. racemosa, and La. racemosa are 159,687 bp, 159,473 bp, and 158,311 bp in size. All three cp genomes host 130 genes including 85 protein-coding genes, 37 tRNAs, and 4 rRNAs. A comparative analysis of those three genomes revealed the high similarity of genes in coding-regions and conserved gene order in the IR and LSC/SSC regions. The differences between Lumnitzera and Laguncularia cp genomes are the locations of rps19 and rpl2 genes in the IR/SC boundary regions. Investigating the effects of selection events on shared protein-coding genes showed a relaxed selection had acted on the ycf2, ycf1, and matK genes of Combretaceae mangroves compared to the nonmangrove species Eucalyptus aromaphloia. The phylogenetic analysis based on the whole chloroplast genome sequence with one outgroup species strongly supported three Combretaceae mangroves together with other two Combretaceae species formed a cluster in Combretaceae. This study is the first report on the comparative analysis of three Combretaceae mangrove chloroplast genomes, which will provide the significant information for understanding photosynthesis and evolution in Combretaceae mangrove plants.
Wubeizi Ointment Suppresses Keloid Formation through Modulation of the mTOR Pathway
Background. Wubeizi (Rhus chinensis Mill.) ointment has been shown as an effective treatment for keloids. However, the protective mechanisms of Wubeizi ointment are not fully understood. The mammalian target of rapamycin (mTOR) has been demonstrated to be associated with keloid pathogenesis. In the present study, we investigated if Wubeizi ointment suppressed keloid formation through the modulation of key molecules of the rapamycin (mTOR) pathway including phosphatase and tensin homolog (PTEN), phosphatidylinositol 3-kinase (PI3K), and protein kinase B (Akt). Methods. A keloid mouse model and human keloid-derived fibroblasts were developed and treated with Galla chinensis. Immunohistochemistry, western blot, and reverse transcription-PCR were used to detect PI3K, PTEN, Akt, and mTOR in keloid tissues and keloid fibroblasts. The apoptosis and proliferation rate of keloid fibroblasts was, respectively, analyzed by flow cytometry according to the MTT assay. Statistical analysis was done using SPSS version 20.0. For two variable comparisons, a two independent samples -test was used. For multiple variable comparisons, data were analyzed by one-way analysis of variance (ANOVA) followed by pairwise -tests. Results. Our in vivo and in vitro studies showed that Wubeizi ointment suppressed keloid formation through inhibition of fibroblast proliferation and promotion of fibroblast apoptosis. The underlying basis involves downregulation of p-Akt and p-mTOR as well as upregulation of PTEN. Conclusion. These findings may contribute to a better understanding of the mechanisms of Wubeizi ointment for treating keloids.
Machine Learning-Based Differentiation of Nontuberculous Mycobacteria Lung Disease and Pulmonary Tuberculosis Using CT Images
An increasing number of patients infected with nontuberculous mycobacteria (NTM) are observed worldwide. However, it is challenging to identify NTM lung diseases from pulmonary tuberculosis (PTB) due to considerable overlap in classic manifestations and clinical and radiographic characteristics. This study quantifies both cavitary and bronchiectasis regions in CT images and explores a machine learning approach for the differentiation of NTM lung diseases and PTB. It involves 116 patients and 103 quantitative features. After the selection of informative features, a linear support vector machine performs disease classification, and simultaneously, discriminative features are recognized. Experimental results indicate that bronchiectasis is relatively more informative, and two features are figured out due to promising prediction performance (area under the curve, 6; accuracy, ; sensitivity, ; and specificity, ). This study provides insight into machine learning-based identification of NTM lung diseases from PTB, and more importantly, it makes early and quick diagnosis of NTM lung diseases possible that can facilitate lung disease management and treatment planning.
Identification of Circular RNA-MicroRNA-Messenger RNA Regulatory Network in Atrial Fibrillation by Integrated Analysis
Background. Circular RNA (circRNA) is a noncoding RNA that forms a closed-loop structure, and its abnormal expression may cause disease. We aimed to find potential network for circRNA-related competitive endogenous RNA (ceRNA) in atrial fibrillation (AF). Methods. The circRNA, miRNA, and mRNA expression profiles in the heart tissue from AF patients were retrieved from the Gene Expression Omnibus database and analyzed comprehensively. Differentially expressed circRNAs (DEcircRNAs), differentially expressed miRNAs (DEmiRNAs), and differentially expressed mRNAs (DEmRNAs) were identified, followed by the establishment of DEcircRNA-DEmiRNA-DEmRNA regulatory network. Functional annotation analysis of host gene of DEcircRNAs and DEmRNAs in ceRNA regulatory network was performed. In vitro experiment and electronic validation were used to validate the expression of DEcircRNAs, DEmiRNAs, and DEmRNAs. Results. A total of 1611 DEcircRNAs, 51 DEmiRNAs, and 1250 DEmRNAs were identified in AF. The DEcircRNA-DEmiRNA-DEmRNA network contained 62 circRNAs, 14 miRNAs, and 728 mRNAs. Among which, two ceRNA regulatory pairs of hsa-circRNA-100053-hsa-miR-455-5p-TRPV1 and hsa-circRNA-005843-hsa-miR-188-5p-SPON1 were identified. In addition, six miRNA-mRNA regulatory pairs including hsa-miR-34c-5p-INMT, hsa-miR-1253-DDIT4L, hsa-miR-508-5p-SMOC2, hsa-miR-943-ACTA1, hsa-miR-338-3p-WIPI1, and hsa-miR-199a-3p-RAP1GAP2 were also obtained. MTOR was a significantly enriched signaling pathway of host gene of DEcircRNAs. In addition, arrhythmogenic right ventricular cardiomyopathy, dilated cardiomyopathy, and hypertrophic cardiomyopathy were remarkably enriched signaling pathways of DEmRNAs in DEcircRNA-DEmiRNA-DEmRNA regulatory network. The expression validation of hsa-circRNA-402565, hsa-miR-34c-5p, hsa-miR-188-5p, SPON1, DDIT4L, SMOC2, and WIPI1 was consistent with the integrated analysis. Conclusion. We speculated that hsa-circRNA-100053-hsa-miR-455-5p-TRPV1 and hsa-circRNA-005843-hsa-miR-188-5p-SPON1 interaction pairs may be involved in AF.