Mechanistic insights into genomic structure and functions of a novel oncogene YEATS4

As a novel oncogene, the role of YEATS domain-containing protein 4 (YEATS4) in the occurrence, development, and treatment of tumors is now beginning to be appreciated. YEATS4 plays an important role in regulating DNA repair during replication. The upregulation of YEAST4 promotes DNA damage repair and prevents cell death, whereas its downregulation inhibits DNA replication and induces apoptosis. Additionally, accumulating evidence indicates that the aberrant activation of YEATS4 leads to changes in drug resistance, epithelial-mesenchymal transition and also in the migration and invasion capacity of tumor cells. Therefore, specific inhibition of the expression or activity of YEATS4 protein may be an effective strategy for inhibiting the proliferation, motility, differentiation, and/or survival of tumor cells. Taken together, YEATS4 has emerged as a potential target for multiple cancers and is an attractive protein for the development of small-molecule inhibitors. However, research on YEAST4 in tumor-related fields is limited and its biological functions, metabolism, and the regulatory mechanism of YEATS4 in numerous cancers remain undetermined. This review comprehensively and extensively summarizes the functions, structure and oncogenic roles of YEATS4 in cancer progression and aims to further contribute to the study of its underlying molecular mechanism and targeted drugs

Molecular genetic analysis of phosphomannomutase genes in Triticum monococcum

AbstractIn higher plants, phosphomannomutase (PMM) is essential for synthesizing the antioxidant ascorbic acid through the Smirnoff–Wheeler pathway. Previously, we characterized six PMM genes (TaPMM-A1, A2, B1, B2, D1 and D2) in common wheat (Triticum aestivum, AABBDD). Here, we report a molecular genetic analysis of PMM genes in Triticum monococcum (AmAm), a diploid wheat species whose Am genome is closely related to the A genome of common wheat. Two distinct PMM genes, TmPMM-1 and TmPMM-2, were found in T. monococcum. The coding region of TmPMM-1 was intact and highly conserved. In contrast, two main TmPMM-2 alleles were identified, with TmPMM-2a possessing an intact coding sequence and TmPMM-2b being a pseudogene. The transcript level of TmPMM-2a was much higher than that of TmPMM-2b, and a bacterially expressed TmPMM-2a recombinant protein displayed relatively high PMM activity. In general, the total transcript level of PMM was substantially higher in accessions carrying TmPMM-1 and TmPMM-2a than those harboring TmPMM-1 and TmPMM-2b. However, total PMM protein and activity levels did not differ drastically between the two genotypes. This work provides new information on PMM genes in T. monococcum and expands our understanding on Triticeae PMM genes, which may aid further functional and applied studies of PMM in crop plants

Role of WDHD1 in Human Papillomavirus-Mediated Oncogenesis Identified by Transcriptional profiling of E7-expressing cells

The E7 oncoprotein of the high-risk human papillomavirus (HPV) plays a major role in HPV-induced carcinogenesis. E7 abrogates the G(1) cell cycle checkpoint and induces genomic instability, but the mechanism is not fully understood. In this study, we performed RNA sequencing (RNA-seq) to characterize the transcriptional profile of keratinocytes expressing HPV 16 (HPV-16) E7. At the transcriptome level, 236 genes were differentially expressed between E7 and vector control cells. A subset of the differentially expressed genes, most of them novel to E7-expressing cells, was further confirmed by real-time PCR. Of interest, the activities of multiple transcription factors were altered in E7-expressing cells. Through bioinformatics analysis, pathways altered in E7-expressing cells were investigated. The upregulated genes were enriched in cell cycle and DNA replication, as well as in the DNA metabolic process, transcription, DNA damage, DNA repair, and nucleotide metabolism. Specifically, we focused our studies on the gene encoding WDHD1 (WD repeat and high mobility group [HMG]-box DNA-binding protein), one of the genes that was upregulated in E7-expressing cells. WDHD1 is a component of the replisome that regulates DNA replication. Recent studies suggest that WDHD1 may also function as a DNA replication initiation factor as well as a G(1) checkpoint regulator. We found that in E7-expressing cells, the steady-state level of WDHD1 protein was increased along with the half-life. Moreover, downregulation of WDHD1 reduced E7-induced G(1) checkpoint abrogation and rereplication, demonstrating a novel function for WDHD1. These studies shed light on mechanisms by which HPV induces genomic instability and have therapeutic implications. IMPORTANCE The high-risk HPV types induce cervical cancer and encode an E7 oncoprotein that plays a major role in HPV-induced carcinogenesis. However, the mechanism by which E7 induces carcinogenesis is not fully understood; specific anti-HPV agents are not available. In this study, we performed RNA-seq to characterize transcriptional profiling of keratinocytes expressing HPV-16 E7 and identified more than 200 genes that were differentially expressed between E7 and vector control cells. Through bioinformatics analysis, pathways altered in E7-expressing cells were identified. Significantly, the WDHD1 gene, one of the genes that is upregulated in E7-expressing cells, was found to play an important role in E7-induced G(1) checkpoint abrogation and rereplication. These studies shed light on mechanisms by which HPV induces genomic instability and have therapeutic implications

Stress and psychological maladaptation in Chinese junior school and high school students : focusing on endogenous stress in adolescence

Adolescence is a critical period for individual growth and development. Influenced by the physiological changes of adolescence, individual characteristics and environmental factors, adolescents tend to show cognitive, emotional and behavioral maladjustment. Based on the stress diathesis model, this study proposes the concept of endogenous pressure in adolescence and discusses the psychological process of psychological maladjustment caused by stressful life events by using the method of structural equation model. The endogenous stress, as a mediating variable, interacts with stressful life events and coping styles, and jointly ACTS on psychological maladjustment of adolescents. A total of 9,565 middle and high school students participated in the questionnaire. The results showed that :(1) according to the correlation analysis, there was a moderate positive correlation between stressful life events and endogenous stress and psychological maladjustment; Stress coping style was negatively correlated with stressful life events. Stress coping style was positively correlated with endogenous stress and psychological maladjustment to a moderate degree. With age, the endogenous stress of middle school students increases significantly, which may be related to the process of puberty. (2) from the perspective of gender difference, male students experience more stressful events, use more negative coping methods and have higher psychological maladjustment than female students. In terms of endogenous stress, girls experience more stress in terms of selfdiscipline and self-awareness than boys, and boys experience more stress in terms of sexual awareness. (3) through the establishment of structural equation model analysis, it is found that, among middle school students, endogenous pressure in adolescence plays a part of mediating role in the impact of stressful events on coping styles and psychological maladjustment. Specifically, stress events affect coping strategies through endogenous stress, and the three factors jointly affect the level of psychological maladjustment. The main fitting indexes of the model all reach the ideal standard. The stress diathesis model emphasizes that individuals with vulnerability to stress are prone to psychopathological problems when confronted with major stress events. This study focuses on the characteristics of adolescence, a special developmental stage, which is also the characteristics of the vulnerability to stress of the adolescent group, and it is worth further discussion. This study provides a new perspective in the discussion of adolescent depression, and new ideas for adolescent mental health education

PTEN transcript variants caused by illegitimate splicing in “aged” blood samples and EBV-transformed cell lines

PTEN is one of the most frequently mutated tumor suppressor genes in human cancers. Mutations occur in either heritable or sporadic fashion. Sequencing of cDNA from patients and normal individuals often reveals splicing variants (SVs) of PTEN, some of which are non-mutation related. To investigate whether these SVs were the result of illegitimate splicing (a general decrease of fidelity in splicing site selection in “aged” samples), we tested “aged” blood from individuals who had normal PTEN transcripts in their “fresh” mononuclear cells. Blood from 20 normal individuals was collected and split into two aliquots. Total RNA and DNA were extracted immediately (“fresh”) and 48 h later (“aged”), respectively. Using RT-PCR, subcloning and sequencing, we found seven types of SVs. No mutation was detected in the related intron–exon flanking region in genomic DNA in either “fresh” or “aged” samples. Some of the SVs were also consistently present in both the “fresh” and “aged” EBV-transformed lymphoblastoid cells from six normal individuals. Western blot data indicated that the PTEN protein level (in full length) was not altered in the “fresh” EBV-transformed lymphoblastoid cells with SVs. In conclusion, our data demonstrate that PTEN illegitimate splicing often occurs in “aged” blood and EBV-transformed lymphoblastoid cells. Therefore, it is critical to note the time point of RNA extraction when investigating for PTEN aberrant transcripts. We hope that our data will increase awareness about the sample status, because gene expression data may be potentially flawed from “aged” samples, particularly when dealing with clinical samples

The surface effect on axisymmetric wave propagation in piezoelectric cylindrical shells

Based on the surface piezoelectricity theory and first-order shear deformation theory, the surface effect on the axisymmetric wave propagating in piezoelectric cylindrical shells is analyzed. The Gurtin–Murdoch theory is utilized to get the nontraditional boundary conditions and constitutive equations of the surface, in company with classical governing equations of the bulk, from which the basic formulations are obtained. Numerical results show that the surface layer has a profound effect on wave characteristics in nanostructure at a higher mode

Examination Stress Results in Attentional Bias and Altered Neural Reactivity in Test-Anxious Individuals

Examination stress occurs so frequently in the lives of students. The neural mechanisms of attentional bias induced by examination stress in test-anxious individuals remain unclear. Accordingly, we investigated the attentional bias toward test-related threatening words in selected high and low test-anxious participants under the stress of final examinations by using an event-related potential (ERP) technique. A classic dot-probe paradigm was adopted with a test-related/test-unrelated threatening word and a neutral word pair as cues. Results showed attention bias and enhanced N200 amplitude toward test-related threat in high test-anxious individuals, whereas avoidance of test-related threat and decreased N200 amplitude were shown in low test-anxious individuals. Additionally, ERP data revealed the relatively enhanced LPP amplitude in low test-anxious participants compared with that in high test-anxious participants. No attentional bias toward test-unrelated threat was found. In conclusion, examination stress resulted in attentional bias and functional perturbations of a brain circuitry that reacted rapidly to test-related threat in high test-anxious individuals

Development of a sensitive droplet digital PCR according to the HPV infection specificity in Chinese population

Abstract HPV16 and 18 are positively correlated with cervical carcinogenesis. However, HPV prevalence tends to vary according to region, nationality, and environment. The most prevalent high-risk (HR) HPV genotypes are HPV16, 52, 58, 56, 18, 33, and 45), while the low-risk (LR) genotypes are HPV6 and 11 in the Chinese population. Importantly, undetectable low-copy HPV DNA could be an important indicator of integration into the human genome and may be a precursor to cancer progression. The HPV viral load changes dramatically, either increasing or decreasing rapidly during carcinogenesis, and traditional quantitative real-time PCR (qPCR) cannot accurately capture this subtle change. Therefore, in this study, a reliable droplet digital PCR (ddPCR) method was developed to simultaneously detect and quantify HPV genotypes. The ddPCR quantitative results showed high accuracy, sensitivity, and specificity compared to qPCR results employing the same clinical specimens and supplemented the ddPCR assay for HPV52/56/58/6 genotypes according to the infection specificity of the Chinese population. In summary, this procedure is valuable for quantifying HPV DNA, especially under conditions of low template copy number in cervical intraepithelial neoplasia (CIN) and/or cervical cancer. Additionally, this method can dynamically observe the prognosis and outcome of HPV infection and thus be used as an effective means for real-time monitoring of tumor load

Regional characteristics and spatial correlation of haze pollution: Interpretative system analysis in cities of Fenwei Plain in China.

Urban agglomeration is an important model for promoting global economic development and has made important contributions to global economic integration. However, as the core area of urbanization and industrialization, urban agglomerations also contribute to air pollutant emissions primarily due to the agglomeration of population and industry. The mutual influence of air pollution between different cities in urban agglomerations has brought significant challenges to global environmental governance. The Fenwei Plain is one of the most severely polluted areas in China. We collected daily average PM2.5 concentration data of 11 cities in the Fenwei Plain, China in 2019. We then developed an interpretive structural model to statistically analyze the spatial correlation and hierarchical transmission of haze pollution between the 11 cities. The results showed that haze pollution has a strong systematic correlation between the 11 cities, and a regional haze pollution community has formed throughout the region. Haze pollution also exhibits evident transmission and spatial correlations between the cities. The transmission starts from Baoji and ends at Sanmenxia, with mutual interactions between the cities of Xi'an, Xianyang, Weinan, Tongchuan, Jinzhong, Lvliang, Linfen, Yuncheng, and Luoyang. Thus, air pollution prevention and control in the Fenwei Plain should consider the spatial correlation of haze pollution between different cities, especially in autumn and winter, and should rationally be implemented in key urban cluster areas. We recommend building a coordinated governance between cities to improve the overall air quality. Our findings shed a light for coordinated pollution management in urban agglomerations worldwide