Search

Glioma is a lethal malignant brain tumor, it comprises about 80% of all malignant brain tumours. Mounting evidence has reported that YTHDF2 plays a significant role in the cancer progression. However, the effects of YTHDF2 on the prognosis of low-grade gliomas (LGGs) and its correlation with tumor immune infiltration are unclear. The present study was designed to determine the biological functions of YTHDF2 in glioma and to evaluate the association of YTHDF2 expression with glioma progression.Clinical data on patients with glioma were obtained from The Cancer Genome Atlas (TCGA), the Chinese Glioma Genome Atlas (CGGA), the Gene Expression Omnibus (GEO), as well as the Rembrandt and Gravendeel databases. The correlations among YTHDF2 expression, pathological characteristics, glioma progression and clinical outcome were evaluated. In addition, the correlation of YTHDF2 expression with immune cell infiltration was analyzed too.We found that YTHDF2 was significantly up-regulated in LGGs which correlated with tumor grade and poor prognosis. Interestingly, we showed that YTHDF2 expression in LGG was associated with copy number variation, DNA hypomethylation, and induced transcription factor YY1. Besides, KEGG pathway analysis shows that YTHDF2 mainly participates in the immune response and oncogenic signaling pathway. Additionally, YTHDF2 is positively associated with diverse immune cells infiltration, immune cells, and multiple immune checkpoint molecules. Finally, we confirmed that YTHDF2 was highly expressed in LGGs tissues and correlated with the tumor grade with immunohistochemistry assay. More importantly, our results demonstrated that YTHDF2 was elevated in GBM cells. Knockdown of YTHDF2 significantly inhibits the proliferation and migration of GBM cells.YTHDF2 correlates with glioma progression and immune cell infiltration, suggesting that YTHDF2 may be a useful prognostic biomarker for glioma.

Background: There is an increasing demand for minimally invasive myxoma resection. This study aimed to investigate the safety and feasibility of minimally invasive myxoma resection. Methods: In this retrospective study, we collected information from 95 patients who underwent myxoma resection between January 2016 and December 2020. Based on the operative approach, the patients were divided into the minimally invasive myxoma resection (Mini-MR) group (N = 30) and the sternotomy myxoma resection (SMR) group (N = 65). Intraoperative and postoperative data were compared between the two groups. Results: The postoperative ventilator-assisted time, CSICU time, and postoperative hospital stay were shorter in the Mini-MR group than in the SMR (13.05 ± 4.98 vs. 17.07 ± 9.52 h; 1.73 ± 0.29 vs. 2.27 ± 1.53 d; 6.20 ± 1.50 vs. 9.48 ± 3.37 d, respectively), and the difference was statistically significant (P < 0.05). Mini-MR had lower postoperative drainage and blood transfusion rate in the first 24 h compared with SMR (38.93 ± 69.62 vs. 178.25 ± 153.06 ml; 26.6% vs. 63.1%), and the differences were statistically significant (P < 0.05). Conclusion: Mini-MR has the advantages of less CSICU stay time, less ventilator time, less postoperative drainage in the first 24h, less blood transfusion, fewer postoperative hospital stays, and faster recovery. Mini-MR is a safe and feasible surgical procedure for myxoma resection.

The study of yield traits can reveal the genetic architecture of grain yield for improving maize production. In this study, an association panel comprising 362 inbred lines and a recombinant inbred line population derived from X178 × 9782 were used to identify candidate genes for nine yield traits. High-priority overlap (HPO) genes, which are genes prioritized in a genome-wide association study (GWAS), were investigated using coexpression networks. The GWAS identified 51 environmentally stable SNPs in two environments and 36 pleiotropic SNPs, including three SNPs with both attributes. Seven hotspots containing 41 trait-associated SNPs were identified on six chromosomes by permutation. Pyramiding of superior alleles showed a highly positive effect on all traits, and the phenotypic values of ear diameter and ear weight consistently corresponded with the number of superior alleles in tropical and temperate germplasm. A total of 61 HPO genes were detected after trait-associated SNPs were combined with the coexpression networks. Linkage mapping identified 16 environmentally stable and 16 pleiotropic QTL. Seven SNPs that were located in QTL intervals were assigned as consensus SNPs for the yield traits. Among the candidate genes predicted by our study, some genes were confirmed to function in seed development. The gene Zm00001d016656 encoding a serine/threonine protein kinase was associated with five different traits across multiple environments. Some genes were uniquely expressed in specific tissues and at certain stages of seed development. These findings will provide genetic information and resources for molecular breeding of maize grain yield.

Gliomas are the most aggressive primary brain tumors. However, no significant improvement in survival has been achieved with the addition of temozolomide (TMZ) or radiation as initial therapy, although many clinical efforts have been carried out to target various signaling pathways or putative driver mutations. Here, we report that glycosyltransferase 8 domain containing 1 (GLT8D1), induced by HIF-1α under a hypoxic niche, significantly correlates with a higher grade of glioma, and a worse clinical outcome. Depletion of GLT8D1 inhibits self-renewal of glioma stem cell (GSC) in vitro and represses tumor growth in glioma mouse models. GLT8D1 knockdown promotes cell cycle arrest at G2/M phase and cellular apoptosis with or without TMZ treatment. We reveal that GLT8D1 impedes CD133 degradation through the endosomal-lysosomal pathway by N-linked glycosylation and protein-protein interaction. Directly blocking the GLT8D1/CD133 complex formation by CD133

AIMS AND OBJECTIVES This study aimed to determine the knowledge and current practices of ICU nurses regarding aerosol therapy for patients with invasive mechanical ventilation in China. BACKGROUND Aerosol therapy is a routine operation for intensive care unit (ICU) nurses; however, evidence of the knowledge and current practices of ICU nurses regarding aerosol therapy for patients with invasive mechanical ventilation is insufficient in China. DESIGN A total of 433 hospitals in 92 cities (including 31 capital cities) in 31 provinces in China participated in the study. METHODS A questionnaire was used to investigate the knowledge and current practices of ICU nurses regarding aerosol therapy for patients treated with invasive mechanical ventilation, including 42 questions covering five aspects: sociodemographic information, aerosolisation devices, atomised drugs, atomisation operation and atomisation-related knowledge. Descriptive analyses of the distribution of the sample are reported as percentages and medians. Univariate and multivariate analysis was used to detect the factors of the interviewee's atomisation knowledge and practices scores. A STROBE checklist was used to guide the reporting of the research. RESULTS Of the 1995 questionnaires that were returned, 1978 were analysed. Bronchodilators and glucocorticoids were the most frequently administered drugs. Seventy-four per cent of the total respondents reported placing a filter on the expiratory limb during aerosol therapy, and 47% of these reported that the filter was changed once a day. Only 13% of the respondents reported always turning the heating humidifier off during aerosol therapy, and 48% never did. Knowledge about the optimal droplet size or atomisation yield was poor. Work experience in the ICU and frequency of atomisation training were the independent influencing factors for atomisation knowledge and practice scores (F = 279.653, p

Neural stem cells play pivotal roles during prenatal development and throughout life. Here, we report that Paired immunoglobulin-like receptor B (PirB) functions as a suppressor during brain neurogenesis in the adult mouse. PirB expression increased with age during development, and its deficiency promoted neural stem cell proliferation and differentiation in vivo and in vitro. Furthermore, we detected an increase in Type 1 neural stem cells in PirB-deficient mice compared to their wild-type littermates. PirB deficiency promoted stemness marker gene expression of Sox2 and KLF4 by activating Akt1 phosphorylation. These findings suggest that PirB inhibits the self-renewal and differentiation capacities of neural stem cells. Thus, PirB may have the potential to serve as a therapeutic target for treatment of reduced neurogenesis in adults due to aging or other pathological conditions.

Glioblastoma is the most common and severe primary intrinsic tumor of the central nervous system. Glioblastoma harbors glioma stem cells (GSCs) as it not only possesses self-renewal and differentiation properties but also accounts for significant chemotherapy resistance and recurrence. Thus, targeting GSCs may be essential in overcoming the resistance and recurrence thereby improving GBM treatment. However, the underlying mechanism to sustain GSCs remains largely unknown. Here, we report that SH3 domain binding glutamate-rich protein like 2 (SH3BGRL2) is weakly expressed in glioblastoma multiforme (GBM) and isocitrate dehydrogenase1 (IDH1) wildtype GBM and correlated with glioma patients’ poor prognosis. Moreover, ectopic expression of SH3BGRL2 significantly inhibited GBM cell growth, migration, and GSCs self-renewal in vitro as well as tumor growth in vivo. Additionally, we found that SH3BGRL2 suppressed SOX2 and CD133 expression, which are key regulators involved in GSCs self-renewal. Collectively, our findings shed additional light on SH3BGRL2 has potential to serve as a biomarker and a potent therapeutic target for patients with glioma.

We revealed that SNX20 was up-regulated in LGG, and its higher expression was associated with adverse clinical outcomes and poor clinical characteristics, including WHO grade, IDH mutation, 1p/19q codeletion, and primary therapy outcome. The results of the Cox regression analysis revealed that SNX20 was an independent factor for the prognosis of low-grade glioma. Meanwhile, we also established a nomogram based on SNX20 to predict the 1-, 3-, or 5-year survival in LGG patients. Furthermore, we found that DNA hypomethylation results in its overexpression in LGG. In addition, functional annotation confirmed that SNX20 was mainly involved in the immune response and inflammatory response related signaling pathways, including the T cell receptor signaling pathway, natural killer cell-mediated cytotoxicity, and the NF-kappa B signaling pathway. Finally, we determined that increased expression of SNX20 was correlated with infiltration levels of various immune cells and immune checkpoint in LGG. Importantly, we found that SNX20 was highly expressed in glioma cell lines. Depletion of SNX20 significantly inhibits glioma cell proliferation and migration abilities. This is the first study to identify SNX20 as a new potential prognostic biomarker and characterize the functional roles of SNX20 in the progression of LGG, and provides a novel potential diagnostic and therapeutic biomarker for LGG in the future.

The spindle assembly checkpoint (SAC) is a highly conserved monitoring system that ensures a fidelity of chromosome segregation during mitosis. Bub3, a mitotic Checkpoint Protein, is a member of the Bub protein family, and an important factor in the SAC. Abnormal expression of Bub3 results in mitotic defects, defective spindle gate function, chromosomal instability and the development of aneuploidy cells. Aneuploidy is a state of abnormal karyotype that has long been considered as a marker of tumorigenesis. Karyotypic heterogeneity in tumor cells, known as "chromosomal instability" (CIN), can be used to distinguish cancerous cells from their normal tissue counterpart. In this review, we summarize the expression and clinical significance of Bub3 in a variety of tumors and suggest that it has potential in the treatment of cancer.

Low grade glioma is one of the most common lethal cancers in the human nervous system. Emerging evidence has demonstrated that homeobox A cluster (HOXA) gene family plays a critical role in the transcriptional regulation as well as cancer initiation and progression. However, the expression, biological functions and upstream regulatory mechanism of 11 HOXAs in low grade glioma are not yet clear.In this study, we utilized various public databases and bioinformatics analyzed, including TCGA, CGGA, Rembrandt, HPA, LinkedOmics, cBioPortal, TISDIB, single-sample GSEA (ssGSEA), TIMER, LnCeVar, LASSO regression, Cox regression, Kaplan-Meier plot, and receiver operating, characteristic (ROC) analyses, GDSC and CTRP databases to analyzed the mRNA and protein expression profiles, gene mutation, clinical features, diagnosis, prognosis, signaling pathway, TMB, immune subtype, immune cell infiltration, immune modulator, ceRNA network and drug sensitivity of 11 HOXAs. Growth curve and transwell assays were utilized to study the biological characteristics of HOXA6 in LGG progression.In the present study, we found that 11 HOXAs (HOXA1, HOXA2, HOXA3, HOXA4, HOXA5, HOXA6, HOXA7, HOXA9, HOXA10, HOXA11 and HOXA3) were consistently up-regulated in LGG tissues and GBM tissues. Up-regulated of the HOXAs expression were significantly correlated with higher tumor stage, IDH mutation status, 1p/19q co-deletion, histological type and primary therapy outcome. Survival analyses showed that higher expression of HOXA1, HOXA2, HOXA3, HOXA4, HOXA5, HOXA7, HOXA9, HOXA10, HOXA11 and HOXA13 were correlated with shorter overall survival (OS), disease-specific survival (DSS) and progression-free survival (PFS) in LGG patients. Univariate and multivariate analyses revealed that HOXA1, HOXA6 expression and tumor grade, age, primary therapy outcome and age were independent factors affecting the prognosis of LGG patients. ROC curve analysis of HOXAs showed that HOXAs had a high accuracy (AUC0.80) in predicting LGG. Furthermore, gene functional enrichment analysis indicated that HOXAs mainly involved in the inflammatory response and immune regulation signaling pathway. CNV and DNA methylation significantly affect the expression of HOXAs. Finally, we uncover that HOXAs expression are highly correlated with immune cells infiltrate, immune modulator and drug sensitivity. We also uncover that the HOXAs related ceRNA network in LGG. More importantly, we found that HOXA6 was highly expressed in LGG cells lines and significantly affected their proliferation and migration abilities.In conclusion, our data demonstrated that HOXA was correlated with progression and immune infiltration, and could serve as a prognostic biomarker for LGG.

BackgroundIncreasing demand for minimally invasive myxoma resection. This study aimed to investigate the safety and feasibility of minimally invasive myxoma resection. MethodsThis is a retrospective study, we collected information on 95 patients who underwent myxoma resection from January 2016 to December 2020. According to the operative approach, they were divided into a minimally invasive myxoma resection(Mini-MR) group (n=30) and a sternotomy myxoma resection(SMR) group (n=65), we compared the intraoperative and postoperative data between the two groups. ResultsPostoperative ventilator assisted time, CSICU time and postoperative hospital stay of Mini-AVR were shorter than SAVR [(13.05 ± 4.98) VS (17.07 ± 9.52)h ;(1.73 ± 0.29) VS (2.27 ± 1.53)d; (6.20 ± 1.50) VS (9.48 ± 3.37)d], the difference was statistically significant (P

SUMMARY Inorganic phosphorus (Pi) is an essential element in numerous metabolic reactions and signaling pathways, but the molecular details of these pathways remain largely unknown. In this study, metabolite profiles of maize (Zea mays L.) leaves and roots were compared between six low‐Pi‐sensitive lines and six low‐Pi‐tolerant lines under Pi‐sufficient and Pi‐deficient conditions to identify pathways and genes associated with the low‐Pi stress response. Results showed that under Pi deprivation the concentrations of nucleic acids, organic acids and sugars were increased, but that the concentrations of phosphorylated metabolites, certain amino acids, lipid metabolites and nitrogenous compounds were decreased. The levels of secondary metabolites involved in plant immune reactions, including benzoxazinoids and flavonoids, were significantly different in plants grown under Pi‐deficient conditions. Among them, the 11 most stable metabolites showed significant differences under low‐ and normal‐Pi conditions based on the coefficient of variation (CV). Isoleucine and alanine were the most stable metabolites for the identification of Pi‐sensitive and Pi‐resistant maize inbred lines. With the significant correlation between morphological traits and metabolites, five low‐Pi‐responding consensus genes associated with morphological traits and simultaneously involved in metabolic pathways were mined by combining metabolites profiles and genome‐wide association study (GWAS). The consensus genes induced by Pi deficiency in maize seedlings were also validated by reverse‐transcription quantitative polymerase chain reaction (RT‐qPCR). Moreover, these genes were further validated in a recombinant inbred line (RIL) population, in which the glucose‐6‐phosphate‐1‐epimerase encoding gene mediated yield and correlated traits to phosphorus availability. Together, our results provide a framework for understanding the metabolic processes underlying Pi‐deficient responses and give multiple insights into improving the efficiency of Pi use in maize., Significance statement Metabolite profiling and GWAS were applied to reveal maize low‐Pi response mechanisms.

Glioblastoma (GBM) is the most aggressive tumors of the central nervous system. Here, we report that SH3 binding glutamic acid-rich protein like 3 (SH3BGRL3) was extremely highly expressed in GBM and glioma stem cells. SH3BGRL3 high expression associates with worse survival of GBM patients. Functionally, Targeting SH3BGRL3 obviously impairs GSCs self-renewal in vitro. Most importantly, we first report that SH3BGRL3 is a direct transcriptional target gene of signal transducer and activator of transcription 3 (STAT3) and thereby activating STAT3 signaling in turn. Additionally, forced expression of the constitutively activated STAT3 (STAT3-C) rescued GSCs self-renewal inhibited by SH3BGRL3 silencing. Collectively, we first identified a critical positive feedback loop between SH3BGRL3 and STAT3, which facilitates the tumorigenic potential of GBM.

Glioblastoma (GBM) is the most severe malignant tumors of the central nervous system. Glioblastoma stem cells (GSCs) are considered to account for tumor initiation, therapeutic resistance, and tumor relapse. Yet the underlying mechanisms of GSC stemness maintenance remain largely unknown. Abnormal activation of STAT3 signaling is required for GBM tumorigenesis and GSC self-renewal. In this study, we provide evidence that SH3GL3 was weakly expressed in GBM and its high expression correlated with a favorable prognosis for GBM patients. Ectopic of SH3GL3 expression considerably inhibits GBM cell malignant behaviors, including GBM cell proliferation, migration as well as GSCs self-renewal ability. Mechanistically, we first found that SH3GL3 interacts with STAT3, which thereby inhibiting STAT3 nuclear localization. Overexpression of constitutively activated (STAT3-C) restored the growth, migration and self-renewal ability impaired by overexpression of SH3GL3. Together, our work shed insight on a critical regulatory mechanism mediated by SH3GL3 to decrease the stem cell-like property and tumorigenic potential.

N6-methyladenosine (m6A) is the most prevalent, abundant and conserved internal cotranscriptional modification in eukaryotic RNAs, especially within higher eukaryotic cells. m6A modification is modified by the m6A methyltransferases, or writers, such as METTL3/14/16, RBM15/15B, ZC3H3, VIRMA, CBLL1, WTAP, and KIAA1429, and, removed by the demethylases, or erasers, including FTO and ALKBH5. It is recognized by m6A-binding proteins YTHDF1/2/3, YTHDC1/2 IGF2BP1/2/3 and HNRNPA2B1, also known as “readers”. Recent studies have shown that m6A RNA modification plays essential role in both physiological and pathological conditions, especially in the initiation and progression of different types of human cancers. In this review, we discuss how m6A RNA methylation influences both the physiological and pathological progressions of hematopoietic, central nervous and reproductive systems. We will mainly focus on recent progress in identifying the biological functions and the underlying molecular mechanisms of m6A RNA methylation, its regulators and downstream target genes, during cancer progression in above systems. We propose that m6A RNA methylation process offer potential targets for cancer therapy in the future.

Phosphorus (P) is required for numerous developmental processes, such as flowering and reproduction, in maize (Zea mays L.). It is also an essential nutrient in fertilizers to sustain high yields in farmlands with insufficient available phosphate, particularly in acid soils in China. Flowering time is a key factor influencing the adaptation of maize to the local environment and is associated with high yields. However, few studies have focused on the genetic characteristics of flowering time under low phosphate conditions. In this study, a recombinant inbred line (RIL) population derived from a cross between X178 and 9782 was evaluated for three flowering time traits under two phosphates (Pi) levels at four locations. We found that low phosphate significantly delayed the flowering stage of maize and proposed the hypothesis of “Phosphorus Accumulation Effect”. Mixed-model-based composite interval mapping was used to dissect the genetic basis of the flowering time traits. A total of 41 quantitative trait loci (QTL) was identified for the three flowering time traits through four procedures. Among these 41 QTL, 38 focused on four hot regions, including bin 2.02, bin 2.03, bin 5.04, and bin 6.01. These regions and linked markers should be the targets for fine mapping, map-based cloning, and marker-assisted selection of flowering time and phosphate utilization efficiency.

With the wide application of new information technology in the port system, the container port logistics system to large-scale, high-speed, automation, digitization, information technology development direction, the number of terminals is increasing, the scale is expanding, the cargo throughput is increasing, on the port terminal loading and unloading efficiency requirements are constantly improving. This paper will analyze the factors affecting port throughput from the macro and micro aspects, and take the throughput of two quarters as the BP Neural Network data input, find out the relationship coefficient, and select the method of unitary regression prediction to predict the port throughput. The results show that the BP Neural Network optimized by one channel algorithm is feasible and effective in the process of port throughput prediction.

with the rapid development of information technology, the computer processing of information is also changing. Therefore, graphic image processing technology has become a hot topic in recent years. Researchers hope that the computer's "eyes" will no longer have no thoughts, but can process the data seen like a person and then send it to the brain (CPU), which is the formal graphic image processing technology. Graphic image processing technology will be widely used in the future with more diversified computer capabilities, such as image processing detection, computer animation design, image processing and so on. Coding compression technology and image segmentation technology are the key points in graphic image processing, which is also the research direction of this paper.

Triple-negative breast cancer (TNBC) is currently the most malignant subtype of breast cancers without effective targeted therapies. Mifepristone (MIF), a drug regularly used for abortion, has been reported to have anti-tumor activity in multiple hormone-dependent cancers, including luminal type breast cancers. In this study, we showed that MIF suppressed tumor growth of the TNBC cell lines and patient-derived xenografts in NOD-SCID mice. Furthermore, MIF reduced the TNBC cancer stem cell (CSC) population through down-regulating KLF5 expression, a stem cell transcription factor over-expressed in basal type TNBC and promoting cell proliferation, survival and stemness. Interestingly, MIF suppresses the expression of KLF5 through inducing the expression of miR-153. Consistently, miR-153 decreases CSC and miR-153 inhibitor rescued MIF-induced down-regulation of the KLF5 protein level and CSC ratio. Taken together, our findings suggest that MIF inhibits basal TNBC via the miR-153/KLF5 axis and MIF may be used for the treatment of TNBC.

Phosphorus (P) is an essential element involved in numerous biochemical reactions. In plants, stress responses, such as the expression of microRNAs (miRNAs), are induced to help them adapt to low phosphate (Pi) concentrations. In this study, deep sequencing was performed using the roots and leaves of maize seedlings grown under low Pi concentrations to identify miRNAs that are differentially expressed during the early stages of Pi deficiency. Eight small RNA libraries were constructed, and 159 known miRNAs representing 32 miRNA families and 10 novel miRNAs. Members of the miR396 family were extremely abundant. Further, 28 Pi-responsive miRNAs were identified (27 known and 1 novel) of which 8 and 7 were significantly expressed exclusively in leaf and root tissues, respectively. The analysis of Pi-responsive miRNAs target genes suggested that most target genes functioning as transcription factors were involved in root and leaf development. The expression profiles of selected Pi-responsive miRNAs and target genes were confirmed by quantitative real-time polymerase chain reaction (qRT-PCR). Moreover, we discuss the significance of the differences in expression patterns of these miRNAs during the early and later stages of Pi starvation. This study provides useful information concerning the role of miRNAs in response to Pi starvation and will further our understanding of the mechanisms governing Pi homeostasis in maize.

To develop genetic markers associated with tolerance to low phosphorus, we identified candidate phosphate starvation responsive (PSR) genes and developed their intron length polymorphism (ILP) markers in maize on a genome-wide scale. Based on the known plant PSR genes, 161 candidate PSR genes were identified. Of these genes, 138 genes contained at least one intron and were then used to develop 606 PSR-ILP markers by designing PCR primers to the intron-flanking exonic regions. PCR evaluation was performed on 43 randomly selected PSR-ILP markers in 30 maize inbred lines. Of the primers, 88.4% amplified stable and pure products in all maize inbred lines, and 53.5% of the markers showed ILP, with PIC values ranging from 0.06 to 0.80. The result of clustering analysis of the 30 maize inbred lines, based on the polymorphism of 23 ILP markers, suggests that the ILP markers developed in this study are not only efficient for genetic diversity analysis but also potentially useful for marker assisted selection for tolerance to low phosphorus.