39 research outputs found

    How fast can Dominator win in the Maker--Breaker domination game?

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    We study the Maker--Breaker domination games played by two players, Dominator and Staller. We give a structural characterization for graphs with Maker--Breaker domination number equal to the domination number. Specifically, we show how fast Dominator can win in the game on P2□PnP_2 \square P_n, for n≥1n\geq 1

    Histone demethylase PHF8 promotes epithelial to mesenchymal transition and breast tumorigenesis

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    Histone demethylase PHF8 is upregulated and plays oncogenic roles in various cancers; however, the mechanisms underlying its dysregulation and functions in carcinogenesis remain obscure. Here, we report the novel functions of PHF8 in EMT (epithelial to mesenchymal transition) and breast cancer development. Genome-wide gene expression analysis revealed that PHF8 overexpression induces an EMT-like process, including the upregulation of SNAI1 and ZEB1. PHF8 demethylates H3K9me1, H3K9me2 and sustains H3K4me3 to prime the transcriptional activation of SNAI1 by TGF-β signaling. We show that PHF8 is upregulated and positively correlated with MYC at protein levels in breast cancer. MYC post-transcriptionally regulates the expression of PHF8 via the repression of microRNAs. Specifically, miR-22 directly targets and inhibits PHF8 expression, and mediates the regulation of PHF8 by MYC and TGF-β signaling. This novel MYC/microRNAs/PHF8 regulatory axis thus places PHF8 as an important downstream effector of MYC. Indeed, PHF8 contributes to MYC-induced cell proliferation and the expression of EMT-related genes. We also report that PHF8 plays important roles in breast cancer cell migration and tumor growth. These oncogenic functions of PHF8 in breast cancer confer its candidacy as a promising therapeutic target for this disease

    Polyethyleneimine-coated MXene quantum dots improve cotton tolerance to Verticillium dahliae by maintaining ROS homeostasis

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    Verticillium dahliae is a soil-borne hemibiotrophic fungal pathogen that threatens cotton production worldwide. In this study, we assemble the genomes of two V. dahliae isolates: the more virulence and defoliating isolate V991 and nondefoliating isolate 1cd3-2. Transcriptome and comparative genomics analyses show that genes associated with pathogen virulence are mostly induced at the late stage of infection (Stage II), accompanied by a burst of reactive oxygen species (ROS), with upregulation of more genes involved in defense response in cotton. We identify the V991-specific virulence gene SP3 that is highly expressed during the infection Stage II. V. dahliae SP3 knock-out strain shows attenuated virulence and triggers less ROS production in cotton plants. To control the disease, we employ polyethyleneimine-coated MXene quantum dots (PEI-MQDs) that possess the ability to remove ROS. Cotton seedlings treated with PEI-MQDs are capable of maintaining ROS homeostasis with enhanced peroxidase, catalase, and glutathione peroxidase activities and exhibit improved tolerance to V. dahliae. These results suggest that V. dahliae trigger ROS production to promote infection and scavenging ROS is an effective way to manage this disease. This study reveals a virulence mechanism of V. dahliae and provides a means for V. dahliae resistance that benefits cotton production

    The influence of methotrexate-related transporter and metabolizing enzyme gene polymorphisms on peri-engraftment syndrome and graft-versus-host disease after haplo-hematopoietic stem cell transplantation in pediatric patients with malignant hematological diseases

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    BackgroundMethotrexate (MTX), utilized as a graft-versus-host disease (GvHD) prophylactic agent in allogeneic hematopoietic stem cell transplantation (allo-HSCT), has been proven to effectively decrease the occurrence of the peri-engraftment syndrome (Peri-ES) and acute GvHD (aGvHD). Changes in the pharmacodynamics of MTX are closely associated with gene polymorphisms in genes encoding drug-metabolizing enzymes and transporters. Nevertheless, the current studies mainly concentrate on leukemia or autoimmune diseases, and limited studies on allo-HSCT were reported.MethodsHere, we retrospectively assessed the relationship between MTX-related transporter and metabolizing enzyme gene polymorphisms, clinical characteristics, and outcomes in 57 pediatric patients who received haploid HSCT (haplo-HSCT) with malignant tumors at a single center.ResultsWe discovered all gene polymorphisms were in the Hardy–Weinberg equilibrium in our cohort. We discovered a significant correlation between platelet recovery time and ABCB1 (1236C>T) (p = 0.042). Compared with patients with SLCO1B1 (1865+4846T>C) TT, patients with SLCO1B1 (1865+4846T>C) TC/CC had an increased incidence of Peri-ES (p = 0.030). Based on the multivariate Cox analysis, we discovered that SLCO1B1 (1865+4846T>C) TT genotype was an independent protective factor for Peri-ES morbidity (hazard ratio (HR) = 0.464, p = 0.031), and the dose of mononuclear cells reinfused was significantly correlated with II–IV aGvHD (HR = 2.604, p = 0.039).ConclusionIn summary, our findings prove that the host’s genotypes might modify the risk of developing Peri-ES, contribute to a better understanding of the inter-individual difference in efficacy, and facilitate the development of individualized approaches to GvHD prophylaxis

    The Association of Dietary Fiber Intake in Three Meals with All-Cause and Disease-Specific Mortality among Adults: The U.S. National Health and Nutrition Examination Survey, 2003–2014

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    The timing of food intake can significantly alter the body’s metabolism of nutrient intake and affect the occurrence of chronic diseases. However, whether and how the intake time of dietary fiber could influence mortality risks is largely unknown. This study aims to reveal the association between total dietary fiber intake and fiber intake at different times with all-cause, cancer, and cardiovascular disease (CVD) mortality rates. A total of 31,164 adults who enrolled in the National Health and Nutrition Examination Survey from 2003 to 2014 are included in this study. Dietary fiber intake was measured using 2-day, 24 h dietary recall. The main exposures in this study were the intake of dietary fiber at breakfast, lunch, and dinner via regression analysis of the residual method. The main outcomes were the all-cause, cancer, and CVD mortality rates. Cox proportional hazards regression models were used to evaluate the survival relationship between dietary fiber intake at different times and mortality rates. Among the 31,164 adults, 2915 deaths, including 631 deaths due to cancer and 836 deaths due to CVD, were documented. Firstly, after adjusting for potential confounders, compared to the participants in the lowest quintile of total dietary fiber intake, the participants in the highest quintile of fiber intake had lower all-cause (HR = 0.686, 95% CI: 0.589–0.799, p for trend <0.001) and cancer (HR = 0.606, 95% CI: 0.446–0.824, p for trend = 0.015) mortality risks. Secondly, compared to the participants in the lowest quintile of dietary fiber intake at dinner, the participants in the highest quintile of fiber intake had lower all-cause (HR = 0.796, 95% CI: 0.668–0.949, p for trend = 0.009) and cancer (HR = 0.564, 95% CI: 0.388–0.822, p for trend = 0.005) mortality risks. Furthermore, equivalently replacing each standard deviation of dietary fiber consumed at breakfast with that at dinner was associated with lower cancer mortality risks (HR = 0.846, 95% CI: 0.747–0.958). In conclusion, this study demonstrates that, in the NHANES (2003–2014) cohort, to reduce all-cause and cancer mortality risks, the optimal dietary fiber intake time is in the evening
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