MaxCut in graphs with sparse neighborhoods

Let $G$ be a graph with $m$ edges and let $\mathrm{mc}(G)$ denote the size of a largest cut of $G$. The difference $\mathrm{mc}(G)-m/2$ is called the surplus $\mathrm{sp}(G)$ of $G$. A fundamental problem in MaxCut is to determine $\mathrm{sp}(G)$ for $G$ without specific structure, and the degree sequence $d_1,\ldots,d_n$ of $G$ plays a key role in getting the lower bound of $\mathrm{sp}(G)$. A classical example, given by Shearer, is that $\mathrm{sp}(G)=\Omega(\sum_{i=1}^n\sqrt d_i)$ for triangle-free graphs $G$, implying that $\mathrm{sp}(G)=\Omega(m^{3/4})$. It was extended to graphs with sparse neighborhoods by Alon, Krivelevich and Sudakov. In this paper, we establish a novel and stronger result for a more general family of graphs with sparse neighborhoods. Our result can derive many well-known bounds on $\mathrm{sp}(G)$ in $H$-free graphs $G$ for different $H$, such as the triangle, the even cycle, the graphs having a vertex whose removal makes the graph acyclic, or the complete bipartite graph $K_{s,t}$ with $s\in \{2,3\}$. It can also deduce many new (tight) bounds on $\mathrm{sp}(G)$ in $H$-free graphs $G$ when $H$ is any graph having a vertex whose removal results in a bipartite graph with relatively small Tur\'{a}n number, especially the even wheel. This contributes to a conjecture raised by Alon, Krivelevich and Sudakov. Moreover, we give a new family of graphs $H$ such that $\mathrm{sp}(G)=\Omega(m^{3/4+\epsilon(H)})$ for some constant $\epsilon(H)>0$ in $H$-free graphs $G$, giving an evidence to a conjecture suggested by Alon, Bollob\'as, Krivelevich and Sudakov

Modulating CRISPR/Cas9 genome-editing activity by small molecules

Clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9 (CRISPR/Cas9)-mediated genome engineering has become a standard procedure for creating genetic and epigenetic changes of DNA molecules in basic biology, biotechnology, and medicine. However, its versatile applications have been hampered by its overall low precise gene modification efficiency and uncontrollable prolonged Cas9 activity. Therefore, overcoming these problems could broaden the therapeutic use of CRISPR/Cas9-based technologies. Here, we review small molecules with the clinical potential to precisely modulate CRISPR/Cas9-mediated genome-editing activity and discuss their mechanisms of action. Based on these data, we suggest that direct-acting small molecules for Cas9 are more suitable for precisely regulating Cas9 activity. These findings provide useful information for the identification of novel small-molecule enhancers and inhibitors of Cas9 and Cas9-associated endonucleases

CRISPR-mediated ablation of overexpressed EGFR in combination with sunitinib significantly suppresses renal cell carcinoma proliferation

Receptor tyrosine kinases, such as VEGFR, PDGFR and EGFR, play important roles in renal cancer. In this study, we investigated EGFR knockout as a therapeutic approach in renal cell carcinoma (RCC). We showed that a renal cell carcinoma cell line (RC21) has higher expression of EGFR as compared to other frequently used cell lines such as HEK293, A549, Hela and DLD1. Ablation of EGFR by CRISPR/Cas9 significantly restrained tumor cell growth and activated the MAPK (pERK1/2) pathway. The VEGFR and PDGFR inhibitor, sunitinib, attenuated the expression of MAPK (pERK1/2) and pAKT induced by EGFR loss and further inhibited EGFR(-/-) cell proliferation. We showed that loss of EGFR eventually leads to resistance to SAHA and cisplatin. Furthermore, EGFR loss induced G2/M phase arrest and resulted in an increased resistance to TNF-related apoptosis-inducing ligand (TRAIL) in renal cell carcinoma. Thus, ablation of overexpressed EGFR by CRISPR/Cas9 alone or in combination with sunitinib may be a new treatment option for renal cell carcinoma

KMT2A associates with PHF5A-PHF14-HMG20A-RAI1 subcomplex in pancreatic cancer stem cells and epigenetically regulates their characteristics

Pancreatic cancer (PC), one of the most aggressive and life-threatening human malignancies, is known for its resistance to cytotoxic therapies. This is increasingly ascribed to the subpopulation of undifferentiated cells, known as pancreatic cancer stem cells (PCSCs), which display greater evolutionary fitness than other tumor cells to evade the cytotoxic effects of chemotherapy. PCSCs are crucial for tumor relapse as they possess ‘stem cell-like’ features that are characterized by self-renewal and differentiation. However, the molecular mechanisms that maintain the unique characteristics of PCSCs are poorly understood. Here, we identify the histone methyltransferase KMT2A as a physical binding partner of an RNA polymerase-associated PHF5A-PHF14-HMG20A-RAI1 protein subcomplex and an epigenetic regulator of PCSC properties and functions. Targeting the protein subcomplex in PCSCs with a KMT2A-WDR5 inhibitor attenuates their self-renewal capacity, cell viability, and in vivo tumorigenicity

Identification CCL2,CXCR2,S100A9 of the immune-related gene markers and immune infiltration characteristics of inflammatory bowel disease and heart failure via bioinformatics analysis and machine learning

BackgroundRecently, heart failure (HF) and inflammatory bowel disease (IBD) have been considered to be related diseases with increasing incidence rates; both diseases are related to immunity. This study aims to analyze and identify immune-related gene (IRG) markers of HF and IBD through bioinformatics and machine learning (ML) methods and to explore their immune infiltration characteristics.MethodsThis study used gene expressiondata (GSE120895, GSE21610, GSE4183) from the Gene Expression Omnibus (GEO) database to screen differentially expressed genes (DEGs) and compare them with IRGs from the ImmPort database to obtain differentially expressed immune-related genes (DIRGs). Functional enrichment analysis of IRGs was performed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Subsequently, three machine models and protein–protein interactions (PPIs) were established to identify diagnostic biomarkers. The receiver operating characteristic (ROC) curves were applied to evaluate the diagnostic value of the candidate biomarkersin the validation set (GSE1145, GSE36807) and obtain their correlations with immune cells through the Spearman algorithm. Finally, the CIBERSORT algorithm was used to evaluate the immune cell infiltration of the two diseases.ResultsThirty-four DIRGs were screened and GO and KEGG analysis results showed that these genes are mainly related to inflammatory and immune responses. CCL2, CXCR2 and S100A9 were identified as biomarkers.The immune correlation results indicated in both diseases that CCL2 is positively correlated with mast cell activation, CXCR2 is positively correlated with neutrophils and S100A9 is positively correlated with neutrophils and mast cell activation. Analysis of immune characteristics showed that macrophages M2, macrophages M0 and neutrophils were present in both diseases.ConclusionsCCL2, CXCR2 and S100A9 are promising biomarkers that will become potential immunogenetic biomarkers for diagnosing comorbidities of HF and IBD. macrophages M2, macrophages M0, neutrophil-mediated inflammation and immune regulation play important roles in the development of HF and IBD and may become diagnostic and therapeutic targets

Comparison of Adsorption/Desorption of Volatile Organic Compounds (VOCs) on Electrospun Nanofibers with Tenax TA for Potential Application in Sampling.

The objective of this study was to compare the adsorption/desorption of target compounds on homemade electrospun nanofibers, polystyrene (PS) nanofibers, acrylic resin (AR) nanofibers and PS-AR composite nanofibers with Tenax TA. Ten volatile organic compounds (VOCs) were analyzed by preconcentration onto different sorbents followed by desorption (thermal and solvent orderly) and analysis by capillary gas chromatography. In comparison to Tenax TA, the electrospun nanofibers displayed a significant advantage in desorption efficiency and adsorption selectivity. Stability studies were conducted as a comparative experiment between PS-AR nanofibers and Tenax TA using toluene as the model compound. No stability problems were observed upon storage of toluene on both PS-AR nanofibers and Tenax TA over 60 hours period when maintained in an ultra-freezer (-80°C). The nanofibers provided slightly better stability for the adsorbed analytes than Tenax TA under other storage conditions. In addition, the nanofibers also provided slightly better precision than Tenax TA. The quantitative adsorption of PS-AR nanofibers exhibited a good linearity, as evidenced by the 0.988-0.999 range of regression coefficients (R). These results suggest that for VOCs sampling the electrospun nanofibers can be a potential ideal adsorbent

Comparison of Fruit Traits and Yield among Different Olive Cultivars

With the local major cultivar Leccino as the control, the fruit quality, yield and early maturing property of introduced olive cultivars (Koroneiki, Arbequina, Hojiblanca) from Spain were studied. The results showed that there were differences in fruit traits such as single fruit weight, ratio of flesh content, moisture content and oil content between different cultivars. The yield of early maturing property of the introduce cultivars were better than those of Leccino. The introduced varieties can fruit after 1-2a, showing early maturity and high yield. This can provide a theoretical reference for the cultivation of olive in Longnan