N-(2-Hydroxy­ethyl)-1,8-naphthalimide

In the mol­ecule of the title compound, C14H11NO3, the naphthalimide ring system is nearly planar (r.m.s. deviation 0.0139 Å). In the crystal structure, inter­molecular O—H⋯O hydrogen bonds link the mol­ecules into centrosymmetric dimers forming R 2 2(14) ring motifs. π–π contacts between the naphthalimide rings [centroid–centroid distances = 3.648 (3), 3.783 (3), 3.635 (3), 3.722 (3) and 3.755 (3) Å] may further stabilize the structure

Network Representation Learning Guided by Partial Community Structure

Network Representation Learning (NRL) is an effective way to analyze large scale networks (graphs). In general, it maps network nodes, edges, subgraphs, etc. onto independent vectors in a low dimension space, thus facilitating network analysis tasks. As community structure is one of the most prominent mesoscopic structure properties of real networks, it is necessary to preserve community structure of networks during NRL. In this paper, the concept of k-step partial community structure is defined and two Partial Community structure Guided Network Embedding (PCGNE) methods, based on two popular NRL algorithms (DeepWalk and node2vec respectively), for node representation learning are proposed. The idea behind this is that it is easier and more cost-effective to find a higher quality 1-step partial community structure than a higher quality whole community structure for networks; the extracted partial community information is then used to guide random walks in DeepWalk or node2vec. As a result, the learned node representations could preserve community structure property of networks more effectively. The two proposed algorithms and six state-of-the-art NRL algorithms were examined through multi-label classification and (inner community) link prediction on eight synthesized networks: one where community structure property could be controlled, and one real world network. The results suggested that the two PCGNE methods could improve the performance of their own based algorithm significantly and were competitive for node representation learning. Especially, comparing against used baseline algorithms, PCGNE methods could capture overlapping community structure much better, and thus could achieve better performance for multi-label classification on networks that have more overlapping nodes and/or larger overlapping memberships

Metabolomics revealed the toxicity of cationic liposomes in HepG2 cells using UHPLC‐Q‐TOF/MS and multivariate data analysis

Cationic liposomes (CLs) are novel nonviral vectors widely used for delivering drugs or genes. However, applications of CLs are largely hampered by their cytotoxicity, partly because the potential mechanism underlying the cytotoxicity of CLs remains unclear. The aim of the present study was to explore the underlying mechanism of cytotoxicity induced by CLs on HepG2 cells. Differential metabolites were identified and quantified using ultra‐liquid chromatography quadrupole time‐of‐flight mass spectrometry (UHPLC‐Q‐TOF/MS). The toxicity of CLs on HepG2 cells was evaluated by multivariate data analysis and statistics. Additionally, CCK‐8 assay, heatmap, pathway and co‐expression network were carried out to explore the relations between the metabolites and the pathways. The results showed a dose‐dependent toxic effect of CLs on HepG2 cells, with an IC50 value of 119.9 μg/mL. Multivariate statistical analysis identified 42 potential metabolites between CLs exposure and control groups. Pathway analysis showed significant changes in pathways involving amino acid metabolism, energy metabolism, lipid metabolism and oxidative stress in the CLs exposure group vs the control group. Metabolites related to the above‐mentioned pathways included phenylalanine, methionine, creatine, oxalacetic acid, glutathione, oxidized glutathione, choline phosphate and several unsaturated fatty acids, indicating that cells were disturbed in amino acid metabolism, energy and lipid supply when CLs exposure‐induced injury occurred. It is concluded that CLs may induce cytotoxicity by enhancing reactive oxygen species in vitro, affect the normal process of energy metabolism, disturb several vital signaling pathways and finally induce cell death.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/139913/1/bmc4036.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/139913/2/bmc4036_am.pd

2-(7-Meth­oxy-1-naphth­yl)acetonitrile

The mol­ecule of the title compound, C13H11NO, is almost planar (r.m.s. deviation = 0.013 Å), apart from the cyanide group, for which the C and N atoms deviate from the mean plane of the other atoms by 0.341 (3) and 0.571 (4) Å, respectively. In the crystal, weak aromatic π–π stacking [centroid–centroid distance = 3.758 (3) Å] may help to stabilize the structure

Simultaneous Inhibition of MEK and Hh Signaling Reduces Pancreatic Cancer Metastasis

Pancreatic cancer, mostly pancreatic ductal adenocarcinoma (PDAC), is one of the most lethal cancer types, with an estimated 44,330 death in 2018 in the US alone. While targeted therapies and immune checkpoint inhibitors have significantly improved treatment options for patients with lung cancer and renal cell carcinomas, little progress has been made in pancreatic cancer, with a dismal 5-year survival rate currently at ~8%. Upon diagnosis, the majority of pancreatic cancer cases (~80%) are already metastatic. Thus, identifying ways to reduce pancreatic cancer metastasis is an unmet medical need. Furthermore, pancreatic cancer is notorious resistant to chemotherapy. While Kirsten RAt Sarcoma virus oncogene (K-RAS) mutation is the major driver for pancreatic cancer, specific inhibition of RAS signaling has been very challenging, and combination therapy is thought to be promising. In this study, we report that combination of hedgehog (Hh) and Mitogen-activated Protein/Extracellular Signal-regulated Kinase Kinase (MEK) signaling inhibitors reduces pancreatic cancer metastasis in mouse models. In mouse models of pancreatic cancer metastasis using human pancreatic cancer cells, we found that Hh target gene Gli1 is up-regulated during pancreatic cancer metastasis. Specific inhibition of smoothened signaling significantly altered the gene expression profile of the tumor microenvironment but had no significant effects on cancer metastasis. By combining Hh signaling inhibitor BMS833923 with RAS downstream MEK signaling inhibitor AZD6244, we observed reduced number of metastatic nodules in several mouse models for pancreatic cancer metastasis. These two inhibitors also decreased cell proliferation significantly and reduced CD45⁺ cells (particularly Ly6G⁺CD11b⁺ cells). We demonstrated that depleting Ly6G⁺ CD11b⁺ cells is sufficient to reduce cancer cell proliferation and the number of metastatic nodules. In vitro, Ly6G⁺ CD11b⁺ cells can stimulate cancer cell proliferation, and this effect is sensitive to MEK and Hh inhibition. Our studies may help design novel therapeutic strategies to mitigate pancreatic cancer metastasis

5-Fluoro-3-(2-phenyl­hydrazinyl­idene)indolin-2-one

In the title compound, C14H10FN3O, the six- and five-membered rings of the isatin moiety and the six-membered ring of phenyl­hydrazone are nearly planar with r.m.s. deviations of 0.0003, 0.0004 and 0.007 Å, respectively. The dihedral angle between the phenyl ring and the isatin ring system is 6.09 (9)°. The mol­ecular structure is stabilized by a strong intra­molecular N—H⋯O hydrogen bond, leading to the formation of a pseudo-six-membered ring, generating an S(6) ring. The crystal structure features inter­molecular N—H⋯O inter­actions

3,6-Dibromo-7-ethyl­amino-4-methyl-2H-chromen-2-one

In title compound, C12H11Br2NO2, the coumarin ring system is almost planar, the two rings being inclined to one another by 1.40 (15)°. There are two short intra­molecular inter­actions (N—H⋯Br and C—H⋯Br) involving the Br atoms. In the crystal, mol­ecules stack along the a-axis direction via π–π inter­actions; the centroid–centroid distances vary from 3.6484 (19) to 3.7942 (19) Å

Quantum blockade and loop current induced by a single lattice defect in graphene nanoribbons

We investigate theoretically the electronic transport properties in narrow graphene ribbons with an adatom-induced defect. It is found that the lowest conductance step of a metallic graphene nanoribbon may develop a dip even down to zero at certain values of the Fermi energy due to the defect. Accompanying the occurrence of the conductance dip, a loop current develops around the defect. We show how the properties of the conductance dip depend on the parameters of the defect, such as the relative position and severity of the defect as well as the width and edges of the graphene ribbons. In particular, for metallic armchair-edges graphene nanoribbons, whether the conductance dip appears or not, they can be controlled by choosing the position of the single defect.Comment: 6 pages, 6 figure

Copy Number Variation of Cytokinin Oxidase Gene Tackx4 Associated with Grain Weight and Chlorophyll Content of Flag Leaf in Common Wheat

Publisher's version/PDFAs the main pigment in photosynthesis, chlorophyll significantly affects grain filling and grain weight of crop. Cytokinin (CTK) can effectively increase chlorophyll content and chloroplast stability, but it is irreversibly inactivated by cytokinin oxidase (CKX). In this study, therefore, twenty-four pairs of primers were designed to identify variations of wheat CKX (Tackx) genes associated with flag leaf chlorophyll content after anthesis, as well as grain weight in 169 recombinant inbred lines (RIL) derived from Triticum aestivum Jing 411 × Hongmangchun 21. Results indicated variation of Tackx4, identified by primer pair T19-20, was proven to significantly associate with chlorophyll content and grain weight in the RIL population. Here, two Tackx4 patterns were identified: one with two co-segregated fragments (Tackx4-1/Tackx4-2) containing 618 bp and 620 bp in size (as in Jing 411), and another with no PCR product. The two genotypes were designated as genotype-A and genotype-B, respectively. Grain weight and leaf chlorophyll content at 5~15 days after anthesis (DAA) were significantly higher in genotype-A lines than those in genotype-B lines. Mapping analysis indicated Tackx4 was closely linked to Xwmc169 on chromosome 3AL, as well as co-segregated with a major quantitative trait locus (QTL) for both grain weight and chlorophyll content of flag leaf at 5~15 DAA. This QTL explained 8.9~22.3% phenotypic variations of the two traits across four cropping seasons. Among 102 wheat varieties, a third genotype of Tackx4 was found and designated as genotype-C, also having two co-segregated fragments, Tackx4-2 and Tackx4-3 (615bp). The sequences of three fragments, Tackx4-1, Tackx4-2, and Tackx4-3, showed high identity (>98%). Therefore, these fragments could be considered as different copies at Tackx4 locus on chromosome 3AL. The effect of copy number variation (CNV) of Tackx4 was further validated. In general, genotype-A contains both significantly higher grain weight and flag leaf chlorophyll content at 5~15 DAA than those in genotype-B and genotype-C, among 102 varieties under various environments.This work was supported by grants from the National Natural Science Foundation of China (31000705), the China Agriculture Research System (CARS-03), the Scientific Research Special Program of Agricultural Commonwealth (201203033-04), Natural Science Foundation of Anhui Province (1508085MC57), the Agriculture Research System of Anhui Province (AHCYTX-02), Jiangsu Collaborative Innovation Center for Modern Crop Production (JCIC) and the introduced leading talent research team for Universities in Anhui Province. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Cationic liposomes induce cytotoxicity in HepG2 via regulation of lipid metabolism based on whole-transcriptome sequencing analysis

Abstract Backgroud Cationic liposomes (CLs) can be used as non-viral vectors in gene transfer and drug delivery. However, the underlying molecular mechanism of its cytotoxicity has not been well elucidated yet. Methods We herein report a systems biology approach based on whole-transcriptome sequencing coupled with computational method to identify the predominant genes and pathways involved in the cytotoxicity of CLs in HepG2 cell line. Results Firstly, we validated the concentration-dependent cytotoxicity of CLs with an IC50 of 120 μg/ml in HepG2 exposed for 24 h. Subsequently, we used whole-transcriptome sequencing to identify 220 (77 up- and 143 down-regulated) differentially expressed genes (DEGs). Gene ontology (GO) and pathway analysis showed that these DEGs were mainly related to cholesterol, steroid, lipid biosynthetic and metabolic processes. Additionally, “key regulatory” genes were identified using gene act, pathway act and co-expression network analysis, and expression levels of 11 interested altered genes were confirmed by quantitative real time PCR. Interestingly, no cell cycle arrest was observed through flow cytometry. Conclusions These data are expected to provide deep insights into the molecular mechanism of CLs cytotoxicity.https://deepblue.lib.umich.edu/bitstream/2027.42/144776/1/40360_2018_Article_230.pd