Topological neighborhoods of several nodes.

<p>(a) Topological neighborhood of a hub but not top-ranked node: node 209 in the YT. (b) Topological neighborhood of a non-hub but top-ranked node: node 546 in the YT. (c) Topological neighborhood of a not top-ranked node but with the highest betweenness: node 293 in the YT.</p

Additional file 1 of The influence factors of medical disputes in Shanghai and implications - from the perspective of doctor, patient and disease

Additional file 1. The conflict of doctor-patient questionnaire

A real-world biological network and some network motifs.

<p>(a) A Drosophila developmental transcriptional network with 119 nodes and 306 directed edges. (b) Some representative 2, 3 and 4-node motifs.</p

Selective Binding of Antiinfluenza Drugs and Their Analogues to ‘Open’ and ‘Closed’ Conformations of H5N1 Neuraminidase

It was suggested that the open conformation of the 150-loop of H5N1 avian influenza neuraminidase is intrinsically lower in energy than the closed conformation and that oseltamivir (tamiflu) favors binding to the closed conformation through a relatively slow conformational change [Russell, R. J. Nature 2006, 443, 45−49]. In the present work, a systematic computational study is performed to investigate the binding mechanism of five ligands to H5N1 neuraminidase (H5N1 NA) with the 150-loop in both open and closed conformations through molecular docking, molecular dynamics simulations, and MM/PBSA free energy calculation. Our result shows that the electrostatic interactions between polar groups on the 150-loop and the charged groups of the ligands play a key role on the binding selectivity. In particular, ligands having a small positively charged group favor binding to the closed conformation of H5N1 NA, while those having a large positively charged group generally prefer binding to the open conformation. Our analysis suggests that it may be possible to design new inhibitors with large basic groups that are selective for the open conformation and thereby have stronger binding affinity to H5N1 neuraminidase

ROC curves based on the available information in the CEN and ECT.

<p>(a) Performance of different indexes in identifying (a) the 10 command interneurons in the CEN, (b) the 117 interneurons in the CEN, (c) the 7 key global regulators in the ECT, (d) the 18 global regulators in the ECT.</p

Evaluation of <i>I</i>^score via ROC curves with composite reference standards for the five networks.

<p>(a) <i>T</i>₀ = 10%. A node is defined as important if either its rankings by the in, out, total degree, PageRank, motif centrality or the betweenness are at the top-<i>T</i>₀ level. (b) Similarly to (a), but with <i>T</i>₀ = 20%.</p

An illustrative example.

<p>(a) A simple network with six nodes. (b) Subgraphs that are assumed to be motifs in network (a). (c) Members that compose the three types of motifs. (d) Appearances of nodes in each motif as shown in panel (b). (e) Frequency histograms for the six nodes. (f) Cluster analysis reveals that the six nodes can be remarkably classified into three classes. <i>v</i>₁, <i>v</i>₃, <i>v</i>₅ are the most important nodes, and <i>v</i>₂ forms the least important group, <i>v</i>₄, <i>v</i>₆ form another group, which is more important than <i>v</i>₂.</p

<i>iProMix</i>: A Mixture Model for Studying the Function of ACE2 based on Bulk Proteogenomic Data

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused over six million deaths in the ongoing COVID-19 pandemic. SARS-CoV-2 uses ACE2 protein to enter human cells, raising a pressing need to characterize proteins/pathways interacted with ACE2. Large-scale proteomic profiling technology is not mature at single-cell resolution to examine the protein activities in disease-relevant cell types. We propose iProMix, a novel statistical framework to identify epithelial-cell specific associations between ACE2 and other proteins/pathways with bulk proteomic data. iProMix decomposes the data and models cell type-specific conditional joint distribution of proteins through a mixture model. It improves cell-type composition estimation from prior input, and uses a nonparametric inference framework to account for uncertainty of cell-type proportion estimates in hypothesis test. Simulations demonstrate iProMix has well-controlled false discovery rates and favorable powers in nonasymptotic settings. We apply iProMix to the proteomic data of 110 (tumor-adjacent) normal lung tissue samples from the Clinical Proteomic Tumor Analysis Consortium lung adenocarcinoma study, and identify interferon α/γ response pathways as the most significant pathways associated with ACE2 protein abundances in epithelial cells. Strikingly, the association direction is sex-specific. This result casts light on the sex difference of COVID-19 incidences and outcomes, and motivates sex-specific evaluation for interferon therapies. Supplementary materials for this article are available online.</p

Trapping Methylglyoxal by Genistein and Its Metabolites in Mice

Increasing evidence supports dicarbonyl stress such as methylglyoxal (MGO) as one of the major pathogenic links between hyperglycemia and diabetic complications. <i>In vitro</i> studies have shown that dietary flavonoids can inhibit the formation of advanced glycation end products (AGEs) by trapping MGO. However, whether flavonoids can trap MGO <i>in vivo</i> and whether biotransformation limits the trapping capacity of flavonoids remain virtually unknown. In this study, we investigated whether genistein (GEN), the major soy isoflavone, could trap MGO in mice by promoting the formation of MGO adducts of GEN and its metabolites. Two different mouse studies were conducted. In the acute study, a single dose of MGO and GEN were administered to mice via oral gavage. In the chronic study, MGO was given to mice in drinking water for 1 month and then GEN was given to mice for 4 consecutive days via oral gavage. Two mono-MGO adducts of GEN and six mono-MGO adducts of GEN phase I and microbial metabolites were identified in mouse urine samples from these studies using liquid chromatography/electrospray ionization tandem mass spectrometry. The structures of these MGO adducts were confirmed by analyzing their MS^<i>n</i> (<i>n</i> = 1–4) spectra as well as by comparing them with the tandem mass spectra of authentic standards. All of the MGO adducts presented in their phase II conjugated forms in mouse urine samples in the acute and chronic studies. To our knowledge, this is the first <i>in vivo</i> evidence to demonstrate the trapping efficacy of GEN in mice and to show that the metabolites of GEN remain bioactive

Clusters, members, rankings and statistical characteristics of the identified top-30 ranked nodes in the YT.

<p>Clusters, members, rankings and statistical characteristics of the identified top-30 ranked nodes in the YT.</p