The R workspace of bimj202200089.R2

Supplementary information / reproducible research files for the manuscript  Title:  "Model-free conditional screening for ultrahigh-dimensional survival data via conditional distance correlation" Authors:  Hengjian Cui, Yanyan Liu, Guangcai Mao and Jing Zhang Introduction:  It contains all R workspace that can be used to reproduce all results and figures of the manuscript.</p

Surface activities and thermodynamic properties of novel cationic surfactants with hydroxymethyl group

<p>A new series of cationic surfactants, <i>N</i>–alkyl–<i>N,N</i>–dimethyl–<i>N</i>–(<i>p</i>–(hydroxymethyl) benzyl) ammonium chlorides (<i>p</i>-DHBA<i>-m</i>), were synthesized and the structures were characterized by ¹HNMR, ¹³CNMR, FT–IR and ESI–MS. The surface activities, thermodynamic properties and aggregation behaviors of <i>p</i>-DHBA<i>-m</i> in aqueous solutions were respectively studied by means of surface tension, isothermal titration calorimetry and steady-state fluorescence methods. Thermodynamic parameters show that the micellization is an entropy-driven process. According to the fluorescence quenching method, the micelle aggregation numbers (<i>N</i>_agg) of <i>p</i>-DHBA-<i>m</i> were calculated and found that the increase of temperature or the elongation of alkyl chain length could lead to the reduction of the <i>N</i>_agg, respectively.</p

The long non-coding RNA LSINCT5 promotes malignancy in non-small cell lung cancer by stabilizing HMGA2

<p>Long non-coding RNAs (lncRNAs) can actively participate in tumorigenesis in various cancers. However, the involvement of lncRNA long stress induced non-coding transcripts 5 (LSINCT5) in non-small cell lung cancer (NSCLC) remains largely unknown. Here we showed a novel lncRNA signature in NSCLC through lncRNA profiling. Increased LSINCT5 expression positively correlates with malignant clinicopathological features and poor survival. LSINCT5 can promote migration and viability of various NSCLC cells <i>in vitro</i> and also enhance lung cancer progression <i>in vivo</i>. RNA immunoprecipitation followed by mass spectrometry has identified that LSINCT5 interacts with HMGA2. This physical interaction can increase the stability of HMGA2 by inhibiting proteasome-mediated degradation. Therefore, LSINCT5 may possibly contribute to NSCLC tumorigenesis by stabilizing the oncogenic factor of HMGA2. This novel LSINCT5/HMGA2 axis can modulate lung cancer progression and might be a promising target for pharmacological intervention.</p

Lack of Association between NLGN3, NLGN4, SHANK2 and SHANK3 Gene Variants and Autism Spectrum Disorder in a Chinese Population

<div><p>Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by deficits in social communication, absence or delay in language development, and stereotyped or repetitive behaviors. Genetic studies show that neurexin-neuroligin (NRXN-NLGN) pathway genes contribute susceptibility to ASD, which include cell adhesion molecules <i>NLGN3</i>, <i>NLGN4</i> and scaffolding proteins <i>SHANK2</i> and <i>SHANK3</i>. Neuroligin proteins play an important role in synaptic function and trans-synaptic signaling by interacting with presynaptic neurexins. Shank proteins are scaffolding molecules of excitatory synapses, which function as central organizers of the postsynaptic density. Sequence level mutations and structural variations in these genes have been identified in ASD cases, while few studies were performed in Chinese population. In this study, we examined the copy numbers of four genes <i>NLGN4, NLGN3, SHANK2,</i> and <i>SHANK3</i> in 285 ASD cases using multiplex fluorescence competitive polymerase chain reaction (PCR). We also screened the regulatory region including the promoter region and 5′/3′ untranslated regions (UTR) and the entire coding region of <i>NLGN4</i> in a cohort of 285 ASD patients and 384 controls by direct sequencing of genomic DNA using the Sanger method. DNA copy number calculation in four genes showed no deletion or duplication in our cases. No missense mutations in <i>NLGN4</i> were identified in our cohort. Association analysis of 6 common SNPs in <i>NLGN4</i> did not find significant difference between ASD cases and controls. These findings showed that these genes may not be major disease genes in Chinese ASD cases.</p> </div

Competitive Inhibition Mechanism of Acetylcholinesterase without Catalytic Active Site Interaction: Study on Functionalized C₆₀ Nanoparticles via in Vitro and in Silico Assays

Acetylcholinesterase (AChE) activity regulation by chemical agents or, potentially, nanomaterials is important for both toxicology and pharmacology. Competitive inhibition via direct catalytic active sites (CAS) binding or noncompetitive inhibition through interference with substrate and product entering and exiting has been recognized previously as an AChE-inhibition mechanism for bespoke nanomaterials. The competitive inhibition by peripheral anionic site (PAS) interaction without CAS binding remains unexplored. Here, we proposed and verified the occurrence of a presumed competitive inhibition of AChE without CAS binding for hydrophobically functionalized C₆₀ nanoparticles (NPs) by employing both experimental and computational methods. The kinetic inhibition analysis distinguished six competitive inhibitors, probably targeting the PAS, from the pristine and hydrophilically modified C₆₀ NPs. A simple quantitative nanostructure–activity relationship (QNAR) model relating the pocket accessible length of substituent to inhibition capacity was then established to reveal how the geometry of the surface group decides the NP difference in AChE inhibition. Molecular docking identified the PAS as the potential binding site interacting with the NPs via a T-shaped plug-in mode. Specifically, the fullerene core covered the enzyme gorge as a lid through π–π stacking with Tyr72 and Trp286 in the PAS, while the hydrophobic ligands on the fullerene surface inserted into the AChE active site to provide further stability for the complexes. The modeling predicted that inhibition would be severely compromised by Tyr72 and Trp286 deletions, and the subsequent site-directed mutagenesis experiments proved this prediction. Our results demonstrate AChE competitive inhibition of NPs without CAS participation to gain further understanding of both the neurotoxicity and the curative effect of NPs

Nanoporous Carbon Derived from Core–Shells@Sheets through the Template-Activation Method for Effective Adsorption of Dyes

A novel template-activation method was used to create nanoporous carbon materials derived from core–shells@rGO sheets. The carbon materials were prepared through an acid etching and thermal activation procedure with three-dimensional Fe₃O₄@C@rGO composites as precursors and Fe₃O₄ nanoparticles as the structural template. The activation at different temperatures could provide materials with different specific surface areas. The unique nanoporous structures with large surface areas are ideal adsorbents. The nanoporous carbon materials were used as adsorbents for the removal of rhodamine B (Rh-B). C@rGO-650 illustrated better adsorption performance than the other synthesized adsorbents. It displayed good recyclability, and its highest adsorption capacity reached up to 14.8 L·g^–1. The remarkable adsorption properties make nanoporous carbon a useful candidate for wastewater treatment. This template-activation method can also broaden the potential applications of core–shells@sheet structures for the construction of nanoporous carbon, which helps to resolve the related energy and environmental issues

Linkage disequilibrium block of <i>NLGN4</i> gene.

<p>The color of each square from light to dark represents the level of LD from low to high. White: complete recombination; blue: partial linkage; red: complete linkage.</p

The distribution of allele frequencies for 6 SNPs in <i>NLGN4</i> gene.

<p>*P value not corrected for the multiple testing.</p

Assays of copy number in <i>SHANK2</i> and <i>SHANK3</i> genes.

<p>The copy number states of five segments in ASD patients were shown in five panels. Panel A: exon7 of <i>SHANK2</i>; Panel B: intron16-exon17 of <i>SHANK2</i>. Panel C: exon25 of <i>SHANK2</i>; Panel D: exon6 of <i>SHANK3</i>; Panel E: exon22 of <i>SHANK3</i>. Each column indicates a patient. All ASD cases showed two copy of <i>SHANK2/SHANK3.</i></p

Differentially expressed miRNAs in susceptible (rice line MDJ8) and resistance (rice line Rb49) reactions.

<p>Samples were collected before inoculation (ck) and at 2, 4, and 24 h after inoculation of <i>Xoo</i>. A. Number of differentially expressed miRNAs at different times after inoculation of <i>Xoo</i> in Rb49 and MDJ8 compared with corresponding mock-inoculated plants. B. Number of differentially expressed miRNAs in Rb49 compared with MDJ8.</p