Table_1_De novo LAMP2 insertion mutation causes cardiac-only Danon disease: A case report.xlsx

Danon disease is a rare disease caused by glycogen storage lysosomal disorder. It is related to the pathogenic mutation of the LAMP2 gene. In this case report, we present a patient with a novel pathogenic mutation (c.764_765insGA) with cardiac-only symptoms. Her family members do not carry the same mutation she does, suggesting this is a de novo mutation. Further tests revealed vacuoles and glycogen disposition in the patient's heart tissue and a significant decrease in LAMP2 protein expression. Protein structure remodeling of LAMP2 predicted that the mutant protein has conformational change lacking an important transmembrane domain, subsequently causing protein destabilization.</p

Image_1_De novo LAMP2 insertion mutation causes cardiac-only Danon disease: A case report.pdf

Danon disease is a rare disease caused by glycogen storage lysosomal disorder. It is related to the pathogenic mutation of the LAMP2 gene. In this case report, we present a patient with a novel pathogenic mutation (c.764_765insGA) with cardiac-only symptoms. Her family members do not carry the same mutation she does, suggesting this is a de novo mutation. Further tests revealed vacuoles and glycogen disposition in the patient's heart tissue and a significant decrease in LAMP2 protein expression. Protein structure remodeling of LAMP2 predicted that the mutant protein has conformational change lacking an important transmembrane domain, subsequently causing protein destabilization.</p

Biosynthesis of the High-Value Plant Secondary Product Benzyl Isothiocyanate via Functional Expression of Multiple Heterologous Enzymes in <i>Escherichia coli</i>

Plants produce a wide variety of secondary metabolites that are highly nutraceutically and pharmaceutically important. Isothiocyanates, which are found abundantly in cruciferous vegetables, are believed to reduce the risk of several types of cancers and cardiovascular diseases. The challenges arising from the structural diversity and complex chemistry of these compounds have spurred great interest in producing them in large amounts in microbes. In this study, we aimed to synthesize benzyl isothiocyanate in <i>Escherichia coli</i> via gene mining, pathway engineering, and protein modification. Two chimeric cytochrome P450 enzymes were constructed and functionally expressed in <i>E. coli</i>. The <i>E. coli</i> cystathionine β-lyase was used to replace the plant-derived C-S lyase; its active form cannot be expressed in <i>E. coli</i>. Suitable desulfoglucosinolate:PAPS sulfotransferase from <i>Arabidopsis thaliana</i> ecotype Col-0 and myrosinase from <i>Brevicoryne brassicae</i> were successfully mined from the database. Biosynthesis of benzyl isothiocyanate by the combined expression of the optimized enzymes <i>in vitro</i> was confirmed by gas chromatography–mass spectrometry analysis. This study provided a proof of concept for the production of benzyl isothiocyanate by microbially produced enzymes and, importantly, laid the groundwork for further metabolic engineering of microbial cells for the production of isothiocyanates

Reconstructing Biosynthetic Pathway of the Plant-Derived Cancer Chemopreventive-Precursor Glucoraphanin in <i>Escherichia coli</i>

Epidemiological data confirmed a strong correlation between regular consumption of cruciferous vegetables and lower cancer risk. This cancer preventive property is mainly attributed to the glucosinolate products, such as glucoraphanin found in broccoli that is derived from methionine. Here we report the first successful reconstruction of the complete biosynthetic pathway of glucoraphanin from methionine in <i>Escherichia coli</i> <i>via</i> gene selection, pathway design, and protein engineering. We used branched-chain amino transferase 3 to catalyze two transamination steps to ensure the purity of precursor molecules and used cysteine as a sulfur donor to simplify the synthesis pathway. Two chimeric cytochrome P450 enzymes were engineered and expressed in <i>E. coli</i> functionally. The original plant C–S lyase was replaced by the <i>Neurospora crassa</i> hercynylcysteine sulfoxide lyase. Other pathway enzymes were successfully mined from <i>Arabidopsis thaliana</i>, <i>Brassica rapa</i>, and <i>Brassica oleracea</i>. Biosynthesis of glucoraphanin upon coexpression of the optimized enzymes <i>in vivo</i> was confirmed by liquid chromatography–tandem mass spectrometry analysis. No other glucosinolate analogues (except for glucoiberin) were identified that could facilitate the downstream purification processes. Production of glucoraphanin in this study laid the foundation for microbial production of such health-beneficial glucosinolates in a large-scale

Additional file 1: of Single-cell genome-wide bisulfite sequencing uncovers extensive heterogeneity in the mouse liver methylome

Supplementary materials. The supplementary materials include Figures S1–S3, Tables S1–S3, and Supplementary Experimental Procedures. (PDF 473 kb

Liriopesides B inhibited cell growth and decreased CA125 level in human ovarian cancer A2780 cells

<p>To study the effect of liriopesides B on cell growth curve, cell doubling time, the activity of tumour marker CA125 and alkaline phosphatase (AKP) in human ovarian cancer A2780 cells. Both cell growth curve and doubling time were studied by MTT assay, CA125 level and AKP activity were determined by respective kits. Results showed that liriopesides B could shift down the A2780 cells growth curve in a dose-time-dependent manner and inhibit the proliferation in A2780 cells with the maximum inhibitory rate 94.462% at 120 h, the doubling time was prolonged too. CA125 level was decreased in a dose-dependent way as well as AKP activity. Liriopesides B exhibited potential anticancer activity against human ovarian cancer A2780 cells.</p

Optimization of Alkyl Side Chain Length in Polyimide for Gate Dielectrics to Achieve High Mobility and Outstanding Operational Stability in Organic Transistors

Alkyl chain modification strategies in both organic semiconductors and inorganic dielectrics play a crucial role in improving the performance of organic thin-film transistors (OTFTs). Polyimide (PI) and its derivatives have received extensive attention as dielectrics for application in OTFTs because of flexibility, high-temperature resistance, and low cost. However, low-temperature solution processing PI-based gate dielectric for flexible OTFTs with high mobility, low operating voltage, and high operational stability remains an enormous challenge. Furthermore, even though di-n-decyldinaphtho[2,3-b:2′,3′-f]thieno[3,2-b]thiophene (C10-DNTT) is known to have very high mobility as an air-stable and high-performance organic semiconductor, the C10-DNTT-based TFTs on the PI gate dielectrics still showed relatively low mobility. Here, inspired by alkyl side chain engineering, we design and synthesize a series of PI materials with different alkyl side chain lengths and systematically investigate the PI surface properties and the evolution of organic semiconductor morphology deposited on PI surfaces during the variation of alkyl side chain lengths. It is found that the alkyl side chain length has a critical influence on the PI surface properties, as well as the grain size and molecular orientation of semiconductors. Good field-effect characteristics are obtained with high mobilities (up to 1.05 and 5.22 cm2/Vs, which are some of the best values reported to date), relatively low operating voltage, hysteresis-free behavior, and high operational stability in OTFTs. These results suggest that the strategy of optimizing alkyl side-chain lengths opens up a new research avenue for tuning semiconductor growth to enable high mobility and outstanding operational stability of PI-based OTFTs

Self-Healing Surface Hydrophobicity by Consecutive Release of Hydrophobic Molecules from Mesoporous Silica

The paper reports a novel approach to achieve self-healing surface hydrophobicity. Mesoporous silica is used as the reservoir for hydrophobic molecules, i.e., octadecylamine (ODA), that can release and refresh the surface hydrophobicity consecutively. A polymdopamine layer is used to further encapsulate silica–ODA, providing a reactive layer, governing release of the underlying ODA, and improving the dispersivity of silica nanoparticles in bulk resin. The approach arrives at self-healing (super)­hydrophobicity without using any fluoro-containing compounds

Durable, Transparent, and Hot Liquid Repelling Superamphiphobic Coatings from Polysiloxane-Modified Multiwalled Carbon Nanotubes

Although encouraging progress in the field of superamphiphobic coatings has been obtained, the superamphiphobic coatings with high durability, transparency, and repellency to hot liquids are very rare. Here, durable, transparent, and hot liquid-repelling superamphiphobic coatings were successfully prepared using polysiloxane-modified multiwalled carbon nanotubes (MWCNTs@POS) as the templates. The hydrolytic condensation of <i>n</i>-hexadecyltrimethoxysilane (HDTMS) and tetraethoxysilane on the surface of MWCNTs formed MWCNTs@POS, which are highly dispersible in toluene. The superamphiphobic coatings were prepared by spray-coating the homogeneous suspension of MWCNTs@POS in toluene onto glass slides, calcination in air to form the silica nanotubes (SNTs), and then modification with 1<i>H</i>,1<i>H</i>,2<i>H</i>,2<i>H</i>-perfluorodecyltrichlorosilane in dry toluene. The changes in the surface microstructure, surface chemical composition, and wettability were characterized by various techniques such as scanning electron microscopy, transmission electron microscopy, and X-ray photoelectron spectroscopy. It was found that the microstructures of the SNTs have great influences on superamphiphobicity and transparency of the coatings and can be regulated by the concentration of HDTMS and the diameter of MWCNTs. The SNTs with tunable wall thickness and diameter could be obtained using the method. The superamphiphobic coatings showed high contact angles and low sliding angles for various cool and hot liquids of different surface tensions. The superamphiphobic coatings also exhibited high transparency and comprehensive durability

Summary results of simple effect analyses.

<p>*: the interaction between two factors or among three ones;</p><p>NS: not significant.</p><p>Summary results of simple effect analyses.</p