Novel Ratiometric Electrochemical Biosensor for Determination of Cytokeratin 19 Fragment Antigen 21-1 (Cyfra-21-1) as a Lung Cancer Biomarker

Previous studies confirm that aberrant expression of cytokeratin 19 fragment antigen 21-1 (cyfra-21-1) is highly correlated with non-small cell lung cancer (NSCLC). Herein, a proportional electrochemical immunosensor based upon a methylene blue/cadmium telluride/molybdic sulfide (MB/CdTe/MoS2) nanocomposite was successfully fabricated for detecting tumor marker cyfra-21-1. The result indicates that MB/CdTe/MoS2 modified on the surface of a glassy carbon electrode (GCE) supplies a large surface area for immobilizing primary antibodies (Ab1), ensuring high selectivity and sensitivity. To further amplify the sensitivity of the biosensor, ferrocenecarboxylic acid (Fc-COOH) linked with amino-functionalized secondary antibodies through amido bond (Ab2-Fc) as the “signal-on” probe and MB-modified with MoS2 with a large specific surface area as the “signal-off” probe increase the number of active sites for integration of Ab2-Fc/Ag/BSA/Ab1/MB/CdTe/MoS2/GCE electrode with the linker cyfra-21-1 (Ag). Meanwhile, CdTe accelerates the electron transfer and enhances the MB current, improving the sensitivity and detection limit. The presence of cyfra-21-1 led to both the decreasing response of MB and increasing current responses of Fc upon the electrode. Based upon this strategy, the determination of cyfra-21-1 was achieved in a linear range from 10 pg/mL to 10,000 ng/mL with the lowest detectable concentration of 10 pg/mL (signal-to-noise ratio of 3). The electrochemical immunosensor performs a sensitive determination of cyfra-21-1, possibly providing a practical strategy for the clinical analysis of lung cancer.</p

Data_Sheet_1_Bioassay-guided isolation of three new alkaloids from Suillus bovinus and preliminary mechanism against ginseng root rot.docx

In order to control the occurrence of ginseng root rot caused by Fusarium solani (Mart.) Sacc., the antifungal compounds of the mushroom Suillus bovinus were investigated. And three new alkaloids (1–3), named bovinalkaloid A–C, along with one known analog (4), were isolated and identified by bioassay-guided isolation and spectroscopic analyses. Compound 1 strongly inhibited the mycelial growth and spore germination of F. solani with minimum inhibitory concentration of 2.08 mM. Increases in electrical conductivity, nucleic acid, and protein contents, and decreases in lipid content showed that the membrane permeability and integrity were damaged by compound 1. Compound 1 also increased the contents of malondialdehyde and hydrogen peroxide and the activities of antioxidant enzymes, indicating that lipid peroxidation had taken place in F. solani. Compound 1 may serve as a natural alternative to synthetic fungicides for the control of ginseng root rot.</p

Hyperbranched Acidic Polysaccharide from Green Tea

An acidic tea polysaccharide (ALTPS), isolated from green tea (Camellia sinensis), was characterized as a hyperbranched glycoprotein containing the acidic heteropolysaccharide chains and the protein residues from the results of UV−vis, FTIR, one- and two-dimensional NMR, GC, GC-MS, and amino acid analyses. Solution properties of ALTPS were investigated by static and dynamic light scattering analyses and viscometry. The results indicated that the viscosity behavior of ALTPS exhibited a typical polyelectrolyte effect in distilled water, which may be avoided by adding salts. The low intrinsic viscosity of ALTPS in the solutions (8−15 mL/g) is attributed to its hyperbranched structure. By application of the polymer solution theory, it was revealed that ALTPS was present in a sphere-like conformation in the solutions as a result of the hyperbranched structure. The TEM image further confirmed that ALTPS existed in a spherical conformation in aqueous NaCl solution. Glucose was absorbed by ALTPS, which may be one of blood glucose lowering mechanisms of tea polysaccharides

Table_2_Vesicular Ganglioside GM1 From Breast Tumor Cells Stimulated Epithelial-to-Mesenchymal Transition of Recipient MCF-10A Cells.xlsx

Small extracellular vesicles (sEVs) are a type of membrane structure secreted by cells, which are involved in physiological and pathological processes by participating in intercellular communication. Glycosphingolipids (GSLs) are enriched in sEV and can be delivered to recipient cells. In this study, we found that overexpression of B3GALT4, the glycosyltransferase responsible for ganglioside GM1 synthesis, can induce the epithelial–mesenchymal transition (EMT) process in MCF-10A cells. Moreover, GM1 was verified to be presented on sEV from breast cancer cells. Overexpression of B3GALT4 resulted in elevated vesicular GM1 levels and increased sEV secretion in breast cancer cells. Proteomic analysis revealed that eleven sEV secretion-related proteins were differentially expressed, which might contribute to the altered sEV secretion. Of the identified proteins, 15 oncogenic differentially expressed proteins were documented to be presented in sEV. With the treatment of GM1-enriched sEV from breast cancer cells, the EMT process was induced in recipient non-tumorigenic epithelial MCF-10A cells. Our findings demonstrated that GM1-enriched sEVs derived from breast cancer cells induced the EMT process of recipient cells, which might provide essential information on the biological function of vesicular GM1.</p

Table_1_Vesicular Ganglioside GM1 From Breast Tumor Cells Stimulated Epithelial-to-Mesenchymal Transition of Recipient MCF-10A Cells.docx

Small extracellular vesicles (sEVs) are a type of membrane structure secreted by cells, which are involved in physiological and pathological processes by participating in intercellular communication. Glycosphingolipids (GSLs) are enriched in sEV and can be delivered to recipient cells. In this study, we found that overexpression of B3GALT4, the glycosyltransferase responsible for ganglioside GM1 synthesis, can induce the epithelial–mesenchymal transition (EMT) process in MCF-10A cells. Moreover, GM1 was verified to be presented on sEV from breast cancer cells. Overexpression of B3GALT4 resulted in elevated vesicular GM1 levels and increased sEV secretion in breast cancer cells. Proteomic analysis revealed that eleven sEV secretion-related proteins were differentially expressed, which might contribute to the altered sEV secretion. Of the identified proteins, 15 oncogenic differentially expressed proteins were documented to be presented in sEV. With the treatment of GM1-enriched sEV from breast cancer cells, the EMT process was induced in recipient non-tumorigenic epithelial MCF-10A cells. Our findings demonstrated that GM1-enriched sEVs derived from breast cancer cells induced the EMT process of recipient cells, which might provide essential information on the biological function of vesicular GM1.</p

DataSheet_1_Vesicular Ganglioside GM1 From Breast Tumor Cells Stimulated Epithelial-to-Mesenchymal Transition of Recipient MCF-10A Cells.docx

Small extracellular vesicles (sEVs) are a type of membrane structure secreted by cells, which are involved in physiological and pathological processes by participating in intercellular communication. Glycosphingolipids (GSLs) are enriched in sEV and can be delivered to recipient cells. In this study, we found that overexpression of B3GALT4, the glycosyltransferase responsible for ganglioside GM1 synthesis, can induce the epithelial–mesenchymal transition (EMT) process in MCF-10A cells. Moreover, GM1 was verified to be presented on sEV from breast cancer cells. Overexpression of B3GALT4 resulted in elevated vesicular GM1 levels and increased sEV secretion in breast cancer cells. Proteomic analysis revealed that eleven sEV secretion-related proteins were differentially expressed, which might contribute to the altered sEV secretion. Of the identified proteins, 15 oncogenic differentially expressed proteins were documented to be presented in sEV. With the treatment of GM1-enriched sEV from breast cancer cells, the EMT process was induced in recipient non-tumorigenic epithelial MCF-10A cells. Our findings demonstrated that GM1-enriched sEVs derived from breast cancer cells induced the EMT process of recipient cells, which might provide essential information on the biological function of vesicular GM1.</p

Highly Selective and Efficient Rearrangement of Biomass-Derived Furfural to Cyclopentanone over Interface-Active Ru/Carbon Nanotubes Catalyst in Water

Biomass-derived furfural was efficiently converted to valuable cyclopentanone over interface-active Ru/carbon nanotubes (CNTs) catalyst in water. The effect of reaction conditions, including furfural concentration, reaction temperature, hydrogen pressure, speed of stirring, and reaction time on the catalytic performance of Ru/CNTs has been studied in detail. The furfural conversion of 99% and cyclopentanone selectivity of 91% were efficiently achieved at very low concentration of Ru/CNTs catalyst (0.26 wt % Ru) under mild reaction conditions (1 MPa H₂, 160 °C, 500 rpm). Possible reaction pathways of furfural transformation over Ru/CNTs nanoparticles in water are proposed

Servo-Integrated Patterned Media by Hybrid Directed Self-Assembly

A hybrid directed self-assembly approach is developed to fabricate unprecedented servo-integrated bit-patterned media templates, by combining sphere-forming block copolymers with 5 teradot/in.² resolution capability, nanoimprint and optical lithography with overlay control. Nanoimprint generates prepatterns with different dimensions in the data field and servo field, respectively, and optical lithography controls the selective self-assembly process in either field. Two distinct directed self-assembly techniques, low-topography graphoepitaxy and high-topography graphoepitaxy, are elegantly integrated to create bit-patterned templates with flexible embedded servo information. Spinstand magnetic test at 1 teradot/in.² shows a low bit error rate of 10^–2.43, indicating fully functioning bit-patterned media and great potential of this approach for fabricating future ultra-high-density magnetic storage media

A Nuclear Magnetic Resonance-Based Structural Rationale for Contrasting Stoichiometry and Ligand Binding Site(s) in Fatty Acid-Binding Proteins

Liver fatty acid-binding protein (LFABP) is a 14 kDa cytosolic polypeptide, differing from other family members in the number of ligand binding sites, the diversity of bound ligands, and the transfer of fatty acid(s) to membranes primarily via aqueous diffusion rather than direct collisional interactions. Distinct two-dimensional 1H−15N nuclear magnetic resonance (NMR) signals indicative of slowly exchanging LFABP assemblies formed during stepwise ligand titration were exploited, without determining the protein−ligand complex structures, to yield the stoichiometries for the bound ligands, their locations within the protein binding cavity, the sequence of ligand occupation, and the corresponding protein structural accommodations. Chemical shifts were monitored for wild-type LFABP and an R122L/S124A mutant in which electrostatic interactions viewed as being essential to fatty acid binding were removed. For wild-type LFABP, the results compared favorably with the data for previous tertiary structures of oleate-bound wild-type LFABP in crystals and in solution: there are two oleates, one U-shaped ligand that positions the long hydrophobic chain deep within the cavity and another extended structure with the hydrophobic chain facing the cavity and the carboxylate group lying close to the protein surface. The NMR titration validated a prior hypothesis that the first oleate to enter the cavity occupies the internal protein site. In contrast, 1H and 15N chemical shift changes supported only one liganded oleate for R122L/S124A LFABP, at an intermediate location within the protein cavity. A rationale based on protein sequence and electrostatics was developed to explain the stoichiometry and binding site trends for LFABPs and to put these findings into context within the larger protein family

Additional file 1 of Downregulation of MAL2 inhibits breast cancer progression through regulating β-catenin/c-Myc axis

Supplementary Material