Driving force to detect Alzheimer's disease biomarkers: application of a thioflavine T@Er-MOF ratiometric fluorescent sensor for smart detection of presenilin 1, amyloid ß-protein and acetylcholine.

Currently, the highly sensitive detection of Alzheimer's Disease (AD) biomarkers, namely presenilin 1, amyloid ß-protein (Aß), and acetylcholine (ACh), is vital to helping us prevent and diagnose AD. In this work, a novel metal-organic framework [Er(L)(DMF)1.27]n (Er-MOF) (H3L = terphenyl-3,4'',5-tricarboxylic acid) has been synthesized by solvothermal and ultrasonic methods. Further, through the post-synthesis assembly strategy, the fluorescent dye thioflavine T (ThT) has been introduced into Er-MOF to construct a dual-emission ThT@Er-MOF ratiometric fluorescent sensor. This is the first time that ThT@Er-MOF has been successfully applied in the highly sensitive detection of three main Alzheimer's disease biomarkers in the cerebrospinal fluid through three different low cost and facile detection strategies. Firstly, with the spilted DNA strategy, this is the first time that ThT@Er-MOF can be applied in the label-free detection of SSODN (part of the presenilin 1 gene). Secondly, for the detection of Aß, because ThT can be specifically combined with Aß and has an excellent characteristic fluorescence band, the dual-emission ThT@Er-MOF sensor can be selectively applied to detect Aß over the analog protein, which shows far more sensitivity than other Aß sensors. Thirdly, through the acetylcholine esterase (AchE) enzymatic cleavage and release strategy, ThT@Er-MOF enhances the detection of acetylcholine (ACh) with a low limit of detection (LOD) value (0.03226 nM). It should be noticed that the three different detection methods are low cost and facile. This study also provides the first example of utilizing laser scanning confocal microscopy (LSCM) to investigate the fluorescence resonance energy transfer (FRET) detection mechanism by ThT@Er-MOF in more detail. The location of FRET occurrence and FRET efficiency can also be investigated by LSCM, which can be helpful to understand the FRET detection process by these unique MOF-based hybrid materials.

HSF4/COIL complex-dependent R-loop mediates ultraviolet-induced inflammatory skin injury.

Intense ultraviolet (UV) exposure can cause phototoxic reactions, such as skin inflammation, resulting in injury. UV is a direct cause of DNA damage, but the mechanisms underlying transcriptional regulation within cells after DNA damage are unclear. The bioinformatics analysis of transcriptome sequencing data from UV-irradiated and non-UV-irradiated skin showed that transcription-related proteins, such as HSF4 and COIL, mediate cellular response to UV irradiation. HSF4 and COIL can form a complex under UV irradiation, and the preference for binding target genes changed because of the presence of a large number of R-loops in cells under UV irradiation and the ability of COIL to recognize R-loops. The regulation of target genes was altered by the HSF4-COIL complex, and the expression of inflammation and ageing-related genes, such as Atg7, Tfpi, and Lims1, was enhanced. A drug screen was performed for the recognition sites of COIL and R-loop. N6-(2-hydroxyethyl)-adenosine can competitively bind COIL and inhibit the binding of COIL to the R-loop. Thus, the activation of downstream inflammation-related genes and inflammatory skin injury was inhibited.

[Effects of heterogeneous habitats on the coexistence of aquatic ecotype Alternanthera philoxeroides and Paspalum paspaloides]. / 异质生境对水生型空心莲子草-åŒç©—é›€ç¨—å ±å­˜çš„å½±å“.

Species coexistence depends on the comprehensive effects of biological properties and habitat heterogeneity. Based on a large-scale field survey (21°-35° N), we compared the differences on morphological and stoichiometric characteristics between the invasive aquatic species Alternanthera philoxeroides and the native co-occurring species Paspalum paspaloides, and examined the effects of environmental factors on such differences. The results showed that the coverage and importance value (IV) of A. philoxeroides were all significantly greater than P. paspa-loides (34.3% and 104.0%, respectively), whereas the height of P. paspaloides was significantly greater than A. philoxeroides (13.8%). Moreover, the total nitrogen concentration (TN) and N:P of A. philoxeroides were significantly greater than those of P. paspaloides (55.1% and 55.8%, respectively), whereas the total carbon concentration (TC) and C:N of P. paspaloides were significantly greater than those of A. philoxeroides (4.1% and 83.8%, respectively). A. philoxeroides coverage increased with the increases of longitude, and its abundance increased with the increases of water nitrate concentration and longitude, while its IV increased with the increases of water ammonium concentration. However, the coverage, abundance, and IV of P. paspaloides decreased with the increases of ammonium concentration. C:N of A. philoxeroides decreased with the increase of ammonium concentration. Increased mean annual temperature and mean annual precipitation increased C:N but decreased N:P of P. paspa-loides. The C:P of both species decreased with the increases of ammonium concentration and electrical conductivity. N:P of A. philoxeroides was little affected by environment. These results indicated that A. philoxeroides had greater coverage and N absorption capacity than P. paspaloides, and that enriched water nitrogen would aggravate the invasion of A. philoxeroides. Meanwhile, P. paspaloides improved its C-assimilate reserves and chose the growth competition strategy for resisting A. philoxeroides invasion under the superior hydrothermal conditions. Different responses to environmental changes contributed to their coexistence in aquatic ecosystem.

Preparation of Dual-Template Epitope Imprinted Polymers for Targeted Fluorescence Imaging and Targeted Drug Delivery to Pancreatic Cancer BxPC-3 Cells.

Molecularly imprinted polymers were commonly used for drug delivery. However, single-template molecularly imprinted polymers often fail to achieve both drug delivery and precise targeting. To address this issue, a dual-template molecularly imprinted polymer nanoparticle used for targeted diagnosis and drug delivery for pancreatic cancer BxPC-3 cells (FH-MIPNPs) was prepared. In the FH-MIPNPs, the 71-80 peptide of human fibroblast growth-factor-inducible 14 modified with glucose (Glu-FH) and bleomycin (BLM) were used as templates simultaneously, so that the FH-MIPNPs could load BLM and bind to the BxPC-3 cells, which overexpress human fibroblast growth-factor-inducible 14 (FN14). Targeted imaging experiments in vitro show that the FH-MIPNPs could specifically target BxPC-3 cells and that there is no targeting effect on cells without expression of FN14. In vivo antitumor experiment results demonstrated that the FH-MIPNP-loaded BLM (FH-MIPNPs/BLM) could inhibit the growth of xenografts tumor of BxPC-3 (tumor volume increased to 1.05×), which shows that FH-MIPNPs/BLM had obvious targeted therapeutic effect compared to the other three control groups of BLM, FH-NIPNPs/BLM, and physiological saline (tumor volume increased to 1.5×, 1.6×, and 2.4×, respectively). What is more, FH-MIPNPs have low biotoxicity through toxicity experiments in vitro and in vivo, which is favorable toward making molecularly imprinted polymers an effective platform for tumor-targeted imaging and therapy.

Structural investigation of a novel heteropolysaccharide from the fruiting bodies of Boletus edulis.

A novel water-soluble heteropolysaccharide, BEPF1, was isolated from the fruiting bodies of Boletus edulis with boiling water extraction and purified by Sephacryl S-300, with a molecular weight of 1.08×10(4)Da. Sugar composition of BEPF1 showed that it was composed of l-fucose, d-mannose, d-glucose and d-galactose in the ratio of 0.21:0.23:1.17:1.00. Methylation analysis together with (1)H, (13)C and 2D NMR spectroscopy established that BEPF1 was consisted of α-d-(1→6)-galactopyranan backbone with a terminal of α-l-fucosyl unit on O-2 of the 2-d-(2→6)-galactosyl units, ß-d-(1→6)-4-O-Me-glucopyranan and ß-d-(1→6)-glucopyranan backbone with a terminal ß-d-glucosyl unit and it also contained a minor of 2,6-ß-d-Mannopyranan residues.