• Roach Hvass posted an update 1 day, 11 hours ago

    This sustainable all-organic nanocomposite is a promising candidate for biodegradable disposable commodities.A series of 11-substituted sampangine derivatives have been designed, synthesized, and tested for their ability to inhibit cholinesterase. Their chelating ability and selectivity for Cu2+ over other biologically relevant metal ions were demonstrated by isothermal titration calorimetry. Their blood-brain barrier permeability was also tested by parallel artificial membrane permeation assay. Among the synthesized derivatives, compound 11 with the strong anti-acetylcholinesterase activity, high blood-brain barrier penetration ability and high binding affinity to Cu2+ was selected for further research. Western blotting analysis, transmission electron microscopy, DCFH-DA assay and paralysis experiment indicated that compound 11 suppressed the formation of Cu2+-Aβ complexes, alleviated the Cu2+ induced neurotoxicity and inhibited the production of ROS catalyzed by Cu2+ in Aβ42 transgenic C. GS-441524 elegans. Moreover, compound 11 also inhibited the expressions of proinflammatory cytokines, such as NO, TNF-α, IL-6 and IL-1β, induced by Cu2+ + Aβ1-42 in BV2 microglial cells. In general, this work provided new insights into the design and development of potent metal-chelating agents for AD treatment.The prion protein (PrP) misfolding to its infectious form is critical to the development of prion diseases, whereby various ligands are suggested to participate, such as copper and nucleic acids (NA). The PrP globular domain was shown to undergo NA-driven liquid-liquid phase separation (LLPS); this latter may precede pathological aggregation. Since Cu(II) is a physiological ligand of PrP, we argue whether it modulates phase separation altogether with nucleic acids. Using recombinant PrP, we investigate the effects of Cu(II) (at 6 M equivalents) and a previously described PrP-binding GC-rich DNA (equimolarly to protein) on PrP conformation, oligomerization, and phase transitions using a range of biophysical techniques. Raman spectroscopy data reveals the formation of the ternary complex. Microscopy suggests that phase separation is mainly driven by DNA, whereas Cu(II) has no influence. Our results show that DNA can be an adjuvant, leading to the structural conversion of PrP, even in the presence of an endogenous ligand, copper. These results provide new insights into the role of Cu(II) and NA on the phase separation, structural conversion, and aggregation of PrP, which are critical events leading to neurodegeneration.In this study, an uncommon enzymatic-fingerprinting workflow, was proposed for characterization and discrimination of mushroom polysaccharides (MPs) by hydrophilic interaction liquid chromatography-negative electrospray mass spectrometry (HILIC-ESI–MS). Firstly, the HILIC-ESI–MS was used to screen and identify the enzymatic digestion products of MPs using HILIC-Orbitrap based on full scan and MS/MS modes. Secondly, a targeted structural-fingerprinting of polysaccharides (SFP) was built in a multiple-ion monitoring (MIM) mode using the same HILIC separation with a triple quadrupole MS. Thirdly, a case study of polysaccharides in Hericium erinaceus fruiting bodies (HEP) was performed to obtain the expected SFP based on dextranase digestion that allows for visual discrimination of polysaccharides from other five edible mushrooms attributed to Agrocybe cylindracea, Arimillaria mellea, Flammulina velutipes, Pleurotus eryngii, and Lentinula edodes. Furthermore, a major structural backbone of HEP was unveiled by occurrence of → 6(Hex)1 → along with multiple possible substitutions including of terminal GalA, Fuc, acetyl, → 4Hex1 →, and → 3Hex1 →. Finally, the similarity analysis, hierarchical cluster analysis (HCA), and partial least squares discriminant analysis (PLS-DA) were performed to visualize various MPs. As a result, the enzymatic-fingerprinting workflow presents an effective example for quality evaluation of fungi polysaccharides using a SFP strategy.Tissue adhesives have been developed for sealing tissue damaged in surgery. Among these, sheet-type adhesives require a relatively long time to adhere to biological tissue under wet conditions. To address this clinical problem, we fabricated a tissue-adhesive fiber sheet (AdFS) based on decanyl group (C10) modified Alaska pollock-derived gelatin (C10-ApGltn) using electrospinning. Ultraviolet (UV) irradiation of the AdFS was performed to increase the affinity between the AdFS and wet biological tissue by introducing hydrophilic functional groups. The UV irradiated AdFS (UV-C10-AdFS) strongly adhered to porcine pleura within 2 min under wet conditions and showed higher burst strength compared with the original ApGltn (Org-ApGltn) sheet. Hematoxylin-eosin stained sections revealed that a dense UV-C10-AdFS layer remained on the surface of the porcine pleura even after burst strength measurement. Moreover, UV-C10-AdFS has excellent cytocompatibility and efficiently supports the growth of L929 cells. UV-C10-AdFS is a promising adhesive material for sealing wet biological tissue.In the present study, eleven novel complete mitogenomes of Boletus were assembled and compared. The eleven complete mitogenomes were all composed of circular DNA molecules, with sizes ranging from 32,883 bp to 48,298 bp. The mitochondrial gene arrangement of Boletus varied greatly from other Boletales mitogenomes, and gene position reversal were observed frequently in the evolution of Boletus. Across the 15 core protein-coding genes (PCGs) tested, atp9 had the least and rps3 had the largest genetic distances among the eleven Boletus species, indicating varied evolution rates of core PCGs. In addition, the Ka/Ks value for nad3 gene was >1, suggesting that this gene was subject to possible positive selection pressure. Comparative mitogenomic analysis indicated that the intronic region was significantly correlated with the size of mitogenomes in Boletales. Two large-scale intron loss events were detected in the evolution of Boletus. Phylogenetic analyses based on a combined mitochondrial gene dataset yielded a well-supported (BPP ≥ 0.