Alzheimer’s disease (AD) is a neurodegenerative disease with increasing prevalence worldwide, while there are no effective drugs at present. Curcumin, a natural polyphenolic substance isolated from ...turmeric, is a promising natural compound to combat AD, but its pharmacology remains to be fully understood for its poor in vivo bioavalibility. Inspired by the recently reported associations between gut microbiota and AD development, the present study investigated the interactions of curcumin with gut microbiota of APP/PS1 double transgenic mice from two directions: (i) curcumin influences gut microbiota, and (ii) gut microbiota biotransform curcumin. It was found that curcumin administration tended to improve the spatial learning and memory abilities and reduce the amyloid plaque burden in the hippocampus of APP/PS1 mice. On the one hand, curcumin administration altered significantly the relative abundances of bacterial taxa such as
Bacteroidaceae
,
Prevotellaceae
,
Lactobacillaceae
, and
Rikenellaceae
at family level, and
Prevotella
,
Bacteroides
, and
Parabacteroides
at genus level, several of which have been reported to be key bacterial species associated with AD development. On the other hand, a total of 8 metabolites of curcumin biotransformed by gut microbiota of AD mice through reduction, demethoxylation, demethylation and hydroxylation were identified by HPLC-Q-TOF/MS, and many of these metabolites have been reported to exhibit neuroprotective ability. The findings provided useful clues to understand the pharmacology of curcumin and microbiome-targeting therapies for AD.
A 3D regenerated cellulose/graphene oxide (RCE/GO) composite aerogel was prepared via a simple and effective freeze-drying method. The prepared RCE/GO composite aerogel exhibited outstanding dye ...elimination efficiency, adsorption-rate and reusability for methylene blue (MB), which was attributed to the perfect 3D network structure and large specific surface area of GO. Also, the adsorption of RCE/GO composite aerogel was driven by electrostatic interactions and followed pseudo-second-order kinetic and Langmuir isotherm model.
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•RCE/GO composite aerogel was easily prepared via a novel and feasible method.•RCE/GO exhibits good adsorption of MB dye due to the presence of GO.•The adsorption was driven by electrostatic interactions and followed pseudo-second-order kinetic and Langmuir isotherm model.
Composite aerogels consisting of graphene oxide (GO) and regenerated cellulose (RCE) were prepared via a solution mixing-regeneration and freeze-drying process. The prepared RCE/GO composites aerogel exhibited 3D network thin-walled pore structure with large specific surface area, also favorable compression recovery capability, outstanding dye elimination efficiency and reusability after the addition of GO. With addition of only 0.5 wt% GO, the methylene blue (MB) elimination efficiency of RCE/GO aerogel reached 99.0% and still remained at 90.5% after five-time reused under oscillation adsorption. In addition, our research indicates that the excellent MB adsorption of RCE/GO composite aerogel was driven by electrostatic interactions and followed a pseudo-second-order adsorption kinetic and monolayer Langmuir adsorption isotherm. This investigation provides the guidance for the development of green environmental adsorbents to remove organic dye from sewage water.
Over the past decades, molecular knots and links have captivated the chemical community due to their promising mimicry properties in molecular machines and biomolecules and are being realized with ...increasing frequency with small molecules. Herein, we describe how to utilize stacking interactions and hydrogen-bonding patterns to form trefoil knots, figure-eight knots and 2catenanes. A transformation can occur between the unique trefoil knot and its isomeric boat-shaped tetranuclear macrocycle by the complementary concentration effect. Remarkably, the realization and authentication of the molecular figure-eight knot with four crossings fills the blank about 4
knot in knot tables. The 2catenane topology is obtained because the selective naphthalenediimide (NDI)-based ligand, which can engender favorable aromatic donor-acceptor π interactions due to its planar, electron-deficient aromatic surface. The stacking interactions and hydrogen-bond interactions play important roles in these self-assembly processes. The advantages provide an avenue for the generation of structurally and topologically complex supramolecular architectures.
We engineered covalently circularized nanodiscs (cNDs) which, compared with standard nanodiscs, exhibit enhanced stability, defined diameter sizes and tunable shapes. Reconstitution into cNDs ...enhanced the quality of nuclear magnetic resonance spectra for both VDAC-1, a β-barrel membrane protein, and the G-protein-coupled receptor NTR1, an α-helical membrane protein. In addition, we used cNDs to visualize how simple, nonenveloped viruses translocate their genomes across membranes to initiate infection.
Background
Postoperative cognitive dysfunction (POCD) is one of the common postoperative complications, which is more common in aged patients. POCD mainly manifests as cognitive function changes ...after surgery, such as memory decline and inattention. In some severe cases, patients may suffer from personality changes and (or) social behavior decline. The aim of the current study is to confirm the effect and elucidate the mechanism of bone marrow mesenchymal stem cells (BMSCs) in postoperative central inflammatory mice.
Methods
Mice were randomly assigned to four groups: sham, sham+BMSCs, model, and BMSCs group. In the model group, mice were intraperitoneally injected 8 mg/kg per day lipopolysaccharide for 5 days. In sham+BMSCs and BMSCs group, BMSCs (1 × 10
7) in 100 µL saline were injected into sham mice and model mice, respectively.
Results
In the model group, transforming growth factor β (TGF‐β) protein expression was significantly increased, compared with that in the sham group. BMSCs were treated into postoperative central inflammatory mice, which resulted in a decreased of TGF‐β protein expression. TGF‐β and smad2 protein expression were suppressed, and apoptosis rate and inflammation were inhibited in coculture with BMSCs. The suppression of TGF‐β inhibited the effects of BMSCs on apoptosis rate and inflammation in postoperative central inflammatory through a smad2 signaling pathway. The promotion of TGF‐β reduced the effects of BMSCs on apoptosis rate and inflammation in postoperative central inflammatory through a smad2 signaling pathway.
Conclusion
The present study demonstrates that BMSCs regulates TGF‐β to adjust neuroinflammation in postoperative central inflammatory mice.
Abstract
Evidence-based forecasting and estimation indicate that Arctic shipping will grow in volume and diversify over the coming years, and associated challenges need to be met without compromising ...too much either the growing demand for shipping or the sustainability of the Arctic environment. Various initiatives have been put forward by the shipping industry, States and international regulatory bodies to reduce the negative impact of the use of marine fuels on the marine environment in the Arctic. This article examines the current regulatory regime concerning use of marine fuels in the Arctic; discusses how to apply legal principles and approaches to close regulatory gaps and harmonise existing efforts to prevent, reduce and control marine pollution from fuel use; and analyses the underlining architecture for designing a regulatory regime, from a technical perspective, for the use of marine fuels by Arctic shipping.
The Toll/interleukin-1 receptor (TIR) domain is a key component of immune receptors that identify pathogen invasion in bacteria, plants and animals
. In the bacterial antiphage system Thoeris, as ...well as in plants, recognition of infection stimulates TIR domains to produce an immune signalling molecule whose molecular structure remains elusive. This molecule binds and activates the Thoeris immune effector, which then executes the immune function
. We identified a large family of phage-encoded proteins, denoted here as Thoeris anti-defence 1 (Tad1), that inhibit Thoeris immunity. We found that Tad1 proteins are 'sponges' that bind and sequester the immune signalling molecule produced by TIR-domain proteins, thus decoupling phage sensing from immune effector activation and rendering Thoeris inactive. Tad1 can also efficiently sequester molecules derived from a plant TIR-domain protein, and a high-resolution crystal structure of Tad1 bound to a plant-derived molecule showed a unique chemical structure of 1 ''-2' glycocyclic ADPR (gcADPR). Our data furthermore suggest that Thoeris TIR proteins produce a closely related molecule, 1''-3' gcADPR, which activates ThsA an order of magnitude more efficiently than the plant-derived 1''-2' gcADPR. Our results define the chemical structure of a central immune signalling molecule and show a new mode of action by which pathogens can suppress host immunity.
G-protein-coupled receptors (GPCRs) are the largest superfamily of transmembrane proteins and the targets of over 30% of currently marketed pharmaceuticals. Although several structures have been ...solved for GPCR-G protein complexes, few are in a lipid membrane environment. Here, we report cryo-EM structures of complexes of neurotensin, neurotensin receptor 1 and Gα
β
γ
in two conformational states, resolved to resolutions of 4.1 and 4.2 Å. The structures, determined in a lipid bilayer without any stabilizing antibodies or nanobodies, reveal an extended network of protein-protein interactions at the GPCR-G protein interface as compared to structures obtained in detergent micelles. The findings show that the lipid membrane modulates the structure and dynamics of complex formation and provide a molecular explanation for the stronger interaction between GPCRs and G proteins in lipid bilayers. We propose an allosteric mechanism for GDP release, providing new insights into the activation of G proteins for downstream signaling.
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