Hydrogen Attenuates Cognitive Impairment in Rat Models of Vascular Dementia by Inhibiting Oxidative Stress and NLRP3 Inflammasome Activation.

Vascular dementia (VaD) is the second most common form of dementia worldwide. Oxidative stress and neuroinflammation are important factors contributing to cognitive dysfunction in patients with VaD. The antioxidant and anti-inflammatory properties of hydrogen are increasingly being utilized in neurological disorders, but conventional hydrogen delivery has the disadvantage of inefficiency. Therefore, magnesium silicide nanosheets (MSNs) are used to release hydrogen in vivo in larger quantities and for longer periods of time to explore the appropriate dosage and regimen. In this study, it is observed that hydrogen improved learning and working memory in VaD rats in the Morris water maze and Y-maze, which elicits improved cognitive function. Nissl staining of neurons shows that hydrogen treatment significantly improves edema in neuronal cells. The expression and activation of reactive oxygen species (ROS), Thioredoxin-interacting protein (TXNIP), NOD-like receptor protein 3 (NLRP3), caspase-1, and IL-1ß in the hippocampus are measured via ELISA, Western blotting, real-time qPCR, and immunofluorescence. The results show that oxidative stress indicators and inflammasome-related factors are significantly decreased after 7dMSN treatment. Therefore, it is concluded that hydrogen can ameliorate neurological damage and cognitive dysfunction in VaD rats by inhibiting ROS/NLRP3/IL-1ß-related oxidative stress and inflammation.

Metabolic response and correlations between ions and metabolites in Phragmites communis under long-term salinity toxicity.

Phragmites communis has a long history in Songnen grassland of China and has a series of biological, ecological as well as genetic characteristics contributing to its adaptation to the specific local climatic and edaphic conditions. The aim of the present study was to investigate the ions balance and their relationship to metabolites in P. communis under three salinity stress conditions. Results showed that the contents of Na+, Cl-, and SO42- significantly increased in P. communis leaves, while K+, Mg2+, and Mn2+ decreased. Moreover, Na+ and Cl- had significant negative correlations with metabolites involved in the tricarboxylic acid cycle (TCA cycle), and significant positive correlations with glycolysis. The metabolite results showed that high contents of sugars and proline played important roles in developing salinity tolerance, indicating that glycolysis and proline biosynthesis were enhanced; however, this consumes large amounts of energy and likely caused the TCA cycle to be inhibited. The results suggested that P. communis might enhance its salinity tolerance mainly through increased glycolysis and energy consumption. In addition, restricting Na+ accumulation and increasing of Cl-, and rearrangement of metabolite production in P. communis tissues are possible causes of salinity tolerance. Therefore, salinity caused systems alterations in widespread metabolic networks involving TCA cycle, glycolysis and proline biosynthesis. These findings provided new insights for the P. communis metabolic adaptation to salinity and demonstrated the ions balance and metabolites in P. communis are possibly attributable to development of salinity tolerance.

Orthogonal switching of a single supramolecular complex.

Orthogonal control over systems represents an advantage over mono-functional switches as both the nature and order of distinctly different stimuli manifest themselves in a wide array of outcomes. Host-guest complexes with multiple, simultaneously bound guests offer unique opportunities to address a set of 'on' and 'off' states accessible on demand. Here we report cucurbit[8]uril-mediated host-guest heteroternary complexes constructed with both redox- and light-responsive guests in a single, supramolecular entity. The complex responds to orthogonal stimuli in a controlled, reversible manner generating a multifunctional switch between a 'closed' heteroternary complex, a redox-driven 'closed' homoternary complex and a photo-driven 'open' uncomplexed state. We exploit both photochemical and electrochemical control over the supramolecular coding system and its surface wettability to demonstrate the system's complexity, which could be readily visualized on a macroscopic level, thus offering new opportunities in the construction of memory devices.

Triply triggered doxorubicin release from supramolecular nanocontainers.

The synthesis of a supramolecular double hydrophilic block copolymer (DHBC) held together by cucurbit[8]uril (CB[8]) ternary complexation and its subsequent self-assembly into micelles is described. This system is responsive to multiple external triggers including temperature, pH and the addition of a competitive guest. The supramolecular block copolymer assembly consists of poly(N-isopropylacrylamide) (PNIPAAm) as a thermoresponsive block and poly(dimethylaminoethylmethacrylate) (PDMAEMA) as a pH-responsive block. Moreover, encapsulation and controlled drug release was demonstrated with this system using the chemotherapeutic drug doxorubicin (DOX). This triple stimuli-responsive DHBC micelle system represents an evolution over conventional double stimuli-responsive covalent diblock copolymer systems and displayed a significant reduction in the viability of HeLa cells upon triggered release of DOX from the supramolecular micellar nanocontainers.

Size selective supramolecular cages from aryl-bisimidazolium derivatives and cucurbit[8]uril.

A series of bisimidazolium salts were synthesized as novel guests for the macrocyclic host molecule cucurbit[8]uril (CB[8]). These bisimidazolium-CB[8] binary complexes exhibited a unique cage structure with the imidazolium rings acting as lids, leading to a size-dependent binding selectivity by altering the hydrophobic linker between the two imidazolium moieties. This new class of CB[8] complexes was also capable of binding small solvent molecules, including acetone, acetonitrile, diethyl ether, and tetrahydrofuran (THF) in an aqueous environment.

Peptide separation through a CB[8]-mediated supramolecular trap-and-release process.

We demonstrate a supramolecular peptide separation approach by the selective immobilization of peptides bearing an N-terminal tryptophan onto a CB[8]-modified gold substrate, followed by electrochemical release. The CB[8]-stabilized heteroternary complexes were characterized by (1)H NMR, ESI-MS, UV/vis, and fluorescence spectroscopy and cyclic voltammetry. Micropatterned CB[8]-modified gold substrates were found to trap only the recognizable N-tryptophan-containing peptides from a peptide mixture that could be visualized as green peptide arrays under fluorescence microscopy. Subsequently, the bound peptides were released from the modified substrates by the controlled single-electron reduction of viologen. The fully reversible trap-and-release process was repeated for 13 cycles, and the cumulative release profile of the dye-peptide conjugate was monitored by fluorescence spectroscopy, indicating that no degradation occurred.

A systems approach to controlling supramolecular architecture and emergent solution properties via host-guest complexation in water.

The assembly behavior of aryl/alkyl imidazolium ionic liquid salts in aqueous solution has been investigated. These salts undergo self-assembly into one-dimensional stacks via hydrophobic and π-π interactions upon increasing concentration, which led to a substantial increase in the solution viscosity in water. Addition of the macrocyclic host molecules cucurbit[n]urils (CB[n]) were found to effectively alter the supramolecular assemblies, as evidenced from the dramatic increase (by CB[7]) and decrease (by CB[8]) in solution viscosity and aggregation size in water, on account of the different binding stoichiometries, 1:1 complexation with CB[7] and 2:1 complexation with CB[8]. Furthermore, the aggregate architectures were controllably modified by competitive guests for the CB[n] hosts. This complex supramolecular systems approach has tremendous implications in the fields of molecular sensor design, nonlinear viscosity modification, and controlled release of target molecules from a defined supramolecular scaffold in water.

A "green" method for isolation of cucurbit[7]uril via a solid state metathesis reaction.

A method to isolate CB[7] from a CB[5]/CB[7] mixture has been successfully developed by incorporating an alkyl-imidazolium ionic liquid guest of the type [C(n)mim]Br which is only capable of binding with CB[7]. This CB[7]-[C(n)mim]Br complex can be removed from the mixture and a subsequent solid state ion metathesis affords pure CB[7]. Moreover, the imidazolium ionic liquids can be recycled from the aqueous solution after the purification thus providing a 'green' process.