Exploration of Molecular Nanoparticles as Soft Structural Materials and Their Structure-Property Relationship.

The search for alternative chemical systems other than polymers with chain topologies for soft structural materials raises general interests in fundamental materials and chemical sciences. It is also appealing from an engineering perspective for the urgent need to resolve the typical trade-offs of polymer systems. Herein, a subnanometer molecular cluster, polyhedral oligomeric silsesquioxanes, is assembled into molecular nanoparticles (MNPs) with star topology. Broadly tunable viscoelasticity can be realized by fine-tuning the MNPs' deformability. Being analogous to polymeric systems, the hierarchical structural relaxation dynamics can be observed, and their relaxation time and temperature dependence are dominated by the linker flexibilities. This not only provides microscopic understanding on MNP's unique viscoelasticity but also offers enormous opportunities for modulating their mechanical properties via linker engineering. Our work proves the possibility of applying structural units with particle topologies for the design of soft structural materials.

Unique Viscoelasticity and Hierarchical Relaxation Dynamics of Molecular Granular Materials.

Resulting from the dense packing of subnanometer molecular clusters, molecular granular materials (MGMs) are shown to maintain high elasticity far above their apparent glass transition temperature (Tg*). However, our microscopic understanding of their structure-property relationship is still poor. Herein, 1 nm polyhedral oligomeric silsesquioxanes (POSSs) are appended to a backbone chain in a brush configuration with different flexible linker chains. Assemblies of these brush polymers exhibit hierarchical relaxation dynamics with the glass transition arising from the cooperative dynamics of packed POSSs. The interaction among the assemblies can be strengthened by increasing the rigidity of linkers with the MGM relaxation modes changing from colloid- to polymer chain-like behavior, rendering their tunable viscoelasticity. This finally contributes to the decoupling of mechanical and thermal properties by showing elasticity dominant mechanical properties at a temperature 150 K above the Tg*.

Functional Molecular Granular Materials: Advances and Perspectives.

Molecular granular materials (MGMs) are constructed with sub-nanoscale molecular clusters (MCs) as the building units and they have recently been observed to possess enriched functionalities distinct from granular materials of colloid nanoparticles. Herein, the birth and recent research advances in MGMs are summarized with the topics covering the precise synthesis of MC assemblies with target topologies, the hierarchical relaxation dynamics and tuneable viscoelasticity, impact-resistant capacity, and proton conductivity performance. The extremely small size of MC renders them two features: bulk diffusive dynamics with energy scale close to thermal fluctuation energy and the dominant volume fraction of surface structures. This finally leads to the hierarchical relaxation dynamics and broadly tuneable viscoelasticity of MGMs although the structural units are with small sizes and low Mw . Therefore, MGMs have been applied as impact resistant materials and proton conductors for the highly tuneable relaxation dynamics.

Dimerization of sub-nanoscale molecular clusters affords broadly tuneable viscoelasticity above the glass transition temperature.

Materials with promising mechanical performance generally demonstrate requirements for the critical sizes of their key building units, e.g. entanglements and crystal grains. Herein, only with van der Waals interaction, viscoelasticity with broad tunability has been facilely achieved below the critical size limits: the dimers of ∼1 nm polyhedral oligomeric silsesquioxane (POSS) with M w < 4 kD and size < 5 nm, which demonstrate distinct material physics compared to that of polymer nanocomposites of POSS. The dimeric POSSs are confirmed by scattering and calorimetrical measurements to be intrinsic glassy materials with glass transition temperatures (T gs) lower than room temperature. From rheological studies, their viscoelasticity can be broadly tuned through the simple tailoring of the dimer linker structures above their T g. In dimer bulks, each POSS cluster is spatially confined by the POSSs from other dimers and therefore, the correlation of the dynamics of the two linked POSS clusters, which, as indicated by dynamics analysis, is regulated by the length and flexibilities of linkers, contributes to the caging dynamics of POSS confined by their neighbours and the resulting unique viscoelasticity. Our discoveries update the understanding of the structural origin of viscoelasticity and open avenues to fabricate structural materials from the design of sub-nanoscale building blocks.

Short-term effect of ultrasound-guided low-molecular-weight hyaluronic acid injection on clinical outcomes and imaging changes in patients with rheumatoid arthritis of the ankle and foot joints. A randomized controlled pilot trial.

To determine whether hyaluronic acid (HA) injection into rheumatoid arthritis ankles and feet can achieve improvement in foot function and reduce synovial hyper-vascularization. Forty-four patients with RA having unilateral or bilateral painful ankle and foot involvement (N = 75) were studied. All the patients were randomized to receive HA (N = 40) or lidocaine (LI) (N = 35) injection at 2-week intervals; Clinical assessments were performed using a visual analog scale (VAS) and foot function index (FFItotal) including subscales of pain (FFIpain) before injection at baseline, 4 weeks (first evaluation) and 12 weeks (secondary evaluation). Imaging evaluation based on color Doppler ultrasound (CDUS) and synovitis scores was performed simultaneously. HA injection improved the VAS score (p = .009), FFIpain (p = .041), and FFItotal (p = .032) considerably more than LI injections did at the first evaluation. The CDUS values at first evaluation (p = .005) and secondary evaluation (p < .001) decreased significantly compared with the base line values. HA injections reduced the CDUS values of more than half of the joints (54%, p = .042) while the control group exhibited no change (20%, p = .56). However, HA injection did not reduce the CDUS values more than LI injection did. Regarding the evaluation of synovial hypertrophy, no significant difference was observed between or within the groups in the synovitis scores. HA injection improved short-term foot function and pain reduction. HA injection may have a modest effect in reducing synovial hyper-vascularization. Further large-scale study is warranted to confirm this result.

Aloin Protects Skin Fibroblasts from Heat Stress-Induced Oxidative Stress Damage by Regulating the Oxidative Defense System.

Oxidative stress is commonly involved in the pathogenesis of skin damage induced by environmental factors, such as heat stress. Skin fibroblasts are responsible for the connective tissue regeneration and the skin recovery from injury. Aloin, a bioactive compound in Aloe vera, has been reported to have various pharmacological activities, such as anti-inflammatory effects. The aim of this study was to investigate the protective effect of aloin against heat stress-mediated oxidative stress in human skin fibroblast Hs68 cells. Hs68 cells were first incubated at 43°C for 30 min to mimic heat stress. The study was further examined if aloin has any effect on heat stress-induced oxidative stress. We found that aloin protected Hs68 cells against heat stress-induced damage, as assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and lactate dehydrogenase assay. Aloin protected Hs68 cells by regulating reactive oxygen species production and increasing the levels of glutathione, cytosolic and mitochondrial superoxide dismutase. Aloin also prevented the elevation of thiobarbituric acid reactive substances and the reduction of 8-OH-dG induced by heat stress. These results indicated that aloin protected human skin fibroblasts from heat stress-induced oxidative stress damage by regulating the oxidative defense system.

Tropisetron attenuates cardiac injury in a rat trauma-hemorrhage model.

Tropisetron is widely used for antiemesis. Recent evidence shows that tropisetron possesses anti-inflammatory properties. Protein kinase B (Akt) is known to play an important role in negating proinflammatory response in injury. The aim of this study was to determine whether tropisetron provides cardioprotection mediated via an Akt-dependent pathway in trauma-hemorrhaged animals. Male Sprague-Dawley rats underwent trauma-hemorrhage and resuscitation. Tropisetron (1 mg/kg) with or without a PI3K inhibitor (wortmannin, 1 mg/kg) or vehicle was administered intravenously during the resuscitation. At 24 h after either the trauma-hemorrhage or sham operation, the cardiac function parameters (cardiac output, left ventricle pressure variability) were measured. Cardiac myeloperoxidase activity, interleukin 6 and intercellular adhesion molecule 1 levels, Akt activity, and apoptosis were measured. One-way analysis of variance and Tukey test were used for statistical analysis. Cardiac function was depressed and cardiac myeloperoxidase activity, interleukin 6 and intercellular adhesion molecule 1 levels, and cardiac apoptosis were markedly increased after trauma-hemorrhage. Administration of tropisetron significantly improved cardiac function and proinflammatory parameters in the tropisetron-treated rats subjected to trauma-hemorrhage. The increase in cardiac apoptosis was attenuated in rats that received tropisetron. Although trauma-hemorrhage decreased cardiac Akt phosphorylation (p-Akt), tropisetron treatment prevented the same decrease in cardiac p-Akt following trauma-hemorrhage. Coadministration of wortmannin prevented the beneficial effects of tropisetron on the attenuation of proinflammatory responses and cardiac injury after trauma-hemorrhage. Tropisetron attenuates cardiac injury following trauma-hemorrhage, which is, at least in part, through Akt-dependent anti-inflammatory pathway.

Ondansetron attenuates hepatic injury via p38 MAPK-dependent pathway in a rat haemorrhagic shock model.

BACKGROUND: Ondansetron is a 5-HT3 receptor antagonist with potent antiemetic, analgesic, and antiphlogistic effects. Recent evidence suggests that the co-existence of 5-HT3 receptors in various cell types is involved in inflammation. However, the effects that 5-HT3 antagonists produce in haemorrhagic shock and resuscitation remain unknown. In this study, we hypothesized that ondansetron administration in male rats, after haemorrhagic shock, decreases cytokine production and protects against hepatic injury through a p38 mitogen-activated protein kinase (MAPK) pathway. METHODS: Male Sprague-Dawley rats underwent haemorrhagic shock (mean arterial blood pressure 40 mm Hg for 90 min), followed by resuscitation. Various doses of ondansetron (0.1, 0.3, 1, 3 mg kg(-1)) or a single dose of ondansetron (1 mg kg(-1)) with or without a p38 MAPK inhibitor (SB-203580, 2 mg kg(-1)) or vehicle were administered intravenously during resuscitation. Plasma aspartate aminotransferase (AST) and alanine aminotransferase (ALT) concentrations and various liver proinflammatory parameters were measured at 24h after resuscitation. RESULTS: Results show that haemorrhagic shock increases plasma AST and ALT concentrations, hepatic myeloperoxidase activity, cytokine-induced neutrophil chemoattractant (CINC)-1, CINC-3, intercellular adhesion molecule-1 (ICAM-1), interleukin-6 (IL-6) and tumor necrosis factor α (TNF-α) levels. These parameters were significantly improved in the ondansetron-treated rats subjected to haemorrhagic shock. Ondansetron treatment restored phos-p38 MAPK expression as compared with vehicle-treated haemorrhaged rats. Coadministration of SB-203580 prevented the beneficial effects of ondansetron on postresuscitation proinflammatory responses and hepatic injury. CONCLUSION: Ondansetron attenuates hepatic injury following haemorrhagic shock, which is, at least in part, to be due to its anti-inflammatory effect via p38 MAPK signal pathway.