To explore differences in coordination between alkali- and alkaline-earth-metal ions and cucurbit[n]urils, a water-soluble α,α',δ,δ'-tetramethylcucurbit[6]uril (TMeQ[6]) was used to synthesize a series of complexes and their supramolecular assemblies, based on the coordination of TMeQ[6] with alkali- and alkaline-earth-metal ions. The complexes and corresponding supramolecular assemblies were structurally characterized by single-crystal X-ray diffraction. Unlike cucurbituril (Q[6]), which formed the metal-Q[6] polymers based on the direct coordination of carbonyl oxygen atoms to the alkali-metal ions, TMeQ[6] formed metal-TMeQ[6] polymers based on the direct coordination of carbonyl oxygen atoms with the alkaline-earth-metal ions rather than the alkali-metal ions.
The activity of protein kinases IKK-ε and TANK-binding kinase 1 (TBK1) has been shown to be associated with inflammatory diseases. As an inhibitor of IKK-ε and TBK1, amlexanox is an anti-inflammatory, anti-allergic, immunomodulator and used for treatment of ulcer, allergic rhinitis and asthma in clinic. We hypothesized that amlexanox may be used for treatment of osteoclast-related diseases which frequently associated with a low grade of systemic inflammation. In this study, we investigated the effects of amlexanox on RANKL-induced osteoclastogenesis in vitro and ovariectomy-mediated bone loss in vivo. In primary bone marrow derived macrophages (BMMs), amlexanox inhibited osteoclast formation and bone resorption. At the molecular level, amlexanox suppressed RANKL-induced activation of nuclear factor-κB (NF-κB), mitogen-activated protein kinase (MAPKs), c-Fos and NFATc1. Amlexanox decreased the expression of osteoclast-specific genes, including TRAP, MMP9, Cathepsin K and NFATc1. Moreover, amlexanox enhanced osteoblast differentiation of BMSCs. In ovariectomized (OVX) mouse model, amlexanox prevented OVX-induced bone loss by suppressing osteoclast activity. Taken together, our results demonstrate that amlexanox suppresses osteoclastogenesis and prevents OVX-induced bone loss. Therefore, amlexanox may be considered as a new therapeutic candidate for osteoclast-related diseases, such as osteoporosis and rheumatoid arthritis.
Biomechanical forces are emerging as critical regulators of cell function and fluid flow is a potent mechanical stimulus. Although the mechanisms of osteoblasts and osteocytes responding to fluid flow are being elucidated, little is known about how the osteoprogenitors, mesenchymal stem cells (MSCs), respond to fluid flow. Here, we examined the effects of laminar shear stress (LSS) on MSCs in vitro. MSCs from bone marrow of Sprague-Dawley rats were isolated, purified, and subjected to physiological levels of LSS. DNA synthesis and cell cycle were measured through [(3)H]thymidine and by flow cytometry, respectively, to detect the cellular proliferation. Annexin V immunostaining and Bcl-2/Bax mRNA expression were evaluated to determine the effect of LSS on MSCs apoptosis. Results showed that fluid shear stress caused a dose-related reduction of MSCs' proliferation rate with the majority of cells being arrested in the G(0) or G(1) phase. Moreover, it was found that physiological levels of LSS exerted a potent suppression effect on MSC apoptosis. In summary, these data revealed a critical role of LSS in maintaining the quiescence of MSCs.
Uncontrollable dendrite growth and sluggish ion‐transport kinetics are considered as the main obstacles for the further development of high‐performance aqueous zinc ion batteries (AZIBs). Here, a nature‐inspired separator (ZnHAP/BC) is developed to tackle these issues via the hybridization of the biomass‐derived bacterial cellulose (BC) network and nano‐hydroxyapatite particles (HAP). The as‐prepared ZnHAP/BC separator not only regulates the desolvation process of the hydrated Zn2+ ions (Zn(H2O)62+) by suppressing the water reactivity through the surface functional groups, alleviating the water‐induced side‐reactions, but also boosts the ion‐transport kinetics and homogenize the Zn2+ flux, resulting in a fast and uniform Zn deposition. Remarkably, the Zn|Zn symmetric cell with ZnHAP/BC separator harvests a long‐term stability over 1600 h at 1 mA cm−2, 1 mAh cm−2 and endures stable cycling over 1025 and 611 h even at a high depth of discharge (DOD) of 50% and 80%, respectively. The Zn|V2O5 full cell with a low negative/positive (N/P) capacity ratio of 2.7 achieves a superior capacity retention of 82% after 2500 cycles at 10 A g−1. Furthermore, the Zn/HAP separator can be totally degraded within 2 weeks. This work develops a novel nature‐derived separator and provides insights in constructing functional separators toward sustainable and advanced AZIBs.
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