Progress of Wnt Signaling Pathway in Osteoporosis.

Osteoporosis, one of the serious health diseases, involves bone mass loss, bone density diminishing, and degeneration of bone microstructure, which is accompanied by a tendency toward bone fragility and a predisposition to fracture. More than 200 million people worldwide suffer from osteoporosis, and the cost of treating osteoporotic fractures is expected to reach at least $25 billion by 2025. The generation and development of osteoporosis are regulated by genetic factors and regulatory factors such as TGF-ß, BMP, and FGF through multiple pathways, including the Wnt signaling pathway, the Notch signaling pathway, and the MAPK signaling pathway. Among them, the Wnt signaling pathway is one of the most important pathways. It is not only involved in bone development and metabolism but also in the differentiation and proliferation of chondrocytes, mesenchymal stem cells, osteoclasts, and osteoblasts. Dkk-1 and SOST are Wnt inhibitory proteins that can inhibit the activation of the canonical Wnt signaling pathway and block the proliferation and differentiation of osteoblasts. Therefore, they may serve as potential targets for the treatment of osteoporosis. In this review, we analyzed the mechanisms of Wnt proteins, ß-catenin, and signaling molecules in the process of signal transduction and summarized the relationship between the Wnt signaling pathway and bone-related cells. We hope to attract attention to the role of the Wnt signaling pathway in osteoporosis and offer new perspectives and approaches to making a diagnosis and giving treatment for osteoporosis.

The role of Notch signaling pathway in metabolic bone diseases.

Metabolic bone diseases is the third most common endocrine diseases after diabetes and thyroid diseases. More than 500 million people worldwide suffer from metabolic bone diseases. The generation and development of bone metabolic diseases is a complex process regulated by multiple signaling pathways, among which the Notch signaling pathway is one of the most important pathways. The Notch signaling pathway regulates the differentiation and function of osteoblasts and osteoclasts, and affects the process of cartilage formation, bone formation and bone resorption. Genetic mutations in upstream and downstream of Notch signaling genes can lead to a series of metabolic bone diseases, such as Alagille syndrome, Adams-Oliver syndrome and spondylocostal dysostosis. In this review, we analyzed the mechanisms of Notch ligands, Notch receptors and signaling molecules in the process of signal transduction, and summarized the progress on the pathogenesis and clinical manifestations of bone metabolic diseases caused by Notch gene mutation. We hope to draw attention to the role of the Notch signaling pathway in metabolic bone diseases and provide new ideas and approaches for the diagnosis and treatment of metabolic bone diseases.

O6-Corona[6]arenes with Expanded Cavities for Specific Complexation with C70.

O6-Corona[3]arene[3]tetrazines with expanded cavities were synthesized by one-pot SNAr reaction between 3,6-dichlorotetrazine and aromatic diols. The macrocycle-to-macrocycle transformation involving IEDDA of tetrazine moieties with an enamine followed by denitrogenative aromatization afforded O6-corona[3]arene[3]pyridazines. O6-Corona[6]arenes adopted coronary conformations yielding hexagonal cavities of varied sizes. While O6-corona[3]arene[3]pyridazines complexed both C60 and C70 in a virtually nonselective manner, O6-corona[3]arene[3]tetrazines behaved as selective receptors to complex C70 with K1:1 values up to (3.98 ± 0.08) × 104 M-1 in toluene.

Synthesis and Structure of Corona[6](het)arenes Containing Mixed Bridge Units.

A one-pot nucleophilic aromatic substitution reaction of 3,6-dichlorotetrazine with various diphenols and dibenzenethiols produced corona[4]arene[2]tetrazines that contain mixed oxygen, sulfide, methylene, and sulfone linkages. Macrocyclic ring transformations employing an inverse-electron-demand Diels-Alder reaction of tetrazine moieties with enamines and the subsequent sulfide oxidation reaction afforded diverse corona[4]arene[2]pyridazines. The acquired corona[6]arenes adopted three types of conformational structures in the crystalline state.

Synthesis, structure, and properties of O6 -Corona[3]arene[3]tetrazines.

O6 -Corona[3]arene[3]tetraazines, a new class of macrocyclic compounds, were synthesized efficiently in a one-pot reaction from the nucleophilic aromatic substitution reaction between 1,4-dihydroxybenzene derivatives and 3,6-dichlorotetrazine in warm acetonitrile. In the crystalline structure, the resulting macrocycles adopt highly symmetric structures of a regular hexagonal cavity with all bridging oxygen atoms and tetrazine rings located on the same plane with phenylene units orthogonally orientated. The constitutional aromatic rings are able to rotate around the macrocyclic annulus, depending on the steric effect of the substituents and temperature, in solution. The electron-deficient nature revealed by cyclic voltammetry, differential pulse voltammetry, and characteristic absorbances at a visible region show the O6 -corona[3]arene[3]tetrazines to be suitable macrocyclic receptors for electron-rich guests.

Synthesis and characterization of energetic 3-nitro-1,2,4-oxadiazoles.

All new: 3-Nitro-5-guanidino-1,2,4-oxadiazole (NOG) was synthesized from diaminoglycoluril with in situ generated dimethyldioxirane (DMDO). The impact sensitivity of NOG is more than 40 J with a decomposition temperature of 290 °C. Some other energetic derivatives have been prepared and characterized.