Identification of the occurrence and potential mechanisms of heterotopic ossification associated with 17-beta-estradiol targeting MKX by bioinformatics analysis and cellular experiments

Background Tendon heterotopic ossification (HO) is a common condition occurring secondary to tendon injury or surgical trauma that significantly affects the patient’s quality of life. The treatment of tendon HO remains challenging due to a lack of clarity regarding the pathological mechanism. Mohawk (MKX) is a key factor in preventing tendon HO; however, its upstream regulatory mechanism remains to be understood. This study aimed to identify potential compounds that target and regulate MKX and explore their functional mechanisms. Methods Bioinformatics analysis of MKX-related compounds and proteins was performed based on data from the STITCH and OncoBinder databases. Subsequently, the SymMap database was used to study MKX-related traditional Chinese medicine drugs and symptoms. Next, the OncoBinder genomic and proteomic discovery model was applied to identify potential regulators of MKX. The analytical tool Expert Protein Analysis System for proteomics was used to predict the three-dimensional structure of MKX, and the AutoDockTools software was used to identify pockets of activity at potential sites for molecular docking. Furthermore, we evaluated the effect of different doses of 17-beta-estradiol on bone marrow-derived mesenchymal stem cells (BM-MSCs). Results By predicting the three-dimensional structure of MKX and simulating molecular docking, Pro-Tyr and 17-beta-Estradiol were found to target and bind to MKX. Analysis of the STITCH and OncoBinder databases showed that MKX had a significant regulatory correlation with suppressor interacting 3 A/histone deacetylase 1 (SIN3A/HDAC1). The GO and KEGG pathway enrichment analysis revealed that the functions of MKX and its associated proteins were mainly enriched in osteogenic-related pathways. Assessment of the proliferation of BM-MSCs revealed that 17-beta-estradiol possibly upregulated the mRNA expression of the HDAC1-SIN3A/BMP pathway-related RUNX2, thereby promoting the proliferation of BM-MSCs. Conclusions The compounds Pro-Tyr and 17-beta-Estradiol may bind to MKX and thus affect the interaction of MKX with SIN3A/HDAC1.

N-methylimidazolium containing metal phosphate-oxalates: solvent-free synthesis, crystal structure, and proton conduction

Two N-methylimidazolium containing metal phosphate-oxalates (denoted SCU-40 and SCU-42) were prepared under solvent-free conditions. SCU-40 has a three-dimensional structure with a zeolitic crb topology, while SCU-42 has a layered structure...

Quantitative Characterization of Bamboo Cortex’structure Based on X-ray Microtomography

Bamboo is a natural fiber composite with layered structure. Millions of years of evolution have endowed bamboo with the most effective structure in nature. The ingenious microstructure provides bamboo with excellent mechanical properties. Bamboo culm is composed of the cortex, a middle layer, and a pith ring. The cortex refers to the area starting from the periphery of the culm wall to the vascular bundles. The present study obtained the two-dimensional microstructure of bamboo cortex cells by optical microscopy and characterized the three-dimensional structure through high-resolution X-ray microtomography (µCT). Based on the analysis, the bamboo cortex cells were classified into four layers: epidermis layer, hypodermis layer, transitional layer, and parenchyma layer. The average pore volume of the bamboo cortex was about 1.54×10-6 mm3, the porosity was 36.1%, and the relative density was 0.639. The epidermis layer, hypodermis layer, transition layer, and parenchyma layer cells had a cell cavity volume of 917.81 µm3, 714.22 µm3, 1258.19 µm3, and 3117.65 µm3, respectively, an average length3d (L) of 19.38 µm, 25.84 µm, 26.46 µm, and 34.88 µm, respectively, an average breadth3d (W) of 14.11 µm, 9.44 µm, 15.22 µm, and 16.6 µm, respectively, and sphericity of 0.85, 0.76, 0.75, and 0.78, respectively. Studies on bamboo anatomical structure, especially three-dimensional digital characterization, will enrich the bamboo microstructure database. Besides, the three-dimensional structure of the bamboo cortex revealed in this study can provide a reference for optimizing composite material hierarchy and biomimetic design.

On the Regularity of the Electron Configuration of Atoms in the Periodic Table

The current periodic table does not necessarily have a clear position for transition elements. Therefore, the purpose of this paper is to use the basic principle discovered by Mendeleev as it is and to create a periodic table with consistency for transition elements. By setting some hypotheses, it was found that transition elements also have regular periodicity, so we succeeded in clarifying the energy level of electrons in each orbit. In addition, by utilizing its periodicity, the electron configuration for each orbit was predicted for unknown elements. In this paper, we did not take the conventional idea of electron orbitals, that is, the idea of forming a hybrid orbital, but assumed a new orbital. Since the state in which electrons fit in orbits and stabilize is defined as an octet, this idea was used as the basic principle in this paper, but the hypothesis that "there are only three orbits in each shell" was established and verified. The calculation of the energy level of the electrons on the orbit became extremely easy, and the order of each orbit could be clarified. It was also found that the three-dimensional structure of the molecule may be visualized by paying attention to the valence electrons of the outermost shell of the element and the octet of the stability condition. Therefore, in this paper, by slightly expanding the structural formula of Kekulé, it became possible to easily determine whether or not the molecule synthesized by the bond between elements is stable. In addition, it has become possible to predict the three-dimensional structure of the molecule as well. Furthermore, not only will it be easier for students studying chemistry to understand complex chemical reactions, but it will also be useful for researchers in the development and research of new drugs.

Frequent SLC12A3 mutations in Chinese Gitelman syndrome patients: structure and function disorder

Purposes: This study was conducted to identify the frequent mutations from reported Chinese Gitelman syndrome (GS) patients, to predict three-dimensional structure change of human Na-Cl co-transporter (hNCC), and to test the activity of these mutations and some novel mutations in vitro and in vivo. Methods: SLC12A3 gene mutations in Chinese GS patients previously reported in the PubMed, CNKI and Wanfang database were summarized. Predicted configurations of wild type (WT) and mutant proteins were achieved using the I-TASSER workplace. Six missense mutations (T60M, L215F, D486N, N534K, Q617R and R928C) were generated by site-directed mutagenesis. 22Na+ uptake experiment was carried out in the Xenopus laevis oocyte expression system. 35 GS patients and 20 healthy volunteers underwent the thiazide test. Results: T60M, T163M，D486N, R913Q, R928C and R959 frameshift were frequent SLC12A3 gene mutations (mutated frequency >3%) in 310 Chinese GS families. The protein’s three-dimensional structure was predicted to be altered in all mutations. Compared with WT hNCC, the thiazide-sensitive 22Na+ uptake was significantly diminished for all 6 mutations: T60M 22±9.2%, R928C 29±12%, L215F 38±14%, N534K 41±15.5%, Q617R 63±22.1% and D486N 77±20.4%. In thiazide test, the net increase in chloride fractional excretion in 20 healthy controls was significantly higher than GS patients with or without T60M or D486N mutations. Conclusions: Frequent mutations (T60M, D486N, R928C) and novel mutations (L215F, N534K and Q617R) lead to protein structure alternation and protein dysfunction verified by 22Na+ uptake experiment in vitro and thiazide test on patients.