Using Maxwell’s Theory to model and quantify the fracture evolution of cyclothymic deposition phosphate rock

The evolution and stability of fracturing in the cyclothymic deposition of phosphate rocks are strongly affected by the viscoelasticity and structural form of the rock-forming minerals. Presently, there is no standardized method that has been widely accepted to accurately quantify the elastic-plastic deformation and fracturing of such striped structural rock nor reflect the role of the different lithogenous minerals in phosphate rocks when subjected to viscoelastic strain loading. In this study, integrated mathematical equations were formulated for modelling the mechanical and fracture behaviour of cyclothymic deposition in structured phosphate rocks. These constitutive equations were developed based on Maxwell’s Theory after the elastic modulus and damping coefficient of the rock-forming mineral from the mechanical testing were substituted into the derived-equations. In these new models, the apatite stripes and dolomite stripes were incorporated into the transverse isotropic model through the analysis of structural characteristics of the phosphate rock. Through experimental validation, the response curves of the creep and stress relaxation tests were found to be consistent with the deformation curves generated by modelling using the mathematical equations. Overall, the formulated model along with the corresponding equations was found to exhibit good applicability properties to describe phosphate’s mechanical and fracture behaviour under low horizontal compressive stresses. In the study, the creep mechanism in phosphate rocks were satisfactorily analysed from the angles of microscopic morphology, cracks evolution, and inter-crystalline strength. The hard brittle apatite was found to be surrounded and separated by high creep variant dolomite. Furthermore, the analysis showed that dolomite crystals possessing high creep properties dominated the distribution and evolution of secondary structures in the phosphate rock, under the condition of long-term low-stress loading

Mesenchymal Stem Cell-Mediated Functional Tooth Regeneration in Swine

Mesenchymal stem cell-mediated tissue regeneration is a promising approach for regenerative medicine for a wide range of applications. Here we report a new population of stem cells isolated from the root apical papilla of human teeth (SCAP, stem cells from apical papilla). Using a minipig model, we transplanted both human SCAP and periodontal ligament stem cells (PDLSCs) to generate a root/periodontal complex capable of supporting a porcelain crown, resulting in normal tooth function. This work integrates a stem cell-mediated tissue regeneration strategy, engineered materials for structure, and current dental crown technologies. This hybridized tissue engineering approach led to recovery of tooth strength and appearance

Transplantation of mesenchymal stem cells is an optimal approach for plastic surgery

Mesenchymal stem cells (MSCs) are able to differentiate into a variety of cell types, offering promising approaches for stem cell-mediated tissue regeneration. Here, we explored the potential of utilizing MSCs to reconstruct orofacial tissue, thereby altering the orofacial appearance. We demonstrated that bone marrow MSCs were capable of generating bone structures and bone-associated marrow elements on the surfaces of the orofacial bone. This resulted in significant recontouring of the facial appearance in mouse and swine. Notably, the newly formed bone and associated marrow tissues integrated with the surfaces of the recipient bones and re-established a functional bone marrow organ-like system. These data suggested that MSC-mediated tissue regeneration led to a body structure extension, with the re-establishment of all functional components necessary for maintaining the bone and associated marrow organ. In addition, we found that the subcutaneous transplantation of another population of MSCs, the human periodontal ligament stem cells (PDLSCs), could form substantial amounts of collagen fibers and improve facial wrinkles in mouse. By contrast, bone marrow MSCs failed to survive at 8 weeks post-transplantation under the conditions used for the PDLSC transplantation. This study suggested that the mutual interactions between donor MSCs and recipient microenvironment determine long-term outcome of the functional tissue regeneration. Disclosure of potential conflicts of interest is found at the end of this article. Disclosure of potential conflicts of interest is found at the end of this article

MANF/EWSR1/ANXA6 pathway might as the bridge between hypolipidemia and major depressive disorder

Abstract Major depressive disorder (MDD) involves changes in lipid metabolism, but previous findings are contradictory. Mesencephalic astrocyte-derived neurotrophic factor (MANF) is considered to be a regulator of lipid metabolism. To date, the function of MANF has been studied in many brain disorders, but not in MDD. Therefore, to better understand the role of lipids in MDD, this study was conducted to examine lipid levels in the serum of MDD patients and to investigate the potential function of MANF in MDD. First, the data on total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglyceride (TG) in serum from 354 MDD patients and 360 healthy controls (HCs) were collected and analyzed. The results showed that there were significantly lower concentrations of TC and LDL-C in MDD patients compared with HCs, and TC levels were positively correlated with LDL-C levels. Bioinformatics analysis indicated that MANF/EWSR1/ANXA6 pathway might serve as the connecting bridge through which hypolipidemia played a functional role in MDD. Second, to verify this hypothesis, serum samples were collected from 143 MDD patients, and 67 HCs to measure the levels of MANF, EWSR1, and ANXA6 using ELISA kits. The results showed that compared to HCs, MDD patients had a significantly lower level of MANF and higher levels of ANXA6 and EWSR1, and these molecules were significantly correlated with both TC level and Hamilton Depression Rating Scales (HDRS) score. In addition, a discriminative model consisting of MANF, EWSR1, and ANXA6 was identified. This model was capable of distinguishing MDD subjects from HCs, yielded an area under curve of 0.9994 in the training set and 0.9569 in the testing set. Taken together, our results suggested that MANF/EWSR1/ANXA6 pathway might act as the bridge between hypolipidemia and MDD, and these molecules held promise as potential biomarkers for MDD

Changes of gut microbiota and short chain fatty acids in patients with Peutz–Jeghers syndrome

Abstract Peutz–Jeghers Syndromeis a rare autosomal dominant genetic disease characterized by gastrointestinal hamartomatous polyps and skin and mucous membrane pigmentation. The pathogenesis of PJS remains unclear; however, it may be associated with mutations in the STK11 gene, and there is currently no effective treatment available. The gut microbiota plays an important role in maintaining intestinal homeostasis in the human body, and an increasing number of studies have reported a relationship between gut microbiota and human health and disease. However, relatively few studies have been conducted on the gut microbiota characteristics of patients with PJS. In this study, we analyzed the characteristics of the gut microbiota of 79 patients with PJS using 16 S sequencing and measured the levels of short-chain fatty acids in the intestines. The results showed dysbiosis in the gut microbiota of patients with PJS, and decreased synthesis of short-chain fatty acids. Bacteroides was positively correlated with maximum polyp length, while Agathobacter was negatively correlated with age of onset. In addition, acetic acid, propionic acid, and butyric acid were positively correlated with the age of onset but negatively correlated with the number of polyps. Furthermore, the butyric acid level was negatively correlated with the frequency of endoscopic surgeries. In contrast, we compared the gut microbiota of STK11-positive and STK11-negative patients with PJS for the first time, but 16 S sequencing analysis revealed no significant differences. Finally, we established a random forest prediction model based on the gut microbiota characteristics of patients to provide a basis for the targeted diagnosis and treatment of PJS in the future

Characterization of human SCAP in comparison with DPSCs.

<div><p>(<b>A</b>) Western blot analysis to confirm protein expression of genes identified in microarray studies showed greater abundance of survivin in SCAP than in DPSCs, with similar levels of DSP and Cbfa1/Runx2.</p> <p>(<b>B</b>) Flow cytometric analysis showed that <i>ex vivo</i> expanded SCAP contained approximately 7.5% CD24-positive cells, but DPSCs exhibited 0.5% positive staining for CD 24.</p> <p>(<b>C</b>) The proliferation rates of SCAP and DPSCs, derived from the same tooth, were assessed by co-culture with BrdU for 6 hours.</p> <p>The number of BrdU-positive cells was presented as a percentage of the total number of cells counted from five replicate cultures.</p> <p>SCAP showed a significantly higher proliferation rate in comparison with DPSCs (<b>*</b><i>P</i> = 0.0042).</p> <p>(<b>D</b>) Single colony-derived SCAP were able to proliferate to over 70 population doublings, which was significantly higher than DPSCs (<b>*</b><i>P</i> = 0.0192).</p> <p>(<b>E</b>) Dentin regeneration capacity of SCAP was significantly higher than that of DPSCs when transplanted into the same immunocompromised mice (<b>*</b><i>P</i> = 0.0489) using Scion Image analysis system (Scion Image, Rockville, MD).</p> <p>(<b>F</b>) SCAP showed a significant higher telomerase activity than DPSCs at passage 1 (<b>*</b><i>P</i> = 0.015).</p> <p>Cultured BMMSCs at passage 1 were used as a negative control to show an absence of telomerase activity.</p> <p>The telomerase activity was assessed by real time PCR based quantitative telomerase detection kit as described in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0000079#s4" target="_blank">Materials and Methods</a>.</p> <p>(<b>G</b>) Cell motility assessed by a scratch assay.</p> <p>A representative area of SCAP and DPSCs at 72 hours after scratch was presented.</p> <p>Red arrows indicate the ranges of cell migration during 72 hours (<b>*</b><i>P</i> = 0.0033).</p></div

Comined human SCAP/PDLSC-mediated tissue regeneration.

<div><p>(<b>A</b>) On the outside of the HA/TCP carrier (<i>HA</i>), PDLSCs can form structures resembling Sharpey's fibers (arrows) connecting with newly formed cementum (<i>C</i>) on the surface of HA/TCP particles (<i>HA</i>).</p> <p>(<b>B</b>) Immunohistochemical staining showed that SCAP/PDLSC-generated tissues were positive for human specific mitochondria antibody staining (arrows).</p></div