Search

Supplementary Methods and Supplementary Figs. 1-4

Additional file 1. STROBE Checklist.

Additional file 1: Supplemental Figure 1. This matrix is a summary of 90 ROIs from the Anatomical Automatic Labeling template-based statistical parametric maps of functional connectivity analyzed between the MMD group and HC. The matrix is 90 x 90, and each voxel stores a T statistic value ranging from 6 to -6. The red voxels indicate the functional connectivity of the MMD group is greater than HC, and blue is the opposite. The color bar is located at the right. Supplemental Figure 2. A-C The correlation between functional connectivity and tensor metrics of the SMA-IFGorb in the left hemisphere of MMD patients and HC. Supplemental Table 1. Demographics and clinical characteristics of 22 MMD patients.

Type 2 diabetes mellitus (T2DM), a leading cause of osteoporosis, remains a contraindication for bone implant therapy. Although associated with side effects when systemically administered, biphosphonates (BPs) play a positive role in diabetic osteoporosis treatment. We hypothesized that local BP therapy would prevent decayed implant osseointegration under T2DM conditions. To assess cell proliferation and determine the optimal BP concentration, bone marrow-derived mesenchymal stem cells (BMSCs) and bone marrow macrophages (BMMs) were treated with BPs at various relatively low concentrations (10(-9) mmol/L) for different periods of time. Our in vitro study results demonstrated that BP application reversed the process by which high glucose inhibits bone formation and stimulates bone resorption through osteoclast-specific gene and protein expression (P

MicroRNAs (miRNAs) and the Wnt signaling pathway play critical roles in regulating bone development and homeostasis. Our previous study revealed high expression of miR-335-5p in osteoblasts and hypertrophic chondrocytes in mouse embryos and the ability of miR-335-5p to promote osteogenic differentiation by downregulating Wnt antagonist Dickkopf-1 (DKK1). The purpose of this study was to investigate the effects of miR-335-5p constitutive overexpression on bone formation and regeneration in vivo. To that end, we generated a transgenic mouse line specifically overexpressing miR-335-5p in osteoblasts lineage by the osterix promoter and characterized its bone phenotype. Bone histomorphometry and μCT analysis revealed higher bone mass and increased parameters of bone formation in transgenic mice than in wild-type littermates. Increased bone mass in transgenic mice bones also correlated with enhanced expression of osteogenic differentiation markers. Upon osteogenic induction, bone marrow stromal cells (BMSCs) isolated from transgenic mice displayed higher mRNA expression of osteogenic markers than wild-type mice BMSCs cultures. Protein expression of Runx2 and Osx was also upregulated in BMSC cultures of transgenic mice upon osteogenic induction, whereas that of DKK1 was downregulated. Most important, BMSCs from transgenic mice were able to repair craniofacial bone defects as shown by μCT analysis, HE staining, and osteocalcin (OCN) immunohistochemistry of newly formed bone in defects treated with BMSCs. Taken together, our results demonstrate constitutive overexpression of miR-335-5p driven by an osterix promoter in the osteoblast lineage induces osteogenic differentiation and bone formation in mice and support the potential application of miR-335-5p-modified BMSCs in craniofacial bone regeneration. © 2017 American Society for Bone and Mineral Research.

Osteogenesis is mediated by sophisticated interactions of various molecular functions and biological processes, including post-transcriptional regulation. A range of miRNAs have been reported to regulate bone homeostasis and osteoblasts differentiation either positively or negatively through multiple signaling pathways. RNase III endonuclease Dicer is the key enzyme required for the biogenesis of miRNAs and small interfering RNAs. To determine the global influence of miRNAs on regulation of osteogenesis of pre-osteoblast cells, the transcriptional regulation of Dicer and the function of Dicer during osteoblast differentiation and mineralization were investigated. Runx2 binding directly to the Dicer promoter region was characterized in MC3T3-E1 cells by chromatin immunoprecipitation (ChIP) and luciferase promoter reporter assays. Overexpression or knockdown of Runx2 resulted in increase or decrease of Dicer expression, respectively. Furthermore, abatement of Dicer in MC3T3-E1 cells down-regulated the expression of osteogenic marker genes and mineralization ability, at least partly involving Dicer-dependent processing of the miR-21a-5p targeting PTEN via pAKT/pGSK3β/β-catenin signaling pathways. Taken together, the study demonstrates the role of Dicer in osteogenesis and suggests that Dicer is required, in part, for Runx2 regulation of osteoblast differentiation.

Dazu Rock Carvings is an important heritage. In the past, many varieties of damages existed in Dazu Rock Carvings, which impaired aesthetics and safety. Thus, the country is trying to save the rock carvings through preservation of cultural relics. Among those engaged in this endeavor are leaders and experts from Dazu Rock Carving Institute, Chinese Academy of Cultural Heritage, China University of Geosciences, School of Environment of Tsinghua University. In the research hereof, field experiments and field surveys were carried out, and corresponding measures were put forward for analysis of data.

Longmen Grottoes was afflicted with many diseases for a long period such as weathering, seepage water and organism growth. Those adverse factors were threatening to preserve cultural relic. Longmen Grottoes conservation and restoration project being put into effect by UNESCO in 2002. The Longmen Grottoes area environmental monitoring system was built in order to comprehensively master the distribution law of environmental factors over the Longmen Grottoes. The monitoring items contains temperature, humidity, wind direction, wind speed, precipitation, light intensity,water content in soil, the rock surface temperature and so on. At the same time, monitoring three experiment caves, monitoring the inside temperature, humidity, seepage water and the wall face temperature etc. So as to analyze the relationship between cave environment and regional environment. We statistical and arrange the data using Excel software, Kgraph software and DPS software. Through the grey incidence analyze, the incidence matrix and the correlation degree of the environmental factors was obtained[1]. The main environment factors for the formation of the disease had been researched. Based on the existing environmental monitor data, the relevance of seepage water and fracture displacement with other environmental factors had been studied, and the relational order was obtained. Corresponding preventive measures were put forward by the formation mechanism analyze of the disease.

MicroRNAs, a class of 22-nucleotide non-coding RNAs, modulate gene expression by associating with the 3'-untranslated regions (3'-UTRs) of messenger RNAs (mRNAs). Although multiple miRNAs are known to be regulated during angiogenesis, their individual roles in blood vessel development are still not fully understood. Herein, we investigate the role of miR-29c in regulating cell cycle and angiogenic phenotype of endothelial cells. The results showed that IGF-1 is highly expressed and down-regulated by miR-29c in human umbilical vein endothelial cells (HUVEC). Consistent with this preliminary finding, introduction of exogenous miR-29c or miR-29c inhibitor alters cell cycle progression, proliferation and tube formation of HUVEC, respectively. Furthermore, by using luciferase reporter assay, we find that the expression of IGF-1, a suppressor transcription factor, is directly regulated by miR-29c through 3'-UTR. In addition, we show that the selective inhibition of PI3K/AKT pathway prior to miR-29c stimulation prevents the expression of angiogenesis suppressor miRNAs that are family and cluster specific. As a conclusion, we find that miR-29c plays a significant role in regulating cell cycle, proliferation and angiogenic properties of HUVECs. This function is likely mediated through IGF-1 proteins at the post-transcriptional level. As a novel molecular target, miR-29c may have a potential value in the treatment of angiogenesis-associated diseases, such as cardiovascular diseases and cancers.