Functionalized Metal-Organic Framework-Modified Hydrogel That Breaks the Vicious Cycle of Inflammation and ROS for Repairing of Diabetic Bone Defects.

The regeneration of diabetic bone defects remains challenging. Hyperglycemia causes inflammation state and excessive reactive oxygen species (ROS) during bone regeneration period. These two effects reinforce one another and create an endless loop that is also accompanied by mitochondrial dysfunction. However, there is still no effective and inclusive method targeting at the two aspects and breaking the vicious cycle. Herein, nanoparticles-Met@ZIF-8(metformin loaded zeolitic imidazolate frameworks) modified hydrogel that is capable of releasing metformin and Zn elements are constructed. This hydrogel treats hyperglycemia while also controlling mitochondrial function, reducing inflammation, and restoring homeostasis. In addition, the synergetic effect from metformin and Zn ions inhibits ROS-inflammation cascade generation and destroys the continuous progress by taking effects in both ROS and inflammation and further keeping organelles' homeostasis. Furthermore, with the recovery of mitochondria and breakdown of the ROS-inflammation cascade cycle, osteogenesis under a diabetic microenvironment is enhanced in vivo and in vitro. In conclusion, the study provides critical insight into the biological mechanism and potential therapy for diabetic bone regeneration.

A combination of kissing molars, maxillary bilateral supernumerary teeth and macrodontia: a rare case report.

BACKGROUND: Supernumerary teeth (ST) is defined as an additional number of teeth compared to the normal dental formula. The prevalence rate of ST varies from 0.5 to 3.8% in the permanent dentition. When ST located distal to the third molar is acclaimed as distomolar. Moreover, kissing molar is an extremely scarce condition of distomolars, pointed in the opposite direction in a single follicular space. Meanwhile, macrodontia is also a rare shape anomaly characterized by a large crown and tapering root. CASE PRESENTATION: A 22-year-old Chinese man presented a combination of kissing molars, maxillary bilateral supernumerary teeth and macrodontia. Radiographically, two maxillary bilateral distomolars located at the buccal side of adjacent third molars. One mandibular distomolar with the adjacent third molar was contacted by occlusal surfaces while roots were pointed oppositely, which could be diagnosed as KM. Furthermore, the left mandibular third molar can be inferred to be a macrodontia, characterized by a large crown and tapering root. After a thorough investigation, we excluded the possibilities of systemic diseases and genetic inheritance. However, the etiology of this rare combination deserves to be further explored. CONCLUSION: The combination of kissing molars, maxillary bilateral supernumerary teeth and macrodontia is very rare, especially presented in the patient with no syndromes. As there were no complications with these conditions, long-term observation has been recommended for the patient. In addition, the true etiology need a further exploration.

Sustained and enhanced inhibitory effects of allelochemicals on Microcystis Aeruginosa during its recruitment stage.

Microcystis aeruginosa is the main toxic strain in cyanobacterial blooms, and the recruitment stage in its temperature-dependent seasonal succession is considered as the key to its subsequent growth. In this study, a protocol with specific temperature settings was developed as the simulated recruitment stage in order to investigate and confirm the superior inhibitory effects of allelochemicals on M. aeruginosa at that stage of recruitment. One of the most common allelochemicals, gallic acid (GA) (10 mg/L, 20 mg/L) was employed to treat M. aeruginosa under initially low temperature condition (15 °C), then intermediate (20 °C) and last normal (26 °C), which corresponds to the critical temperatures for cyanobacterial recruitment and growth. Growth, metabolism, photosynthetic activity, extracellular polysaccharides (EPS) and microcystins (MCs) release were analyzed and discussed in this study, and a more sustained and better inhibitory effect over a 20-day period was achieved. Notably, GA (10 mg/L) markedly delayed the recruitment of M. aeruginosa from low temperature, with an inhibition efficiency of 85.71 %, and suppressing Fv/Fm and photosynthetic pigments production. It is also observed that M. aeruginosa at recruitment stage exhibited higher sensitivity and poorer resistance to allelochemical treatment, with variable responses suggesting that optimal dosages may alter. The antioxidant enzyme activities remained high under prolonged stress, and the secretion of EPS was stimulated, indicating that cyanobacteria were more inclined to form colonies. While the laboratory-based inhibitory mechanism appeared to increase the release of microcystins in individual cells, the actual concentration of microcystins in natural aquatic environments requires further investigation.

Energy metabolism as therapeutic target for aged wound repair by engineered extracellular vesicle.

Aging skin, vulnerable to age-related defects, is poor in wound repair. Metabolic regulation in accumulated senescent cells (SnCs) with aging is essential for tissue homeostasis, and adequate ATP is important in cell activation for aged tissue repair. Strategies for ATP metabolism intervention hold prospects for therapeutic advances. Here, we found energy metabolic changes in aging skin from patients and mice. Our data show that metformin engineered EV (Met-EV) can enhance aged mouse skin repair, as well as ameliorate cellular senescence and restore cell dysfunctions. Notably, ATP metabolism was remodeled as reduced glycolysis and enhanced OXPHOS after Met-EV treatment. We show Met-EV rescue senescence-induced mitochondria dysfunctions and mitophagy suppressions, indicating the role of Met-EV in remodeling mitochondrial functions via mitophagy for adequate ATP production in aged tissue repair. Our results reveal the mechanism for SnCs rejuvenation by EV and suggest the disturbed energy metabolism, essential in age-related defects, to be a potential therapeutic target for facilitating aged tissue repair.

Rumor Detection With Hierarchical Representation on Bipartite Ad Hoc Event Trees.

The rapid growth of social media has caused tremendous effects on information propagation, raising extreme challenges in detecting rumors. Existing rumor detection methods typically exploit the reposting propagation of a rumor candidate for detection by regarding all reposts to a rumor candidate as a temporal sequence and learning semantics representations of the repost sequence. However, extracting informative support from the topological structure of propagation and the influence of reposting authors for debunking rumors is crucial, which generally has not been well addressed by existing methods. In this article, we organize a claim post in circulation as an ad hoc event tree, extract event elements, and convert it into bipartite ad hoc event trees in terms of both posts and authors, i.e., author tree and post tree. Accordingly, we propose a novel rumor detection model with hierarchical representation on the bipartite ad hoc event trees called BAET. Specifically, we introduce word embedding and feature encoder for the author and post tree, respectively, and design a root-aware attention module to perform node representation. Then we adopt the tree-like RNN model to capture the structural correlations and propose a tree-aware attention module to learn tree representation for the author tree and post tree, respectively. Extensive experimental results on two public Twitter datasets demonstrate the effectiveness of BAET in exploring and exploiting the rumor propagation structure and the superior detection performance of BAET over state-of-the-art baseline methods.

[Morphological changes of upper airway in patients with skeletal Class â ¢ malocclusion after bimaxillary surgery and correlation analysis].

PURPOSE: To analyze the morphological changes of the upper airway and related influencing factors in patients with skeletal Class Ⅲ malocclusion after bimaxillary surgery. METHODS: Twenty skeletal Class Ⅲ patients who underwent Le Fort I osteotomy and bilateral sagittal split ramus osteotomy(BSSRO) for maxillary advancement and mandibular setback were selected. The patients received CT scans before(T0) and 3-6 months after surgery, and the images were reconstructed three-dimensionally with Dolphin Imaging 11.9 software. Changes in the volume, cross-sectional area, and landmarks of each soft and hard tissue of the airway were measured. Statistical analysis of the data was performed using SPSS 25.0 software package. RESULTS: The volume of nasopharyngeal airway increased after operation (P＜0.05), and the volume of oropharyngeal airway decreased significantly(P＜0.01). The cross-sectional area of the airway at the plane of the second cervical vertebra was significantly decreased (P＜0.01), and the coronal and sagittal diameters were decreased(P＜0.05). The change of nasopharyngeal airway volume was moderately positively correlated with the sagittal change of the posterior nasal spine (r=0.460, P＜0.05), and the change of oropharynx and laryngopharyngeal airway volume was positively correlated with the vertical change of the midpoint of the soft palate(r=0.496, 0.696, P＜0.05). The airway cross-sectional area in the second and third cervical vertebra planes and the sagittal diameter of the airway in the third cervical vertebra plane were positively correlated with the vertical changes of the midpoint of the soft palate(r=0.474, 0.629, 0.547, P＜0.05). The change of airway cross-sectional area at the third cervical vertebra plane was moderately negatively correlated with the change of mandibular plane angle(r=-0.536, P＜0.05). CONCLUSIONS: The volume and cross-sectional area of oropharyngeal airway in skeletal Class Ⅲ patients after bimaxillary surgery will decrease. However, the total upper airway volume doesn't change significantly. The changes in the upper airway are correlated with the changes in some soft and hard tissue landmarks.

Transcriptomic analysis provides a new insight: Oleuropein reverses high glucose-induced osteogenic inhibition in bone marrow mesenchymal stem cells via Wnt10b activation.

Adverse events of diabetes mellitus (DM) include bone damages, such as the increased incidence of osteoporosis and bone fractures, which are known as diabetic osteopathy. The pathogenic mechanism of diabetic osteopathy is complex, and hyperglycemia is a vital cause involved in it. Bone marrow mesenchymal stem cells (BMSCs) exert a significant effect on bone formation. Therefore, in this paper, transcriptomic changes of BMSCs cultured in high glucose (35 mM) for 30 days are mainly investigated. In addition, 794 up-regulated genes and 1,162 down-regulated genes were identified. Then, biological functions of the differentially expressed genes in the high glucose microenvironment were investigated by two kinds of functional analyses. Gene Set Enrichment Analysis was also applied to focus on the significant gene sets and it is found that Wnt10b expression witnessed a remarkable decrease in BMSCs under the high glucose microenvironment. At last, in vitro experiments revealed that oleuropein effectively reversed high glucose-induced osteogenic inhibition via activating Wnt10b in BMSCs.