Implications of MCU complex in metabolic diseases.

Metabolic diseases are considered the primary culprit for physical and mental health of individuals. Although the diagnosis of these diseases is relatively easy, more effective and convenient potent drugs are still being explored. Ca2+ across the inner mitochondrial membrane is a vital intracellular messenger that regulates energy metabolism and cellular Ca2+ homeostasis and is involved in cell death. Mitochondria rely on a selective mitochondrial Ca2+ unidirectional transport complex (MCU complex) in their inner membrane for Ca2+ uptake. We found that the channel contains several subunits and undergoes dramatic transformations in various pathological processes, especially in metabolic diseases. In this way, we believe that the MCU complex becomes a target with significant potential for these diseases. However, there is no review linking the two factors, thus hindering the possibility of new drug production. Here, we highlight the connection between MCU complex-related Ca2+ transport and the pathophysiology of metabolic diseases, adding understanding and insight at the molecular level to provide new insights for targeting MCU to reverse metabolism-related diseases.

The role of mitochondria in the peri-implant microenvironment.

NEW FINDINGS: What is the topic of this review? In this review, we consider the key role of mitochondria in the peri-implant milieu, including the regulation of mitochondrial reactive oxygen species and mitochondrial metabolism in angiogenesis, the polarization of macrophage immune responses, and bone formation and bone resorption during osseointegration. What advances does it highlight? Mitochondria contribute to the behaviours of peri-implant cell lines based on metabolic and reactive oxygen species signalling modulations, which will contribute to the research field and the development of new treatment strategies for improving implant success. ABSTRACT: Osseointegration is a dynamic biological process in the local microenvironment adjacent to a bone implant, which is crucial for implant performance and success of the implant surgery. Recently, the role of mitochondria in the peri-implant microenvironment during osseointegration has gained much attention. Mitochondrial regulation has been verified to be essential for cellular events in osseointegration and as a therapeutic target for peri-implant diseases in the peri-implant microenvironment. In this review, we summarize our current knowledge of the key role of mitochondria in the peri-implant milieu, including the regulation of mitochondrial reactive oxygen species and mitochondrial metabolism in angiogenesis, the polarization of macrophage immune responses, and bone formation and resorption during osseointegration, which will contribute to the research field and the development of new treatment strategies to improve implant success. In addition, we indicate limitations in our current understanding of the regulation of mitochondria in osseointegration and suggest topics for further study.

BAP1 and YY1 regulate expression of death receptors in malignant pleural mesothelioma.

Malignant pleural mesothelioma (MPM) is a rare, aggressive, and incurable cancer arising from the mesothelial lining of the pleura, with few available treatment options. We recently reported that loss of function of the nuclear deubiquitinase BRCA1-associated protein 1 (BAP1), a frequent event in MPM, is associated with sensitivity to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis. As a potential underlying mechanism, here we report that BAP1 negatively regulates the expression of TRAIL receptors: death receptor 4 (DR4) and death receptor 5 (DR5). Using tissue microarrays of tumor samples from MPM patients, we found a strong inverse correlation between BAP1 and TRAIL receptor expression. BAP1 knockdown increased DR4 and DR5 expression, whereas overexpression of BAP1 had the opposite effect. Reporter assays confirmed wt-BAP1, but not catalytically inactive BAP1 mutant, reduced promoter activities of DR4 and DR5, suggesting deubiquitinase activity is required for the regulation of gene expression. Co-immunoprecipitation studies demonstrated direct binding of BAP1 to the transcription factor Ying Yang 1 (YY1), and chromatin immunoprecipitation assays revealed BAP1 and YY1 to be enriched in the promoter regions of DR4 and DR5. Knockdown of YY1 also increased DR4 and DR5 expression and sensitivity to TRAIL. These results suggest that BAP1 and YY1 cooperatively repress transcription of TRAIL receptors. Our finding that BAP1 directly regulates the extrinsic apoptotic pathway will provide new insights into the role of BAP1 in the development of MPM and other cancers with frequent BAP1 mutations.

GelMA/κ-carrageenan double-network hydrogels with superior mechanics and biocompatibility.

Hydrogels are crosslinked hydrophilic polymer networks of high-water content. Although they have been widely investigated, preparing hydrogels with excellent mechanical properties and biocompatibility remains a challenge. In the present work, we developed a novel GelMA/κ-carrageenan (GelMA/KC) double network (DN) hydrogel through a dual crosslinking strategy. The three-dimensional (3D) microstructure of KC is the first network, and covalently crosslinked on the κ-carrageenan backbone is the second network. The GelMA/KC hydrogel shows advantages in physical properties, including higher compression strength (10% GelMA/1% KC group, 130 kPa) and Young's modulus (10% GelMA/1% KC group, 300), suggesting its excellent elasticity and compressive capability. When using a higher concentration of GelMA, the hybrid hydrogel has even higher mechanical properties. In addition, the GelMA/KC hydrogel is favorable for cell spreading and proliferation, demonstrating its excellent biocompatibility. This study provides a new possibility for a biodegradable and high-strength hydrogel as a new generation material of orthopedic implants.

Perturbation of mitochondrial dynamics links to the aggravation of periodontitis by diabetes.

Diabetes and periodontitis are prevalent diseases that considerably impact global economy and diabetes is a major risk factor of periodontitis. Mitochondrial dynamic alterations are involved in many diseases including diabetes and this study aims to evaluate their relevance with diabetes aggravated periodontitis. Sixty mice are randomly divided into 4 groups: control, periodontitis, diabetes and diabetic periodontitis. Periodontitis severity is evaluated by alveolar bone loss, inflammation and oxidative stress status. Mitochondrial structural and functional defects are evaluated by the mitochondrial fission/fusion events, mitochondrial reactive oxygen species (ROS) accumulation, complex activities and adenosine triphosphate (ATP) production. Advanced glycation end product (AGE) and Porphyromonas gingivalis are closely related to periodontitis occurrence and development. Human gingival fibroblast cells (HGF-1) are used to investigate the AGE role and lipopolysaccharide (LPS) from Porphyromonas gingivalis (P-LPS) in aggravating diabetic periodontitis by mitochondrial dynamic and function alterations. In vivo, diabetic mice with periodontitis show severe bone loss, increased inflammation and oxidative stress accumulation. Among mice with periodontitis, diabetic mice show worse mitochondrial dynamic perturbations than lean mice, along with fusion protein levels inducing more mitochondrial fission in gingival tissue. In vitro, AGEs and P-LPS co-treatment causes severe.

Aided Recognition and Training of Music Features Based on the Internet of Things and Artificial Intelligence.

With the development of the Internet of Things, many industries have been on the train of the information age, and digital audio technology is also constantly developing. Music retrieval has gradually become a research hotspot in the music industry. Among them, the auxiliary recognition of music characteristics is also a particularly important Task. Music retrieval is mainly to manually extract music signals, but now the music signal extraction technology has encountered a bottleneck. The article uses Internet and artificial intelligence technology to design an SNN music feature recognition model to identify and classify music features. The research results of the article show (1) statistic graphs of the main melody and accompanying melody of different music. The absolute value of the main melody and accompanying melody mainly fluctuates in the range of 0-7, and the proportion of the main melody can reach 36%. The accompanying melody can reach 17%. After the absolute value of the interval reaches 13, the interval ratio of the main melody and the accompanying melody tends to be stable, maintaining between 0.6 and 0.9, and the melody interval ratio value completely coincides; the main melody in the interval variable is X. (1) The relative difference value in the interval of -X(16) fluctuates greatly. After the absolute value of the interval reaches 17, the interval ratio of the main melody and the accompanying melody tends to be stable, maintaining between 0.01 and 0.04 and the main melody. The value of the difference is always higher than the accompanying melody. (2) When the number of feature maps is 24∗5, the recognition result is the most accurate, MAP recognition result can reach 78.8, and the recognition result of precision@ is 79.2; when the feature map size is 5∗5, the recognition result is the most accurate, MAP recognition result can reach 78.9, the recognition result of precision@ is 79.2, and the recognition result of HAM2 (%) is 78.6. The detection accuracy of the SNN music recognition model proposed in the article is the highest. When the number of bits is 64, the detection accuracy of the SNN detection model is 59.2%, and the detection accuracy of the improved SNN music recognition model is 79.3%, which is better than the detection rate of ITQ music recognition model of 17.9%, which is 61.4% higher. The experimental data further shows that the detection efficiency of the ITQ music recognition model is the highest. (3) The SNN music recognition model proposed in the article has the highest detection accuracy, regardless of whether it is in a noisy or no-noise music environment, with an accuracy rate of 97.97% and a detection accuracy value of 0.88, which is 5 types of music. The highest one among the recognition models, the ITQ music recognition model, has the lowest detection accuracy, with a detection accuracy of 67.47% in the absence of noise and a detection accuracy of 70.23% in the presence of noise. Although there is a certain noise removal technology, it can suppress noise interference to a certain extent, but cannot accurately describe music information, and the detection accuracy rate is also low.

Nutrient Element Decorated Polyetheretherketone Implants Steer Mitochondrial Dynamics for Boosted Diabetic Osseointegration.

As a chronic metabolic disease, diabetes mellitus (DM) creates a hyperglycemic micromilieu around implants, resulting inthe high complication and failure rate of implantation because of mitochondrial dysfunction in hyperglycemia. To address the daunting issue, the authors innovatively devised and developed mitochondria-targeted orthopedic implants consisted of nutrient element coatings and polyetheretherketone (PEEK). Dual nutrient elements, in the modality of ZnO and Sr(OH)2 , are assembled onto the sulfonated PEEK surface (Zn&Sr-SPEEK). The results indicate the synergistic liberation of Zn2+ and Sr2+ from coating massacres pathogenic bacteria and dramatically facilitates cyto-activity of osteoblasts upon the hyperglycemic niche. Intriguingly, Zn&Sr-SPEEK implants are demonstrated to have a robust ability to recuperate hyperglycemia-induced mitochondrial dynamic disequilibrium and dysfunction by means of Dynamin-related protein 1 (Drp1) gene down-regulation, mitochondrial membrane potential (MMP) resurgence, and reactive oxygen species (ROS) elimination, ultimately enhancing osteogenicity of osteoblasts. In vivo evaluations utilizing diabetic rat femoral/tibia defect model at 4 and 8 weeks further confirm that nutrient element coatings substantially augment bone remodeling and osseointegration. Altogether, this study not only reveals the importance of Zn2+ and Sr2+ modulation on mitochondrial dynamics that contributes to bone formation and osseointegration, but also provides a novel orthopedic implant for diabetic patients with mitochondrial modulation capability.

Anterior aesthetic restoration with ultrathin porcelain veneers on asymmetric faces assisted by a four-dimensional smile design: a case report and literature review / 口腔疾病防治

Objective@#To explore the application effect of a four-dimensional smile design as the leading and facial streamline as the reference system in the aesthetic restoration of anterior teeth.@*Methods@# A case of scattered space in anterior teeth was treated with a four-dimensional smile design and digital aesthetic restoration with ultrathin porcelain veneer. The digital information of the patients was obtained through oral and facial scanning, and a four-dimensional smile design and prediction were carried out. After the treatment plan was jointly determined by doctors and patients, minimally invasive abutment preparation was carried out, and ultrathin porcelain veneer was made and bonded in place. After the operation, the esthetic degree and marginal fit were observed and reexamined one year after the repair.@* Results @#The edges of the ultrathin ceramic veneers were naturally tight, and the color was coordinated, with satisfying pink and white esthetics. The face was more harmonious and natural when smiling. One year after the restoration, the facial aesthetics were wonderful, the abutment teeth and periodontal tissues were healthy, and the patients were satisfied. The results of the literature review showed that the fitting of temporal facial scanning and intraoral scanning data can accurately predict four-dimensional smile aesthetics, simulate the real state of the dynamic smile and pronunciation process, and combine it with facial streamlines to design a natural and coordinated personalized smile for patients with asymmetric faces. However, for patients with occlusal changes, unstable occlusion or temporomandibular joint disorder, it is necessary to add data fitting, such as electronic facial arch and cone beam CT, to more accurately simulate postoperative mandibular movement.@*Conclusion@# With a four-dimensional smile design as the leading and facial streamline as the reference system, the whole process digital design assisted the restoration of asymmetric anterior teeth with ultrathin porcelain veneer and had a good effect. The postoperative smiling of patients is harmonious and beautiful, which is in line with the expected effect. Patient participation and satisfaction are high; thus, this method is worthy of clinical promotion.