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Background: Periodontal ligament stem cells (PDLSCs) are important seed cells in tissue engineering and clinical applications. They are the priority receptor cells for sensing various mechanical stresses. Yes-associated protein (YAP) is a recognized mechanically sensitive transcription factor. However, the role of YAP in regulating the fate of PDLSCs under tension stress (TS) and its underlying mechanism is still unclear. Methods: The effects of TS on the morphology and fate of PDLSCs were investigated using fluorescence staining, transmission electron microscopy, flow cytometry and quantitative real-time polymerase chain reaction (qRT-PCR). Then qRT-PCR, western blotting, immunofluorescence staining and gene knockdown experiments were performed to investigate the expression and distribution of YAP and its correlation with PDLSCs proliferation. The effects of cytoskeleton dynamics on YAP nuclear translocation were subsequently explored by adding cytoskeleton inhibitors. The effect of cytoskeleton dynamics on the expression of the LINC complex was proved through qRT-PCR and western blotting. After destroying the LINC complex by adenovirus, the effects of the LINC complex on YAP nuclear translocation and PDLSCs proliferation were investigated. Mitochondria-related detections were then performed to explore the role of mitochondria in YAP nuclear translocation. Finally, the in vitro results were verified by constructing orthodontic tooth movement models in Sprague-Dawley rats. Results: TS enhanced the polymerization and stretching of F-actin, which upregulated the expression of the LINC complex. This further strengthened the pull on the nuclear envelope, enlarged the nuclear pore, and facilitated YAP's nuclear entry, thus enhancing the expression of proliferation-related genes. In this process, mitochondria were transported to the periphery of the nucleus along the reconstructed microtubules. They generated ATP to aid YAP's nuclear translocation and drove F-actin polymerization to a certain degree. When the LINC complex was destroyed, the nuclear translocation of YAP was inhibited, which limited PDLSCs proliferation, impeded periodontal tissue remodeling, and hindered tooth movement. Conclusions: Our study confirmed that appropriate TS could promote PDLSCs proliferation and periodontal tissue remodeling through the mechanically driven F-actin/LINC complex/YAP axis, which could provide theoretical guidance for seed cell expansion and for promoting healthy and effective tooth movement in clinical practice. [ABSTRACT FROM AUTHOR]

Inflammatory bowel disease (IBD) is a chronic disease that includes Crohn’s disease (CD) and ulcerative colitis (UC). Although genome-wide association studies (GWASs) have identified many relevant genetic risk loci, the impact of these loci on protein abundance and their potential utility as clinical therapeutic targets remain uncertain. Therefore, this study aimed to investigate the pathogenesis of IBD and identify effective therapeutic targets through a comprehensive and integrated analysis. We systematically integrated GWAS data related to IBD, UC and CD (N = 25,305) by the study of de Lange KM with the human blood proteome (N = 7213) by the Atherosclerosis Risk in Communities (ARIC) study. Proteome-wide association study (PWAS), mendelian randomisation (MR) and Bayesian colocalisation analysis were used to identify proteins contributing to the risk of IBD. Integrative analysis revealed that genetic variations in IBD, UC and CD affected the abundance of five (ERAP2, RIPK2, TALDO1, CADM2 and RHOC), three (VSIR, HGFAC and CADM2) and two (MST1 and FLRT3) cis-regulated plasma proteins, respectively (P < 0.05). Among the proteins identified via Bayesian colocalisation analysis, CADM2 was found to be an important common protein between IBD and UC. A drug and five druggable target genes were identified from DGIdb after Bayesian colocalisation analysis. Our study's findings from genetic and proteomic approaches have identified compelling proteins that may serve as important leads for future functional studies and potential drug targets for IBD (UC and CD). [ABSTRACT FROM AUTHOR]

Rechargeable aqueous zinc–metal batteries (AZBs) are a promising complimentary technology to the existing lithium‐ion batteries and the re‐emerging lithium–metal batteries to satisfy the increasing demands on energy storage. Despite considerable progress achieved in the past years, the fundamental understanding of the solid‐electrolyte interphase (SEI) formation and how its composition influences the SEI properties are limited. This review highlights the functionalities of anion‐tuned SEI on the reversibility of zinc–metal anode, with a specific emphasis on new structural insights obtained through advanced characterizations and computational techniques. Recent efforts in terms of key variables that govern the interfacial behaviors to improve the long‐term stability of zinc anode, i.e., Coulombic efficiency, plating morphology, dendrite formation, and side‐reactions, are comprehensively reviewed. Lastly, the remaining challenges and future perspectives are presented, providing insights into the rational design of practical high‐performance AZBs. [ABSTRACT FROM AUTHOR]

Background Orthodontic space closure of extraction sites can be initiated early, within 1-week post-extraction, or it can be delayed for a month or more. Objective This systematic review aimed to evaluate the effect of early versus delayed initiation of space closure after tooth extraction on the rate of orthodontic tooth movement. Search methods Unrestricted search of 10 electronic databases was conducted until September 2022. Selection criteria Randomized controlled trials (RCTs) investigating the initiation time of space closure of extraction sites in patients undergoing orthodontic treatment were included. Data collection and analysis Data items were extracted using a pre-piloted extraction form. The Cochrane's risk of bias tool (ROB 2.0) and the Grading of Recommendations, Assessment, Development, and Evaluation approach were used for quality assessment. Meta-analysis was undertaken if there are at least two trials reporting the same outcome. Results Eleven RCTs met the inclusion criteria. Meta-analysis revealed that early canine retraction resulted in a statistically significant higher rate of maxillary canine retraction when compared to delayed canine retraction [mean difference (MD); 0.17 mm/month, 95% CI: 0.06 to 0.28, P  = 0.003, 4 RCTs, moderate quality]. Duration of space closure was shorter in the early space closure group, but not statistically significant (MD; 1.11 months, 95% CI: −0.27 to 2.49, P  = 0.11, 2 RCTs, low quality). The incidence of gingival invaginations was not statistically different between early and delayed space closure groups (Odds ratio; 0.79, 95% CI: 0.27 to 2.29, 2 RCTs, P  = 0.66, very low quality). Qualitative synthesis found no statistically significant differences between the two groups regarding anchorage loss, root resorption, tooth tipping, and alveolar bone height. Conclusions Based on the available evidence, early traction within the first week after tooth extraction has a minimal clinically significant effect on the rate of tooth movement compared to delayed traction. Further high-quality RCTs with standardized time points and measurement methods are still needed. Registration PROSPERO (CRD42022346026). [ABSTRACT FROM AUTHOR]

Background: Diabetes mellitus (DM) and periodontitis are two prevalent diseases with mutual influence. Accumulation of advanced glycation end products (AGEs) in hyperglycemia may impair cell function and worsen periodontal conditions. N6-methyladenosine (m6A) is an important post-transcriptional modification in RNAs that regulates cell fate determinant and progression of diseases. However, whether m6A methylation participates in the process of periodontitis with diabetes is unclear. Thus, we aimed to investigate the effects of AGEs on bone marrow mesenchymal stem cells (BMSCs), elucidate the m6A modification mechanism in diabetes-associated periodontitis. Methods: Periodontitis with diabetes were established by high-fat diet/streptozotocin injection and silk ligation. M6A modifications in alveolar bone were demonstrated by RNA immunoprecipitation sequence. BMSCs treated with AGEs, fat mass and obesity associated (FTO) protein knockdown and sclerostin (SOST) interference were evaluated by quantitative polymerase chain reaction, western blot, immunofluorescence, alkaline phosphatase and Alizarin red S staining. Results: Diabetes damaged alveolar bone regeneration was validated in vivo. In vitro experiments showed AGEs inhibited BMSCs osteogenesis and influenced the FTO expression and m6A level in total RNA. FTO knockdown increased the m6A levels and reversed the AGE-induced inhibition of BMSCs differentiation. Mechanically, FTO regulated m6A modification on SOST transcripts, and AGEs affected the binding of FTO to SOST transcripts. FTO knockdown accelerated the degradation of SOST mRNA in presence of AGEs. Interference with SOST expression in AGE-treated BMSCs partially rescued the osteogenesis by activating Wnt Signaling. Conclusions: AGEs impaired BMSCs osteogenesis by regulating SOST in an m6A-dependent manner, presenting a promising method for bone regeneration treatment of periodontitis with diabetes. [ABSTRACT FROM AUTHOR]