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Epigenetic regulation of metabolism profoundly influences cell fate commitment. During osteoclast differentiation, the activation of RANK signaling is accompanied by metabolic reprogramming, but the epigenetic mechanisms by which RANK signaling induces this reprogramming remain elusive. By transcriptional sequence and ATAC analysis, this study identifies that activation of RANK signaling upregulates PRMT6 by epigenetic modification, triggering a metabolic switching from fatty acids oxidation toward glycolysis. Conversely, Prmt6 deficiency reverses this shift, markedly reducing HIF‐1α‐mediated glycolysis and enhancing fatty acid oxidation. Consequently, PRMT6 deficiency or inhibitor impedes osteoclast differentiation and alleviates bone loss in ovariectomized (OVX) mice. At the molecular level, Prmt6 deficiency reduces asymmetric dimethylation of H3R2 at the promoters of genes including Ppard, Acox3, and Cpt1a, enhancing genomic accessibility for fatty acid oxidation. PRMT6 thus emerges as a metabolic checkpoint, mediating metabolic switch from fatty acid oxidation to glycolysis, thereby supporting osteoclastogenesis. Unveiling PRMT6's critical role in epigenetically orchestrating metabolic shifts in osteoclastogenesis offers a promising target for anti‐resorptive therapy. [ABSTRACT FROM AUTHOR]

The shapes of micro‐ and nano‐products have profound influences on their functional performances, which has not received sufficient attention during the past several decades. Electrohydrodynamic atomization (EHDA) techniques, mainly include electrospinning and electrospraying, are facile in manipulate their products' shapes. In this review, the shapes generated using EHDA for modifying drug release profiles are reviewed. These shapes include linear nanofibers, round micro‐/nano‐particles, and beads‐on‐a‐string hybrids. They can be further divided into different kinds of sub‐shapes, and can be explored for providing the desired pulsatile release, sustained release, biphasic release, delayed release, and pH‐sensitive release. Additionally, the shapes resulted from the organizations of electrospun nanofibers are discussed for drug delivery, and the shapes and inner structures can be considered together for developing novel drug delivery systems. In future, the shapes and the related shape–performance relationships at nanoscale, besides the size, inner structure and the related structure–performance relationships, would further play their important roles in promoting the further developments of drug delivery field. This article is categorized under:Therapeutic Approaches and Drug Discovery > Emerging Technologies [ABSTRACT FROM AUTHOR]

Background. Rheumatoid arthritis (RA) remains one of the most prevalent chronic joint diseases. However, due to the heterogeneity among RA patients, there are still no robust diagnostic and therapeutic biomarkers for the diagnosis and treatment of RA. Methods. We retrieved RA-related and pan-cancer information datasets from the Gene Expression Omnibus and The Cancer Genome Atlas databases, respectively. Six gene expression profiles and corresponding clinical information of GSE12021, GSE29746, GSE55235, GSE55457, GSE77298, and GSE89408 were adopted to perform differential expression gene analysis, enrichment, and immune component difference analyses of RA. Four machine learning algorithms, including LASSO, RF, XGBoost, and SVM, were used to identify RA-related biomarkers. Unsupervised cluster analysis was also used to decipher the heterogeneity of RA. A four-signature-based nomogram was constructed and verified to specifically diagnose RA and osteoarthritis (OA) from normal tissues. Consequently, RA-HFLS cell was utilized to investigate the biological role of CRTAM in RA. In addition, comparisons of diagnostic efficacy and biological roles among CRTAM and other classic biomarkers of RA were also performed. Results. Immune and stromal components were highly enriched in RA. Chemokine- and Th cell-related signatures were significantly activated in RA tissues. Four promising and novel biomarkers, including CRTAM, PTTG1IP, ITGB2, and MMP13, were identified and verified, which could be treated as novel treatment and diagnostic targets for RA. Nomograms based on the four signatures might aid in distinguishing and diagnosing RA, which reached a satisfactory performance in both training (AUC = 0.894) and testing (AUC = 0.843) cohorts. Two distinct subtypes of RA patients were identified, which further verified that these four signatures might be involved in the immune infiltration process. Furthermore, knockdown of CRTAM could significantly suppress the proliferation and invasion ability of RA cell line and thus could be treated as a novel therapeutic target. CRTAM owned a great diagnostic performance for RA than previous biomarkers including MMP3, S100A8, S100A9, IL6, COMP, LAG3, and ENTPD1. Mechanically, CRTAM could also be involved in the progression through immune dysfunction, fatty acid metabolism, and genomic instability across several cancer subtypes. Conclusion. CRTAM, PTTG1IP, ITGB2, and MMP13 were highly expressed in RA tissues and might function as pivotal diagnostic and treatment targets by deteriorating the immune dysfunction state. In addition, CRTAM might fuel cancer progression through immune signals, especially among RA patients. [ABSTRACT FROM AUTHOR]

Background and Aim: Cervical hyperextension injury is very frequent with anterior longitudinal ligament (ALL) injury, and the ligament damage has a remarkable effect on whether and what type of operation should be performed. This study aims to establish a new scoring system for the accurate diagnosis of ALL damage. Methods: The imaging data of the consecutive patients was measured and scored by four radiologists. Intraoperative exploration was performed by three surgeons. The crude and adjusted odds ratios (cOR and aOR) and receiver operating characteristic curve (ROC) were constructed to assess the diagnostic accuracy of the scoring system. Results: A total of 255 patients with cervical spine trauma were included in this study. There was no statistical difference in the relationship between demographics and ALL injuries (P > 0.05). Thickness of prevertebral soft tissue (aOR = 11.922, P = 0.004), intervertebral disk angle (aOR = 13.21, P = 0.002), avulsion fracture of the anterior edge of the vertebral body (aOR = 13.844, P = 0.029), ALL disrupted in T1-weighted sequence (aOR = 18.349, P < 0.001), and high signal area in T2-weighted sequence (aOR = 20.898, P = 0.002) had significantly higher diagnostic accuracy. The scoring system's sensitivity and specificity were 94.0% and 88.1%, respectively, and the accuracy was 90.8%. Conclusion: The study established a new scoring system for ALL injuries based on the analysis of a series of clinical data and statistics. A total of five scoring items, a total score of 7 points, and an ALL injury may be diagnosed when the score is not less than 3 points. This scoring system enables an efficient and accurate diagnosis of all injuries. [ABSTRACT FROM AUTHOR]

Objective: Previous studies have neither explored the usage of cross‐links nor investigated the optimal position of the cross‐links in posterior lumbar interbody fusion (PLIF). This study evaluates biomechanical properties of cross‐links in terms of different fixation segments and optimal position in single‐ and multi‐segment posterior lumbar interbody fusion. Methods: Two finite element (FE) models of instrumented lumbosacral spine with single‐(L4/5) and multi‐segment (L3‐S1) PLIF surgery were simulated. On the basis of the two models, the benefits of the usage of cross‐links were assessed and compared with the status of no application of cross‐links. Moreover, the effects of position of cross‐links on multi‐segment PLIF surgery were studied in Upper, Middle, and Lower positions. Results: No significant difference was found in the range of motion (ROM), intersegmental rotational angle (IRA) of adjacent segments, and intradiscal pressure (IDP) regardless of the usage of cross‐links in the single‐segment PLIF surgery, while the cross‐link increased the maximum von Mises stress in the fixation (MSF) under the axial rotation (53.65 MPa vs 41.42 MPa). In the multi‐segment PLIF surgery, the usage of cross‐links showed anti‐rotational advantages indicated by ROM (Without Cross‐link 2.35o, Upper, 2.24o; Middle, 2.26o; Lower, 2.30o) and IRA (Without Cross‐link 1.19o, Upper, 1.08o; Middle, 1.09o; Lower, 1.13o). The greatest values of MSF were found in without cross‐link case under the flexion, lateral bending, and axial rotation (37.48, 62.61, and 86.73 MPa). The application of cross‐links at the Middle and Lower positions had lower values of MSF (48.79 and 69.62 MPa) under the lateral bending and axial rotation, respectively. Conclusion: The application of cross‐links was not beneficial for the single‐segment PLIF, while it was found highly advantageous for the multi‐segment PLIF. Moreover, the usage of cross‐links at the Middle or Lower positions resulted in a better biomechanical stability. [ABSTRACT FROM AUTHOR]