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Abstract Background Prefabricated myofunctional appliance can guide tooth eruption, improve dentition alignment, correct myofunctional disorders and harmful oral habits. However, its application to skeletal discrepancy may result in unsatisfactory tooth inclination. This study aimed to construct a novel appliance with overjet design to avoid this side effect and investigated its shape and mechanical changes under occlusion using three-dimensional finite element method. Methods We established three samples of prefabricated myofunctional appliances. The first one was edge to edge without overjet, and the outer shield of both jaws were flattened. The second one was 3 mm overjet with stepped the outer shield. The last one was 3 mm overjet, and the outer shield of both jaws were flatted, which meant the front wall of lower jaw was strengthened with bumper, termed as lower bumper. A complete dentition model was applied to the study. 150 N occlusal force was applied to each type of appliance and the deformation displacement and the changes in stress was recorded. Results The deformation was significant in the incisors regions, especially in the vertical and lateral dimensions. The maximum displacements of 3 mm overjet with step shield group were 7.08 mm (vertical), 3.99 mm (lateral), and 2.90 mm (sagittal), while it decreased to 3.92 mm(vertical), 1.94 mm (lateral), and 1.55 mm (sagittal) in overjet with bumper group. Moreover, the upper molar regions exhibited higher vertical and sagittal displacement in 3 mm overjet with step shield group, which were 3.03 mm (vertical) and 1.99 mm (sagittal), and the bumper design could decrease the maximum displacement to 1.72 mm (vertical) and 0.72 mm (sagittal). In addition, the Von Mises stress of appliances was analyzed, and results indicated that 3 mm overjet with step shield generated higher stress than other groups, with the maximum Von Mises stress was 0.9387 MP, which were 0.5858 and 0.5657 MP in edge to edge group and 3 mm overjet with lower bumper group, respectively. Conclusion The prefabricated myofunctional appliances may cause deformation during occlusion. Compared to step shield group, the application of lower bumper exhibited better resistance to occlusal force.

Purpose: Liposomes co-encapsulating doxorubicin (DOX) and verapamil (VER), and conjugated to transferrin (Tf-L-DOX/VER) were synthesized and evaluated in K562 leukemia cells. The design of this formulation was aimed at selective targeting of tumor cells, reducing cardiotoxicity of DOX and VER, as well as overcoming P-glycoprotein (Pgp)-mediated multidrug resistance (MDR) phenotype., Methods: The liposomes were prepared by polycarbonate membrane extrusion, followed by pH-gradient driven remote loading and Tf conjugation. Kinetics of in vitro release of DOX and VER from liposomes was determined by measuring changes in the concentration of encapsulated drugs. Uptake of Tf-conjugated liposomes by K562 cells was evaluated by fluorescence microscopy and by fluorometry. Cytotoxicities of various formulations of DOX were determined by a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolum bromide (MTT) assay., Results: Efficiencies for liposomal loading of DOX and VER were 95% and 70%, respectively. The mean particle diameter for the liposomes was approximately 110nm. Rates of release for DOX and VER were similar in singly-loaded and co-loaded liposomes. Tf-L-DOX/VER showed efficient uptake by the TfR+ K562 cells. In DOX-resistant K562 cells (K562/DOX), Tf-L-DOX/VER showed 5.2 and 2.8 times greater cytotoxicity (IC50 = 4.18 muM) than non-targeted liposomes (L-DOX/VER) (IC50 = 21.7 muM) and Tf-targeted liposomes loaded with DOX alone (Tf-L-DOX) (IC50 = 11.5 muM), respectively., Conclusions: The combination of TfR targeting and co-encapsulation of DOX and VER was highly effective in overcoming drug resistance in K562 leukemia cells.