Mechanical force system of double key loop with finite element analysis.

BACKGROUND: The mechanics of double key loop (DKL) are not well defined, and this finite element study was designed to explore its force system. METHODS: A simplified 3-dimensional finite element model of single and double key loops with an archwire between the lateral incisor and second premolar was established in Ansys Workbench 17.0. Activation in Type-1 (retraction at the distal end), Type-2 (retraction at the distal key) and Type-3 (Type-2 plus ligation between keys) was simulated. The vertical force, load/deflection ratio and moment/force ratio of stainless-steel and titanium-molybdenum alloy (TMA) loops were calculated and compared. RESULTS: The double key loop generated approximately 40% of the force of a single key loop. Type-2 loading of DKL showed a higher L/D ratio than Type-1 loading with a similar M/F ratio. Type-3 loading of DKL showed the highest M/F ratio with a similar L/D ratio as single key loop. The M/F ratio in Type-3 loading increased with the decreasing of retraction force. The DKL of TMA produced approximately 40% of the force and moment compared with those of SS in all loading types. When activated at equal distances below 1 mm, the M/F ratios of SS and TMA DKL with equal preactivation angles were almost the same. CONCLUSION: The M/F ratio on anterior teeth increases with the preactivation angle and deactivation of DKL. The M/F ratio at a certain distance of activation mainly depends on the preactivation angle instead of the wire material. TMA is recommended as a substitute for SS in DKL for a lower magnitude of force.

Noninvasive model for predicting future ischemic strokes in patients with silent lacunar infarction using radiomics.

BACKGROUND: This study aimed to investigate integrating radiomics with clinical factors in cranial computed tomography (CT) to predict ischemic strokes in patients with silent lacunar infarction (SLI). METHODS: Radiomic features were extracted from baseline cranial CT images of patients with SLI. A least absolute shrinkage and selection operator (LASSO)-Cox regression analysis was used to select significant prognostic factors based on ModelC with clinical factors, ModelR with radiomic features, and ModelCR with both factors. The Kaplan-Meier method was used to compare stroke-free survival probabilities. A nomogram and a calibration curve were used for further evaluation. RESULTS: Radiomic signature (p < 0.01), age (p = 0.09), dyslipidemia (p = 0.03), and multiple infarctions (p = 0.02) were independently associated with future ischemic strokes. ModelCR had the best accuracy with 6-, 12-, and 18-month areas under the curve of 0.84, 0.81, and 0.79 for the training cohort and 0.79, 0.88, and 0.75 for the validation cohort, respectively. Patients with a ModelCR score < 0.17 had higher probabilities of stroke-free survival. The prognostic nomogram and calibration curves of the training and validation cohorts showed acceptable discrimination and calibration capabilities (concordance index [95% confidence interval]: 0.7864 [0.70-0.86]; 0.7140 [0.59-0.83], respectively). CONCLUSIONS: Radiomic analysis based on baseline CT images may provide a novel approach for predicting future ischemic strokes in patients with SLI. Older patients and those with dyslipidemia or multiple infarctions are at higher risk for ischemic stroke and require close monitoring and intensive intervention.

[Finite-element investigation on center of resistance of maxillary anterior teeth].

A three-dimensional finite element model of premaxillary bone and anterior teeth was established with ANSYS 13.0. The anterior teeth were fixed with strong stainless labial archwire and lingual frame. In the horizontal loading experiments, a horizontal retraction force of 1.5 N was applied bilaterally to the segment through hooks at the same height between 7 and 21 mm from the incisal edge of central incisor; in vertical loading experiments, a vertical intrusion force of 1.5 N was applied at the midline of lingual frame with distance between 4 and 16 mm from the incisal edge of central incisor. After loading, solution was done and displacement and maximum principle stress were calculated. After horizontal loading, lingual displacement and stress in periodontal membrane (PDM) was most homogeneous when the traction force was 14 mm from the edge of central incisor; after vertical loading, intrusive displacement and stress in PDM were most homogeneous when the traction force was 12 mm from the incisal edge of central incisor. The results of this study suggested that the location of center of resistance (CRe) of six maxillary anterior teeth is about 14 mm gingivally and 12 mm lingually to incisal edge of central incisor. The location can provide evidence for theoretical and clinical study in orthodontics.

A natural compound melatonin enhances the effects of Nimotuzumab via inhibiting EGFR in glioblastoma.

Sleep disorders are prevalent and debilitating symptoms in primary brain tumor patients, notably those receiving radiation therapy. Nevertheless, the relationship between sleep disorders, melatonin - a circadian rhythm regulatory hormone, and gliomas is underexplored. Melatonin exhibits various biological functions, one of them being anti-tumor activity. In the context of gliomas, often overexpressing EGFR, the humanized monoclonal antibody Nimotuzumab targets this marker. Our research discovered that variations in circadian rhythm significantly influence tumor growth in mice through impacting melatonin secretion. Harnessing proteogenomic, we identified that melatonin could inhibit the phosphorylation of EGFR and its downstream effectors, key elements in angiogenesis and tumor progression. Building on structural simulations, we propose that melatonin may amplify Nimotuzumab's anti-glioma efficacy by inhibiting EGFR TK dimerization. This proposition was validated in our in vitro and in vivo studies where melatonin synergistically augmented cytotoxicity and apoptosis in Nimotuzumab-treated glioma cells. Thus, melatonin shows promise as a beneficial addition to Nimotuzumab treatment in glioma patients.

Mesoporous Hydroxyapatite Nanoparticles Mediate the Release and Bioactivity of BMP-2 for Enhanced Bone Regeneration.

Efficient delivery of bone morphogenetic protein-2 (BMP-2) with desirable bioactivity is still a great challenge in the field of bone regeneration. In this study, a silk fibroin/chitosan scaffold incorporated with BMP-2-loaded mesoporous hydroxyapatite nanoparticles (mHANPs) was prepared (SCH-L). BMP-2 was preloaded onto mHANPs with a high surface area before mixing with a silk fibroin/chitosan composite. Bare (without BMP-2) silk fibroin/chitosan/mHANP (SCH) scaffolds and SCH scaffolds with directly absorbed BMP-2 (SCH-D) were investigated in parallel for comparison. In vitro release kinetics indicated that BMP-2 released from the SCH-L scaffold showed a significantly lower initial burst release, followed by a more sustained release over time than the SCH-D scaffold. In vitro cell viability, osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs), and the in vivo osteogenic effect of scaffolds in a rat calvarial defect were evaluated. The results showed that compared with bare SCH and SCH-D scaffolds, the SCH-L scaffold significantly promoted the osteogenic differentiation of BMSCs in vitro and induced more pronounced bone formation in vivo. Further studies demonstrated that the mHANP-mediated satisfactory conformational change and sustained release benefited the protection of the released BMP-2 bioactivity, as confirmed by alkaline phosphatase (ALP) activity and a mineralization deposition assay. More importantly, the interaction of BMP-2/mHANPs enhanced the binding ability of BMP-2 to cellular receptors, thereby maintaining its biological activity in osteogenic differentiation and osteoinductivity well, which contributed to the markedly promoted in vitro and in vivo osteogenic efficacy of the SCH-L scaffold. Taken together, these results provide strong evidence that mHANPs represent an attractive carrier for binding BMP-2 to scaffolds. The SCH-L scaffold shows promising potential for bone tissue regeneration applications.

Graphene oxide coated Titanium Surfaces with Osteoimmunomodulatory Role to Enhance Osteogenesis.

Graphene oxide (GO) and its derivatives are currently being explored for the modification of bone biomaterials. However, the effect of GO coatings on immunoregulation and subsequent impacts on osteogenesis are not known. In this study, GO was coated on pure titanium using dopamine. GO-coated titanium (Ti-GO) surfaces exhibited good biocompatibility, with the ability to stimulate the expression of osteogenic genes, and extracellular matrix mineralization in human mesenchymal stromal cells (hMSCs). Interestingly, it was found that GO-coated surfaces could manipulate the polarization of macrophages and expression of inflammatory cytokines via the Toll-like receptor pathway. Under physiological conditions, Ti-GO activated macrophages and induced mild inflammation and a pro-osteogenic environment, characterized by a slight increase in the levels of proinflammatory cytokines, as well as increased expression of the TGF-ß1 and oncostatin M genes. In an environment mimicking acute inflammatory conditions, Ti-GO attenuated inflammatory responses, as shown by the downregulation of proinflammatory cytokines. Conditioned medium collected from macrophages stimulated by Ti-GO played a significant stimulatory role in the osteogenic differentiation of hMSCs. In summary, GO-coated surfaces displayed beneficial immunomodulatory effects in osteogenesis, indicating that GO could be a potential substance for the modification of bone scaffolds and implants.

Synergistic regulation of osteoimmune microenvironment by IL-4 and RGD to accelerate osteogenesis.

The control of early inflammatory reactions and recruitment of progenitor cells are critical for subsequent tissue repair and regeneration after biomaterial implantation. The aim of this study was to design a multi-functional biomaterial with a controlled drug delivery system to create an optimal local environment for early osteogenesis. Here, the anti-inflammatory cytokine IL-4 and pro-osteogenic RGD peptide were assembled layer-by-layer on TiO2 nanotubes. A poly(dopamine) (DOP) coating was employed onto TiO2 nanotubes (T/DOP) to functionalized with IL-4 (T/DOP-IL4). Then, a carboxymethyl chitosan hydrogel layer (CG) was generated on T/DOP-IL4 to control IL-4 release and RGD peptide immobilization. Cell co-culture models were applied to study macrophage polarization on various material surfaces and the regulation of mesenchymal stromal cell (MSC) osteogenic differentiation. Our data suggest that T/DOP-IL4/CG-RGD surfaces developed in this study are multi-functional, and can not only drive phenotypic changes in macrophages (switching to anti-inflammatory M2 phenotype), resulting in the production of reparative cytokines such as IL-10, but also enhance MSC differentiation related to the activation of BMP/SMAD/RUNX2 signaling. This study further confirmed that the introduction of anti-inflammatory cytokine (IL-4) and cell adhesive motif (RGD) onto Ti substrate can work synergistically to generate a more favorable early-stage osteo-immune environment with superior osteogenic properties, thus representing a potential ideal surface for the generation of bone biomaterials.

Inhibition of Caspase-1 Ameliorates Ischemia-Associated Blood-Brain Barrier Dysfunction and Integrity by Suppressing Pyroptosis Activation.

Ischemic cerebral infarction represents a significant cause of disability and death worldwide. Caspase-1 is activated by the NLRP3/ASC pathway and inflammasomes, thus triggering pyroptosis, a programmed cell death. In particular, this death is mediated by gasdermin D (GSDMD), which induces secretion of interleukin (IL)-1ß and IL-18. Accordingly, inhibition of caspase-1 prevents the development and worsening of multiple neurodegenerative diseases. However, it is not clear whether inhibition of caspase-1 can preserve blood-brain barrier (BBB) integrity following cerebral infarction. This study therefore aimed at understanding the effect of caspase-1 on BBB dysfunction and its underlying mechanisms in permanent middle cerebral artery occlusion (MCAO). Our findings in rat models revealed that expression of caspase-1 was upregulated following MCAO-induced injury in rats. Consequently, pharmacologic inhibition of caspase-1 using vx-765 ameliorated ischemia-induced infarction, neurological deficits, and neuronal injury. Furthermore, inhibition of caspase-1 enhanced the encapsulation rate of pericytes at the ischemic edge, decreased leakage of both Evans Blue (EB) and matrix metalloproteinase (MMP) proteins, and upregulated the levels of tight junctions (TJs) and tissue inhibitors of metalloproteinases (TIMPs) in MCAO-injured rats. This in turn improved the permeability of the BBB. Meanwhile, vx-765 blocked the activation of ischemia-induced pyroptosis and reduced the expression level of inflammatory factors such as caspase-1, NLRP3, ASC, GSDMD, IL-1ß, and IL-18. Similarly, vx-765 treatment significantly reduced the expression levels of inflammation-related receptor for advanced glycation end products (RAGE), high-mobility family box 1 (HMGB1), mitogen-activated protein kinase (MAPK), and nuclear factor-κB (NF-κB). Evidently, inhibition of caspase-1 significantly improves ischemia-associated BBB permeability and integrity by suppressing pyroptosis activation and the RAGE/MAPK pathway.

[Three-dimensional finite element analysis on En mass intrusion and retraction of maxillary anterior teeth with J-hook headgear].

OBJECTIVE: To investigate the biomechanics of J-hook headgear in En mass intrusion and retraction of maxillary anterior teeth and provide guidance for clinical treatment. METHODS: A three-dimensional finite element model of maxillary teeth, periodontium, straight wire appliance and maxillary bone was established in ANSYS 14.0. En mass retraction of anterior teeth with force of 1.5 N through J-hook headgear was stimulated. Force was applied mesial to lateral incisor in group A and distal to lateral incisor in group B. The force direction was 30° to the sagittal plane and 20° to 60° to the occlusal plane. Force direction to the occlusal plane was changed every 5° and 18 cases were calculated. Displacement of upper anterior teeth and stress distribution in the periodontium were analyzed. RESULTS: As the degrees of force direction to the occlusal plane increased, the moving pattern of upper anterior teeth changed from clockwise rotation (lingual movement with intrusion) to bodily retraction and intrusion, and counter- clockwise rotation (intrusion with labial movement). With the force direction of 35° to occlusal plane applied mesial to lateral incisor or force direction of 45° to the occlusal plane applied distal to lateral incisor, bodily movement of upper anterior teeth without rotation was achieved. CONCLUSIONS: Placement of J-hook mesial to lateral incisor enable orthodontists to maintain better en mass intrusion and retraction of upper anterior teeth. The direction of J-hook should be adjusted according to individual condition and treatment objective.

[3-D finite element analysis on center of resistance of upper anterior teeth].

PURPOSE: To investigate the location of center of resistance(CRe) of six upper anterior teeth. METHODS: A three-dimensional finite element model of premaxillary bone and anterior teeth was established in ANSYS 8.1 software. Anterior teeth were fixed with stainless archwire of 2 mm × 2 mm. A horizontal retraction force of 150 g was applied bilaterally to the segment through hooks of 2 to 14 mm. After loading, solution was done and displacement and maximum principle stress were calculated. RESULTS: Displacement and stress distribution of anterior teeth varied according to the increase of height of horizontal retraction force. Labiolingual displacement of incisors varied from crown lingual tipping to lingual translation and lingual controlling root movement, while canine mainly showed lingual crown tipping. The displacements of teeth increased with the length of hook but their moving tendency remained unchanged. Stress distribution in PDL was in accordance with direction and magnitude of teeth displacement. In all cases, lingual displacement and stress in PDL were most homogeneous when hook was 10 mm long. CONCLUSION: The results of this study suggest that perpendicular location of center of resistance of six upper anterior teeth is about 14 mm gingivally to incisal edge of central incisor.