Osteoclast-Driven Osteogenesis, Bone Remodeling and Biomaterial Resorption: A New Profile of BMP2-CPC-Induced Alveolar Bone Regeneration.

This bedside-to-bench study aimed to systematically investigate the value of applying BMP2-loaded calcium phosphate cement (BMP2-CPC) in the restoration of large-scale alveolar bone defects. Compared to deproteinized bovine bone (DBB), BMP2-CPC was shown to be capable of inducing a favorable pattern of bone regeneration and bone remodeling accompanied by active osteoclastogenesis and optimized biomaterial resorption when applied in reconstructive periodontally accelerated osteogenic orthodontics (PAOO) surgery. To verify the regulatory role of osteoclasts in the BMP2-CPC-induced pattern of bone regeneration, in vitro and in vivo studies were designed to elucidate the underlying mechanism. Our results revealed that osteoclasts played a multifaceted role (facilitating osteogenesis, bone remodeling and biomaterial resorption) in the BMP2-CPC-induced bone regeneration. Osteoclasts contributed to the osteogenic differentiation of mesenchymal stem cells (MSCs) by secreting calcium ions, CTHRC1 and PDGF-B. Moreover, the increased osteoclasts promoted the remodeling of new bone and BMP2-CPC resorption, leading to a harmonized replacement of biomaterials with mature bone. In conclusion, the in vitro and in vivo experimental results corresponded with the clinical results and showed the optimized properties of BMP2-CPC in activating osteoclast-driven bone regeneration and remodeling, thus indicating the highly promising prospects of BMP2-CPC as an ideal therapeutic for alveolar bone defects.

Satb2 expression in Foxc1-promoted osteogenic differentiation of MC3T3-E1 cells is negatively regulated by microRNA-103-3p.

The forkhead transcription factor C1 (Foxc1) is a cell-fate-determining factor that controls cranial bone development and osteogenic differentiation. Previously, it was demonstrated that various microRNAs (miRNAs) play important roles in osteogenesis and regulate the complex process of osteogenic differentiation. However, it remains unclear how miRNA expression changes during Foxc1-promoted osteogenic differentiation. In this study, we successfully overexpressed the Foxc1 gene in MC3T3-E1 cells and investigated the alterations in the miRNA expression profile on day 3 after osteogenic induction by using a miRNA microarray. Nine downregulated miRNAs and eight upregulated miRNAs were found to be differentially expressed. Among these miRNAs, miR-103-3p was consistently downregulated in the Foxc1-overexpressing MC3T3-E1 cells and was identified as a negative regulator of osteogenic differentiation by using a gain- and lose-of-function assay. The special AT-rich sequence-binding protein 2 (Satb2), a pivotal osteogenic transcription factor, was identified as the miR-103-3p targeting gene and was verified by real-time polymerase chain reaction, western blot analysis, and luciferase assay. Overexpression of miR-103-3p markedly inhibited the expression of Satb2 and attenuated Foxc1-promoted osteogenic differentiation. Taken together, our results elucidated the miRNA expression profiles of MC3T3-E1 cells in the early stage of Foxc1-promoted osteogenic differentiation and suggested that miR-103-3p acts as a negative regulator of the osteogenic differentiation of MC3T3-E1 cells by directly targeting Satb2.

Detection of Glutathione in Oral Squamous Cell Carcinoma Cells With a Fluorescent Probe During the Course of Oxidative Stress and Apoptosis.

PURPOSE: To detect glutathione (GSH) in oral squamous carcinoma cells (OSCCs) with a GSH selective fluorescent probe during the course of oxidative stress and apoptosis. MATERIALS AND METHODS: A novel GSH probe was applied to assess GSH in human tongue squamous cell carcinoma cells (cal-27). The cellular GSH and reactive oxygen species (ROS) levels were assessed with a GSH probe and DCF-DA (2,7-dichlorofluorescin diacetate) probe. The mitochondrial GSH and ROS levels were assessed with a GSH probe, DCF-DA probe, and Mitotracker Red CM-H2XRos probe (Invitrogen, Carlsbad, CA). To further study whether oxidative stress would induce apoptosis of OSCCs, we then applied a GSH probe and annexin V-fluorescein isothiocyanate probe to assess cellular GSH levels and eversion of phosphatidylserine, and the cellular GSH levels and mitochondrial membrane potential (ΔΨm) were assessed with a GSH probe and JC-1 probe during the course of oxidative stress and apoptosis induced by hydrogen peroxide and ethacrynic acid. The fluorescence was observed under laser confocal fluorescence microscopy. RESULTS: The intensity of fluorescence that represented intracellular alteration of GSH levels, cellular ROS formation, mitochondrial ROS formation, and apoptosis occurrence, respectively, could be visualized under laser confocal fluorescence microscopy. CONCLUSIONS: The GSH selective fluorescent probe can evaluate cellular GSH levels sensitively during the course of oxidative stress and apoptosis of OSCCs induced by exogenous hydrogen peroxide, which could be enhanced by depletion of mitochondrial GSH.

Extracting Useful Emergency Information from Social Media: A Method Integrating Machine Learning and Rule-Based Classification.

User-generated contents (UGCs) on social media are a valuable source of emergency information (EI) that can facilitate emergency responses. However, the tremendous amount and heterogeneous quality of social media UGCs make it difficult to extract truly useful EI, especially using pure machine learning methods. Hence, this study proposes a machine learning and rule-based integration method (MRIM) and evaluates its EI classification performance and determinants. Through comparative experiments on microblog data about the "July 20 heavy rainstorm in Zhengzhou" posted on China's largest social media platform, we find that the MRIM performs better than pure machine learning methods and pure rule-based methods, and that its performance is influenced by microblog characteristics such as the number of words, exact address and contact information, and users' attention. This study demonstrates the feasibility of integrating machine learning and rule-based methods to mine the text of social media UGCs and provides actionable suggestions for emergency information management practitioners.

How do online users perceive health risks during public health emergencies? Empirical evidence from China.

Background: The global COVID-19 pandemic has posed a major threat to human life and health, and new media technologies have intensified the spread of risk perception. Purpose: This study aimed to explore the impact of risk information ground on online users' perceived health risks, and further explore the mediating role of psychological distance and the moderating role of self-efficacy. Methods: A total of 25 Internet users from different provinces in China were interviewed in-depth, NVIVO.11 was used to qualitatively analyze the interview text data and construct a theoretical model. A total of 492 interviewees were recruited in order to complete a scenario questionnaire, SPSS-27 was used to perform orthogonal experiments, generate eight combinatorial scenarios, analyze demographic data, and clean and prepare data for testing hypotheses. SmartPLS 3.0 was used to test the conceptual model using the structural equation model (SEM) of the partial least squares (PLS). Results: The analysis of the SEM model shows that all planned hypotheses (Information fluency → Information diagnosability, Information extensibility → Information diagnosability, Information diagnosability → Psychological distance, Platform interactivity → Scenario embeddedness, Network connectivity → Scenario embeddedness, Scenario embeddedness → Psychological distance, Psychological distance → Risk perception, Psychological distance → Self-efficacy → Risk perception, Information fluency → Information diagnosability → Psychological distance → Risk perception, Information extensibility → Information diagnosability → Psychological distance → Risk perception, Platform interactivity → Scenario embeddedness → Psychological distance → Risk perception, Network connectivity → Scenario embeddedness → Psychological distance → Risk perception) are confirmed. Conclusion: This study found that the information ground factors significantly affect online users' perceptions of health risks, psychological distance mediates the effect of information ground factors on risk perception, and self-efficacy negatively moderates the effect of psychological distance on risk perception.

[In vitro biological evaluation of PEGylated poly(glycerol sebacate)/ß-TCP-coating modified magnesium alloy].

PURPOSE: To prepare PEGS/ß-TCP modified magnesium alloy (PEGS/ß-TCP/MZG) membranes by forming a glycolated poly(sebacate)/ß-tricalcium phosphate (PEGS/ß-TCP) coating on the surface of magnesium-zinc-gadolinium alloy (MZG) membranes, and to evaluate the osteogenic induction activity and immunomodulatory properties of PEGS/ß-TCP/MZG using the material extract medium. METHODS: PEGS/ß-TCP coating was prepared on the surface of MZG by solvent method, and the PEGS/ß-TCP/MZG membrane was fabricated and compared with PEGS/ß-TCP and MZG to examine the morphology, composition, and hydrophilicity. The amount of magnesium ions released and the pH value of the materials were tested after 3 days of immersion. The cell viability and osteogenic differentiation of MC3T3 cells induced by extract medium were investigated by CCK-8 assay, ALP and mineralized nodule staining. The cell viability and polarization of RAW cells induced by extract medium were then investigated. The expression of macrophage-secreted cytokines was examined by PCR analysis. GraphPad Prism 9.0 software package was used for statistical analysis. RESULTS: PEGS/ß-TCP/MZG membranes with PEGS/ß-TCP coating tightly embedded with MZG were successfully fabricated, and the material had good hydrophilicity. The results of degradation experiments indicated that the PEGS/ß-TCP coating effectively slowed down the degradation rate of MZG, leading to a lower pH value and concentration of Mg2+ ion in the extract medium of PEGS/ß-TCP/MZG group. The results of in vitro cell experiments showed that PEGS/ß-TCP/MZG had no significant effect on the proliferation activity of both MC3T3-E1 and macrophages. PEGS/ß-TCP/MZG significantly enhanced the expression of ALP and mineralized nodule staining in MC3T3-E1. Although there was no significant difference in macrophage polarization pattern between PEGS/ß-TCP and PEGS/ß-TCP/MZG groups, PEGS/ß-TCP/MZG further reduced inflammation based on the immunomodulation of PEGS/ß-TCP coating related TNF-α expression and increased osteogenesis related TGF-ß expression. CONCLUSIONS: MZG membrane modified by PEGS/ß-TCP may provide a new material option for the development of bone tissue engineering.

Pandemics and Human Capital: Panel Data Evidence From 122 Countries.

This study investigates the determinants of human capital stocks, measured by the Penn World Table data, in the panel dataset of 122 countries from 1996 to 2019. The special role is given to the World Pandemics Uncertainty index to measure pandemics uncertainty across countries. The paper finds that per capita gross domestic product and population increase human capital stocks. The decline in fertility rates leads to a higher level of human capital. The interesting evidence is that pandemics' uncertainty decreases human capital. These findings are valid when we focus on both the high-income and the middle/low-income economies. These results are against the Becker-Lewis theory's validity since sources of uncertainty are negatively related to human capital.

The strategy of composite grafting with BMP2-Loaded calcium phosphate cements and autogenous bone for alveolar cleft reconstruction.

Purpose: To remedy the drawbacks of traditional autogenous bone harvesting in alveolar bone grafting (ABG), a novel strategy of composite grafting with BMP2-loaded calcium phosphate cements (BMP2-CPC) and autogenous bone harvested by minimally invasive technique was developed and evaluated for its bone-repairing efficacy. Materials and methods: A chart review was conducted for 19 patients with unilateral alveolar clefts who underwent secondary ABG from 2017 to 2020. Of the enrolled patients, 9 patients underwent grafting with autogenous bone harvested by traditional trap door technique (group I), and 10 patients underwent grafting with the composite graft comprising BMP2-CPC and autogenous bone harvested by minimally invasive technique at a ratio of 1:1 by volume (group II). The clinical performance of the composite graft was comprehensively evaluated in terms of clinical, radiographic and histological perspectives. Results: The present results demonstrated that the composite graft exhibited satisfactory bone-repairing efficacy comparable to that of the autogenous bone graft on the premise of lower amount of harvested bone. The post-surgical resorption of bone volume and vertical height of grafted area was significantly slower in group II. The favourable resorption performance of BMP2-CPC contributed to preserving the post-surgical bony contour reconstructed with the composite graft. Conclusion: The composite graft comprising BMP2-CPC and autogenous bone harvested by minimally invasive technique was demonstrated to be an eligible alternative for application in ABG, especially for its improved resorption performance in preserving post-surgical bony contour.

The association between digitalization and mental health: The mediating role of wellbeing at work.

The study aims to measure the mediating relationship of wellbeing at work between digitalization (IT infrastructure, IT business spanning, and IT proactive stance) and their effect on mental health. The study uses primary data collection techniques to gather data and used purposive sampling to analyze the data. The sample size of the study is 349 respondents. The research uses Smart PLS software to measure the relationship through bootstrapping and algorithms. The study finds a significant positive mediating role of wellbeing between digitalization (IT infrastructure, IT business spanning, and IT proactive stance) and their effect on mental health. The study outcomes are helpful for managers and policymakers.

Effects of Social Mobility and Stringency Measures on the COVID-19 Outcomes: Evidence From the United States.

This paper examines the effects of stringency measures (provided by the Oxford Coronavirus Government Response Tracker) and total time spent away from home (provided by the Google COVID-19 Community Mobility Reports) on the COVID-19 outcomes (measured by total COVID-19 cases and total deaths related to the COVID-19) in the United States. The paper focuses on the daily data from March 11, 2020 to August 13, 2021. The ordinary least squares and the machine learning estimators show that stringency measures are negatively related to the COVID-19 outcomes. A higher time spent away from home is positively associated with the COVID-19 outcomes. The paper also discusses the potential economic implications for the United States.

Experimental and clinical evaluation of BMP2-CPC graft versus deproteinized bovine bone graft for guided bone regeneration: A pilot study.

In this study, we proposed BMP2-incorporated calcium phosphate cement (BMP2-CPC), for application in guided bone regeneration (GBR) and compared the experimental bone restoration performance and clinical alveolar bone reconstruction outcome of BMP2-CPC with those of deproteinized bovine bone (DBB). The animal study indicated that, compared to DBB, which induced the slow ingrowth of new bone, BMP2-CPC induced numerous small growth centers for bone regeneration and facilitated a significant amount of bone regeneration in rabbit calvarial bone defects. Fewer residual graft particles remained in the BMP2-CPC-treated defects than in the DBB-treated defects. The clinical study indicated that BMP2-CPC was similar to DBB in remedying alveolar bone insufficiency and maintaining implant stability. In conclusion, the results of this present study indicate that compared to DBB, BMP2-CPC can significantly enhance in vivo bone regeneration and remodeling in rabbit calvarial bone defects and shows preliminary support on its clinical application in GBR surgeries.

Improved BMP2-CPC-stimulated osteogenesis in vitro and in vivo via modulation of macrophage polarization.

This study aimed to explore the in vitro and in vivo roles of macrophages in the osteogenesis stimulated by BMP2-CPC. In vitro, the alteration of macrophage polarization and cytokine secretion induced by BMP2-CPC or CPC was investigated. The influence of conditioned medium derived from BMP2-CPC- or CPC-stimulated macrophages on the migration and osteogenic differentiation of MSCs were evaluated. The in vivo relationship between macrophage polarization and osteogenesis was examined in a rabbit calvarial defect model. The in vitro results indicated that BMP2-CPC and CPC induced different patterns of macrophage polarization and subsequently resulted in distinct patterns of cytokine expression and secretion. Conditioned medium derived from BMP2-CPC- or CPC-stimulated macrophages both exhibited apparent osteogenic effect on MSCs. Notably, BMP2-CPC induced more M2-phenotype polarization and higher expression of anti-inflammatory cytokines and growth factors than did CPC, which led to the better osteogenic effect of conditioned medium derived from BMP2-CPC-stimulated macrophages. The rabbit calvarial defect model further confirmed that BMP2-CPC facilitated more bone regeneration than CPC did by enhancing M2-phenotype polarization in local macrophages and then alleviating inflammatory reaction. In conclusion, this study revealed that the favorable immunoregulatory property of BMP2-CPC contributed to the strong osteogenic capability of BMP2-CPC by modulating macrophage polarization.

The Transcription Factor Foxc1 Promotes Osteogenesis by Directly Regulating Runx2 in Response of Intermittent Parathyroid Hormone (1-34) Treatment.

Parathyroid hormone (PTH) is crucial for bone remodeling. Intermittent PTH (1-34) administration stimulates osteogenesis and promotes bone formation; however, the possible targets and underlying mechanisms still remain unclear. In this study, functional links between PTH and Foxc1, a transcription factor reported to be predominant in skeletal development and formation, were indicated. We determined the impacts of Foxc1 on in vitro osteogenic differentiation and in vivo bone regeneration under intermittent PTH induction, and further explored its possible targets. We found that the expression level of Foxc1 was upregulated during osteogenic induction by intermittent PTH treatment, and the elevated expression of Foxc1 induced by PTH was inhibited by PTH1R silencing, while rescued by intermittent PTH supplement. By gain- and loss-of-function strategies targeting Foxc1 in MC3T3-E1 cells, we demonstrated that Foxc1 could promote in vitro osteogenic differentiation by intermittent PTH induction. Moreover, immunofluorescence analysis indicated the nuclear co-localization of Foxc1 with Runx2. Luciferase-reporter and chromatin immunoprecipitation analysis further confirmed that Foxc1 could bind to the P1 promoter region of Runx2 directly, which plays an indispensable part in osteogenic differentiation and bone mineralization. Meanwhile, we also revealed that Foxc1 could promote bone regeneration induced by intermittent PTH treatment in vivo. Taken together, this study revealed the role and mechanism of Foxc1 on in vitro osteogenic differentiation and in vivo bone regeneration in response of intermittent PTH treatment.

Biomechanical Analysis of Grafted and Nongrafted Maxillary Sinus Augmentation in the Atrophic Posterior Maxilla with Three-Dimensional Finite Element Method.

This study is aimed at determining the optimal sinus augmentation approach considering the poor bone condition in the zone of atrophic posterior maxilla. A series of simplified maxillary segment models varying in residual bone height (RBH) and bone quality were established. A 10 mm standard implant combined with two types of maxillary sinus augmentation methods was applied with the RBH, which was less than 10 mm in the maxilla. The maximal equivalent von Mises (EQV) stress in residual bone was evaluated. Bone quality had an enormous impact on the stress magnitude of supporting bone. Applying sinus augmentation combined with grafts was suitable for stress distribution, and high-stiffness graft performed better than low-stiffness one. For 7 mm and 5 mm atrophic maxilla, nongrafted maxillary sinus augmentation was feasible in D3 bone. Poor bone quality was a negative factor for the implant in the region of atrophic posterior maxilla, which could be improved by grafts. Meanwhile, the choice of maxillary sinus augmentation approaches should be determined by the RBH and quality.

Effects of inferior alveolar nerve rupture on bone remodeling of the mandible: A preliminary study.

Although various animal studies have indicated that sensory nerves played an important role in bone metabolism and nerve injury could impair the process of bone remodeling, the actual effect of sensory nerve rupture on human bones remains unclear. The aim of this preliminary study was to investigate the effect of inferior alveolar nerve (IAN) rupture on mandibular bone remodeling of patients underwent bilateral sagittal split ramus osteotomy (BSSRO).Ten patients with unilateral IAN rupture during BSSRO were involved in this study. Neurosensory examinations were employed to assess the sensory function of bilateral IAN. The remodeling process of the post-operational mandible was evaluated by panoramic radiographs and computed tomography (CT) scans.Neurosensory examinations indicated that nerve rupture resulted in significant hypoesthesia at the IAN-rupture side. Assessment of panoramic radiographs showed no evident alterations of bone structure at the IAN-rupture side of mandible. Evaluation of CT images also indicated no statistical difference in bone density and thickness between IAN-rupture side and contralateral side.Accordingly, our study indicated that IAN rupture may not significantly impair the short-term bone remodeling process of human mandible.

3D bioprinting and in vitro study of bilayered membranous construct with human cells-laden alginate/gelatin composite hydrogels.

Extrusion-based 3D bioprinting of cell-laden hydrogels is a potential technology for regenerative medicine, which enables the fabrication of constructs with spatially defined cell distribution. However, the limited assessment of rheological behaviors of hydrogel before printing is still a major issue for the advancement of 3D bioprinting. In this work, we systematically investigated the rheological behaviors (i.e. viscosity, storage modulus (G'), and loss modulus (G")) of alginate/gelatin composite hydrogels first for 3D printing complex constructs. The rheological studies revealed that viscosity of alginate/gelatin hydrogels is temperature-dependent and shear thinning. Sol-gel transition (intersection of G' and G") study provided indication for printing temperature, which are in the range of 18.8 °C (H2/7.5) to 24.5 °C (H2/24.5). The alginate (2 wt%) /gelatin (15 wt%) composite hydrogel sample was chosen to print the constructs and subsequent bioprinting. Complex constructs (i.e. nose and ear) were obtained with high printing resolution (151 ±â€¯13.04 µm) in a low temperature (4 °C) chamber and crosslinking with 2 wt% CaCl2 subsequently without extra supports. Human amniotic epithelial cells (AECs) showed superior potential to differentiate into epithelial cells, while Wharton's jelly derived mesenchymal stem cells (WJMSCs) showed a superior angiogenic potential and fibroblastic phenotype. For the in vitro study, AECs and WJMSCs as seed cells, encapsulated in alginate/gelatin composite hydrogels, were bioprinted to form biomimetic bilayered membranous construct. High cell viability (> 95%) were observed up to 6 days after printing. The presented 3D bioprinting of human AECs and WJMSCs-laden alginate/gelatin composite hydrogels provides promising potentials for future skin tissue engineering.