Activating Wnt/ß-catenin signaling by autophagic degradation of APC contributes to the osteoblast differentiation effect of soy isoflavone on osteoporotic mesenchymal stem cells.

The functional role of autophagy in regulating differentiation of bone marrow mesenchymal stem cells (MSCs) has been studied extensively, but the underlying mechanism remains largely unknown. The Wnt/ß-catenin signaling pathway plays a pivotal role in the initiation of osteoblast differentiation of mesenchymal progenitor cells, and the stability of core protein ß-catenin is tightly controlled by the APC/Axin/GSK-3ß/Ck1α complex. Here we showed that genistein, a predominant soy isoflavone, stimulated osteoblast differentiation of MSCs in vivo and in vitro. Female rats were subjected to bilateral ovariectomy (OVX); four weeks after surgery the rats were orally administered genistein (50 mg·kg-1·d-1) for 8 weeks. The results showed that genistein administration significantly suppressed the bone loss and bone-fat imbalance, and stimulated bone formation in OVX rats. In vitro, genistein (10 nM) markedly activated autophagy and Wnt/ß-catenin signaling pathway, and stimulated osteoblast differentiation in OVX-MSCs. Furthermore, we found that genistein promoted autophagic degradation of adenomatous polyposis coli (APC), thus initiated ß-catenin-driven osteoblast differentiation. Notably, genistein activated autophagy through transcription factor EB (TFEB) rather than mammalian target of rapamycin (mTOR). These findings unveil the mechanism of how autophagy regulates osteogenesis in OVX-MSCs, which expands our understanding that such interplay could be employed as a useful therapeutic strategy for treating postmenopausal osteoporosis.

Quantitative Segmentation Analysis of the Radiological Changes by Using ITK-SNAP: Risk Assessment of the Severity and Recurrence of Medication-related Osteonecrosis of the Jaw.

Background and purpose: Medication-related osteonecrosis of the jaw (MRONJ) severely impairs patients' quality of life and is remarkably refractory to treatment. There are lots of studies about identification of the radiographic features of MRONJ, yet reports about quantitative radiographic analysis for the risk assessment of the severity and recurrence of MRONJ are rarely heard. The aim of this study was to investigate the volumes of osteolytic lesions and radiodensity values of osteosclerotic lesions in MRONJ patients by using ITK-SNAP for severity prediction and prognosis evaluation. Materials and methods: Of 78 MRONJ patients (78 lesions) involved in this retrospective study, 53 were presented as osteolytic lesions and 25 were presented as osteosclerotic changes alone. Comprehensive CBCT images, demographics and clinical data of patients were investigated. The volumetric analysis and radiodensity measurement were performed by ITK-SNAP. SPSS 25.0 were used for statistical analysis. Results: The osteolytic lesion volumes in MRONJ patients receiving intravenous bisphosphonates (P=0.004) and patients without osteoporosis (P=0.027) were significantly large. No significant correlation between the volumes and bisphosphonates duration was found (P=0.094). The radiodensity values of osteosclerotic lesions was significantly correlated with bisphosphonates duration (P=0.040). The surrounding area of post-surgical lesions in MRONJ patients with recurrence showed significantly great radiodensity values (P=0.025). No significant correlation between the radiodensity values and the transformation from osteosclerotic lesions to osteolytic lesions was observed (P=0.507). Conclusion: MRONJ patients receiving intravenous bisphosphonates develop into large volumes of osteolytic lesions more easily. Long-term bisphosphonates duration is possibly related with higher bone density of osteosclerotic lesions, while higher density is not associated with the transformation from osteosclerotic lesions to osteolytic lesions. A rise of bone mineral density nearby post-surgical lesions is probably a predictor for MRONJ recurrence.

What Affects Older Adults' Viewing Behaviors in Neighborhood Open Space: A Study in Hong Kong.

Research on older adults' behaviors, living environments, and their quality of life (QoL) has grown rapidly. Viewing behaviors, although broadly acknowledged as critical for older adults' QoL, have not been systematically examined in situ. What affects the viewing behaviors of older adults in neighborhood open space (NOS) is still unclear. This study conducted unobtrusive continuous observations in NOS of two residential estates in Hong Kong. With spatio-temporal analyses with ArcGIS Pro and statistical analyses with SPSS, principal influential factors to viewing behaviors of older adults in NOS were identified, including distances for viewing, landscape attractiveness, body supporting elements, as well as moving and interactive behaviors. How these factors would affect older adults' well-being and QoL is discussed from the perspectives of supportive landscape design, sense of control, prospect and refuge, and social support, etc. Corresponding design implications are proposed to enrich existing NOS design knowledge for older adults' quality of life.

Downregulation of mitogen-activated protein kinases (MAPKs) in chronic ethanol-induced fatty liver.

Mitogen-activated protein kinases (MAPKs) are versatile proteins that have been suggested to be involved in the regulation of lipid metabolism. This study was designed to investigate the responses of MAPK signaling to chronic ethanol exposure in vivo and in vitro, and try to explore its role in the pathogenesis of alcoholic fatty liver (AFL). Mice were fed with Lieber-Decarli liquid diet (5% ethanol, w/v) for 4 weeks to induce fatty liver, and the chronological changes of MAPK phosphorylation were measured using western blotting. We found that chronic ethanol feeding led to accumulation of triglyceride (TG), decreased phosphorylation of MAPKs, decreased protein level of peroxisomal proliferator activation receptor α (PPARα), and increased protein expression of cytochrome P4502E1 (CYP2E1) in mice liver. In vitro study showed that overexpression of CYP2E1 blunted the response of MAPKs to ethanol, and MAPK phosphatase 1 (MKP-1) knockdown by siRNA led to upregulation of PPARα protein level. Lastly, epidermal growth factor (EGF), a well-known MAPK activator, significantly suppressed chronic ethanol-induced hepatic fat accumulation and decline of PPARα expression in mice liver. Collectively, MAPK suppression, possibly due to the activation of hepatic CYP2E1, may be involved in chronic ethanol-induced hepatic steatosis.

[Characteristics of extreme ultraviolet emission from tin plasma using CO2 laser for lithography].

The extreme ultraviolet (EUV) emission characteristics from Sn plasma for lithography produced by a pulse discharge CO2 laser was investigated under different conditions. Extreme ultraviolet spectral measurements were made throughout the wavelength region of 6.5 nm to 16.8 nm using a grazing incidence flat-field spectrograph coupled with an X-ray charge-coupled device camera for detection of time-integrated spectra. The dependence of spectral properties of the EUV emission on pulse duration, incidence pulse energy, and buffer gas pressure was investigated. The results show that the peak of EUV spectra was located at 13.5 nm. The intensity of EUV emission increased with increasing laser energy ranging from 30 mJ to 600 mJ in a nonlinear manner with saturation effect. The critical energy of incident pulse laser for the generation of EUV emission is near 30 mJ in our experiment. The highest conversion efficiency of 1.2% in producing 13.5 nm EUV light with 0.27 nm bandwidth was achieved at pump energy of 425 mJ. The EUV spectra from a plate target produced by laser pulse with full width at half maximum range from 50 ns to 120 ns were recorded and negligible differences in their spectral features noticed even though higher spectral intensity was observed by shorter pulse duration. The 2% in-band EUV intensity with 52 ns pulse duration was 1.6 times higher than that with 120 ns pulse duration due to the increase in laser intensity. It was also found that the detected EUV spectral intensity rapidly decreased with increasing buffer air pressure, and the EUV emission could be totally absorbed at the pressure of 200 Pa, while weak EUV emission could be still detected at the buffer He gas pressure of 7 x 10(4) Pa. The experimental results showed that the absorption coefficient of 13.5 nm light at air buffer gas pressure of 100 Pa was 3.0 m(-1), while the absorption coefficient was 0.96 m(-1) at the same He buffer gas pressure.

Sequential fluorescent labeling observation of maxillary sinus augmentation by a tissue-engineered bone complex in canine model.

AIM: To evaluate the effects of maxillary sinus floor elevation by a tissue-engineered bone complex of beta-tricalcium phosphate (beta-TCP) and autologous osteoblasts in dogs. METHODOLOGY: Autologous osteoblasts from adult Beagle dogs were cultured in vitro. They were further combined with beta-TCP to construct the tissue-engineered bone complex. 12 cases of maxillary sinus floor elevation surgery were made bilaterally in 6 animals and randomly repaired with the following 3 groups of materials: Group A (osteoblasts/beta-TCP); Group B (beta-TCP); Group C (autogenous bone) (n=4 per group). A polychrome sequential fluorescent labeling was performed post-operatively and the animals were sacrificed 24 weeks after operation for histological observation. RESULTS: Our results showed that autologous osteoblasts were successfully expanded and the osteoblastic phenol-types were confirmed by ALP and Alizarin red staining. The cells could attach and proliferate well on the surface of the beta-TCP scaffold. The fluorescent and histological observation showed that the tissue-engineered bone complex had an earlier mineralization and more bone formation inside the scaffold than beta-TCP along or even autologous bone. It had also maximally maintained the elevated sinus height than both control groups. CONCLUSION: Porous beta-TCP has served as a good scaffold for autologous osteoblasts seeding. The tissue-engineered bone complex with beta-TCP and autologous osteoblasts might be a better alternative to autologous bone for the clinical edentulous maxillary sinus augmentation.