PTH1R-CaSR Cross Talk: New Treatment Options for Breast Cancer Osteolytic Bone Metastases.

Metastatic breast cancer (BrCa) is currently incurable despite great improvements in treatment of primary BrCa. The incidence of skeletal metastases in advanced BrCa occurs up to 70%. Recent findings have established that the distribution of BrCa metastases to the skeleton is not a random process but due to the favorable microenvironment for tumor invasion and growth. The complex interplay among BrCa cells, stromal/osteoblastic cells, and osteoclasts in the osseous microenvironment creates a bone-tumor vicious cycle (a feed-forward loop) that results in excessive bone destruction and progressive tumor growth. Both the type 1 PTH receptor (PTH1R) and extracellular calcium-sensing receptor (CaSR) participate in the vicious cycle and influence the skeletal metastatic niche. Thus, this review focuses on how the PTH1R and CaSR signaling pathways interact and contribute to the pathogenesis of BrCa bone metastases. The effects of intermittent PTH and allosteric modulators of CaSR for the use of bone-anabolic agents and prevention of BrCa bone metastases constitute a proof of principle for therapeutic consideration. Understanding the interplay between PTH1R and CaSR signaling in the development of BrCa bone metastases could lead to a novel therapeutic approach to control both osteolysis and tumor burden in the bone

Higher Education on Buildings: Case Study in the North Dakota Region

Because of the growing demand for local skilled professionals to improve the health, energy efficiency, and sustainability of residential and commercial buildings in North Dakota, this case study reports the current situation of higher education relating to buildings in the state’s vicinity, including Minnesota, Montana, North Dakota, and South Dakota. In this region, 116 programs relating to buildings were found in 41 postsecondary institutions, and both their majors and courses were then studied with frequency lists. The frequency information was analyzed over nine sets of curriculum areas at both graduate and undergraduate levels for the four states. After the current state of buildings in North Dakota was investigated, strategies were then proposed to rectify current issues regarding higher education on buildings, including but not limited to forming a comprehensive and interdisciplinary program on buildings (e.g., architectural engineering), providing more graduate programs, developing more courses in areas that lack adequate coursework, and increasing student enrollment. These strategies will greatly promote the health, energy efficiency, and sustainability for new and existing buildings in the four-state region of Minnesota, Montana, North Dakota, and South Dakota

Ixazomib enhances parathyroid hormone-induced β-catenin/T-cell factor signaling by dissociating β-catenin from the parathyroid hormone receptor.

The anabolic action of PTH in bone is mostly mediated by cAMP/PKA and Wnt-independent activation of β-catenin/T-cell factor (TCF) signaling. β-Catenin switches the PTH receptor (PTHR) signaling from cAMP/PKA to PLC/PKC activation by binding to the PTHR. Ixazomib (Izb) was recently approved as the first orally administered proteasome inhibitor for the treatment of multiple myeloma; it acts in part by inhibition of pathological bone destruction. Proteasome inhibitors were reported to stabilize β-catenin by the ubiquitin-proteasome pathway. However, how Izb affects PTHR activation to regulate β-catenin/TCF signaling is poorly understood. In the present study, using CRISPR/Cas9 genome-editing technology, we show that Izb reverses β-catenin-mediated PTHR signaling switch and enhances PTH-induced cAMP generation and cAMP response element-luciferase activity in osteoblasts. Izb increases active forms of β-catenin and promotes β-catenin translocation, thereby dissociating β-catenin from the PTHR at the plasma membrane. Furthermore, Izb facilitates PTH-stimulated GSK3β phosphorylation and β-catenin phosphorylation. Thus Izb enhances PTH stimulation of β-catenin/TCF signaling via cAMP-dependent activation, and this effect is due to its separating β-catenin from the PTHR. These findings provide evidence that Izb may be used to improve the therapeutic efficacy of PTH for the treatment of osteoporosis and other resorptive bone diseases

Accessibility Analysis of A-level Lin Pan Scenic Spot in Dayi County Based on Road Network

Chengdu vigorously promotes the construction and development of Lin Pan. Aiming at the distribution of A-level Lin Pan in Dayi County, this study analyzed the accessibility of A-level Lin Pan by using ArcGIS software, OD cost matrix analysis method and two-step mobile search method, and found that: (1) Accessibility of different A-class Lin Pan varies greatly, and the longest arrival time is almost twice that of the shortest. (2) The A-level Lin Pan scenic spot has A general economic driving effect on the local economy, and it is suggested to increase the construction of Lin Pan scenic spot according to the distribution of Lin Pan

Phytoestrogen -zearalanol ameliorates memory impairment and neuronal DNA oxidation in ovariectomized mice

OBJECTIVE: The aim of this study was to evaluate the effect of a novel phytoestrogen, α-Zearalanol, on Alzheimer's disease-related memory impairment and neuronal oxidation in ovariectomized mice. METHODS: Female C57/BL6 mice were ovariectomized or received sham operations and treatment with equivalent doses of 17β-estradiol or α-Zearalanol for 8 weeks. Their spatial learning and memory were analyzed using the Morris water maze test. The antioxidant enzyme activities and reactive oxygen species generation, neuronal DNA oxidation, and MutT homolog 1 expression in the hippocampus were measured. RESULTS: Treatment with 17β-estradiol or α-Zearalanol significantly improved spatial learning and memory performance in ovariectomized mice. In addition, 17β-estradiol and α-Zearalanol attenuated the decrease in antioxidant enzyme activities and increased reactive oxygen species production in ovariectomized mice. The findings indicated a significant elevation in hippocampi neuronal DNA oxidation and reduction in MutT homolog 1 expression in estrogen-deficient mice, but supplementation with 17β-estradiol or α-Zearalanol efficaciously ameliorated this situation. CONCLUSION: These results demonstrate that α-Zearalanol is potentially beneficial for improving memory impairments and neuronal oxidation damage in a manner similar to that of 17β-estradiol. Therefore, the compound may be a potential therapeutic agent that can ameliorate neurodegenerative disorders related to estrogen deficiency

Frosting performance of a nanoporous hydrophilic aluminum surface

© 2018 by the authors. As an efficient energy-saving piece of equipment, an air-source heat pump can not only reduce the energy consumption required for heating, but can also reduce the pollution from fossil consumption. However, when an air-source heat pump operates under low temperatures and high humidity, the heat exchanger surface of its outdoor evaporator often get covered with frost. The growth of the frost layer seriously affects the operation efficiency of the equipment and limits its engineering application. Looking for materials that can actively inhibit frost forming is a good strategy to solve the problem mentioned above. Numerous studies show that a hydrophilic surface (contact angle less than 90◦) can inhibit the normal freezing process. Manufacturing nanostructures on the surface also affect frosting performance. In this paper, nanoporous hydrophilic aluminum sheets, with contact angles of 47.8◦ (Sample 2), 35.9◦ (Sample 3), and 22.9◦ (Sample 4), respectively, were fabricated by the anodic oxidation method. The frosting performance of the nanoporous hydrophilic aluminum was studied compared with polished aluminum, with a contact angle of 60.2◦ (Sample 1). The frosting performance of the aluminum surface was systematically studied by observing the frost structure from top and side cameras and measuring the frost thickness, frost mass, and frosting rate. It was found that nanoporous hydrophilic aluminum can reduce the frost thickness and frost mass. The frost mass reduction rate of sample 2 reached a maximum of 65.9% at the surface temperature of −15 ◦C, under test conditions. When the surface temperature was −15 ◦C, the frosting rate of Sample 2 was 1.71 g/(m2·min), which was about one-third of that on sample 1 (polished aluminum). Nanoporous hydrophilic aluminum behaved better at lessening frost than polished aluminum, which revealed that manufacturing nanopores and promoting hydrophilicity can delay the formation of frost

The \u3ci\u3eAPOA5\u3c/i\u3e rs662799 polymorphism is associated with dyslipidemia and the severity of coronary heart disease in Chinese women

Background: The APOA5 rs662799 polymorphism has been widely reported regarding its associations with the plasma lipid levels and the occurrence of coronary heart disease (CHD), whereas its relationship with the severity of CHD has not yet been explored. Methods: Four hundred and seventy-eight angiografically defined subjects (325 CHD patients and 153 CHD-free controls) were enrolled in this study. The rs662799 polymorphism was genotyped, and the fasting lipid data were collected for all participants. The severity of CHD was evaluated for the CHD patients by using Gensini scores. Results: The variant C allele of the rs662799 polymorphism was associated with lower levels of HDL-C in CHD-free women, and higher levels of TG and TG/HDL-C in women with CHD (P \u3c 0.05 for all). The C allele was associated with higher prevalence of dyslipidemia and higher levels of Gensini scores only in women (P \u3c 0.05 for both), but not in men. Multivariate linear regression analysis showed that the rs662799 polymorphism was independently associated with the Gensini scores in women after adjustment for other potential CHD risk factors (Beta = 0.157, 95 % CI: 0.017–0.298, P = 0.028). Conclusion: Our data indicate that the rs662799 polymorphism is associated with dyslipidemia and the severity of CHD in Chinese women