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Long-term use of zoledronic acid (ZA) increases the risk of medication-related osteonecrosis of the jaw (MRONJ). This may be attributed to ZA-mediated reduction of viable mesenchymal stem cells (MSCs). ZA inhibits protein geranylgeranylation, thus suppressing cell viability and proliferation. Geranylgeraniol (GGOH), which is a naturally found intermediate compound in the mevalonate pathway, has positive effects against ZA. However, precise mechanisms by which GGOH may help preserve stem cell viability against ZA are not fully understood. The objective of this study was to investigate the cytoprotective mechanisms of GGOH against ZA. The results showed that while ZA dramatically decreased the number of viable MSCs, GGOH prevented this negative effect. GGOH-rescued ZA-exposed MSCs formed mineralization comparable to that produced by normal MSCs. Mechanistically, GGOH preserved the number of viable MSCs by its reversal of ZA-mediated Ki67+ MSC number reduction, cell cycle arrest and apoptosis. Moreover, GGOH prevented ZA-suppressed RhoA activity and YAP activation. The results also established the involvement of Rho-dependent YAP and YAP-mediated CDK6 in the cytoprotective ability of GGOH against ZA. In conclusion, GGOH preserves a pool of viable MSCs with osteogenic potency against ZA by rescuing the activity of Rho-dependent YAP activation, suggesting GGOH as a promising agent and YAP as a potential therapeutic target for MRONJ.Identifying areas in the sole of the foot which are routinely overloaded during daily living is extremely important for the management of the diabetic foot. This work showcases the feasibility of reliably detecting overloading using a low-cost non-electronic technique. This technique uses thin-wall structures that change their properties differently when they are repeatedly loaded above or below a tuneable threshold. Flexible hexagonal thin-wall structures were produced using three-dimensional printing, and their mechanical behaviour was assessed before and after repetitive loading at different magnitudes. These structures had an elastic mechanical behaviour until a critical pressure (P crit = 252 kPa ± 17 kPa) beyond which they buckled. Assessing changes in stiffness after simulated use enabled the accurate detection of whether a sample was loaded above or below P crit (sensitivity = 100%, specificity = 100%), with the overloaded samples becoming significantly softer. No specific P crit value was targeted in this study. However, finite-element modelling showed that P crit can be easily raised or lowered, through simple geometrical modifications, to become aligned with established thresholds for overloading (e.g. 200 kPa) or to assess overloading thresholds on a patient-specific basis. Bcl-2 inhibitor Although further research is needed, the results of this study indicate that clinically relevant overloading could indeed be reliably detected without the use of complex electronic in-shoe sensors.In this paper, the thermoelectric properties of p-type and n-type GeSe are studied systematically by using first principles and Boltzmann transport theory. The calculation includes electronic structure, electron relaxation time, lattice thermal conductivity and thermoelectric transport properties. The results show that GeSe is an indirect band gap semiconductor with band gap 1.34 eV. Though p-type GeSe has a high density of states near Fermi level, the electronic conductivity is relative low because there is no carrier transport pathway along the a-axis direction. For n-type GeSe, a charge density channel is formed near conduction band minimum, which improves the electrical conductivity of n-type GeSe along the a-axis direction. At 700 K, the optimal ZT value reaches 2.5 at 4 × 1019 cm-3 for n-type GeSe, while that is 0.6 at 1 × 1020 cm-3 for p-type GeSe. The results show n-type GeSe has better thermoelectric properties than p-type GeSe, indicating that n-type GeSe is a promising thermoelectric material in middle temperature.This paper presents a graphical method for determining the linearized stiffness and stability of prestressed trusses consisting of rigid bars connected at pinned joints and which possess kinematic freedoms. Key to the construction are the rectangular areas which combine the reciprocal form and force diagrams in the unified Maxwell-Minkowski diagram. The area of each such rectangle is the product of the bar tension and the bar length, and this corresponds to the rotational stiffness of the bar that arises due to the axial force that it carries. The prestress stability of any kinematic freedom may then be assessed using a weighted sum of these areas. The method is generalized to describe the out-of-plane stability of two-dimensional trusses, and to describe three-dimensional trusses in general. The paper also gives a graphical representation of the 'product forces' that were introduced by Pellegrino and Calladine to describe the prestress stability of trusses.Considering the recent developments of deep mining, investigating the rock properties under high ground stress periodic load is highly demanded. Studies show that these characteristics are important factors affecting the long-term steadiness of rock. However, the mechanical properties of rock mass without macro failure after cyclic load should be studied. In the present study, granite in a mine is considered as the research object. A rock pre-damage experiment is conducted with the same cycles under different confining pressures and constant cycle upper and lower limit loads. The pre-damaged rock sample is subjected to a uniaxial compression test, and a high-speed charge couple device camera is used to record the speckle field image of the sample surface during the whole loading process. The digital speckle techniques are used to analyse the image of the pre-damaged sample, the deformation field of the specimen surface, the displacement dislocation value of the localized deformation area and the deformation energy value of the specimen surface. The results show that for the same cycle times, the confining pressure is less than 80 MPa, which has a weakening effect on the rock's axial strength. As the confining pressure approaches 120 MPa, the pre-damaged rock uniaxial peak strength increases. The characteristics of displacement dislocation energy evolution of the localized deformation bound are divided into three stages (pre-peak stage, peak point and post-peak stage). After pre-damage under the same cycle times and different confining pressure conditions, the deformation field evolution of rock is relatively consistent.
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