Effects of scriptaid on osteocytes skeletal homeostasis and metabolic functions

Bone has several crucial functions including mechanical support of movement, hematopoiesis, maintenance of mineral homeostasis, and energy regulation. Bone also undergoes continuous remodeling to maintain its structural integrity, which suggests it has strong respiration and energy consumption capability. It has been shown that during development, bones, in particular, osteoblasts, rely on glucose uptake for proper skeletal development. However, the effect of energy utilization on osteocytes’ function is currently unknown. Osteocytes are terminally differentiated osteoblasts and are deeply embedded into the mineralized matrix of bone. Previous studies have shown that PTH promotes bone anabolism, in part, by stimulating osteoblasts anaerobic glycolysis while suppressing glucose oxidation through the TCA cycle. In osteocytes, PTH suppresses Sost expression (the gene encoding a potent inhibitor of bone formation) by inducing HDAC4/5 nuclear translocation and MEF2C inhibition. Recently, Scriptaid, an HDAC complex inhibitor, has been shown to induce Mef2 expression and exercise-like adaptation in mouse muscles. In myocytes, Scriptaid disrupts the HDACs co-repressor complex and induces nuclear export of HDAC4/5 with MEF2 activation. This will subsequently increase the expressions of several genes related to energy utilization such as Glut4 and Pdk4. Thus we hypothesized that Scriptaid might regulate Sost and Glut4 expression in osteocytes. To investigate the effect of Scriptaid on osteocytes, we treated a mouse osteocytic cell line, Ocy454-12H, with Scriptaid. Unexpectedly, Scriptaid potently suppressed Sost, whereas it increased Glut4 expression. Scriptaid stimulated osteocyte respiration and glucose consumption rate. Mechanistically, Scriptaid treatment of Ocy454-12H induced nuclear translocation of Hdac5 whereas it did not affect Hdac4. Silencing of Hdac5 expression with shRNA increased Sost basal expression and blocked Sost suppression induced by Scriptaid. However, Glut4 up-regulation by Scriptaid was independent of the HDAC4/5-MEF2C pathway. Glut4 luciferase reporter assays demonstrated that two additional transcription factors binding sites, O/E&NF1 and C/EBPα, may mediate Scriptaid-induced Glut4 up-regulation. Taken together, these data demonstrate that in osteocytes Scriptaid suppresses Sost expression through regulating HDAC5-MEF2C signaling. However, Scriptaid increases Glut4 expression through Hdac5-independent mechanisms, and dependent on O/E&NF1 and C/EBPα

Delegation to Virtual Agents in Critical Scenarios: Influencing Factors and Immersive Settings

Favored by the rapid advance of technologies such as artificial intelligence and computer graphics, virtual agents have been increasingly accessible, capable, and autonomous over the past decades. As a result of their growing technological prowess, interaction with virtual agents has been gradually evolving from a traditional user-tool relationship to one resembling interpersonal delegation, where users empower virtual agents to autonomously carry out specific tasks on their behalf. Forming a delegatory relationship with virtual agents can facilitate the user-agent interaction in numerous aspects, particularly regarding convenience and efficiency. Yet, it also comes with problems and challenges that may harm users drastically in critical scenarios and thus deserves extensive research. This thesis presents a thorough discussion of delegation to virtual agents based on a series of studies my colleagues and I conducted over the past four years. Several factors --including agent representation, theory of mind, rapport, and technological immersion-- are examined individually via empirical approaches to reveal their impacts on delegation to virtual agents. A conceptual model featuring three interrelated dimensions is proposed, constituting a theoretical framework to integrate the empirical findings. An overall evaluation of these works indicates that users' decisions on delegating critical tasks to virtual agents are mainly based on rational thinking. Performance-related factors have a significant impact on delegation, whereas affective cues --such as rapport, agent representation, and theory of mind-- are influential only to a limited extent. Furthermore, the usage of immersive media devices (e.g., head-mounted displays) has a marginal effect on users' delegatory decisions. Thus, it is advisable for developers to focus on performance-related aspects when designing virtual agents for critical tasks

Vitamin D Supplementation Enhances the Fixation of Titanium Implants in Chronic Kidney Disease Mice

Vitamin D (Vit D) deficiency is a common condition in chronic kidney disease (CKD) patients that negatively affects bone regeneration and fracture healing. Previous study has shown that timely healing of titanium implants is impaired in CKD. This study aimed to investigate the effect of Vit D supplementation on implant osseointegration in CKD mice. Uremia was induced by 5/6 nephrectomy in C57BL mice. Eight weeks after the second renal surgery, animals were given 1,25(OH)2D3 three times a week intraperitoneally for four weeks. Experimental titanium implants were inserted into the distal end of femurs two weeks later. Serum measurements confirmed decreased 1,25(OH)2D levels in CKD mice, which could be successfully corrected by Vit D injections. Moreover, the hyperparathyroidism observed in CKD mice was also corrected. X-ray examination and histological sections showed successful osseointegration in these mice. Histomorphometrical analysis revealed that the bone-implant contact (BIC) ratio and bone volume (BV/TV) around the implant were significantly increased in the Vit D-supplementation group. In addition, resistance of the implant, as measured by a push-in method, was significantly improved compared to that in the vehicle group. These results demonstrate that Vit D supplementation is an effective approach to improve the fixation of titanium implants in CKD

TencentPretrain: A Scalable and Flexible Toolkit for Pre-training Models of Different Modalities

Recently, the success of pre-training in text domain has been fully extended to vision, audio, and cross-modal scenarios. The proposed pre-training models of different modalities are showing a rising trend of homogeneity in their model structures, which brings the opportunity to implement different pre-training models within a uniform framework. In this paper, we present TencentPretrain, a toolkit supporting pre-training models of different modalities. The core feature of TencentPretrain is the modular design. The toolkit uniformly divides pre-training models into 5 components: embedding, encoder, target embedding, decoder, and target. As almost all of common modules are provided in each component, users can choose the desired modules from different components to build a complete pre-training model. The modular design enables users to efficiently reproduce existing pre-training models or build brand-new one. We test the toolkit on text, vision, and audio benchmarks and show that it can match the performance of the original implementations

Technological Immersion and Delegation to Virtual Agents

Interacting with virtual agents in immersive settings is becoming increasingly common thanks to the proliferation of dedicated media devices, such as consumer-grade virtual and augmented reality headsets. These technologies offer many advantages, e.g., in terms of presence and engagement, and can impact user behavior and attitudes toward virtual agents. Recognizing and understanding these effects is essential, especially in critical contexts involving the delegation of high-stake decisions to virtual agents. This article presents two experiments that explore users’ delegatory behavior toward virtual agents experienced via different media devices that vary in their technological immersion, i.e., a device’s technical capacity to deliver immersive experiences. The experiments’ results suggest that technological immersion is not a significant factor in users’ delegation decisions. Thus, for virtual agents designed to carry out critical tasks, developers may focus on other relevant factors, such as agents’ trustworthiness or performance