SIRT1 regulates osteoblast senescence through SOD2 acetylation and mitochondrial dysfunction in the progression of Osteoporosis caused by Cadmium exposure.

Environmental Cadmium (Cd) is a toxicant with widespread exposure, documented adverse effects on bone homeostasis, and makes the onset of osteoporosis (OP), one of the age-related chronic diseases an enormous burden to modern societies worldwide. Aging is the largest risk factor for a multitude of age-related diseases and osteoblasts senescence reduces bone formation and is a key factor for osteoporosis. Despite anti-aging molecules the nuclear silent information regulator of transcription 1 (SIRT1) actions in chondrocytes and bone cells are critical for normal skeletal development and homeostasis, much less is known about the role of SIRT1 in osteoporosis. Here, we aim to demonstrate that SIRT1 mediates osteoblasts' senescence response to OP caused by Cd. The senescent osteoblasts accumulation and their viability were analyzed after Cd exposure. To explore the effects and mechanism of SIRT1 in Cd-induced osteoblastic senescence, we generated SIRT1-overexpressed osteoblast and SIRT1 conditional overexpression in the rat femur. Meanwhile, the OP rat model was established by removing bilateral ovaries. We found decreased SIRT1 expression and senescent osteoblasts accumulation after Cd exposure. Meanwhile, Cd exposure increased P53, P16INK4a, and P21CIPI proteins level, triggered DNA damage response (DDR) through the phosphorylation of ATM and H2AX, and caused mitochondrial dysfunction by the increased acetylation of SOD2 and excessive mitophagy. SIRT1 overexpression attenuated DDR and mitochondrial dysfunction and downregulated the increase of hall makers senescence caused by Cd in osteoblasts. We found overexpression of osteoblastic SIRT1 protects against Cd-induced senescence, which is likely driven by ATM-mediated DDR and SOD2ace-mediated mitochondrial dysfunction. Our study demonstrates the mechanism of SIRT1 in mediating bone homeostasis via senescence. Further mechanistic studies using specific SIRT1 mutations elucidating how SIRT1 modulates bone cell senescence, will provide new therapeutic strategies for human osteoporosis.

Modeling the Effect of Stress Ratio, Loading Frequency and Fiber Orientation on the Fatigue Response of Composite Materials.

Fatigue life models are widely used to predict the fatigue behavior at arbitrary cycle counts of composite structures subjected to cyclic or highly dynamic loads. However, their predictive capacity and determination of model parameters are strongly dependent on loading conditions and large experimental efforts. This research aims to develop a new model which uses a single model parameter to predict the variation trend and distribution pattern of fatigue experimental data points subjected to different stress ratios, loading frequencies and fiber orientations. Validation of the model with several sets of experimental data shows that the proposed model is capable of adequately considering the effects of stress ratio, loading frequency and fiber orientation on the fatigue behavior of composite materials and correctly predicting the variation trend of the experimental data points using only one set of model parameters regardless of stress ratios, loading frequencies and fiber orientations.

Moral Observer-Licensing in Cyberspace.

Moral observer-licensing happens when observers condone actors' morally questionable conduct due to the actors' history of moral behaviors. In four studies (N = 808), we investigated this phenomenon in the context of cyberspace and its contributing factors and boundary conditions. The pilot study determined what participants perceived as typically moral and immoral behaviors in cyberspace. Then, in Study 1, participants condemned a story character's online immoral behavior less often when they were informed of the character's prior online moral behavior than when they were not, which indicates moral observer-licensing in cyberspace. Study 2 confirmed the presence of moral observer-licensing in cyberspace and further demonstrated that a character's prior moral or immoral behavior online respectively reduces or intensifies the perceived negativity of the character's subsequent immoral behavior. Finally, Study 3 showed that participants who identified with the victim in a hypothetical scenario showed less forgiveness and more condemnation of a character's immoral behavior than those who identified with the perpetrator or the bystander. These findings are of theoretical and practical significance for our understanding of cyber ethics.