Crif1 Promotes Osteoporosis in Mice after Radiation

Abstract Radiation induces rapid bone loss and enhances bone resorption and RANKL expression. RANKL provides the crucial signal to induce osteoclast differentiation and plays an important role in bone resorption. However, the mechanisms of radiation-induced osteoporosis are not fully understood. Here, we show that Crif1 expression increases in bone marrow cells after radiation. Conditional Crif1 deletion in bone marrow cells causes decreases in RANKL expression and the RANKL/OPG ratio, and relieves bone loss after radiation in mice. We further demonstrated in vitro that Crif1 promotes RANKL secretion via the cAMP/PKA pathway. Moreover, protein-protein docking screening identified five compounds as Crif1 inhibitors; these compounds dramatically suppressed RANKL secretion and CREB phosphorylation when cells were exposed to forskolin. This study enriches current knowledge of the pathogenesis of osteoporosis and provides insights into potential therapeutic strategies for osteoporosis treatment

Nurse-led cognitive screening model for older adults in primary care

Author version made available in accordance with publisher copyright. Under 12 month embargo from date of publication [26 September 2014]. This is the accepted version of the following article: [Yang, Y., Xiao, L. D., Deng, L., Wang, Y., Li, M. and Ullah, S. (2014), Nurse-led cognitive screening model for older adults in primary care. Geriatrics & Gerontology International.], which has been published in final form at [doi: 10.1111/ggi.12339]. In addition, authors may also transmit, print and share copies with colleagues, provided that there is no systematic distribution of the submitted version, e.g. posting on a listserve, network or automated delivery.Aim The present study aimed to establish a nurse-led cognitive screening model for community-dwelling older adults with subjective memory complaints from seven communities in Chongqing, China, and report the findings of this model. Methods Screenings took place from July 2012 to June 2013. Cognitive screening was incorporated into the annual health assessment for older adults with subjective memory complaints in a primary care setting. Two community nurses were trained to implement the screening using the Mini-Mental State Examination and Montreal Cognitive Assessment. Results Of 733 older adults, 495 (67.5%) reported having subjective memory complaints. Of the 249 individuals who participated in the cognitive screening, 102 (41%) had mild cognitive impairment, whereas 32 (12.9%) had cognitive impairment. A total of 80 participants (78.4%) with mild cognitive impairment agreed to participate in a memory support program. Participants with cognitive impairment were referred to specialists for further examination and diagnosis; only one reported that he had seen a specialist and had been diagnosed with dementia. Conclusions Incorporating cognitive screening into the annual health assessment for older adults with subjective memory complaints was feasible, though referral rates from primary care providers remained unchanged. The present study highlights the urgent need for simple screenings as well as community-based support services in primary care for older adults with cognitive or mild cognitive impairments

Role of mitochondria in early molecular diagnosis and prognosis of cancer

Background:Earlier clinical detection of cancer may improve survival as well as offer opportunities for less invasive treatment options. This thesis explores whether the mitochondria and its related genes in the nuclear genome can be used as novel methods for the diagnosis and prognosis of cancers.Aims and Methods:Paper I: To investigate if mitochondrial dysfunction (characterized by mtDNA copy number variations) is associated with prevalent, incident cancer and cancer mortality – droplet digital PCR (ddPCR).Paper II: To investigate the potential causal relationship between mitochondrial dysfunction (characterized by genetic predispositions in all mitochondrial-related genes) and common cancer risks – Mendelian randomization, colocalization.Paper III: To investigate mitochondrial mutations as potential biomarkers for the early diagnosis of breast cancer – whole mitochondrial genome sequencing, bioinformatics, ddPCR.Paper IV: To investigate the mitochondrial-related gene expression signature as a prognostic model to predict the clinical outcome for breast cancer patients – machine learning.Results and conclusions:Paper I: We found that mtDNA-CN was significantly associated with prevalent and incident cancer as well as cancer mortality. However, these associations were cancer-type specific and need further investigation.Paper II: We identified potential causal relationships between mitochondrial-related genes and breast, prostate and lung cancer. Furthermore, this study identified candidate genes that can be the targets of potential pharmacological agents for cancer prevention.Paper III: We comprehensively characterized the mtDNA mutation landscape of breast cancer biopsies and matched baseline whole blood samples. Notably, we have identified and validated mt.16093T>C mutation, which was associated with a 67% increased risk of developing breast cancer, and could potentially be used as early breast cancer diagnostic biomarkers.Paper IV: We built a novel 14 genes mitochondrial signature model that could be an independent prognostic predictor and together with clinical variables as an improved model for predicting overall earlystage of breast cancer survival

Genetic and Environmental Effects on Liver Diseases

The understanding of risk factors for liver diseases, including genetic and environmental factors, has expanded in the last decade. Genetic susceptibility to complex liver diseases, combined with multi-factors such as lifestyle and gut microbiome, provide us with a more complete picture of disease pathophysiology. Liver transplantation, an inevitable treatment for end-stage liver diseases, has been on the rise over the last 20 years. The early postoperative complications, such as thrombosis and graft rejection account for the high morbidity and mortality of transplant patients. Donor genetic risk and the genetic variation mismatches between donors and recipients have been recognized as contributors to the transplantation outcomes. The following messages could be concluded from this thesis: 1) Accomplishing the first genome-wide association study in liver transplantation highlights the importance of the genetic research in this field, as this is a worthwhile way to determine pathophysiological differences between individuals compared to the general population; 2) Investigation of multiple risk factors, including demographics, environmental, and genetic risk factors for the complex disease help us create a more complete understanding of the etiology of complex liver diseases; 3) Beyond one layer of genetic analysis, the development of “multi-omics” studies and the combination of “multi-methods” analysis in liver diseases will provide frameworks for future fundamental research and translational medicine. We indicate that the clinical implementation of rapidly developing technologies and the interpretation of the accumulating genetic data are challenging, but integrative genetic studies are enabling us to unveil pathogenesis processes in complex liver diseases

The genesis, evolution, and expansion of the theory of literary aesthetic ideology

The core concept of the theory of literary aesthetic ideology is that literature is a reflection of real social life and is an ideology; at the same time, it is a reflection that has played subjectivity and initiative, and is an aesthetic ideology. From the perspective of philosophical foundations, the theory of aesthetic ideology is epistemological; from the process of concept formation, it has not been able to get rid of the "essence—feature" thinking mode; therefore, the essence of literature is still ideology, and aesthetics is just a feature. In view of this, we propose to construct a literary view of "aesthetic practice" based on the theory of practice. Different from the epistemological view of literature, the literary view of aesthetic practice not only sees literature as a means to reflect social life but also sees literature as a basic way of human activity and existence. Because of its aesthetic characteristics, this way of activity determines that literature can play a great role in negating, criticizing, and guiding reality. Therefore, literature not only plays a role that is subordinate to ideology but also plays a role in resisting ideology. The theory of literary practice and the view of aesthetic practice are both an inheritance and a transcendence of the theory of literary reflection and the view of aesthetic ideology literature

Learning-by-Doing in Non-Homogeneous Tasks: An Empirical Study of Content Creator Performance on A Music Streaming Platform

With the development of high-speed internet and better mobile connections, online streaming platforms with user-generated videos are becoming popular. The success of these platforms relies on content creators who can effectively enhance user engagement (e.g., subscribing to a content creator’s channel). As opposed to homogeneous production scenarios (e.g., assembling automobiles in a factory), creating user-generated videos is a more complex task in which learning might happen. In this study, we empirically test the effect of prior experience on content creators’ performance. Furthermore, we examine the role of specialization in learning. We use a dataset from NetEase Cloud Music, one of the most popular music streaming platforms in China, with 21,549 content creators and 252,762 user-generated videos. The findings indicate that: (1) prior experience has a positive effect on creators’ performance; (2) specialized experience across distinct video categories has a nonlinear effect on creators’ performance. These results have implications for improving user engagement for online user-generated video streaming platforms

Global Dynamics and Applications of an Epidemiological Model for Hepatitis C Virus Transmission in China

An epidemiological model is proposed and studied to understand the transmission dynamics and prevalence of HCV infection in China. Theoretical analysis indicates that the basic reproduction number R0 provides a threshold value determining whether the disease dies out or not. Two Lyapunov functions are constructed to prove the global asymptotic stability of the disease-free and the endemic equilibria, respectively. Based on data reported by the National Health and Family Planning Commission of China, the basic reproduction number is estimated as approximately R0=1.9897, which is much less than that for the model when a treatment strategy is not considered. An ever-increasing HCV infection is predicted in the near future. Numerical simulations, performed to investigate the potential effect of antiviral treatment, show that increasing the treatment cure rate and enlarging the treatment rate for patients at the chronic stage remain effective in reducing the number of new infections and the equilibrium prevalence. The finding suggests that treatment measures are significantly beneficial for disease control in terms of reducing new infections and, in particular, more attention should be paid to treatment for patients at the chronic stage