Research progress in the relationship between mitochondrial dysfunction and osteoporosis

Osteoporosis (OP) is a chronic senile bone disease characterized by decreased bone mass and increased bone fragility. There are many inducing factors and the pathogenesis is complex. To explore the mechanism of OP and improve clinical efficacy has always been a hot topic in life science. In recent years, it has been found that mitochondria play an important role in the pathogenesis of OP. Functional abnormalities such as mitochondrial energy metabolism, mitochondrial oxidative stress, mitochondrial autophagy, mitochondrial-mediated apoptosis and mitochondrial dynamics can interfere with the differentiation of bone marrow mesenchymal stem cells through different signal pathways, cytokines and protein expression to regulate osteoblast activity, proliferation and differentiation, and start the process of osteoclast apoptosis. Therefore, taking mitochondria as the target, regulating the functions of mitochondrial energy metabolism, oxidative stress, autophagy and kinetics, inducing osteogenic differentiation of bone marrow mesenchymal stem cells, promoting osteoblast differentiation and mineralization, and inducing osteoclast apoptosis are potential strategies for the prevention and treatment of OP. In this article, the mechanism of mitochondrial dysfunction in OP was reviewed by referring to relevant literature at home and abroad, in order to lay a foundation for further research

Disruption of the AMPK-TBC1D1 nexus increases lipogenic gene expression and causes obesity in mice via promoting IGF1 secretion

Tre-2/USP6, BUB2, cdc16 domain family member 1 (the TBC domain is the GTPase activating protein domain) (TBC1D1) is a Rab GTPase activating protein that is phosphorylated on Ser(231) by the AMP-activated protein kinase (AMPK) in response to intracellular energy stress. However, the in vivo role and importance of this phosphorylation event remains unknown. To address this question, we generated a mouse model harboring a TBC1D1(Ser231Ala) knockin (KI) mutation and found that the KI mice developed obesity on a normal chow diet. Mechanistically, TBC1D1 is located on insulin-like growth factor 1 (IGF1) storage vesicles, and the KI mutation increases endocrinal and paracrinal/autocrinal IGF1 secretion in an Rab8a-dependent manner. Hypersecretion of IGF1 causes increased expression of lipogenic genes via activating the protein kinase B (PKB; also known as Akt)–mammalian target of rapamycin (mTOR) pathway in adipose tissues, which contributes to the development of obesity, diabetes, and hepatic steatosis as the KI mice age. Collectively, these findings demonstrate that the AMPK–TBC1D1 signaling nexus interacts with the PKB–mTOR pathway via IGF1 secretion, which consequently controls expression of lipogenic genes in the adipose tissue. These findings also have implications for drug discovery to combat obesity

AS160 deficiency causes whole-body insulin resistance via composite effects in multiple tissues.

AS160 (Akt substrate of 160 kDa) is a Rab GTPase-activating protein implicated in insulin control of GLUT4 (glucose transporter 4) trafficking. In humans, a truncation mutation (R363X) in one allele of AS160 decreased the expression of the protein and caused severe postprandial hyperinsulinaemia during puberty. To complement the limited studies possible in humans, we generated an AS160-knockout mouse. In wild-type mice, AS160 expression is relatively high in adipose tissue and soleus muscle, low in EDL (extensor digitorum longus) muscle and detectable in liver only after enrichment. Despite having lower blood glucose levels under both fasted and random-fed conditions, the AS160-knockout mice exhibited insulin resistance in both muscle and liver in a euglycaemic clamp study. Consistent with this paradoxical phenotype, basal glucose uptake was higher in AS160-knockout primary adipocytes and normal in isolated soleus muscle, but their insulin-stimulated glucose uptake and overall GLUT4 levels were markedly decreased. In contrast, insulin-stimulated glucose uptake and GLUT4 levels were normal in EDL muscle. The liver also contributes to the AS160-knockout phenotype via hepatic insulin resistance, elevated hepatic expression of phosphoenolpyruvate carboxykinase isoforms and pyruvate intolerance, which are indicative of increased gluconeogenesis. Overall, as well as its catalytic function, AS160 influences expression of other proteins, and its loss deregulates basal and insulin-regulated glucose homoeostasis, not only in tissues that normally express AS160, but also by influencing liver function

New Structural Design Tool for Integration of Heavy Crane on Offshore Vessels

In this thesis, a simple hand calculation tool is established for heavy crane integration on offshore vessels at an early stage of design. This tool can be used for varying positions and diameters of the crane. It is verified by FEM analysis and an example case study. This hand calculation tool is demonstrated to be feasible in this condition but still has some limitations. The most important is the assumptions and simplifications and the way of thinking and solving engineering problems

Two-stage Hierarchical Framework for Solar Flare Prediction

Solar flares, often accompanied by coronal mass ejections and other solar phenomena, are one of the most important sources affecting space weather. It is important to investigate the forecast approach of solar flares to mitigate their destructive effect on the Earth. Statistical analysis, associated with data from 2010 to 2017 in Space-weather HMI Active Region Patches (SHARPs) collected by the Solar Dynamics Observatory's Helioseismic and Magnetic Imager, reveals that there is a distribution divergence between the two types of active regions (ARs) of solar flares. A two-stage hierarchical prediction framework is formulated to better utilize this intrinsic distribution information. Specially, we pick up the ARs where at least one solar flare event occurs within the next 48 hr as flaring ARs through balanced random forest and naive Bayesian methods and then predict the events from flaring ARs by a cascade module of learning models. The empirical evaluation of SHARPs data from 2016 to 2019 verifies the promising performance of our framework, e.g., 0.727 for the true skill statistic

Research Progress in Pre-harvest Sprouting of Rice

Pre-harvest sprouting is a serious problem in global agricultural production. After a long period of domestication, the dormancy level of cultivated crops is generally lower than that of wild ancestors. Although the shortening of dormancy period may increase the reproductive generation and agricultural production value of crops, premature dormancy release will cause crop sprouting before harvest, resulting in huge economic losses. In this paper, the physiological mechanism, QTL and genes, prevention and control of pre-harvest sprouting are systematically reviewed. It is believed that high water content is the precondition of rice seed germination and pre-harvest sprouting, during this process, the increases of amylase activity and soluble sugar content provide energy for pre-harvest sprouting; the contents of plant hormones ABA and GA in rice grains and the sensitivity of seeds to them are the key factors to determine the pre-harvest germination. In recent years, the excavation of QTL and its functional genes related to pre-harvest sprouting will provide an important basis for clarifying the mechanism of pre-harvest sprouting in rice and breeding resistant varieties. In the long run, through extensive evaluation of rice germplasm resources, especially searching for the lost dormancy genes in wild rice and local varieties, and gathering such genes through molecular breeding, breeding lines (varieties) resistant to sprouting, it is of great significance to solve the problem of sprouting, improve rice yield and quality, and ensure national food security