Icariin Protects Bone Marrow Mesenchymal Stem Cells Against Iron Overload Induced Dysfunction Through Mitochondrial Fusion and Fission, PI3K/AKT/mTOR and MAPK Pathways

Iron overload has been reported to contribute to bone marrow mesenchymal stem cells (BMSCs) damage, but the precise mechanism still remains elusive. Icariin, a major bioactive monomer belonging to flavonoid glucosides isolated from Herba Epimedii, has been shown to protect cells from oxidative stress induced apoptosis. The aim of this study was to investigate whether icariin protected against iron overload induced dysfunction of BMSCs and its underlying mechanism. In this study, we found that iron overload induced by 100 μM ferric ammonium citrate (FAC) caused apoptosis of BMSCs, promoted cleaved caspase-3 and BAX protein expressions while inhibited Bcl-2 protein expression, which effects were significantly attenuated by icariin treatment. In addition, iron overload induced significant depolarization of mitochondrial membrane potential (MMP), reactive oxygen species (ROS) generation and inhibition of mitochondrial fusion/fission, which effects were also attenuated by icariin treatment. Meanwhile, we found that iron overload induced by 100 μM FAC significantly inhibited mitochondrial fission protein FIS1 and fusion protein MFN2 expressions, inhibited DRP1 and Cytochrome C protein translocation from the cytoplasm to mitochondria. Icariin at concentration of 1 μM was able to promote mitochondrial fission protein FIS1 and fusion protein MFN2 expressions, and increase DRP1 and cytochrome C protein translocation from the cytoplasm to mitochondria. Further, osteogenic differentiation and proliferation of BMSCs was significantly inhibited by iron overload, but icariin treatment rescued both osteogenic differentiation and proliferation of BMSCs. Further studies showed that icariin attenuated iron overload induced inactivation of the PI3K/AKT/mTOR pathway and activation of the ERK1/2 and JNK pathways. In summary, our study indicated that icariin was able to protect against iron overload induced dysfunction of BMSCs. These effects were potentially related to the modulation of mitochondrial fusion and fission, activation of the PI3K/AKT/mTOR pathway and inhibition of ERK1/2 and JNK pathways

Aging Relevant Metabolite Itaconate Inhibits Inflammatory Bone Loss

Progressive bone loss during aging makes osteoporosis one of the most common and life impacting conditions in geriatric populations. The bone homeostasis is maintained through persistent remodeling mediated by bone-forming osteoblast and bone-resorbing osteoclast. Inflammaging, a condition characterized by increased pro-inflammatory markers in the blood and other tissues during aging, has been reported to be associated with skeletal stem/progenitor cell dysfunction, which will result in impaired bone formation. However, the role of age-related inflammation and metabolites in regulation of osteoclast remains largely unknown. In the present study, we observed dichotomous phenotypes of anti-inflammatory metabolite itaconate in responding to inflammaging. Itaconate is upregulated in macrophages during aging but has less reactivity in responding to RANKL stimulation in aged macrophages. We confirmed the inhibitory effect of itaconate in regulating osteoclast differentiation and activation, and further verified the rescue role of itaconate in lipopolysaccharides induced inflammatory bone loss animal model. Our findings revealed that itaconate is a crucial regulatory metabolite during inflammaging that inhibits osteoclast to maintain bone homeostasis

Mathematical Model Construction of the Production Workshop Based on the Complex Network and Markov Theory

Because of the advantages of the complex network in describing the interaction between nodes, the complex network theory is introduced into the production process of the modern workshop in this paper. According to the characteristics of the workshop, based on extracted key nodes, the complex network model of the workshop is constructed to realize the mathematical description of the production process of the workshop. Aiming at the multidisturbance factors in the production process of the workshop, the key disturbance factors are predicted based on the Markov method, and the propagation dynamics model close to the actual production of the workshop is established. Finally, the bottleneck prediction model of the workshop under the disturbance environment is established. The simulation results show that the proposed prediction model is in good agreement with the actual data, and the coincidence rate is as high as 93.7%

A temperature prediction model for coal spontaneous combustion based on PSO-SRU deep artificial neural networks

Traditional temperature prediction models for coal spontaneous combustion typically have low generality and robustness. This paper improves them by proposing a coal spontaneous combustion temperature prediction model based on particle swarm optimization and simple recurrent unit(PSO-SRU). It firstly pre-processes the gas concentration data collected from temperature programmed oxidation tests, selects the concentration data of O2, CO, CO2, CH4, C2H4 that highly relate to the coal temperature as the prediction indicators, and further separates the indicators into training and testing data sets. Then, a SRU based prediction model over the training data set is trained to learn the nonlinear relationship between the coal spontaneous combustion temperature and the indicators. Mean absolute error(MAE) forms the fitness function and PSO algorithms are involved to optimize the SRU prediction model's parameters. Finally, the PSO-SRU model with optimized parameters are applied over the testing data set to predict the coal spontaneous combustion temperature. Experiments show the PSO-SRU model can improve the prediction accuracy, as the model's MAE and root mean square error(RMSE), comparing with those generated by support vector regression(SVR), random forest(RF), and back propagation(BP), decreases by 12.58, 7.65, 5.91 ℃, and 22.65, 17.45, 8.94 ℃ respectively. The PSO-SRU model also demonstrates a good generality and robustness, as the difference of determination coefficient (R2) of the model over the training and testing data sets is only 0.03

EFFECT OF DIFFERENT MAINTENANCE DOSES OF CAFFEINE CITRATE ON EARLY-STAGE PULMONARY FUNCTION AND COMPLICATIONS IN PRETERM INFANTS

Objective To investigate the effect of different maintenance doses of caffeine citrate treatment on early-stage pulmonary function and complications in preterm infants. Methods A total of 78 preterm infants with a gestational age of 28 weeks to 33+6 weeks who were admitted to our hospital from April 2019 to January 2022 and did not need invasive mechanical ventilation after birth were enrolled as subjects, and they were divided into high-maintenance-dose caffeine citrate group with 40 infants and low-maintenance-dose caffeine citrate group with 38 infants using a random number table. Both groups were given peripheral intravenous pumping of caffeine citrate at a loading dose of 20 mg/(kg·d) at 2 h after birth, and then the high and low maintenance dose groups were given caffeine citrate at a maintenance dose of 10 mg/(kg·d) and 5 mg/(kg·d), respectively, after 24 h. The two groups were compared in terms of pulmonary function, complications (necrotizing enterocolitis, retinopathy of prematurity, and intraventricular hemorrhage), and adverse reactions (feeding intolerance, hyperglycemia, and tachycardia) on days 7 and 14 after birth and at the corrected gestational age of 40 weeks. Results Compared with the low maintenance dose group, the high maintenance dose group had significantly higher tidal volume, ratio of time to peak tidal expiratory flow to total expiratory time, and ratio of volume to peak tidal expiratory flow to total expiratory volume on days 7 and 14 after birth and at the corrected gestational age of 40 weeks, as well as a significantly higher respiratory rate on days 7 and 14 after birth (t=2.107-4.128,P<0.05). There were no significant differences in the incidence rates of complications and adverse reactions between the high and low maintenance dose groups (P>0.05). Conclusion A high maintenance dose of caffeine citrate can significantly improve early-stage pulmonary function in preterm infants without increasing related complications and adverse reactions

Formation processes of shallow ground ice in permafrost in the Northeastern Qinghai-Tibet Plateau: A stable isotope perspective

The Source Area of the Yellow River (SAYR) on the Northeastern Qinghai-Tibet Plateau (QTP) stores substantial amounts of ground ice, which plays a significant role in understanding the hydrological processes and past permafrost evolution on the QTP. However, little is known about the initial sources and controlling factors of the ground ice in the SAYR. In this study, for the first time, ground ice stable isotope data (δ18O, δD, and d-excess) are presented, along with cryostratigraphic information for nine sites is integrated into three cryostratigraphic units (palsa, thermo-gully, and lake-affected sites) in the central SAYR. The ground ice in the nine sites exhibited diverse structures, ice contents, and stable isotopes due to differences in the initial water sources, ice formation mechanisms, soil types, and climate conditions. All of the freezing lines of ground ice are below those of the precipitation, streams, and lakes in most cases, suggesting the freezing of liquid water. The near-surface ground ice (NSGI) originated from precipitation, active layer water, and precipitation-fed springs. The NSGI was formed by quick freezing at the thermo-gully site (TG-1). In contrast, the formation of the NSGI at the palsa site (Palsa-1) experienced a slow segregation process during the permafrost aggradation. The NSGI was formed by quick freezing at the lake-affected sites under colder climate conditions. Conversely, the deep-layer ground ice (DLGI) at the lake-affected sites was fed by isotopically negative water and lake water occurred during a colder climate period. The DLGI at the TG-1 and Palsa-1 formed via similarly slow segregation of supra-permafrost water (mixed with precipitation), but had opposite water migration directions. The stable isotope compositions of the DLGI at the lake-affected sites became gradually more positive with decreasing distance from WL Lake, emphasizing the large influence of the lake changes on the growth of ice. The two end-member mixing model estimated that the contributions of paleo-lake water to the DLGI ranged from 9.8 % to 63.4 % towards the lake at the lake-affected sites, while the meltwater from past permafrost/ground ice contributed 36.6–90.2 % of the total input. A conceptual diagram of the δ18O trajectories of ground ice was constructed, the water migration patterns and ground ice formation processes between the palsa, thermo-gully, and lake-affected sites were clarified. The results of this study emphasize the influence of lake changes and past permafrost evolution on ground ice growth and improve our understanding of permafrost changes on the QTP