Myricetin alleviates H2O2-induced senescence and apoptosis in rat nucleus pulposus-derived mesenchymal stem cells

Introduction. Transplantation of mesenchymal stem cells (MSCs) has been reported to be a novel promising target for the regeneration of degenerated intervertebral discs (IVDs). However, the culture and survival limitations of MSCs remain challenging for MSC-based biological therapy. Myricetin, a common natural flavonoid, has been suggested to possess antiaging and antioxidant abilities. Therefore, we investigated the biological function of myricetin, and its related mechanisms involving cell senescence in intervertebral disc degeneration (IDD). Material and methods. The nucleus pulposus-derived mesenchymal stem cells (NPMSCs) were isolated from 4-month-old Sprague-Dawley (SD) rats and identified by examining surface markers and multipotent differentiation. Rat NPMSCs were cultured in an MSC culture medium or culture medium with different concentrations of H2O2. Myricetin or the combination of myricetin and EX527 were added to the culture medium to investigate the effects of myricetin. Cell viability was evaluated by cell counting kit-8 assays (CCK-8). The apoptosis rate was determined using Annexin V/PI dual staining. The mitochondrial membrane potential (MMP) was analyzed by a fluorescence microscope after JC-1 staining. The cell senescence was determined by SA-β-Gal staining. MitoSOX green was used to selectively estimate mitochondrial reactive oxygen species (ROS) Apoptosis-associated proteins (Bax, Bcl2, and cleaved caspase-3), senescence markers (p16, p21, and p53), and SIRT1/PGC-1α signaling pathway-related proteins (SIRT1 and PGC-1α) were evaluated by western blotting. Results. The cells isolated from nucleus pulposus (NP) tissues met the criteria for MSCs. Myricetin showed no cytotoxicity up to a concentration of 100 μM in rat NPMSCs cultured for 24 h. Myricetin pretreatment exhibited protective effects against H2O2-induced apoptosis. Myricetin could also alleviate H2O2-induced mitochondrial dysfunctions of increased mitochondrial ROS production and reduced MMP. Moreover, myricetin pretreatment delayed rat NPMSC senescence, as evidenced by decreased senescence indicators and reduced SA-β-Gal activity. Pretreatment of NPMSCs with 10 μM EX527, a selective inhibitor of SIRT1, prior to exposure to 100 μM H2O2, reversed the inhibitory effects of myricetin on cell apoptosis. Conclusions. Myricetin could affect the SIRT1/PGC-1α pathway to protect mitochondrial functions and alleviate cell senescence in H2O2-treated NPMSCs

Dynamic Responses of Tree-Ring Growth to Multiple Dimensions of Drought

Droughts, which are characterized by multiple dimensions including frequency, duration, severity and onset timing, can impact tree growth profoundly. Different dimensions of drought influence tree growth independently or jointly, which makes the development of accurate predictions a formidable challenge. Measurement-based tree-ring data have obvious advantages for studying the drought responses of trees. Here, we explored the use of abundant tree-ring records for quantifying regional response patterns to key dimensions of drought. Specifically, we designed a series of regional-scaled “natural experiments”, based on 357 tree-ring chronologies from Southwest USA and location-matched monthly water balance anomalies, to reveal how tree-ring growth responds to each dimension of drought. Our results showed that tree-ring growth was affected significantly more by the water balance condition in the current hydrological year than that in the prior hydrological year. Within the current hydrological year, increased drought frequency (number of dry months) and duration (maximum number of consecutive dry months) resulted in “cumulative effects” which amplified the impacts of drought on trees and reduced the drought resistance of trees. Drought events that occurred in the pre-growing seasons strongly affected subsequent tree growth. Both the onset timing and severity of drought increased “legacy effects” on tree growth, which reduced the drought resilience of trees. These results indicated that the drought impact on trees is a dynamic process: even when the total water deficits are the same, differences among the drought processes could lead to considerably different responses from trees. This study thus provides a conceptual framework and probabilistic patterns of tree-ring growth response to multiple dimensions of drought regimes, which in turn may have a wide range of implications for predictions, uncertainty assessment and forest management

Enhanced entanglement and output squeezing in electro-optomechanical system with an optical parametric amplifier

We investigate the entanglement phenomena, assisted by an electro-optical hybrid system with an optical parametric amplifier. The system consists of one mechanical oscillator that is coupled to another oscillator via a Coulomb force and also to an optical cavity via an optomechanical interaction. If the coupling between the cavity field and the optical parametric amplifier and between the two mechanical oscillators is suitable, the system exhibits the phenomena of stationary entanglement. Specifically, the entanglement is strongly affected by the parameter gain and the Coulomb interaction, and larger parameter gain and stronger Coulomb coupling induce an increasing amount of entanglement. We also study the output squeezing, and the results reveal that the output entanglement is affected by the resonator frequency, the parameter gain, and the Coulomb coupling

Influence of NaCl solution on dynamic characteristics of clay under cyclic loading and microscopic mechanism analysis

Aiming at the problem that the change of the pore solution environment has a great influence on the dynamic characteristics of clay, graded loading tests were performed on clay samples under simulated traffic cyclic loads by using a GDS true/dynamic triaxial apparatus. The effects of different concentrations of NaCl pore solution and vibration frequency on the stress-strain relationship and dynamic elastic modulus of the soil were studied, and the development rules of the backbone curve and elastic modulus were analyzed. Combined with electron microscope scanning, the pore distribution law of samples before and after changing the NaCl solution concentration and vibration frequency was analyzed to obtain the relationship between micro-pore size and dynamic characteristics. The results show that with the increase of NaCl solution concentration and vibration frequency, the stress-strain curve and dynamic elastic modulus curve show an upward trend; the damping ratio-dynamic strain curve rises with the increase of vibration frequency and decreases with the increase of NaCl solution concentration; at higher NaCl solution concentration, the increase of colloid produced by the hydration reaction can effectively reduce small pores; increasing vibration frequency compresses the distance between flaky particles, reduces the layered structure and makes the soil more compact, effectively reducing large pores. The influence of pore solution and vibration frequency on clay with NaCl solution is obtained, which provides some reference for intensity change of clay under other environment

An Attribute-Based Access Control Policy Retrieval Method Based on Binary Sequence

With the widespread application of new technologies, fine-grained authorization requires a large number of access control policies. However, the existing policy retrieval method applied to a large-scale policy environment has the problem of low retrieval efficiency. Therefore, this paper proposes an attribute access control policy retrieval method based on the binary sequence. This method uses binary identification and binary code to express access control requests and policies. When the policy is retrieved, the appropriate group is selected through the logical operation of the access control request and the policy binary identification. Within the group, the binary code of the access control request is matched with the binary code of all rules to find suitable rules, thereby reducing the number of matching attribute-value pairs in the rule and improving the efficiency of policy retrieval. Experimental results show that the policy retrieval method proposed in this paper has higher retrieval efficiency

Entanglement of two movable mirrors and two-mode cavity fields generated by a single four-level atom

We present a scheme using a single four-level atom to entangle two mesoscopic mirrors. If the coupling between the cavity fields and the atom is suitable, then our study shows entanglement between the two movable mirrors, between the two-mode fields, and also between the mirror and the distant cavity mode. Because the energy difference between the two lowest levels of the four-level atom is not negligible, the entanglement of the mirrors as well as the squeezing spectrum of the output cavity fields display a splitting phenomenon. In the present scheme, only a single trapped atom is used, which sheds new light on the use of microscopic atomic coherence for the production of mesoscopic entanglement

Development and verification of large deformation model considering stiffness deterioration and shear dilation effect in FLAC3D

The existing constitutive models of rock with strain softening cannot successfully reflect the damage-induced anisotropy and nonlinearity of the post-peak failure behavior under progressive loading. In order to better reflect the nonlinear stress-strain behavior of rock, especially for the post-peak failure behavior, with expected stiffness degradation and large deformation, a modified constitutive model of rock considering stiffness degradation and dilatation behavior at large deformation was proposed in this study. This study analyzes and discusses various attenuation parameters in the proposed nonlinear plastic constitutive model using FLAC3D software. The excavation-induced stress in rocks was calculated by FLAC3D using the Mohr-Coulomb model, conventional strain model, and the proposed modified model. The obtained results of these models were analyzed and compared with field data. This study shows that the simulated results using the proposed new constitutive model matched much more closely with the measured field data, with an average error less than 5%. This new model can successfully reflect the damage-induced stiffness degradation at large deformation, and can provide a theoretical basis for stability design and evaluation of underground excavation. Keywords: Stiffness degradation, Dilatancy behavior, Nonlinearity, Post-peak failure behavior, Deep soft rock roadway, FLAC3

Pollution characteristics and ecological risk assessment of heavy metals in the surface sediments from a source water reservoir

Surface sediment samples were collected from a source water reservoir in Zhejiang Province, East of China to investigate pollution characteristics and potential ecological risk of heavy metals. The BCR sequential extraction method was used to determine the four chemical fractions of heavy metals such as acid soluble, easily reducible, easily oxidizable and residual fractions. The heavy metals pollution and potential ecological risk were evaluated systematically using geoaccumulation index (Igeo) and Hakanson potential ecological risk index (H′). The results showed that the sampling sites from the estuaries of tributary flowing through downtowns and heavy industrial parks showed significantly (p < 0.05) higher average concentrations of heavy metals in the surface sediments, as compared to the other sampling sites. Chemical fractionation showed that Mn existed mainly in acid extractable fraction, Cu and Pb were mainly in reducible fraction, and As existed mainly in residual fraction in the surface sediments despite sampling sites. The sampling sites from the estuary of tributary flowing through downtown showed significantly (p < 0.05) higher proportions of acid extractable and reducible fractions than the other sampling sites, which would pose a potential toxic risk to aquatic organisms as well as a potential threat to drinking water safety. As, Pb, Ni and Cu were at relatively high potential ecological risk with high Igeo values for some sampling locations. Hakanson potential ecological risk index (H′) showed the surface sediments from the tributary estuaries with high population density and rapid industrial development showed significantly (p < 0.05) higher heavy metal pollution levels and potential ecological risk in the surface sediments, as compared to the other sampling sites