Identification of the osteoarthritis signature gene PDK1 by machine learning and its regulatory mechanisms on chondrocyte autophagy and apoptosis

BackgroundOsteoarthritis (OA) is a degenerative joint disease frequently diagnosed in the elderly and middle-aged population. However, its specific pathogenesis has not been clarified. This study aimed to identify biomarkers for OA diagnosis and elucidate their potential mechanisms for restoring OA-dysregulated autophagy and inhibiting chondrocyte apoptosis in vitro.Material and methodsTwo publicly available transcriptomic mRNA OA-related datasets (GSE10575 and GSE51588) were explored for biomarker identification by least absolute shrinkage and selection operator (LASSO) regression, weighted gene co-expression network analysis (WGCNA), and support vector machine recursive feature elimination (SVM-RFE). We applied the GSE32317 and GSE55457 cohorts to validate the markers’ efficacy for diagnosis. The connections of markers to chondrocyte autophagy and apoptosis in OA were also comprehensively explored in vitro using molecular biology approaches, including qRT-PCR and Western blot.ResultsWe identified 286 differentially expressed genes (DEGs). These DEGs were enriched in the ECM-receptor interaction and PI3K/AKT signaling pathway. After external cohort validation and protein-protein interaction (PPI) network construction, PDK1 was finally identified as a diagnostic marker for OA. The pharmacological properties of BX795-downregulated PDK1 expression inhibited LPS-induced chondrocyte inflammation and apoptosis and rescued OA-dysregulated autophagy. Additionally, the phosphorylation of the mediators associated with the MAPK and PI3K/AKT pathways was significantly downregulated, indicating the regulatory function of PDK1 in apoptosis and autophagy via MAPK and PI3K/AKT-associated signaling pathways in chondrocytes. A significantly positive association between the PDK1 expression and Neutrophils, Eosinophils, Plasma cells, and activated CD4 memory T cells, as well as an evident negative correlation between T cells follicular helper and CD4 naive T cells, were detected in the immune cell infiltration analysis.ConclusionsPDK1 can be used as a diagnostic marker for OA. Inhibition of its expression can rescue OA-dysregulated autophagy and inhibit apoptosis by reducing the phosphorylation of PI3K/AKT and MAPK signaling pathways

Probing the Galactic halo with RR Lyrae stars -- IV. On the Oosterhoff dichotomy of RR Lyrae stars

We use 3653 (2661 RRab, 992 RRc) RR Lyrae stars (RRLs) with 7D (3D position, 3D velocity, and metallicity) information selected from SDSS, LAMOST, and Gaia EDR3, and divide the sample into two Oosterhoff groups (Oo I and Oo II) according to their amplitude-period behaviour in the Bailey Diagram. We present a comparative study of these two groups based on chemistry, kinematics, and dynamics. We find that Oo I RRLs are relatively more metal rich, with predominately radially dominated orbits and large eccentricities, while Oo II RRLs are relatively more metal poor, and have mildly radially dominated orbits. The Oosterhoff dichotomy of the Milky Way's halo is more apparent for the inner-halo region than for the outer-halo region. Additionally, we also search for this phenomenon in the halos of the two largest satellite galaxies, the Large and Small Magellanic clouds (LMC, SMC), and compare over different bins in metallicity. We find that the Oosterhoff dichotomy is not immutable, and varies based on position in the Galaxy and from galaxy-to-galaxy. We conclude that the Oosterhoff dichotomy is the result of a combination of stellar and galactic evolution, and that it is much more complex than the dichotomy originally identified in Galactic globular clusters

H2O2 Is Involved in the Metallothionein-Mediated Rice Tolerance to Copper and Cadmium Toxicity

Cadmium (Cd) and excess copper (Cu) are toxic to plants, causing a wide range of deleterious effects including the formation of reactive oxygen species. Metallothioneins (MTs) may protect plant cells from heavy metal toxicity by chelating heavy metals via cysteine thiol groups. They may also function as antioxidants. The study investigated the relationship of H2O2 production and ricMT expression in rice radicles and rice suspension cells under Cu or Cd stress. The results showed that H2O2 production in the rice radicles increased before Cu-induced ricMT expression, and after Cd-induced ricMT expression. Rice suspension cells of sense- and antisense-ricMT transgenic lines were obtained by an Agrobacterium-mediated transformation. Overexpression of ricMT significantly decreased the death rate of rice cells, which was accompanied by blocked H2O2 accumulation in rice suspension cells subject to Cu and Cd stress. Our findings confirm that H2O2 is involved in the MT-mediated tolerance of Cu and Cd toxicity in rice

Modeling and Control of Hysteresis Characteristics of Piezoelectric Micro-Positioning Platform Based on Duhem Model

The hysteresis characteristic of piezoelectric micro-positioning platforms seriously affects its positioning accuracy in precision positioning. It is important to design an effective hysteresis model and control scheme. Based on the analysis of the Duhem model, this paper proposes to divide the hysteresis curve into two parts, the step-up section and the step-down section, to identify the model parameters, respectively, and a hybrid intelligent optimization algorithm based on the artificial fish swarm algorithm and the bat algorithm is proposed. The simulation experiment verified that the error of the improved model was reduced by 48.97%, which greatly improved the identification accuracy of the Duhem model. Finally, an inverse model of the Duhem model for the segmental identification of the improved artificial fish swarm algorithm is established, and a composite controller integrating feedforward, feedback and decoupling control is designed on the basis of the inverse model, and an experimental verification is carried out. The results show that the displacement errors of the composite controller under different voltage signals are all within 0.25%. Therefore, the established model can accurately express the hysteresis characteristics of the platform, and the use of the composite controller can effectively reduce the accuracy error caused by the hysteresis characteristics

FTCN: A Reservoir Parameter Prediction Method Based on a Fusional Temporal Convolutional Network

Predicting reservoir parameters accurately is of great significance in petroleum exploration and development. In this paper, we propose a reservoir parameter prediction method named a fusional temporal convolutional network (FTCN). Specifically, we first analyze the relationship between logging curves and reservoir parameters. Then, we build a temporal convolutional network and design a fusion module to improve the prediction results in curve inflection points, which integrates characteristics of the shallow convolution layer and the deep temporal convolution network. Finally, we conduct experiments on real logging datasets. The results indicate that compared with the baseline method, the mean square errors of FTCN are reduced by 0.23, 0.24 and 0.25 in predicting porosity, permeability, and water saturation, respectively, which shows that our method is more consistent with the actual reservoir geological conditions. Our innovation is that we propose a new reservoir parameter prediction method and introduce the fusion module in the model innovatively. Our main contribution is that this method can well predict reservoir parameters even when there are great changes in formation properties. Our research work can provide a reference for reservoir analysis, which is conducive to logging interpreters’ efforts to analyze rock strata and identify oil and gas resources

Modeling and Control of Hysteresis Characteristics of Piezoelectric Micro-Positioning Platform Based on Duhem Model

The hysteresis characteristic of piezoelectric micro-positioning platforms seriously affects its positioning accuracy in precision positioning. It is important to design an effective hysteresis model and control scheme. Based on the analysis of the Duhem model, this paper proposes to divide the hysteresis curve into two parts, the step-up section and the step-down section, to identify the model parameters, respectively, and a hybrid intelligent optimization algorithm based on the artificial fish swarm algorithm and the bat algorithm is proposed. The simulation experiment verified that the error of the improved model was reduced by 48.97%, which greatly improved the identification accuracy of the Duhem model. Finally, an inverse model of the Duhem model for the segmental identification of the improved artificial fish swarm algorithm is established, and a composite controller integrating feedforward, feedback and decoupling control is designed on the basis of the inverse model, and an experimental verification is carried out. The results show that the displacement errors of the composite controller under different voltage signals are all within 0.25%. Therefore, the established model can accurately express the hysteresis characteristics of the platform, and the use of the composite controller can effectively reduce the accuracy error caused by the hysteresis characteristics

Effects of Chlorogenic Acid on Performance, Anticoccidial Indicators, Immunity, Antioxidant Status, and Intestinal Barrier Function in Coccidia-Infected Broilers

The effects of chlorogenic acid (CGA) on growth performance, anticoccidial indicators (oocysts per gram of excreta, cecal lesion score, and bloody diarrhea score), immunity, antioxidant status, and intestinal barrier function in coccidia-infected broilers were investigated. A total of 240 one-day-old Arbor Acres broilers were randomly divided into four groups with six replicates of ten broilers each for 42 days. Four treatments included control diet (non-infected control, NC), control diet +Eimeria infection (infected control, IC), control diet +0.5 g/kg CGA + Eimeria infection (CGA0.5), and control diet +1 g/kg CGA + Eimeria infection (CGA1). At day 14, each broiler in IC, CGA0.5, and CGA1 groups was orally inoculated with 1 mL saline containing 4 × 105 sporulated oocysts. The results showed that the CGA1 group increased the average daily gain by 12.57% (p < 0.001) and decreased the feed/gain ratio (p = 0.010) and mortality (p = 0.030) by 13.00% and 77.76%, respectively, of broilers from 14 to 42 days compared with the IC group. The CGA1 group decreased the oocysts per gram of excreta (p < 0.001) and bloody diarrhea score (p = 0.001) compared with the IC group. The CGA0.5 and CGA1 groups increased total antioxidant capacity (p < 0.001) at day 21 and villus height (p < 0.001) in the duodenum and jejunum at day 42, and decreased the levels of interleukin 6 (IL-6) (p = 0.002), malondialdehyde (MDA) (p < 0.001), D-lactic acid (p < 0.001), and diamine oxidase (DAO) (p < 0.001) at day 21 and the levels of MDA (p < 0.001) and D-lactic acid (p = 0.003) at day 42 compared with the IC group. In the CGA1 group, villus height in the duodenum (p < 0.001) and jejunum (p = 0.017) increased at day 21 and in the ileum (p < 0.001) at day 42, and the level of DAO (p < 0.001) decreased at day 42 compared with the IC group. Broilers in the IC group had a higher IL-6 level (p = 0.048) at day 42 and lower IL-10 (p = 0.027) and immunoglobulin A (p = 0.042) levels at day 21, and IL-10 level (p = 0.017) at day 42 than those in the NC group, while no significant differences were observed among the NC, CGA0.5, and CGA1 groups. In conclusion, dietary supplementation with 1 g/kg CGA improved growth performance, immunity, antioxidant status, and intestinal barrier function in coccidia-infected broilers

Numerical Study of Bond Slip between Section Steel and Recycled Aggregate Concrete with Full Replacement Ratio

In this paper, the bond deterioration mechanism of recycled aggregate concrete (RAC) with a full replacement ratio was studied through experimental and numerical simulations. To study the bond behavior and the bond slip between section steel and RAC, nine push-out specimens were designed using the control variable method. The effects of the concrete strength, the embedded length, the cover thickness, and the lateral stirrup ratio on the bond behavior and the bond slip were investigated in detail. The loading process and failure mode of the specimens were observed, and the test curves of the loading end and free end of the specimens were analyzed. Based on the experiment, the finite element method (FEM) was used to simulate the specimens, and the simulation results were analyzed by comparing the experiment data. The analysis of the results showed that the developed model is capable of representing the characteristic bond strength value between section steel and RAC with sufficient accuracy, and the main differences of bond slip between the simulation and the test results are the slippage at the limit state and the moment at which the free end starts to slip

Influences of Trypsin Pretreatment on the Structures, Composition, and Functional Characteristics of Skin Gelatin of Tilapia, Grass Carp, and Sea Perch

Fish skin gelatin is an important functional product in the food, cosmetics, and biomedicine industries, and establishing a green and effective fish skin gelatin extraction method is an effective way to obtain high-quality gelatin and improve its production efficiency. In this study, a trypsin method was used to extract the skin gelatin of sea perch, tilapia, and grass carp, and the microstructures of skin gelatin of these three fish species were analyzed, with such functional characteristics as thermal stability, gel strength, and emulsifying properties measured. The study results show that the skin gelatin of sea perch and tilapia obtained through the trypsin method has a relatively big molecular mass, a dense network structure, and a stable trihelix conformation. In addition, the skin gelatin of these three fish species has a relatively high β-turn content in the secondary structure, good gel strength, and water absorption properties. The compositions of the collagen-associated proteins in the skin gelatins of these three fish species extracted with the trypsin method are significantly different from each other, with positive effects of decorin and biglycan on the stability of the network structure of gelatin and a certain damaging effect of metalloendopeptidase on the network structure of gelatin. The skin gelatin of tilapia has high thermal stability and good emulsifying performance. Therefore, this gelatin type has bright application prospects in such fields as food processing, cosmetics, and drug development. In contrast, the skin gelatin of grass carp has poor functional properties. Therefore, there are significant differences among the structures and functions of skin gelatin extracted from different kinds of fish through the trypsin method. This finding has provided a useful reference for the production of customized fish gelatin according to demand