Lp-PLA2 silencing ameliorates inflammation and autophagy in nonalcoholic steatohepatitis through inhibiting the JAK2/STAT3 pathway

Background Nonalcoholic steatohepatitis (NASH), a common cause of liver-related morbidity and mortality worldwide, is characterized by inflammation and hepatocellular injury. Our research focuses on lipoprotein-associated phospholipase A2 (Lp-PLA2), an inflammation-related biomarker that has recently garnered interest in the context of NASH due to its potential roles in disease pathogenesis and progression. Methods We established a NASH mouse model using a high-fat diet (HFD) and treated it with sh-Lp-PLA2 and/or rapamycin (an mTOR inhibitor). Lp-PLA2 expression in NASH mice was detected by qRT-PCR. Serum levels of liver function parameters and inflammatory cytokines were detected using corresponding assay kits. We examined pathological changes in liver using hematoxylin-eosin, oil red O, and Masson staining, and observed autophagy through transmission electron microscopy. The protein levels of Lp-PLA2, mTOR, light chain 3 (LC3) II/I, phosphorylated Janus kinase 2 (p-JAK2)/JAK2, and phosphorylated signal transducer and activator of transcription 3 (p-STAT3)/STAT3 were determined by western blotting. Kupffer cells extracted from C57BL/6J mice were treated to replicate NASH conditions and treated with sh-Lp-PLA2, rapamycin, and/or a JAK2-inhibitor to further verify the roles and mechanisms of Lp-PLA2 in NASH. Results Our data indicate an upregulation of Lp-PLA2 expression in HFD-induced NASH mice. Silencing Lp-PLA2 in NASH mice reduced liver damage and inflammation markers (aspartate aminotransferase (AST), alanine aminotransferase (ALT), total cholesterol (TC), triglycerides (TG), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6)), while increasing IL-10 levels, an anti-inflammatory cytokine. Additionally, Lp-PLA2 silencing decreased lipid and collagen accumulation and promoted autophagy. The beneficial effects of sh-Lp-PLA2 on NASH were enhanced by rapamycin. Furthermore, Lp-PLA2 silencing resulted in the downregulation of the expression of p-JAK2/JAK2 and p-STAT3/STAT3 in NASH mice. Similar results were observed in Kupffer cells treated under NASH conditions; Lp-PLA2 silencing promoted autophagy and repressed inflammation, effects which were potentiated by the addition of rapamycin or a JAK2-inhibitor. Conclusion Our findings suggest that silencing Lp-PLA2 promotes autophagy via deactivating the JAK2/STAT3 signaling pathway, thereby restraining NASH progression. This highlights the potential therapeutic value of targeting Lp-PLA2, adding a new dimension to our understanding of NASH pathogenesis and treatment strategies

Multi-Target Parameter Estimation of the FMCW-MIMO Radar Based on the Pseudo-Noise Resampling Method

Subspace methods are widely used in FMCW-MIMO radars for target parameter estimations. However, the performances of the existing algorithms degrade rapidly in non-ideal situations. For example, a small number of snapshots may result in the distortion of the covariance matrix estimation and a low signal-to-noise ratio (SNR) can lead to subspace leakage problems, which affects the parameter estimation accuracy. In this paper, a joint DOA–range estimation algorithm is proposed to solve the above issues. Firstly, the improved unitary root-MUSIC algorithm is applied to reduce the influence of non-ideal terms in building the covariance matrix. Subsequently, the least squares method is employed to process the data and obtain paired range estimation. However, in a small number of snapshots and low SNR scenarios, even if the impact of non-ideal terms is reduced, there will still be cases where the estimators sometimes deviate from the true target. The estimators that deviate greatly from targets are regarded as outliers. Therefore, threshold detection is applied to determine whether outliers exist. After that, a pseudo-noise resampling (PR) technology is proposed to form a new data observation matrix, which further alleviates the error of the estimators. The proposed method overcomes performance degradation in a small number of snapshots or low SNRs simultaneously. Theoretical analyses and simulation results demonstrate the effectiveness and superiority

FRICTION PROPERTIES AND DISTRIBUTION RULE OF LUBRICANT FILM OF FULL CERAMIC BALL BEARING UNDER DIFFERENT SERVICE CONDITION

Full ceramic ball bearings are widely used in extreme and complex conditions, such as ultra-high/low temperature, ultra-high speed, corrosion and insulation, because of their material specificity. In order to reveal the friction and lubrication properties, improve the service performance life of all ceramic ball bearings, a mathematical model of the oil lubrication for full ceramic ball bearings has been established in this paper. The distribution rule of the lubricant film in the contact area under different speeds and loads were analysed. The main factors influencing the peak mutation of the lubricant film pressure are clearly defined. The results are compared and analysed by using a ball-disc rolling lubricant film test machine. The study found that the thickness of the lubricant film of a full ceramic ball bearing is positively correlated with the bearing speed and negatively correlated with the bearing loads. The bearing speed has a relatively large effect on the change in the lubricant film thickness. The pressure of the lubricant film in the contact area is positively correlated with the bearing speed, but it is not affected by the bearing load. Unlike metal ball bearings, the thickness and pressure of the lubricant film have a greater relative rate of change in different positions in the contact area of full ceramic ball bearings. With an increase in the bearing speed, the necking-down effect has a greater influence on the peak mutation of the oil pressure. Only one pressure peak occurs in the oil film in the contact area. The results of this paper play an important role in revealing the friction and lubrication properties of full ceramic ball bearings and improving their service performance and life under oil lubrication conditions

Establishment and application of a survival rate graph model based on biomarkers and imaging indexes after primary hepatocellular carcinoma resection

Abstract Background Primary liver cancer (PLC) is a highly malignant disease. This study developed an effective and convenient tool to evaluate survival times of patients after hepatectomy, which can provide a reference point for clinical decisions. Methods Clinical and laboratory data of 243 patients with PLC after hepatectomy were collected. Univariate cox regression analysis, Lasso regression analysis and multivariate cox regression analysis were used to determine the best prediction index. Multivariate cox regression analysis was used to construct a survival prediction model. A receiver operating characteristic (ROC) curve, calibration curve and decision curve analysis (DCA) were used to verify the model. The patients in this model were divided into was divided into high‐risk and low‐risk groups according to the optimal cut‐off value of the ROC curve for different prognostic years. Kaplan–Meier survival analysis and log‐rank test were used to analyse the survival differences between the two groups. Results Tumour size, portal vein thrombosis, distant metastasis, alpha‐fetoprotein and protein induced by vitamin K absence or antagonist‐II levels were independent risk factors for overall survival (OS) after PLC surgery. The area under the concentration‐time curve for 2‐, 3‐ and 4‐year survival of patients was 0.710, 0.825 and 0.919, respectively, with a good calibration of the Hosmer–Lemeshow test (p > 0.05) and net benefit. The mortality rates in patients with 2, 3 and 4 years of survival were 70.59%, 67.83% and 66.67% for the high‐risk group and 21.84%, 22.50% and 22.67% for the low‐risk group, respectively. The mortality rate of the high‐risk group was significantly higher than that of the low‐risk group (p < 0.05). Conclusion The OS model of prognosis after PLC surgery constructed in this study can be used to predict the 2‐, 3‐ and 4‐year survival prognoses of patients, and patients with different prognosis years can be re‐stratified so that they achieve more accurate and personalised assessment, thereby providing a reference point for clinical decision‐making

Thermal Dynamic Exploration of Full-Ceramic Ball Bearings under the Self-Lubrication Condition

A silicon nitride ceramic bearing has good self-lubricating characteristics. It still has a good operational status under the condition of a lack of oil. However, the temperature distribution of a silicon nitride ceramic bearing during its operation is unclear. To clarify the thermal distribution of a full-ceramic ball silicon nitride ceramic bearing under self-lubricating conditions, the changing trend of the rolling friction temperature between the rolling elements and channels with different accuracies is analyzed using the friction testing machine. The bearing heat generation model based on the silicon nitride material coefficient is established, and the life test machine measures the temperature of the bearing to verify the accuracy of the simulation model. The results show that the friction temperature between the ceramic ball and channel decreases with the increase in ceramic ball level. With an increase in the ceramic ball pressure and temperature, the friction temperature rises. Under self-lubrication, when the bearing bears a heavy load, the influence of the rotating speed on temperature rise tends to decrease. Under the condition of high speed, with the increase in load, the change range of temperature rise shows an upward trend. The important relationship between the bearing’s heat and bearing’s load and speed is revealed. It provides some theoretical guidance for the thermal analysis of a silicon nitride ceramic ball bearing under the self-lubricating condition to improve the service life and reliability of full-ceramic ball bearings