Rhizoma Alismatis Decoction improved mitochondrial dysfunction to alleviate SASP by enhancing autophagy flux and apoptosis in hyperlipidemia acute pancreatitis.

BACKGROUND: Acute pancreatitis (AP) is an inflammatory disorder of the exocrine pancreas, especially hyperlipidemia acute pancreatitis (HLAP) is the third leading cause of acute pancreatitis which is more severe with a greater incidence of persistent multiorgan failure. HLAP inflicts injury upon the organelles within the acinar cell, particularly mitochondria, the endolysosomal-autophagy system, and is accompanied by senescence-associated secretory phenotype (SASP). RAD, only two consists of Rhizoma Alismatis and Atractylodes macrocephala Rhizoma, which is best known for its ability to anti-inflammatory and lipid-lowering. Nevertheless, the mechanism by which RAD alleviates HLAP remains obscure, necessitating further investigation. PURPOSE: The study aimed to assess the effects of the RAD on HLAP and to elucidate the underlying mechanism in vivo and in vitro, offering a potential medicine for clinical treatment for HLAP. STUDY DESIGN AND METHODS: C57BL/6 mice with hyperlipidemia acute pancreatitis were induced by HFD and CER, then administrated with RAD. AR42J were stimulated by cerulein or conditioned medium and then cultured with RAD. Serums were analyzed to evaluate potential pancreas and liver damage. Furthermore, tissue samples were obtained for histological, and protein investigations by H&E, Oil red staining, and Western blot. In addition, western blot and immunofluorescent staining were utilized to estimate the effect of RAD on mitochondrial function, autophagy flux, and SASP. RESULTS: In vivo, RAD considerably alleviated systemic inflammation while attenuating TC, TG, AMY, LPS, inflammatory cytokines, histopathology changes, oxidative damage, mitochondrial fission, and autophagy markers in HLAP mice. Impaired autophagy flux and mitochondrial dysfunction resulted in a significant enhancement of NLRP3 and IL-1ß in the pancreas. RAD could reverse these changes. In vitro, RAD significantly restored mitochondrial membrane potential and oxidative phosphorylation levels. RAD decreased Beclin-1 and LC3-II expression and increased LAMP-1 and Parkin-Pink expression, which showed that RAD significantly ameliorated HLAP-induced damage to the mitochondria function by suppressing mitochondrial oxidative damage and enhancing autophagy flux and mitophagy to remove the damaged mitochondria. In addition, we found that RAD could up-regulate the expression of BAX, and Bad and down-regulate the expression of p16, and p21, indicating that RAD could promote damaged cell apoptosis and alleviate SASP. CONCLUSIONS: This study revealed that RAD ameliorates mitochondrial function to alleviate SASP through enhancing autophagy flux, mitophagy, and apoptosis which provided a molecular basis for the advancement and development of protection strategies against HLAP.

Fine Classification of UAV Urban Nighttime Light Images Based on Object-Oriented Approach.

Fine classification of urban nighttime lighting is a key prerequisite step for small-scale nighttime urban research. In order to fill the gap of high-resolution urban nighttime light image classification and recognition research, this paper is based on a small rotary-wing UAV platform, taking the nighttime static monocular tilted light images of communities near Meixi Lake in Changsha City as research data. Using an object-oriented classification method to fully extract the spectral, textural and geometric features of urban nighttime lights, we build four types of classification models based on random forest (RF), support vector machine (SVM), K-nearest neighbor (KNN) and decision tree (DT), respectively, to finely extract five types of nighttime lights: window light, neon light, road reflective light, building reflective light and background. The main conclusions are as follows: (i) The equal division of the image into three regions according to the visual direction can alleviate the variable scale problem of monocular tilted images, and the multiresolution segmentation results combined with Canny edge detection are more suitable for urban nighttime lighting images; (ii) RF has the highest classification accuracy among the four classification algorithms, with an overall classification accuracy of 95.36% and a kappa coefficient of 0.9381 in the far view region, followed by SVM, KNN and DT as the worst; (iii) Among the fine classification results of urban light types, window light and background have the highest classification accuracy, with both UA and PA above 93% in the RF classification model, while road reflective light has the lowest accuracy; (iv) Among the selected classification features, the spectral features have the highest contribution rates, which are above 59% in all three regions, followed by the textural features and the geometric features with the smallest contribution rates. This paper demonstrates the feasibility of nighttime UAV static monocular tilt image data for fine classification of urban light types based on an object-oriented classification approach, provides data and technical support for small-scale urban nighttime research such as community building identification and nighttime human activity perception.

Corydalis saxicola Bunting Total Alkaloids ameliorate diet-induced non-alcoholic steatohepatitis by regulating hepatic PI3K/Akt and TLR4/NF-κB pathways in mice.

Corydalis saxicola Bunting (Yanhuanglian), distributed in Southwest China, is mainly used for treatment of hepatitis, oral mucosal erosion, conjunctivitis, dysentery, acute abdominal pain and hemorrhoids in the folk. Corydalis saxicola Bunting Total Alkaloids (CSBTA) are the active ingredients extracted from the root of C. saxicola bunting. Non-alcoholic steatohepatitis (NASH) is the hinge between steatosis and cirrhosis in the spectrum of Non-alcoholic fatty liver disease (NAFLD), which has become one of the most common chronic liver diseases in the world. CSBTA can reduce tumors and brain diseases through anti-inflammatory and antioxidant pathways. Our study was designed to clarify the effects of CSBTA on the HFHC (High fat and high carbohydrate drinking) diet induced mice. In our research, A HFHC diet induced NASH mice model was applied to investigate the effects of CSBTA in vivo and obeticholic acid (OA) was set as positive control. Moreover, the underlying mechanisms were explored by palmitic acid (PA) and lipopolysaccharide (LPS) stimulated HepG2 cells in vitro. The in vivo study illustrated that CSBTA could alleviate mice away from the onset of NASH, and reduce intrahepatocellular lipid accumulation and hepatocyte inflammation under high fat condition. Further in vitro analysis confirmed that CSBTA attenuated inflammation and hepatic lipid accumulation by improving hepatic PI3K/Akt and suppressing hepatic TLR4/NF-κB pathways. In summary, this study demonstrated that CSBTA might be a promising compound for the treatment of NAFLD.

Corydalis Saxicola Bunting Total Alkaloids Attenuate Walker 256-Induced Bone Pain and Osteoclastogenesis by Suppressing RANKL-Induced NF-κB and c-Fos/NFATc1 Pathways in Rats.

Metastatic bone pain is characterized by insufferable bone pain and abnormal bone structure. A major goal of bone cancer treatment is to ameliorate osteolytic lesion induced by tumor cells. Corydalis saxicola Bunting total alkaloids (CSBTA), the alkaloid compounds extracted from the root of C. saxicola Bunting, have been shown to possess anticancer and analgesic properties. In this study, we aimed to verify whether CSBTA could relieve cancer induced bone pain and inhibit osteoclastogenesis. The in vivo results showed that CSBTA ameliorated Walker 256 induced bone pain and osteoporosis in rats. Histopathological changes also supported that CSBTA inhibited Walker 256 cell-mediated osteolysis. Further in vitro analysis confirmed that CSBTA reduced the expression of RANKL and downregulate the level of RANKL/OPG ratio in breast cancer cells. Moreover, CSBTA could inhibit osteoclastogenesis by suppressing RANKL-induced NF-κB and c-Fos/NFATc1 pathways. Collectively, this study demonstrated that CSBTA could attenuate cancer induced bone pain via a novel mechanism. Therefore, CSBTA might be a promising candidate drug for metastatic bone pain patients.

Influence of High-Temperature Oxidation and Test Conditions on the Dynamic Mechanical Properties of 2.5D SiCf/SiCm Composites.

The influence of microstructure evolution on the dynamic mechanical properties, including storage modulus and internal friction, of the 2.5D SiCf/SiCm composites after high-temperature treatment (800 °C and 1400 °C) in the air was investigated by three-point bending vibration test. The effects of test frequency and amplitude on storage modulus and internal friction were also evaluated. The results show that as-prepared samples have maximum storage modulus and internal friction. However, the composites treated at 800 °C in the air have the minimum storage modulus due to a large number of defects produced within the composite structure, and the composites treated at 1400 °C have the minimum internal friction due to the formation of α-cristobalite in the interface between the matrix and fibers, resulting in stronger interface bonding. With regard to test conditions, the storage modulus is sensitive to amplitude but not frequency; however, the internal friction is sensitive to both frequency because of anelasticity and amplitude due to the static hysteresis.