DC32, a Dihydroartemisinin Derivative, Ameliorates Collagen-Induced Arthritis Through an Nrf2-p62-Keap1 Feedback Loop

Artemisinins have been reported to have diverse functions, such as antimalaria, anticancer, anti-inflammation, and immunoregulation activities. DC32 [(9α,12α-dihydroartemisinyl) bis(2′-chlorocinnmate)], a dihydroartemisinin derivative possessing potent immunosuppressive properties, was synthesized in our previous study. Collagen-induced arthritis (CIA) in DBA/1 mice and inflammatory model in NIH-3T3 cells were established to evaluate the effect of DC32 on RA and discover the underlying mechanisms. The results showed that DC32 could markedly alleviate footpad inflammation, reduce cartilage degradation, activate the Nrf2/HO-1 signaling pathway, and increase the transcription of p62 in DBA/1 mice with CIA. Further mechanistic exploration with NIH-3T3 cells indicated that DC32 could increase the transcription, expression, and nuclear translocation of Nrf2. In addition, DC32 promoted degradation of Keap1 protein and upregulated HO-1 and p62 expression. Furthermore, the effect of DC32 on Keap1 degradation could be prevented by p62 knockdown using siRNA. Administration of DC32 could inhibit the activation of Akt/mTOR and ERK, and pretreatment of NIH-3T3 cells with the autophagy inhibitor 3-methyladenine (3-MA) attenuated the degradation of Keap1 induced by DC32. These results suggest that DC32 inhibits the degradation of Nrf2 by promoting p62-mediated selective autophagy and that p62 upregulation contributed to a positive feedback loop for persistent activation of Nrf2. In summary, our present study demonstrated that DC32 significantly suppressed rheumatoid arthritis (RA) via the Nrf2-p62-Keap1 feedback loop by increasing the mRNA and protein levels of Nrf2 and inducing p62 expression. These findings provide new mechanisms for artemisinins in RA treatment and a potential strategy for discovering antirheumatic drugs

Effect of Schizochytrium limacinum supplementation to a low fish-meal diet on growth performance, lipid metabolism, apoptosis, autophagy and intestinal histology of Litopenaeus vannamei

In this experiment, we aimed to evaluate the relationship between the addition of Schizochytrium limacinum to low fish meal diets on growth performance, apoptosis, autophagy, lipid metabolism, and intestinal health of Lipenaeus vanamei. The diet containing 25% fish meal was used as a positive control (FM) and the other three diets contained 15% fish meal and were supplemented with 0, 0.3, and 0.6% S. Limacinum (LF, LFLD, LFHD). The shrimp (0.22 ± 0.00 g) were divided into four replicates of 40 shrimp per tank and fed four times daily to apparent satiation for 8 weeks. Results showed that the final weight (FBW) and weight gain rate (WGR) of shrimp fed FM and LFHD diets were significantly increased compared to those fed the LFLD diet (P<0.05), and there was no significant difference in survival rate (SR) and feed conversion rate (FCR) among the groups (P>0.05). Supplementation of S. Limacinum in low fish meal diets had no effects on shrimp body composition (P<0.05). There were significant differences (P<0.05) in low-density lipoprotein (LDL-C) glucose (GLU), triglycerides (TG), and total cholesterol (TC) in the hemolymph of shrimp fed the LF diet compared to those fed the LFLD and LFHD diets. HE staining and transmission electron microscopy (TEM) results showed that the microvilli height, mucosal folds height, mucosal folds width and muscle layer thickness in the intestine of shrimp fed the LF diet were significantly reduced compared to those fed the other three diets (P<0.05). Swelling of the endoplasmic reticulum and irregular mitochondria in the gut of shrimp fed the LF diet was also observed by TEM, and the endoplasmic reticulum and mitochondria of shrimp fed the LFHD diet returned to a healthy state. Hepatopancreas genes expression results were showed that the gene expression of 5′ -AMP-activated protein kinase (ampk), stearoyl-CoA desaturase (scd1), acetyl-CoA carboxylase 1 (acc1), and malonyl-CoA decarboxylase (mcd) of shrimp fed the LF diet was significantly increased compared to those fed the FM diet (P<0.05). The gene expression of sterol regulatory element-binding protein (srbep) and carnitine palmitoyl transferase 1 (cpt-1) of shrimp fed the LFLD diet was significantly increased compared to those fed the LF diet (P<0.05). The gene expression of acc1, mcd and scd1 of shrimp fed the LFHD diet was significantly reduced compared to those fed the LF diet (P<0.05). Results of genes expression associated with apoptosis in the hepatopancreas showed that the gene expression of B lymphocytoma-2 (bcl-2), BCL2 associated X apoptosis regulator (bax) and cysteinyl aspartate specific proteinase 8 (caspase 8) of shrimp fed the LF diet was significantly reduced compared to those fed the FM diet (P<0.05). The gene expression of bcl-2 of shrimp fed the LFHD diet was significantly reduced compared to those fed the LF diet (P<0.05). Genes related to autophagy in the hepatopancreas showed that the expression of autophagy-related protein 12 (atg 12), autophagy-related protein 13 (atg 13) and beclin1 of shrimp fed LF the diet was significantly reduced compared to those fed the FM diet (P<0.05). The gene expression of atg 12 and atg 13 of shrimp fed the LFHD diet was significantly increased compared to those fed the LF diet (P<0.05). In summary, reducing fish meal is detrimental to the growth performance and intestinal health of shrimp, and 0.6% S. Limacinum supplementation can improve the growth performance, promotes hepatopancreas lipid metabolism, reduces apoptosis, promotes autophagy and improve intestinal health of Litopenaeus vannamei

Neural oscillations during acupuncture imagery partially parallel that of real needling

IntroductionTasks involving mental practice, relying on the cognitive rehearsal of physical motors or other activities, have been reported to have similar patterns of brain activity to overt execution. In this study, we introduced a novel imagination task called, acupuncture imagery and aimed to investigate the neural oscillations during acupuncture imagery.MethodsHealthy volunteers were guided to watch a video of real needling in the left and right KI3 (Taixi point). The subjects were then asked to perform tasks to keep their thoughts in three 1-min states alternately: resting state, needling imagery left KI3, and needling imagery right KI3. Another group experienced real needling in the right KI3. A 31-channel-electroencephalography was synchronously recorded for each subject. Microstate analyses were performed to depict the brain dynamics during these tasks.ResultsCompared to the resting state, both acupuncture needling imagination and real needling in KI3 could introduce significant changes in neural dynamic oscillations. Moreover, the parameters involving microstate A of needling imagery in the right KI3 showed similar changes as real needling in the right KI3.DiscussionThese results confirm that needling imagination and real needling have similar brain activation patterns. Needling imagery may change brain network activity and play a role in neural regulation. Further studies are needed to explore the effects of acupuncture imagery and the potential application of acupuncture imagery in disease recovery

Numerical Studies On The Influences Of The South-To-North Water Transfer Project On Groundwater Level Changes In The Beijing Plain, China

Groundwater is an important component of the water supply, and overexploitation has triggered many problems in the Beijing Plain. The South-to-North Water Transfer Project has been proposed as a promising solution to alleviate these problems. Evaluation of different scenarios of groundwater management after the implementation of the South-to-North Water Transfer Project is necessarily required. In this study, a numerical model of groundwater flow was established using FEFLOW software and was well calibrated by parameter optimization and groundwater withdrawal inversion in the Beijing Plain. Sixteen scenarios that considered groundwater exploitation, artificial recharge, and precipitation were designed to simulate the groundwater dynamics after 11 years of the project. The results showed that the groundwater level in the study area would recover to various degrees due to the reductions of groundwater withdrawal and the increments of infiltration; additionally, it was concluded that groundwater was significantly affected by precipitation. Generally, in the designed scenarios, the groundwater-level increment in the upper streams of the model area was higher than that in the lower streams. The groundwater level would obviously increase from artificial recharge in the immediate and adjacent areas. In addition, modes of reducing exploitation had no significant influence on the change in groundwater level during the 11-year study period. The developed model offers a reliable and effective way to improve groundwater management

A bilayer color digital image correlation method for the measurement of the topography of a liquid interface

One of the most essential characteristics of the liquid interface is the topography dominated by hydrodynamics or capillary effects. Although there have developed 3D imaging techniques for the measurement of such topography, their setups, operations and reconstructions are relatively complex and suffer from low efficiency. Here we report a bilayer color digital image correlation (BC-DIC) method for the measurement of the topography of a liquid interface. The basic principle of the new method is the refraction of beneath bilayer color speckle patterns at the liquid interface, which makes it possible to perform 3D reconstruction through 2D measurement of the virtual displacement field of the speckle patterns. The equations for BC-DIC in different situations are deduced and discussed in detailed. Validation experiments are carried out to reconstruct the topography of triangular prism, planoconvex, complex transparent surface and sloshing water surface. The results show that BC-DIC is feasible and accurate for measuring the topography of transparent objects, including liquid interface. This new method paves the way for investigating surface and interface phenomena, such as capillarity and wetting issues, hydrodynamics on liquid interface, etc

Surrogate Models For Sub-Region Groundwater Management In The Beijing Plain, China

Overexploitation of groundwater resources has caused groundwater-related problems all over the world. Effective groundwater governance is a favorable guarantee for its protection and sustainable utilization. Accurate prediction of groundwater level (GWL) or depth to groundwater (GWD) plays an important role in groundwater resource management. Due to the limitations and complexity of numerical models, this study aims to develop surrogate models that can dually control the GWL (or GWD) and groundwater quantity (GWQ) in each district of the Beijing Plain, China, using the methods of multiple linear regression (MLR) and back propagation artificial neural network (BP-ANN). This study used 180 monthly GWD data records, including the first 168 data records for model development (training) and the remaining 12 data records for model verification. The results indicate that the Nash-Sutcliffe efficiency coefficient (NSE) and correlation coefficient (R) for both the MLR and BP-ANN models are high in most districts and that the MLR models are more appropriate in this study. Fifteen scenarios under different conditions of groundwater use and precipitation are designed to demonstrate the applicability of the developed model in groundwater management. The surrogate models are effective tools that can be used by decision-makers for groundwater management