M2-like macrophages in the fibrotic liver protect mice against lethal insults through conferring apoptosis resistance to hepatocytes.

Acute injury in the setting of liver fibrosis is an interesting and still unsettled issue. Most recently, several prominent studies have indicated the favourable effects of liver fibrosis against acute insults. Nevertheless, the underlying mechanisms governing this hepatoprotection remain obscure. In the present study, we hypothesized that macrophages and their M1/M2 activation critically involve in the hepatoprotection conferred by liver fibrosis. Our findings demonstrated that liver fibrosis manifested a beneficial role for host survival and apoptosis resistance. Hepatoprotection in the fibrotic liver was tightly related to innate immune tolerance. Macrophages undertook crucial but divergent roles in homeostasis and fibrosis: depleting macrophages in control mice protected from acute insult; conversely, depleting macrophages in fibrotic liver weakened the hepatoprotection and gave rise to exacerbated liver injury upon insult. The contradictory effects of macrophages can be ascribed, to a great extent, to the heterogeneity in macrophage activation. Macrophages in fibrotic mice exhibited M2-preponderant activation, which was not the case in acutely injured liver. Adoptive transfer of M2-like macrophages conferred control mice conspicuous protection against insult. In vitro, M2-polarized macrophages protected hepatocytes against apoptosis. Together, M2-like macrophages in fibrotic liver exert the protective effects against lethal insults through conferring apoptosis resistance to hepatocytes

Knockdown of a novel lincRNA AATBC suppresses proliferation and induces apoptosis in bladder cancer

Long intergenic noncoding RNAs (lincRNAs) play important roles in regulating various biological processes in cancer, including proliferation and apoptosis. However, the roles of lincRNAs in bladder cancer remain elusive. In this study, we identified a novel lincRNA, which we termed AATBC. We found that AATBC was overexpressed in bladder cancer patient tissues and positively correlated with tumor grade and pT stage. We also found that inhibition of AATBC resulted in cell proliferation arrest through G1 cell cycle mediated by cyclin D1, CDK4, p18 and phosphorylated Rb. In addition, inhibition of AATBC induced cell apoptosis through the intrinsic apoptosis signaling pathway, as evidenced by the activation of caspase-9 and caspase-3. The investigation for the signaling pathway revealed that the apoptosis following AATBC knockdown was mediated by activation of phosphorylated JNK and suppression of NRF2. Furthermore, JNK inhibitor SP600125 could attenuate the apoptotic effect achieved by AATBC knockdown, confirming the involvement of JNK signaling in the induced apoptosis. Moreover, mouse xenograft model revealed that knockdown of AATBC led to suppress tumorigenesis in vivo. Taken together, our study indicated that AATBC might play a critical role in pro-proliferation and anti-apoptosis in bladder cancer by regulating cell cycle, intrinsic apoptosis signaling, JNK signaling and NRF2. AATBC could be a potential therapeutic target and molecular biomarker for bladder cancer

Long Non-Coding RNA LUCAT1 Promotes Proliferation and Invasion in Clear Cell Renal Cell Carcinoma Through AKT/GSK-3β Signaling Pathway

Background/Aims: Long non-coding RNAs (lncRNAs) have emerged as new regulators and biomarkers in several cancers. However, few lncRNAs have been well characterized in clear cell renal cell carcinoma (ccRCC). Methods: We investigated the lncRNA expression profile by microarray analysis in 5 corresponding ccRCC tissues and adjacent normal tissues. Lung cancer–associated transcript 1 (LUCAT1) expression was examined in 90 paired ccRCC tissues by real-time PCR and validated by The Cancer Genome Atlas (TCGA) database. Kaplan-Meier analysis was used to examine the prognostic value of LUCAT1 and CXCL2 in ccRCC patients. Loss and gain of function were performed to explore the effect of LUCAT1 on proliferation and invasion in ccRCC cells. Western blotting was performed to evaluate the underlying mechanisms of LUCAT1 in ccRCC progression. Chemokine stimulation assay was performed to investigate possible mechanisms controlling LUCAT1 expression in ccRCC cells. Enzyme-linked immunosorbent assays were performed to determine serum CXCL2 in ccRCC patients and healthy volunteers. Receiver operating characteristic curve analysis was performed to examine the clinical diagnostic value of serum CXCL2 in ccRCC. Results: We found that LUCAT1 was significantly upregulated in both clinical ccRCC tissues (n = 90) and TCGA ccRCC tissues (n = 448) compared with normal tissues. Statistical analysis revealed that the LUCAT1 expression level positively correlated with tumor T stage (P < 0.01), M stage (P < 0.01), and TNM stage (P < 0.01). Overall survival and disease-free survival time were significantly shorter in the high-LUCAT1-expression group than in the low-LUCAT1-expression group (log-rank P < 0.01). LUCAT1 knockdown inhibited ccRCC cell proliferation and colony formation, induced cell cycle arrest at G1 phase, and inhibited cell migration and invasion. Overexpression of LUCAT1 promoted proliferation, migration, and invasion of ccRCC cells. Mechanistic investigations showed that LUCAT1 induced cell cycle G1 arrest by regulating the expression of cyclin D1, cyclin-dependent kinase 4, and phosphorylated retinoblastoma transcriptional corepressor 1. Moreover, LUCAT1 promoted proliferation and invasion in ccRCC cells partly through inducing the phosphorylation of AKT and suppressing the phosphorylation of GSK-3β. We also revealed that chemokine CXCL2, upregulated in ccRCC, induced LUCAT1 expression and might be a diagnostic and prognostic biomarker in ccRCC. Conclusions: LUCAT1 was upregulated in ccRCC tissues and renal cancer cell lines, and significantly correlated with malignant stage and poor prognosis in ccRCC. LUCAT1 promoted proliferation and invasion in ccRCC cells through the AKT/GSK-3β signaling pathway. We also revealed that LUCAT1 overexpression was induced by chemokine CXCL2. These findings indicate that the CXCL2/LUCAT1/AKT/GSK-3β axis is a potential therapeutic target and molecular biomarker for ccRCC

Smoothing Approximation to the Square-Order Exact Penalty Functions for Constrained Optimization

A method is proposed to smooth the square-order exact penalty function for inequality constrained optimization. It is shown that, under some conditions, an approximately optimal solution of the original problem can be obtained by searching an approximately optimal solution of the smoothed penalty problem. An algorithm based on the smoothed penalty functions is given. The algorithm is shown to be convergent under mild conditions. Two numerical examples show that the algorithm seems efficient

Estimation of Ground Thermal Properties of Shallow Coaxial Borehole Heat Exchanger Using an Improved Parameter Estimation Method

Ground thermal properties are prerequisites for designing the size of borehole heat exchanger. In this study, a 3D heat transfer model is developed to simulate the thermal response test (TRT) of shallow coaxial borehole heat exchanger (SCBHE), and effects of ground thermal properties on the slope of the mean value of inlet and outlet fluid temperatures are studied. The results show that the slope is strongly affected by ground thermal conductivity and is slightly affected by ground thermal capacity, and that ground thermal capacity only has a small effect on the slope. Then, by using the difference between the experimental slope and calculated slope as the objective function to estimate ground thermal conductivity, an improved parameter estimation method (PEM) is proposed to estimate ground thermal properties of SCBHE using the simulated TRT data, and it is compared with the direct method. The results show that ground thermal conductivity and thermal capacity estimated by the improved PEM are accurate for different ground thermal properties, and that ground thermal conductivity estimated by the direct method probably has some errors especially for small ground thermal conductivity or thermal capacity, indicating that the improved PEM has much higher precision than the direct method and can be applied for estimating the ground thermal properties of SCBHE

Estimation of Ground Thermal Properties of Shallow Coaxial Borehole Heat Exchanger Using an Improved Parameter Estimation Method

Ground thermal properties are prerequisites for designing the size of borehole heat exchanger. In this study, a 3D heat transfer model is developed to simulate the thermal response test (TRT) of shallow coaxial borehole heat exchanger (SCBHE), and effects of ground thermal properties on the slope of the mean value of inlet and outlet fluid temperatures are studied. The results show that the slope is strongly affected by ground thermal conductivity and is slightly affected by ground thermal capacity, and that ground thermal capacity only has a small effect on the slope. Then, by using the difference between the experimental slope and calculated slope as the objective function to estimate ground thermal conductivity, an improved parameter estimation method (PEM) is proposed to estimate ground thermal properties of SCBHE using the simulated TRT data, and it is compared with the direct method. The results show that ground thermal conductivity and thermal capacity estimated by the improved PEM are accurate for different ground thermal properties, and that ground thermal conductivity estimated by the direct method probably has some errors especially for small ground thermal conductivity or thermal capacity, indicating that the improved PEM has much higher precision than the direct method and can be applied for estimating the ground thermal properties of SCBHE

Chronic Caloric Restriction and Exercise Improve Metabolic Conditions of Dietary-Induced Obese Mice in Autophagy Correlated Manner without Involving AMPK

Aim. To investigate the role of AMPK activation and autophagy in mediating the beneficial effects of exercise and caloric restriction in obesity. Methods. Dietary-induced obesity mice were made and divided into 5 groups; one additional group of normal mice serves as control. Mice in each group received different combinations of interventions including low fat diet, caloric restriction, and exercise. Then their metabolic conditions were assessed by measuring serum glucose and insulin, serum lipids, and liver function. AMPK phosphorylation and autophagy activity were detected by western blotting. Results. Obese mice models were successfully induced by high fat diet. Caloric restriction consistently improved the metabolic conditions of the obese mice, and the effects are more prominent than the mice that received only exercise. Also, caloric restriction, exercise, and low fat diet showed a synergistic effect in the improvement of metabolic conditions. Western blotting results showed that this improvement was not related with the activation of AMPK in liver, skeletal muscle, or heart but correlates well with the autophagy activity. Conclusion. Caloric restriction has more prominent beneficial effects than exercise in dietary-induced obese mice. These effects are correlated with the autophagy activity and may be independent of AMPK activation

Comparative Study on Exponentially Weighted Moving Average Approaches for the Self-Starting Forecasting

Recently, a number of data analysists have suffered from an insufficiency of historical observations in many real situations. To address the insufficiency of historical observations, self-starting forecasting process can be used. A self-starting forecasting process continuously updates the base models as new observations are newly recorded, and it helps to cope with inaccurate prediction caused by the insufficiency of historical observations. This study compared the properties of several exponentially weighted moving average methods as base models for the self-starting forecasting process. Exponentially weighted moving average methods are the most widely used forecasting techniques because of their superior performance as well as computational efficiency. In this study, we compared the performance of a self-starting forecasting process using different existing exponentially weighted moving average methods under various simulation scenarios and real case datasets. Through this study, we can provide the guideline for determining which exponentially weighted moving average method works best for the self-starting forecasting process

Study on the Influence of Borehole Heat Capacity on Deep Coaxial Borehole Heat Exchanger

Based on a semi-analytical model established previously for heat transfer in coaxial borehole heat exchangers, the influences of the heat capacities of different parts of the borehole (fluid, pipes and grout) on the performance of deep coaxial borehole heat exchanger (DCBHE) are analyzed. The results are as follows: the heat transfer performance of DCBHE will be underestimated if the heat capacities of different parts of the borehole are ignored; the influences of the heat capacities of different parts of the borehole on the performance of DCBHE are more obvious in the early stage, and gradually weaken with the increasing of time; among the heat capacities of different parts of the borehole, the influence of the fluid heat capacity on the performance of DCBHE is the greatest, and the influence of the pipe heat capacities is the least. Under the working condition studied in this paper, the results obtained with considering the heat capacities of different parts of the borehole are compared to ones ignoring heat capacities of selected elements. It was found that ignoring the fluid heat capacity led to a 0.29 °C lower estimated outlet fluid temperature after 60 h. Omitting the heat capacities of pipes and grout gave 0.03 °C and 0.13 °C lower outlet fluid temperatures after 60 h, respectively. The larger the borehole radius, the greater the influence of borehole heat capacity. The geothermal gradient has little effect on the influence of borehole heat capacity on the performance of DCBHE. The results show that the heat capacities of different parts of the borehole have important effects on the performance of DCBHE, especially in the early stage and for a large borehole radius