Role of Complement 3 in TNF-α-Induced Mesenchymal Transition of Renal Tubular Epithelial Cells In Vitro

Injured renal tubular epithelial cells (RTECs) have been recently thought to directly contribute to the accumulation of myofibroblasts in renal tubulointerstitial fibrosis through a process of epithelial to mesenchymal transition (EMT). However, the factors inducing RTECs to undergo EMT and the underlying mechanisms need to be further elucidated. This study aimed to determine the EMT-inducing activity of proinflammatory cytokine TNF-α and the role for complement 3 (C3) in this activity in an in vitro model of human RTECs (HK-2 cells). Wild type HK-2 cells were treated with TNF-α, IFN-γ or C3a; C3 siRNA- or control siRNA-carrying HK-2 cells were treated with TNF-α. Changes in the cell morphology and phenotype were assessed by microscopy, RT-PCR, western blotting, and immunostaining. TNF-α effectively induced HK-2 cells to express C3 and to transform into morphologically myofibroblast-like cells that lost E-cadherin (a classical epithelial cell marker) expression but acquired alpha-smooth muscle actin (α-SMA, a classical myofibroblast differentiation marker) expression. C3 siRNA robustly attenuated all the morphologic and phenotypic changes induced by TNF-α but the control siRNA showed no effect. Our preliminary observations suggest that TNF-α may induce EMT in RTECs through inducing C3 expression.     

Quantitative Ecological Risk Analysis by Evaluating China's Eco-Efficiency and Its Determinants

Industrial production can produce large amounts of harmful by-products, causing serious pollution and ecological risk. In addition, if government regulations are subjected into the industries, huge cost risk will be faced. This article adopts a two-stage slack-based undesirable-output data envelope analysis (DEA) model to measure the eco-efficiency of China. In the first stage, we analyze the eco-efficiency of each province of China, and in the second stage, we employed a truncated bootstrap method to understand the determinants of eco-efficiency. The results indicate that whereas the eco-efficiency of the eastern region was the highest, that of the western region was the lowest. The western region's economy lagged behind that of other regions, and its environment suffered from heavy pollution. It was found that the level of industrialization did not contribute to eco-efficiency. However, promotion of the service industry, investment for the environment, and regional innovation have positive effects on eco-efficiency.     

Oxaliplatin induces immunogenic cells death and enhances therapeutic efficacy of checkpoint inhibitor in a model of murine lung carcinoma

Abstract

Background: Platinum compounds are commonly used for lung cancer treatment. However, the severe side effects and relatively poor prognosis limit their therapeutic effect. Therefore, developing novel platinum derivative and treatment strategy are critical for current lung cancer therapy.

Methods: Flow cytometry, HMGB1 and ATP release, and immunoblotting were performed to evaluate the Oxaliplatin-induced immunogenic cell death (ICD) in two lung carcinoma cells. Vaccination approach and subcutaneous tumor models were created to analyze the tumor regression effect of Oxaliplatin. PD-L1 mRNA and protein levels were detected in LLC (Lewis lung carcinoma). Enhanced therapeutic efficacy of LLC was assessed by co-administration Oxaliplatin and aPD-L1 in murine lung tumor model.

Results: Oxaliplatin induced robust ICD in LLC cells, activated dendritic cells (DCs, CD80⁺CD86⁺) and enhanced cytotoxic T cells (CD8⁺) in LLC tumor tissues, which resulted in tumor regression. Co-administration of Oxaliplatin and checkpoint inhibitor, aPD-L1, could enhance the therapeutic efficacy of LLC in murine lung carcinoma.

Conclusion: This study reveals Oxaliplatin can induce robust ICD in tumor tissues and suppress tumor growth by activating DCs and enhancing T-cell infiltration. Notably, the Oxaliplatin-induced ICD provides an immunogenic microenvironment, which enhances the checkpoint inhibitor therapeutic efficacy of LLC.     

PGC-1 Coactivators Regulate MITF and the Tanning Response

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Highlights? PGC-1 induces pigment formation in melanocytes ? PGC-1s activate expression of MITF ? α-MSH induces PGC-1s, which are required for induction of melanogenic genes ? eQTLs in human PGC-1β are associated with tanning ability and melanoma protection     

Granulation of activated sludge in a continuous flow airlift reactor by strong drag force

Most aerobic granule cultivation has been based on the sequencing batch reactor (SBR) and then the factors that affect aerobic granulations were developed in the SBR. However, little work has been done to cultivate aerobic granules in a continuous-flow bioreactor with simple structure that is realistic for engineering. This work is the first to cultivate aerobic granules in a continuous flow airlift fluidized bed reactor (CAFB) possesses a very simple structure and without settling time and starvation time controlling. The configuration of CAFB was the simplest continuous-flow aerobic granular bioreactor reported by now. The majority of granules could be formatted in the CAFB after 12 days cultivation. The effluent COD concentration maintained at 50 ± 10 mg/L for the variable COD loading rate of 3.5 g COD/L/d and 4.8 g COD/L/d, which confirmed that the CAFB performed good anti-shock abilities. CAFB performed good nitrification ability, however, little denitrification was found under the operating conditions of this study. The shear stress acting on the solid phase were hundreds of times stronger in the CAFB than in the SBR at the same aeration strength. It seems CAFB is very efficient for granulation due to the strong shear-force exertion, which is promising for continuous-flow aerobic granular bioreactor. Protein, positive to the hydrophobicity, was predominant in extracellular polymeric substances in the granules, and favored the granules formation in the CAFB combined with the polysaccharides. However, filamentous bulking always happened in 35 days operation of the CAFB, thus further study on the stability of this bioreactor is urgently necessary.     

Synthesis and interaction of bovine serum albumin with p‐hydroxybenzoic acid derivatives

Three novel p‐hydroxybenzoic acid derivatives (HSOP, HSOX, HSCP) were synthesized from p‐hydroxybenzoic acid and sulfonamides (sulfamonomethoxine sodium, sulfamethoxazole and sulfachloropyridazine sodium) and characterized by elemental analysis, HNMR and MS. Interactions between derivatives and bovine serum albumin (BSA) were studied by fluorescence quenching spectra, UV–vis absorption spectra and time‐resolved fluorescence spectra. Based on fluorescence quenching calculation and Förster's non‐radioactive energy transfer theory, the values of the binding constants, basic thermodynamic parameters and binding distances were obtained. Experimental results indicated that the three derivatives had a strong ability to quench fluorescence from BSA and that the binding reactions of the derivatives with BSA were a static quenching process. Thermodynamic parameters showed that binding reactions were spontaneous and exothermic and hydrogen bond and van der Waals force were predominant intermolecular forces between the derivatives and BSA. Synchronous fluorescence spectra suggested that HSOX and HSCP had little effect on the microenvironment and conformation of BSA in the binding reactions but the microenvironments around tyrosine residues were disturbed and polarity around tyrosine residues increased in the presence of HSOP. Copyright © 2012 John Wiley & Sons, Ltd.     

The New Perspectives on Genetic Studies of Type 2 Diabetes and Thyroid Diseases

Recently, genome-wide association studies (GWAS) have led to the discovery of hundreds of susceptibility loci that are associated with complex metabolic diseases, such as type 2 diabetes and hyperthyroidism. The majority of the susceptibility loci are common across different races or populations; while some of them show ethnicity-specific distribution. Though the abundant novel susceptibility loci identified by GWAS have provided insight into biology through the discovery of new genes or pathways that were previously not known, most of them are in introns and the associated variants cumulatively explain only a small fraction of total heritability. Here we reviewed the genetic studies on the metabolic disorders, mainly type 2 diabetes and hyperthyroidism, including candidate genes-based findings and more recently the GWAS discovery; we also included the clinical relevance of these novel loci and the gene-environmental interactions. Finally, we discussed the future direction about the genetic study on the exploring of the pathogenesis of the metabolic diseases.