Effects of cadmium exposure on tissue structure, antioxidant enzyme activity, serum biochemical indices and gene expression in the liver of juvenile largemouth bass (<em>Micropterus salmoides</em>)

This study aimed to understand the effect of various levels of waterborne cadmium exposure and associated integrated response in largemouth bass (Micropterus salmoides). The experimental fish were randomly divided into 4 groups: Group H (high concentration group): 0.25 mg/L of water (100% of the LC~50~); Group M (medium concentration group): 0.01 mg/L of water (50% of the LC~50~); group L (low concentration group): 0.05 mg/L of water (12.5% of the LC~50~) and group C (control). Experimental fish in group C (control group) were cultured in cadmium (Cd)-free tap water. After 28 days of Cd exposure, the gill and liver tissues were collected for histological analysis and antioxidant enzyme activities assay. Serum biochemical indices and the expression levels of HSP70, HSP90, Cyp1a, and MT in the liver were assayed. Results indicated Cd exposure in group H could significantly damage the gill and liver. The SOD activity of gill and liver exhibited an increasing trend with Cd concentrations increasing, and SOD activities increased significantly in group M compared to that of group C. Still, SOD activity significantly decreased in group H. MDA content increased significantly in both the gill and liver, while T-AOC activities were not significantly different in both the gill and liver. By comparison with group C, the activities of ALT and AST in serum were significantly increased in group M and group H; the contents of ALB and TP significantly decreased in group M and group H except for the content slightly increased in the group L; the contents of GLU, TG, and TC did not show significant changes in the group L and the group M, but increased significantly in the group H. The expression levels of HSP70 and HSP90 in the liver exhibited the highest level in group M, whereas the expression levels of MT and Cyp1a were highest in groups H and L, respectively. Our results are intended to provide a reference basis for the safety risk evaluation of Cd and healthy fish farming

Dual blockage of STAT3 and ERK1/2 eliminates radioresistant GBM cells.

Radiotherapy (RT) is the major modality for control of glioblastoma multiforme (GBM), the most aggressive brain tumor in adults with poor prognosis and low patient survival rate. To improve the RT efficacy on GBM, the mechanism causing tumor adaptive radioresistance which leads to the failure of tumor control and lethal progression needs to be further elucidated. Here, we conducted a comparative analysis of RT-treated recurrent tumors versus primary counterparts in GBM patients, RT-treated orthotopic GBM tumors xenografts versus untreated tumors and radioresistant GBM cells versus wild type cells. The results reveal that activation of STAT3, a well-defined redox-sensitive transcriptional factor, is causally linked with GBM adaptive radioresistance. Database analysis also agrees with the worse prognosis in GBM patients due to the STAT3 expression-associated low RT responsiveness. However, although the radioresistant GBM cells can be resensitized by inhibition of STAT3, a fraction of radioresistant cells can still survive the RT combined with STAT3 inhibition or CRISPR/Cas9-mediated STAT3 knockout. A complementally enhanced activation of ERK1/2 by STAT3 inhibition is identified responsible for the survival of the remaining resistant tumor cells. Dual inhibition of ERK1/2 and STAT3 remarkably eliminates resistant GBM cells and inhibits tumor regrowth. These findings demonstrate a previously unknown feature ofSTAT3-mediated ERK1/2 regulation and an effective combination of two targets in resensitizing GBM to RT

A fluorescent double-network-structured hybrid nanogel as embeddable nanoglucometer for intracellular glucometry

National Natural Science Foundation of China [21274118, 91227120]; Program for New Century Excellent Talents in Fujian Province University; Fundamental Research Funds for the Central Universities [2012121016]; National Found for Fostering Talents of Basic Science [J1030415]The development of embeddable and remotely interrogatable nanomaterials that allow dynamic quantification of intracellular glucose levels can contribute to a better understanding of physiology. We develop a fluorescent hybrid nanogel glucometer (FNG) that is applicable for intracellular glucometry. Such a FNG (<200 nm) is comprised of ZnO quantum dots covalently bonded onto a loosely-crosslinked gel network of poly(acrylamide), which is interpenetrated in another relatively highly-crosslinked gel network of poly(N-isopropylacrylamide-co-2-acrylamidomethyl-5-fluorophenylboronic acid). This newly developed double-network-structured FNG can adapt to surrounding media of varying glucose levels, and convert the disruptions in homeostasis of glucose level with high reversibility, sensitivity, and selectivity into fluorescence signals at a fast time response. We demonstrate that the FNG can enter the model B16F10 cells and employ the signal transduction ability for fluorescent intracellular glucometry. Furthermore, we show that intracellular glucose level variations associated with a model biological reaction process can be monitored with a high glucose resolution by using the FNG embedded in cells, whilst the reaction mechanism remains nearly unchanged

Rab25-Mediated EGFR Recycling Causes Tumor Acquired Radioresistance.

Tumor acquired radioresistance remains as the major limit in cancer radiotherapy (RT). Rab25, a receptor recycling protein, has been reported to be enhanced in tumors with aggressive phenotype and chemotherapy resistance. In this study, elevated Rab25 expression was identified in an array of radioresistant human cancer cell lines, in vivo radioresistant xenograft tumors. Clinical investigation confirmed that Rab25 expression was also associated with a worse prognosis in patients with lung adenocarcinoma (LUAD) and nasopharyngeal carcinoma (NPC). Enhanced activities of EGFR were observed in both NPC and LUAD radioresistant cells. Rab25 interacts with EGFR to enhance EGFR recycling to cell surface and to decrease degradation in cytoplasm. Inhibition of Rab25 showed synergized radiosensitivity with reduced aggressive phenotype. This study provides the clinical and experimental evidence that Rab25 is a potential therapeutic target to alleviate the hyperactive EGFR signaling and to prevent RT-acquired tumor resistance in patients with LUAD and NPC

Determination of incommensurate modulated structure in Bi2Sr1.6La0.4CuO6+{\delta} by aberration-corrected transmission electron microscopy

Incommensurate modulated structure (IMS) in Bi2Sr1.6La0.4CuO6+{\delta} (BSLCO) has been studied by aberration corrected transmission electron microscopy in combination with high-dimensional (HD) space description. Two images in the negative Cs imaging (NCSI) and passive Cs imaging (PCSI) modes were deconvoluted, respectively. Similar results as to IMS have been obtained from two corresponding projected potential maps (PPMs), but meanwhile the size of dots representing atoms in the NCSI PPM is found to be smaller than that in PCSI one. Considering that size is one of influencing factors of precision, modulation functions for all unoverlapped atoms in BSLCO were determined based on the PPM obtained from the NCSI image in combination with HD space description