Pesticide fate at watershed scale: A new framework integrating multimedia behavior with hydrological processes.

Pesticide pollution has been one serious ecological and environmental issue due to its wide application, high toxicity, and complex environmental behavior. The fugacity model has been widely used to quantify biogeochemical cycles of pesticides due to its clear compartments, simple structure, and easy-accessible data. However, the lack of detailed hydrological processes limits its application for large and heterogeneous watershed. In present study, a new framework was proposed through integration of hydrological processes of SWAT and pesticide fate of fugacity model, and was applied into a typical watershed in the Three Gorges Reservoir Area, China. The results showed that surface runoff, soil erosion, and percolation varied spatiotemporally, which highlighted the importance of considering regional and seasonal heterogeneity of pesticide transport variables in the fugacity model. The amount of dichlorvos (DDV) and chlorpyrifos (CHP) in air, water, soil, and sediment phase were estimated as 0.26 kg, 19.77 kg, 1.06 × 104 kg, and 0.55 kg, respectively. Spatiotemporally, pesticide concentrations in water phase peaked in summer, while the middle and southwest regions of the watershed were identified as the hotspots for pesticide pollution. Compared with the classical model, the new framework provided technical support for the pesticide assessment at watershed scale with heterogeneous hydrological conditions, which can be easily extended to other watersheds, and integrated with other models for comprehensive agricultural management.

Post-transcriptional regulation of cancer/testis antigen MAGEC2 expression by TRIM28 in tumor cells.

BACKGROUND: Cancer/testis antigen MAGEC2 (also known as HCA587) is highly expressed in a wide variety of tumors and plays an active role in promoting growth and metastasis of tumor cells. However, little is known for the regulation of MAGEC2 expression in cancer cells. METHODS: Western blotting and quantitative RT-PCR were performed to analyze MAGEC2 expression. Co-immunoprecipitation assay was applied for detecting the endogenous interaction of MAGEC2 and TRIM28 in tumor cells. Overexpression and knockdown assays were used to examine the effects of TRIM28 on the expression of MAGEC2 protein. Immunohistochemistry (IHC) staining was performed in hepatocellular carcinoma patients to evaluate the association between the expression of MAGEC2 and TRIM28. Proteasome inhibitors MG132 or PS-341 and lysosome inhibitor Chloroquine (CQ) were used to inhibit proteasomal or lysosomal-mediated protein degradation respectively. RESULTS: We demonstrate that MAGEC2 interacts with TRIM28 in melanoma cells and MAGEC2 expression in tumor cells depends on the expression of TRIM28. The expression level of MAGEC2 protein was significantly reduced when TRIM28 was depleted in tumor cells, and no changes were observed in MAGEC2 mRNA level. Furthermore, expression levels of MAGEC2 and TRIM28 are positively correlated in MAGEC2-positive human hepatocellular carcinoma tissues (p = 0.0011). Mechanistic studies indicate that the regulatory role of TRIM28 on MAGEC2 protein expression in tumor cells depends on proteasome-mediated pathway. CONCLUSIONS: Our findings show that TRIM28 is necessary for MAGEC2 expression in cancer cells, and TRIM28 may serve as a new potential target for immunotherapy of cancer.

Evaluation of KIF23 variant 1 expression and relevance as a novel prognostic factor in patients with hepatocellular carcinoma.

BACKGROUND: KIF23 (kinesin family member 23) is a kinesin-like motor protein and plays an important role in cytokinesis. In search for genes associated with hepatocellular carcinoma (HCC) by cDNA microarray, we found that KIF23 was upregulated in HCC tissues. At present, much less is known about its expression and functions in tumor cells. In this work, we aimed to investigate the expression of KIF23 in HCC and the correlation between its expression and clinical features. METHODS: Total RNA was extracted from 16 HCC and paired adjacent non-cancerous tissues. The expressions of the two KIF23 splice variants (KIF23 V1 and KIF23 V2) in normal and HCC tissues were determined by reverse transcriptase polymerase chain reaction (RT-PCR). Polyclonal antibody specific to KIF23 V1 was prepared, and the specificity of the antibody was confirmed by siRNA knockdown and Western blotting experiments. KIF23 protein expression in HCC was examined by immunohistochemistry staining with anti-KIF23 V1 or anti-KIF23 (commercially available for recognizing both KIF23 V1 and V2) antibodies, respectively. Univariate and Multivariate Cox regression analyses were used to determine the correlation between KIF23 protein expression and overall survival of HCC patients. RESULTS: The two splicing variants of KIF23 mRNA were not detected in normal liver tissue by RT-PCR, but they were aberrantly expressed in HCC tissues. Immunohistochemistry staining with anti-KIF23 V1 antibody revealed that KIF23 V1 was mainly distributed in the nucleus, whereas the positive staining signals were predominantly in the cytoplasm when using anti-KIF23 antibody, suggesting that KIF23 V2 might localize in the cytoplasm of HCC cells. KIF23 V1 protein was detected in 57.6% (83/144) HCC patients and the mean H-score was 42, while KIF23 V2 was detected in 94.4% (135/143) HCC samples and the mean H-score was 68. Follow-up study showed that HCC patients with expression of KIF23 V1 had a longer 5-year survival (p=0.0052), however, expression of KIF23 V2 protein did not associate with 3- and 5-year survival. CONCLUSION: In this study we show for the first time that KIF23 V1 and V2 have different localizations in HCC cells. Furthermore, KIF23 V1 protein expression might be a marker of longer overall survival in HCC patients.

G-protein coupled receptor 34 knockdown impairs the proliferation and migration of HGC-27 gastric cancer cells in vitro.

BACKGROUND: Overexpression of G-protein coupled receptor 34 (GPR34) affects the progression and prognosis of human gastric adenocarcinoma, however, the role of GPR34 in gastric cancer development and progression has not been well-determined. The current study aimed to investigate the effect of GPR34 knockdown on the proliferation, migration, and apoptosis of HGC-27 gastric cancer cells and the underlying mechanisms. METHODS: The expression of GPR34 in gastric cancer cell line HGC-27 was detected by quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting. HGC-27 cells were employed to construct the stable GPR34 knockdown cell model in this study. Real-time RT-PCR and Western blotting were applied to validate the effect of short hairpin RNA (ShRNA) on the expression of GPR34 in HGC-27 gastric cells. The proliferation, migration of these cells were examined by Cell Counting Kit-8 and transwell. We also measured expression profile of PI3K/PDK1/AKT and ERK using Western blotting. RESULTS: The ShRNA directed against GPR34 effectively inhibited both endogenous mRNA and protein expression levels of GPR34, and significantly down-regulated the expression of PIK3CB (P < 0.01), PIK3CD (P < 0.01), PDK1 (P < 0.01), phosphorylation of PDK1 (P < 0.01), Akt (P < 0.01), and ERK (P < 0.01). Furthermore, GPR34 knockdown resulted in an obvious reduction in HGC-27 cancer cell proliferation and migration activity (P < 0.01). CONCLUSIONS: GPR34 knockdown impairs the proliferation and migration of HGC-27 gastric cancer cells in vitro and provides a potential implication for therapy of gastric cancer.

Complement factor I polymorphism is not associated with neovascular age-related macular degeneration and polypoidal choroidal vasculopathy in a chinese population.

PURPOSE: To identify the associations of the two complement factor I (CFI) polymorphisms rs10033900 and rs2285714 with risk of neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV) in a Chinese case-control study. METHODS: A total of 900 subjects - 300 controls, 300 cases with nAMD and 300 cases with PCV - were included in the present study. Genomic DNA was extracted from venous blood leukocytes. The allelic variants of rs10033900 and rs2285714 were determined by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. The differences in allele distribution between the cases and controls were tested by a χ(2) test with age and gender adjusted for by logistic regression analysis. We also performed a meta-analysis of the case-control studies of rs10033900 and rs2285714 based on the currently available evidence from the literature. The meta-analysis was conducted via an inverse-variance, fixed-effects model, as previously described. RESULTS: No statistically significant association was observed between the two polymorphisms of CFI and AMD risk, including nAMD, PCV and combined AMD (p > 0.05 for all comparisons). By meta-analysis, we detected significant associations between both of the SNPs and late AMD, which is consistent with previous results (odds ratio, OR, rs10033900 = 0.814, p rs10033900 < 0.001; OR rs2285714 = 1.221, p rs2285714 < 0.001). For rs2285714, the results of the meta-analysis were less reliable due to its heterogeneity. CONCLUSIONS: In our case-control study, neither of the two SNPs most studied (rs10033900 or rs2285714) in the CFI gene was a risk factor for developing nAMD or PCV in a Chinese population. Additional large, comprehensive and well-designed association studies are needed to better understand the role of ethnicity and other gene interactions in the association between the CFI gene and AMD.

Simultaneous measurements of serum AFP, GPC-3 and HCCR for diagnosing hepatocellular carcinoma.

BACKGROUND/AIMS: Hepatocellular carcinoma (HCC) is a prevalent malignant tumor. Tumor markers are very useful in early diagnosis; however a single marker is rather limited. We launched a test to increase the diagnostic sensitivity through the combined detection. METHODOLOGY: Serum concentration of three tumor-markers, Glypican-3 (GPC-3), Human-Cervical-Cancer-Oncogene (HCCR) and a-fetoprotein (AFP), were determined in 189 samples: 101 cases of HCC, 40 cases of cirrhosis, 18 cases of hepatitis and 30 cases of control healthy donors. Every marker was evaluated for its diagnostic value by one-way-analysis-of-variance and receiver-operating-characteristics analysis. RESULTS: GPC-3 was the best marker with an area under the curve (AUC) of 0.892; using 26.8ng/mL as the cut-off for HCC diagnosis, GPC-3 has a sensitivity of 51.5% and maintains a specificity of 92.8%. HCCR, with an AUC of 0.831, can reach a sensitivity of 22.8% and maintain a specificity of 90.9% if the cut-off is set as 58.8mAU/mL. With an AUC of 0.827, the efficacy and sensitivity of AFP were 36.6% and 98.5% when using 199.3ng/mL as the cut-off. No significant correlation was found between these three markers. Simultaneously detecting three markers can significantly increases the sensitivity to 80.2%, much higher than AFP alone. CONCLUSIONS: GPC-3 and HCCR are useful tumor markers complementary to AFP for clinical diagnosis of HCC.

Experimental autoimmune thyroiditis in nonobese diabetic mice lacking interferon regulatory factor-1.

Interferon regulatory factor-1 (IRF-1) is pivotal in the regulation of interferon (IFN)-mediated immune reactions, and studies suggest that IRF-1 is involved in the development of autoimmune diseases. IRF-1+/+, +/-, and -/- nonobese diabetic (NOD) mice were immunized with mouse thyroglobulin (mTg) to determine whether IRF-1 is required in experimental autoimmune thyroiditis (EAT), a murine model for Hashimoto's thyroiditis (HT). IRF-1-deficient mice developed EAT and anti-mTg antibodies comparable to IRF-1+/+ and +/- mice. Whereas both CD4+ and CD8+ T cells were found in thyroids of IRF-1+/+ mice, the latter was not in IRF-1-/- mice. Major histocompatibility complex class II antigen was comparably expressed in thyroids of IRF-1+/+ and -/- mice. Lack of IRF-1 resulted in decreased CD8+ T cell number in the spleen and reduced IFNgamma production by splenocytes. Our results suggest that IRF-1 is not pivotal in EAT in NOD mice.