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Existing literature has examined the contextual effects on individual environmental activism, but little research has been conducted to investigate how local-level governance factors affect individ...

Recent studies show p85α up-regulates epidermal growth factor (EGF) receptor, thereby promoting malignant cell transformation and migration in normal mouse embryonic fibroblasts (MEFs). However, the potential role of p85α in human bladder cancer (BC) remains unknown. Here, we show that p85α is down-regulated in BC tumor tissues. Ectopic expression of p85α inhibited cell invasion, but not migration, whereas p85α knockdown promoted invasion in BC cells, revealing that p85α inhibits BC invasion. Overexpression of kinase-deficient p110 in T24 T(p85α) cells inhibited BC cell migration, but not invasion, suggesting that the inhibition of p85α on invasion is independent of PI3K activity. The effect of p85α on inhibiting BC invasion was mediated by the inactivation of MMP-2 concomitant with the up-regulation of TIMP-2 and down-regulation of MMP-14. Mechanistic studies revealed c-Jun inactivation was associated with p85α knockdown-induced MMP-14 expression, and down-regulated miR-190, leading to ATG7 mRNA degradation. This suppressed the autophagy-dependent removal of TIMP-2 in human BC cells. The present results identify a novel function of p85α and clarify the mechanisms underlying its inhibition of BC invasion, providing insight into the role of p85α in normal and cancer cells.

PHLPP1 (PH domain and leucine rich repeat protein phosphatase 1) is a newly identified family of Ser/Thr phosphatases that catalyzes the dephosphorylation of a conserved regulatory motif of the AGC kinases resulting in a tumor suppressive function, while CDKN1B/p27 also acts as a tumor suppressor by regulating cell cycle, senescence, apoptosis, and cell motility. Our most recent studies reveal that CDKN1B is required for PHLPP1 abundance, which contributes to the inhibition of carcinogenic arsenite-induced cell malignant transformation through inhibition of RPS6-mediated Hif1a translation. However, nothing is known about the mechanisms underlying the crosstalk between these 2 key tumor suppressors in intact cells. Here, for the first time to the best of our knowledge, we show that CDKN1B is able to promote PHLPP1 protein translation by attenuating the abundance of Mir6981, which binds directly to the 5'untranslated region (UTR) of Phlpp1 mRNA. Further studies indicate that the attenuation of Mir6981 expression is due to macroautophagy/autophagy-mediated degradation of Mir6981 in an SQSTM1/p62-dependent fashion. Moreover, we have determined that Sqstm1 is upregulated by CDKN1B at the level of transcription via enhancing SP1 protein stability in an HSP90-depdendent manner. Collectively, our studies prove that: 1) SQSTM1 is a CDKN1B downstream effector responsible for CDKN1B-mediated autophagy; 2) by promoting the autophagy-mediated degradation of Mir6981, CDKN1B exerts a positive regulatory effect on PHLPP1 translation; 3) Mir6981 suppresses PHLPP1 translation by binding directly to its mRNA 5'-UTR, rather than classical binding to the 3'-UTR. These findings provide significant insight into understanding the crosstalk between CDKN1B and PHLPP1. Abbreviations: ATG: autophagy related; ACTB: actin beta; BAF: bafilomycin; BECN1: beclin 1; Cdkn1b/p27: cyclin-dependent kinase inhibitor 1B; CHX: cycloheximide; DMEM: dulbecco's modified eagle medium; FBS: fetal bovine serum; GAPDH: glyceraldehyde -3-phosphate dehydrogenase; Hif1a: hypoxia inducible factor 1, alpha subunit; Hsp90: heat shock protein 90; JUN: Jun proto-oncogene, AP1 transcription factor subunit; MAP1LC3/LC3: microtubule-associated protein 1 light chain 3; MG132: proteasome inhibitor; Mtor: mechanistic target of rapamycin kinase; Phlpp1: PH domain and leucine rich repeat protein phosphatase 1; Phlpp2: PH domain and leucine rich repeat protein phosphatase 2; Pp2c: protein phosphatase 2 C; RPS6: ribosomal protein S6; Sp1: trans-acting transcription factor 1; Sqstm1/p62: sequestosome 1; TUBA: alpha tubulin; 3'-UTR; 3'-untranslated region; 5'-UTR: 5'-untranslated region.

Using data from the China Social Survey 2013 and statistics from the Ministry of Environment Protection of China and the Institute of Public & Environment Affairs, this study empirically examines the relationship between actual and perceived air pollution and the moderating effect of environmental transparency on that relationship with a multilevel ordered logistic strategy. Estimations indicate a significant congruence of actual (both particulate matter less than 10 µm in diameter and sulfur dioxide) and perceived air pollution. More importantly, environmental transparency of local government is found to moderate the relationship between actual and perceived air pollution by neutralizing the halo effects and building more alert perceptions when local air quality deteriorates. Our findings not only challenge the work of identifying a mismatch of actual–perceived air pollution in some developed countries but also suggest that, apart from abating actual air pollution, environmental transparency should be emphasized and strengthened in institutional buildings to help address pollution challenges in developing countries.

Our previous studies have demonstrated that XIAP promotes bladder cancer metastasis through upregulating RhoGDIβ/MMP-2 pathway. However, the molecular mechanisms leading to the XIAP upregulation was unclear. In current studies, we found that XIAP was overexpressed in human high grade BCs, high metastatic human BCs, and in mouse invasive BCs. Mechanistic studies indicated that XIAP overexpression in the highly metastatic T24T cells was due to increased mRNA stability of XIAP that was mediated by downregulated miR-200c. Moreover, the downregulated miR-200c was due to CREB inactivation, while miR-200c downregulation reduced its binding to the 3’-UTR region of XIAP mRNA. Collectively, our results demonstrate the molecular basis leading to XIAP overexpression and its crucial role in BC invasion.

PHLPP1 (PH domain and leucine rich repeat protein phosphatase 1) is a newly identified family of Ser/Thr phosphatases that catalyzes the dephosphorylation of a conserved regulatory motif of the AGC kinases resulting in a tumor suppressive function, while CDKN1B/p27 also acts as a tumor suppressor by regulating cell cycle, senescence, apoptosis, and cell motility. Our most recent studies reveal that CDKN1B is required for PHLPP1 abundance, which contributes to the inhibition of carcinogenic arsenite-induced cell malignant transformation through inhibition of RPS6-mediated Hif1a translation. However, nothing is known about the mechanisms underlying the crosstalk between these 2 key tumor suppressors in intact cells. Here, for the first time to the best of our knowledge, we show that CDKN1B is able to promote PHLPP1 protein translation by attenuating the abundance of Mir6981, which binds directly to the 5ʹuntranslated region (UTR) of Phlpp1 mRNA. Further studies indicate that the attenuation of Mir6981 expression is due to macroautophagy/autophagy-mediated degradation of Mir6981 in an SQSTM1/p62-dependent fashion. Moreover, we have determined that Sqstm1 is upregulated by CDKN1B at the level of transcription via enhancing SP1 protein stability in an HSP90-depdendent manner. Collectively, our studies prove that: 1) SQSTM1 is a CDKN1B downstream effector responsible for CDKN1B-mediated autophagy; 2) by promoting the autophagy-mediated degradation of Mir6981, CDKN1B exerts a positive regulatory effect on PHLPP1 translation; 3) Mir6981 suppresses PHLPP1 translation by binding directly to its mRNA 5ʹ-UTR, rather than classical binding to the 3ʹ-UTR. These findings provide significant insight into understanding the crosstalk between CDKN1B and PHLPP1. Abbreviations: ATG: autophagy related; ACTB: actin beta; BAF: bafilomycin; BECN1: beclin 1; Cdkn1b/p27: cyclin-dependent kinase inhibitor 1B; CHX: cycloheximide; DMEM: dulbecco’s modified eagle medium; FBS: fetal bovine serum; GAPDH: glyceraldehyde −3-phosphate dehydrogenase; Hif1a: hypoxia inducible factor 1, alpha subunit; Hsp90: heat shock protein 90; JUN: Jun proto-oncogene, AP1 transcription factor subunit; MAP1LC3/LC3: microtubule-associated protein 1 light chain 3; MG132: proteasome inhibitor; Mtor: mechanistic target of rapamycin kinase; Phlpp1: PH domain and leucine rich repeat protein phosphatase 1; Phlpp2: PH domain and leucine rich repeat protein phosphatase 2; Pp2c: protein phosphatase 2 C; RPS6: ribosomal protein S6; Sp1: trans-acting transcription factor 1; Sqstm1/p62: sequestosome 1; TUBA: alpha tubulin; 3ʹ-UTR; 3ʹ-untranslated region; 5ʹ-UTR: 5ʹ-untranslated region.

Pleckstrin homology domain leucine-rich repeat protein phosphatase 2 (PHLPP2) is a tumor suppressor that catalyzes the de-phosphorylation of the AGC kinases, while p27 acts as a tumor suppressor that regulates cell cycle, apoptosis, and cell motility. Our previous studies have identified that PHLPP2 participates in inhibition of transformation of human bronchial epithelial cells following lung carcinogen B[a]P/B[a]PDE exposure. However, nothing was known about the association of p27 with regulation of PHLPP2 expression and the role of PHLPP2 in bladder cancer (BC) invasion. In our current studies, we demonstrated that PHLPP2 inhibited BC invasion through promoting MMP2 degradation via p62-mediated autophagy; and p27 expression was able to stabilize PHLPP2 protein by inhibiting protein degradation of Hsp90, which could directly bind to PHLPP2 and protect it from degradation. More in-depth studies discovered that stabilization of Hsp90 by p27 was mediated by calpain1 proteolysis system, whereas p27 inhibited calpain1 gene transcription by attenuating Jak1/Stat1 cascade in human invasive BC cells. Collectively, we for the first time revealed PHLPP2 downregulation in BCs and its participating in promotion of BC invasion, as well as novel role of p27 and mechanisms underlying its regulation of PHLPP2 protein degradation through Hsp90-dependent manner. Our findings improve our understanding of p27 and PHLPP2 roles and their crosstalk in regulation of BC invasion, which further contributes to improve the current strategy for invasive bladder cancer therapy.

Frequent and intense forest fires have posed severe challenges to forest management in many countries worldwide. Since human experts may overlook important signals, the development of reliable prediction models with various types of data generated by automatic tools is crucial for establishing rigorous and effective forest firefighting plans. This study applied recently emerged ensemble learning methods to predict the burned area of forest fires and the occurrence of large-scale forest fires using the forest fire dataset from the University of California, Irvine machine learning repository collected from the northeastern region of Portugal. The results showed that the tuned random forest approach performed better than other regression models did with regard to the prediction accuracy of the burned area. In addition, extreme gradient boosting outperformed other classification models in terms of its predictive accuracy of large-scale fire occurrences. The findings showed that ensemble learning methods not only have great potential for broader application in forest fire automatic precaution and prevention systems but also provide important techniques for forest firefighting decision making in terms of fire resource allocation and strategies, which can ultimately improve the efficiency of forest fire management worldwide.

Using the zero-inflated model and nationally representative sample data from the Chinese General Social Surveys 2013, this study systematically explored the effects of religion, modernizing factors, and traditional culture on attitudes toward homosexuality in China. The findings indicate that most Chinese people generally hold conservative attitudes toward homosexuality, as approximately 78.53% of the respondents believed that "same-sex sexual behavior is always wrong." Modernizing factors (i.e., education, exposure to Internet information, and liberal inclinations) predicted greater tolerance for homosexuality, whereas Islamic beliefs negatively influenced respondents' attitudes toward homosexuality. In contrast to the findings of the existing literature, Christian beliefs and traditional culture did not have significant effects on attitudes toward homosexuality. These findings may contribute to the literature by not only quantitatively testing the applicability of several factors identified in most Western studies of this topic but also providing new knowledge of attitudes toward homosexuality in the social context of China.

The compressed and dehydrated mud was made into filter cake, and then fly ash, silica fume and cement were added to it to prepare foamed concrete with sodium α-olefin sulfonate as foaming agent. By analysing the changing characteristics of the compressive strength, apparent density, water absorption and microstructure of the foam concrete, the key mechanism of making the foam concrete was analysed in depth. The results show that mud filter cake can improve the comprehensive performance of foamed concrete. The best mix ratio is 20% of mud filter cake, 50% of cement addition, 20% of fly ash, 10% of silica fume, 0.55 of water cement ratio and 55% of foam volume. The compressive strength of foam concrete is 1.6MPa and the apparent density is 660.26kg/m3. The water absorption rate is 23.73%, which accords with China Construction Industry Standard JG / T266-2011. Proper addition of mud filter cake can improve the pore structure and cementing material matrix of foamed concrete, and enhance the strength of foamed concrete. However, too much addition will produce connected pores and cracks, and reduce compressive strength. The results can provide theoretical basis and technical reference for mud resource utilization.

Our most recent studies demonstrate that RhoGDIβ is able to promote human bladder cancer (BC) invasion and metastasis in an X‐link inhibitor of apoptosis protein‐dependent fashion accompanied by increased levels of matrix metalloproteinase (MMP)‐2 protein expression. We also found that RhoGDIβ and MMP‐2 protein expressions are consistently upregulated in both invasive BC tissues and cell lines. In the present study, we show that knockdown of RhoGDIβ inhibited MMP‐2 protein expression accompanied by a reduction of invasion in human BC cells, whereas ectopic expression of RhoGDIβ upregulated MMP‐2 protein expression and promoted invasion as well. The mechanistic studies indicated that MMP‐2 was upregulated by RhoGDIβ at the transcriptional level by increased specific binding of the transcription factor Sp1 to the mmp‐2 promoter region. Further investigation revealed that RhoGDIβ overexpression led to downregulation of miR‐200c, whereas miR‐200c was able directly to target 3′‐UTR of jnk2 mRNA and attenuated JNK2 protein translation, which resulted in attenuation of Sp1 mRNA and protein expression in turn, inhibiting Sp1‐dependent mmp‐2 transcription. Collectively, our studies demonstrate that RhoGDIβ overexpression inhibits miR‐200c abundance, which consequently results in increases of JNK2 protein translation, Sp1 expression, mmp‐2 transcription, and BC invasion. These findings, together with our previous results showing X‐link inhibitor of apoptosis protein mediating mRNA stabilization of both RhoGDIβ and mmp‐2, reveal the nature of the MMP‐2 regulatory network, which leads to MMP‐2 overexpression and BC invasion.

The X-linked inhibitor of apoptosis protein (XIAP) contains three N-terminal BIR domains that mediate anti-apoptosis and one C-terminal RING finger domain whose function(s) are not fully defined. Here we show that the RING domain of XIAP strongly inhibits the expression of p63α, a known tumor suppressor. XIAP knockdown in urothelial cells or RING deletion in knockin mice markedly upregulates p63α expression. This RING-mediated p63α downregulation is critical for the malignant transformation of normal urothelial cells following EGF treatment. We further show that the RING domain promotes Sp1-mediated transcription of miR-4295 which targets the 3'UTR of p63α mRNA and consequently inhibits p63α translation. Our results reveal a previously unknown function of the RING of XIAP in promoting miR-4295 transcription, thereby reducing p63α translation and enhancing urothelial transformation. Our data offer novel insights into the multifunctional effects of the XIAP RING domain on urothelial tumorigenesis and the potential for targeting this frequently overexpressed protein as a therapeutic alternative.

Yang Zhang,1 Linjuan Xu,2 Minggang Peng2 1Department of Clinical Laboratory, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; 2Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China Objective: To deeply verify the clinical significance of CXCR3 in prediction of cancer patients’ prognosis.Data sources: We performed a meta-analysis including 12 studies searched from PubMed, Web of Science, Embase, and Cochrane databases. A total of 1,751 patients were used to analyze the association between CXCR3 and patients’ prognosis, based on either overall survival or time to tumor progression.Study selection: Studies evaluating CXCR3 expression for predicting prognosis in human solid tumors were included.Results: It showed that patients with higher expression of CXCR3 had significantly shorter OS (pooled hazard ratio =2.315, 95% CI: 1.162–4.611, P=0.017). In addition, higher CXCR3 expression was associated with distant metastasis (yes vs no: pooled relative ratio [RR] =1.828, 95% CI: 1.140–2.931, P=0.012) in solid tumors and indicated advanced tumor stage (III/IV vs I/II, RR =2.656, 95% CI: 1.809–3.900, P

China has established a petition system to elicit information about grievances. However, the petition system may have perverse effects because it also reveals to the center the failure of local-level officials to resolve those grievances. Anecdotal accounts suggest that local officials have incentive to silence petitioners, often with the use of repression. In this article we study whether non-regime threatening petitions would provoke local governments' coercive response. To tackle the endogenous relationship between petition and repression, we take advantage of a natural experiment afforded by a change in hydroelectricity policy in China. In particular, we use provincial hydropower outputs as an instrument to identify citizen petitions. We find that citizen petitions significantly increase a province's spending on its repressive apparatus. The results suggest a paradoxical outcome of China's petition system: while it may help reduce the national authority's use of repression, it has caused an explosion of repression within the authoritarian system as a whole.

This article examines the issue of party unity in Hong Kong’s Legislative Council (LegCo). By analysing the LegCo roll-call votes, one can see that the voting patterns of its members are characterised by strong party unity. In particular, a cross-party comparison reveals that for the pro-establishment parties, the Liberal Party had a higher level of unity than the Democratic Alliance for the Betterment and Progress of Hong Kong (DAB); for the pro-democracy parties, the Civic Party had a higher level of cohesion than the Democratic Party. Furthermore, this article shows that strong party unity is likely to be the joint product of party discipline and policy homogeneity among partisan members. Based on the empirical results, the article questions the traditional wisdom that party politics in Hong Kong is necessarily underdeveloped for its simple juxtaposition of party politics with the performance of political parties in elections. Instead, it is suggested that for a better understanding of party politics in Hong Kong, due attention should be paid to the legislative process.

The tumor microenvironment is thought to affect malignant transformation and tumor progression. The histone methyltransferase, enhancer of zeste homologue 2 (EZH2), has recently been suggested to play a critical role in the tumorigenesis of several types of human cancer. The aim of this study was to investigate the effects of cancer-associated fibroblasts (CAFs) on the expression of EZH2 and the migration ability of ovarian cancer cells, in order to explore the link between the tumor microenvironment and epigenetic regulation. The ovarian cancer cell lines, A2780, SKOV3 and ES2, were indirectly co-cultured with primary ovarian CAFs or normal fibroblasts (NFs). The migration ability of the ovarian cancer cells was determined by Transwell migration assay. The expression levels of EZH2 were assessed by quantitative reverse transcription PCR (qRT-PCR) and western blot analysis. The A2780-shEZH2 cells (A2780 cells transfected with shRNA targeting EZH2) were indirectly co-cultured with CAFs or NFs, and the changes in the expression levels of EZH2 and the migration ability of the cells were detected. The migration ability of the A2780, SKOV3 and ES2 cells co-cultured with CAFs was significantly enhanced (P0.05) compared with the NF group and the cells cultured alone. The expression of EZH2 in the A2780, SKOV3 and ES2 cells was significantly increased following co-culture with CAFs (P0.001) compared with the cells cultured alone but not those cultured with NFs. The migration ability of the A2780-shEZH2 cells was not significantly increased following co-culture with CAFs (P0.05). Our data indicate that CAFs enhance the migration ability of ovarian cancer cells partly by increasing EZH2 expression.