How can open public data promote efficient and equitable green production? Evidence from eco-efficiency in China.

Nowadays, concurrent attention to economic development and ecological issues is becoming an important trend. In this paper, we measure the eco-efficiency of 285 Chinese cities from 2003 to 2019 using a non-radial directional distance function and the data envelopment analysis method, based on which we analyze the club convergence of cities' eco-efficiency using the logt test; we estimate the impact of open public data platforms on eco-efficiency and its convergence using a multi-period difference in difference model and panel-ordered logit model, respectively. We find that, first, open public data platforms improve cities' eco-efficiency by about 6.5%, and the impact mechanisms include scale efficiency, technical efficiency, and total factor productivity, or, at the micro level, increasing the economic agglomeration degree, boosting the amount of foreign investment used, and increasing green innovation level. Second, there are three convergence clubs of eco-efficiency in China's cities, whose average eco-efficiency trends are above, close to, and below average, respectively. Third, public data platforms significantly increase the probability of cities belonging to the convergence clubs of high and medium eco-efficiency (Clubs 1 and 2) and decrease the probability of belonging to the low one (Club 3). However, the mechanisms only include technical efficiency and total factor productivity, or the amount of foreign investment used and the green innovation level at the micro level.

Carbon emissions trading schemes and economic growth: New evidence on the Porter Hypothesis from 285 China's prefecture-level cities.

The Chinese government has established carbon emissions trading schemes (CETS) to cope with climate change and reduce carbon emissions. This paper uses the multi-period difference in difference (DID) model to explore the impact of CETS on cities' GDP and GDP growth rates in China based on data from 285 prefecture-level cities from 2008-2019. We find that CETS increase the level of GDP by 3.4% and the GDP growth rate by 0.004. The mechanism of increasing GDP includes promoting investment and innovation, and the mechanism of increasing the GDP growth rate includes only promoting the investment growth rate. Thus, CETS satisfy both the weak and strong versions of the Porter Hypothesis from the GDP and growth rate perspectives. In the heterogeneity analysis, we find that the impacts of CETS on cities' GDP and GDP growth rates decrease with the increase of the corresponding dependent variable. In the spatial spillover analysis, we find that the establishment of CETS has a positive spillover effect on the GDP of cities around 50 km and 150 km, and a negative spillover effect on the GDP of cities around 200 km, but there is no spatial spillover effect on the GDP growth rate.

Do energy-environmental efficiency benefit from advanced policy zones? Evidence from national new zones of China.

As global climate change aggravates, reducing energy consumption and environmental pollution is essential to sustainable economic development. This paper measures the energy-environmental efficiency of 284 prefecture-level cities in China using a non-radial directional distance function (NDDF) and data envelopment analysis (DEA), and evaluates the impact of the establishment of national new zones on energy-environmental efficiency using the multi-period difference-in-difference model (DID). The results are: first, establishing national new zones improves the energy-environmental efficiency of the prefecture-level cities in which they are located by 13%-25%, and the mechanisms include enhancing the green technical efficiency and scale efficiency. Second, national new zones have both negative and positive spatial spillover effects. Third, in terms of heterogeneity, the impact of establishing national new zones on energy-environmental efficiency increases with larger quantile of the latter; national new zones with the one-city layout have significant stimulating impacts on energy-environmental efficiency, but those with the two-city layout have no significant impact, which means there is no significant green synergistic development impact among cities. We also discuss the policy implications of the research, including enhanced policy support and regulation to support the energy environment sector.

Gut microbial evidence chain in high-salt diet exacerbates intestinal aging process.

Although excessive salt consumption appears to hasten intestinal aging and increases susceptibility to cardiovascular disease, the molecular mechanism is unknown. In this study, mutual validation of high salt (HS) and aging fecal microbiota transplantation (FMT) in C56BL/6 mice was used to clarify the molecular mechanism by which excessive salt consumption causes intestinal aging. Firstly, we observed HS causes vascular endothelial damage and can accelerate intestinal aging associated with decreased colon and serum expression of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and increased malondialdehyde (MDA); after transplantation with HS fecal microbiota in mice, vascular endothelial damage and intestinal aging can also occur. Secondly, we also found intestinal aging and vascular endothelial damage in older mice aged 14 months; and after transplantation of the older mice fecal microbiota, the same effect was observed in mice aged 6-8 weeks. Meanwhile, HS and aging significantly changed gut microbial diversity and composition, which was transferable by FMT. Eventually, based on the core genera both in HS and the aging gut microbiota network, a machine learning model was constructed which could predict HS susceptibility to intestinal aging. Further investigation revealed that the process of HS-related intestinal aging was highly linked to the signal transduction mediated by various bacteria. In conclusion, the present study provides an experimental basis of potential microbial evidence in the process of HS related intestinal aging. Even, avoiding excessive salt consumption and actively intervening in gut microbiota alteration may assist to delay the aging state that drives HS-related intestinal aging in clinical practice.

MicroRNA-1252-5p, regulated by Myb, inhibits invasion and epithelial-mesenchymal transition of pancreatic cancer cells by targeting NEDD9.

MicroRNAs (miRNAs) are known to be involved in the development and progression of pancreatic cancer (PAC). The expression levels and roles of miR-1252-5p in PAC remain unclear. Quantitative real-time PCR and in situ hybridization were used to detect miR-1252-5p expression in PAC cells and human tissues. We studied the gain and loss of function of miR-1252-5p in the PAC cell lines in vitro and in vivo. The direct targets of miR-1252-5p were analyzed using public databases and a dual-luciferase reporter assay. Expression levels of miR-1252-5p are downregulated in PAC cell lines and tissue samples, and its expression is negatively associated with adverse clinical features and poor prognosis. In vitro and in vivo experiments show that miR-1252-5p overexpression inhibits the proliferation, migration, invasion, and epithelial-mesenchymal transition of PAC cells, and miR-1252-5p knockdown enhances these biological behaviors. MiR-1252-5p negatively regulates neural precursor cell expressed, developmentally downregulated 9 (NEDD9) by directly binding its 3'- untranslated region. Further mechanism research revealed that the SRC/STAT3 pathway is involved in miR-1252-5p/NEDD9 mediation of PAC's biological behaviors. We also verified that Myb inhibited miR-1252-5p by directly binding at its promoter. MiR-1252-5p may act as a tumor-suppressing miRNA in PAC and may be a potential therapeutic target for PAC patients.

CD137 agonist induces gastric cancer cell apoptosis by enhancing the functions of CD8+ T cells via NF-κB signaling.

BACKGROUND: CD137 is a target for tumor immunotherapy. However, the role of CD137 in gastric cancer (GC), especially in inducing GC cell apoptosis, has not been studied. METHODS: Foxp3+ and CD8+ T cells in GCs were investigated using immunohistochemistry (IHC). CD137 expression in GCs was detected using flow cytometry, IHC and immunofluorescence (IF). Peripheral blood mononuclear cells (PBMCs) and CD8+ T cells isolated from peripheral blood were stimulated with a CD137 agonist in vitro. CD8+ T cell proliferation and p65 expression was examined using flow cytometry. P65 nuclear translocation was analyzed using IF. IL-10, TGF-ß, IFN-γ, perforin and granzyme B were detected using real-time quantitative PCR (real-time PCR). PBMCs and primary GC cells were cocultured and stimulated with a CD137 agonist in vitro. Apoptosis of primary GC cells was detected using flow cytometry. RESULTS: Our data demonstrated that GC tumors showed characteristics of an immunosuppressive microenvironment. CD137 was predominantly expressed in CD8+ T cells in GCs and had a positive correlation with tumor cell differentiation. The CD137 agonist promoted CD8+ T cell proliferation and increased the secretion of IFN-γ, perforin and granzyme B, which induced primary GC cell apoptosis. Mechanistically, this study found that the CD137 agonist induced NF-κB nuclear translocation in CD8+ T cells. CONCLUSION: Our results demonstrated that a CD137 agonist induced primary GC cell apoptosis by enhancing CD8+ T cells via activation of NF-κB signaling.

Anti-Proliferative and Apoptosis-Promoting Effect of microRNA-125b on Pancreatic Cancer by Targeting NEDD9 via PI3K/AKT Signaling.

PURPOSE: The expression of microRNA-125b (miR-125b) is low in a variety of cancers, including gastric, lung, bladder, thyroid, and esophageal cancers. However, its specific mechanism in pancreatic ductal adenocarcinoma (PDAC) remains unclear. This study is aimed to explore the role of miR-125b in PDAC. METHODS: PDAC tissues and adjacent tissues were collected for miR-125b analysis by qRT-PCR. Different PDAC cell lines were cultured for miR-125b detection by qRT-PCR, and CAPAN1 cells were selected for the downstream experiments. Cell proliferation was characterized by methyl thiazolyl tetrazolium (MTT) and 5-bromo-2-deoxyUridine (BrdU) staining. Flow cytometry was utilized for apoptosis and cell cycle changes. Cell invasion was determined by the Transwell assay and the dual-luciferase assay was utilized for validating the target gene. Western blotting was used to detect apoptosis related and PI3K/AKT signaling proteins. RESULTS: miR-125b was significantly down-regulated in human PDAC tissues and cell lines (P < 0.05). miR-125b inhibited the growth and invasion of CAPAN1 cells, facilitated apoptosis, and blocked the cell cycle at the G0/G1 phase. Furthermore, miR-125 directly targeted NEDD9. The high expression of NEDD9 impaired the anti-proliferative and anti-apoptotic activity of miR-125b. miR-125b also inhibited apoptosis-related proteins and PI3K/AKT signaling pathways via NEDD9. CONCLUSION: miR-125b decreased cell growth and invasion, and facilitated apoptosis in CAPAN1 cells through PI3K/AKT inhibition via targeting NEDD9.

6-gingerol alleviates inflammatory injury in DSS-induced ulcerative colitis mice by regulating NF-κB signaling.

BACKGROUND: The imbalance of Treg/Thl7 cells and inflammatory injury are believed to be involved in the development of ulcerative colitis (UC). Meanwhile, 6-gingerol has been reported to alleviate intestinal inflammatory damage in mice models, but the underlying mechanism remains elusive. METHODS: In this study, dextran sulfate sodium (DSS)-induced colitis mice models were established to examine the effects of 6-gingerol on IL-17 and IL-10 secretion, and the activation of NF-κB signaling was evaluated using enzyme-linked immunosorbent assay (ELISA), Western blotting, and immunohistochemistry. RESULTS: 6-gingerol could significantly reduce the weight loss caused by DSS in mice models (P<0.05), which is similar to the therapeutic drug, mesalazine. Immunohistochemistry showed that 6-gingerol can repair the damaged glandular structure gradually caused by DSS, significantly decrease the IL-17 level, and increase IL-10 level in bowel tissue. ELISA revealed that 6-gingerol could significantly decrease the IL17 level and increase IL-10 level in both serum and bowel tissue, and the differences were all statistically significant (P<0.05). In addition, 6-gingerol could suppress the phosphorylation level of IκBα and p65, which was up-regulated by DSS. Further analysis with immunohistochemistry indicated p-p65 staining was mainly in the nucleus with some in the cytoplasm after DSS treatment, and the treatment with 6-gingerol could significantly weaken the density of p-p65 both in the cytoplasm and nucleus. CONCLUSIONS: Our study suggests that 6-gingerol may alleviate inflammatory injury in UC mice by regulating NF-κB signaling pathway.

The effect of 6-gingerol on inflammatory response and Th17/Treg balance in DSS-induced ulcerative colitis mice.

BACKGROUND: Ulcerative colitis (UC) is a non-specific chronic intestinal inflammatory disease with unclear etiology. Previous studies have suggested that the imbalance of Treg/Thl7 cells may be involved in the development of UC. It was found that 6-gingerol can alleviate the intestinal inflammatory damage and improve the weight loss of colitis mice. However, whether 6-gingerol can regulate the balance of Th17/Treg cells and inhibit the intestinal inflammatory response remains to be clarified. METHODS: In this study, a dextran sulfate sodium (DSS)-induced colitis mouse model was established, and the effects of 6-gingerol on cytokines and the balance of Th17/Treg cells were observed usingserial assays, including enzyme-linked immunosorbent assay (ELISA), quantitative real time-polymerase chain reaction (qPCR), and Western blotting. RESULTS: DSS caused the damage of bowel tissue and a 100% weight loss rate in colitis mice. The treatment of 6-gingerol can significantly relieve bowel damage and reduce incidence of weight loss to 16.7% at a low or high dose (P<0.05), which was similar to the therapeutic effect of mesalazine. It was found that DSS can up-regulate the mRNA levels of IL-6 and IL-17 in serum (by qPCR), and the serum and bowel levels of IL-6 and IL-17 (by ELISA); these levels were significantly different from those of the blank group (P<0.05). Furthermore, 6-gingerol was found to inhibit the increase of mRNA levels and serum and bowel levels of IL-6 and IL-17 induced by DSS, which is similar with mesalazine. It was also found that DSS can down-regulate the mRNA level of IL-10 in serum, along with the serum and bowel level of IL-10, with this being significantly different from the levels of the blank group (P<0.05). 6-gingerol could also inhibit the decrease of mRNA levels and serum and bowel levels of IL-10 induced by DSS, which is also similar to mesalazine. In addition, DSS could increase Th17 cell count and decrease Treg cell count in blood, with significant difference from that of the blank group (P<0.05). 6-gingerol could significantly (P<0.05) inhibit the increase of Th17 cells and the decrease of Treg cells induced by DSS, which is similar to the effect of mesalazine. The detection of expression levels of transcription factors RORγT for Th17 and FOXP3 for Treg at both mRNA and protein levels showed that DSS can up-regulate the mRNA and protein levels of RORγT, and down-regulate the mRNA and protein levels of FOXP3. Furthermore, 6-gingerol could significantly (P<0.05) inhibit the up-regulation of RORγT mRNA and protein, and the down-regulation of FOXP3 mRNA and protein induced by DSS, which is similar to the effect of mesalazine. CONCLUSIONS: 6-gingerol showed efficacy in the treatment of DSS-induced UC in mice, by regulating the cell balance of Th17/Treg, and by relieving inflammatory responses both systematically and locally.

Correlation between Claudin-18 expression and clinicopathological features and prognosis in patients with gastric cancer.

BACKGROUND: To investigate the correlation between Claudin-18 expression and the clinicopathological features and prognosis of gastric cancer. METHODS: A total of 63 patients who underwent gastric cancer surgery from December 2012 to June 2013 were recruited as the research participants. The clinicopathological data and prognostic information of the participants were collected, and expression levels of Claudin-18 in gastric cancer and adjacent tissues were detected by immunohistochemical (IHC) staining. The correlation between Claudin-18 expression and clinicopathological features of gastric cancer patients was analyzed. The Cox regression model was used to analyze the risk factors associated with the prognosis of gastric cancer patients. RESULTS: The expression of Claudin-18 was positive in 35 (55.6%) of the participants' gastric cancer tissues, which was significantly lower than that in the adjacent tissues (51 tissues/81.0%), and the difference was statistically significant (P=0.002). In addition, the IHC staining score of Claudin-18 expression in gastric cancer tissues (1.49±1.69), was significantly lower than that in the adjacent tissues (4.61±1.81), and the difference was statistically significant (P=0.016), The incidence of nerve invasion in patients with low expression of Claudin-18 was significantly higher than that in patients with high expression of Claudin-18 (P=0.038). In addition, univariate Cox regression analysis showed that nerve invasion, Claudin-18 staining score, tumor size, and positive count of lymph nodes were risk factors associated with the survival of gastric cancer patients. Multivariate Cox regression analysis showed that Claudin-18 staining score and tumor size were independent risk factors associated with the survival of gastric cancer patients. The overall survival (OS) of patients with low Claudin-18 staining score or larger tumor size was significantly reduced. CONCLUSIONS: The low expression of Claudin-18 was closely related to nerve invasion in gastric cancer, which indicated the poor clinical prognosis of gastric cancer patients.

Expression of receptor interacting protein 3 and mixed lineage kinase domain-like protein-key proteins in necroptosis is upregulated in ulcerative colitis.

BACKGROUND: Ulcerative colitis (UC) is a chronic inflammatory colonic disease strongly associated with intestinal epithelial cell (IEC) death. Necroptosis is characterized by a newly programmed cell death through a caspase-independent pathway. Receptor interacting protein 3 (RIP3) and mixed lineage kinase domain-like protein (MLKL) are very important in the pathway of necroptosis. However, their expression in UC remains unelucidated. This study aimed to investigate the expression of RIP3 and MLKL in patients with UC, along with its correlation with disease activity. METHODS: Colonic tissue samples were taken from 22 UC patients and 19 healthy controls. RIP3 and MLKL expression levels were evaluated by immunohistochemical staining and western blotting. RESULTS: RIP3 and MLKL were upregulated in inflamed tissues of UC (P<0.01). No variations were observed in healthy control subjects and non-inflamed colons (P>0.05). RIP3 and MLKL were positively correlated with UC disease activity (P<0.01). CONCLUSIONS: Our results suggest that necroptosis is strongly associated with intestinal inflammation in patients with UC. Further studies of necroptosis may be helpful in future treatments of UC.

Silencing NEDD9 by lentivirus-delivered shRNA inhibits the growth of BxPC-3 cells in vitro and in vivo.

BACKGROUND: Neural precursor cell-expressed, developmentally downregulated protein 9 (NEDD9) is an invasion and metastasis-related gene. It has been proven to be highly expressed and closely associated with tumor proliferation and invasion in several types of human cancers including pancreatic adenocarcinoma. The present study was aimed to investigate and characterize the efficacy of silencing NEDD9 by lentivirus-delivered shRNA in pancreatic cancer (PC) BxPC-3 cells in vivo and in vitro. METHODS: Five kinds of PC cell lines were used to determine the cell line which expressed NEDD9 the most with qRT-PCR and western blotting. Then, we transduced the lentivirus-delivered NEDD9 shRNA into the human PC BxPC-3 cells to obtain a stable cell line expressing shRNA targeting NEDD9. NEDD9 mRNA and protein expression were measured by qRT-PCR and western blotting, respectively. Cell proliferation, migration, and invasion were assessed by cell colony formation, scratch wound healing, and Transwell assays, respectively. Mouse tumor xenografts were established by injecting tumor cells into the right flank of BALB/c nude mice. The effects of silencing NEDD9 on the growth of BxPC-3 cells in vivo were also examined. RESULTS: Among 5 kinds of PC cell lines, BxPC-3 cells were selected as the most suitab to carry out the following experiment. Transduction of lentivirus-delivered NEDD9 shRNA efficiently reduced NEDD9 expression in pancreatic adenocarcinoma BxPC-3 cells. Silencing NEDD9 by RNAi inhibited proliferation, migration, and invasion of BxPC-3 cells in cell culture. Importantly, it significantly reduced the growth of BxPC-3 cells in mouse xenografts. CONCLUSIONS: Silencing NEDD9 by lentivirus-delivered shRNA efficiently inhibited the growth of PC BxPC-3 cells both in vitro and in vivo, and may prove to be a potential new therapeutic agent for human PC.

NEDD9 expression is correlated with epithelial-to-mesenchymal transition markers in colorectal cancer.

The epithelial-to-mesenchymal transition (EMT) is a critical step in tumor metastasis. NEDD9 has been shown to be an oncogene in colorectal cancer. However, little is known about the relationship between NEDD9 and EMT in colorectal cancer metastasis. A total of 63 pairs of freshly frozen colorectal cancer tissues and adjacent noncancerous tissues were evaluated for NEDD9 gene expression using quantitative real-time PCR. The expression of NEDD9 and three epithelial-mesenchymal transition (EMT)-related proteins (E-cadherin, ß-catenin and vimentin) was examined in 122 colorectal cancers by immunohistochemistry. The expression of NEDD9 was markedly increased in colorectal cancer tissues compared with adjacent noncancerous tissues. The expression level of NEDD9 was positively correlated and TNM stage but not with other clinicopathological features of colorectal tumors. Furthermore, the expression of NEDD9 was strongly associated with the loss of epithelial marker E-cadherin and acquired expression of the mesenchymal markers nuclear ß-catenin and vimentin. These findings suggested that NEDD9 might promote EMT and the progression of colorectal cancer, and thus may be a potential therapeutic target of colorectal cancers.

DLC-1 is a candidate biomarker methylated and down-regulated in pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDA) is one of the most aggressive malignancies in humans, and its prognosis is generally poor even after surgery. Many advances have been made to understand the pathogenesis of PDA; however, the molecular mechanisms that lead to pancreatic carcinogenesis are still not clearly understood. The aims of this study were to investigate the relationship between DLC-1 methylation status and clinicopathological characteristics of PDA patients and evaluate the role of DLC-1 methylation status in PDA. The expression of DLC-1 mRNA in PDA tissues was analyzed by real-time PCR. The methylation status of DLC-1 was analyzed by methylation-specific polymerase chain reaction (MSP). Furthermore, we determined the prognostic importance of DLC-1 methylation status in PDA patients. Our results showed that the expression level of DLC-1 mRNA in PDA tissues was lower than that in non-cancerous tissues. The rate of DLC-1 promoter methylation was significantly higher in PDA tissues than in adjacent non-cancerous tissues (p < 0.001). Downregulation of DLC-1 was strongly correlated with promoter methylation (P = 0.003). The presence of DLC-1 methylation in PDA tissue samples was significantly correlated with clinical stage (P = 0.005), histological differentiation (P = 0.05), and lymph node metastasis (P = 0.006). Kaplan-Meier survival analysis showed that DLC-1 methylation status was inversely correlated with overall survival of the PDA patients. Further, Cox multivariate analysis indicated that DLC-1 methylation status was an independent prognostic factor for the overall survival rate of PDA patients. In conclusion, our data suggest that downregulation of DLC-1 may be explained by DNA methylation; DLC-1 may be a biomarker for PDA.