Epistemic community in transboundary river regime: a case study in the Mekong River Commission regarding mainstream hydropower development.

Despite the importance of transboundary water management, cooperation mechanisms are limited, especially in the case of Mekong River basin where environmental and social aspects are threatened by recent anthropogenic pressures like hydropower development. Existing transboundary mechanism such as the Mekong River Commission (MRC) is challenged to facilitate the cooperation between riparian states. An epistemic community (EC) is considered to effectively influence international governance and is studied as part of transboundary river regimes. The existence of an MRC EC is part of that regime but understanding about its characteristics is yet limited. This research aims to fill in the gap by unraveling the main features of the EC in relation to hydropower development. We analyze shared causal beliefs and policy goals that developed in the EC framework of Haas applying literature review and semi-structured interviews of experts. Results show that the community experts share causal beliefs and policy goals only to a limited extent while disagreeing on many aspects. It resembles a "disciplined" or "professional" group rather than an EC. This suggests that the knowledge factor has not gained proper influence and attention in the region, resulting in incoherent policy advice leading to policymakers developing policies based on incomplete and fragmented knowledge. The role of the MRC in the decision-making process could become more relevant if it would facilitate the development of an EC. Bringing key stakeholders including policymakers and experts into a platform where policy goals and causal beliefs are facilitated to reach possible consensus is recommended. Narrowing the science-policy gap while acknowledging differences in interests and policy objectives is crucial to reach a sustainable transboundary management of the Mekong River given its rapid development, especially on hydropower.

LPS-enhanced IGF-IIR pathway to induce H9c2 cardiomyoblast cell hypertrophy was attenuated by Carthamus tinctorius extract via IGF-IR activation.

The use of herbs as alternative cardiovascular disease treatment has attracted a great deal of attention owing to their lower toxicity. Whether Carthamus tinctorius extract prevent cardiomyoblast cell hypertrophy remains unclear. The present study was performed to investigate the effect of C tinctorius extract (CTF) on rat cardiomyoblast cell H9c2 and the possible molecular mechanisms. H9c2 cells were treated with lipopolysaccharide (LPS; 2 µg/mL) for 12 hours, subsequently treated with CTF (1-25 µg/mL) The incubation continued for another 24 hours, and the cells were analyzed with actin staining assay, western blot analysis, and siRNA transfection assays. In the present study, the increased cell size induced by LPS was significantly decreased by pretreating at a concentration of 1-25 µg/mL CTF. It was found that CTF could inhibit cardiac hypertrophy induced by LPS and decrease hypertrophic proteins calcineurin, p-GATA-4, GATA-4, atrial natriuretic peptide, and B-type natriuretic peptide levels in H9c2 cells. Additionally, LPS-induced insulin-like growth factor-II receptor (IGF-IIR) hypertrophy pathway was downregulated by CTF. Moreover, IGF-IR siRNA or inhibitors both reversed the CTF effects, confirming that CTF activates IGF-1R to prevent LPS-induced H9c2 cardiomyoblast cell hypertrophy. The current findings indicate that CTF activates IGF-IR to inhibit IGF-IIR signaling pathway which resulted in reducing H9c2 cardiomyoblast cell hypertrophy induced by LPS.

Novel hybrid models between bivariate statistics, artificial neural networks and boosting algorithms for flood susceptibility assessment.

Across the world, the flood magnitude is expected to increase as well as the damage caused by their occurrence. In this case, the prediction of areas which are highly susceptible to these phenomena becomes very important for the authorities. The present study is focused on the evaluation of flood potential within Trotuș river basin in Romania using six ensemble models created by the combination of Analytical Hierarchy Process (AHP), Certainty Factor (CF) and Weights of Evidence (WOE) on one hand, and Gradient Boosting Trees (GBT) and Multilayer Perceptron (MLP) on the other hand. A number of 12 flood predictors, 172 flood locations and 172 non-flood locations were used. A percentage of 70% of flood and non-flood locations were used as input in models. From the input data, 70% were used as training sample and 30% as validating sample. The highest accuracy was obtained by the MLP-CF model in terms of both training (0.899) and testing (0.889) samples. A percentage between 21.88% and 36.33% of study area is covered with high and very high flood potential. The results validation, performed through the ROC Curve method, highlights that the MLP-CF model provided the most accurate results.

Zanthoxylum avicennae extract enhances GSK-3ß to attenuate ß-catenin via phosphatase 2A to block metastatic effects of HA22T cells and hepatocellular carcinoma xenografted nude mice.

Hepatocellular carcinoma (HCC) metastasis is often associated with the activation of Wnt/ß-catenin signaling pathway. Zanthoxylum avicennae (Ying Bu Bo, YBB), a traditional herb with hepatoprotective effect, has been proven to inhibit human HCC in in vivo models however, the in vitro and in vivo effect of YBB on tumor metastasis is not clear yet. To determine whether YBB could inhibit HA22T human HCC cell by acting on ß-catenin metastatic signaling in vitro and in vivo, HA22T cells were treated with different concentrations of YBB extracts (YBBE) and analyzed by Immunofluorescence staining assay, western blot analysis, siRNA mediated gene knock-down assays and co-immunoprecipitation assay. Additionally, the HA22T-implanted xenograft nude mice were used to confirm the assessed cellular effects. Mice treated with YBBEs showed a strong increasing trend in PP2Acα, GSK-3ß, APC, and ß-TrCP/HOS levels, however the expression of ß-catenin, p-GSK-3ß, TBX 3, and IL8 proteins showed a decreasing trend. YBBE significantly downregulated the nuclear and cytosolic ß-catenin levels by facilitating the proteosomal degradation of ß-catenin. Moreover, as observed by co-immunoprecipitation assay, YBBE directly promoted the protein interactions between GSK-3ß, ß-TrCP, APC, PP2A, and ß-catenin. In conclusion, both in vitro and in vivo models clearly demonstrated that YBBE inhibits ß-catenin involved metastatic signaling in highly metastatic HA22T cells through PP2A activation.

Suppression of plasminogen activators and the MMP-2/-9 pathway by a Zanthoxylum avicennae extract to inhibit the HA22T human hepatocellular carcinoma cell migration and invasion effects in vitro and in vivo via phosphatase 2A activation.

This study shows that the ECM degradation-associated pathway, including uPA and tPA and the downstream MMP-2/-9 protein, was significantly suppressed in HA22T cells treated with a Zanthoxylum avicennae extract (YBBE). The endogenous inhibitors, including TIMP-1/-2 and PAI-1, were enhanced in HA22T cells by the YBBE treatment. The expression of MMP-2/-9 and TIMP-1/-2 was respectively assessed by using RT-PCR and a zymography assay. The mRNA levels and enzymatic activity of MMP-2/-9 were down-regulated by the YBBE treatment in a dose-dependent manner, while the TIMP-1/-2 levels were conversely markedly increased. The PP2A siRNA or PP2A inhibitor totally reversed the YBBE effects, confirming the essential role of PP2A in YBBE inhibiting the HA22T cell migration and invasion effects. Xenografted animal experiments on nude mice demonstrated similiar results to the in vitro system. Both the in vitro and in vivo models clearly demonstrate that YBBE inhibited the highly metastatic HA22T liver cancer cell migration and invasion effects through PP2A activation.

How the saline water intrusion has reshaped the agricultural landscape of the Vietnamese Mekong Delta, a review.

Once a key factor behind Vietnam's successful Doi Moi (restoration) economic reforms, the rice-centered agriculture of the VMD is now confronted by the new pressure of climate change impacts, including the intensifying salinity intrusion (SI). The SI menace has partly triggered the delta-wide emergence of new adaptive livelihood models across the VMD, including the prawn rice rotational crop (PRRC) that is arguably the most prominent. Research on the SI-driving factors is rapidly increasing in numbers, yet little synthesis has been done. Likewise, several studies have investigated the economic benefits of PRRC; less emphasis has placed on environmental and societal aspects, hence the questionable sustainability. This study, therefore, contributes a composite literature review, targeting two SI-related aspects: (i) key factors driving the intensification of SI in recent years across the Mekong Delta, and (ii) current understanding of the sustainability of PRRC. Results from the first review assignment highlight the four key SI-driving factors: riverbed incision, land subsidence, upstream dams, and sea-level rise. Also remarked are the critical absence of studies addressing multiple drivers and the need for a decoupling model to quantify the relative importance of each factor to strategize the adaptive measures. For PRRC, we reveal that while economic benefits have been widely reported, potential negative impacts of this model related to environmental and social aspects are lacking. Therefore, while the lucrative prawn trade might financially benefit the farmers', the economic benefit is marred by the underlying negative environmental impacts and social inequalities, limiting overall sustainability. This study also provides a case study to notify the spatial-temporal trends of PRRC in the last three decades and evaluate the associated geographical and social factors. Kien Giang province was selected as the study site since it is the largest PRRCacross the VMD. The lessons from Kien Giang can also be applied to other transformative agricultural models in both Mekong Delta and other deltas worldwide.

Intensifying saline water intrusion and drought in the Mekong Delta: From physical evidence to policy outlooks.

This paper assesses the recently intensified saline water intrusion (SI) and drought in the Vietnamese Mekong Delta (VMD). While the existing literature predominantly points the cause of drought to the hydropower dams in the upstream of the Mekong Basin, we contribute new physical evidence of the intensification of saline water intrusion (through backwater effect) in the VMD caused by three anthropogenic drivers: riverbed incision (due to both riverbed mining and dam construction), sea level rise and land subsidence. Thereupon, we highlight that it is critical to not underestimate the impacts from the localized factors, especially the riverbed-mining which can incise the channel by up to 15 cm/year and amplify the salinity intrusion. Our analysis is based on the extensive sets of hourly-to-daily hydrological time series from 11 gauge stations across the VMD. First, several signs of significantly increased tidal amplification (up to 66%) were revealed through the spectral analysis of the hourly water level data. This trend was further validated through the changes in slopes of the rating curves at the tidal zones, implying the relationships between the shift of the backwater effects on the rivers in VMD and the lowered water levels caused by the riverbed incision. Finally, we introduce a novel approach using the annual incision rates of the riverbed to compare four SI driving factors in terms of their relative contributions to the balance between fresh and saline water in the VMD.

Zanthoxylum avicennae extracts inhibit cell proliferation through protein phosphatase 2A activation in HA22T human hepatocellular carcinoma cells in vitro and in vivo.

Hepatocellular carcinoma is a common type of cancer that is usually associated with poor prognosis. In this study, we examined the in vitro and in vivo mechanisms of the traditional Vietnamese herb Zanthoxylum avicennae on the inhibition of HA22T human hepatocellular carcinoma cell proliferation. HA22T cells were treated with different concentrations of Zanthoxylum avicennae extracts (YBBEs) and analyzed with the MTT assay, western blot analysis, flow cytometry, siRNA transfection assays and co-immunoprecipitation assay. Additionally, the HA22T-implanted xenograft nude mouse model was applied to confirm the cellular effects. YBBEs showed a strong inhibition of HA22T cell viability in a dose-dependent manner and significantly reduced cell proliferation-related proteins as well as induced cell cycle arrest in the G2/M phase. Protein phosphatase 2A (PP2A) siRNA or okadaic acid totally blocked YBBE-mediated cell proliferation inhibition. In addition, an HA22T-implanted nude mouse model further confirmed that YBBEs inhibit HA22T tumor cell growth and downregulate the survival and cell cycle regulating proteins, as well as activate the PP2A protein. Our findings indicate that the inhibition of HA22T cell proliferation by YBBEs is mediated through PP2A activation.

PP2A mediates diosmin p53 activation to block HA22T cell proliferation and tumor growth in xenografted nude mice through PI3K-Akt-MDM2 signaling suppression.

Hepatocellular carcinoma is a common type of cancer with poor prognosis. This study examines the in vitro and in vivo mechanisms of diosmin on human hepato-cellular carcinoma HA22T cell proliferation inhibition. HA22T cells were treated with different diosmin concentrations and analyzed with Western blot analysis, MTT assay, wound healing, flow cytometry, siRNA transfection assays and co-immuno-precipitation assay. The HA22T-implanted xeno-graft nude mice model was applied to confirm the cellular effects. Diosmin showed strong HA22T cell viability inhibition in a dose dependent manner and significantly reduced the cell proliferative proteins as well as inducing cell cycle arrest in the G2/M phase through p53 activation and PI3K-Akt-MDM2 signaling pathway inhibition. However, protein phosphatase 2A (PP2A) siRNA or PP2A inhibitor totally reversed the diosmin effects. The HA22T-implanted nude mice model further confirmed that diosmin inhibited HA22T tumor cell growth and down regulated the PI3K-Akt-MDM2 signaling and cell cycle regulating proteins, as well as activating PP2A and p53 proteins. Our findings indicate that HA22T cell proliferation inhibition and tumor growth suppression by diosmin are mediated through PP2A activation.

Zanthoxylum avicennae extracts induce cell apoptosis through protein phosphatase 2A activation in HA22T human hepatocellular carcinoma cells and block tumor growth in xenografted nude mice.

The use of herbs as alternative cancer therapies has attracted a great deal of attention owing to their lower toxicity. Whether Zanthoxylum avicennae (Ying Bu Bo, YBB) induces liver cancer cell apoptosis remains unclear. In this study, we investigated the effect of YBB extracts (YBBEs) on HA22T human hepatocellular carcinoma cells in vitro and in an in vivo mouse xenograft model. HA22T cells were treated with different concentrations of YBBEs and analyzed with Western blot analysis, TUNEL, JC-1 staining and siRNA transfection assays. Additionally, the HA22T-implanted xenograft nude mice model was applied to confirm the cellular effects. YBBEs-induced apoptosis, up-regulated death receptor apoptotic pathway markers as well as mitochondrial proteins, and suppressed the survival proteins in a dose-dependent manner. Pro-survival Bcl-2 family proteins were inhibited and the pro-apoptotic ones were increased. Protein phosphatase 2A (PP2A) siRNA or okadaic acid reversed the YBBEs effects, confirming the role of PP2A in YBBEs-induced HA22T apoptosis. All our experimental evidence indicates that YBBEs significantly promote HA22T apoptosis and reduce tumor sizes in xenograft nude mice via PP2A in a dose-dependent manner.