Investigating impact of CORDEX-based predicted climatic and LCM-based LULC scenarios on hydrologic response of a semi-gauged Indian catchment.

The present study aims at documenting the impact of different climate and land use change scenarios on runoff in the Kangsabati River basin. While the study relies on India Meteorological Department (IMD), National Oceanic and Atmospheric Administration's Physical Sciences Laboratory (NOAA-PSL), and a multi-model ensemble of six driving models from Coordinated Regional Downscaling Experiment-Regional Climate Models (CORDEX RCM) for climate data input, it depends on IDRISI Selva's Land Change Modeller (LCM) and Soil and Water Assessment Tool (SWAT) model to generate projected land use land change maps and simulate its streamflow response, respectively. A total of four land use and land cover (LULC) scenarios, representing four projected land use change, were modelled across three climatic scenarios, called Representative Concentration Pathways (RCPs). With runoff being predominantly impacted more by climate change than LULC, volumetric runoff is expected to be 12-46% higher than the baseline period of 1982-2017. Conversely, while surface runoff is expected to decrease by 4-28% in lower parts of the basin, it will increase by 2-39% in the rest of it, depending on the subtle alterations in land use and climatic variability.

Inhibition of cancer progression by a novel trans-stilbene derivative through disruption of microtubule dynamics, driving G2/M arrest, and p53-dependent apoptosis.

Resveratrol, a trans-stilbene polyphenolic compound and its synthetic analogs are widely used bioactive molecules due to their remarkable chemo-preventive potential. Here, we have identified a novel synthetic trans-stilbene compound, Z-DAN-11 ((Z)-3-(3, 4-dimethoxyphenyl)-2-(3, 4, 5-trimethoxyphenyl) acrylonitrile) which shows remarkable efficacy in blocking tumor growth and progression both in vitro and in vivo. Z-DAN-11 inhibits proliferation of cancer cells in vitro through microtubule depolymerization that induced G2/M arrest and consequently leads to apoptotic cell death. More importantly, Z-DAN-11 shows limited cytotoxicity to normal cells as compared to cancer cells. Quite interestingly, we have found that Z-DAN-11-mediated ROS production helps in dramatic alteration in the mitochondrial redox status which critically contributes to the apoptosis. Mechanistic studies reveal that Z-DAN-11 induces the expression of pro-apoptotic proteins and decreases anti-apoptotic protein expression that decisively helps in the activation of caspase 8, caspase 9, and caspase 3, leading to cleavage of PARP1 and cell death via intrinsic and extrinsic pathways of apoptosis. Moreover, Z-DAN-11-mediated apoptosis of cancer cells is through a partial p53-dependent pathway, since both HCT116 p53-/- cells as well as p53-silenced cells (siRNA) were able to block apoptosis partially but significantly. Importantly, Z-DAN-11 also imparts its anti-tumorigenic effect by inhibiting clonogenic property and anchorage-independent growth potential of cancer cells at concentrations at least 10 times lower than that required for inducing apoptosis. Finally, in vivo study with immuno-competent syngeneic mice shows Z-DAN-11 to be able to impede tumor progression without any adverse side-effects. Hence, we identified a novel, synthetic trans-stilbene derivative with anti-tumorigenic potential which might tremendously help in devising potential therapeutic strategy against cancer.