Interactions of oleanane pentacyclic triterpenoids with human organic anion transporting polypeptide 1B1 and 1B3.

Oleanane pentacyclic triterpenoids have been widely used in clinical practice. However, studies on their interactions with hepatic transporters remain limited. In this study, we systematically investigated the inhibitory effects of 14 oleanane pentacyclic triterpenoids on organic anion transporting polypeptide 1B1 and 1B3 (OATP1B1 and OATP1B3), two liver-specific uptake transporters. Through fluorescence-based cellular uptake assays, we identified three potent OATP1B1 inhibitors (saikosaponin B1, saikosaponin A and 18ß-glycyrrhetinic acid) and five potent OATP1B3 inhibitors (echinocystic acid, 3-oxo-16α-hydroxy-olean-12-en-28ß-oic acid, chikusetsu saponin IVa, saikosaponin B1 and 18ß-glycyrrhetinic acid). Structural analysis revealed that free oleanane triterpenoids inhibited OATP1B1/1B3 more potently than triterpene glycosides. Despite their similar structures, 18ß-glycyrrhetinic acid exhibited much stronger inhibition on OATP1B1/1B3 than 18α-glycyrrhetinic acid, while both were substrates of OATP1B3. Interestingly, OATP1B3 overexpression significantly increased reactive oxygen species (ROS) levels in HepG2 cells after treatment with 18ß-glycyrrhetinic acid. To conclude, this study highlights the potential interactions of oleanane pentacyclic triterpenoids with OATP1B1/1B3, and provides novel insights into the anti-cancer activity of 18ß-glycyrrhetinic acid.

Environmental Regulation in Evolution and Governance Strategies.

Environmental regulation faces theoretical and practical research challenges on global scale, due to differences such as language and policy environment. Research reflects the beneficial exploration of scholars, policymakers, and enterprises in the cognitive and behavioural norms of economic development, environmental protection, and social governance. This study demonstrated that the relevant research is motivated by the enaction of environmental regulations and discussed the influence of relevant research on the evolution of environmental regulations. Under the assumption that environmental regulations are consistent with related research, this study used 9185 papers in the field of environmental regulation from 2000 to 2019 to construct a research network panorama and explored the development and revelation of environmental regulation. The results revealed that environmental regulation research is motivated by the introduction of policies, and regulation is influenced by research evolution with the path of 'competitiveness-technological change-innovation.' In addition, after the twenty-first session of the Conference of the Parties (COP21), the number of studies increased significantly, with the USA in the leading position in the research field. Furthermore, governance strategies were inspired by real events, including the increasing concern with climate change, regional research preferences, and the promotion of information disclosure. These results suggest that environmental governors should focus on climate change, localisation, and mechanisms of information disclosure.

Trapping endoplasmic reticulum with amphiphilic AIE-active sensor via specific interaction of ATP-sensitive potassium (KATP).

The current aggregation-induced emission luminogens (AIEgens) sometimes suffer from poor targeting selectivity due to undesirable aggregation in the hydrophilic biosystem with 'always-on' fluorescence or unspecific aggregation in the lipophilic organelle with prematurely activated fluorescence. Herein, we report an unprecedented 'amphiphilic AIEgen' sensor QM-SO3-ER based on the AIE building block of quinoline-malononitrile (QM). The introduced hydrophilic sulfonate group can well control the specific solubility in a hydrophilic system with desirable initial 'fluorescence-off' state. Moreover, the incorporated p-toluenesulfonamide group plays two roles: enhancing the lipophilic dispersity, and behaving as binding receptor to the adenosine triphosphate (ATP)-sensitive potassium (KATP) on the endoplasmic reticulum (ER) membrane to generate the docking assay confinement effect with targetable AIE signal. The amphiphilic AIEgen has for the first time settled down the predicament of unexpected 'always-on' fluorescence in the aqueous system and the untargetable aggregation signal in the lipophilic organelle before binding to ER, thus successfully overcoming the bottleneck of AIEgens' targetability.