How does central-local interaction affect local environmental governance? Insights from the transformation of central environmental protection inspection in China.

In recent years, one of the most important and innovative policy initiatives introduced by the Chinese government in the field of environmental protection and ecological civilization construction is the Central Environmental Protection Inspection (CEPI). CEPI is seen as a vital tool to encourage local implementation of environmental protection responsibility. Over the course of its operation (eight years), CEPI has transformed from the "campaign" phase to the "convention" phase. It is noted that while provincial governments face a common high-pressure environment created by CEPI, governance scenarios, behaviors, and performance vary across the country significantly. To better understand local governments' environmental governance behaviors under the transformation of CEPI, an integrated analysis framework consisting of two key elements, "central dominance" and "local proactiveness", is constructed based on the central-local interactions under the principal-agent model. Based on this framework, we conducted a multi-case comparative analysis of four classic cases, with the following findings. (1) Along with the operation of CEPI and its transformation, the interaction between the central and local governments leads to four governance scenarios: "control-active cooperation", "control-passive cooperation", "guidance-active promotion", and "guidance-passive promotion". (2) Influenced by various factors such as pressure by the central government, local governments' capabilities and governance motivations, local governments form governance behaviors with varying degrees of proactiveness and autonomy. (3) After examining the governance performance of varying behaviors, it is found that local government's "active promotion" behavior can achieve higher governance effectiveness in the "convention" phase. Therefore, it is of policy implication that local governments should be guided to transit from "passive cooperation" to "active promotion". This paper has important guiding significance for understanding local environmental governance behaviors under strong top-down institutional pressure.

Inhibiting NF-κB-S100A11 signaling and targeting S100A11 for anticancer effects of demethylzeylasteral in human colon cancer.

Colon cancer is a common and deadly malignancy of the gastrointestinal tract. Targeting proteins that inhibit tumor proliferation could lead to innovative treatment strategies for this disease. Demethylzeylasteral, extracted naturally from Tripterygium wilfordii Hook. f., demonstrates incredible anti-colon cancer activity. However, the molecular mechanism behind this requires further investigation. This study aims to identify crucial targets and mechanisms of demethylzeylasteral in treating colon cancer, making it a promising candidate for anti-tumor therapy. Through gene knockout, overexpression techniques, and double Luciferase experiments, we confirmed that demethylzeylasteral reduces S100A11 expression in HT29 cells and in vivo tumor models to anti-colon cancer. By conducting Surface Plasmon Resonance, immunofluorescence staining, and confocal laser microscopy observations, we verified the direct interaction between demethylzeylasteral and S100A11, and explored the impact of S100A11's subcellular localization on cell proliferation. Demethylzeylasteral inhibited S100A11 expression and exhibited anti-cancer activity in both in vitro and in vivo colon cancer models. Conversely, overexpression of S100A11 hindered apoptosis induced by demethylzeylasteral. Additionally, we found that knockdown or overexpression of NF-κB respectively decreased or increased S100A11 expression, subsequently affecting cell proliferation. The dual Luciferase reporting experiment revealed that NF-κB is an upstream transcription factor regulating S100A11 expression. And Surface plasmon resonance confirmed that S100A11 can directly interact with demethylzeylasteral, this interaction limited the transport of S100A11 from the cytoplasm to nucleus, attenuation S100A11 mediated cell proliferation effect.

Microbial Transformation of Yakuchinone A and Cytotoxicity Evaluation of Its Metabolites.

Yakuchinone A (1) is a bioactive diarylheptanoid isolated from the dried fruits of Alpinia oxyphylla. Microbial transformation has been recognized as an efficient method to produce new biologically active derivatives from natural products. In the present study, microbial transformation of yakuchinone A was performed with the fungus Mucor hiemalis KCTC 26779, which led to the isolation of nine new metabolites (2, 3a, 3b, and 4-9). Their structures were elucidated as (3S)-oxyphyllacinol (2), (3S,7R)- and (3S,7S)-7-hydroxyoxyphyllacinol (3a and 3b), (3S)-oxyphyllacinol-4'-O-ß-d-glucopyranoside (4), (3S)-4″-hydroxyoxyphyllacinol (5), (3S)-3″-hydroxyoxyphyllacinol (6), (3S)-2″-hydroxyoxyphyllacinol (7), (3S)-2″-hydroxyoxyphyllacinol-2″-O-ß-d-glucopyranoside (8), and (3S)-oxyphyllacinol-3-O-ß-d-glucopyranoside (9) based on the comprehensive spectroscopic analyses and the application of modified Mosher's method. All compounds were evaluated for their cytotoxic activities against melanoma, as well as breast, lung, and colorectal cancer cell lines. Compound 9, which was O-glucosylated on the diarylheptanoid alkyl chain, exhibited the most selective cytotoxic activities against melanoma cell lines with the IC50 values ranging from 6.09 to 9.74 µM, indicating that it might be considered as a possible anti-cancer lead compound.

Effects of Microbial Transformation on the Biological Activities of Prenylated Chalcones from Angelica keiskei.

Microbial transformation is an alternative method for structural modification. The current study aimed at application of microbial transformation for discovering new derivatives and investigating the structure-activity relationship of isobavachalcone (1), 4-hydroxyderricin (2), and xanthoangelol (3) isolated from the herb Angelica keiskei. In the initial screening process, 1-3 were incubated with microbes using a two-stage fermentation method and analyzed through TLC monitoring. The screening results showed that Rhizopus oryzae and Mucor hiemalis were able to transform 1 and 2, respectively. Additionally, M. hiemalis and Mortierella ramanniana var. angulispora were able to transform 3. Following scale-up fermentation, four new (4, 5, 7, and 10) and five known (6, 8, 9, 11, and 12) metabolites were produced. Cytotoxicity of all the compounds (1-12) was investigated using three human cancer cell lines including A375P, HT-29, and MCF-7 by MTT method. Meanwhile, the tyrosinase inhibitory activity of 1-12 was evaluated using l-tyrosine as a substrate. Overall, 1 and 3 displayed the highest cytotoxicity, and 5 and 7 exhibited the most potent tyrosinase inhibitory activity with relatively low cytotoxicity. This allowed us to postulate that the introduction of 4'-O-glucopyranosyl group led to the reduction in cytotoxicity and improvement in tyrosinase inhibitory activity.

Biotransformation of the Phenolic Constituents from Licorice and Cytotoxicity Evaluation of Their Metabolites.

Biotransformation of four bioactive phenolic constituents from licorice, namely licoisoflavanone (1), glycyrrhisoflavone (2), echinatin (3), and isobavachalcone (4), was performed by the selected fungal strain Aspergillus niger KCCM 60332, leading to the isolation of seventeen metabolites (5-21). Structures of the isolated compounds were determined on the basis of extensive spectroscopic methods, twelve of which (5-7, 10-17 and 19) have been previously undescribed. A series of reactions including hydroxylation, hydrogenation, epoxidation, hydrolysis, reduction, cyclization, and alkylation was observed in the biotransformation process. All compounds were tested for their cytotoxic activities against three different human cancer cell lines including A375P, MCF-7, and HT-29. Compounds 1 and 12 exhibited most considerable cytotoxic activities against all the cell lines investigated, while compounds 2 and 4 were moderately cytotoxic. These findings will contribute to expanding the chemical diversity of phenolic compounds, and compounds 1 and 12 may serve as leads for the development of potential cancer chemopreventive agents.

Microbial Conjugation Studies of Licochalcones and Xanthohumol.

Microbial conjugation studies of licochalcones (1-4) and xanthohumol (5) were performed by using the fungi Mucor hiemalis and Absidia coerulea. As a result, one new glucosylated metabolite was produced by M. hiemalis whereas four new and three known sulfated metabolites were obtained by transformation with A. coerulea. Chemical structures of all the metabolites were elucidated on the basis of 1D-, 2D-NMR and mass spectroscopic data analyses. These results could contribute to a better understanding of the metabolic fates of licochalcones and xanthohumol in mammalian systems. Although licochalcone A 4'-sulfate (7) showed less cytotoxic activity against human cancer cell lines compared to its substrate licochalcone A, its activity was fairly retained with the IC50 values in the range of 27.35-43.07 µM.

Microbial Transformation of Broussochalcones A and B by Aspergillus niger.

Broussochalcones A (BCA, 1) and B (BCB, 2) are major bioactive constituents isolated from Broussonetia papyrifera, a polyphenol-rich plant belonging to the family Moraceae. Due to their low yields from natural sources, BCA (1) and BCB (2) were prepared synthetically by employing Claisen-Schmidt condensation, and these were used as substrates for microbial transformation to obtain novel derivatives. Microbial transformation of BCA (1) and BCB (2) with the endophytic fungus Aspergillus niger KCCM 60332 yielded 10 previously undescribed chalcones (1a-1e and 2a-2e). Their structures were established based on the spectroscopic methods. The cytotoxicity of BCA (1), BCB (2), and their metabolites (1a-1e and 2a-2e) was determined by human cancer cell lines A375P, A549, HT-29, MCF-7, and HepG2, with 1e shown to be most cytotoxic.

Microbial Transformation of Prenylquercetins by Mucor hiemalis.

Quercetin, one of the most widely distributed flavonoids, has been found to show various biological activities including antioxidant, anticancer, and anti-inflammatory effects. It has been reported that bioactivity enhancement of flavonoids has often been closely associated with nuclear prenylation, as shown in 8-prenylquercetin and 5'-prenylquercetin. It has also been revealed in many studies that the biological activities of flavonoids could be improved after glucosylation. Three prenylated quercetins were prepared in this study, and microbial transformation was carried out in order to identify derivatives of prenylquercetins with increased water solubility and improved bioavailability. The fungus M. hiemalis was proved to be capable of converting prenylquercetins into more polar metabolites and was selected for preparative fermentation. Six novel glucosylated metabolites were obtained and their chemical structures were elucidated by NMR and mass spectrometric analyses. All the microbial metabolites showed improvement in water solubility.

Microbial Transformation of Licochalcones.

Microbial transformation of licochalcones B (1), C (2), D (3), and H (4) using the filamentous fungi Aspergillus niger and Mucor hiemalis was investigated. Fungal transformation of the licochalcones followed by chromatographic separations led to the isolation of ten new compounds 5-14, including one hydrogenated, three dihydroxylated, three expoxidized, and three glucosylated metabolites. Their structures were elucidated by combined analyses of UV, IR, MS, NMR, and CD spectroscopic data. Absolute configurations of the 2″,3″-diols in the three dihydroxylated metabolites were determined by ECD experiments according to the Snatzke's method. The trans-cis isomerization was observed for the metabolites 7, 11, 13, and 14 as evidenced by the analysis of their 1H-NMR spectra and HPLC chromatograms. This could be useful in better understanding of the trans-cis isomerization mechanism of retrochalcones. The fungal transformation described herein also provides an effective method to expand the structural diversity of retrochalcones for further biological studies.

Microbial transformation of quercetin and its prenylated derivatives.

The microbial transformation studies of 7-O-prenylquercetin (1), 4'-O-prenylquercetin (2) and quercetin (3) were investigated with 20 different microbial strains to discover new metabolites. It was revealed that the fungus Mucor hiemalis was the most appropriate micro-organism which was capable of transforming these flavonoids. Structures of the three new (4-6) and one known (7) metabolites were elucidated as 7-O-prenylquercetin 3-O-ß-D-glucopyranoside (4), 4'-O-prenylquercetin 3-O-ß-D-glucopyranoside (5), 4'-O-prenylquercetin 3'-O-ß-D-glucopyranoside (6) and quercetin 5-O-ß-D-glucopyranoside (7) by the spectroscopic methods.

Microbial transformation of naringenin derivatives.

Microbial transformations of (±)-7-O-prenylnaringenin (7-PN, 1) and (±)-7-O-allylnaringenin (7-AN, 2) have isolated four metabolites (3-6). Structures of these novel compounds were identified as 5,4'-dihydroxy-7-O-[(2E)-4-hydroxy-3-methyl-2-buten-1-yl]flavanone (3), 5,4'-dihydroxy-7-O-(2,3-dihdroxy-3-methylbutyl)flavanone (4), 5,4'-dihydroxy-7-O-(2,3-dihdroxypropyl)flavanone (5), and 5-O-ß-D-glucopyranosyl-7-O-allyl-4'-hydroxyflavanone (6) based on spectroscopy. Compounds 1-6 were evaluated for their radical scavenging capacity using DPPH (2,2-diphenyl-1-picrylhydrazyl). The derivatives 3-6 exhibited more potent antioxidant activity than their corresponding substrates 1 and 2.

'BRICS without straw'? A systematic literature review of newly emerging economies' influence in global health.

BACKGROUND: Since 2010, five newly emerging economies collectively known as 'BRICS' (Brazil, India, Russia, China and South Africa) have caught the imagination, and scholarly attention, of political scientists, economists and development specialists. The prospect of a unified geopolitical bloc, consciously seeking to re-frame international (and global) health development with a new set of ideas and values, has also, if belatedly, begun to attract the attention of the global health community. But what influence, if any, do the BRICS wield in global health, and, if they do wield influence, how has that influence been conceptualized and recorded in the literature? METHODS: We conducted a systematic literature review in (March-December 2012) of documents retrieved from the databases EMBASE, PubMed/Medline, Global Health, and Google Scholar, and the websites of relevant international organisations, research institutions and philanthropic organisations. The results were synthesised using a framework of influence developed for the review from the political science literature. RESULTS: Our initial search of databases and websites yielded 887 documents. Exclusion criteria narrowed the number of documents to 71 journal articles and 23 reports. Two researchers using an agreed set of inclusion criteria independently screened the 94 documents, leaving just 7 documents. We found just one document that provided sustained analysis of the BRICS' collective influence; the overwhelming tendency was to describe individual BRICS countries influence. Although influence was predominantly framed by BRICS countries' material capability, there were examples of institutional and ideational influence - particularly from Brazil. Individual BRICS countries were primarily 'opportunity seekers' and region mobilisers but with potential to become 'issue leaders' and region organisers. CONCLUSION: Though small in number, the written output on BRICS influence in global health has increased significantly since a similar review conducted in 2010 found just one study. Whilst it may still be 'early days' for newly-emerging economies influence in global health to have matured, we argue that there is scope to further develop the concept of influence in global health, but also to better understand the ontology of groups of countries such as BRICS. The BRICS have made a number of important commitments towards reforming global health, but if they are to be more than a memorable acronym they need to start putting those collective commitments into action. Keywords BRICS, global health, influence, newly emerging economies, Brazil, Russia, India, China, South Africa.