Discovery of Natural Potent HMG-CoA Reductase Degraders for Lowering Cholesterol.

Exploitation of key protected wild plant resources makes great sense, but their limited populations become the major barrier. A particular strategy for breaking this barrier was inspired by the exploration of a resource-saving fungal endophyte Penicillium sp. DG23, which inhabits the key protected wild plant Schisandra macrocarpa. Chemical studies on the cultures of this strain afforded eight novel indole diterpenoids, schipenindolenes A-H (1-8), belonging to six diverse skeleton types. Importantly, semisyntheses suggested some key nonenzymatic reactions constructing these molecules and provided targeted compounds, in particular schipenindolene A (Spid A, 1) with low natural abundance. Remarkably, Spid A was the most potent HMG-CoA reductase (HMGCR) degrader among the indole diterpenoid family. It degraded statin-induced accumulation of HMGCR protein, decreased cholesterol levels and acted synergistically with statin to further lower cholesterol. Mechanistically, transcriptomic and proteomic profiling suggested that Spid A potentially activated the endoplasmic reticulum-associated degradation (ERAD) pathway to enhance the degradation of HMGCR, while simultaneously inhibiting the statin-activated expression of many key enzymes in the cholesterol and fatty acid synthesis pathways, thereby strengthening the efficacy of statins and potentially reducing the side effects of statins. Collectively, this study suggests the potential of Spid A for treating cardiovascular disease.

Chemical Constituents of Species in the Genus Pleione (Orchidaceae) and the Implications from Molecular Phylogeny.

Pleiones are popular ornamental orchids and different species of Pleione are long being used as traditional medicine in many Asian countries. However, previous chemical investigations of the genus Pleione are restricted to only a few species. In the present study, high performance liquid chromatography (HPLC) fingerprint of Pleione plants was established, which in particular, eight common peaks were confirmed in 16 species/hybrids. Three of the compounds corresponding to the chromatographic peaks were identified by electrospray ionization tandem mass spectrometry (ESI-tandem-MS). HPLC analysis confirmed the studied taxa shared most of chemical compounds but the content of chemical compounds was significantly different between species. Comparison of hierarchical clustering result with phylogenetic tree revealed that closely related species have higher similarities in chemical constituents. In consideration of low chemical similarity between spring-flowering and autumn-flowering species, we suggest a discrimination of these two groups during medicinal use of the genus Pleione. Species with a large pseudobulb and with high content of a certain compound should be given priority in future artificial cultivation and medicinal cultivar breeding. We hope our findings will contribute to the quality control and promote conservation of such endangered plant group.

Entropically driven formation of ultralong helical mesostructured organosilica nanofibers.

Ultralong helical organosilica nanofibers (length up to millimeter) with ordered helical mesoporous channels are synthesized using achiral cationic surfactant as single-structure-directing agent and anionic citrate as counterions. The surfactant molecules form micelles for silica condensation and the counterions reduce the polarity of the surfactant-silicate micelles via electrostatic balance, leading to the self-assembly and growth of the final product. The detailed mechanistic shape-shifting studies reveal that an entropy increase is the main driving force behind the plastic deformation of the solids.

Multifunctional Co0.85Se/graphene hybrid nanosheets: controlled synthesis and enhanced performances for the oxygen reduction reaction and decomposition of hydrazine hydrate.

Ultrathin nanosheets possess novel electronic structures and physical properties as compared with their corresponding bulk samples. However, the controlled synthesis of ultrathin monolayer nanosheets still remains a great challenge due to the lack of an intrinsic driving force for anisotropic growth of two-dimensional (2D) structures. Here we demonstrate, for the first time to our knowledge, the in situ synthesis of large-scale ultrathin single-crystalline Co0.85Se nanosheets on graphene oxide (GO) sheets, with a thickness of 3 nm. Owing to the synergetic chemical coupling effects between GO and Co0.85Se, the Co0.85Se/graphene hybrid nanosheets exhibit the highest catalytic performance among the available cobalt chalcogenide-based catalysts for the oxygen reduction reaction (ORR). Moreover, Co0.85Se/graphene hybrid nanosheets can catalyze the decomposition of hydrazine hydrate rapidly, with 97% of hydrazine hydrate being degraded in 12 min and the degradation rate remaining constant over 10 consecutive cycles, thus having great potential as long-term catalysts in wastewater treatment.

Dodecahedral Au@Pd nanocrystals with high-index facets and excellent electrocatalytic activity and highly efficient surface-enhanced Raman scattering enhancement.

We synthesize the three-fold symmetric shield-like Au@Pd core-shell nanocrystals, enclosed predominantly by high-index {541} facets with kinks, through the simultaneous reduction of Au and Pd ions in the presence of triangular Au nanocrystal seeds in aqueous solution at room-temperature. The obtained shield-like Au@Pd core-shell nanocrystals exhibit superior electrocatalytic activity for the oxidation of ethanol and unique near-field enhancement property with a highly sensitive surface-enhanced Raman scattering (SERS) response. These excellent properties can be ascribed to the presence of sharp corners and edges as well as high-index faceted Pd-rich shell in the shield-like Au@Pd core-shell structure. We also investigate the mechanism for the formation of three-fold symmetric shield-like Au@Pd core-shell nanocrystals.

Controlled growth of concave gold nanobars with high surface-enhanced Raman-scattering and excellent catalytic activities.

Highly monodispersed concave gold nanobars with 24 high-index {730} facets are synthesized through a seed-mediated growth in aqueous solution. The transformation from the truncated rectangular nanobars to rectangular nanobars, then transitional products, and final concave rectangular nanobars is observed with the fine control of silver nitrate in the growth solution, and their corresponding transverse surface plasmons can be well tuned, too. These concave gold nanobars exhibit good optical property, excellent catalytic activity, and high surface-enhanced Raman-scattering (SERS) response.

Highly branched concave Au/Pd bimetallic nanocrystals with superior electrocatalytic activity and highly efficient SERS enhancement.

Superstar: branched concave Au/Pd bimetallic nanocrystals were synthesized in high yield by seed-mediated co-reduction of Au and Pd metal precursors in an aqueous solution at room temperature. The branches are concave and have high-index facets on their surfaces. These nanocrystals show superior electrocatalytic activity for the oxidation of ethanol and highly efficient SERS enhancement.

Novel CeO2 yolk-shell structures loaded with tiny Au nanoparticles for superior catalytic reduction of p-nitrophenol.

Direct fabrication of core-shell or yolk-shell functional nanomaterials via a facile template-free method remains a challenge. In this work, we present a novel approach that involves straightforward chemical transformation and thermal treatment of the infinite coordination polymer particles to obtain composition-tunable CeO(2) yolk-shell structures. Uniform CeO(2) yolk-shell hollow spheres with a high surface area are promising support materials for tiny gold nanoparticles (ca. 4 nm), forming Au-CeO(2) nanocomposites which exhibit a remarkable catalytic activity and high stability for the reduction of p-nitrophenol. A possible mechanism for the formation of CeO(2) yolk-shell microspheres is also proposed.

Facile synthesis of concave decahedra enclosed by high-index facets and truncated decahedra with a large size.

Nanostructures with concave surfaces are not common, and their synthesis is still challenging. In this paper, we have successfully synthesized two kinds of five-fold-twinned Au decahedra and dodecagonal plates by changing the reaction conditions. 40 high-index {221} facets were observed in the concave decahedron. The truncated decahedral gold nanocrystals (NCs) with a large size of 250-350 nm were obtained for the first time, which breaks the assumption that the truncated five-fold-twinned Au nanoparticles (NPs) can only be obtained with a size below 5 nm. The growth mechanism and the evolution process of the gold nanostructures were discussed. This work provides a facile way to synthesize concave decahedra, truncated decahedra and dodecagonal plates with controlled nanostructures.