Circular Dichroism Spectroscopy Study of Crystalline‐to‐Amorphous Transformation in Chiral Platinum(II) Complexes

Two couples of enantiomeric platinum(II) complexes: Pt(L_1a)Cl ( 1a ), Pt(L_1b)Cl ( 1b ) and Pt(L_1a)(C ≡ C ? Ph) ( 2a ), Pt(L_1b)(C ≡ C ? Ph) ( 2b ) (L_1a = (+)‐1,3‐di‐(2‐(4,5‐pinene)pyridyl)benzene, L_1b = (?)‐1,3‐di‐(2‐(4,5‐pinene)pyridyl)benzene) were synthesized and characterized. Their absolute configurations were determined by single crystal X‐ray diffraction and further verified by circular dichroism (CD) spectra (including electronic circular dichroism [ECD] and vibrational circular dichroism [VCD]). These complexes show interesting mechanoluminescence and/or vapoluminescence due to crystalline‐to‐amorphous transformation. The crystalline solids, grinding‐induced amorphous powders, and vapor‐induced amorphous powders of complexes 2a and 2b were comparatively investigated by solid‐state ECD and VCD spectra. The transformation from crystalline solids to amorphous powders was accompanied by significant variances of the spectral feature in both ECD and VCD spectra. Chirality 25:384–392, 2013. © 2013 Wiley Periodicals, Inc.     

Ostericum atropurpureum sp. nov. (Apiaceae) from Zhejiang,China

Ostericum atropurpureum G. Y. Li, G. H. Xia & W. Y. Xie (Apiaceae, Apioideae) from Zhejiang, China, is described and illustrated. It is closely related to O. huadongense Z. H. Pan & X. H. Li and O. sieboldii (Miquel) Nakai, but differs in having leaves with 1.5–9.0 cm long petiole, linear bracteoles 6–12 mm long, 5–9 rays, 7–14‐flowered umbellules, dark purple petals, broadly winged dorsal and lateral fruit ribs, 1.0–1.5 mm broad, 3–6 vittae in each furrow and 4–8 on the commissure.     

Novel technique for internal structure and elemental distribution analyses of granular sludge from reactors for wastewater treatment

A novel technique for internal structure and elemental distribution analyses of granular sludge is presented. Sludge samples were freeze-dried and embedded in epoxy resin to form a module, which were then ground and polished to obtain sequential cross-sections. The cross-sections were analyzed by scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy (EDX). SEM observations showed that one granule was formed having several cores with different inorganic minerals, rather than a single core. EDX results indicate that the main elements of the granules are O, Ca, Mg, and P. In addition, the distribution areas of calcium and magnesium in the granule do not coincide.     

miR‐10a restores human mesenchymal stem cell differentiation by repressing KLF4

miRNAs have recently been shown to play a significant role in human aging. However, data demonstrating the effects of aging‐related miRNAs in human mesenchymal stem cells (hMSCs) are limited. We observed that hMSC differentiation decreased with aging. We also identified that miR‐10a expression was significantly decreased with age by comparing the miRNA expression of hMSCs derived from young and aged individuals. Therefore, we hypothesized that the downregulation of miR‐10a may be associated with the decreased differentiation capability of hMSCs from aged individuals. Lentiviral constructs were used to up‐ or downregulate miR‐10a in young and old hMSCs. Upregulation of miR‐10a resulted in increased differentiation to adipogenic, osteogenic, and chondrogenic lineages and in reduced cell senescence. Conversely, downregulation of miR‐10a resulted in decreased cell differentiation and increased cell senescence. A chimeric luciferase reporter system was generated, tagged with the full‐length 3′‐UTR region of KLF4 harboring the seed‐matched sequence with or without four nucleotide mutations. These constructs were cotransfected with the miR‐10a mimic into cells. The luciferase activity was significantly repressed by the miR‐10a mimic, proving the direct binding of miR‐10a to the 3′‐UTR of KLF4. Direct suppression of KLF4 in aged hMSCs increased cell differentiation and decreased cell senescence. In conclusion, miR‐10a restores the differentiation capability of aged hMSCs through repression of KLF4. Aging‐related miRNAs may have broad applications in the restoration of cell dysfunction caused by aging. J. Cell. Physiol. 228: 2324–2336, 2013. © The Authors. Published by Wiley Periodicals, Inc.     

Overexpression of acetyl-CoA synthetase increased the biomass and fatty acid proportion in microalga Schizochytrium

High acetate accumulation was produced during glucose fermentation in high cell density cultures, which is harmful to cell growth. In order to reduce the negative impact of acetate accumulation on the fermentation products, we introduced the Escherichia coli acetyl-CoA synthetase (ACS) gene into the marine microalga Schizochytrium sp. TIO1101, generating genetically modified ACS transformants. The results of PCR and blotting analyses showed that the exogenous ACS gene was incorporated into the genome and successfully expressed. The engineered Schizochytrium increased the pH value and reduced the acetate concentration in the final fermentation medium significantly. Furthermore, the ACS transformants exhibited faster growth and glucose consumption rates than the wild-type strain. The biomass and fatty acid proportion of ACS transformants increased by 29.9 and 11.3 %, respectively. Taken together, the data suggest that ACS overexpression in Schizochytrium might improve the utilization of carbon resource and decrease the production of acetate byproduct. These results demonstrate that application of ACS in metabolic genetic engineering could improve the properties of Schizochytrium significantly.     

Sex steroid changes during temperature‐induced gonadal differentiation in Paralichthys olivaceus (Temminck & Schegel, 1846)

Sex steroid changes during temperature‐induced gonadal differentiation were evaluated in the olive flounder, Paralichthys olivaceus. Larvae were reared at 21 ± 0.5°C, 24 ± 0.5°C and 28 ± 0.5°C from day 40 post‐hatching (dph) to 90 dph. The proportion of males was 61.1, 76.7, 87.8 and 47.8% in 21°C, 24°C, 28°C and in control groups, respectively. Gonadal differentiation was circa 65 dph, when fishes were a mean 39 mm total length (TL). The gonads developed faster when fishes were reared in higher temperatures. Radioimmunoassay (RIA) analyses indicated that the level of estradiol‐17β (E2) changed during the period of gonadal differentiation and peaked at an onset of ovarian differentiation in all groups. Compared with fish in control groups, the levels of E2 were lower in thermal‐treated groups, especially in the highest temperature groups. The present results indicate that E2 plays a major role in the process of ovarian differentiation, and suggest that temperature‐induced masculinization in P. olivaceus is mainly due to a decrease in the E2 level during the period of ovarian differentiation.     

De novo design of novel DNA–gyrase inhibitors based on 2D molecular fingerprints

As increasing drug-resistance poses an emerging threat to public health, the development of novel antibacterial agents is critical. We developed a workflow consisting of various methods for de novo design. In the workflow, 2D-QSAR model based on molecular fingerprints was constructed to extract the bioactive molecular fingerprints from a data set of DNA–gyrase inhibitors with new structure and mechanism. These fingerprints were converted into molecular fragments which were recombined to generate compound library. The new compound library was virtually screened by LigandFit and Gold docking, and the results were further investigated by pharmacophore validation and binding mode analysis. The workflow successfully achieved a potential DNA–gyrase inhibitor. It could be applied to design more novel potential DNA–gyrase inhibitors and provide theoretical basis for further optimization of the hit compounds.     

Design and bio-evaluation of indole derivatives as potent Kv1.5 inhibitors

Atrial fibrillation (AF) is one of the common arrhythmias that threaten human health. Kv1.5 potassium channel is reported as an efficacious and safe target for the treatment of AF. In this paper, we designed and synthesized three series of compounds through modifying the lead compound RH01617 that was screened out by the pharmacophore model we reported earlier. All of the compounds were evaluated by the whole-patch lamp technology and most of them possessed potent inhibitory activities against Kv1.5. Compounds IIIi and IIIl were evaluated for the target selectivity as well as the pharmacodynamic effects in an isolated rat model. Due to the promising pharmacological behavior, compound IIIl deserves further pharmacodynamic and pharmacokinetic evaluations.