Synthesis and evaluation of 1,4-diphenylbutadiene derivatives as inhibitors of plasminogen activator inhibitor-1 (PAI-1) production

Butadiene-imide 1 (T-686) derivatives were synthesized and evaluated for their inhibitory activity against PAI-1 production and their ADMET (DMPK and toxicology) profiles. Among these derivatives, compound 15k (T-2639) showed good antithrombotic activity in two rat thrombosis models without affecting bleeding time, indicating reduction of haemorrhagic risk. We also describe in this report a practical synthesis of 15k suitable for scale-up using Z,E-selective Stobbe condensation.     

溶菌酶及其分子改造研究进展

溶菌酶是一种优异的天然抗菌蛋白,可以成为抗生素和化学防腐剂的有效替代物,解决日益严峻的细菌耐药性问题和抗生素残留、化学防腐剂超标等食品安全问题。因此,深入研究并构建具有新型广谱杀菌能力的溶菌酶,对食品、医药、畜牧等行业的发展有着重要意义。对溶菌酶的分类、胞壁质酶活性和非酶活性杀菌性质以及蛋白质改造方法,特别是利用现代生物技术对溶菌酶进行抗菌活性增强、抗菌谱拓展的研究进行了综述和展望。     

MiR-133a Is Functionally Involved in Doxorubicin-Resistance in Breast Cancer Cells MCF-7 via Its Regulation of the Expression of Uncoupling Protein 2

The development of novel targeted therapies holds promise for conquering chemotherapy resistance, which is one of the major hurdles in current breast cancer treatment. Previous studies indicate that mitochondria uncoupling protein 2 (UCP-2) is involved in the development of chemotherapy resistance in colon cancer and lung cancer cells. In the present study we found that lower level of miR133a is accompanied by increased expression of UCP-2 in Doxorubicin-resistant breast cancer cell cline MCF-7/Dox as compared with its parental cell line MCF-7. We postulated that miR133a might play a functional role in the development of Doxorubicin-resistant in breast cancer cells. In this study we showed that: 1) exogenous expression of miR133a in MCF-7/Dox cells can sensitize their reaction to the treatment of Doxorubicin, which is coincided with reduced expression of UCP-2; 2) knockdown of UCP-2 in MCF-7/Dox cells can also sensitize their reaction to the treatment of Doxorubicin; 3) intratumoral delivering of miR133a can restore Doxorubicin treatment response in Doxorubicin-resistant xenografts in vivo, which is concomitant with the decreased expression of UCP-2. These findings provided direct evidences that the miR133a/UCP-2 axis might play an essential role in the development of Doxorubicin-resistance in breast cancer cells, suggesting that the miR133a/UCP-2 signaling cohort could be served as a novel therapeutic target for the treatment of chemotherapy resistant in breast cancer.     

Machilus parapauhoi sp. nov. and a new synonym of Machilus (Lauraceae) from east Asia

A new species of the genus Machilus Nees (Lauraceae) from China, M. parapauhoi F. N. Wei, S. C. Tang & W. B. Xu is described and illustrated. The new species is similar to M. pauhoi Kanehira, but differs in its densely appressed pubescent branchlets and petioles, shorter petiole, 0.8–1.2 cm long and an infructescence conspicuously shorter than the leaf. It is also similar to M. kwangtungensis Yang, but differs by its oblique leaves, with falcately curved apex and 14–18 lateral veins on both sides of the midrib. Based on a study of the type and isotype specimens of M. balansae (Airy Shaw) F. N. Wei & S. C. Tang and M. grandifolia S. Lee & F. N. Wei, M. grandifolia is regarded as a new synonym of M. balansae.     

The field-dependence of the solid-state photo-CIDNP effect in two states of heliobacterial reaction centers

The solid-state photo-CIDNP (photochemically induced dynamic nuclear polarization) effect is studied in photosynthetic reaction centers of Heliobacillus mobilis at different magnetic fields by ¹³C MAS (magic-angle spinning) NMR spectroscopy. Two active states of heliobacterial reaction centers are probed: an anaerobic preparation of heliochromatophores (“Braunstoff”, German for “brown substance”) as well as a preparation of cells after exposure to oxygen (“Grünstoff”, “green substance”). Braunstoff shows significant increase of enhanced absorptive (positive) signals toward lower magnetic fields, which is interpreted in terms of an enhanced differential relaxation (DR) mechanism. In Grünstoff, the signals remain emissive (negative) at two fields, confirming that the influence of the DR mechanism is comparably low.     

How to Deal with Resource Productivity

Resource productivity enhancement stands at the center of tackling issues on environmental pollution and resource scarcity. Identifying influential socioeconomic factors should be the first step in establishing and improving resource management policy. This study compares and analyzes data from multiple countries to construct a resource productivity simulation model. The socioeconomic factors and their characteristic patterns are discussed in detail. The results demonstrate that the major factors influencing resource productivity include income level, population density, economic structure, energy structure, and raw material trade. Among these factors, the three most important are income level, population density, and economic structure. The influencing patterns can be summarized as follows: (1) Resource productivity increases with increasing income levels. (2) Countries with high population density are inclined to demonstrate high resource productivity. (3) The economic structure shows a biphase influence on resource productivity, that is, during industrialization, decreased agricultural activity and increased industrial activity lead to higher resource productivity. On the other hand, after industrialization, decreasing industrial activity and an expanding service sector become the major impetus of resource productivity enhancement. (4) Raw material export demonstrates a negative effect on resource productivity. Countries that depend heavily on raw material export show a unique resource productivity evolution pattern. For these countries, relatively high resource productivity in low income phases and relatively low resource productivity in high income phases show only small increases in resource efficiency and economic growth. Finally, insights from the study are transformed into suggestions for sustainable resource management and resource productivity enhancement.