Bis(2,4-dioxo-5,5-diphenyl­imidazol­idin­ido-κN 3)bis­(propane-1,3-diamine-κ2 N,N′)cobalt(II)

The complex mol­ecule of the title compound, [Co(C15H11N2O2)2(C3H10N2)2], has crystallographically imposed inversion symmetry. The CoII atom displays a distorted octa­hedral coordination geometry. In the phenytoin anion, the two phenyl rings form dihedral angles of 62.26 (8) and 57.47 (9)° with the central imidazole ring. Intra­molecular N—H⋯O and C—H⋯O hydrogen bonds occur. In the crystal, N—H⋯O and C—H⋯O hydrogen bonds forming a three-dimensional network

trans-Bis(5,5-diphenyl­hydantoinato-κN 3)bis­(propane-1,2-diamine-κ2 N,N′)nickel(II)

The asymmetric unit of the title complex, [Ni(pht)2(pn)2] (pht is 5,5-diphenyl­hydantoinate and pn is propane-1,2-diamine) or [Ni(C15H11N2O2)2(C3H10N2)2], contains one-half [Ni(pht)2(pn)2] mol­ecule. The NiII atom is situated on a crystallographic center of inversion and shows a distorted octa­hedral coordination geometry. A three-dimensional network structure is assembled by inter- and intra­molecular N—H⋯O=C inter­actions

Identification, Characterization and Application of a G-Quadruplex Structured DNA Aptamer against Cancer Biomarker Protein Anterior Gradient Homolog 2

Background: Anterior gradient homolog 2 (AGR2) is a functional protein with critical roles in a diverse range of biological systems, including vertebrate tissue development, inflammatory tissue injury responses, and cancer progression. Clinical studies have shown that the AGR2 protein is overexpressed in a wide range of human cancers, including carcinomas of the esophagus, pancreas, breast, prostate, and lung, making the protein as a potential cancer biomarker. However, the general biochemical functions of AGR2 in human cells remain undefined, and the signaling mechanisms that drive AGR2 to inhibit p53 are still not clearly illustrated. Therefore, it is of great interest to develop molecular probes specifically recognizing AGR2 for its detection and for the elucidation of AGR2-associated molecular mechanism. Methodology/Principal Findings: Through a bead-based and flow cytometry monitored SELEX technology, we have identified a group of DNA aptamers that can specifically bind to AGR2 with K-d values in the nanomolar range after 14 rounds of selections. Aptamer C14B was chosen to further study, due to its high binding affinity and specificity. The optimized and shortened C14B1 has special G-rich characteristics, and the G-rich region of this binding motif was further characterized to reveal an intramolecular parallel G-quadruplex by CD spectroscopy and UV spectroscopy. Our experiments confirmed that the stability of the G-quadruplex structure was strongly dependent on the nature of the monovalent ions and the formation of G-quadruplex structure was also important for the binding capacity of C14B1 to the target. Furthermore, we have designed a kind of allosteric molecule beacon (aMB) probe for selective and sensitive detection of AGR2. Conclusion/Significance: In this work, we have developed new aptamer probes for specific recognition of the AGR2. Structural study have identified that the binding motif of aptamer is an intramolecular parallel G-quadruplex structure and its structure and binding affinity are strongly dependent on the nature of the monovalent ion. Furthermore, with our design of AGR2-aMB, AGR2 could be sensitively and selectively detected. This aptamer probe has great potential to serve as a useful tool for early diagnosis and prognosis of cancer and for fundamental research to elucidate the biochemical functions of AGR2.National Basic Research Program of China [2010CB732402]; National Instrumentation Program [2011YQ03012412]; Natural Science Foundation of Fujian Province for Distinguished Young Scholars [2010 J06004]; National Found for Fostering Talents of Basic Science [J1030415

The miR-21-5p enriched in the apoptotic bodies of M2 macrophage-derived extracellular vesicles alleviates osteoarthritis by changing macrophage phenotype

Macrophages (Mφs) play a crucial role in the pathological progression of osteoarthritis (OA) by regulating inflammation and tissue repair. Decreasing pro-inflammatory M1-Mφs and increasing anti-inflammatory M2-Mφs can alleviate OA-related inflammation and promote cartilage repair. Apoptosis is a natural process associated with tissue repair. A large number of apoptotic bodies (ABs), a type of extracellular vesicle, are produced during apoptosis, and this is associated with a reduction in inflammation. However, the functions of apoptotic bodies remain largely unknown. In this study, we investigated the role of M2-Mφs-derived apoptotic bodies (M2-ABs) in regulating the M1/M2 balance of macrophages in a mouse model of OA. Our data show that M2-ABs can be targeted for uptake by M1-Mφs, and this reprograms M1-to-M2 phenotypes within 24 h. The M2-ABs significantly ameliorated the severity of OA, alleviated the M1-mediated pro-inflammatory environment, and inhibited chondrocyte apoptosis in mice. RNA-seq revealed that M2-ABs were enriched with miR-21–5p, a microRNA that is negatively correlated with articular cartilage degeneration. Inhibiting the function of miR-21–5p in M1-Mφs significantly reduced M2-ABs-guided M1-to-M2 reprogramming following in vitro cell transfection. Together, these results suggest that M2-derived apoptotic bodies can prevent articular cartilage damage and improve gait abnormalities in OA mice by reversing the inflammatory response caused by M1 macrophages. The mechanism underlying these findings may be related to miR-21-5p-regulated inhibition of inflammatory factors. The application of M2-ABs may represent a novel cell therapy, and could provide a valuable strategy for the treatment of OA and/or chronic inflammation

Highway constructions on the Qinghai-Tibet Plateau: Challenge, research and practice

Summary: Highway constructions on the Qinghai-Tibet Plateau (QTP) face great challenges induced by the unique local environmental, geological, and engineering conditions. The large area of permafrost, great temperature variability, strong UV rays, and complex geological conditions are the major factors that adversely influence the long-term performance of pavement systems. Since 1960s, Chinese engineers and researchers have started conducting research on the QTP to enhance the performance and durability of pavement systems. The present paper provide a comprehensive review of challenge, research and practice of highway constructions on the QTP including the special environmental and geological conditions, history of highway constructions on the QTP, major challenges and the state-of-the-art technology of subgrade constructions on permafrost, developments of the pavement structures and materials, performance prediction and maintenance methods of pavement surfaces, and applications of the research achievements on the first expressway on the QTP (i.e., Gongyu Expressway). Based on the comprehensive literature review, it can be found that (1) frost heave and thaw weakening induced subgrade disease and longitudinal cracks on the pavement surface are complex coupled water-thermal-load problems. Engineering solutions are focusing on active cooling and thermal insulation methods, which can help to reduce temperature variations in the subgrade and thus improving its stability, (2) the harsh environmental and construction conditions may reduce the early strength and induce premature damage of cement-treated base materials. Some field validations showed that geocell-reinforced or asphalt-treated flexible base materials can provide better long-term performance, (3) the large temperature variability and strong UV rays can significantly accelerate aging of asphalt binders and greatly reduce the service life of asphalt mixtures. Various binder modification methods were developed for improving their viscoelasticity and enhance the low-temperature cracking resistance of pavement surface materials but are still lack of field validation data and comparisons of their life cycle costs. Therefore, it is recommended that a demonstration research project build test sections to examine a range of pavement structures and materials, and compare their long-term performance and life cycle costs, which can serve as important reference for future highway constructions on the QTP