Regulating cell behavior via regional patterned distribution of heparin-like polymers.

Molecular patterning on biomaterial surfaces is an effective strategy to regulate biomaterial properties. Among the specific molecules, due to their biological functions, such as regulating cell behavior, heparin-like polymers (HLPs) have attracted much attention. In this study, HLP-distributed regional patterned surfaces (300 µm diameter circular array) were prepared by the combination of visible light-induced graft polymerization, transfer imprinting, and self-assembly to regulate the behavior of human umbilical vein endothelial cells (HUVECs) and human umbilical vein smooth muscle cells (HUVSMCs). The introduction of the regional pattern on HLP-modified surfaces enhanced the promotion effect of sulfonate-containing polymer (pSS) and sulfonate-, and glyco-containing copolymer (pS-co-pM), and slightly weakened the inhibition effect of glyco-containing polymer (pMAG) on the growth of HUVECs and HUVSMCs. Compared with flat surfaces, it was found that the unmodified regional patterned surfaces inhibit the spreading of HUVECs and HUVSMCs, while significantly promoting the spreading of HUVECs and HUVSMCs on all the HLP-distributed regional patterned surfaces. The patterned surface modified with pS-co-pM had the highest average spread area of HUVECs (∼10,554 µm2), which was 193 % higher than that of the unmodified flat surface. This trend was somewhat related to surface VEGF adsorption. The combination of regional divisive patterns and different HLP distributions enriched the potential of further exploring the influences of HLP chemical distributions and complex surface environments on cell-material interactions.

Multistage Anticoagulant Surfaces: A Synergistic Combination of Protein Resistance, Fibrinolysis, and Endothelialization.

Anticoagulant surface modification of blood-contacting materials has been shown to be effective in preventing thrombosis and reducing the dose of anticoagulant drugs that patients take. However, commercially available anticoagulant coatings, that is, both bioinert and bioactive coatings, are typically based on a single anticoagulation strategy. This puts the anticoagulation function of the coating at risk of failure during long-term use. Considering the several pathways of the human coagulation system, the synergy of multiple anticoagulation theories may provide separate, targeted effects at different stages of thrombosis. Based on this presumption, in this work, negatively charged poly(sodium p-styrenesulfonate-co-oligo(ethylene glycol) methyl ether methacrylate) and positively charged poly(lysine-co-1-adamantan-1-ylmethyl methacrylate) were synthesized to construct matrix layers on the substrate by electrostatic layer-by-layer self-assembly (LBL). Amino-functionalized ß-cyclodextrin (ß-CD-PEI) was subsequently immobilized on the surface by host-guest interactions, and heparin was grafted. By adjusting the content of poly(oligo(ethylene glycol) methyl ether methacrylate) (POEGMA), the interactions between modified surfaces and plasma proteins/cells were regulated. This multistage anticoagulant surface exhibits inertness at the initial stage of implantation, resisting nonspecific protein adsorption (POEGMA). When coagulation reactions occur, heparin exerts its active anticoagulant function in a timely manner, blocking the pathway of thrombosis. If thrombus formation is inevitable, lysine can play a fibrinolytic role in dissolving fibrin clots. Finally, during implantation, endothelial cells continue to adhere and proliferate on the surface, forming an endothelial layer, which meets the blood compatibility requirements. This method provides a new approach to construct a multistage anticoagulant surface for blood-contacting materials.

Highly Stereoselective Diels-Alder Reactions Catalyzed by Diboronate Complexes.

A highly enantioselective catalytic system for exo-Diels-Alder reactions was developed based on the newly discovered bispyrrolidine diboronates (BPDB). Activated by various Lewis or Brønsted acids, BPDB can catalyze highly stereoselective asymmetric exo-Diels-Alder reactions of monocarbonyl-based dienophiles. When 1,2-dicarbonyl-based dienophiles are used, the catalyst can sterically distinguish between the two binding sites, which leads to highly regioselective asymmetric Diels-Alder reactions. BPDB can be prepared as crystalline solids on a large scale and are stable under ambient condition. Single-crystal X-ray analysis of the structure for acid-activated BPDB indicated that its activation involves cleavage of a labile B←N bond.

Self-Assembly of Intracellular Multivalent RNA Complexes Using Dimeric Corn and Beetroot Aptamers.

DNA and RNA can spontaneously self-assemble into various structures, including aggregates, complexes, and ordered structures. The self-assembly reactions cannot be genetically encoded to occur in living mammalian cells since the double-stranded nucleic acids generated by current self-assembly approaches are unstable and activate innate RNA immunity pathways. Here, we show that recently described dimeric aptamers can be used to create RNAs that self-assemble and create RNA and RNA-protein assemblies in cells. We find that incorporation of five copies of Corn, a dimeric fluorogenic RNA aptamer, into an RNA causes the RNA to form large clusters in cells, reflecting multivalent RNA-RNA interactions enabled by these RNAs. Here, we also describe a second dimeric fluorogenic aptamer, Beetroot, which shows partial sequence similarity to Corn. Both Corn and Beetroot form homodimers with themselves but do not form Corn-Beetroot heterodimers. We thus use Corn and Beetroot to encode distinct RNA-protein assemblies in the same cells. Overall, these studies provide an approach for inducing RNA self-assembly, enable multiplexing of distinct RNA assemblies in cells, and demonstrate that proteins can be recruited to RNA assemblies to genetically encode intracellular RNA-protein assemblies.

Chloride Transport Behaviour and Service Performance of Cracked Concrete Linings in Coastal Subway Tunnels.

The concrete lining in subway tunnels often undergoes cracking damage in coastal cities. The combination of cracked tunnel lining structures and high concentrations of corrosive ions in the groundwater (e.g., chlorine) can accelerate concrete erosion, reduce the mechanical performance of the lining structures and shorten the tunnel service life. This paper investigates the chloride ion concentration in the groundwater of several subway tunnels in the coastal city of Qingdao, China. Indoor experiments and numerical simulations are conducted to investigate the chloride ion transport behaviour and service performance of cracked concrete linings. The results are applied to predict the service life of lining structures. The crack depth in concrete linings is found to have the most significant effect on the transport rate of chloride ions, followed by the crack width. The numerical simulations are carried out using COMSOL software to study the chloride transport behaviour in cracked specimens and predict the service lifetimes of lining structures of different thicknesses, and the results correspond well with the experimental data. The durability of a concrete lining can be enhanced by increasing the thickness of the protective concrete layer. Additional measures are proposed for treating cracked concrete linings to resist chloride ion attack in subway tunnels.

Ir-Catalyzed Regio- and Enantioselective Hydroalkynylation of Trisubstituted Alkene to Access All-Carbon Quaternary Stereocenters.

The stereoselective construction of all-carbon quaternary stereocenters, especially acyclic ones, represents an important challenge in organic synthesis. In particular, homopropargyl amides with a quaternary stereocenter ß to a nitrogen atom are valuable synthetic intermediates, which could be transformed to diverse chiral structures through alkyne transformations. However, highly enantioselective synthetic methods for homopropargyl amides with a ß quaternary stereocenter are extremely rare. We report here unprecedented substrate-directed, iridium-catalyzed enantioselective hydroalkynylations of trisubstituted alkenes to form an acyclic all-carbon quaternary stereocenter ß to a nitrogen atom. The hydroalkynylation of enamide occurred with unconventional selectivity, favoring the more hindered reaction site. Homopropargyl amides with ß-stereocenters were prepared in high regio- and enantioselectivities. Combined experimental and computational studies revealed the origin of the regio- and enantioselectivities.

Noninvasive quantification of nonhuman primate dynamic 18F-FDG PET imaging.

18F-FDG uptake rate constant Ki is the main physiology parameter measured in dynamic PET studies. A model-independent graphical analysis using Patlak plot with plasma input function (PIF) is a standard approach used to estimate Ki . The PIF is the 18F-FDG time activity curve (TAC) in plasma that is obtained by serial arterial blood sampling. The purpose of the study is to evaluate a Patlak plot-based optimization approach with reduced blood samples for noninvasive quantification of dynamic 18F-FDG PET imaging. Eight 60 min rhesus monkey brain dynamic 18F-FDG PET scans with arterial blood samples were collected. The measured PIF (mPIF) was determined by arterial blood samples. TACs of seven cerebral regions of interest were generated from each study. With a given number of blood samples, the population-based PIF (pPIF) was determined by either interpolation or extrapolation method using scale calibrated population mean of normalized PIF. The optimal sampling scheme with given blood sample size was determined by maximizing the correlations between the Ki estimated from pPIF and those obtained by mPIF. A leave-two-out cross-validation method was used for evaluation. The linear correlations between the Ki estimates from pPIF with optimal sampling schemes and those from mPIF were: Ki (pPIF 1 sample at 40 min) = 1.015 Ki (mPIF) - 0.000, R 2 = 0.974; Ki (pPIF 2 samples at 35 and 50 min) = 1.052 Ki (mPIF) - 0.001, R 2 = 0.976; Ki (pPIF 3 samples at 12, 40, and 50 min) = 1.030 Ki (mPIF) - 0.000, R 2 = 0.985; and Ki (pPIF 4 samples at 10, 20, 40, and 50 min) = 1.016 Ki (mPIF)- 0.000, R 2 = 0.993. As the sample size became greater or equal to 4, the Ki estimates from pPIF with the optimal protocol were almost identical to those from mPIF. The Patlak plot-based optimization approach is a reliable method to estimate PIF for noninvasive quantification of non-human primate dynamic 18F-FDG PET imaging and is potentially extendable to further translational human studies.

Effect of High-Dispersible Graphene on the Strength and Durability of Cement Mortars.

Graphene's outstanding properties make it a potential material for reinforced cementitious composites. However, its shortcomings, such as easy agglomeration and poor dispersion, severely restrict its application in cementitious materials. In this paper, a highly dispersible graphene (TiO2-RGO) with better dispersibility compared with graphene oxide (GO) is obtained through improvement of the graphene preparation method. In this study, both GO and TiO2-RGO can improve the pore size distribution of cement mortars. According to the results of the mercury intrusion porosity (MIP) test, the porosity of cement mortar mixed with GO and TiO2-RGO was reduced by 26% and 40%, respectively, relative to ordinary cement mortar specimens. However, the TiO2-RGO cement mortars showed better pore size distribution and porosity than GO cement mortars. Comparative tests on the strength and durability of ordinary cement mortars, GO cement mortars, and TiO2-RGO cement mortars were conducted, and it was found that with the same amount of TiO2-RGO and GO, the TiO2-RGO cement mortars have nearly twice the strength of GO cement mortars. In addition, it has far higher durability, such as impermeability and chloride ion penetration resistance, than GO cement mortars. These results indicate that TiO2-RGO prepared by titanium dioxide (TiO2) intercalation can better improve the strength and durability performance of cement mortars compared to GO.

Highly Enantioselective Synthesis of Propargyl Amide with Vicinal Stereocenters through Ir-Catalyzed Hydroalkynylation.

Chiral propargyl amines are valuable synthetic intermediates for the preparation of biologically active compounds and functionalized amines. Catalytic methods to access propargyl amines containing vicinal stereocenters with high diastereoselectivity are particularly rare. We report an unprecedented strategy for the synthesis of enantioenriched propargyl amines with two stereogenic centres. An iridium complex, ligated by a phosphoramidite ligand, catalyzes the hydroalkynylation of ß,ß-disubstituted enamides to afford propargyl amides in a highly regio-, diastereo-, and enantioselective fashion. Stereodivergent synthesis of all four possible stereoisomers was achieved using this strategy.

Association between Gene Polymorphisms of Vitamin D Receptor and Gestational Diabetes Mellitus: A Systematic Review and Meta-Analysis.

(1) Background: Studies on the association between Vitamin D receptor gene polymorphism and gestational diabetes mellitus have been inconsistent. The aim of this study was to summarize available evidence on the association between polymorphisms of Vitamin D receptor genes and susceptibility to gestational diabetes mellitus. (2) Methods: We searched databases of PubMed, Web of Science, Embase, China national knowledge infrastructure (CNKI), China science and technology journal database (VIP), and Wanfang Data for relevant articles. A systematic review and a meta-analysis were done to compare the distribution of Vitamin D receptor gene polymorphisms in gestational diabetes mellitus patients with those in controls using allelic, codominant, dominant, and recessive models. (3) Results: A total of eight eligible articles were included in the systematic review and of them, six articles were included in the meta-analysis. The vitamin D receptor gene rs7975232 polymorphism was associated with gestational diabetes mellitus under the allelic model (odds ratio = 1.28, 95% confidence interval 1.06-1.56), codominant model (CC vs. AA odds ratio = 1.97, 95% confidence interval 1.28-3.05), and recessive model (odds ratio = 1.83, 95% confidence interval 1.27-2.64) in the case of low heterogeneity. High heterogeneity existed in studies on the association of vitamin D receptor genes rs1544410, rs2228570, and rs731236 with gestational diabetes mellitus, and the most common sources of heterogeneity were the year of publication and matching. (4) Conclusion: Polymorphism of the vitamin D receptor gene rs7975232 may be associated with risk of developing gestational diabetes mellitus. Future studies should be designed to include standardized data collection and matching for important confounding factors such as body mass index, age, and race.

Asymmetric Total Synthesis of Lancifodilactone G Acetate. 2. Final Phase and Completion of the Total Synthesis.

The asymmetric total synthesis of lancifodilactone G acetate was accomplished in 28 steps. The key steps in this synthesis include (i) an asymmetric Diels-Alder reaction for formation of the scaffold of the BC ring; (ii) an intramolecular ring-closing metathesis reaction for the formation of the trisubstituted cyclooctene using a Hoveyda-Grubbs II catalyst; (iii) an intramolecular Pauson-Khand reaction for construction of the sterically congested F ring; (iv) sequential cross-metathesis, hydrogenation, and lactonization reactions for installation of the anomerically stabilized bis-spiro ketal fragment of lancifodilactone G; and (v) a Dieckmann-type condensation reaction for installation of the A ring. The strategy and chemistry developed for the total synthesis will be useful in the synthesis of other natural products and complex molecules.

Catalytic and Enantioselective Diels-Alder Reactions of (E)-4-Oxopent-2-enoates.

Novel oxazaborolidines activated by the strong acid triflimide or AlBr3 form cationic chiral catalysts. These are effective catalysts for highly regio- and enantioselective Diels-Alder reactions using substituted (E)-4-oxopent-2-enoates as dienophiles.

Asymmetric Total Synthesis of Lancifodilactone G Acetate.

Asymmetric total synthesis of structurally intriguing and highly oxygenated lancifodilactone G acetate (7) has been achieved for the first time in 28 steps from a cheap commodity chemical, 2-(triisopropylsiloxy)-1,3-butadiene.

Design and synthesis of novel ß-diketo derivatives as HIV-1 integrase inhibitors.

A series of novel ß-diketo derivatives which combined the virtues of 1,3-diketo, 1,2,3-triazole and polyhydroxylated aromatics moieties, were designed and synthesized as potential HIV-1 integrase (IN) inhibitors and evaluated their inhibition to the strand transfer process of HIV-1 integrase. The result indicates that 3,4,5-trihydroxylated aromatic derivatives exhibit good inhibition to HIV-1 integrase, but dihydroxylated aromatic derivatives and corresponding methoxy aromatic derivatives appear little inhibition to HIV-1 integrase.