Awake rabbit model of ischemic spinal cord injury with delayed paraplegia: The role of ambient temperature.

BACKGROUND: Paraplegia after spinal cord ischemia is a devastating condition in the clinic. Here, we develop an awake rabbit model of spinal cord ischemia with delayed paraplegia and explore the influence of ambient temperature on the outcomes after injury. METHODS: A total of 47 male rabbits were involved in the present study. Transient spinal cord ischemia was induced by occluding the infrarenal abdominal aorta of awake rabbits at different ambient temperatures. To find the optimal conditions for developing delayed paraplegia, hindlimb motor function after ischemia was evaluated between experiments. RESULTS: The onset and magnitude of ischemic injury varied with the ambient temperature maintained during the peri-ischemia period. More serious spinal cord injury occurred when ischemia was induced at higher temperatures. At 18°C, 25-minute ischemia resulted in 74% of rabbits developing delayed paraplegia. At a temperature of 28°C or higher, most of the animals developed acute paraplegia immediately. While at 13°C, rabbits usually regained normal motor function without paraplegia. CONCLUSION: This awake rabbit model is highly reproducible and will be helpful in future studies of delayed paraplegia after spinal cord ischemia. The ambient temperature must be considered while using this model during investigation of therapeutic interventions.

Catalytic Asymmetric Umpolung Tandem Reactions of Hemiacetals via Dinuclear Zinc Cooperative Catalysis.

The umpolung activity of hemiacetals serving as α-carbon nucleophiles has been reported via dinuclear zinc cooperative catalysis. This umpolung strategy has been applied to catalytic asymmetric tandem reactions of 1-tosylindoline-2,3-diols with ß,γ-unsaturated-α-keto compounds, providing a broad series of structurally diverse tetrahydrofuran spirooxindoles and dihydrofurans, respectively. In addition, products could be transformed to quinazoline and quinoline derivatives.

Enantioselective synthesis of indanone spiro-isochromanone derivatives via a dinuclear zinc-catalyzed Michael/transesterification tandem reaction.

An enantioselective Michael/transesterification tandem reaction of α-hydroxy indanones with ortho-ester chalcones was realized using dinuclear zinc catalysts. A series of enantiomerically pure spiro[indanone-2,3'-isochromane-1-one] derivatives were obtained in good yields with excellent stereoselectivities (up to >20 : 1 dr, up to >99% ee). This protocol could be conducted on a gram scale without affecting its stereoselectivities. In addition, the absolute stereochemistry of the products was determined by X-ray crystallographic analysis of 3ac, and a positive nonlinear effect was observed. Finally, a possible catalytic cycle was proposed to explain the origin of the enantioselectivity.

Dinuclear Zinc-Catalyzed Asymmetric Tandem Reaction of α-Hydroxy-1-indanone: Access to Spiro[1-indanone-5,2'-γ-butyrolactones].

A highly efficient method for the enantioselective build of spiro[1-indanone-5,2'-γ-butyrolactones] has been developed through the tandem Michael/transesterification reaction of α-hydroxy-1-indanone and α,ß-unsaturated esters. A broad range of spiro(1-indanone-butyrolacones) with contiguous stereocenters have been synthesized with excellent stereoselectivities (up to >20:1 dr, up to >99% ee) under the catalysis of dinuclear zinc complex. Moreover, the reaction can be run on a gram scale without affecting its stereoselectivities. A possible mechanism is proposed.

Access to Chiral 2,5-Pyrrolidinyl Dispirooxindoles via Dinuclear Zinc-Catalyzed Asymmetric Cascade Reactions.

A series of new nonsymmetric semi-azacrown ether ligands were developed and applied to the asymmetric Michael/cyclic keto-imine formation/Friedel-Crafts alkylation reactions of 3-amino oxindole hydrochlorides and ß,γ-unsaturated α-keto amides. A diversity of 2,5-pyrrolidinyl dispirooxindoles containing two nonadjacent spiro-quaternary stereocenters were obtained in excellent diastereoselectivities and moderate to excellent enantioselectivities (up to 95% ee). A possible catalytic cycle was proposed to explain the origin of the asymmetric induction.

Synthesis of Chiral Bispirotetrahydrofuran Oxindoles by Cooperative Bimetallic-Catalyzed Asymmetric Cascade Reaction.

A new, efficient route for the enantioselective construction of bispirotetrahydrofuran oxindoles is described via the cooperative dinuclear zinc-AzePhenol catalyst. Under mild conditions, a broad range of bispirotetrahydrofuran oxindoles have been synthesized with excellent stereoselectivities through the cascade Michael/hemiketalization/Friedel-Crafts reaction of ß,γ-unsaturated α-ketoamide and 2-hydroxy-1-indanone. The reaction can be performed on a gram scale with low catalyst loading (2 mol %) without impacting its efficiency.

Azetidine-derived dinuclear zinc catalyzed asymmetric phospha-Michael addition of dialkyl phosphite to α,ß-unsaturated carbonyl compounds.

The asymmetric phospha-Michael addition of dialkyl phosphite to α,ß-unsaturated carbonyl compounds by using an azetidine-derived dinuclear zinc catalyst was described. The catalyst was proved to be general and efficient for a broad spectrum of enones and α,ß-unsaturated N-acylpyrroles. A series of phosphonate-containing compounds were generated with excellent enantioselectivities (up to 99% ee) and chemical yields (up to 99%) under mild conditions without using additives. The products were obtained with more than 95% ee for 23 examples of α,ß-unsaturated carbonyl compounds. A positive nonlinear effect was observed and the possible mechanism was proposed.

Dinuclear zinc complex catalyzed asymmetric methylation and alkynylation of aromatic aldehydes.

A general AzePhenol dinuclear zinc catalytic system has been successfully developed and introduced into the asymmetric addition of dimethylzinc and alkynylzinc to aromatic aldehydes. In this system, an azetidine derived chiral ligand has proven to be an effective enantioselective promoter. Under the optimal reaction conditions, a series of chiral 1-hydroxyethyl (up to 99% ee) and secondary propargylic alcohols (up to 96% ee) were generated with good yields and enantioselectivities. Additionally, this novel catalytic system showed good functional group compatibility. Remarkably, the substituent's electronic nature alone is not sufficient to allow for exclusive enantioselectivity, an additional substituent's location also had an effect. We proposed that the formation of a stable and structural rigid transition state by the chelation of ortho substituted benzaldehydes to the zinc atom was responsible for the observed higher enantioselectivity. The possible catalytic cycles of both transformations accounting for the stereoselectivity were described accordingly.

Current applications and future prospects of nanomaterials in tumor therapy.

Tumors are one of the most serious human diseases and cause numerous global deaths per year. In spite of many strategies applied in tumor therapy, such as radiation therapy, chemotherapy, surgery, and a combination of these treatments, tumors are still the foremost killer worldwide among human diseases, due to their specific limitations, such as multidrug resistance and side effects. Therefore, it is urgent and necessary to develop new strategies for tumor therapy. Recently, the fast development of nanoscience has paved the way for designing new strategies to treat tumors. Nanomaterials have shown great potential in tumor therapy, due to their unique properties, including passive targeting, hyperthermia effects, and tumor-specific inhibition. This review summarizes the recent progress using the innate antitumor properties of metallic and nonmetallic nanomaterials to treat tumors, and related challenges and prospects are discussed.

Alendronate-anchored PEGylation of ceria nanoparticles promotes human hepatoma cell proliferation via AKT/ERK signaling pathways.

Previous work has suggested that ceria nanoparticles (CNPs) have regenerative antioxidant properties, which have motivated researchers to consider CNPs as therapeutic agents for treating a number of diseases, including cancer. Recent studies have shown CNPs to be toxic to cancer cells, to inhibit invasion and sensitize cancer cells to radiotherapy. In addition, several hydrophilic polymers have been used to coat the CNP surface in order to enhance its properties of extensive biocompatibility and systemic nontoxicity to normal cells and tissues. However, the results of previous studies were based on high CNP doses (10 µg/mL or more), and these doses may cause serious side effects in clinical applications. The impact of low CNP doses on tumor cells remains unknown. In this study, we report experiments indicating that CNPs-AL- polyethylene glycol (PEG)600, a type of surface-modified CNP that is more stable and less toxic than traditional CNPs could promote proliferation of hepatoma cells in a dose-dependent manner. In addition, further research showed that a low dose (0.01 µg/mL) of CNPs-AL-PEG600 could reduce hepatoma cell apoptosis and activate AKT/ERK signaling pathways. These results may provide information that is important for using CNPs-AL-PEG600 as a therapeutic agent in clinical cancer treatments.

Cerium oxide nanoparticles inhibit the migration and proliferation of gastric cancer by increasing DHX15 expression.

Gastric cancer is one of the leading causes of tumor-related deaths in the world. Current treatment options do not satisfy doctors and patients, and new therapies are therefore needed. Cerium oxide nanoparticles (CNPs) have been studied as a potential therapeutic approach for treating many diseases. However, their effects on human gastric cancer are currently unknown. Therefore, in this study, we aimed to characterize the effects of CNPs on human gastric cancer cell lines (MKN28 and BGC823). Gastric cancer cells were cocultured with different concentrations of CNPs, and proliferation and migration were measured both in vitro and in vivo. We found that CNPs inhibited the migration of gastric cancer cells when applied at different concentrations, but only a relatively high concentration (10 µg/mL) of CNPs suppressed proliferation. Furthermore, we found that CNPs increased the expression of DHX15 and its downstream signaling pathways. We therefore provide evidence showing that CNPs may be a promising approach to suppress malignant activity of gastric cancer by increasing the expression of DHX15.

Enantioselective Friedel-Crafts alkylation of pyrrole with chalcones catalyzed by a dinuclear zinc catalyst.

A highly enantioselective Friedel-Crafts (F-C) alkylation of pyrrole with a wide range of simple nonchelating chalcone derivatives catalyzed by a chiral (Zn2EtL)n (L = (S,S)-1) complex has been developed. The catalyst (Zn2EtL)n complex was prepared in situ by reacting the chiral ligand (S,S)-1 with 2 equiv of diethylzinc. A series of ß-pyrrole-substituted dihydrochalcones were usually formed mostly in excellent yields (up to 99%) and excellent enantioselectivity [up to 99% enantiomeric excess (ee)] by using 15 mol % catalyst loading under mild conditions. The absolute stereochemistry of the products was determined to be the S-configuration by X-ray crystallographic analysis of 13g. Meanwhile, a weak negative nonlinear effect was observed. On the basis of the experimental results and previous reports, a possible mechanism was proposed to explain the origin of the asymmetric induction.

Enzyme-amplified array sensing of proteins in solution and in biofluids.

We have developed an enzyme-nanoparticle sensor array where the sensitivity is amplified through enzymatic catalysis. In this approach cationic gold nanoparticles are electrostatically bound to an enzyme (beta-galactosidase, beta-Gal), inhibiting enzyme activity. Analyte proteins release the beta-Gal, restoring activity and providing an amplified readout of the binding event. Using this strategy we have been able to identify proteins in buffer at a concentration of 1 nM, substantially lower than current strategies for array-based protein sensing. Moreover, we have obtained identical sensitivity in studies where the proteins are spiked into the complex protein matrix provided by desalted human urine ( approximately 1.5 muM total protein; spiked protein concentrations were 0.067% of the overall protein concentration), demonstrating the potential of the method for diagnostic applications.

Catalytic microcapsules assembled from enzyme-nanoparticle conjugates at oil-water interfaces.

Involuntary association: Anionic beta-galactosidase enzymes associate with positively charged Au nanoparticles to produce reduced-charge conjugates, which assemble at oil-water interfaces to result in stable microcapsules (see picture). The microcapsules were formed quickly and showed high enzymatic activity, which makes them promising materials for biotechnology applications.