Multimetallic catalysis can effectively enhance the selectivity for the heterocoupling product over homocoupling products in cross-electrophilic couplings. We report the selective cross-coupling of aryl bromides with aryl fluorosulfonates via palladium and nickel cooperative catalysis for the synthesis of biaryls, which can be carried out at room temperature while having marvelous chemoselectivity. In addition, the reaction also has a good performance on the gram-scale reaction.

In this update, we developed a mild, efficient and practical method using fluorosulfuryl imidazolium salt A as an environment friendly promoter for conversion of oximes to nitriles or amides via β-elimination or Beckmann rearrangement in almost quantitative yield in 10 minutes. The target products were generated in gram-scale and could be collected through crystallization without silica gel column purification in excellent yield.

Isocyanate is an important intermediate in organic synthesis, which could be prepared via the reaction of Hoffman rearrangement, Curtis rearrangement or Lossen rearrangement. Considering avoiding the hazardous and potentially explosive reagents, chemists have focused on Lossen rearrangement and made the progress and applications of this reaction. The development and applications of the typical reactions of Lossen rearrangement based on its mechanism are systematically summarized. The direction of future research is also prospected.

In this update, we report a simple, mild and practical method for the synthesis of symmetrical urea via Lossen rearrangement promoted by SO2F2, which achieves the conversion from hydroxamic acid to symmetrical urea in high selectivity and provides a new method for facile initiation of Lossen rearrangement. Meanwhile, the reaction within amine or thiol also provide the efficient synthetic strategy towards unsymmetrical urea or thiocarbamates. Significant for gram-scale application, we afford the desired product on gram-scale by filtration without further purification. A plausible mechanism which is supported by control experimental and spectral data is proposed.

Observation of brain activities in freely moving animals has become an important approach for neuroscientists to understand the correlation between brain function and behavior. We describe an extendable fiber-optic-based multi-modal imaging system that can concurrently carry out laser speckle contrast imaging (LSCI) of blood flow and optical intrinsic signal (OIS) imaging in freely moving animals, and it could be extended to fluorescence imaging. Our imaging system consists of a multi-source illuminator, a fiber multi-channel optical imaging unit, and a head-mounted microscope. The imaging fiber bundle delivers optical images from the head-mounted microscope to the multi-channel optical imaging unit. Illuminating multi-mode fiber bundles transmit light to the head-mounted microscope which has a mass of less than 1.5 g and includes a gradient index lens, giving the animal maximum movement capability. The internal optical components are adjustable, allowing for a change in magnification and field of view. We test the system by observing hemodynamic changes during cortical spreading depression (CSD) in freely moving and anesthetized animals by simultaneous LSCI and dual-wavelength OIS imaging. Hemodynamic parameters were calculated. Significant differences in CSD propagation durations between the two states were observed. Furthermore, it is capable of performing fluorescence imaging to explore animal behavior and the underlying brain functional activity further.

It is well known that combination therapy can significantly enhance the cytotoxicity and bypass some resistance mechanisms. However, the different solubility and pharmacokinetics of drugs limit the applications of combination therapy. In this study, novel glucose-functionalized polymeric micelle nanoparticles containing multidrugs were successfully fabricated and characterized. Two chemotherapeutic agents, cytarabine (Ara-C) and fluorodeoxyuridine (FUDR), were conjugated to a glucose-functionalized amphiphilic random terpolymer to create a novel nanocarrier for the delivery of multiple drugs simultaneously with an identical pharmacokinetic profile. The incorporation of d-glucose markedly increased the dispersity and biocompatibility of the novel polymeric micelles. In vitro drug release studies showed the two anticancer agents could be simultaneously released from multidrug-conjugating nanoparticles. Cellular uptake assay observed by confocal laser scanning microscopy and cytotoxicity tests performed by MTT assay against hepG2 human hepatoma cells indicated that glucose-functionalized multidrug-conjugating nanoparticles could be effectively internalized by HepG2 cells and showed much more effective growth-inhibitory activity than two single-drug-conjugating polymer aggregates or free drugs. This finding, therefore, illustrated that the d-glucose functionalized nanoparticles could be used as a novel potential multidrug delivery vehicle.

In this study we fabricated and characterized novel galactose-functionalized multidrug-containing nanoparticles, and in vitro evaluated their enhanced anti-tumorous cell cytotoxicity and hepatoma-targeting ability for the controlled delivery of two synergistic anticancer drugs. A chemo-enzymatic synthesis strategy was used to prepare a galactose-functionalized amphiphilic random copolymer containing cytarabine (Ara-C) and fluorodeoxyuridine (FUDR). The formed nanoparticles were characterized for their critical aggregation concentration (CAC), morphology, cellular uptake, cell cytotoxicity, hepatoma targeting ability and controlled drug release. The micellization ability of the galactose-functionalized amphiphilic random copolymer was confirmed. In vitro drug release studies showed that the two anticancer agents could be simultaneously released from the nanoparticles. Cellular uptake assay and cytotoxicity tests demonstrated that these nanoparticles could be effectively internalized by HepG2 cells and had an evident targeting function through the selective recognition of galactose pendants of the copolymer by ASGP-R of HepG2 cells. Furthermore, the enhanced anti-tumorous cell cytotoxicity indicated the combination of Ara-C, FUDR and D-galactose in one copolymer may have a better synergistic effect. This encouraging finding illustrated that the D-galactose functionalized nanoparticles could be used as a novel potential hepatoma-targeting multidrug delivery vehicle.

Cortical spreading depression (CSD) is a self-propagating wave of cellular depolarization that plays an important role in the development of cerebral pathology following ischemia or trauma. Optical intrinsic signal (OIS) imaging has been widely used to investigate CSD. Sources of OIS are complex and related to the changes in brain tissue absorption and scattering. The absorbing chromophores may include oxy-hemoglobin, deoxy-hemoglobin, cytochromes, flavin adenine dinucleotide (FAD) and nicotinamide adenine dinucleotide (NADH). Considering only one or part of these elements in studies involving OIS may cause inaccurate results. Thus, we simultaneously calculated changes in HbO, HbR, FAD, cytochrome c, cytochrome aa3 and light scattering during CSD by applying multi-spectral OIS imaging at 450, 470, 500, 530, 550, 570, 600, 630, and 650 nm in the rat brain. We also showed that the hemodynamic changes during CSD may not be correctly estimated if the scattering and other chromophores such as FAD, cytochrome c and cytochrome aa3, are not included in the fitting model of multi-wavelength data analysis. As shown in our results, if considering the changes in scattering and other chromophores in data fitting model, deoxy-hemoglobin (HbR) showed a triphasic change while only a monophasic decrease in HbR will be resolved without considering changes in scattering and other chromophores as reported in previous studies. Moreover, our results showed that changes in cytochrome c was tightly related to OIS at 550 nm, cytochrome aa3 was closely related to OIS at 450, 600 and 650 nm, and FAD was closely related to OIS at 450 and 470 nm during CSD. It indicates that if the contribution by these related chromophores is not considered, using OIS at these wavelengths to determine the hemoglobin changes during CSD may lead to inaccurate results.

A direct approach to 1,4-dihydropyridines by lipase-catalyzed unprecedented three-component Hantzsch-type reaction of aldehyde with 1,3-dicarbonyl compounds and acetamide in non-aqueous solvent has been developed. Some control experiments have been performed to demonstrate the specific catalytic effect of CAL-B. Acetamide was utilized as a novel ammonia source in the Hantzsch-type reaction for the first time. An array of 1,4-dihydropyridines was successfully synthesized through this methodology.

Automatic separation of arteries and veins in optical cerebral cortex images is important in clinical practice and preclinical study. In this paper, a simple but effective automatic artery-vein separation method which utilizes single-wavelength coherent illumination is presented. This method is based on the relative temporal minimum reflectance analysis of laser speckle images. The validation is demonstrated with both theoretic simulations and experimental results applied to the rat cortex. Moreover, this method can be combined with laser speckle contrast analysis so that the artery-vein separation and blood flow imaging can be simultaneously obtained using the same raw laser speckle images data to enable more accurate analysis of changes of cerebral blood flow within different tissue compartments during functional activation, disease dynamic, and neurosurgery, which may broaden the applications of laser speckle imaging in biology and medicine.

Novel multidrug nanoparticles were self-assembled from the random copolymer containing cytarabine and fluorodeoxyuridine. The multidrug copolymer carrying 28.7wt.% of cytarabine and 29.1wt.% of fluorodeoxyuridine was prepared by radical polymerization combined with enzymatic selective transesterification. Homopolymers of the two drugs were also synthesized by the same method. And the polymers were characterized by FTIR, (1)H NMR, and gel permeation chromatography (GPC). Self-assembly of the multidrug copolymer was verified by UV-vis and fluorescence spectroscopy. The morphology of nanoparticles formed from the copolymer was investigated by transmission electron microscopy (TEM) and dynamic light scattering (DLS), which indicated that the nanoparticles were regular spheres with a diameter of 133+/-28nm. In vitro drug release studies illustrated that the two synergistic anticancer agents could be simultaneously released from the multidrug nanoparticles.