Successful development of ultra-sensitive molecular imaging nanoprobes for the detection of targeted biological objects is a challenging task. Although magnetic nanoprobes have the potential to perform such a role, the results from probes that are currently available have been far from optimal. Here we used artificial engineering approaches to develop innovative magnetic nanoprobes, through a process that involved the systematic evaluation of the magnetic spin, size and type of spinel metal ferrites. These magnetism-engineered iron oxide (MEIO) nanoprobes, when conjugated with antibodies, showed enhanced magnetic resonance imaging (MRI) sensitivity for the detection of cancer markers compared with probes currently available. Also, we successfully visualized small tumors implanted in a mouse. Such high-performance, nanotechnology-based molecular probes could enhance the ability to visualize other biological events critical to diagnostics and therapeutics.

The trifluoromethyl group can dramatically influence the properties of organic molecules, thereby increasing their applicability as pharmaceuticals, agrochemicals, or building blocks for organic materials. Despite the importance of this substituent, no general method exists for its installment onto functionalized aromatic substrates. Current methods either require the use of harsh reaction conditions or suffer from a limited substrate scope. Herein, we report the palladium-catalyzed trifluoromethylation of aryl chlorides under mild conditions, allowing the transformation of a wide range of substrates, including heterocycles, in excellent yields. The process tolerates functional groups such as esters, amides, ethers, acetals, nitriles, and tertiary amines and therefore should be applicable to late-stage modifications of advanced intermediates. We also have prepared all the putative intermediates in the catalytic cycle and demonstrated their viability in the process.

The control of a reaction that can form multiple products is a highly attractive and challenging concept in synthetic chemistry. A set of valuable CF3 -containing molecules, namely trifluoromethylated alkenyl iodides, alkenes, and alkynes, were selectively generated from alkynes and CF3 I by environmentally benign and efficient visible-light photoredox catalysis. Subtle differences in the combination of catalyst, base, and solvent enabled the control of reactivity and selectivity for the reaction between an alkyne and CF3 I.

Somatic cells can be reprogrammed into induced pluripotent stem cells (iPSCs) by transduction of reprogramming factors, including Oct4, Sox2, Klf4, and c-Myc. A coordinated network of these factors was suggested to confer a pluripotency of iPSCs. Together with Oct4, Sox2 plays a major role as a master regulator in ESCs. However, the underlying mechanisms by which Sox2 contributes to selfrenewal or reprogramming processes remain to be determined. Here, we provide new evidence for a phosphorylation-based regulation of Sox2 activity. Akt directly interacts with Sox2 and promotes its stabilization through phosphorylation at Thr118, which enhances the transcriptional activity of Sox2 in ESCs. Moreover, phosphorylation of Sox2 cooperates in the reprogramming of mouse embryonic fibroblasts by enabling more efficient induction of iPSCs. Overall, our studies provide new insights into the regulatory mechanism of Sox2 in ESCs and also provide a direct link between phosphorylation events and somatic cell reprogramming.

A new naphthalene derivative containing a urea group at the 1,8-position of naphthalene was synthesized and showed a unique absorption and fluorescence peak with a fluoride ion. Calculations suggested that a new peak was attributed to the increased anion character of urea nitrogen due to the strong interaction of the fluoride and N-H protons.

The ultrasensitive detection of cancer in its earliest stage would greatly help the ensuing treatment process, and therefore various imaging modalities and image-enhancing methods are being developed.[1] In particular, metal oxide nanoparticles prove to be promising contrast agents in magnetic resonance imaging (MRI) for the ultrasensitive detection of cancer, and the principles for enhancing MRI contrast have been deciphered recently.[2] For example, it is advantageous to employ superparamagnetic metal oxide nanoparticles with high magnetization values (emu g À1 ) for improved T 2 image contrast.[3] In addition, clusters of superparamagnetic nanoparticles exhibit greater T 2 contrast abilities than individual nanoparticles.[4] Therefore, the clustering of magnetic nanoparticles with high magnetization values is advantageous because of both improved T 2 contrast and the frugal usage of targeting moieties. For enhanced T 1 contrast, nanoparticles should have numerous high-spin metal ions exposed on the surface for facilitated interactions with the surrounding water molecules. [5,6] This calls for the use of smaller nanoparticles with a high surface-to-volume ratio, but simply using a high number of small nanoparticles is not compatible with the frugal usage of targeting moieties. In the case of large nanoparticles, the non-exposed metal ions in the core cannot contribute to the MRI T 1 contrast; the T 1 -weighted image obtained with metal ions is much poorer than that from conventional ion-based contrast agents.We reasoned that the highest surface area for a nanoparticle of a given diameter would be provided by an urchinlike morphology as shown in Figure 1. As a model system to prove our concept, manganese oxides were investigated that had been previously used as an MRI T 1 contrast agent. This system is particularly interesting because of the easy conversion of MnO to Mn 3 O 4 and the different stabilities of these two manganese oxide phases under physiological conditions. It is envisaged that the MnO nanoparticle trapped in the thin shell of an urchin-shaped stable Mn 3 O 4 phase can be unloaded in the form of Mn II ions to the low-pH sites (< pH 7) in the tumor. While the low pH of tumor cells has been exploited for the fabrication of numerous activatable drug-delivery systems, [7] a nanoparticle-based pH-activatible MRI agent is unprecedented to our knowledge. The combination of the T 1 contrast effect from the empty Mn 3 O 4 urchin shell with a high surface area and the released Mn II ions should make the MnO@Mn 3 O 4 nanourchin a powerful MRI T 1 contrast agent. Herein we report the synthesis of the MnO@Mn 3 O 4 nanourchin through facet-selective etching as well as its successful application as a pH-responsive activatable T 1 contrast agent,

BackgroundLignocellulosic biomass is an attractive renewable resource for future liquid transport fuel. Efficient and cost-effective production of bioethanol from lignocellulosic biomass depends on the development of a suitable pretreatment system. The aim of this study is to investigate a new pretreatment method that is highly efficient and effective for downstream biocatalytic hydrolysis of various lignocellulosic biomass materials, which can accelerate bioethanol commercialization.ResultsThe optimal conditions for the hydrogen peroxide–acetic acid (HPAC) pretreatment were 80 °C, 2 h, and an equal volume mixture of H2O2 and CH3COOH. Compared to organo-solvent pretreatment under the same conditions, the HPAC pretreatment was more effective at increasing enzymatic digestibility. After HPAC treatment, the composition of the recovered solid was 74.0 % cellulose, 20.0 % hemicelluloses, and 0.9 % lignin. Notably, 97.2 % of the lignin was removed with HPAC pretreatment. Fermentation of the hydrolyzates by S. cerevisiae resulted in 412 mL ethanol kg−1 of biomass after 24 h, which was equivalent to 85.0 % of the maximum theoretical yield (based on the amount of glucose in the raw material).ConclusionThe newly developed HPAC pretreatment was highly effective for removing lignin from lignocellulosic cell walls, resulting in enhanced enzymatic accessibility of the substrate and more efficient cellulose hydrolysis. This pretreatment produced less amounts of fermentative inhibitory compounds. In addition, HPAC pretreatment enables year-round operations, maximizing utilization of lignocellulosic biomass from various plant sources.Electronic supplementary materialThe online version of this article (doi:10.1186/s13068-015-0419-4) contains supplementary material, which is available to authorized users.

Owing to their unique biological, physical, and chemical properties, fluoroalkylated organic substances have attracted significant attention from researchers in a variety of disciplines. Fluoroalkylated compounds are considered particularly important in pharmaceutical chemistry because of their superior lipophilicity, binding selectivity, metabolic stability, and bioavailability to those of their nonfluoroalkylated analogues. We have developed various methods for the synthesis of fluoroalkylated substances that rely on the use of visible-light photoredox catalysis, a powerful preparative tool owing to its environmental benignity and mechanistic versatility in promoting a large number of synthetically important reactions with high levels of selectivity. In this Account, we describe the results of our efforts, which have led to the development of visible-light photocatalytic methods for the introduction of a variety of fluoroalkyl groups (such as, -CF, -CFR, -CHCF, -CF, and -CF) and arylthiofluoroalkyl groups (such as, -CFSPh, -CFSAr, and -CFSAr) to organic substances. In these studies, electron-deficient carbon-centered fluoroalkyl radicals were successfully generated by the appropriate choice of fluoroalkyl source, photocatalyst, additives, and solvent. The redox potentials of the photocatalysts and the fluoroalkyl sources and the choice of sacrificial electron donor or acceptor as the additive affected the photocatalytic pathway, determining whether an oxidative or reductive quenching pathway was operative for the generation of key fluoroalkyl radicals. Notably, we have observed that additives significantly affect the efficiencies and selectivities of these reactions and can even change the outcome of the reaction by playing additional roles during its course. For instance, a tertiary amine as an additive in the reaction medium can act not only as a sacrificial electron donor in photoredox catalysis but also as a hydrogen atom source, an elimination base for dehydrohalogenation of the intermediate, and also a Brønsted base for deprotonation. In the same context, the selection of solvent is also critical since it affects the rate and selectivity of reactions depending upon its polarity and reagent solubilizing ability and plays additional roles in the process, for example, as a hydrogen atom source. By clearly understanding the roles of additives and solvent, we designed several controlled fluoroalkylation reactions where different products were formed selectively from the same starting substrates. In addition, we could exploit one of the most important advantages of radical reactions, that is, the use of unactivated π-systems such as alkenes, alkynes, arenes, and heteroarenes as radical acceptors without prefunctionalization. Furthermore, fluoroalkylation processes under mild room-temperature reaction conditions tolerate various functional groups and are therefore easily applicable to late-stage modifications of highly functionalized advanced intermediates.