Evidence for Carbene Intermediates in Isocyanide Homologation by Aluminium(I).

The C-C bond formation between C1 molecules plays an important role in chemistry as manifested by the Fischer-Tropsch (FT) process. Serving as models for the FT process, we report here the reactions between a neutral AlI complex (Me NacNac)Al (1, Me NacNac=HC[(CMe)(NDipp)]2 , Dipp=2,6-diisopropylphenyl) and various isocyanides. The step-by-step coupling mechanism was studied in detail by low-temperature NMR monitoring, isotopic labeling, as well as quantum chemical calculations. Three different products were isolated in reaction of 1 with the sterically encumbered 2,6-bis(benzhydryl)-4-Me-phenyl isocyanide (BhpNC). These products substantiate carbene intermediates. The reaction between 1 and adamantyl isocyanide (AdNC) generated a trimerization product, and a corresponding carbene intermediate could be trapped in the form of a molybdenum(0) complex. Tri-, tetra-, and even pentamerization products were isolated with the sterically less congested phenyl and p-methoxyphenyl isocyanides (PhNC and PMPNC) with concurrent construction of quinoline or indole heterocycles. Overall, this study provides evidence for carbene intermediates in FT-type chemistry of aluminium(I) and isocyanides.

A Borane Lewis Acid in the Secondary Coordination Sphere of a Ni(II) Imido Imparts Distinct C-H Activation Selectivity.

Two borane-functionalized bidentate phosphine ligands that vary in tether length have been prepared to examine cooperative metal-substrate interactions. Ni(0) complexes react with aryl azides at low temperatures to form structurally unusual κ2-(N,N)-N3Ar adducts. Warming these adducts affords products of N2 extrusion and in one case, a Ni-imido compound that is capped by the appended borane. Reactions with 1-azidoadamantane (AdN3) provide a distinct outcome, where a proposed nickel imido intermediate activates the sp2 C-H bonds of arenes, even in the presence of benzylic C-H sites. Combined experimental and computational mechanistic studies demonstrate that the unique reactivity is a consequence of Lewis-acid-induced polarization of the Ni-NR bond, potentially providing a synthetic strategy for chemoselective reaction engineering.

Selective export of autotaxin from the endoplasmic reticulum.

Autotaxin (ATX) or ectonucleotide pyrophosphatase/phosphodiesterase 2 (ENPP2) is a secretory glycoprotein and functions as the key enzyme for lysophosphatidic acid generation. The mechanism of ATX protein trafficking is largely unknown. Here, we demonstrated that p23, a member of the p24 protein family, was the protein-sorting receptor required for endoplasmic reticulum (ER) export of ATX. A di-phenylalanine (Phe-838/Phe-839) motif in the human ATX C-terminal region was identified as a transport signal essential for the ATX-p23 interaction. Knockdown of individual Sec24 isoforms by siRNA revealed that ER export of ATX was impaired only if Sec24C was down-regulated. These results suggest that ATX is selectively exported from the ER through a p23, Sec24C-dependent pathway. In addition, it was found that AKT signaling played a role in ATX secretion regulation to facilitate ATX ER export by enhancing the nuclear factor of activated T cell-mediated p23 expression. Furthermore, the di-hydrophobic amino acid motifs (FY) also existed in the C-terminal regions of human ENPP1 and ENPP3. Such a p23, Sec24C-dependent selective ER export mechanism is conserved among these ENPP family members.

Autotaxin is induced by TSA through HDAC3 and HDAC7 inhibition and antagonizes the TSA-induced cell apoptosis.

BACKGROUND: Autotaxin (ATX) is a secreted glycoprotein with the lysophospholipase D (lysoPLD) activity to convert lysophosphatidylcholine (LPC) into lysophosphatidic acid (LPA), a bioactive lysophospholipid involved in diverse biological actions. ATX is highly expressed in some cancer cells and contributes to their tumorigenesis, invasion, and metastases, while in other cancer cells ATX is silenced or expressed at low level. The mechanism of ATX expression regulation in cancer cells remains largely unknown. RESULTS: In the present study, we demonstrated that trichostatin A (TSA), a well-known HDAC inhibitor (HDACi), significantly induced ATX expression in SW480 and several other cancer cells with low or undetectable endogenous ATX expression. ATX induction could be observed when HDAC3 and HDAC7 were down-regulated by their siRNAs. It was found that HDAC7 expression levels were low in the cancer cells with high endogenous ATX expression. Exogenous over-expression of HDAC7 inhibited ATX expression in these cells in a HDAC3-dependent manner. These data indicate that HDAC3 and HDAC7 collaboratively suppress ATX expression in cancer cells, and suggest that TSA induce ATX expression by inhibiting HDAC3 and HDAC7. The biological significance of this regulation mechanism was revealed by demonstrating that TSA-induced ATX protected cancer cells against TSA-induced apoptosis by producing LPA through its lysoPLD activity, which could be reversed by BrP-LPA and S32826, the inhibitors of the ATX-LPA axis. CONCLUSIONS: We have demonstrated that ATX expression is repressed by HDAC3 and HDAC7 in cancer cells. During TSA treatment, ATX is induced due to the HDAC3 and HDAC7 inhibition and functionally antagonizes the TSA-induced apoptosis. These results reveal an internal HDACi-resistant mechanism in cancer cells, and suggest that the inhibition of ATX-LPA axis would be helpful to improve the efficacy of HDACi-based therapeutics against cancer.

Biomass-Derived Carbon Paper to Sandwich Magnetite Anode for Long-Life Li-Ion Battery.

Metal oxides can deliver high capacity to Li-ion batteries, surpassing conventional graphite, but they suffer from a huge volume change during charging-discharging and poor cycle life. Herein, we merge the dual strategies of 3D-network support and sandwiching design to tackle such issue. We develop a skillful O2-NH3 reactive pyrolysis of cellulose, where the preoxidation and the aminolysis result in the spatially separated charring of cellulose chains. A cellulose fiber is wonderfully converted into several ultrathin twisted graphenic sheets instead of a dense carbon fiber, and consequently, a cellulose paper is directly transformed into a porous flexible carbon paper with high surface area and conductivity (denoted as CP). CP is further fabricated as a 3D-network support into the hybrid CP@Fe3O4@RGO, where RGO is reduced graphene oxide added for sandwiching Fe3O4 particles. As a binder-free free-standing anode, CP@Fe3O4@RGO effectively fastens Fe3O4 and buffers the volume changes on cycling, which stabilizes the passivating layer and lifts the Coulombic efficiency. The anode thus presents an ultralong cycle life of >2000 running at a high capacity level of 1160 mAh g-1. It additionally facilitates electron and ion transports, boosting the rate capability. CP and CP@Fe3O4@RGO represent a technological leap underpinning next-generation long-life high-capacity high-power batteries.

Study on sandstorm PM10 exposure assessment in the large-scale region: a case study in Inner Mongolia.

The current exposure-effect curves describing sandstorm PM10 exposure and the health effects are drawn roughly by the outdoor concentration (OC), which ignored the exposure levels of people's practical activity sites. The main objective of this work is to develop a novel approach to quantify human PM10 exposure by their socio-categorized micro-environment activities-time weighed (SCMEATW) in strong sandstorm period, which can be used to assess the exposure profiles in the large-scale region. Types of people's SCMEATW were obtained by questionnaire investigation. Different types of representatives were trackly recorded during the big sandstorm. The average exposure levels were estimated by SCMEATW. Furthermore, the geographic information system (GIS) technique was taken not only to simulate the outdoor concentration spatially but also to create human exposure outlines in a visualized map simultaneously, which could help to understand the risk to different types of people. Additionally, exposure-response curves describing the acute outpatient rate odds by sandstorm were formed by SCMEATW, and the differences between SCMEATW and OC were compared. Results indicated that acute outpatient rate odds had relationships with PM10 exposure from SCMEATW, with a level less than that of OC. Some types of people, such as herdsmen and those people walking outdoors during a strong sandstorm, have more risk than office men. Our findings provide more understanding of human practical activities on their exposure levels; they especially provide a tool to understand sandstorm PM10 exposure in large scale spatially, which might help to perform the different categories population's risk assessment regionally.