Application of transition metal phosphides (TMPs) for electrochemical energy conversion and storage has great potential to alleviate the energy crisis. Although there are many methods to get TMPs, it is still immensely challenging to fabricate hierarchical porous TMPs with superior electrochemical performances by a simple, green, and secure approach. Herein, we report a facile method to synthesize the CoP/C nanoboxes by pyrolysis of phytic acid (PA) cross-linked Co complexes that are acquired from reaction of PA and ZIF-67. The PA can not only slowly etch ZIF-67 and gain a hollow structure but also act as a source of phosphorus to prepare CoP/C nanoboxes. The CoP/C nanoboxes deliver an ultrahigh specific capacity (868 mA h g −1 at 100 mA g −1 ) and excellent cycle stability (523 mA h g −1 after 1000 cycles at 500 mA h g −1 ) when used as anode materials for lithium-ion batteries. Moreover, when used as an electrocatalyst for hydrogen evolution reaction, the CoP/C nanoboxes exhibit ultralow overpotential, small Tafel slope, and excellent durability in acidic media.

IntroductionAn array of chronic inflammatory diseases, including Crohn disease, psoriasis, rheumatoid arthritis, and multiple sclerosis, cause widespread and severe health problems. These and other immune diseases can be considered to have a predominantly T helper cell type 1 (Th1) bias. Although injectable biologic treatments such as antibodies and soluble protein that block TNF-␣ have provided significant clinical benefit, there is still a high unmet medical need, particularly for a safe targeted drug that can be taken orally.Interleukin-12 (IL-12) is a heterodimeric cytokine (p70) composed of 2 independently regulated protein subunits, p35 and p40. IL-12 plays a central role in the immune response by bridging innate resistance and antigen-specific adaptive immunity. 1 It is produced from phagocytic cells and antigen-presenting cells, in particular macrophages and dendritic cells, upon stimulation with bacteria, bacterial products such as lipopolysaccharide (LPS), and intracellular parasites. 2,3 The well-documented biologic functions of IL-12 are the induction of interferon-␥ (IFN-␥) expression from T and natural killer (NK) cells 4,5 and the differentiation of naive T cells toward a Th1-cell type. 6,7 IL-12 also appears to be critical in the expansion and maintenance of the Th1 phenotype. [8][9][10] IL-23, a more recently discovered member of the IL-12 family, also promotes Th1 response, but has distinct functions from IL-12. IL-23 is required for the generation of effector memory T cells. 11 IL-23 is also needed for the generation of IL-17-producing T cells, which play a significant role in the inflammatory response. 12 Through these activities, IL-23 plays a critical role in chronic inflammatory diseases.Although the inflammatory effector function of Th1 is essential for the clearance of intracellular pathogens, the excessive production of proinflammatory cytokines leads to serious tissue damage typical of organ-specific autoimmunity, 13,14 including type 1 diabetes, 15 multiple sclerosis, 16,17 rheumatoid arthritis, 18,19 inflammatory bowel disease, 20 psoriasis, 21 and sepsis. 22 IL-12/IL-23 has been validated as an attractive clinical target by a number of studies. Mice lacking the gene encoding the p40 subunit shared by IL-12 and IL-23 or lacking the IL-23-specific subunit p19 have proven the integral role of IL-12/IL-23 to the pathogenesis of these disorders, implying that blockade of the cytokines could be effective in the treatment of a variety of autoimmune diseases. 21,[23][24][25][26][27][28] Monoclonal antibodies to the IL-12/23 p40 subunit have been shown to be effective in human clinical trials in patients with Crohn disease and psoriasis. 29,30 While antibodies against IL-12/IL-23 could provide significant medical benefit, a small-molecule IL-12/IL-23 inhibitor that could be administered orally would be highly desirable. Although some compounds weakly or nonselectively inhibit IL-12, there are no potent and selective small-molecule IL-12 inhibitors. To find an effective inhibitor against the...

The old one two: A sequential iridium-catalyzed borylation and copper-catalyzed trifluoromethylation of arenes is described (see scheme; Pin = pinacol). The reaction is conducted under mild reaction conditions and tolerates a variety of functional groups. The advantages of this tandem procedure are demonstrated by the late-stage trifluoromethylation of a number of biologically active molecules.

Summary The ErbB receptor family member ErbB3 has been implicated in breast cancer growth but it has yet to be determined whether its disruption is therapeutically valuable. In a mouse model of mammary carcinoma driven by the polyomavirus middle T (PyVmT) oncogene, the ErbB2 tyrosine kinase inhibitor lapatinib reduced the activation of ErbB3 and Akt along with tumor cell growth. In this phosphatidylinositol-3 kinase (PI3K)-dependent tumor model, ErbB2 is part of a complex containing PyVmT, p85 (PI3K), ErbB3, and Src, that is disrupted by treatment with lapatinib. Thus, full engagement of PI3K/Akt by ErbB2 in this oncogene-induced mouse tumor model may involve its ability to dimerize with and phosphorylate ErbB3, which itself directly binds PI3K. Here we report that ErbB3 is critical for PI3K/AKT-driven tumor formation triggered by the PyVmT oncogene. Tissue-specific, Cre-mediated deletion of ErbB3 reduced Akt phosphorylation, primary tumor growth and pulmonary metastasis. Further EZN-3920, a chemically stabilized antisense oligonucleotide that targets the ErbB3 mRNA in vivo, produced similar effects while causing no mouse toxicity. Our findings offer further preclinical evidence that ErbB3 ablation may be therapeutically effective in tumors where ErbB3 engages PI3K/Akt signaling.

Usually, small interfering RNAs and most antisense molecules need mechanical or chemical delivery methods to down-modulate the targeted mRNA. However, these delivery approaches complicate the interpretations of biological consequences. We show that locked nucleic acid (LNA)-based antisense oligonucleotides (LNA–ONs) readily down-modulate genes of interest in multiple cell lines without any delivery means. The down-modulation of genes was quick, robust, long-lasting and specific followed by potent down-modulation of protein. The efficiency of the effect varied among the 30 tumor cell lines investigated. The most robust effects were found in those cells where nuclear localization of the LNA–ON was clearly observed. Importantly, without using any delivery agent, we demonstrated that HER3 mRNA and protein could be efficiently down-modulated in cells and a tumor xenograft model. These data provide a simple and efficient approach to identify potential drug targets and animal models. Further elucidation of the mechanism of cellular uptake and trafficking of LNA–ONs may enhance not only the therapeutic values of this platform but also antisense molecules in general.

A novel Sb/C polyhedra composite is successfully fabricated by a galvanic replacement reaction technique using metal organic frameworks as templates. In this composite, the ultrasmall Sb nanoparticles with an average size of 15 nm are homogeneously encapsulated into the carbon matrixes, forming a hierarchical porous structure with nanosized building blocks. Used as an anode material for lithium ion batteries, this composite exhibits high lithium storage capacities, excellent rate capability and superior cycle stability, higher than many reported results. Notably, a discharge capacity of 565 mAh g −1 at a current density of 0.2 A g −1 is delivered after 100 repeated cycles. Even at a high current density of 1 A g −1 , a discharge capacity of 400.5 mAh g −1 is also maintained after 500 cycles. Such superior cycling stability and rate discharge performance of the designed Sb/C composite can be attributed to the synergistic effect between Sb nanoparticles and the porous carbon matrixes.

Abstract. Vegetation plays a key role in maintaining soil quality, but long-term changes in soil quality due to plant species change and successive planting are rarely reported. Using the space-for-time substitution method, adjacent plantations of Pinus and first, second, third and fourth generations of Eucalyptus in Guangxi, China were used to study changes in soil quality caused by converting Pinus to Eucalyptus and successive Eucalyptus planting. Soil chemical and biological properties were measured and a soil quality index was calculated using principal component analysis. Soil organic carbon, total nitrogen, alkaline hydrolytic nitrogen, microbial biomass carbon, microbial biomass nitrogen, cellobiosidase, phenol oxidase, peroxidase and acid phosphatase activities were significantly lower in the first and second generations of Eucalyptus plantations compared with Pinus plantation, but they were significantly higher in the third and fourth generations than in the first and second generations and significantly lower than in Pinus plantation. Soil total and available potassium were significantly lower in Eucalyptus plantations (1.8-2.5 g kg −1 and 26-66 mg kg −1 ) compared to the Pinus plantation (14.3 g kg −1 and 92 mg kg −1 ), but total phosphorus was significantly higher in Eucalyptus plantations (0.9-1.1 g kg −1 ) compared to the Pinus plantation (0.4 g kg −1 ). As an integrated indicator, soil quality index was highest in the Pinus plantation (0.92) and lowest in the first and second generations of Eucalyptus plantations (0.24 and 0.13). Soil quality index in the third and fourth generations (0.36 and 0.38) was between that in Pinus plantation and in first and second generations of Eucalyptus plantations. Changing tree species, reclamation and fertilization may have contributed to the change observed in soil quality during conversion of Pinus to Eucalyptus and successive Eucalyptus planting. Litter retention, keeping understorey coverage, and reducing soil disturbance during logging and subsequent establishment of the next rotation should be considered to help improving soil quality.

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