(meso-5,7,7,12,14,14-Hexamethyl-1,4,8,11-tetra­azacyclo­tetra­deca-4,11-diene)nickel(II) bis­[O,O′-bis(4-methyl­phen­yl) dithio­phosphate]

In the title compound, [Ni(C16H32N4)](C14H14O2PS2)2 or [Ni(trans[14]dien)][S2P(OC6H4Me-4)2]2, where trans[14]dien is meso-5,7,7,12,14,14-hexa­methyl-1,4,8,11-tetra­azacyclo­tetra­deca-4,11-diene, the NiII ion lies across a centre of inversion and is four-coordinated in a relatively undistorted square-planar arrangement by the four N atoms of the macrocyclic ligand trans[14]dien. The two O,O′-di(4-methyl­phen­yl)dithio­phos­phates act as counter-ions to balance the charge. Important geometric data include Ni—N = 1.9135 (16) and 1.9364 (15) Å

Drug resistance and new therapies in colorectal cancer

Colorectal cancer (CRC) is often diagnosed at an advanced stage when tumor cell dissemination has taken place. Chemo- and targeted therapies provide only a limited increase of overall survival for these patients. The major reason for clinical outcome finds its origin in therapy resistance. Escape mechanisms to both chemo- and targeted therapy remain the main culprits. Here, we evaluate major resistant mechanisms and elaborate on potential new therapies. Amongst promising therapies is α-amanitin antibody-drug conjugate targeting hemizygous p53 loss. It becomes clear that a dynamic interaction with the tumor microenvironment exists and that this dictates therapeutic outcome. In addition, CRC displays a limited response to checkpoint inhibitors, as only a minority of patients with microsatellite instable high tumors is susceptible. In this review, we highlight new developments with clinical potentials to augment responses to checkpoint inhibitors

Protective efficacy of a broadly cross-reactive swine influenza DNA vaccine encoding M2e, cytotoxic T lymphocyte epitope and consensus H3 hemagglutinin

BACKGROUND: Pigs have been implicated as mixing reservoir for the generation of new pandemic influenza strains, control of swine influenza has both veterinary and public health significance. Unlike human influenza vaccines, strains used for commercially available swine influenza vaccines are not regularly replaced, making the vaccines provide limited protection against antigenically diverse viruses. It is therefore necessary to develop broadly protective swine influenza vaccines that are efficacious to both homologous and heterologous virus infections. In this study, two forms of DNA vaccines were constructed, one was made by fusing M2e to consensus H3HA (MHa), which represents the majority of the HA sequences of H3N2 swine influenza viruses. Another was made by fusing M2e and a conserved CTL epitope (NP147-155) to consensus H3HA (MNHa). Their protective efficacies against homologous and heterologous challenges were tested. RESULTS: BALB/c mice were immunized twice by particle-mediated epidermal delivery (gene gun) with the two DNA vaccines. It was shown that the two vaccines elicited substantial antibody responses, and MNHa induced more significant T cell-mediated immune response than MHa did. Then two H3N2 strains representative of different evolutional and antigenic clusters were used to challenge the vaccine-immunized mice (homosubtypic challenge). Results indicated that both of the DNA vaccines prevented homosubtypic virus infections completely. The vaccines’ heterologous protective efficacies were further tested by challenging with a H1N1 swine influenza virus and a reassortant 2009 pandemic strain. It was found that MNHa reduced the lung viral titers significantly in both challenge groups, histopathological observation showed obvious reduction of lung pathogenesis as compared to MHa and control groups. CONCLUSIONS: The combined utility of the consensus HA and the conserved M2e and CTL epitope can confer complete and partial protection against homologous and heterologous challenges, respectively, in mouse model. This may provide a basis for the development of universal swine influenza vaccines

Distribution patterns of small-molecule ligands in the protein universe and implications for origin of life and drug discovery

Ligand-protein mapping was found to follow a power law and the preferential attachment principle, leading to the identification of the molecules, mostly nucleotide-containing compounds, that are likely to have evolved earliest

{N′-[(E)-1-(5-Bromo-2-oxidophen­yl)ethyl­idene]-4-chloro­benzohydrazidato}pyridinenickel(II)

The title complex, [Ni(C15H10BrClN2O2)(C5H5N)], displays a square-planar coordination geometry around the NiII ion, formed by the tridentate hydrazone and monodentate pyridine ligands, with the N atoms in a trans arrangement about the Ni center

Synthesis of MnO

Hierarchical MnO2 microfibers were prepared by using cotton as the template and KMnO4 as the precursor via an ultrasonic assistance route. The results of scanning electron microscope characterization showed that the concentration of KMnO4 had a significant effect on the morphology of MnO2 microfiber. At low concentration of KMnO4, the microfiber was composed of MnO2 nanorods with single crystal structure. With increasing the concentration of KMnO4, the secondary nanostructure of MnO2 microfibers had a transformation from nanorod to nanoparticle. The results of N2 adsorption-desorption analysis indicated that MnO2 microfibers had BET surface area of about 25 m2/g. This synthesis provides a new way to control the secondary nanostructure of MnO2 microfiber by adjusting the concentration of precursor. Furthermore, the mechanism for the replication was proposed and discussed

TMRT observations of 26 pulsars at 8.6 GHz

Integrated pulse profiles at 8.6~GHz obtained with the Shanghai Tian Ma Radio Telescope (TMRT) are presented for a sample of 26 pulsars. Mean flux densities and pulse width parameters of these pulsars are estimated. For eleven pulsars these are the first high-frequency observations and for a further four, our observations have a better signal-to-noise ratio than previous observations. For one (PSR J0742-2822) the 8.6~GHz profiles differs from previously observed profiles. A comparison of 19 profiles with those at other frequencies shows that in nine cases the separation between the outmost leading and trailing components decreases with frequency, roughly in agreement with radius-to-frequency mapping, whereas in the other ten the separation is nearly constant. Different spectral indices of profile components lead to the variation of integrated pulse profile shapes with frequency. In seven pulsars with multi-component profiles, the spectral indices of the central components are steeper than those of the outer components. For the 12 pulsars with multi-component profiles in the high-frequency sample, we estimate the core width using gaussian fitting and discuss the width-period relationship.Comment: 33 pages, 49 figures, 5 Tables; accepted by Ap