Electrocatalytic and Hg2+ Fluorescence Identifiable Bifunctional Sensors for a Series of Keggin Compounds.

By using a 2,2'-dimethyl-4,4'-bithiazole (dm4bt) ligand, Keggin polyanions, and different metal ions, nine Keggin-based compounds, namely, {[Ag(dm4bt)2][Ag2(dm4bt)3]}2(PW12O40)(H2PWV2WVI10O40) (1), [CuI(dm4bt)2][CuII(dm4bt)2(PW12O40)] (2), [CuI(dm4bt)2]4(SiW12O40) (3), {[Zn(dm4bt)2]2(SiW12O40)} (4), [Zn(dm4bt)2(H2O)]2(HPMoV2MoVI10O40)·2H2O (5), [Zn(dm4bt)2(Mo2O7)] (6), [Cd(dm4bt)3][Cd(dm4bt)2(H2O)(PMo12O40)]2·2H2O (7), [Cd(dm4bt)3](PMo12O40)·(Hdm4bt) (8), and [Cd(dm4bt)2(H2O)2]2(HPMoV2MoVI10O40)·2H2O (9), have been hydrothermally synthesized and characterized by single-crystal X-ray diffraction analysis, IR spectroscopy, and elemental analyses. Compounds 1-9 are zero-dimensional structures except compound 6, which exhibits a one-dimensional structure. In compound 1, there are three isolated subunits: Keggin anions, binuclear [Ag2(dm4bt)3]2+, and mononuclear [Ag(dm4bt)2]+ clusters. The binuclear [Ag2(dm4bt)3]2+ cluster has a Ag-Ag bond. In compound 2, a monosupporting anion {[CuII(dm4bt)2](PW12O40)}- and an isolated [Cu(dm4bt)2]+ cluster exist. By changing the transition metal ions, we obtained two different structures: a supramolecular 3 and a bisupporting anion in 4. By a one-pot method, we successfully obtained compounds 5 and 6, 7 and 8, respectively. In compound 5, the [Zn(dm4bt)2(H2O)]2+ subunit links adjacent PMo12 anions via S···O interactions to form a one-dimensional (1D) supramolecular chain. In compound 6, some PMo12 ions have transformed to [Mo2O7] n2 n- chains. The [Zn(dm4bt)2]2+ clusters buckle up and down the chain. Compound 7 has a monosupporting anion and an isolated [Cd(dm4bt)3]2+ cluster. Compound 8 has isolated anions and [Cd(dm4bt)3]2+ clusters. By changing the pH of 7 and 8, a distinct supramolecular compound 9 was obtained. Additionally, the optical band gap, electrochemical, and photocatalytic properties of 1-9 have been investigated in detail. The carbon paste electrodes can be used as bifunctional amperometric and fluorescence sensors for recognition of Hg2+. The n-CPEs as electrochemical sensors can show accurate selectivity for NO2- ions in some common ions. In the fluorescence sensor experiment, fluorescence intensities decrease more than 80% when quenched by Hg2+.

Genetic Variation and Regulation of MICA Alters Natural Killer Cell-Mediated Immunosurveillance in Early-Onset Colorectal Cancer.

The incidence of colorectal cancer (CRC) among individuals under age 50, or early-onset CRC (EOCRC), has been rising over the past few decades for unclear reasons, and the etiology of the disease remains largely unknown. Known genetic risk factors do not explain this increase, pointing to possible environmental and as-yet unidentified genetic contributors and their interactions. Previous research linked genetic variation on chromosome 6 to increased CRC risk. This region harbors multiple immune genes, including the gene encoding Major Histocompatibility Complex (MHC) class I polypeptide-related sequence A (MICA). MICA is a polygenic ligand for the Natural Killer Group 2D receptor (NKG2D), a receptor expressed on Natural Killer (NK) cells and other lymphocytes. Given that intra-tumoral NK cell infiltration correlates with favorable CRC outcomes, we hypothesized that germline genetic variation in MICA could influence CRC risk. In a discovery set of 40,125 cases and controls, we show that the minor G allele at Chr6:31373718C>G (hg19) is associated with increased risk for CRC (odds ratio (OR) = 1.09, 95% confidence interval (CI) 1.04 - 1.15, p = 0.0009). The effect is stronger in EOCRC (OR = 1.26, 95% CI 1.08 - 1.44, p = 0.0023) than in those 50 and over (OR = 1.07, 95% CI 1.02 - 1.13; p = 0.012) (Ratio of ORs = 1.32, 95% CI 1.14 - 1.52, p = 0.0002). In an independent validation set of 77,983 cases and controls, the adjusted interaction by age-of-onset was significant at OR = 1.15 (95% CI 1.03 - 1.34, p = 0.0150) with a higher risk in EOCRC. Expression quantitative trait locus analysis in normal colonic epithelia showed that MICA RNA expression decreases linearly with each additional copy of the minor G allele (p = 3.345 × 10e-18). Bulk RNA analysis of the tumor immune microenvironment revealed that tumors from patients with CG or GG genotypes have lower resting and activated NK cell infiltration as compared to tumors from patients with CC genotype. Multiplex immunofluorescence analysis demonstrated that patients with a G allele (i.e. CG or GG genotype, but not CC genotype) have a statistically significant decrease in the number of NK cells in tumor compared to adjacent normal colonic mucosa. Taken together, population-based epidemiologic, molecular, genetic, cellular and immunologic evidence demonstrate that MICA genotype is associated with increased risk of EOCRC and reduced number of NK cells in colorectal tumors, suggesting that patients with a G allele have altered NK cell-mediated immunosurveillance. These novel findings suggest that EOCRC may have a previously unrecognized innate immune-mediated etiology which merits further investigation.

Two genome-wide interaction loci modify the association of nonsteroidal anti-inflammatory drugs with colorectal cancer.

Regular, long-term aspirin use may act synergistically with genetic variants, particularly those in mechanistically relevant pathways, to confer a protective effect on colorectal cancer (CRC) risk. We leveraged pooled data from 52 clinical trial, cohort, and case-control studies that included 30,806 CRC cases and 41,861 controls of European ancestry to conduct a genome-wide interaction scan between regular aspirin/nonsteroidal anti-inflammatory drug (NSAID) use and imputed genetic variants. After adjusting for multiple comparisons, we identified statistically significant interactions between regular aspirin/NSAID use and variants in 6q24.1 (top hit rs72833769), which has evidence of influencing expression of TBC1D7 (a subunit of the TSC1-TSC2 complex, a key regulator of MTOR activity), and variants in 5p13.1 (top hit rs350047), which is associated with expression of PTGER4 (codes a cell surface receptor directly involved in the mode of action of aspirin). Genetic variants with functional impact may modulate the chemopreventive effect of regular aspirin use, and our study identifies putative previously unidentified targets for additional mechanistic interrogation.

Synthesis of Ni-B Compounds by High-Pressure and High-Temperature Method.

Nickel borides are promising multifunctional materials for high hardness and excellent properties in catalysis and magnetism. However, it is still a blank of intrinsic properties in Ni-B compounds, because crystallization of the single phases of Ni-B compounds with micro-size is a challenge. In this work, single phases of Ni2B (I4/mcm), α-Ni4B3 (Pnma), ß-Ni4B3 (C2/c), and NiB (Cmcm) are synthesized by high pressure and high temperature (HPHT). The results indicate that synthesizing α-Ni4B3 and ß-Ni4B3 requires more energy than Ni2B and NiB. The growth process of Ni-B compounds is that Ni covers B to form Ni-B compounds under HPHT, which also makes the slight excess of B necessary. So, generating homogeneous distribution of starting materials and increasing the interdiffusion between Ni and B are two keys to synthesize well crystallized and purer samples by HPHT. This work uncovers the growth process of Ni-B compounds, which is significant to guide the synthesis of highly crystalline transition metal borides (TMBs) in the future.