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The K64Q mutation results in altered binding profiles with the highest binding affinity to PIP(4,5)P2 with specific acyl chains. Mutation of R92 to Pro, a residue found in Kir6.2, results in promiscuous binding of PIP isoforms. Kir3.2 with the K194A mutation results in a distinct binding preference for PIP(3,4,5)P3 over other PIP isoforms. Taken together, our results underscore the utmost importance of protein quality for protein-lipid binding studies and a single mutation in Kir3.2 can alter the selectivity toward PIPs.As part of a continuing research program aiming to identify chemical probes to interrogate Parkinson's disease (PD), we have investigated the Australian plants Gloriosa superba and Alangium villosum. The chemical investigations of G. superba resulted in the isolation of four new alkaloids, β-lumicolchicosides A-C (1-3) and γ-lumicolchicoside A (4), together with four lumicolchicine derivatives (5-8) and six colchicine analogues (9-14) as known structures. The chemical investigations of A. villosum resulted in the isolation of four new benzoquinolizidine N-oxides, tubulosine Nβ5-oxide (15), isotubulosine Nα5-oxide (16), 9-demethyltubulosine Nβ5-oxide (17), and 9-demethylisotubulosine Nα5-oxide (18), together with five known benzoquinolizidine alkaloids (19-23). The chemical structures of the new compounds (1-4 and 15-18) were characterized unambiguously by extensive analysis of their NMR and MS data. Unbiased multidimensional profiling was used to investigate the phenotypic profiles of all of the metabolites. The results show that the lead probes have different effects on cellular organelles that are implicated in PD in patient-derived cells.The present study exposed adult zebrafish to 0, 10, and 100 μg/L perfluorobutanesulfonate (PFBS) with or without dietary supplement of probiotic Lactobacillus rhamnosus. Interaction between probiotic and PFBS on sex endocrine and reproduction was investigated. It was striking to find that PFBS and probiotic coexposures almost ceased the fecundity, which was accompanied by disturbances in sex hormones and oocyte maturation in females. In contrast, probiotic additive efficiently antagonized the estrogenic activity of PFBS in males. For the first time, this study reported that probiotic heavily depended on sex to modulate the endocrine disruption and reproductive toxicity of aquatic pollutants.Methyl jasmonate (MeJA), a natural phytohormone, played a critical role not only in plant growth but also in plant defense response to biotic and abiotic stresses. MYC2, a basic helix-loop-helix transcription factor, is a master regulator in MeJA signaling pathway. In the present work, slmyc2 mutants were generated by the clustered regularly interspaced short palindromic repeats and associated Cas9 protein (CRISPR/Cas9) system to investigate the role of SlMYC2 in tomato plant growth and fruit disease resistance induced by exogenous MeJA. The results showed that slmyc2 mutants possessed a higher number of flowers and a lower fruit setting rate in comparison with wild-type plants. In addition, the fruit shape of slmyc2 mutant was prolate, while the control fruits were oblate. Knockout of SlMYC2 significantly decreased the activities of disease defensive and antioxidant enzymes, as well as the expression levels of pathogen-related (PR) genes (SlPR-1 and SlPR-STH2) and the key genes related to jasmonic acid (JA) biosynthesis and signaling pathway including allene oxide cyclase (SlAOC), lipoxygenase D (SlLOXD), SlMYC2, and coronatine insensitive 1 (SlCOI1), and consequently aggravated the disease symptoms. By contrast, the disease symptoms were largely reduced in MeJA-treated fruit that possessed higher activities of these enzymes and expression levels of genes. However, the induction effects of MeJA on fruit disease resistance and these enzymes' activities and genes' expressions were significantly attenuated by knockout of SlMYC2. find more Therefore, the results indicated that SlMYC2 played positive regulatory roles not only in the growth of tomato plants but also in MeJA-induced disease resistance and the antioxidant process in tomato fruits.As an important organic intermediate, benzonitrile (BN) is widely involved in organic synthetic chemistry and pharmaceutical and dyestuff industries. However, the exploration of a more efficient and controllable synthesis technique and the corresponding greener catalysts for the synthesis of BN still poses a great challenge. Herein, with multimetallic two-dimensional conductive metal-organic frameworks (2D cMOF) as anodic electrocatalysts, we develop a green, convenient, and highly efficient electrochemical synthesis strategy for BN. Thanks to the intrinsic 2D electrically conductive structure and the optimized the multimetallic coupling catalytic effect, the resulting multimetallic 2D cMOFs exhibit excellent benzylamine (BA) electrooxidation performance. Especially, the trimetallic 2D cMOF (NiCoFe-CAT) requires an ultralow potential of 1.29 V vs reversible hydrogen electrode (RHE) to achieve a 10 mA·cm-2 current density, which indicates the fastest reaction and the most favorable thermodynamic condition. A very high yield (0.058 mmol·mg-1·h-1) and faradic efficiency (∼87%) of benzonitrile are both achieved during the BA electrooxidation reaction at 1.45 V. The reaction mechanism investigations indicated that the various redox mediators of MII/MIII (Ni, Co, Fe) may be regarded as multimetal active species to promote BA conversion. Also, the excellent cycling durability of multimetallic 2D cMOFs further promotes their potential practical applications. These electrocatalytic performances are considered excellent and nearly surpass all other reported Ni-based inorganics or MOF-based electrocatalysts for the electrocatalytic oxidation of benzylamine.A critical point for the successful development of a fluorescent quantum dot (QD)-based immunoassay is maintaining the high fluorescence quantum yield of QDs during hydrophilization and bioconjugation. In this paper, we carefully designed CdSe/CdS and CdSe/CdS/ZnS core-shell heterostructures and extended them with silica coating of different surface composition allowing preservation of fluorescence quantum yield as high as 70% in aqueous media. The silanized QDs containing epoxy and carboxy surface groups were bioconjugated with monoclonal antibodies. The synthesized fluorescent conjugates were used in a multicolor lateral flow immunoassay for simultaneous determination of two mycotoxins. Zearalenone and deoxynivalenol were chosen as a proof of concept. Cutoff levels for the zearalenone and deoxynivalenol detection were adjusted to be at 40 and 400 μg kg-1, respectively, complying with the European Commission regulation. Validation of the developed test was performed by analysis of 34 naturally contaminated maize and wheat samples; as a confirmatory method, LC-MS/MS was used.
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