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This results in hexagonal nanostructures of predefined order and complexity, including few-nanometer-thin nanoribbons and nanojunctions. Thus, this method enables future studies of a broad range of TMD metamaterials through atomically precise control of the structure.An amendment to this paper has been published and can be accessed via a link at the top of the paper.An amendment to this paper has been published and can be accessed via a link at the top of the paper.Thalidomide and its derivatives exert not only therapeutic effects as immunomodulatory drugs (IMiDs) but also adverse effects such as teratogenicity, which are due in part to different C2H2 zinc-finger (ZF) transcription factors, IKZF1 (or IKZF3) and SALL4, respectively. Here, we report the structural bases for the SALL4-specific proteasomal degradation induced by 5-hydroxythalidomide, a primary thalidomide metabolite generated by the enzymatic activity of cytochrome P450 isozymes, through the interaction with cereblon (CRBN). GLPG3970 molecular weight The crystal structure of the metabolite-mediated human SALL4-CRBN complex and mutagenesis studies elucidate the complex formation enhanced by the interaction between CRBN and an additional hydroxy group of (S)-5-hydroxythalidomide and the variation in the second residue of β-hairpin structure that underlies the C2H2 ZF-type neo-morphic substrate (neosubstrate) selectivity of 5-hydroxythalidomide. These findings deepen our understanding of the pharmaceutical action of IMiDs and provide structural evidence that the glue-type E3 ligase modulators cause altered neosubstrate specificities through their metabolism.Prediabetes is a state of glycaemic dysregulation below the diagnostic threshold of type 2 diabetes (T2D). Globally, ~352 million people have prediabetes, of which 35-50% develop full-blown diabetes within five years. T2D and its complications are costly to treat, causing considerable morbidity and early mortality. Whether prediabetes is causally related to diabetes complications is unclear. Here we report a causal inference analysis investigating the effects of prediabetes in coronary artery disease, stroke and chronic kidney disease, complemented by a systematic review of relevant observational studies. Although the observational studies suggest that prediabetes is broadly associated with diabetes complications, the causal inference analysis revealed that prediabetes is only causally related with coronary artery disease, with no evidence of causal effects on other diabetes complications. In conclusion, prediabetes likely causes coronary artery disease and its prevention is likely to be most effective if initiated prior to the onset of diabetes.Understanding and controlling the properties of water-splitting assemblies in dye-sensitized photoelectrosynthesis cells is a key to the exploitation of their properties. We demonstrate here that, following surface loading of a [Ru(bpy)3]2+ (bpy = 2,2'-bipyridine) chromophore on nanoparticle electrodes, addition of the molecular catalysts, Ru(bda)(L)2 (bda = 2,2'-bipyridine-6,6'-dicarboxylate) with phosphonate or pyridyl sites for water oxidation, gives surfaces with a 51 chromophore to catalyst ratio. Addition of the surface-bound phosphonate derivatives with L = 4-pyridyl phosphonic acid or diethyl 3-(pyridin-4-yloxy)decyl-phosphonic acid, leads to well-defined surfaces but, following oxidation to Ru(III), they undergo facile, on-surface dimerization to give surface-bound, oxo-bridged dimers. The dimers have a diminished reactivity toward water oxidation compared to related monomers in solution. By contrast, immobilization of the Ru-bda catalyst on TiO2 with the 4,4'-dipyridyl anchoring ligand can maintain the monomeric structure of catalyst and gives relatively stable photoanodes with photocurrents that reach to 1.7 mA cm-2 with an optimized, applied bias photon-to-current efficiency of 1.5%.Toward smart building and smart home, floor as one of our most frequently interactive interfaces can be implemented with embedded sensors to extract abundant sensory information without the video-taken concerns. Yet the previously developed floor sensors are normally of small scale, high implementation cost, large power consumption, and complicated device configuration. Here we show a smart floor monitoring system through the integration of self-powered triboelectric floor mats and deep learning-based data analytics. The floor mats are fabricated with unique "identity" electrode patterns using a low-cost and highly scalable screen printing technique, enabling a parallel connection to reduce the system complexity and the deep-learning computational cost. The stepping position, activity status, and identity information can be determined according to the instant sensory data analytics. This developed smart floor technology can establish the foundation using floor as the functional interface for diverse applications in smart building/home, e.g., intelligent automation, healthcare, and security.Actinobacteria produce antibacterial and antifungal specialized metabolites. Many insects harbour actinobacteria on their bodies or in their nests and use these metabolites for protection. However, some actinobacteria produce metabolites that are toxic to insects and the evolutionary relevance of this toxicity is unknown. Here we explore chemical interactions between streptomycetes and the fruit fly Drosophila melanogaster. We find that many streptomycetes produce specialized metabolites that have potent larvicidal effects against the fly; larvae that ingest spores of these species die. The mechanism of toxicity is specific to the bacterium's chemical arsenal cosmomycin D producing bacteria induce a cell death-like response in the larval digestive tract; avermectin producing bacteria induce paralysis. Furthermore, low concentrations of volatile terpenes like 2-methylisoborneol that are produced by streptomycetes attract fruit flies such that they preferentially deposit their eggs on contaminated food sources. The resulting larvae are killed during growth and development. The phenomenon of volatile-mediated attraction and specialized metabolite toxicity suggests that some streptomycetes pose an evolutionary risk to insects in nature.
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