In observational analyses, children living in housing units that appeared clean had 12-17% lower concentrations of these phthalate metabolites and monobenzyl phthalate, compared to children living in housing units with more dust accumulation. Features of this lead hazard intervention and measures to control dust may reduce children's exposure to phthalates found in building materials and household furnishings.Past health impact assessments of ambient fine particulate matter (particles with an aerodynamic diameter ≤2.5 μm; PM2.5) have generally considered mass concentration only, despite PM2.5 being a heterogeneous mixture. Given constant changes in the concentration and the composition of atmospheric aerosol, uncertainty exists as to whether the current focus on PM2.5 mass or individual components may fully characterize the health burden of PM2.5. We proposed a component-adjusted method that jointly estimates the health impacts of PM2.5 and its major components while allowing for a potential nonlinear PM2.5-outcome relationship. Using this method, we quantified the effects of PM2.5 on the risks of developing acute myocardial infarction (AMI) and dying from cardiovascular causes in comparison to three traditional approaches in the entire adult population across Ontario, Canada. We observed that PM2.5 was positively associated with AMI incidence and cardiovascular mortality with all four methods. Compared to the traditional approaches, however, the new component-adjusted approach demonstrated a significant improvement in explaining the health impacts of PM2.5, especially in the presence of a nonlinear PM2.5-outcome relationship. Using the new approach, we found that the effects of PM2.5 on AMI incidence and cardiovascular mortality may be 10% to 27% higher than what would be estimated from the conventional approaches examining PM2.5 alone.Aberrant expression of PDGFR-β is associated with a number of diseases. The G-quadruplexes (G4s) formed in PDGFR-β gene promoter are transcriptional modulators and amenable to small molecule targeting. The major G4 formed in the PDGFR-β gene promoter was previously shown to have a broken G-strand. Herein, we report that the PDGFR-β gene promoter sequence forms a vacancy G-quadruplex (vG4) which can be filled in and stabilized by physiologically relevant guanine metabolites, such as dGMP, GMP, and cGMP, as well as guanine-derivative drugs. We determined the NMR structure of the dGMP-fill-in PDGFR-β vG4 in K+ solution. This is the first structure of a guanine-metabolite-fill-in vG4 based on a human gene promoter sequence. Our structure and systematic analysis elucidate the contributions of Hoogsten hydrogen bonds, sugar, and phosphate moieties to the specific G-vacancy fill-in. Intriguingly, an equilibrium of 3'- and 5'-end vG4s is present in the PDGFR-β promoter sequence, and dGMP favors the 5'-end fill-in. https://www.selleckchem.com/products/lomeguatrib.html Guanine metabolites and drugs were tested and showed a conserved selectivity for the 5'-vacancy, except for cGMP. cGMP binds both the 3'- and 5'-end vG4s and forms two fill-in G4s with similar population. Significantly, guanine metabolites are involved in many physiological and pathological processes in human cells; thus, our results provide a structural basis to understand their potential regulatory functions by interaction with promoter vG4s. Moreover, the NMR structure can guide rational design of ligands that target the PDGFR-β vG4.Bismuth is gaining importance as a key element of functional quantum materials. The effects of spin-orbit coupling (SOC) are at the heart of many exciting proposals for next-generation quantum technologies, including topological materials for efficient information transmission and energy-saving applications. The "heavy" element bismuth and its compounds are predestined for SOC-induced topological properties, but materials design is challenged by a complex link between them and the chemical composition and crystal structure. Nevertheless, a lot can be learned about a certain property by testing its limits with compositional and/or structure modifications. We survey a handful of topological bismuth-based materials that bear structural and chemical semblance to the early topological insulators, antimony-doped elemental bismuth, Bi2Se3 and Bi2Te3. Chemical bonding via p orbitals and modular structure underlie all considered bismuth chalcogenides, subhalides, and chalcogenide halides and allow us to correlate the evolution of chemical bonding and structure with variability of the topological properties, although materials design should not be regarded as a building blocks set. Over the past decade, material discoveries have unearthed a plethora of topological properties, and bismuth is very fertile as a progenitor of a rich palette of exotic quantum materials, ranging from strong and weak 3D and crystalline topological insulators over topological metals and semimetals to magnetic topological insulators, while preserving the general layered structure motif.The measurement of receptor occupancy (RO) using positron emission tomography (PET) has been instrumental in guiding discovery and development of CNS directed therapeutics. We and others have investigated muscarinic acetylcholine receptor 4 (M4) positive allosteric modulators (PAMs) for the treatment of symptoms associated with neuropsychiatric disorders. In this article, we describe the synthesis, in vitro, and in vivo characterization of a series of central pyridine-related M4 PAMs that can be conveniently radiolabeled with carbon-11 as PET tracers for the in vivo imaging of an allosteric binding site of the M4 receptor. We first demonstrated its feasibility by mapping the receptor distribution in mouse brain and confirming that a lead molecule 1 binds selectively to the receptor only in the presence of the orthosteric agonist carbachol. Through a competitive binding affinity assay and a number of physiochemical properties filters, several related compounds were identified as candidates for in vivo evaluation. These candidates were then radiolabeled with 11C and studied in vivo in rhesus monkeys. This research eventually led to the discovery of the clinical radiotracer candidate [11C]MK-6884.