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Our study suggested that dimer destabilization could be an effective strategy for the discovery of RNase L inhibitors and that targeting the ATP-binding pocket in the PK domain of RNase L was an efficient approach for modulating its ribonuclease activity.Linear metabolic pathways are the simplest network architecture we find in metabolism and are a good starting point to gain insight into the operating principles of metabolic control. Linear pathways possess some well-known properties, such as a bias of flux control towards the first few steps of the pathway as well as the lack of flux control at reactions close to equilibrium. In both cases, a rationale for these behaviors is given in terms of how elasticities transmit changes through a pathway. A discussion is given on the fundamental role that two reaction step sections play in a linear pathway when transmitting changes. For a pathway with irreversible steps, the deconstruction is straight forward and includes a product of local response coefficients that cascade along the pathway. When reversibility is included, the picture became more complex but a relationship in terms of the local response coefficients if derived that includes the reverse response coefficients and highlights the interplay between the forward and backward transmission of changes during a perturbation.The paper by Dr von Ehrenstein et al (Am J Epidemiol. 2020;000(00)000-000) adds to the large and growing literature on the potentially causal association between prenatal exposure to maternal smoking and neuropsychiatric health. In addition to statewide, prospectively collected data, a particular strength was their ability to perform a sibling comparison design, contrasting the rate of autism spectrum disorder in siblings discordantly exposed to maternal smoking. AR-13324 solubility dmso Unfortunately, the estimate from the sibling pairs could neither confirm nor refute the conclusions based on the full cohort. Interpretation was hampered by broad confidence limits, and even had power been higher, the authors acknowledge a range of potential biases that would have made it difficult to draw any firm conclusions from a similarity or difference in the sibling pair estimate and estimate from the full cohort. Was the addition of the sibling comparison actually worth the effort? In this commentary, I will briefly summarize the benefits and limitations of this design, and, with some caveats, argue that its inclusion in the study by Dr von Ehrenstein et al. was indeed a strength and not just an ornamentation.The initial aim of environmental epidemiology is to estimate the causal effects of environmental exposures on health outcomes. However, due to lack of enough covariates in most environmental data sets, current methods without enough adjustments for confounders inevitably lead to residual confounding. We propose a negative-control exposure based on a time-series studies (NCE-TS) model to effectively eliminate unobserved confounders using an after-outcome exposure as a negative-control exposure. We show that the causal effect is identifiable and can be estimated by the NCE-TS for continuous and categorical outcomes. Simulation studies indicate unbiased estimation by the NCE-TS model. The potential of NCE-TS is illustrated by 2 challenging applications We found that living in areas with higher levels of surrounding greenness over 6 months was associated with less risk of stroke-specific mortality, based on the Shandong Ecological Health Cohort during January 1, 2010, to December 31, 2018. In addition, we found that the widely established negative association between temperature and cancer risks was actually caused by numbers of unobserved confounders, according to the Global Open Database from 2003-2012. The proposed NCE-TS model is implemented in an R package (R Foundation for Statistical Computing, Vienna, Austria) called NCETS, freely available on GitHub.We examined associations between maternal smoking and autism spectrum disorder (ASD) in children in a statewide population-based cohort and sibling comparison design using California birth records (n=2,015,104) with information on maternal smoking, demographics and pregnancy (2007-2010). ASD cases (n=11,722) were identified through California Department of Developmental Services records with diagnoses based on the Diagnostic and Statistical Manual of Mental Disorders-IV-R. We estimated odds ratios (OR) for ASD with/without intellectual disability in the full cohort using logistic regression, and conditional logistic regression in a sibling comparison. In the full cohort, the adjusted OR for ASD and maternal smoking 3-months before/during pregnancy compared to non-smoking was 1.15 (95%CI 1.04, 1.26), and was similar in cases with (OR=1.12, 95%CI 0.84, 1.49) and without intellectual disability (OR=1.15, 95%CI 1.04, 1.27); heavy prenatal smoking (20+ cigarettes/day in any trimester) was related to 58% risk increase (95%CI 23%, 101%). In the sibling comparison, the OR for heavy smoking was similarly elevated but the CI was wide. Our findings are consistent with an increased risk for ASD in offspring of mothers who smoked 20+ cigarettes/day during pregnancy; associations with lighter smoking were weaker.In electrochemiluminescence sensing platforms, co-reaction accelerators are specific materials used to catalyze the dissociation of co-reactants into active radicals, which can significantly boost the ECL emission of luminophores. Deep insight into the correlation between the structure and ECL performance will guide the rational design of highly active co-reaction accelerators, which is imperative for constructing sensitive and reliable ECL biosensors. In this review, a brief introduction about the basic ECL mechanisms based on the co-reactant pathway is presented. After that, recent developments with various co-reaction accelerators are further discussed regarding different luminophore systems, including luminol, g-C3N4, quantum dots, nanoclusters and others. Furthermore, synergistic amplification strategies based on efficient co-reaction accelerators and enzyme immune and hybrid chain reactions are elucidated. Finally, the outlook for the preparation of high-performance ECL sensors with efficient co-reaction accelerators is discussed as well.