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With the perpetuation of soil salinization, it is imperative to improve the salt and alkaline tolerance of crops. Sorghum bicolor, a C4 crop, is often grown in semiarid areas due to its high tolerance of various abiotic stresses. Whether to improve the resistance of the sorghum itself or that of other crops, it is necessary to understand the response of sorghum under saline-alkali stress. An integrative analysis of the metabolome and transcriptome of sorghum under normal conditions and treatments of moderate and severe saline-alkali stress was performed. Among the different accumulated metabolites (DAMs) and differentially expressed genes (DEGs), flavonoid-related DAMs and DEGs were clearly changed. The level of flavonoids was increased under saline-alkali stress, and the change in flavonoids was dynamic as to whether total flavonoids or most flavonoid components accumulated more under moderate saline-alkali stress compared to severe stress. Some flavonoid metabolites were significantly correlated with the expression of flavonoid biosynthesis genes. MYB transcription factors may also contribute to the regulation of flavonoids levels. These findings present the dynamic changes and possible molecular mechanisms of flavonoids under different saline-alkali stresses and provide a foundation for future research and crop improvement.Broflanilide, a novel insecticide, is classified as a negative allosteric modulator (NAM) of insect γ-aminobutyric acid (GABA) receptors (GABARs) as desmethyl-broflanilide (DMBF) allosterically inhibits the GABA-induced responses. The G277M mutation of the Drosophila melanogaster GABAR subunit has been reported to abolish the inhibitory activity of DMBF. The binding mode of DMBF in insect GABARs needs to be clarified to understand the underlying mechanism of this mutation and to develop novel, efficient NAMs of insect GABARs. Here, we found that a hydrogen bond formed between DMBF and G277 of the D. melanogaster GABAR model might be the key interaction for the antagonism of DMBF by in silico simulations. The volume increase induced by the G277M mutation blocks the entrance of the binding pocket, making it difficult for DMBF to enter the binding pocket and thereby decreasing its activity. The following virtual screening and bioassay results identified a novel NAM candidate of insect GABARs. Overall, we reported a possible binding mode of DMBF in insect GABARs and proposed the insensitivity mechanism of the G277M mutant GABAR to DMBF using molecular simulations. The identified NAM candidates might provide more alternatives or potentials for the design of GABAR-targeting insecticides.Urban environments are characterized by pronounced spatiotemporal heterogeneity, which can present sampling challenges when utilizing conventional greenhouse gas (GHG) measurement systems. In Salt Lake City, Utah, a GHG instrument was deployed on a light rail train car that continuously traverses the Salt Lake Valley (SLV) through a range of urban typologies. Muramyl dipeptide solubility dmso CO2 measurements from a light rail train car were used within a Bayesian inverse modeling framework to constrain urban emissions across the SLV during the fall of 2015. The primary objectives of this study were to (1) evaluate whether ground-based mobile measurements could be used to constrain urban emissions using an inverse modeling framework and (2) quantify the information that mobile observations provided relative to conventional GHG monitoring networks. Preliminary results suggest that ingesting mobile measurements into an inverse modeling framework generated a posterior emission estimate that more closely aligned with observations, reduced posterior emission uncertainties, and extends the geographical extent of emission adjustments.An unprecedented Rh(III)-catalyzed cascade C-H activation/Lossen rearrangement of aromatic amides with methyleneoxetanones has been realized along with a tunable C-N bond reductive elimination/trans esterification, giving divergent access to quinolinones and dihydroisoquinolinones via selective ring-opening of the four-membered lactone unit. Combined computational and experimental mechanistic studies defined the solvent-involved distinguished reaction paths, the origin of the observed chemodivergence, as well as the role of the substituent attached at the oxidizing directing group in tuning the reaction outcomes.There is mounting evidence that subclinical nonpathological high blood pressure and heart rate during youth and adulthood steadily increase the risk of developing a cardiovascular disease at a later stage. For this reason, it is important to understand the mechanisms underlying the subclinical elevation of blood pressure and heart rate in healthy, relatively young individuals. In the present study, we present a network-based metabolomic study of blood plasma metabolites and lipids measured using nuclear magnetic resonance spectroscopy on 841 adult healthy blood donor volunteers, which were stratified for subclinical low and high blood pressure (systolic and diastolic) and heart rate. Our results indicate a rewiring of metabolic pathways active in high and low groups, indicating that the subjects with subclinical high blood pressure and heart rate could present latent cardiometabolic dysregulations.Protein arginine methyltransferases (PRMTs) are of great interest for the development of therapeutics due to their involvement in a number of malignancies, such as lung and colon cancer. PRMT5 catalyzes the formation of symmetrical dimethylarginine of a wide variety of substrates and is responsible for the majority of this mark within cells. To gain insight into the mechanism of PRMT5 inhibition, we co-expressed the human PRMT5MEP50 complex (hPRMT5MEP50) in insect cells for a detailed mechanistic study. In this report, we carry out steady state, product, and dead-end inhibitor studies that show hPRMT5MEP50 uses a rapid equilibrium random order mechanism with EAP and EBQ dead-end complexes. We also provide evidence of ternary complex formation in solution using hydrogen/deuterium exchange mass spectrometry. Isotope exchange and intact protein mass spectrometry further rule out ping-pong as a potential enzyme mechanism, and finally, we show that PRMT5 exhibits a pre-steady state burst that corresponds to an initial slow turnover with all four active sites of the hetero-octamer being catalytically active.

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