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Large-scale randomized findings shows that device learning-based coaching aids people commit to memory better.
ELABELA (ELA) is the second endogenous ligand of the apelin receptor (APJ). Although apelin-13 and ELA both target APJ, there is limited information on structure-activity relationship (SAR) of ELA. In the present work, we identified the shortest bioactive C-terminal fragment ELA23-32, which possesses high affinity for APJ (K i 4.6 nM) and produces cardiorenal effects in vivo similar to those of ELA. SAR studies on conserved residues (Leu25, His26, Val29, Pro30, Phe31, Pro32) show that ELA and apelin-13 may interact differently with APJ. find more His26 and Val29 emerge as important for ELA binding. Docking and binding experiments suggest that Phe31 of ELA may bind to a tight groove distinct from that of Phe13 of Ape13, while the Phe13 pocket may be occupied by Pro32 of ELA. Further characterization of signaling profiles on the Gαi1, Gα12, and β-arrestin2 pathways reveals the importance of aromatic residue at the Phe31 or Pro32 position for receptor activation.Dietary starch is usually associated with elevated postprandial glycemic response. This is a potential risk factor of type 2 diabetes. Here, a 1,4-α-glucan branching enzyme (GBE) was employed to reassemble α-1,4 and α-1,6 glycosidic bonds in starch molecules. Structural characterization showed that GBE-catalyzed molecular reassembly created an innovative short-clustered maltodextrin (SCMD), which showed a dense internal framework along with shortened external chains. Such short-clustered molecules obstructed digestive enzymes attack and displayed dramatically reduced digestibility. Therefore, SCMD was served as a dietary starch substitute to improve postprandial glucose homeostasis. A 22.3% decrease in glycemic peak was therefore detected in ICR mice following SCMD intake (10.7 mmol/L), compared with that in the control (13.8 mmol/L). Moreover, an attenuated insulin response (40.5% lower than that in control) to SCMD intake was regarded suitable for diabetes management. These novel discoveries demonstrate that enzymatically rebuilding starch molecules may be a meaningful strategy for diabetes management.Sulfamethoxazole (SMX) is a veterinary antibiotic that is not efficiently removed from wastewater by routine treatment and therefore can be detected widely in the environment. Here, we investigated whether microbial anaerobic transformation can contribute to the removal of SMX in constructed systems. We enriched SMX-transforming mixed cultures from sediment of a constructed wetland and from digester sludge of a wastewater treatment plant. Transformation of SMX was observed in both sulfate-reducing and methanogenic cultures, whereas nitrate-reducing cultures showed no SMX transformation. In sulfate-reducing cultures, up to 90% of an initial SMX concentration of 100-250 μM was removed within 6 weeks of incubation, and the experiments demonstrated that the transformation was microbially catalyzed. The transformation products in sulfate-reducing cultures were identified as the reduced and isomerized forms of the isoxazole SMX moiety. The transformation products did not spontaneously reoxidize to SMX after oxygen exposure, and their antibacterial activity was significantly decreased compared to SMX. Population analyses in sequential transfers of the sulfate-reducing cultures revealed a community shift toward the genus Desulfovibrio. We therefore tested a deposited strain of Desulfovibrio vulgaris Hildenborough for its capacity to transform SMX and observed the same transformation products and similar transformation rates as in the enrichment cultures. Our work suggests that an initial anaerobic step in wastewater treatment can reduce the concentration of SMX in effluents and could contribute to decreased SMX concentrations in the environment.We explored the effects of dietary supplementation with phlorizin on redox state-related gut microbiota homeostasis in an obesity mouse model. Mice (C57BL/6J) were grouped as follows for 12 weeks normal chow diet group (NCD), high-fat and cholesterol diet group (HFD), and treatment groups fed with HFD along with three levels of phlorizin. Phlorizin alleviated the hyperlipidemia and redox status and increased the total ccal SCFA content (1.88 ± 0.25 mg/g). Additionally, phlorizin regulated gene expression related to lipid metabolism, redox status, and cecum barrier and rebuilt gut microbiota homeostasis. After interference by antibiotics, the total phloretin content in the feces was decreased about 4-fold, and most of the health-promoting effects were abolished, indicating that phlorizin might be susceptible to microbial biotransformation and that microecology is indispensable for maintaining the redox state capacities of phlorizin. Phlorizin treatment could be an advantageous option for improving HFD-related obesity and redox states related to gut microbiota homeostasis.The development of several-nanometer-scale π-conjugated systems for efficient intramolecular hopping charge transport remains a significant challenge. To construct localized electronic structures at the same energy in a molecule, a series of oligothiophenes, with lengths up to 10 nm and periodically twisted structures, was synthesized. Single-molecule conductance measurements of the twisted molecules revealed resistances lower than those of planar oligothiophenes. This study provides a rational molecular design to improve the intramolecular hopping charge transport in materials.Absorption and reactive properties of fluids in porous media are key to the design and improvement of numerous energy related applications. Molecular simulations of these systems require accurate force fields that capture the involved chemical reactions and have the ability to describe the vapor-liquid equilibrium (VLE). Two new reactive force fields (ReaxFF) for CO2 and H2O are developed, which are capable of not only modeling bond breaking and formation in reactive environments but also predicting their VLEs at saturation conditions. These new force fields include extra terms (ReaxFF-lg) to improve the long-range interactions between the molecules. For validation, we have developed a new Gibbs ensemble Monte Carlo (GEMC-ReaxFF) approach to predict the VLE. Computed VLE data show good agreement with National Institute of Standards and Technology reference data as well as existing nonreactive force fields. This validation proves the applicability of the GEMC-ReaxFF method to test new reactive force fields, and simultaneously it proves the applicability to extend newly developed ReaxFF force fields to other more complex reactive systems.The misfolding and aggregation of α-synuclein (α-syn) in Lewy bodies are implicated in the pathogenesis of various neurodegenerative disorders, such as Parkinson's disease and dementia. The formation of α-syn fibrils is a complex process, involving various intermediates and oligomeric forms. These intermediates establish at an early stage of aggregation and subsequently lead to fibrillation. Determining which conformations are accessible to monomeric α-syn and especially, as shown in a recent work, to the central amino acids from residue 35 to residue 97 (63 residues) is thus crucial to understand the formation of these oligomers. Here, we carry out extensive replica exchange molecular dynamics (total time-18 μs) with an all-atom model and explicit solvent to characterize the free-energy landscape of human α-syn (residue 35 to residue 97). The simulation results lead us to identify two free-energy basins. Clustering analysis for the deepest free-energy minimum reveals a compact structure, with a secondary structure predominantly α-helix, while the shallower minimum corresponds to an elongated conformation, also predominantly α-helix. Furthermore, at physiological temperature, we find that conformational rearrangements happen via helix breaks due to the presence of glycine. We also show that the most likely conformations are characterized by the α-helix structure rather than the β-hairpin structure (for residue 38 to residue 53), in contrast with prior simulation studies using coarse-grained models or an implicit solvent. For higher temperatures, we observe a shift in secondary structure with a decrease in the population of α-helix in favor of random coils, β-bend, and β-turns.Carbohydrates are among the most complex class of biomolecules, and even subtle variations in their structures are attributed to diverse biological functions. Mass spectrometry has been essential for large scale glycomics and glycoproteomics studies, but the gas-phase structures and sometimes anomalous fragmentation properties of carbohydrates present long-standing challenges. Here we investigate the gas-phase properties of a panel of isomeric protonated disaccharides differing in their linkage configurations. Multiple conformations were evident for most of the structures based on their fragment ion abundances by tandem mass spectrometry, their ion mobilities in several gases, and their deuterium uptake kinetics by gas-phase hydrogen-deuterium exchange. Most notably, we find that the properties of the Y-ion fragments are characteristically influenced by the precursor carbohydrate's linkage configuration. This study reveals how protonated carbohydrate fragment ions can retain "linkage memory" that provides structural insight into their intact precursor.For modern tissue engineering, we need not only develop new hydrogels but also suitable processing methods for them. Polypeptides and polysaccharides are potential candidates because they can be methacrylated, processed before photocross-linking, and yielded into hydrogels with given shape and form. In this study, we successfully methacrylated collagen, gelatin, hyaluronan, and alginate to 30 and 60% degree of modification. We studied methacrylated compositions (i.e., precursors) to investigate their processability. The precursors of collagen and gelatin with 60% methacrylation exhibited suitable yield stress, shear-thinning properties, and fiber-forming capability for injecting and 3D bioprinting. On the contrary, the 30% methacrylated precursors had properties suitable for casting purposes. Our study also showed that the mechanical properties of hydrogels corresponded to the used photocross-linking conditions and the degree of modification. These results underline the importance of tunability of the precursors and resulting hydrogels according to the specific fabrication method and tissue engineering application.Recently, silver nanowire-based transparent conductive films (AgNW-based TCFs) with excellent comprehensive performance have aroused wide and great interest. However, it is always difficult to simultaneously improve the performances of TCFs in all aspects. In this work, by introducing silica nanoparticles (SiO2-NPs) with a smaller particle size, several properties of AgNW-based TCFs were optimized successfully. The transmittance and conductivity were improved simultaneously, and smaller particle size was proven to be more suitable to achieve TCFs with excellent optoelectrical properties. Typically, an AgNW/SiO2-based TCF with a sheet resistance of 250 Ω/sq and transmittance of 93.6% (including the poly (ethylene terephthalate) substrate, abbreviated as PET) could be obtained by using SiO2-NPs with a size of ∼21 nm, and this transmittance is even higher than that of the bare PET (91.8%) substrate. We demonstrated that the layer formed through self-assembly of SiO2-NPs can cut down the light scattering on the AgNW surface through total reflection, thus leading to a low haze of AgNW/SiO2-based TCFs.
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