Mackinnontran5647

For these mutants, all peptide fragments follow the same kinetics, acquiring solvent protection at the same time, further supporting that there are no significant populations of intermediate species under our experimental conditions. The results demonstrate the potential of pulsed HDX-MS for resolving the region-specific aggregation behavior of Aβ42 isoforms in solution where X-ray crystallography and solid-state NMR (ssNMR) are challenged.Strain engineering of perovskite quantum dots (pQDs) enables widely tunable photonic device applications. However, manipulation at the single-emitter level has never been attempted. Here, we present a tip-induced control approach combined with tip-enhanced photoluminescence (TEPL) spectroscopy to engineer strain, bandgap, and the emission quantum yield of a single pQD. Single CsPbBrxI3-x pQDs are clearly resolved through hyperspectral TEPL imaging with ∼10 nm spatial resolution. NADPH tetrasodium salt ic50 The plasmonic tip then directly applies pressure to a single pQD to facilitate a bandgap shift up to ∼62 meV with Purcell-enhanced PL increase as high as ∼105 for the strain-induced pQD. Furthermore, by systematically modulating the tip-induced compressive strain of a single pQD, we achieve dynamical bandgap engineering in a reversible manner. In addition, we facilitate the quantum dot coupling for a pQD ensemble with ∼0.8 GPa tip pressure at the nanoscale estimated theoretically. Our approach presents a strategy to tune the nano-opto-electro-mechanical properties of pQDs at the single-crystal level.Short- and medium-chain chlorinated paraffins (SCCPs and MCCPs, respectively) have raised environmental concern due to their potential for persistence, long-range transport, bioaccumulation, and toxicity. However, little is known about the production, use, and environmental emissions of SCCPs and MCCPs in China, the world's largest producer and consumer. In this study, we estimated the amounts of SCCPs and MCCPs produced and used in China in 2018-2019 based on a nationwide survey and measurements of concentrations in products, from which we estimated the environmental emissions of SCCPs and MCCPs in China. Our results show that 225.2 and 236.4 metric kilotons (kt) of SCCPs and 428.5 and 450.2 kt of MCCPs were used in China in 2018 and 2019, respectively, with poly(vinyl chloride) (PVC) products dominating SCCP and MCCP usage. Moreover, a total of 3.9 and 4.2 kt SCCPs and 3.8 and 4.1 kt MCCPs were emitted into China's environment in 2018 and 2019, respectively. Although less MCCPs are released into the air relative to SCCPs, their level exceeds the emission of SCCPs into soil. Finally, detailed mass balance calculation indicates that, although emissions from the use of PVC products dominate SCCP and MCCP inputs into the air, emissions from the use of polyurethane foam adhesives are more closely related to input into surface waters for SCCPs and MCCPs. For input into soil, the main emission sources are the use of polyurethane foam adhesives (for SCCPs) and rubber products (for MCCPs). This study provides a preliminary overview of the distributions of SCCPs and MCCPs in products and insight into the mass balance of SCCPs and MCCPs from their production and use to emission in China. This assessment also provides an important foundation for better understanding the environmental risks and fates associated with SCCPs and MCCPs in China and around the world.The design of small molecules that inhibit disease-relevant proteins represents a longstanding challenge of medicinal chemistry. Here, we describe an approach for encoding this challenge-the inhibition of a human drug target-into a microbial host and using it to guide the discovery and biosynthesis of targeted, biologically active natural products. This approach identified two previously unknown terpenoid inhibitors of protein tyrosine phosphatase 1B (PTP1B), an elusive therapeutic target for the treatment of diabetes and cancer. Both inhibitors appear to target an allosteric site, which confers selectivity, and can inhibit PTP1B in living cells. A screen of 24 uncharacterized terpene synthases from a pool of 4464 genes uncovered additional hits, demonstrating a scalable discovery approach, and the incorporation of different PTPs into the microbial host yielded alternative PTP-specific detection systems. Findings illustrate the potential for using microbes to discover and build natural products that exhibit precisely defined biochemical activities yet possess unanticipated structures and/or binding sites.Adaptability could meet basic technological application requirements. Therefore, a hydrogel-based transducer with durable adhesion, ultrahigh toughness, and super resilience was highly demanded. Here, a skin-like hydrogel transducer was successfully prepared through introducing carboxymethyl chitosan and sodium caseinate into a polyacrylamide hydrogel system. In addition, the polyacrylamide-sodium casein-carboxymethyl chitosan (PAAM-SC-CC) hydrogel has strong mechanical properties and excellent mechanical flexibility, largely due to the adequate energy dissipation mechanism. Surprisingly, the PAAM-SC-CC hydrogel exhibited stable and reproducible adhesion to various solid substrates and the human skin. Due to abundant free ions driven from sodium caseinate, the PAAM-SC-CC hydrogel could maintain stable and sensitive ionic conductivity without adding additional fillers. Experiments have proved that it can be applied to the field of human motion monitoring with complex signals. Therefore, the PAAM-SC-CC hydrogel sensor could monitor human movement in different strain ranges, including throat movement and joint extension. Such a flexible hydrogel-based transducer with various properties is conceivable to broaden the application field of bioelectrodes, human machines, personalized medical health fields, etc.Chiral light-matter interactions have emerged as a promising area in biophysics and quantum optics. Great progress in enhancing chiral light-matter interactions have been investigated through passive resonators or spontaneous emission. Nevertheless, the interaction between chiral biomolecules and stimulated emission remains unexplored. Here we introduce the concept of a biological chiral laser by amplifying chiral light-matter interactions in an active resonator through stimulated emission process. Green fluorescent proteins or chiral biomolecules encapsulated in Fabry-Perot microcavity served as the gain material while excited by either left-handed or right-handed circularly polarized pump laser. Owing to the nonlinear pump energy dependence of stimulated emission, significant enhancement of chiral light-matter interactions was demonstrated. Detailed experiments and theory revealed that a lasing dissymmetry factor is determined by molecular absorption dissymmetry factor at its excitation wavelength. Finally, chirality transfer was investigated under a stimulated emission process through resonance energy transfer. Our findings elucidate the mechanism of stimulated chiral light-matter interactions, providing better understanding of light-matter interaction in biophysics, chiral sensing, and quantum biophotonics.At present, both native and immobilized nanoparticles are of great importance in many areas of science and technology. In this paper, we have studied magnetic iron oxide nanoparticles and their aggregates bound on woven cotton textiles employing two simple modification procedures. One modification was based on the treatment of textiles with perchloric-acid-stabilized magnetic fluid diluted with methanol followed by drying. The second procedure was based on the microwave-assisted conversion of ferrous sulfate at high pH followed by drying. The structure and functional properties of these modified textiles were analyzed in detail. Scanning electron microscopy of native and modified textiles clearly showed the presence of iron oxide nanoparticles on the surface of the modified cotton fibers. All of the modified textile materials exhibited light to dark brown color depending on the amount of the bound iron oxide particles. Magnetic measurements showed that the saturation magnetization values reflect the amount ofsuch as decolorization and degradation of selected organic dyes and other important pollutants. Other types of textile-bound nanozymes can be prepared and used as low-cost catalysts for a variety of applications.Staphylococcus epidermidis is a leading cause of hospital-acquired infections. Traditional antibiotics have significantly reduced efficacy against this pathogen due to its ability to form biofilms on abiotic surfaces and drug resistance. The accessory gene regulator (agr) quorum sensing system is directly involved in S. epidermidis pathogenesis. Activation of agr is achieved via binding of the autoinducing peptide (AIP) signal to the extracellular sensor domain of its cognate receptor, AgrC. Divergent evolution has given rise to four agr specificity groups in S. epidermidis defined by the unique AIP sequence used by each group (AIPs-I-IV) with observed cross-group activities. As agr agonism has been shown to reduce biofilm growth in S. epidermidis, the development of pan-group activators of the agr system is of interest as a potential antivirulence strategy. To date, no synthetic compounds have been identified that are capable of appreciably activating the agr system of more than one specificity group of S. epidermidis or, to our knowledge, of any of the other Staphylococci. Here, we report the characterization of the structure-activity relationships for agr agonism by S. epidermidis AIP-II and AIP-III and the application of these new SAR data and those previously reported for AIP-I for the design and synthesis of the first multigroup agr agonists. These non-native peptides were capable of inducing the expression of critical biofilm dispersal agents (i.e., phenol-soluble modulins) in cell culture and represent new tools to study the role of quorum sensing in S. epidermidis infections.Despite their high potency, the widespread implementation of natural antimicrobial peptides is still challenging due to their low scalability and high hemolytic activities. Herein, we address these issues by employing a modular approach to mimic the key amino acid residues present in antimicrobial peptides, such as lysine, leucine, and serine, but on the highly biocompatible poly(ethylene glycol) (PEG) backbone. A series of these PEG-based peptides (PEGtides) were developed using functional epoxide monomers, corresponding to each key amino acid, with several possessing highly potent bactericidal activities and controlled selectivities, with respect to their hemolytic behavior. The critical role of the composition and the structure of the PEGtides in their selectivities was further supported by coarse-grained molecular dynamic simulations. This modular approach is anticipated to provide the design principles necessary for the future development of antimicrobial polymers.Chemokines are secreted proteins that regulate leukocyte migration during inflammatory responses by signaling through chemokine receptors. Full length CC chemokine ligand 14, CCL14(1-74), is a weak agonist for the chemokine receptor CCR1, but its activity is substantially enhanced upon proteolytic cleavage to CCL14(9-74). CCL14 is O-glycosylated at Ser7, adjacent to the site of proteolytic activation. To determine whether glycosylation regulates the activity of CCL14, we used native chemical ligation to prepare four homogeneously glycosylated variants of CCL14(1-74). Each protein was assembled from three synthetic peptide fragments in "one-pot" using two sequential ligation reactions. We show that while glycosylation of CCL14(1-74) did not affect CCR1 binding affinity or potency of activation, sialylated variants of CCL14(1-74) exhibited reduced activity after treatment with plasmin compared to nonsialylated forms. These data indicate that glycosylation may influence the biological activity of CCL14 by regulating its conversion from the full-length to the truncated, activated form.