Polymeric microcomponents are widely used in microelectromechanical systems (MEMS) and lab-on-a-chip devices, but they suffer from the lack of complex motion, effective addressability and precise shape control. To address these needs, we fabricated polymeric nanocomposite microactuators driven by programmable heterogeneous magnetic anisotropy. Spatially modulated photopatterning was applied in a shape-independent manner to microactuator components by successive confinement of self-assembled magnetic nanoparticles in a fixed polymer matrix. By freely programming the rotational axis of each component, we demonstrate that the polymeric microactuators can undergo predesigned, complex two- and three-dimensional motion.
Innate immunity plays a crucial role in the response to sterile inflammation such as liver ischemia/reperfusion (I/R) injury. The initiation of liver I/R injury results in the release of damage associated molecular patterns (DAMPs), which trigger innate immune and inflammatory cascade via pattern recognition receptors. Neutrophils are recruited to the liver after I/R and contribute to the organ damage, innate immune and inflammatory responses. Formation of neutrophil extracellular trap (NET) has been recently found in response to various stimuli. However, the role of NETs during liver I/R injury remains unknown. We show that NETs form in the sinusoids of ischemic liver lobes in vivo. This was associated with increased NET markers, serum level of myeloperoxidase (MPO)-DNA complexes and tissue level of citrullinated-histone H3 compared to control mice. Treatment with peptidyl-arginine-deiminase (PAD) 4 inhibitor or DNase I significantly protected hepatocytes and reduced inflammation after liver I/R as evidenced by inhibition of NET formation, indicating the pathophysiological role of NETs in liver I/R injury. In vitro, NETs increase hepatocyte death and induce Kupffer cells to release proinflammatory cytokines. DAMPs, such as HMGB1 and histones, released by injured hepatocytes stimulate NET formation through Toll-like receptor (TLR4)- and TLR9-MyD88 signaling pathways. After neutrophil depletion in mice, the adoptive transfer of TLR4 knockout (KO) or TLR9 KO neutrophils confers significant protection from liver I/R injury with significant decrease in NET formation. In addition, we found inhibition of NET formation by PAD4 inhibitor or DNase I reduces HMGB1 and histone-mediated liver I/R injury. Conclusion DAMPs released during liver I/R promotes NET formation through TLRs signaling pathway. Development of NETs subsequently exacerbates organ damage and initiates inflammatory responses during liver I/R.
Mast cells contribute importantly to both protective and pathological IgE-dependent immune responses. We show that the mast cell–expressed orphan serpentine receptor mCCRL2 is not required for expression of IgE-mediated mast cell–dependent passive cutaneous anaphylaxis but can enhance the tissue swelling and leukocyte infiltrates associated with such reactions in mice. We further identify chemerin as a natural nonsignaling protein ligand for both human and mouse CCRL2. In contrast to other “silent” or professional chemokine interreceptors, chemerin binding does not trigger ligand internalization. Rather, CCRL2 is able to bind the chemoattractant and increase local concentrations of bioactive chemerin, thus providing a link between CCRL2 expression and inflammation via the cell-signaling chemerin receptor CMKLR1.
Encoded particles have a demonstrated value for multiplexed high-throughput bioassays such as drug discovery and clinical diagnostics. In diverse samples, the ability to use a large number of distinct identification codes on assay particles is important to increase throughput. Proper handling schemes are also needed to readout these codes on free-floating probe microparticles. Here we create vivid, free-floating structural coloured particles with multi-axis rotational control using a colour-tunable magnetic material and a new printing method. Our colour-barcoded magnetic microparticles offer a coding capacity easily into the billions with distinct magnetic handling capabilities including active positioning for code readouts and active stirring for improved reaction kinetics in microscale environments. A DNA hybridization assay is done using the colour-barcoded magnetic microparticles to demonstrate multiplexing capabilities.
There are clusters of basic amino acids on many cytoplasmic proteins that bind transiently to membranes (e.g., protein kinase C) as well as on the cytoplasmic domain of many intrinsic membrane proteins (e.g., glycophorin). To explore the possibility that these basic residues bind electrostatically to monovalent acidic lipids, we studied the binding of the peptides Lysn and Argn (n = 1-5) to bilayer membranes containing phosphatidylserine (PS) or phosphatidylglycerol (PG). We made electrophoretic mobility measurements using multilamellar vesicles, fluorescence and equilibrium binding measurements using large unilamellar vesicles, and surface potential measurements using monolayers. None of the peptides bound to vesicles formed from the zwitterionic lipid phosphatidylcholine (PC) but all bound to vesicles formed from PC/PS or PC/PG mixtures. None of the peptides exhibited specificity between PS and PG. Each lysine residue that was added to Lys2 decreased by one order of magnitude the concentration of peptide required to reverse the charge on the vesicle; equivalently it increased by one order of magnitude the binding affinity of the peptides for the PS vesicles. The simplest explanation is that each added lysine binds independently to a separate PS with a microscopic association constant of 10 M-1 or a free energy of approximately 1.4 kcal/mol. Similar, but not identical, results were obtained with the Argn peptides. A simple theoretical model combines the Gouy-Chapman theory (which accounts for the nonspecific electrostatic accumulation of the peptides in the aqueous diffuse double layer adjacent to the membrane) with mass action equations (which account for the binding of the peptides to greater than 1 PS). This model can account qualitatively for the dependence of binding on both the number of basic residues in the peptides and the mole fraction of PS in the membrane.
Purpose-The purpose of this study is to test the efficacy of a culturally tailored comprehensive type 2 diabetes management intervention for Korean American immigrants (KAIs) with type 2 diabetes.Methods-A randomized controlled pilot trial with 2 parallel arms (intervention vs control) with a delayed intervention design was used. A total of 79 KAIs, recruited from the Baltimore-Washington area, completed baseline, 18-week, and 30-week follow-ups (intervention, n = 40; control, n = 39). All participants had uncontrolled type 2 diabetes (hemoglobin A1C ≥7.5%) at baseline. The authors' comprehensive, self-help intervention program for type 2 diabetes management (SHIP-DM) consisted of a 6-week structured psychobehavioral education, home glucose monitoring with teletransmission, and bilingual nurse telephone counseling for 24 weeks. The primary outcome of the study was A1C level, and secondary outcomes included an array of psychobehavioral variables.Results-Using analysis of covariance, the findings support that the proposed intervention was effective in significantly lowering A1C and fasting glucose and also in improving psychosocial outcomes in the sample. Specifically, the amount of reduction in A1C among intervention group participants was 1.19% at 18 weeks and 1.31% at 30 weeks, with 10% and 15.5% of the participants achieving the suggested goal of A1C <7% at 18 and 30 weeks of follow-up, respectively. Conclusions-The results highlight the clinical efficacy of the SHIP-DM intervention composed of a 6-week education program, self-monitoring, and follow-up counseling, in terms of maintaining the improved intervention effects obtained and in terms of glucose control.Type 2 diabetes mellitus is a serious health problem in Asian American communities, including the Korean American immigrant (KAI) community. KAIs, one of the most underserved and understudied minority populations in the United States, are at particularly high risk of developing type 2 diabetes. This risk is compounded by the fact that Asians who have emigrated to the West tend to gain weight and develop chronic diseases, including type 2 diabetes, after immigration. [1][2][3] Although studies of this new immigrant group are scare, available research has indicated that an overwhelming number of KAIs suffer not only from uncontrolled diabetes 4 but also from a loss of self-confidence and social isolation stemming from language and cultural barriers. 5 Researchers have found that currently available interventions for ethnic minority groups with type 2 diabetes are largely inadequate and ineffective because of insufficient integration of cultural framework and tailored strategies, which often results in suboptimal outcomes. [12][13][14][15][16] Today's KAIs, predominantly first-generation immigrants with strong ties to their traditional culture, are in great need of culturally relevant care. Integrating traditional diet and exercise and tailored counseling on pharmacological regimens based on their use of traditional herbal medicine and behavioral ...
All-inorganic CsPbI3 perovskite quantum dots have received substantial research interest for photovoltaic applications because of higher efficiency compared to solar cells using other quantum dots materials and the various exciting properties that perovskites have to offer. These quantum dot devices also exhibit good mechanical stability amongst various thin-film photovoltaic technologies. We demonstrate higher mechanical endurance of quantum dot films compared to bulk thin film and highlight the importance of further research on high-performance and flexible optoelectronic devices using nanoscale grains as an advantage. Specifically, we develop a hybrid interfacial architecture consisting of CsPbI3 quantum dot/PCBM heterojunction, enabling an energy cascade for efficient charge transfer and mechanical adhesion. The champion CsPbI3 quantum dot solar cell has an efficiency of 15.1% (stabilized power output of 14.61%), which is among the highest report to date. Building on this strategy, we further demonstrate a highest efficiency of 12.3% in flexible quantum dot photovoltaics.
Several groups have observed that phosphorylation causes the MARCKS (Myristoylated Alanine-Rich C Kinase Substrate) protein to move off cell membranes and phospholipid vesicles. Our working hypothesis is that significant membrane binding of MARCKS requires both hydrophobic insertion of the N-terminal myristate into the bilayer and electrostatic association of the single cluster of basic residues in the protein with acidic lipids and that phosphorylation reverses this electrostatic association. Membrane binding measurements with myristoylated peptides and phospholipid vesicles show this hydrophobic moiety could, at best, barely attach proteins to plasma membranes. We report here membrane binding measurements with basic peptides that correspond to the phosphorylation domains of MARCKS and neuromodulin. Binding of these peptides increases sigmoidally with the percent acidic lipid in the phospholipid vesicle and can be described by a Gouy-Chapman/mass action theory that explains how electrostatics and reduction of dimensionality produce apparent cooperativity. The electrostatic affinity of the MARCKS peptide for membranes containing 10% acidic phospholipids (10(4) M-1 = chi/[P], where chi is the mole ratio of peptide bound to the outer monolayer of the vesicles and [P] is the concentration of peptide in the aqueous phase) is the same as the hydrophobic affinity of the myristate moiety for bilayer membranes. Phosphorylation decreases the affinity of the MARCKS peptide for membranes containing 15% acidic lipid about 1000-fold and produces a rapid (t1/2 < 30 s) dissociation of the peptide from phospholipid vesicles.
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