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Since the discovery of X-rays by Roentgen in 1895, its use has been ubiquitous, from medical and environmental applications to materials sciences1-5. X-ray characterization requires a large number of atoms and reducing the material quantity is a long-standing goal. Here we show that X-rays can be used to characterize the elemental and chemical state of just one atom. Using a specialized tip as a detector, X-ray-excited currents generated from an iron and a terbium atom coordinated to organic ligands are detected. The fingerprints of a single atom, the L2,3 and M4,5 absorption edge signals for iron and terbium, respectively, are clearly observed in the X-ray absorption spectra. The chemical states of these atoms are characterized by means of near-edge X-ray absorption signals, in which X-ray-excited resonance tunnelling (X-ERT) is dominant for the iron atom. The X-ray signal can be sensed only when the tip is located directly above the atom in extreme proximity, which confirms atomically localized detection in the tunnelling regime. Our work connects synchrotron X-rays with a quantum tunnelling process and opens future X-rays experiments for simultaneous characterizations of elemental and chemical properties of materials at the ultimate single-atom limit.
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Rechargeable lithium (Li) metal batteries face challenges in achieving stable cycling due to the instability of the solid electrolyte interphase (SEI). The Li-ion solvation structure and its desolvation process are crucial for the formation of a stable SEI on Li metal anodes and improving Li plating/stripping kinetics. This research introduces an interfacial desolvation coating technique to actively modulate the Li-ion solvation structure at the Li metal interface and regulate the participation of the electrolyte solvent in SEI formation. Through experimental investigations conducted using a carbonate electrolyte with limited compatibility to Li metal, the optimized desolvation coating layer, composed of 12-crown-4 ether-modified silica materials, selectively displaces strongly coordinating solvents while simultaneously enriching weakly coordinating fluorinated solvents at the Li metal/electrolyte interface. This selective desolvation and enrichment effect reduce solvent participation to SEI and thus facilitate the formation of a LiF-dominant SEI with greatly reduced organic species on the Li metal surface, as conclusively verified through various characterization techniques including XPS, quantitative NMR, operando NMR, cryo-TEM, EELS, and EDS. The interfacial desolvation coating technique enables excellent rate cycling stability (i.e., 1C) of the Li metal anode and prolonged cycling life of the Li||LiCoO2 pouch cell in the conventional carbonate electrolyte (E/C 2.6 g/Ah), with 80% capacity retention after 333 cycles.
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There is much interest in developing new energy storage systems to replace currently available ones that mainly work based on Li-ion intercalations. One attractive area is the Li-air battery for which most of the research has involved liquid electrolytes. There have been few studies on the use of a solid electrolyte in a Li-air battery. Recently, we reported the successful use of a solid-state electrolyte in a Li-air battery resulting in a Li2O product and potentially much higher energy density than in a Li-air battery based on either a Li2O2 or LiO2 product (Science, 2023, 379, 499). In this paper we discuss how the discharge mechanism involved in this solid-state Li-air battery differs from that of a Li-air battery with a liquid electrolyte. The solid-state mechanism is further explored with density functional studies of various interfaces involving the discharge product. We discuss the relevance of the results to the discharge mechanism in the solid-state Li-air battery.
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Lithium-air batteries are considered to be a potential alternative to lithium-ion batteries for transportation applications, owing to their high theoretical specific energy. So far, however, such systems have been largely restricted to pure oxygen environments (lithium-oxygen batteries) and have a limited cycle life owing to side reactions involving the cathode, anode and electrolyte. In the presence of nitrogen, carbon dioxide and water vapour, these side reactions can become even more complex. Moreover, because of the need to store oxygen, the volumetric energy densities of lithium-oxygen systems may be too small for practical applications. Here we report a system comprising a lithium carbonate-based protected anode, a molybdenum disulfide cathode and an ionic liquid/dimethyl sulfoxide electrolyte that operates as a lithium-air battery in a simulated air atmosphere with a long cycle life of up to 700 cycles. We perform computational studies to provide insight into the operation of the system in this environment. This demonstration of a lithium-oxygen battery with a long cycle life in an air-like atmosphere is an important step towards the development of this field beyond lithium-ion technology, with a possibility to obtain much higher specific energy densities than for conventional lithium-ion batteries.
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PURPOSE OF REVIEW: Platelet factor 4 (PF4, CXCL4), the most abundant α-granule platelet-specific chemokine, forms tetramers with an equatorial ring of high positive charge that bind to a wide range of polyanions, after which it changes conformation to expose antigenic epitopes. Antibodies directed against PF4 not only help to clear infection but can also lead to the development of thrombotic disorders such as heparin-induced thrombocytopenia (HIT) and vaccine-induced thrombocytopenia and thrombosis (VITT). This review will outline the different mechanisms through which PF4 engagement with polyanions combats infection but also contributes to the pathogenesis of inflammatory and thrombotic disease states. RECENT FINDINGS: Recent work has shown that PF4 binding to microbial polyanions may improve outcomes in infection by enhancing leukocyte-bacterial binding, tethering pathogens to neutrophil extracellular traps (NETs), decreasing the thrombotic potential of NET DNA, and modulating viral infectivity. However, PF4 binding to nucleic acids may enhance their recognition by innate immune receptors, leading to autoinflammation. Lastly, while HIT is induced by platelet activating antibodies that bind to PF4/polyanion complexes, VITT, which occurs in a small subset of patients treated with COVID-19 adenovirus vector vaccines, is characterized by prothrombotic antibodies that bind to PF4 alone. SUMMARY: Investigating the complex interplay of PF4 and polyanions may provide insights relevant to the treatment of infectious disease while also improving our understanding of the pathogenesis of thrombotic disorders driven by anti-PF4/polyanion and anti-PF4 antibodies.
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COVID-19 , Trombocitopenia , Humanos , Heparina/efectos adversos , Factor Plaquetario 4/química , Factor Plaquetario 4/metabolismo , Trombocitopenia/patología , Anticuerpos/efectos adversosRESUMEN
Variable temperature electron paramagnetic resonance (VT-EPR) was used to investigate the role of the environment and oxidation states of several coordinated Eu compounds. We find that while Eu(III) chelating complexes are diamagnetic, simple chemical reduction results in the formation of paramagnetic species. In agreement with the distorted D3h symmetry of Eu molecular complexes investigated in this study, the EPR spectrum of reduced complexes showed axially symmetric signals (g⥠= 2.001 and g⥠= 1.994) that were successfully simulated with two Eu isotopes with nuclear spin 5/2 (151Eu and 153Eu with 48% and 52% natural abundance, respectively) and nuclear g-factors 151Eu/153Eu = 2.27. Illumination of water-soluble complex Eu(dipic)3 at 4 K led to the ligand-to-metal charge transfer (LMCT) that resulted in the formation of Eu(II) in a rhombic environment (gx = 2.006, gy = 1.995, gz = 1.988). The existence of LMCT affects the luminescence of Eu(dipic)3, and pre-reduction of the complex to Eu(II)(dipic)3 reversibly reduces red luminescence with the appearance of a weak CT blue luminescence. Furthermore, encapsulation of a large portion of the dipic ligand with Cucurbit[7]uril, a pumpkin-shaped macrocycle, inhibited ligand-to-metal charge transfer, preventing the formation of Eu(II) upon illumination.
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DNA toroids are compact torus-shaped bundles formed by one or multiple DNA molecules being condensed from the solution due to various condensing agents. It has been shown that the DNA toroidal bundles are twisted. However, the global conformations of DNA inside these bundles are still not well understood. In this study, we investigate this issue by solving different models for the toroidal bundles and performing replica-exchange molecular dynamics (REMD) simulations for self-attractive stiff polymers of various chain lengths. We find that a moderate degree of twisting is energetically favorable for toroidal bundles, yielding optimal configurations of lower energies than for other bundles corresponding to spool-like and constant radius of curvature arrangements. The REMD simulations show that the ground states of the stiff polymers are twisted toroidal bundles with the average twist degrees close to those predicted by the theoretical model. Constant-temperature simulations show that twisted toroidal bundles can be formed through successive processes of nucleation, growth, quick tightening, and slow tightening of the toroid, with the two last processes facilitating the polymer threading through the toroid's hole. A relatively long chain of 512 beads has an increased dynamical difficulty to access the twisted bundle states due to the polymer's topological constraint. Interestingly, we also observed significantly twisted toroidal bundles with a sharp U-shaped region in the polymer conformation. It is suggested that this U-shaped region makes the formation of twisted bundles easier by effectively reducing the polymer length. This effect can be equivalent to having multiple chains in the toroid.
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ADN , Simulación de Dinámica Molecular , Conformación de Ácido Nucleico , PolímerosRESUMEN
Lithium-oxygen batteries are among the most attractive alternatives for future electrified transportation. However, their practical application is hindered by many obstacles. Due to the insulating nature of Li2 O2 product and the slow kinetics of reactions, attaining sustainable low charge overpotentials at high rates becomes a challenge resulting in the battery's early failure and low round trip efficiency. Herein, outstanding characteristics are discovered of a conductive metal organic framework (c-MOF) that promotes the growth of nanocrystalline Li2 O2 with amorphous regions. This provides a platform for the continuous growth of Li2 O2 units away from framework, enabling a fast discharge at high current rates. Moreover, the Li2 O2 structure works in synergy with the redox mediator (RM). The conductivity of the amorphous regions of the Li2 O2 allows the RM to act directly on the Li2 O2 surface instead of catalyst edges and then transport through the electrolyte to the Li2 O2 surface. This direct charge transfer enables a small charge potential of <3.7 V under high current densities (1-2 A g-1 ) sustained for a long cycle life (100-300 cycles) for large capacities (1000-2000 mAh g-1 ). These results open a new direction for utilizing c-MOFs towards advanced energy storage systems.
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BACKGROUND: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with increased risk of cardiac dysfunction. The pathophysiological mechanisms are poorly understood, and prognostic markers are warranted. PURPOSE: We aimed to identify SLE-characteristics associated with measures of cardiac size and function during a five-year follow-up. METHODS: We included 108 patients with SLE: 90% females, mean age 46 ± 13 years, median disease duration 14 (range 7-21) years. We performed blood sampling for potential biomarkers as well as a standard echocardiography at baseline and at a 5-year follow-up. To investigate associations with baseline and prospective 5-year changes in echocardiographic parameters, we performed multivariate regression analyses of SLE-related baseline variables (clinical disease activity, lupus nephritis, chronic kidney disease, anti-cardiolipin and/or anti-beta-2 glycoprotein I antibodies, and lupus anticoagulant (LAC)) and adjusted for traditional risk factors. RESULTS: During follow-up, diastolic function regressed in two out of five echocardiographic measures (E/A ratio 1.4 ± 0.5 vs. 1.3 ± 0.5, p = 0.002; tricuspid regurgitation peak velocity 2.0 ± 0.6 vs. 2.2 ± 0.4 mmHg, p < 0.001). Left ventricular (LV) end-diastolic volume index increased (43.7 ± 13.9 vs. 52.5 ± 15.7 mL/m2, p < 0.001). Left and right ventricular systolic function remained stationary. LAC was associated with inferior diastolic function: lower E/A ratio (p = 0.04) and higher E/e' ratio at baseline (p = 0.04) and increased left ventricular atrial volume index during follow-up (p = 0.01). LAC was further associated with LV dilatation during follow-up (p = 0.01). CONCLUSION: Presence of LAC was associated with measures of diastolic function as well as progressive LV dilatation during the 5-year follow-up. Thus, LAC might be a predictor of cardiac dysfunction in SLE patients. LAC is known to have implications for the microvascular circulation, but the clinical significance of the present findings is yet to be elucidated.
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Síndrome Antifosfolípido , Cardiopatías , Lupus Eritematoso Sistémico , Nefritis Lúpica , Humanos , Femenino , Niño , Adolescente , Adulto Joven , Adulto , Masculino , Inhibidor de Coagulación del Lupus , Estudios de Seguimiento , Estudios Prospectivos , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/diagnóstico , EcocardiografíaRESUMEN
Using a q+ atomic force microscopy at low temperature, a sexiphenyl molecule is slid across an atomically flat Ag(111) surface along the direction parallel to its molecular axis and sideways to the axis. Despite identical contact area and underlying surface geometry, the lateral force required to move the molecule in the direction parallel to its molecular axis is found to be about half of that required to move it sideways. The origin of the lateral force anisotropy observed here is traced to the one-dimensional shape of the molecule, which is further confirmed by molecular dynamics simulations. We also demonstrate that scanning tunneling microscopy can be used to determine the comparative lateral force qualitatively. The observed one-dimensional lateral force anisotropy may have important implications in atomic scale frictional phenomena on materials surfaces.
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Spleen tyrosine kinase (Syk) and Bruton's tyrosine kinase (BTK) play critical roles in platelet physiology, facilitating intracellular immunoreceptor tyrosine-based activation motif (ITAM)-mediated signaling downstream of platelet glycoprotein VI (GPVI) and GPIIb/IIIa receptors. Small molecule tyrosine kinase inhibitors (TKIs) targeting Syk and BTK have been developed as antineoplastic and anti-inflammatory therapeutics and have also gained interest as antiplatelet agents. Here, we investigate the effects of 12 different Syk and BTK inhibitors on GPVI-mediated platelet signaling and function. These inhibitors include four Syk inhibitors, Bay 61-3606, R406 (fostamatinib), entospletinib, TAK-659; four irreversible BTK inhibitors, ibrutinib, acalabrutinib, ONO-4059 (tirabrutinib), AVL-292 (spebrutinib); and four reversible BTK inhibitors, CG-806, BMS-935177, BMS-986195, and fenebrutinib. In vitro, TKIs targeting Syk or BTK reduced platelet adhesion to collagen, dense granule secretion, and alpha granule secretion in response to the GPVI agonist cross-linked collagen-related peptide (CRP-XL). Similarly, these TKIs reduced the percentage of activated integrin αIIbß3 on the platelet surface in response to CRP-XL, as determined by PAC-1 binding. Although all TKIs tested inhibited phospholipase C γ2 (PLCγ2) phosphorylation following GPVI-mediated activation, other downstream signaling events proximal to phosphoinositide 3-kinase (PI3K) and PKC were differentially affected. In addition, reversible BTK inhibitors had less pronounced effects on GPIIb/IIIa-mediated platelet spreading on fibrinogen and differentially altered the organization of PI3K around microtubules during platelets spreading on fibrinogen. Select TKIs also inhibited platelet aggregate formation on collagen under physiological flow conditions. Together, our results suggest that TKIs targeting Syk or BTK inhibit central platelet functional responses but may differentially affect protein activities and organization in critical systems downstream of Syk and BTK in platelets.
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Agammaglobulinemia Tirosina Quinasa/antagonistas & inhibidores , Plaquetas/efectos de los fármacos , Activación Plaquetaria/efectos de los fármacos , Inhibidores de Agregación Plaquetaria/farmacología , Glicoproteínas de Membrana Plaquetaria/metabolismo , Inhibidores de Proteínas Quinasas/farmacología , Quinasa Syk/antagonistas & inhibidores , Agammaglobulinemia Tirosina Quinasa/metabolismo , Plaquetas/enzimología , Femenino , Humanos , Masculino , Terapia Molecular Dirigida , Adhesividad Plaquetaria/efectos de los fármacos , Agregación Plaquetaria/efectos de los fármacos , Transducción de Señal , Quinasa Syk/metabolismoRESUMEN
The interplay between mesenchymal stem/stromal cells (MSCs) and preservation conditions is critical to maintain the viability and functionality of these cells before administration. We observed that Ringer lactate (RL) maintained high viability of bone marrow-derived MSCs for up to 72 h at room temperature (18°C-22°C), whereas adipose-derived and umbilical cord-derived MSCs showed the highest viability for 72 h at a cold temperature (4°C-8°C). These cells maintained their adherence ability with an improved recovery rate and metabolic profiles (glycolysis and mitochondrial respiration) similar to those of freshly harvested cells. Growth factor and cytokine analyses revealed that the preserved cells released substantial amounts of leukaemia inhibitory factors (LIFs), hepatocyte growth factor (HGF) and vascular endothelial growth factor-A (VEGF-A), as well as multiple cytokines (eg IL-4, IL-6, IL-8, MPC-1 and TNF-α). Our data provide the simplest clinically relevant preservation conditions that maintain the viability, stemness and functionality of MSCs from perinatal and adult tissue sources.
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Criopreservación , Células Madre Mesenquimatosas/citología , Células Madre Mesenquimatosas/metabolismo , Tejido Adiposo/citología , Biomarcadores , Células de la Médula Ósea/citología , Criopreservación/métodos , Citocinas/metabolismo , Metabolismo Energético , Femenino , Humanos , Masculino , Cordón Umbilical/citologíaRESUMEN
Temperature coefficients (TCs) for either electrochemical cell voltages or potentials of individual electrodes have been widely utilized to study the thermal safety and cathode/anode phase changes of lithium (Li)-ion batteries. However, the fundamental significance of single electrode potential TCs is little known. In this work, we discover that the Li-ion desolvation process during Li deposition/intercalation is accompanied by considerable entropy change, which significantly contributes to the measured Li/Li+ electrode potential TCs. To explore this phenomenon, we compare the Li/Li+ electrode potential TCs in a series of electrolyte formulations, where the interaction between Li-ion and solvent molecules occurs at varying strength as a function of both solvent and anion species as well as salt concentrations. As a result, we establish correlations between electrode potential TCs and Li-ion solvation structures and further verify them by ab initio molecular dynamics simulations. We show that measurements of Li/Li+ electrode potential TCs provide valuable knowledge regarding the Li-ion solvation environments and could serve as a screening tool when designing future electrolytes for Li-ion/Li metal batteries.
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Lithium-oxygen (Li-O2 ) batteries possess the highest theoretical energy density (3500 Wh kg-1 ), which makes them attractive candidates for modern electronics and transportation applications. In this work, an inexpensive, flexible, and wearable Li-O2 battery based on the bifunctional redox mediator of InBr3 , MoS2 cathode catalyst, and Fomblin-based oxygen permeable membrane that enable long-cycle-life operation of the battery in pure oxygen, dry air, and ambient air is designed, fabricated, and tested. The battery operates in ambient air with an open system air-breathing architecture and exhibits excellent cycling up to 240 at the high current density of 1 A g-1 with a relative humidity of 75%. The electrochemical performance of the battery including deep-discharge capacity, and rate capability remains almost identical after 1000 cycle in a bending fatigue test. This finding opens a new direction for utilizing high performance Li-O2 batteries for applications in the field of flexible and wearable electronics.
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Suministros de Energía Eléctrica , Litio , Catálisis , Electrodos , OxígenoRESUMEN
Experimental evidence has demonstrated that the presence of water in non-aqueous electrolytes significantly affects Li-O2 electrochemistry. Understanding the reaction mechanism for Li2O2 formation in the presence of water impurities is important to understand Li-O2 battery performance. A recent experiment has found that very small amounts of water (as low as 40 ppm) can significantly affect the product formation in Li-O2 batteries as opposed to essentially no water (1 ppm). Although experimental as well as theoretical work has proposed mechanisms of Li2O2 formation in the presence of much larger amounts of water, none of the mechanisms provide an explanation for the observations for very small amounts of water. In this work, density functional theory (DFT) was utilized to obtain a mechanistic understanding of the Li-O2 discharge chemistry in a dimethoxyethane (DME) electrolyte containing an isolated water and no water. The reaction pathways for Li2O2 formation from LiO2 on a model system were carefully evaluated with different level of theories, i.e. PBE (PW), B3LYP/6-31G(2df,p), B3LYP/6-311++G(2df,p) and G4MP2. The results indicate that the LiO2 disproportionation reaction to Li2O2 can be promoted by the water in DME electrolyte, which explains why there is a significant difference compared to when no water is present in the experimentally observed discharge product distributions. Ab initio molecular dynamics calculations were also used to investigate the disproportionation of LiO2 dimer in explicit DME. This work adds to the fundamental understanding of the discharge chemistry of a Li-O2 battery.
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The core structure of the extracellular basement membrane is made up of self-assembling networks of collagen and laminin which associate with each other through the bridging adapter proteins including the sulfated monomeric glycoprotein nidogen. While collagen and laminin are known to support platelet adhesion and activation via ß1 integrins and glycoprotein (GP) VI, respectively, whether nidogen contributes to platelet activation and hemostasis is unknown. In this study, we demonstrate that recombinant human nidogen-1 supports platelet adhesion and stimulates platelet activation in a phospholipase-C γ-2 (PLCγ2), Src and Syk kinase-dependent manner downstream. Platetet adhesion to nidogen-1 was inhibited by blocking the platelet receptors GPVI and ß1 integrins. Platelet adhesion to nidogen-1 activated the IκB kinase (IKK) complex, while pharmacological inhibition of IKK blocked platelet spreading on nidogen. Taken together our results suggest that nidogen may play a redundant role in hemostasis by activating platelets downstream of GPVI.
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Glicoproteínas de Membrana/metabolismo , Activación Plaquetaria/fisiología , Adhesividad Plaquetaria/fisiología , HumanosRESUMEN
Objective- Activation of coagulation FXI (factor XI) by FXIIa (activated factor XII) is a prothrombotic process. The endothelium is known to play an antithrombotic role by limiting thrombin generation and platelet activation. It is unknown whether the antithrombotic role of the endothelium includes sequestration of FXIa (activated factor XI) activity. This study aims to determine the role of endothelial cells (ECs) in the regulation of the intrinsic pathway of coagulation. Approach and Results- Using a chromogenic assay, we observed that human umbilical veins ECs selectively blocked FXIa yet supported kallikrein and FXIIa activity. Western blotting and mass spectrometry analyses revealed that FXIa formed a complex with endothelial PAI-1 (plasminogen activator inhibitor-1). Blocking endothelial PAI-1 increased the cleavage of a chromogenic substrate by FXIa and the capacity of FXIa to promote fibrin formation in plasma. Western blot and immunofluorescence analyses showed that FXIa-PAI-1 complexes were either released into the media or trafficked to the early and late endosomes and lysosomes of ECs. When baboons were challenged with Staphylococcus aureus to induce a prothrombotic phenotype, an increase in circulating FXIa-PAI-1 complex levels was detected by ELISA within 2 to 8 hours postchallenge. Conclusions- PAI-1 forms a complex with FXIa on ECs, blocking its activity and inducing the clearance and degradation of FXIa. Circulating FXIa-PAI-1 complexes were detected in a baboon model of S. aureus sepsis. Although ECs support kallikrein and FXIIa activity, inhibition of FXIa by ECs may promote the clearance of intravascular FXIa. Visual Overview- An online visual overview is available for this article.
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Coagulación Sanguínea , Células Endoteliales/fisiología , Factor XIa/fisiología , Inhibidor 1 de Activador Plasminogénico/fisiología , Animales , Factor XIa/antagonistas & inhibidores , Factor XIa/química , Humanos , Papio ursinus , Inhibidor 1 de Activador Plasminogénico/químicaRESUMEN
Despite the transient hyporeactivity of neonatal platelets, full-term neonates do not display a bleeding tendency, suggesting potential compensatory mechanisms which allow for balanced and efficient neonatal hemostasis. This study aimed to utilize small-volume, whole blood platelet functional assays to assess the neonatal platelet response downstream of the hemostatic platelet agonists thrombin and adenosine diphosphate (ADP). Thrombin activates platelets via the protease-activated receptors (PARs) 1 and 4, whereas ADP signals via the receptors P2Y1 and P2Y12 as a positive feedback mediator of platelet activation. We observed that neonatal and cord blood-derived platelets exhibited diminished PAR1-mediated granule secretion and integrin activation relative to adult platelets, correlating to reduced PAR1 expression by neonatal platelets. PAR4-mediated granule secretion was blunted in neonatal platelets, correlating to lower PAR4 expression as compared to adult platelets, while PAR4 mediated GPIIb/IIIa activation was similar between neonatal and adult platelets. Under high shear stress, cord blood-derived platelets yielded similar thrombin generation rates but reduced phosphatidylserine expression as compared to adult platelets. Interestingly, we observed enhanced P2Y1/P2Y12-mediated dense granule trafficking in neonatal platelets relative to adults, although P2Y1/P2Y12 expression in neonatal, cord, and adult platelets were similar, suggesting that neonatal platelets may employ an ADP-mediated positive feedback loop as a potential compensatory mechanism for neonatal platelet hyporeactivity.
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Plaquetas/metabolismo , Gránulos Citoplasmáticos/metabolismo , Adenosina Difosfato/metabolismo , Adenosina Trifosfato/metabolismo , Transporte Biológico , Biomarcadores , Coagulación Sanguínea , Humanos , Recién Nacido , Integrinas/metabolismo , Activación Plaquetaria , Agregación Plaquetaria , Resistencia al Corte , Trombina/metabolismoRESUMEN
Protein posttranslational modifications critically regulate a range of physiological and disease processes. In addition to tyrosine, serine, and threonine phosphorylation, reversible N-ε acylation and alkylation of protein lysine residues also modulate diverse aspects of cellular function. Studies of lysine acyl and alkyl modifications have focused on nuclear proteins in epigenetic regulation; however, lysine modifications are also prevalent on cytosolic proteins to serve increasingly apparent, although less understood roles in cell regulation. Here, the methyl-lysine (meK) proteome of anucleate blood platelets is characterized. With high-resolution, multiplex MS methods, 190 mono-, di-, and tri-meK modifications are identified on 150 different platelet proteins-including 28 meK modifications quantified by tandem mass tag (TMT) labeling. In addition to identifying meK modifications on calmodulin (CaM), GRP78 (HSPA5, BiP), and EF1A1 that have been previously characterized in other cell types, more novel modifications are also uncovered on cofilin, drebin-like protein (DBNL, Hip-55), DOCK8, TRIM25, and numerous other cytoplasmic proteins. Together, the results and analyses support roles for lysine methylation in mediating cytoskeletal, translational, secretory, and other cellular processes. MS data for this study have been deposited into the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifier PXD012217.
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Plaquetas/química , Lisina/análisis , Procesamiento Proteico-Postraduccional , Proteoma/química , Plaquetas/citología , Chaperón BiP del Retículo Endoplásmico , Humanos , Metilación , Proteómica , Espectrometría de Masas en TándemRESUMEN
Lithium-oxygen (Li-O2) batteries are a promising class of rechargeable Li batteries with a potentially very high achievable energy density. One of the major challenges for Li-O2 batteries is the high charge overpotential, which results in a low energy efficiency. In this work size-selected subnanometer Ir clusters are used to investigate cathode materials that can help control lithium superoxide formation during discharge, which has good electronic conductivity needed for low charge potentials. It is found that Ir particles can lead to lithium superoxide formation as the discharge product with Ir particle sizes of â¼1.5 nm giving the lowest charge potentials. During discharge these 1.5 nm Ir nanoparticles surprisingly evolve to larger ones while incorporating Li to form core-shell structures with Ir3Li shells, which probably act as templates for growth of lithium superoxide during discharge. Various characterization techniques including DEMS, Raman, titration, and HRTEM are used to characterize the LiO2 discharge product and the evolution of the Ir nanoparticles. Density functional calculations are used to provide insight into the mechanism for formation of the core-shell Ir3Li particles. The in situ formed Ir3Li core-shell nanoparticles discovered here provide a new direction for active cathode materials that can reduce charge overpotentials in Li-O2 batteries.