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The present investigation deals with the columnar structured growth of Mn doped ZnO (MZO) thin films by radio frequency sputtering technique. The X-ray diffraction and the processed electron diffraction pattern confirmed the hexagonal wurtzite structure and the film growth direction along (101) plane. The structure of grown film was compared with the pristine ZnO film and the JCPDS card No. 00-36-1451. The microstructures of the pristine ZnO and MZO films were studied by scanning electron microscopy and atomic force microscopy. The columnar structure growth of MZO was confirmed by transmission electron microscopy using TEM cross-section sample. The presence of constituent elements and their concentrations in the films were recorded by energy dispersive X-ray diffraction spectroscopy. The optical transmittance, absorption edge and band gap of the material were studied by UV-Visible transmission spectroscopy. The field dependent magnetization at room-temperature was analysed by using vibrating sample magnetometer and magneto-optic Kerr effect. [ABSTRACT FROM AUTHOR]

Lung tissue from human patients and murine models of sickle cell disease pulmonary hypertension (SCD-PH) show perivascular regions with excessive iron accumulation. The iron accumulation arises from chronic hemolysis and extravasation of hemoglobin (Hb) into the lung adventitial spaces, where it is linked to nitric oxide depletion, oxidative stress, inflammation, and tissue hypoxia, which collectively drive SCD-PH. Here, we tested the hypothesis that intrapulmonary delivery of hemopexin (Hpx) to the deep lung is effective at scavenging heme-iron and attenuating the progression of SCD-PH. Herein, we evaluated in a murine model of hemolysis driven SCD-PH, if intrapulmonary Hpx administration bi-weekly for 10 weeks improves lung iron deposition, exercise tolerance, cardiovascular function, and multi-omic indices associated with SCD-PH. Data shows Hpx delivered with a micro-sprayer deposits Hpx in the alveolar regions. Hpx extravasates into the perivascular compartments but does not diffuse into the circulation. Histological examination shows Hpx therapy decreased lung iron deposition, 4-HNE, and HO-1 expression. This was associated with improved exercise tolerance, cardiopulmonary function, and multi-omic profile of whole lung and RV tissue. Our data provides proof of concept that treating lung heme-iron by direct administration of Hpx to the lung attenuates the progression of PH associated with SCD., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: David Irwin, Paul Buehler reports financial support was provided by National Institutes of Health. Andre Palmer, Angelo D'Allessandro, reports financial support was provided by National Institutes of Health. Christina Lisk reports financial support was provided by American Heart Association Inc. David Irwin and Paul Buehler reports a relationship with National Institutes of Health that includes: funding grants. Christina Lisk reports a relationship with American Heart Association that includes: funding grants. Andre Palmer and Angelo D'allessandro reports a relationship with National Institutes of Health that includes grant support. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025. Published by Elsevier Inc.)

We previously identified a small molecule, UM101, predicted to bind to the substrate-binding groove of p38aMitogen-activated Protein Kinase (MAPK) near the binding site of its proinflammatory substrate, MAPK-activated protein kinase (MK2). UM101 exhibited anti-inflammatory, endothelial-stabilizing, and lung-protective effects. To overcome its limited aqueous solubility and p38a binding affinity, we designed an analog of UM101, GEn-1124, with improved aqueous solubility, stability, and p38a binding affinity. Compared with UM101, GEn-1124 has 18-fold greater p38a-binding affinity as measured by Surface Plasmon Resonance (SPR), 11-fold greater aqueous solubility, enhanced barrier-stabilizing activity in thrombin-stimulated human pulmonary artery endothelial cells (hPAEC) in vitro, and greater lung protection in vivo GEn-1124 improved survival from 10% to 40% in murine acute lung injury (ALI) induced by combined exposure to intratracheal bacterial endotoxin lipopolysaccharide (LPS) instillation and febrile-range hyperthermia (FRH) and from 0% to 50% in a mouse influenza pneumonia model. Gene expression analysis by RNASeq in TNFa-treated hPAEC showed that the gene-modifying effects of GEn-1124 were much more restricted to TNFa-inducible genes than the catalytic site p38 inhibitor, SB203580. Gene expression pathway analysis, confocal immunofluorescence analysis of p38aand MK2 subcellular trafficking, and SPR analysis of phosphorylated p38a:MK2 binding affinity supports a novel mechanism of action. GEn-1124 destabilizes the activated p38a:MK2 complex, dissociates nuclear export of MK2 and p38a, thereby promoting intranuclear retention and enhanced intranuclear signaling by phosphorylated p38a retention, and accelerated inactivation of p38-free cytosolic MK2 by unopposed phosphatases. Significance Statement We describe an analog of our first-in-class small molecule modulator of p38a/MK2 signaling targeted to a pocket near the ED substrate binding domain of p38a, which destabilizes the p38a:MK2 complex without blocking p38 catalytic activity or ablating downstream signaling. The result is a rebalancing of downstream pro- and anti-inflammatory signaling, yielding anti-inflammatory, endothelial-stabilizing, and lung-protective effects with therapeutic potential in ARDS., (© 2024 The Authors. This is an open access article under the terms of the Creative Commons Attribution CC BY License, which permits use, distribution, and reproduction in any medium, provided that the original work is properly cited.)

The investigation focuses on determining the effects of canola oil-based cutting fluid with three different volume percentages of boric acid additives over the machining forces and surface roughness while turning hardened AISI 1018 mild steel. Experiments were carried out under Taguchi's design of the experiment concept. The minimum quantity lubrication (MQL) technique was followed to minimize the cutting fluid consumption. The homogeneity of the additives dispersed in the fluid has been validated through a zeta potential study. Machining forces and surface roughness were considered as chief machining objectives. The hybrid mathematical model, grey relational analysis (GRA)-artificial neural network (ANN), has been implemented to assess the performance of developed cutting fluid. The results explored that the canola oil cutting fluid with 5 wt% of boric acid additive exhibits lesser cutting forces and surface roughness. The optimal machining parameters identified by the hybrid modeling are 665 rpm of cutting speed, 35 mm/min of feed rate, and 0.3 mm of depth of cut, along with 5 wt% of boric acid composition in cutting fluid. The results explore the 2.677 times improvement in machining objective in comparison with a non-optimal set of parameters. The implementation of hybrid modeling is considered to be a novel attempt to minimize the machining objectives. It has been recorded a negligible error percentage of 0.66% between GRA and ANN prediction., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Polymerized human hemoglobin (PolyhHb) has shown promise in preclinical hemorrhagic shock settings. Different synthetic and purification schemes can control the size of PolyhHbs, yet research is lacking on the impact of polymerized hemoglobin size on tissue oxygenation following hemorrhage and resuscitation in specialized animal models that challenge their resuscitative capabilities. Pre-existing conditions that compromise the vasculature and end organs, such as the liver, may limit the effectiveness of resuscitation and exacerbate the toxicity of these molecules, which is an important but minimally explored therapeutic dimension. In this study, we compared the effective oxygen delivery of intermediate molecular weight PolyhHb (PolyhHb-B3; 500-750 kDa) to high molecular weight PolyhHb (PolyhHb-B4; 750 kDa-0.2 μm) for resuscitative effectiveness in guinea pig models subjected to hemorrhagic shock. We evaluated how the size of PolyhHb impacts hemodynamics and tissue oxygenation in normal guinea pigs and guinea pigs on an atherogenic diet. We observed that while PolyhHb-B3 and -B4 equivalently restore hemodynamic parameters of normal-dieted guinea pigs, high-fat-dieted guinea pigs resuscitated with PolyhHb-B4 have lower mean arterial pressures, impaired tissue oxygenation, and higher plasma lactate levels than those receiving PolyhHb-B3. We characterized the plasma of these animals following resuscitation and found that despite similar oxygen delivery kinetics, circulating PolyhHb-B3 and -B4 demonstrated a size-dependent increase in the plasma viscosity, consistent with impaired perfusion in the PolyhHb-B4 transfusion group. We conclude that intermediate-sized PolyhHbs (such as -B3) are ideal for further research given the effective resuscitation of hemorrhagic shock based on tissue oxygenation in hypercholesterolemic guinea pigs.