PEDOT-Carbon Nanotube Counter Electrodes and Bipyridine Cobalt (II/III) Mediators as Universally Compatible Components in Bio-Sensitized Solar Cells Using Photosystem I and Bacteriorhodopsin

In nature, solar energy is captured by different types of light harvesting protein–pigment complexes. Two of these photoactivatable proteins are bacteriorhodopsin (bR), which utilizes a retinal moiety to function as a proton pump, and photosystem I (PSI), which uses a chlorophyll antenna to catalyze unidirectional electron transfer. Both PSI and bR are well characterized biochemically and have been integrated into solar photovoltaic (PV) devices built from sustainable materials. Both PSI and bR are some of the best performing photosensitizers in the bio-sensitized PV field, yet relatively little attention has been devoted to the development of more sustainable, biocompatible alternative counter electrodes and electrolytes for bio-sensitized solar cells. Careful selection of the electrolyte and counter electrode components is critical to designing bio-sensitized solar cells with more sustainable materials and improved device performance. This work explores the use of poly (3,4-ethylenedioxythiophene) (PEDOT) modified with multi-walled carbon nanotubes (PEDOT/CNT) as counter electrodes and aqueous-soluble bipyridine cobalt^II/III complexes as direct redox mediators for both PSI and bR devices. We report a unique counter electrode and redox mediator system that can perform remarkably well for both bio-photosensitizers that have independently evolved over millions of years. The compatibility of disparate proteins with common mediators and counter electrodes may further the improvement of bio-sensitized PV design in a way that is more universally biocompatible for device outputs and longevity.     

N-acetylcysteine Reduces Inflammasome Activation Induced by SARS-CoV-2 Proteins In Vitro

Inflammasome activation is one of the first steps in initiating innate immune responses. In this work, we studied the activation of inflammasomes in the airways of critically ill COVID-19 patients and the effects of N-acetylcysteine (NAC) on inflammasomes. Tracheal biopsies were obtained from critically ill patients without COVID-19 and no respiratory disease (control, n = 32), SARS-CoV-2 B.1 variant (n = 31), and B.1.1.7 VOC alpha variant (n = 20) patients. Gene expression and protein expression were measured by RT-qPCR and immunohistochemistry. Macrophages and bronchial epithelial cells were stimulated with different S, E, M, and N SARS-CoV-2 recombinant proteins in the presence or absence of NAC. NLRP3 inflammasome complex was over-expressed and activated in the COVID-19 B.1.1.7 VOC variant and associated with systemic inflammation and 28-day mortality. TLR2/MyD88 and redox NOX4/Nrf2 ratio were also over-expressed in the COVID-19 B.1.1.7 VOC variant. The combination of S-E-M SARS-CoV-2 recombinant proteins increased cytokine release in macrophages and bronchial epithelial cells through the activation of TLR2. NAC inhibited SARS-CoV-2 mosaic (S-E-M)-induced cytokine release and inflammasome activation. In summary, inflammasome is over-activated in severe COVID-19 and increased in B.1.1.7 VOC variant. In addition, NAC can reduce inflammasome activation induced by SARS-CoV-2 in vitro, which may be of potential translational value in COVID-19 patients.     

Prospect Theory,Discrete Emotions,and Freedom Threats: An Extension of Psychological Reactance Theory

Consistent with earlier research supporting the use of narratives to increase message persuasiveness, this study examined the role of guilt and happiness following exposure to organ donation narratives presented in professionally produced radio ads. As hypothesized, the loss‐frame narrative was significantly associated with heightened guilt, which was related to greater freedom threat perceptions and psychological reactance. Conversely, the loss‐frame narrative was negatively associated (p = .06) with increased happiness. Contrary to what was hypothesized, reactance was not significantly negatively associated with favorable attitudes toward registering as an organ donor. Instead, freedom threat was directly negatively related to favorable attitudes. Our results are discussed with an emphasis on the theoretical and practical implications.     

Role of JAK/STAT in Interstitial Lung Diseases; Molecular and Cellular Mechanisms

Interstitial lung diseases (ILDs) comprise different fibrotic lung disorders characterized by cellular proliferation, interstitial inflammation, and fibrosis. The JAK/STAT molecular pathway is activated under the interaction of a broad number of profibrotic/pro-inflammatory cytokines, such as IL-6, IL-11, and IL-13, among others, which are increased in different ILDs. Similarly, several growth factors over-expressed in ILDs, such as platelet-derived growth factor (PDGF), transforming growth factor β1 (TGF-β1), and fibroblast growth factor (FGF) activate JAK/STAT by canonical or non-canonical pathways, which indicates a predominant role of JAK/STAT in ILDs. Between the different JAK/STAT isoforms, it appears that JAK2/STAT3 are predominant, initiating cellular changes observed in ILDs. This review analyzes the expression and distribution of different JAK/STAT isoforms in ILDs lung tissue and different cell types related to ILDs, such as lung fibroblasts and alveolar epithelial type II cells and analyzes JAK/STAT activation. The effect of JAK/STAT phosphorylation on cellular fibrotic processes, such as proliferation, senescence, autophagy, endoplasmic reticulum stress, or epithelial/fibroblast to mesenchymal transition will be described. The small molecules directed to inhibit JAK/STAT activation were assayed in vitro and in in vivo models of pulmonary fibrosis, and different JAK inhibitors are currently approved for myeloproliferative disorders. Recent evidence indicates that JAK inhibitors or monoclonal antibodies directed to block IL-6 are used as compassionate use to attenuate the excessive inflammation and lung fibrosis related to SARS-CoV-2 virus. These altogether indicate that JAK/STAT pathway is an attractive target to be proven in future clinical trials of lung fibrotic disorders.     

MUC16 Is Overexpressed in Idiopathic Pulmonary Fibrosis and Induces Fibrotic Responses Mediated by Transforming Growth Factor-β1 Canonical Pathway

Several transmembrane mucins have demonstrated that they contribute intracellularly to induce fibrotic processes. The extracellular domain of MUC16 is considered as a biomarker for disease progression and death in IPF patients. However, there is no evidence regarding the signalling capabilities of MUC16 that contribute to IPF development. Here, we demonstrate that MUC16 was overexpressed in the lung tissue of IPF patients (n = 20) compared with healthy subjects (n = 17) and localised in fibroblasts and hyperplastic alveolar type II cells. Repression of MUC16 expression by siRNA-MUC16 transfection inhibited the TGF-β1-induced fibrotic processes such as mesenchymal/ myofibroblast transformations of alveolar type II A549 cells and lung fibroblasts, as well as fibroblast proliferation. SiRNA-MUC16 transfection also decreased the TGF-β1-induced SMAD3 phosphorylation, thus inhibiting the Smad Binding Element activation. Immunoprecipitation assays and confocal immunofluorescence showed the formation of a protein complex between MUC16/p-SMAD3 in the cell membrane after TGF-β1 stimulation. This study shows that MUC16 is overexpressed in IPF and collaborates with the TGF-β1 canonical pathway to induce fibrotic processes. Therefore, direct or indirect targeting of MUC16 could be a potential drug target for human IPF.     

Metal-Bound Methisazone; Novel Drugs Targeting Prophylaxis and Treatment of SARS-CoV-2, a Molecular Docking Study

SARS-CoV-2 currently lacks effective first-line drug treatment. We present promising data from in silico docking studies of new Methisazone compounds (modified with calcium, Ca; iron, Fe; magnesium, Mg; manganese, Mn; or zinc, Zn) designed to bind more strongly to key proteins involved in replication of SARS-CoV-2. In this in silico molecular docking study, we investigated the inhibiting role of Methisazone and the modified drugs against SARS-CoV-2 proteins: ribonucleic acid (RNA)-dependent RNA polymerase (RdRp), spike protein, papain-like protease (PlPr), and main protease (MPro). We found that the highest binding interactions were found with the spike protein (6VYB), with the highest overall binding being observed with Mn-bound Methisazone at −8.3 kcal/mol, followed by Zn and Ca at −8.0 kcal/mol, and Fe and Mg at −7.9 kcal/mol. We also found that the metal-modified Methisazone had higher affinity for PlPr and MPro. In addition, we identified multiple binding pockets that could be singly or multiply occupied on all proteins tested. The best binding energy was with Mn–Methisazone versus spike protein, and the largest cumulative increases in binding energies were found with PlPr. We suggest that further studies are warranted to identify whether these compounds may be effective for treatment and/or prophylaxis.     

Mortality from cold waves in Castile — La Mancha, Spain

Introduction

As is known, the effects of extreme temperatures on mortality are characterised by an annual periodicity, with a rise centred in the winter months. The most recent epidemiological studies show that mortality caused by cold waves is, in many cases, comparable to that caused by the severest heat waves. This study sought to quantify the rise in mortality due to extreme cold and the factors that determine the relationship between these variables in Castile-La Mancha (Spain).

Methods

We examined the effect of extreme winter temperature on daily non accidental cause mortality in Castile — La Mancha from 1975 to 2003, for all ages. Quantitative analyses were performed using ARIMA models, with other covariates, such as influenza, pressure trends, relative humidity, and cold wave duration and chronological number.

Results

There were two mortality peaks: a short-term peak (with a lag of 3 to 7 days); and a longer term peak (of under two weeks). Excess mortality during cold waves was around 10% per degree centigrade below the threshold temperature for all the provinces except Guadalajara, where an increase of only 4.61% was detected.Mortality increased in response to rises in cold-wave duration and relative humidity. Cold waves occurring at the end of the “winter” season caused the greatest mortality.

Conclusions

This study confirms that daily mortality in Castile — La Mancha increases during cold waves. Efficient cold-wave prevention plans must therefore be implemented. Such plans should be based on in-depth knowledge of the causes that underlie and modulate the relationship between low temperatures and health effects.     

α-particle emission probabilities in the decay of U

²³⁵U decays by α-particle emission to ²³¹Th. The decay scheme of this nuclide is very complex, with more than 20 alpha branches. Recommended values for P_α of this nuclide are based on measurements carried out in 1975. This work presents the results of new measurements made with Si detectors and sources of enriched uranium in the frame of the EUROMET 591 cooperation project. The use of improved measurement techniques and numerical analysis of spectra allowed a new set of P_α values for 13 lines with improved uncertainties to be obtained.     

Chilled Storage of Pressurized Octopus (Octopus vulgaris) Muscle

ABSTRACT: Samples were subjected to continuous and step-pulsed pressurization, in both cases at 7 and 40 °C. There was a reduction of microbial flora (total viable count and lactic bacteria) after pressurization and during storage at 2.5 to 3.0 °C, chiefly in the lot pressurized by step-pulse at 400 MPa, 40 °C. Pressure-induced modification of the microbial flora resulted in a lower level of nitrogenous compounds. Pressurization reduced autolytic activity, but shear strength values remained stable throughout storage. There was less drip loss in the pressurized lots at 7 °C that at 40 °C, and the WHC values decreased during storage. Shelf life of the pressurized octopus overall was 43 d longer than unpressurized.