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BACKGROUND: Xenotransplantation has made significant advances recently using pigs genetically engineered to remove carbohydrate antigens, either alone or with addition of various human complement, coagulation, and anti-inflammatory 'transgenes'. Here we evaluated results associated with gene-edited (GE) pig hearts transplanted in baboons using an established costimulation-based immunosuppressive regimen and a cold-perfused graft preservation technique. METHODS: Eight baboons received heterotopic abdominal heart transplants from 3-GE (GalKO.ß4GalNT2KO.hCD55, n=3), 9-GE (GalKO.ß4GalNT2KO.GHRKO.hCD46.hCD55. TBM.EPCR.hCD47.HO-1, n=3) or 10-G (9-GE+CMAHKO, n=2) pigs using Steen's cold continuous perfusion for ischemia minimization. Immunosuppression (IS) included induction with anti-thymocyte globulin and αCD20, ongoing αCD154, MMF, and tapered corticosteroid. RESULTS: All three 3-GE grafts functioned well initially, but failed within 5 days. One 9-GE graft was lost intraoperatively due to a technical issue and another was lost at POD 13 due to antibody mediated rejection (AMR) in a baboon with a strongly positive pre-operative cross-match. One 10-GE heart failed at POD113 with combined cellular and antibody mediated rejection. One 9-GE and one 10-GE hearts had preserved graft function with normal myocardium on protocol biopsies, but exhibited slowly progressive graft hypertrophy until elective necropsy at POD393 and 243 respectively. Elevated levels of IL-6, MCP-1, C-reactive protein, and human thrombomodulin were variably associated with conditioning, the transplant procedure, and clinically significant postoperative events. CONCLUSION: Relative to reference genetics without thrombo-regulatory and anti-inflammatory gene expression, 9- or 10-GE pig hearts exhibit promising performance in the context of a clinically applicable regimen including ischemia minimization and αCD154-based IS, justifying further evaluation in an orthotopic model.
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This paper reports on a novel approach for the fabrication of composite multilayered bioink-nanofibers construct. This work achieves this by using a hands-free 3D (bio)printing integrated touch-spinning approach. Additionally, this work investigates the interaction of fibroblasts in different bioinks with the highly aligned touch-spun nanofibers. This work conducts a comprehensive characterization of the rheological properties of the inks, starting with low-strain oscillatory rheology to analyze the viscoelastic behavior, when the material structure remains intact. Moreover, this work performs amplitude sweeps to investigate the stability of the inks under large deformations, rotational rheology to examine the shear thinning profile, and a three-step creep experiment to study time-dependent rheological behavior. The obtained rheological results are correlated to visual observation of the flow behavior of inks. These behaviors span from an ink with zero-shear viscosity, very weak shear thinning, and no thixotropic behavior to inks exhibiting flow stress, pronounced shear thinning, and thixotropy. It is demonstrated that inks have an essential effect on cell behavior. While all bioinks allow a preferred directionality of the fibroblasts along the fiber direction, cells tend to form aggregates in bioinks with higher viscosity, and a considerable number of agglomerates are observed in the presence of laponite-RD.
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Nanofibras , Comunicação Celular , Impressão Tridimensional , ReologiaRESUMO
OBJECTIVE: Health communication aims to modify attitudes and behaviors, which is why it uses, among others, persuasive strategies and the use of cognitive biases. Both elements have been investigated in previous studies, however, no research precedents have been found that evaluate government messages from both perspectives at the same time. The objective of this research was to analyze the type of information related to the COVID-19 vaccination that was distributed on the official page of the Government of Spain, evaluating its persuasive capacity and the use of cognitive biases as tools against vaccination reluctance. METHODS: The information from the official page on vaccination of COVID-19 of the Government of Spain was analysed, taking into account both its structure and the content of the information. Special attention was paid to the communication strategy developed to develop pro-vaccine messages. RESULTS: First, the information coming from the Government was presented in a concise, clear and simple way on a well-structured webpage. Second, the content shared revolved around certain recurring themes such as the benefits and the vaccination process. Third, the content had a highly scientific nature and was supported by arguments to overthrow cognitive biases against vaccination. Lastly, the communication strategy was based on content that were more informative (rational) than persuasive (emotional). CONCLUSIONS: Knowing the techniques of persuasion and the implication of cognitive biases, especially in the area of vaccination, will help guide communication strategies in Public Health.
OBJETIVO: La comunicación en salud pretende modificar actitudes y comportamientos, por lo que se vale, entre otros, de estrategias persuasivas y de sesgos cognitivos. Ambos elementos han sido investigados en estudios previos, pero no se han encontrado precedentes de investigaciones que evalúen los mensajes gubernamentales desde ambas perspectivas a la vez. El objetivo de esta investigación fue analizar el tipo de información relacionada con la vacunación contra la COVID-19 que se distribuía en la página oficial del Gobierno de España, evaluando su capacidad persuasiva y el uso de sesgos cognitivos como herramientas contra la renuencia a la vacunación. METODOS: Se analizó la información de la página oficial sobre vacunación contra la COVID-19 del Gobierno de España, teniendo en cuenta tanto su estructura como el contenido de la información. Se prestó especial atención a la estrategia comunicativa desarrollada para elaborar mensajes provacunas. RESULTADOS: En primer lugar, la información proveniente del Gobierno de España se presentaba de forma concisa, clara y sencilla en una web bien estructurada. En segundo lugar, el contenido compartido giraba en torno a ciertos temas recurrentes como los beneficios y el proceso de la vacunación. En tercer lugar, el contenido poseía un gran carácter científico y se apoyaba en argumentos para derribar sesgos cognitivos contrarios a la vacunación. Por último, la estrategia comunicativa se basa en contenidos más informativos (racionales) que persuasivos (emocionales). CONCLUSIONES: Conocer las técnicas de persuasión y la implicación de sesgos cognitivos, especialmente en el área de la vacunación, ayudará a orientar las estrategias comunicativas de Salud Pública.
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Vacinas contra COVID-19 , COVID-19 , Humanos , Espanha/epidemiologia , COVID-19/prevenção & controle , Saúde Pública , Comunicação , Estudos RetrospectivosRESUMO
Since the onset of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, numerous sequelae of this devastating virus have come to light. One organ known to be impacted by SARS-CoV-2 is the liver, as many SARS-CoV-2 patients demonstrate elevated liver enzymes on routine laboratory tests. In this case report, we present a patient with SARS-CoV-2 whose liver enzymes remained persistently elevated throughout his hospitalization. Due to the duration of his elevated liver enzymes, etiologies outside of SARS-CoV-2 were explored. This workup revealed that the patient had alpha-1 antitrypsin (A1AT) deficiency. Thus, this case serves to remind clinicians to continue investigating lab abnormalities despite a presumed etiology, such as SARS-CoV-2, so as not to miss the presentation of new diagnoses.
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Single-molecule fluorescence in situ hybridization (smFISH) enables the detection and localization of individual mRNAs in tissue sections with single-molecule resolution while preserving spatial context, and thus, is a useful tool for examining gene expression in biological systems. In particular, the growing reliance on single-cell RNA sequencing (scRNA-seq) to explore cellular heterogeneity has reinvigorated this approach as a validation tool to spatially re-map mRNA expression patterns described in isolated cells to their parent tissue. While use of antibody-based methods, such as indirect immunofluorescence (IIF), remain popular as validation strategies, smFISH often affords superior specificity and maintains congruency with scRNA-seq. Here, we present a detailed protocol that combines multiplexed smFISH using the RNAscope approach with IIF to co-visualize mRNAs and proteins within sections of mouse testes. We provide step-by-step guidelines from testis preparation through visualization that enables mapping of combinations of up to four mRNA/protein targets in frozen sections on the RNAscope platform.
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Mamíferos , Testículo , Camundongos , Masculino , Animais , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Testículo/metabolismo , Hibridização in Situ Fluorescente/métodos , Mamíferos/genética , NanotecnologiaRESUMO
Dietary lipids, particularly omega-3 polyunsaturated fatty acids, are speculated to impact behaviors linked to the dopaminergic system, such as movement and control of circadian rhythms. However, the ability to draw a direct link between dopaminergic omega-3 fatty acid metabolism and behavioral outcomes has been limited to the use of diet-based approaches, which are confounded by systemic effects. Here, neuronal lipid metabolism was targeted in a diet-independent manner by manipulation of long-chain acyl-CoA synthetase 6 (ACSL6) expression. ACSL6 performs the initial reaction for cellular fatty acid metabolism and prefers the omega-3 polyunsaturated fatty acid, docosahexaenoic acid (DHA). The loss of Acsl6 in mice (Acsl6-/- ) depletes neuronal membranes of DHA content and results in phenotypes linked to dopaminergic control, such as hyperlocomotion, impaired short-term spatial memory, and imbalances in dopamine neurochemistry. To investigate the role of dopaminergic ACSL6 on these outcomes, a dopaminergic neuron-specific ACSL6 knockout mouse was generated (Acsl6DA-/- ). Acsl6DA-/- mice demonstrated hyperlocomotion and imbalances in striatal dopamine neurochemistry. Circadian rhythms of both the Acsl6-/- and the Acsl6DA-/- mice were similar to control mice under basal conditions. However, upon light entrainment, a mimetic of jet lag, both the complete knockout of ACSL6 and the dopaminergic-neuron-specific loss of ACSL6 resulted in a longer recovery to entrainment compared to control mice. In conclusion, these data demonstrate that ACSL6 in dopaminergic neurons alters dopamine metabolism and regulation of light entrainment suggesting that DHA metabolism mediated by ACSL6 plays a role in dopamine neuron biology.
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Neurônios Dopaminérgicos , Metabolismo dos Lipídeos , Camundongos , Animais , Neurônios Dopaminérgicos/metabolismo , Dopamina , Gorduras na Dieta , Dieta , Camundongos Knockout , Ácidos Docosa-Hexaenoicos/metabolismo , Coenzima A Ligases/genética , Coenzima A Ligases/metabolismoRESUMO
Introduction: Chronic nicotine exposure induces changes in the expression of key regulatory genes associated with metabolic function and neuronal alterations in the brain. Many bioregulatory genes have been associated with exposure to nicotine, but the modulating effects of sex and diet on gene expression in nicotine-exposed brains have been largely unexplored. Both humans and rodents display motivation for nicotine use and the emergence of withdrawal symptoms during abstinence. Research comparing pre-clinical models with human subjects provides an important opportunity to understand common biomarkers of the harmful effects of nicotine as well as information that may help guide the development of more effective interventions for nicotine cessation. Methods: Human postmortem dorsolateral prefrontal cortex (dLPFC) tissue BA9 was collected from female and male subjects, smokers and non-smokers (N = 12 per group). Rat frontal lobes were collected from female and male rats that received a regular diet (RD) or a high-fat diet (HFD) (N = 12 per group) for 14 days following implantation of a osmotic mini-pump (Alzet) that delivered nicotine continuously. Controls (control-s) received a sham surgical procedure. RNA was extracted from tissue from human and rat samples and reversed-transcribed to cDNA. Gene expression of CHRNA10 (Cholinergic receptor nicotinic alpha 10), CERKL (Ceramide Kinase-Like), SMYD1 (SET and MYD Domin Containing 1), and FA2H (Fatty Acid 2-Hydrolase) in humans was compared to rats in each subset of groups and quantified by qPCR methods. Additionally, protein expression of FA2H was analyzed by immunohistochemistry (IHC) in human dLPFC. Results: Humans with a history of smoking displayed decreased CHRNA10 (p = 0.0005), CERKL (p ≤ 0.0001), and SMYD1 (p = 0.0005) expression and increased FA2H (p = 0.0097) expression compared to non-smokers (p < 0.05). Similar patterns of results were observed in nicotine exposed vs. control rats. Interestingly, sex-related differences in gene expression for CERKL and FA2H were observed. In addition, ANCOVA analysis showed a significant effect of nicotine in a sex-different manner, including an increase in CERKL in male and female rats with RD or HFD. In rats exposed to an HFD, FA2H gene expression was lower in nicotine-treated rats compared to RD rats treated with nicotine. Protein expression of FA2H (p = 0.001) by IHC was significantly higher in smokers compared to non-smokers. Conclusion: These results suggest that a history of long-term nicotine exposure in humans alters the expression of sphingolipid metabolism-related (CERKL, SMYD1, and FA2H) and neuronal (CHRNA10) marker genes similarly as compared to rats. Sex- and diet-dependent differences appear in nicotine-exposed rats, critical in regulating sphingolipid metabolism and nicotinic acetylcholine receptors. This research enhances the construct validity of rat models of nicotine usage by showing a similar pattern of changes in gene expression in human subjects with a smoking history.
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The platform wound device (PWD) is a wound coverage system that is designed to decrease wound infection rates by allowing for direct delivery of topical antibiotics and antimicrobials while creating a sealed, protective barrier around the area of injury. This study evaluated the safety and efficacy of the PWD as a protective dressing and a delivery system for topical antibiotics compared to the current standard of care (SoC). This was a multi-center, prospective, randomised, controlled clinical trial. The wounds were treated with the PWD with gentamicin cream or SoC dressings. The wounds were evaluated before the start of treatment and after 48-96 hours via clinical assessment, photographs, and qualitative bacterial swabs for bacterial analysis. The delivery of gentamicin via the PWD was safe and did not cause any adverse effects. The treatment decreased both inflammation and bacterial growth during the study period. No significant differences in the SoC were observed. The PWD is a transparent and impermeable polyurethane chamber that encloses and protects the injured area. The delivery of topical gentamicin via the PWD was safe and effective. Clinical assessment for infection found the PWD to be non-inferior to the current SoC treatment options.
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Gentamicinas , Infecção dos Ferimentos , Humanos , Estudos Prospectivos , Cicatrização , Antibacterianos/uso terapêutico , Infecção dos Ferimentos/tratamento farmacológicoRESUMO
Cell-extracellular matrix (ECM) adhesion mediated by integrins is a highly regulated process involved in many vital cellular functions such as motility, proliferation and survival. However, the influence of lateral integrin clustering in the coordination of cell front and rear dynamics during cell migration remains unresolved. For this purpose, we describe a novel protocol to fabricate 1D micro-nanopatterned stripes by integrating the block copolymer micelle nanolithography (BCMNL) technique and maskless near UV lithography-based photopatterning. The photopatterned 10 µm-wide stripes consist of a quasi-perfect hexagonal arrangement of gold nanoparticles, decorated with the RGD (arginine-glycine-aspartate) motif for single integrin heterodimer binding, and placed at a distance of 50, 80, and 100 nm to regulate integrin clustering and focal adhesion dynamics. By employing time-lapse microscopy and immunostaining, we show that the displacement and speed of fibroblasts changes according to the nanoscale spacing of adhesion sites. We found that as the lateral spacing of adhesive peptides increased, fibroblast morphology was more elongated. This was accompanied by a decreased formation of mature focal adhesions and stress fibers, which increased cell displacement and speed. These results provide new insights into the migratory behavior of fibroblasts in 1D environments and our protocol offers a new platform to design and manufacture confined environments in 1D for integrin-mediated cell adhesion.
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INTRODUCTION: Hypertrophic burn scars (HTBSs) remain a significant source of morbidity. Contemporary treatment has evolved to use CO2 lasers and/or pulse-dye lasers (PDLs) to reduce scar thickness (ST) and erythema. This study seeks to compare treatment efficacy with CO2 or PDL individually and in combination. METHODS: Patients undergoing laser treatments for HTBSs were enrolled. Three 3 × 3 cm squares of HTBSs were randomized to receive treatment with CO2 laser, PDL or CO2 + PDL. Patients underwent 3 treatments, 4 to 6 weeks apart and were followed up over 3 to 6 months. Scar assessments occurred at each visit before treatment and consisted of photographs, ultrasound, colorimetry, and the Patient and Observer Scar Assessment Score. RESULTS: Twenty-five patients were enrolled. Twenty completed 2 treatments (80%) and 11 completed all 3 treatments (44%). Median initial ST was 0.3 cm. Median time since injury was 8 months. Hypertrophic burn scars treated with CO2 or PDL showed a significant decrease in Patient and Observer Scar Assessment Scale score from visit 1 to 3 (P = 0.01 and 0.01, respectively). When separated by ST, thick scars (≥0.3 cm) showed a significant decrease in thickness between visit 1 and 2 using all laser modalities (CO2 + PDL, P = 0.01; CO2, P = 0.02; PDL, P = 0.03). Thin scars (<0.3 cm) showed a reduction in thickness by visit 3 after CO2 + PDL or PDL alone (P = 0.01 and 0.04, respectively). Separating scars by age, younger scars (<9 months) showed a significant reduction in thickness between visit 1 and 2 for CO2 treatment (P = 0.04), and between visit 2 and 3 for CO2 + PDL treatment (P = 0.04). Hypertrophic burn scars treated with PDL did not demonstrate a significant reduction in thickness until visit 3 (P = 0.002). Older scars (≥9 months) showed a significant reduction in thickness between visit 1 and 2 only after CO2 + PDL (P = 0.01). CONCLUSIONS: Hypertrophic burn scars of varying ages, etiologies, and thicknesses were examined in this study with greater degree of early reduction seen in thicker scars using all laser modalities of CO2, PDL or in combination. However, there was no clinically meaningful benefit found with combination as compared with individual treatment. These data support the use of laser to improve HTBS but does not support one modality or combination of modalities over another.
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Queimaduras , Cicatriz Hipertrófica , Lasers de Corante , Lasers de Gás , Queimaduras/complicações , Queimaduras/terapia , Dióxido de Carbono , Cicatriz Hipertrófica/etiologia , Cicatriz Hipertrófica/patologia , Cicatriz Hipertrófica/cirurgia , Humanos , Hipertrofia , Lactente , Lasers de Corante/uso terapêutico , Lasers de Gás/uso terapêutico , Resultado do TratamentoRESUMO
Recent global geopolitical tensions have exacerbated the scarcity of rare-earth elements (REEs), which are critical across many industries. REE-rich coal fly ash (CFA), a coal combustion residual, has been proposed as a potential source. Conventional REE-CFA recovery methods are energy- and material-intensive and leach elements indiscriminately. This study has developed a new valorization process based on the ionic liquid (IL) betainium bis(trifluoromethylsulfonyl)imide ([Hbet][Tf2N]) for preferential extraction of REEs from different CFAs. Efficient extraction relies on [Hbet][Tf2N]'s thermomorphic behavior with water: upon heating, water and the IL form a single liquid phase, and REEs are leached from CFA via a proton-exchange mechanism. Upon cooling, the water and IL separate, and leached elements partition between the two phases. REEs were preferentially extracted over bulk elements from CFAs into the IL phase and then recovered in a subsequent mild-acid stripping step, regenerating the IL. Alkaline pretreatment significantly improved REE leaching efficiency from recalcitrant Class-F CFAs, and additional betaine improved REE and bulk element separation. Weathered CFA showed slightly higher REE leaching efficiency than unweathered CFA, and Class-C CFA demonstrated higher leaching efficiency but less selective partitioning than Class-F CFAs. Significantly, this method consistently exhibits a particularly high extraction efficiency for scandium across different CFAs.
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Líquidos Iônicos , Metais Terras Raras , Carvão Mineral , Cinza de Carvão/análise , ÁguaRESUMO
The omega-3 fatty acid docosahexaenoic acid (DHA) inversely relates to neurological impairments with aging; however, limited nondietary models manipulating brain DHA have hindered a direct linkage. We discovered that loss of long-chain acyl-CoA synthetase 6 in mice (Acsl6-/-) depletes brain membrane phospholipid DHA levels, independent of diet. Here, Acsl6-/- brains contained lower DHA compared with controls across the life span. The loss of DHA- and increased arachidonate-enriched phospholipids were visualized by MALDI imaging predominantly in neuron-rich regions where single-molecule RNA in situ hybridization localized Acsl6 to neurons. ACSL6 is also astrocytic; however, we found that astrocyte-specific ACSL6 depletion did not alter membrane DHA because astrocytes express a non-DHA-preferring ACSL6 variant. Across the life span, Acsl6-/- mice exhibited hyperlocomotion, impairments in working spatial memory, and increased cholesterol biosynthesis genes. Aging caused Acsl6-/- brains to decrease the expression of membrane, bioenergetic, ribosomal, and synaptic genes and increase the expression of immune response genes. With age, the Acsl6-/- cerebellum became inflamed and gliotic. Together, our findings suggest that ACSL6 promotes membrane DHA enrichment in neurons, but not in astrocytes, and is important for neuronal DHA levels across the life span. The loss of ACSL6 impacts motor function, memory, and age-related neuroinflammation, reflecting the importance of neuronal ACSL6-mediated lipid metabolism across the life span.
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Envelhecimento/genética , Encéfalo/metabolismo , Coenzima A Ligases/genética , Ácidos Docosa-Hexaenoicos/metabolismo , Neuroproteção/genética , Envelhecimento/metabolismo , Envelhecimento/patologia , Envelhecimento/fisiologia , Animais , Encéfalo/patologia , Cerebelo/metabolismo , Cerebelo/patologia , Colesterol/biossíntese , Coenzima A Ligases/metabolismo , Expressão Gênica , Gliose/genética , Gliose/metabolismo , Gliose/patologia , Locomoção/fisiologia , Memória de Curto Prazo/fisiologia , Camundongos , Camundongos Knockout , Doenças Neuroinflamatórias/metabolismo , Memória Espacial/fisiologia , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por MatrizRESUMO
Marine microbes are known to degrade hydrocarbons; however, microbes inhabiting deep-sea sediments remain largely unexplored. Previous studies into the classical pathways of marine microbial metabolism reveal diverse chemistries; however, metabolic profiling of marine microbes cultured with hydrocarbons is limited. In this study, taxonomic (amplicon sequencing) profiles of two environmental deep-sea sediments (>1,200 m deep) were obtained, along with taxonomic and metabolomic (mass spectrometry-based metabolomics) profiles of microbes harbored in deep-sea sediments cultured with hydrocarbons as the sole energy source. Samples were collected from the Gulf of México (GM) and cultured for 28 days using simple (toluene, benzene, hexadecane, and naphthalene) and complex (petroleum API 40) hydrocarbon mixtures as the sole energy sources. The sediment samples harbored diverse microbial communities predominantly classified into Woeseiaceae and Kiloniellaceae families, whereas Pseudomonadaceae and Enterobacteriaceae families prevailed after sediments were cultured with hydrocarbons. Chemical profiling of microbial metabolomes revealed diverse chemical groups belonging primarily to the lipids and lipid-like molecules superclass, as well as the organoheterocyclic compound superclass (ClassyFire annotation). Metabolomic data and prediction of functional profiles indicated an increase in aromatic and alkane degradation in samples cultured with hydrocarbons. Previously unreported metabolites, identified as intermediates in the degradation of hydrocarbons, were annotated as hydroxylated polyunsaturated fatty acids and carboxylated benzene derivatives. In summary, this study used mass spectrometry-based metabolomics coupled to chemoinformatics to demonstrate how microbes from deep-sea sediments could be cultured in the presence of hydrocarbons. This study also highlights how this experimental approach can be used to increase the understanding of hydrocarbon degradation by deep-sea sediment microbes.IMPORTANCE High-throughput technologies and emerging informatics tools have significantly advanced knowledge of hydrocarbon metabolism by marine microbes. However, research into microbes inhabiting deep-sea sediments (>1,000 m) is limited compared to those found in shallow waters. In this study, a nontargeted and nonclassical approach was used to examine the diversity of bacterial taxa and the metabolic profiles of hydrocarbon-degrading deep-sea microbes. In conclusion, this study used metabolomics and chemoinformatics to demonstrate that microbes from deep-sea sediment origin thrive in the presence of toxic and difficult-to-metabolize hydrocarbons. Notably, this study provides evidence of previously unreported metabolites and the global chemical repertoire associated with the metabolism of hydrocarbons by deep-sea microbes.
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The reaction between [TBA]2[Zn(dmit)2] and 3-chloro-2,4-penta-nedione yielded single crystals of the title compound, (3E,3'E)-3,3'-[(2-sulfanylidene-1,3-dithiole-4,5-diyl)bis(sulfanediyl)]bis(4-hydroxypent-3-en-2-one), C13H14O4S5, after solvent evaporation. The title compound crystallizes in the triclinic space group P with two mol-ecules related by an inversion center present in the unit cell. The central thione ring moiety contains a carbon-carbon double bond covalently linked to two sulfoxide substituents located outside of the plane of the ring. The S-C-C-S torsion angles are -176.18â (8) and -0.54â (18)°. Intra-molecular hydrogen bonds occur within the two dione substituents (1.67-1.69â Å). Adjacent asymmetric units are linked by C-Hâ¯S (2.89-2.90â Å), Sâ¯S [3.569â (1)â Å] and Oâ¯H [2.56-2.66â Å between non-stacked thione rings] short contacts.
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Resumen A raíz de la pandemia de COVID-19 provocada por el SARS-CoV 2, en tan solo seis meses de su existencia se han adoptado distintas medidas de protección y atención a la población mundial. Los trabajadores de la salud han realizado grandes esfuerzos para combatir la enfermedad a nivel hospitalario. De forma paradójica, se han identificado actos de discriminación y agresión en contra del personal sanitario, que incluyen la negación de servicios, amenazas, daño físico y patrimonial, principalmente. El propósito de este trabajo es describir algunos elementos que permitan comprender el comportamiento social de discriminación que sufren los trabajadores sanitarios. Se describe el estado de la salud mental en la población general y del personal intrahospitalario durante la pandemia, así como los antecedentes de agresiones al personal de salud previos a esta condición, que permiten tener un panorama general desde distintas perspectivas, con el fin de establecer lineamientos generales útiles para su prevención.
Abstract Within six months only of its existence as result of the ongoing pandemic of COVID-19 caused by the SARSCoV2, various safety measures have been applied in order to offer both protection and attention to the worldwide population. Healthcare professionals have been making great efforts to fight the disease on a hospital care level but paradoxically, acts of aggressive discrimination have been presented towards the health personnel, which mainly include: denying services, threats, and physical damage as well as patrimonial. This paper's purpose is to describe some of the elements that help understand the mass social discriminative behaviour showing up towards healthcare workers. Healthcare personnel and general population's mental health states during this pandemic are both described, as well as background checks of aggression towards healthcare workers predating the present pandemic, allowing a bigger picture to be examined, with the intention of establishing new general guidelines to prevent future acts of discrimination.
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Humanos , Pessoal de Saúde , Discriminação Social , COVID-19 , Saúde Mental , AgressãoRESUMO
Acoustic standing wave devices offer excellent potential applications in biological sciences for drug delivery, cell manipulation and tissue engineering. However, concerns have been raised about possible destructive effects on cells due to the applied acoustic field, in addition to other produced secondary factors. Here, we report a systematic study employing a 1D resonant acoustic trapping device to evaluate the cell viability and cell metabolism for a healthy cell line (Human Dermal Fibroblasts, HDF) and a cervical cancer cell line (HeLa), as a function of time and voltages applied (4-10 Vpp) under temperature-controlled conditions. We demonstrate that high cell viability can be achieved reliably when the device is operated at its minimum trapping voltage and tuned carefully to maximise the acoustic standing wave field at the cavity resonance. We found that cell viability and reductive metabolism for both cell lines are kept close to control levels at room temperature and at 34 °C after 15 minutes of acoustic exposure, while shorter acoustic exposures and small changes on temperature and voltages, had detrimental effects on cells. Our study highlights the importance of developing robust acoustic protocols where the operating mode of the acoustic device is well defined, characterized and its temperature carefully controlled, for the application of acoustic standing waves when using live cells and for potential clinical applications.
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Acústica/instrumentação , Fibroblastos/metabolismo , Microfluídica/instrumentação , Neoplasias do Colo do Útero/metabolismo , Sobrevivência Celular , Feminino , Fibroblastos/citologia , Humanos , Neoplasias do Colo do Útero/patologia , VibraçãoAssuntos
Encefalite Antirreceptor de N-Metil-D-Aspartato/tratamento farmacológico , Antagonistas de Aminoácidos Excitatórios/farmacologia , Fatores Imunológicos/farmacologia , Memantina/farmacologia , Adulto , Quimioterapia Combinada , Antagonistas de Aminoácidos Excitatórios/administração & dosagem , Feminino , Humanos , Fatores Imunológicos/administração & dosagem , Memantina/administração & dosagemRESUMO
Docosahexaenoic acid (DHA) is an ω-3 dietary-derived polyunsaturated fatty acid of marine origin enriched in testes and necessary for normal fertility, yet the mechanisms regulating the enrichment of DHA in the testes remain unclear. Long-chain ACSL6 (acyl-CoA synthetase isoform 6) activates fatty acids for cellular anabolic and catabolic metabolism by ligating a CoA to a fatty acid, is highly expressed in testes, and has high preference for DHA. Here, we investigated the role of ACSL6 for DHA enrichment in the testes and its requirement for male fertility. Acsl6-/- males were severely subfertile with smaller testes, reduced cauda epididymal sperm counts, germ cell loss, and disorganization of the seminiferous epithelium. Total fatty acid profiling of Acsl6-/- testes revealed reduced DHA and increased ω-6 arachidonic acid, a fatty acid profile also reflected in phospholipid composition. Strikingly, lipid imaging demonstrated spatial redistribution of phospholipids in Acsl6-/- testes. Arachidonic acid-containing phospholipids were predominantly interstitial in control testes but diffusely localized across Acsl6-/- testes. In control testes, DHA-containing phospholipids were predominantly within seminiferous tubules, which contain Sertoli cells and spermatogenic cells but relocalized to the interstitium in Acsl6-/- testes. Taken together, these data demonstrate that ACSL6 is an initial driving force for germ cell DHA enrichment and is required for normal spermatogenesis and male fertility.