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Carbon monoxide (CO) has emerged as a promising therapeutic agent, yet ensuring safe and precise CO delivery remains challenging. Here, we report a removable hydrogel-forming microneedle (MN) reactor for CO delivery via photocatalysis, with an emphasis on chemosensitization. Upon application, body fluids absorbed by the MNs dissolve the effervescent agents, leading to the generation of carbon dioxide (CO2) and triggering the release of the chemotherapeutics cisplatin. Meanwhile, the photocatalysts (PCs) trapped within MNs convert CO2 to CO under 660 nm light irradiation. These PCs can be removed by hydrogel-forming MNs, thereby mitigating potential biological risks associated with residual PCs. Both in vitro and in vivo experiments showed that MN-mediated CO delivery significantly improved tumor sensitivity to cisplatin by suppressing DNA repair, using an A375/CDDP melanoma model. This removable photocatalysis MN reactor offers safe and precise local delivery of CO, potentially creating new opportunities for CO or its combination therapies.
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Signaling via the T cell antigen receptor (TCR) during the CD4(+)CD8(+) double-positive developmental stage determines thymocyte selection and lineage commitment. Here we describe a previously uncharacterized T cell-expressed protein, Tespa1, with critical functions during the positive selection of thymocytes. Tespa1(-/-) mice had fewer mature thymic CD4(+) and CD8(+) T cells, which reflected impaired thymocyte development. Tespa1 associated with the TCR signaling components PLC-γ1 and Grb2, and Tespa1 deficiency resulted in attenuated TCR signaling, as reflected by defective activation of the Erk-AP-1 and Ca(2+)-NFAT pathways. Our findings demonstrate that Tespa1 is a component of the TCR signalosome and is essential for T cell selection and maturation through the regulation of TCR signaling during T cell development.
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Receptores de Antígenos de Linfócitos T/imunologia , Linfócitos T/imunologia , Timo/imunologia , Proteínas Adaptadoras de Transdução de Sinal/imunologia , Sequência de Aminoácidos , Animais , Sequência de Bases , Diferenciação Celular/imunologia , Clonagem Molecular , Proteína Adaptadora GRB2/imunologia , Ativação Linfocitária , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos , Dados de Sequência Molecular , Fosfolipase C gama/imunologia , RNA Mensageiro/química , RNA Mensageiro/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Alinhamento de Sequência , Transdução de Sinais/imunologia , Timo/citologiaRESUMO
The term "zwitterionic polymers" refers to polymers that bear a pair of oppositely charged groups in their repeating units. When these oppositely charged groups are equally distributed at the molecular level, the molecules exhibit an overall neutral charge with a strong hydration effect via ionic solvation. The strong hydration effect constitutes the foundation of a series of exceptional properties of zwitterionic materials, including resistance to protein adsorption, lubrication at interfaces, promotion of protein stabilities, antifreezing in solutions, etc. As a result, zwitterionic materials have drawn great attention in biomedical and engineering applications in recent years. In this review, we give a comprehensive and panoramic overview of zwitterionic materials, covering the fundamentals of hydration and nonfouling behaviors, different types of zwitterionic surfaces and polymers, and their biomedical applications.
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Materiais Biocompatíveis , Polímeros , Adsorção , ProteínasRESUMO
The widespread ozone (O3) pollution is extremely hazardous to human health and ecosystems. Catalytic decomposition into O2 is the most promising method to eliminate ambient O3, while the fast deactivation of catalysts under humid conditions remains the primary challenge for their application. Herein, we elaborately developed a splendidly active and stable Mn-based catalyst with double hydrophobic protection of active carbon (AC) and CeO2 (CeMn@AC), which possessed abundant interfacial oxygen vacancies and excellent desorption of peroxide intermediates (O22-). Under extremely humid (RH = 90%) conditions and a high space velocity of 1200 L h-1 g-1, the optimized CeMn@AC achieved nearly 100% O3 conversion (140 h) at 5 ppm, showing unprecedented catalytic activity and moisture resistance toward O3 decomposition. In situ DRIFTS and theory calculations confirmed that the exceptional moisture resistance of CeMn@AC was ascribed to the double protection effect of AC and CeO2, which cooperatively prevented the competitive adsorption of H2O molecules and their accumulation on the active sites of MnO2. AC provided a hydrophobic reaction environment, and CeO2 further alleviated moisture deterioration of the MnO2 particles exposed on the catalyst surface via the moisture-resistant oxygen vacancies of MnO2-CeO2 crystal boundaries. This work offers a simple and efficient strategy for designing moisture-resistant materials and facilitates the practical application of the O3 decomposition catalysts in various environments.
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Ozônio , Ozônio/química , Catálise , Carbono/química , Compostos de Manganês/química , Cério/química , Óxidos/químicaRESUMO
The establishment of an appropriate costimulatory phenotype is crucial for dendritic cells (DCs) to maintain a homeostatic state with optimal immune surveillance and immunogenic activities. The upregulation of CD80/86 and CD40 is a hallmark costimulatory phenotypic switch of DCs from a steady state to an activated one for T cell activation. However, knowledge of the regulatory mechanisms underlying this process remains limited. In this study, we identified a Zbtb46 homolog from a zebrafish model. Zbtb46 deficiency resulted in upregulated cd80/86 and cd40 expression in kidney marrow-derived DCs (KMDCs) of zebrafish, which was accompanied with a remarkable expansion of CD4+/CD8+ T cells and accumulation of KMDCs in spleen of naive fish. Zbtb46 -/- splenic KMDCs exhibited strong stimulatory activity for CD4+ T cell activation. Chromatin immunoprecipitation-quantitative PCR and mass spectrometry assays showed that Zbtb46 was associated with promoters of cd80/86 and cd40 genes by binding to a 5'-TGACGT-3' motif in resting KMDCs, wherein it helped establish a repressive histone epigenetic modification pattern (H3K4me0/H3K9me3/H3K27me3) by organizing Mdb3/organizing nucleosome remodeling and deacetylase and Hdac3/nuclear receptor corepressor 1 corepressor complexes through the recruitment of Hdac1/2 and Hdac3. On stimulation with infection signs, Zbtb46 disassociated from the promoters via E3 ubiquitin ligase Cullin1/Fbxw11-mediated degradation, and this reaction can be triggered by the TLR9 signaling pathway. Thereafter, cd80/86 and cd40 promoters underwent epigenetic reprogramming from the repressed histone modification pattern to an activated pattern (H3K4me3/H3K9ac/H3K27ac), leading to cd80/86 and cd40 expression and DC activation. These findings revealed the essential role of Zbtb46 in maintaining DC homeostasis by suppressing cd80/86 and cd40 expression through epigenetic mechanisms.
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Linfócitos T CD8-Positivos , Peixe-Zebra , Animais , Antígeno B7-1/genética , Antígeno B7-1/metabolismo , Antígenos CD40 , Moléculas de Adesão Celular/metabolismo , Células Dendríticas , Epigênese Genética , Ativação LinfocitáriaRESUMO
Oat products have gained widespread recognition as a health food due to their rich and balanced nutritional profile and convenience. However, the unique matrix composition of oats, which differs significantly from other cereals, presents specific challenges for mycotoxin analysis. This study presents an ultrahigh-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method enhanced with an innovative egg white gel pretreatment for the simultaneous analysis of 13 regulated and unregulated trichothecenes in oats. The method demonstrated excellent performance with high accuracy (> 87.5%), repeatability (< 5.7%), and reproducibility (< 8.1%). Analysis of 100 commercial oat products revealed a concerning detection rate (78%) for at least one of the 11 trichothecenes investigated. Notably, deoxynivalenol, exceeding the standard limit in 2% of samples, exhibited the highest detection rate (62%). Additionally, concerning co-occurrence patterns and positive correlations were observed, highlighting potential synergistic effects. The first-time detection of unregulated mycotoxins (T-2 triol, 4,15-diacetoxyscirpenol, 15-acetoxyscirpenol, and neosolaniol) underscores the need for comprehensive monitoring. This method, while developed for oats, shows potential for broader application to other cereals, though further investigation and confirmation are necessary. These findings suggest a potentially underestimated risk of trichothecenes in oats, necessitating continuous monitoring to ensure consumer safety.
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Avena , Contaminação de Alimentos , Limite de Detecção , Espectrometria de Massas em Tandem , Tricotecenos , Avena/química , Espectrometria de Massas em Tandem/métodos , Cromatografia Líquida de Alta Pressão/métodos , Tricotecenos/análise , Contaminação de Alimentos/análise , Géis/química , Reprodutibilidade dos TestesRESUMO
Organic phosphorescent materials are excellent candidates for use in tumor imaging. However, a systematic comparison of the effects of the intensity, lifetime, and wavelength of phosphorescent emissions on bioimaging performance has not yet been undertaken. In addition, there have been few reports on organic phosphorescent materials that specifically distinguish tumors from normal tissues. This study addresses these gaps and reveals that longer lifetimes effectively increase the signal intensity, whereas longer wavelengths enhance the penetration depth. Conversely, a strong emission intensity with a short lifetime does not necessarily yield robust imaging signals. Building upon these findings, an organo-phosphorescent material with a lifetime of 0.94â s was designed for tumor imaging. Remarkably, the phosphorescent signals of various organic nanoparticles are nearly extinguished in blood-rich organs because of the quenching effect of iron ions. Moreover, for the first time, we demonstrated that iron ions universally quench the phosphorescence of organic room-temperature phosphorescent materials, which is an inherent property of such substances. Leveraging this property, both the normal liver and hepatitis tissues exhibit negligible phosphorescent signals, whereas liver tumors display intense phosphorescence. Therefore, phosphorescent materials, unlike chemiluminescent or fluorescent materials, can exploit this unique inherent property to selectively distinguish liver tumor tissues from normal tissues without additional modifications or treatments.
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The ever-increasing threats of multidrug-resistant bacteria and their biofilm-associated infections have bred a desperate demand for alternative remedies to combat them. Near-infrared (NIR)-absorbing photothermal agent (PTAs)-mediated photothermal therapy (PTT) is particularly attractive for biofilm ablation thanks to its superiorities of noninvasive intervention, satisfactory antibacterial efficiency, and less likelihood to develop resistance. Herein, three butterfly-shaped aggregation-induced emission luminogens (AIEgens) with balanced nonradiative decay (for conducting PTT) and radiative decay (for supplying fluorescence in the NIR-II optical window) are rationally designed for imaging-assisted photothermal obliteration of bacterial biofilms. After being encapsulated into cationic liposomes, AIEgens-fabricated nanoparticles can eradicate a wide spectrum of biofilms formed by Gram-positive bacteria (methicillin-resistant Staphylococcus aureus and Enterococcus faecalis) and Gram-negative bacteria (Escherichia coli and Pseudomonas aeruginosa) upon an 808 nm laser irradiation. In vivo experiments firmly demonstrate that the NIR-II AIE liposomes with excellent biocompatibility perform well in both the P. aeruginosa biofilm-induced keratitis mouse model and the MSRA biofilm-induced skin infection mouse model.
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Staphylococcus aureus Resistente à Meticilina , Camundongos , Animais , Lipossomos , Bactérias , Antibacterianos/farmacologia , BiofilmesRESUMO
Zonulin is a physiologic epithelial and endothelial permeability modulator. Zonulin increases antigen trafficking from the gut lumen into the bloodstream and in between body compartments, a mechanism linked to many chronic inflammatory diseases. Upon its initial discovery, it was noted that zonulin was not a single protein, but rather a family of structurally and functionally related proteins referred to as the zonulin family proteins (ZFPs). ZFPs are members of the mannose associated serine proteases (MASP) family and are the result of high mutation rates leading to many zonulin polymorphisms. Pre-haptoglobin 2, the precursor of haptoglobin 2, was identified as the first eukaryotic member of the ZFPs, and properdin, a key positive regulator of the alternative pathway, as a second member. In this study, we report two additional proteins that are likely ZFPs. Human coagulation factor X (FX) and CD5 antigen-like (CD5L). Both FX and CD5L recombinant proteins were detected by anti-zonulin antibody in Western immunoblot analysis, and both proteins decreased epithelial barrier competency of Caco-2 cell monolayers as established by the Trans Epithelial Electrical Resistance (TEER) assay. These results indicate that FX and CD5L have structural and functional similarities with previously identified ZFPs and, therefore, can be considered new members of this family of proteins.
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Fator X , Haptoglobinas , Humanos , Haptoglobinas/análise , Antígenos CD5/metabolismo , Fator X/metabolismo , Células CACO-2 , Proteínas de Transporte/metabolismo , Permeabilidade , Mucosa Intestinal/metabolismoRESUMO
Transition metal ions are served as disinfectant thousand years ago. However, the in vivo antibacterial application of metal ions is strongly restricted due to its high affinity with proteins and lack of appropriate bacterial targeting method. Herein, for the first time, Zn2+ -gallic acid nanoflowers (ZGNFs) are synthesized by a facile one-pot method without additional stabilizing agents. ZGNFs are stable in aqueous solution while can be easily decomposed in acidic environments. Besides, ZGNFs can specifically adhere onto Gram-positive bacteria, which is mediated by the interaction of quinone from ZGNFs and amino groups from teichoic acid of Gram-positive bacteria. ZGNFs exhibit high bactericidal effect toward various Gram-positive bacteria in multiple environments, which can be ascribed to the in situ Zn2+ release on bacterial surface. Transcriptome studies reveal that ZGNFs can disorder basic metabolic processes of Methicillin-resistant Staphylococcus aureus (MRSA). Moreover, in a MRSA-induced keratitis model, ZGNFs exhibit long-term retention in the infected corneal site and prominent MRSA elimination efficacy due to the self-targeting ability. This research not only reports an innovative method to prepare metal-polyphenol nanoparticles, but also provides a novel nanoplatform for targeted delivery of Zn2+ in combating Gram-positive bacterial infections.
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Staphylococcus aureus Resistente à Meticilina , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Bactérias Gram-Positivas , Íons , Zinco/farmacologia , Testes de Sensibilidade MicrobianaRESUMO
Drug resistance in pathogenic bacteria has become a major threat to global health. The misuse of antibiotics has increased the number of resistant bacteria in the absence of rapid, accurate, and cost-effective diagnostic tools. Here, an amplification-free CRISPR-Cas12a time-resolved fluorescence immunochromatographic assay (AFC-TRFIA) is used to detect drug-resistant Salmonella. Multi-locus targeting in combination crRNA (CcrRNA) is 27-fold more sensitive than a standalone crRNA system. The lyophilized CRISPR system further simplifies the operation and enables one-pot detection. Induction of nucleic acid fixation via differentially charged interactions reduced the time and cost required for flowmetric chromatography with enhanced stability. The induction of nucleic acid fixation via differentially charged interactions reduces the time and cost required for flowmetric chromatography with enhanced stability. The platform developed for the detection of drug-resistant Salmonella has an ultra-sensitive detection limit of 84 CFU mL-1 within 30 min, with good linearity in the range of 102 -106 CFU mL-1 . In real-world applications, spiked recoveries range from 76.22% to 145.91%, with a coefficient of variation less than 10.59%. AFC-TRFIA offers a cost-effective, sensitive, and virtually equipment-independent platform for preventing foodborne illnesses, screening for drug-resistant Salmonella, and guiding clinical use.
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Doenças Transmitidas por Alimentos , Ácidos Nucleicos , Humanos , Antibacterianos , Fluorescência , Salmonella/genética , Técnicas de Amplificação de Ácido NucleicoRESUMO
Spring viremia of carp virus (SVCV) is a severe infectious pathogen that causes high rates of mortality in cyprinids and other fish species. Despite numerous investigations of SVCV infection, the underlying molecular mechanisms remain poorly understood. In this study, we found that the SVCV matrix protein (SVCV-M) played an inhibitory role in the host interferon (IFN) response by targeting the MAVS/TRAF3 signaling axis, thereby uncovering a previously unrecognized mechanism of SVCV escape from host innate antiviral immunity. Mechanistically, SVCV-M was located at the mitochondria independent of MAVS, which allowed SVCV-M to build an arena for competition with the MAVS platform. A microscale thermophoresis assay showed that SVCV-M had a high affinity for TRAF3, as indicated by a lower equilibrium dissociation constant (KD) value than that of MAVS with TRAF3. Therefore, the association of MAVS with TRAF3 was competitively impaired by SVCV-M in a dose-dependent manner. Accordingly, SVCV-M showed a potent ability to inhibit the K63-linked polyubiquitination of TRAF3. This inhibition was accompanied by the impairment of the IFN response, as shown by the marked decline in IFN-φ1-promoter (pro) luciferase reporter activity. By constructing truncated TRAF3 and SVCV-M proteins, the RING finger, zinc finger, and coiled-coil domains of TRAF3 and the hydrophobic-pocket-like structure formed by the α2-, α3-, and α4-helices of SVCV-M may be the major target and antagonistic modules responsible for the protein-protein interaction between the TRAF3 and SVCV-M proteins. These findings highlighted the intervention of SVCV-M in host innate immunity, thereby providing new insights into the extensive participation of viral matrix proteins in multiple biological activities. IMPORTANCE The matrix protein of SVCV (SVCV-M) is an indispensable structural element for nucleocapsid condensation and virion formation during viral morphogenesis, and it connects the core nucleocapsid particle to the outer membrane within the mature virus. Previous studies have emphasized the architectural role of SVCV-M in viral construction; however, the potential nonstructural functions of SVCV-M in viral replication and virus-host interactions remain poorly understood. In this study, we identified the inhibitory role of the SVCV-M protein in host IFN production by competitively recruiting TRAF3 from the MAVS signaling complex and impairing TRAF3 activation via inhibition of K63-linked polyubiquitination. This finding provided new insights into the regulatory role of SVCV-M in host innate immunity, which highlighted the broader functionality of rhabdovirus matrix protein apart from being a structural protein. This study also revealed a previously unrecognized mechanism underlying SVCV immune evasion by inhibiting the IFN response by targeting the MAVS/TRAF3 signaling axis.
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Carpas , Infecções por Rhabdoviridae/veterinária , Rhabdoviridae/fisiologia , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Animais , Imunidade Inata , Interferons/metabolismo , Infecções por Rhabdoviridae/imunologia , Fator 3 Associado a Receptor de TNF/genética , Fator 3 Associado a Receptor de TNF/metabolismo , Proteínas da Matriz Viral/metabolismo , Viremia/veterináriaRESUMO
Mycotoxins are secondary metabolites produced by fungi in food and feed, which can cause serious health problems. Bioenzymatic degradation is gaining increasing popularity due to its high specificity, gentle degradation conditions, and environmental friendliness. We reviewed recently reported biosynthetic mycotoxin-degrading enzymes, traditional and novel expression systems, enzyme optimization strategies, food and feed applications, safety evaluation of both degrading enzymes and degradation products, and commercialization potentials. Special emphasis is given to the novel expression systems, advanced optimization strategies, and safety considerations for industrial use. Over ten types of recombinases such as oxidoreductase and hydrolase have been studied in the enzymatic hydrolysis of mycotoxins. Besides traditional expression system of Escherichia coli and yeasts, these enzymes can also be expressed in novel systems such as Bacillus subtilis and lactic acid bacteria. To meet the requirements of industrial applications in terms of degradation efficacy and stability, genetic engineering and computational tools are used to optimize enzymatic expression. Currently, registration and technical difficulties have restricted commercial application of mycotoxin-degrading enzymes. To overcome these obstacles, systematic safety evaluation of both biosynthetic enzymes and their degradation products, in-depth understanding of degradation mechanisms and a comprehensive evaluation of their impact on food and feed quality are urgently needed.
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Prevention is more important than treatment, and the incidence of intracerebral hemorrhage can be effectively reduced by intervening on the risk factors of intracerebral hemorrhage. By studying the risk factors of spontaneous intracerebral hemorrhage, we can identify the risk factors to achieve the target of treatment and prevention. Through the use of the Least Absolute Shrinkage and Selection Operator (LASSO) and the Support Vector Machine (SVM), the two essential SICH-related genes, NUAK1 and ERO1L, were eliminated from consideration. A Venn analysis was performed, and based on the two important modules, it found that SICH was related with four critical genes: VCM1, CRNDE, COL6A2, and HSPB6. One gene (NUAK1) was dramatically downregulated in the illness group compared to the control group, whereas three essential genes (ERO1L, VCAM1, and COL6A2) were significantly upregulated in the disease group. In the end, the genes ERO1L, VCAM1, COL6A2, and NUAK1 were shown to be the most important ones for SICH. It is anticipated that these genes will become novel biomarkers as well as targets for the development of new pharmacotherapies for SICH.
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Hemorragia Cerebral , Máquina de Vetores de Suporte , Humanos , Hemorragia Cerebral/genética , Hemorragia Cerebral/epidemiologia , Fatores de Risco , Biomarcadores , Proteínas Quinases , Proteínas RepressorasRESUMO
AIMS: Left bundle branch area pacing (LBBAP) is a promising method for delivering cardiac resynchronization therapy (CRT), but its relative physiological effectiveness compared with His bundle pacing (HBP) is unknown. We conducted a within-patient comparison of HBP, LBBAP, and biventricular pacing (BVP). METHODS AND RESULTS: Patients referred for CRT were recruited. We assessed electrical response using non-invasive mapping, and acute haemodynamic response using a high-precision haemodynamic protocol. Nineteen patients were recruited: 14 male, mean LVEF of 30%. Twelve had time for BVP measurements. All three modalities reduced total ventricular activation time (TVAT), (ΔTVATHBP -43 ± 14 ms and ΔTVATLBBAP -35 ± 20 ms vs. ΔTVATBVP -19 ± 30 ms, P = 0.03 and P = 0.1, respectively). HBP produced a significantly greater reduction in TVAT compared with LBBAP in all 19 patients (-46 ± 15 ms, -36 ± 17 ms, P = 0.03). His bundle pacing and LBBAP reduced left ventricular activation time (LVAT) more than BVP (ΔLVATHBP -43 ± 16 ms, P < 0.01 vs. BVP, ΔLVATLBBAP -45 ± 17 ms, P < 0.01 vs. BVP, ΔLVATBVP -13 ± 36 ms), with no difference between HBP and LBBAP (P = 0.65). Acute systolic blood pressure was increased by all three modalities. In the 12 with BVP, greater improvement was seen with HBP and LBBAP (6.4 ± 3.8 mmHg BVP, 8.1 ± 3.8 mmHg HBP, P = 0.02 vs. BVP and 8.4 ± 8.2 mmHg for LBBAP, P = 0.3 vs. BVP), with no difference between HBP and LBBAP (P = 0.8). CONCLUSION: HBP delivered better ventricular resynchronization than LBBAP because right ventricular activation was slower during LBBAP. But LBBAP was not inferior to HBP with respect to LV electrical resynchronization and acute haemodynamic response.
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Terapia de Ressincronização Cardíaca , Insuficiência Cardíaca , Humanos , Masculino , Fascículo Atrioventricular , Terapia de Ressincronização Cardíaca/efeitos adversos , Terapia de Ressincronização Cardíaca/métodos , Bloqueio de Ramo/diagnóstico , Bloqueio de Ramo/terapia , Eletrocardiografia/métodos , Resultado do Tratamento , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/terapia , Hemodinâmica , Estimulação Cardíaca Artificial/métodosRESUMO
AIMS: Left bundle branch pacing (LBBP) can deliver physiological left ventricular activation, but typically at the cost of delayed right ventricular (RV) activation. Right ventricular activation can be advanced through anodal capture, but there is uncertainty regarding the mechanism by which this is achieved, and it is not known whether this produces haemodynamic benefit. METHODS AND RESULTS: We recruited patients with LBBP leads in whom anodal capture eliminated the terminal R-wave in lead V1. Ventricular activation pattern, timing, and high-precision acute haemodynamic response were studied during LBBP with and without anodal capture. We recruited 21 patients with a mean age of 67 years, of whom 14 were males. We measured electrocardiogram timings and haemodynamics in all patients, and in 16, we also performed non-invasive mapping. Ventricular epicardial propagation maps demonstrated that RV septal myocardial capture, rather than right bundle capture, was the mechanism for earlier RV activation. With anodal capture, QRS duration and total ventricular activation times were shorter (116 ± 12 vs. 129 ± 14â ms, P < 0.01 and 83 ± 18 vs. 90 ± 15â ms, P = 0.01). This required higher outputs (3.6 ± 1.9 vs. 0.6 ± 0.2â V, P < 0.01) but without additional haemodynamic benefit (mean difference -0.2 ± 3.8â mmHg compared with pacing without anodal capture, P = 0.2). CONCLUSION: Left bundle branch pacing with anodal capture advances RV activation by stimulating the RV septal myocardium. However, this requires higher outputs and does not improve acute haemodynamics. Aiming for anodal capture may therefore not be necessary.
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Fascículo Atrioventricular , Estimulação Cardíaca Artificial , Masculino , Humanos , Idoso , Feminino , Estimulação Cardíaca Artificial/métodos , Sistema de Condução Cardíaco , Hemodinâmica , Ventrículos do Coração , Eletrocardiografia/métodosRESUMO
Ozone (O3) pollution is highly detrimental to human health and the ecosystem due to it being ubiquitous in ambient air and industrial processes. Catalytic decomposition is the most efficient technology for O3 elimination, while the moisture-induced low stability represents the major challenge for its practical applications. Here, activated carbon (AC) supported δ-MnO2 (Mn/AC-A) was facilely synthesized via mild redox in an oxidizing atmosphere to obtain exceptional O3 decomposition capacity. The optimal 5Mn/AC-A achieved nearly 100% of O3 decomposition at a high space velocity (1200 L g-1 h-1) and remained extremely stable under entire humidity conditions. The functionalized AC provided well-designed protection sites to inhibit the accumulation of water on δ-MnO2. Density functional theory (DFT) calculations confirmed that the abundant oxygen vacancies and a low desorption energy of intermediate peroxide (O22-) can significantly boost O3 decomposition activity. Moreover, a kilo-scale 5Mn/AC-A with low cost (â¼1.5 $/kg) was used for the O3 decomposition in practical applications, which could quickly decompose O3 pollution to a safety level below 100 µg m-3. This work offers a simple strategy for the development of moisture-resistant and inexpensive catalysts and greatly promotes the practical application of ambient O3 elimination.
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Ozônio , Humanos , Óxidos , Carvão Vegetal , Umidade , Compostos de Manganês , Ecossistema , Oxigênio , CatáliseRESUMO
Ozone catalytic oxidation (OZCO) has gained great interest in environmental remediation while it still faces a big challenge during the deep degradation of refractory volatile organic compounds (VOCs) at room temperature. Hydroxylation of the catalytic surface provides a new strategy for regulating the catalytic activity to boost VOC degradation. Herein, OZCO of toluene at room temperature over hydroxyl-mediated MnOx/Al2O3 catalysts was originally demonstrated. Specifically, a novel hydroxyl-mediated MnOx/Al2O3 catalyst was developed via the in situ AlOOH reconstruction method and used for toluene OZCO. The toluene degradation performance of MnOx/Al2O3 was significantly superior to those of most of the state-of-the-art catalysts, and 100% toluene was removed with an excellent mineralization rate (82.3%) and catalytic stability during OZCO. ESR and in situ DRIFTs results demonstrated that surface hydroxyl groups (HGs) greatly improved the reactive oxygen species generation, thus dramatically accelerating the benzene ring breakage and deep mineralization. Furthermore, HGs provided anchoring sites for uniformly dispersing MnOx and greatly enhanced toluene adsorption and ozone activation. This work paves a way for deep decomposition of aromatic VOCs at room temperature.
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Ozônio , Óxidos , Temperatura , Tolueno , Oxirredução , Radical Hidroxila , CatáliseRESUMO
IgZ or its equivalent IgT is a newly discovered teleost specific Ig class that is highly specialized in mucosal immunity. However, whether this IgZ/IgT class participates in other biological processes remains unclear. In this study, we unexpectedly discovered that IgZ is highly expressed in zebrafish ovary, accumulates in unfertilized eggs, and is transmitted to offspring from eggs to zygotes. Maternally transferred IgZ in zygotes is found at the outer and inner layers of chorion, perivitelline space, periphery of embryo body, and yolk, providing different lines of defense against pathogen infection. A considerable number of IgZ+ B cells are found in ovarian connective tissues distributed between eggs. Moreover, pIgR, the transporter of IgZ, is also expressed in the ovary and colocalizes with IgZ in the zona radiata of eggs. Thus, IgZ is possibly secreted by ovarian IgZ+ B cells and transported to eggs through association with pIgR in a paracrine manner. Maternal IgZ in zygotes showed a broad bacteriostatic activity to different microbes examined, and this reactivity can be manipulated by orchestrating desired bacteria in water where parent fish live or immunizing the parent fish through vaccination. These observations suggest that maternal IgZ may represent a group of polyclonal Abs, providing protection against various environmental microbes encountered by a parent fish that were potentially high risk to offspring. To our knowledge, our findings provide novel insights into a previously unrecognized functional role of IgZ/IgT Ig in the maternal transfer of immunity in fish, greatly enriching current knowledge about this ancient Ig class.
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Resistência à Doença/imunologia , Doenças dos Peixes/imunologia , Cadeias Pesadas de Imunoglobulinas/imunologia , Isotipos de Imunoglobulinas/imunologia , Proteínas de Peixe-Zebra/imunologia , Peixe-Zebra/imunologia , Aeromonas hydrophila/imunologia , Aeromonas hydrophila/fisiologia , Animais , Resistência à Doença/genética , Embrião não Mamífero/embriologia , Embrião não Mamífero/imunologia , Embrião não Mamífero/microbiologia , Feminino , Doenças dos Peixes/microbiologia , Expressão Gênica/imunologia , Interações Hospedeiro-Patógeno/imunologia , Cadeias Pesadas de Imunoglobulinas/genética , Cadeias Pesadas de Imunoglobulinas/metabolismo , Isotipos de Imunoglobulinas/genética , Isotipos de Imunoglobulinas/metabolismo , Masculino , Herança Materna/genética , Herança Materna/imunologia , Vibrio/classificação , Vibrio/imunologia , Vibrio/fisiologia , Peixe-Zebra/genética , Peixe-Zebra/microbiologia , Proteínas de Peixe-Zebra/genética , Proteínas de Peixe-Zebra/metabolismo , Zigoto/imunologia , Zigoto/metabolismo , Zigoto/microbiologiaRESUMO
Drug-resistant Salmonella is widely distributed in the meat production chain, endangering food safety and public health. Acidification of meat products during processing can induce acid stress, which may alter antibiotic resistance. Our study investigated the effects of acid stress on the antibiotic resistance and metabolic profile of Salmonella Typhimurium, and explored the underlying mechanisms using metabolomic and transcriptomic analysis. We found that acid-stressed 14028s was more sensitive to small molecule hydrophobic antibiotics (SMHA) while more resistant to meropenem (MERO). Metabolomic analysis revealed that enhanced sensitivity to SMHA was correlated with increased purine metabolism and tricarboxylic acid cycle. Transcriptomic analysis revealed the downregulation of chemotaxis-related genes, which are also associated with SMHA sensitivity. We also found a significant downregulation of the ompF gene, which encodes a major outer membrane protein OmpF of Salmonella. The decreased expression of OmpF porin hindered the influx of MERO, leading to enhanced resistance of the bacteria to the drug. Our findings contribute to greatly improve the understanding of the relationship between Salmonella metabolism, gene expression, and changes in drug resistance after acid stress, while providing a structural framework for exploring the relationship between bacterial stress responses and antibiotic resistance.