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Unavoidable water formation during the reduction of solid catalyst precursors has long been known to influence the nanoparticle size and dispersion in the active catalyst. This in situ transmission electron microscopy study provides insight into the influence of water vapor at the nanoscale on the nucleation and growth of the nanoparticles (2-16 nm) during the reduction of a nickel phyllosilicate catalyst precursor under H2/Ar gas at 700 °C. Water suppresses and delays nucleation, but counterintuitively increases the rate of particle growth. After full reduction is achieved, water vapor significantly enhances Ostwald ripening which in turn increases the likelihood of particle coalescence. This study proposes that water leads to formation of mobile nickel hydroxide species, leading to faster rates of particle growth during and after reduction.
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BACKGROUND: Keratoconus is a degenerative disorder of the cornea leading to a protrusion and thinning with loss of visual acuity. The only treatment to halt the progression is corneal crosslinking (CXL), which uses riboflavin and UV-A light to stiffen the cornea. Recent ultra-structural examinations show that the disease is regional and does not affect the entire cornea. Treating only the affected zone with CXL could be as good as the standard CXL, that treats the entire cornea. METHODS: We set up a multicentre non-inferiority randomized controlled clinical trial comparing standard CXL (sCXL) and customized CXL (cCXL). Patients between 16 and 45 years old with progressive keratoconus were included. Progression is based on one or more of the following changes within 12 months: 1 dioptre (D) increase in keratometry (Kmax, K1, K2); or 10% decrease of corneal thickness; or 1 D increase in myopia or refractive astigmatism, requiring corneal crosslinking. DISCUSSION: The goal of this study is to evaluate whether the effectiveness of cCXL is non-inferior to sCXL in terms of flattening of the cornea and halting keratoconus progression. Treating only the affected zone could be beneficial for minimalizing the risk of damaging surrounding tissues and faster wound healing. Recent non-randomized studies suggest that a customized crosslinking protocol based on the tomography of the patient's cornea may stop the progression of keratoconus and result in flattening of the cornea. TRIAL REGISTRATION: This study was prospectively registered at ClinicalTrials.gov on August 31st, 2020, the identifier of the study is NCT04532788.
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Ceratocone , Fotoquimioterapia , Humanos , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Ceratocone/tratamento farmacológico , Fármacos Fotossensibilizantes/uso terapêutico , Colágeno/uso terapêutico , Córnea , Refração Ocular , Riboflavina/uso terapêutico , Fotoquimioterapia/métodos , Reagentes de Ligações Cruzadas/uso terapêutico , Topografia da Córnea/métodos , Raios Ultravioleta , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Multicêntricos como AssuntoRESUMO
Elevated activation of the autophagy pathway is currently thought to be one of the survival mechanisms allowing therapy-resistant cancer cells to escape elimination, including for cytarabine (AraC)-resistant acute myeloid leukemia (AML) patients. Consequently, the use of autophagy inhibitors such as chloroquine (CQ) is being explored for the re-sensitization of AraC-resistant cells. In our study, no difference in the activity of the autophagy pathway was detected when comparing AraC-Res AML cell lines to parental AraC-sensitive AML cell lines. Furthermore, treatment with autophagy inhibitors CQ, 3-Methyladenine (3-MA), and bafilomycin A1 (BafA1) did not re-sensitize AraC-Res AML cell lines to AraC treatment. However, in parental AraC-sensitive AML cells, treatment with AraC did activate autophagy and, correspondingly, combination of AraC with autophagy inhibitors strongly reduced cell viability. Notably, the combination of these drugs also yielded the highest level of cell death in a panel of patient-derived AML samples even though not being additive. Furthermore, there was no difference in the cytotoxic effect of autophagy inhibition during AraC treatment in matched de novo and relapse samples with differential sensitivity to AraC. Thus, inhibition of autophagy may improve AraC efficacy in AML patients, but does not seem warranted for the treatment of AML patients that have relapsed with AraC-resistant disease.
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Antimetabólitos Antineoplásicos/farmacologia , Autofagia/efeitos dos fármacos , Cloroquina/farmacologia , Citarabina/farmacologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Leucemia Mieloide Aguda/tratamento farmacológico , Linhagem Celular Tumoral , Humanos , Células Tumorais CultivadasRESUMO
The advent of immunotherapy has had a major impact on the outcome and overall survival in many types of cancer. Current immunotherapeutic strategies typically aim to (re)activate anticancer T cell immunity, although the targeting of macrophage-mediated anticancer innate immunity has also emerged in recent years. Neutrophils, although comprising ≈ 60% of all white blood cells in the circulation, are still largely overlooked in this respect. Nevertheless, neutrophils have evident anticancer activity and can induce phagocytosis, trogocytosis, as well as the direct cytotoxic elimination of cancer cells. Furthermore, therapeutic tumor-targeting monoclonal antibodies trigger anticancer immune responses through all innate Fc-receptor expressing cells, including neutrophils. Indeed, the depletion of neutrophils strongly reduced the efficacy of monoclonal antibody treatment and increased tumor progression in various preclinical studies. In addition, the infusion of neutrophils in murine cancer models reduced tumor progression. However, evidence on the anticancer effects of neutrophils is fragmentary and mostly obtained in in vitro assays or murine models with reports on anticancer neutrophil activity in humans lagging behind. In this review, we aim to give an overview of the available knowledge of anticancer activity by neutrophils. Furthermore, we will describe strategies being explored for the therapeutic activation of anticancer neutrophil activity.
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Citotoxicidade Celular Dependente de Anticorpos/imunologia , Imunoterapia/métodos , Neoplasias/terapia , Neutrófilos/imunologia , Animais , Antineoplásicos Imunológicos/farmacologia , Membrana Celular/patologia , Citocinas/imunologia , Citocinas/metabolismo , Humanos , Imunidade Inata , Região Variável de Imunoglobulina/imunologia , Região Variável de Imunoglobulina/metabolismo , Camundongos , Neoplasias/imunologia , Neutrófilos/fisiologia , Fagocitose/imunologia , Fatores de Necrose Tumoral/imunologia , Fatores de Necrose Tumoral/metabolismoRESUMO
BACKGROUND: Lack of oxygen and biomechanical stimulation during static cold storage (SCS) of donor livers compromises endothelial cell function. We investigated the effect of end-ischemic oxygenated hypothermic machine perfusion (HMP) on endothelial cell function of extended criteria donor (ECD) livers. METHODS: Eighteen livers, declined for transplantation, were transported to our center using static cold storage (SCS). After SCS, 6 livers underwent two hours of HMP, and subsequent normothermic machine perfusion (NMP) to assess viability. Twelve control livers underwent NMP immediately after SCS. mRNA expression of transcription factor Krüppel-like-factor 2 (KLF2), endothelial nitric oxide synthase (eNOS), and thrombomodulin (TM) was quantified by RT-PCR. Endothelial cell function and injury were assessed by nitric oxide (NO) production and release of TM into the perfusate. RESULTS: In HMP livers, mRNA expression of KLF2 (p = 0.043), eNOS (p = 0.028), and TM (p = 0.028) increased significantly during NMP. In parallel, NO levels increased during NMP in HMP livers but not in controls. At the end of NMP cumulative TM release was significantly lower HMP livers, compared to controls (p = 0.028). CONCLUSION: A short period of two hours oxygenated HMP restores endothelial cell viability after SCS and subsequent normothermic reoxygenation of ECD livers.
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Temperatura Baixa , Células Endoteliais/metabolismo , Hepatectomia , Transplante de Fígado/métodos , Fígado/cirurgia , Preservação de Órgãos/métodos , Oxigênio/metabolismo , Perfusão/métodos , Doadores de Tecidos/provisão & distribuição , Idoso , Sobrevivência Celular , Seleção do Doador , Células Endoteliais/patologia , Feminino , Regulação da Expressão Gênica , Hepatectomia/efeitos adversos , Humanos , Fatores de Transcrição Kruppel-Like/genética , Fatores de Transcrição Kruppel-Like/metabolismo , Fígado/metabolismo , Fígado/patologia , Transplante de Fígado/efeitos adversos , Masculino , Pessoa de Meia-Idade , Países Baixos , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo III/genética , Óxido Nítrico Sintase Tipo III/metabolismo , Preservação de Órgãos/efeitos adversos , Preservação de Órgãos/instrumentação , Perfusão/efeitos adversos , Perfusão/instrumentação , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Trombomodulina/genética , Trombomodulina/metabolismo , Fatores de TempoRESUMO
Purpose: We describe a patient after customized crosslinking (CXL) for progressive keratoconus who developed corneal edema with spontaneous resolution. Observations: A 24-year-old male with progressive keratoconus of the left eye underwent a customized CXL procedure with a total energy of 10 J/cm2 for 16.4 minutes. Preoperative corrected distance visual acuity (CDVA) was 20/30 with a maximum keratometry (K)-value of 58.6 diopter (D) and the thinnest point measured 414 µm. The preoperative endothelial cell density (ECD) was 2414 cells/mm2. During treatment, corneal thickness was 325 µm after epithelial debridement and 375 µm after the application of 0.1 % riboflavin containing HPMC. After the treatment, antibiotic and steroid drops were prescribed for 5 days and 3 weeks, respectively. At the 1-month post-CXL visit the patient had no complaints, visual acuity and clinical examination showed no irregularities. At the 4-months post-CXL visit the patient complained of blurry vision. The CDVA was 20/100 and slit-lamp examination showed microcystic corneal edema. The corneal thickness at the thinnest point measured 440 µm. One month later the edema had resolved spontaneously and CDVA had restored to 20/25. Corneal thickness at the thinnest point measured 415 µm, the ECD was 1514 cells/mm2 and confocal microscopy showed normal structural changes in the anterior stroma after CXL, with the demarcation line located at a depth of 414 µm, just above the corneal endothelium. Conclusions and importance: We report a case of corneal edema following customized CXL with endothelial cell loss that resolved spontaneously. We recommend either adhering to a minimal stromal thickness of 400 µm before administering UV-A irradiation, using a contact lens or adjusting the irradiation to prevent this complication.
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Gold nanoparticle-loaded titania (Au/TiO2) inverse opals are highly ordered three-dimensional photonic structures with enhanced photocatalytic properties. However, fine control over the placement of the Au nanoparticles in the inverse opal structures remains challenging with traditional preparative methods. Here, we present a multi-component co-assembly strategy to prepare high-quality Au/TiO2 inverse opal films in which Au nanoparticles are either located on, or inside the TiO2 matrix, as verified using electron tomography. We report that Au nanoparticles embedded in the TiO2 support exhibit enhanced thermal and mechanical stability compared to non-embedded nanoparticles that are more prone to both leaching and sintering.
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Viruses critically rely on various proteases to ensure host cell entry and replication. In response to viral infection, the host will induce acute tissue inflammation pulled by granulocytes. Upon hyperactivation, neutrophil granulocytes may cause undue tissue damage through proteolytic degradation of the extracellular matrix. Here, we assess the potential of protease inhibitors (PI) derived from potatoes in inhibiting viral infection and reducing tissue damage. The original full spectrum of potato PI was developed into five fractions by means of chromatography and hydrolysis. Individual fractions showed varying inhibitory efficacy towards a panel of proteases including trypsin, chymotrypsin, ACE2, elastase, and cathepsins B and L. The fractions did not interfere with SARS-CoV-2 infection of Vero E6 cells in vitro. Importantly, two of the fractions fully inhibited elastin-degrading activity of complete primary human neutrophil degranulate. These data warrant further development of potato PI fractions for biomedical purposes, including tissue damage crucial to SARS-CoV-2 pathogenesis. KEY MESSAGES: Protease inhibitor fractions from potato differentially inhibit a series of human proteases involved in viral replication and in tissue damage by overshoot inflammation. Protease inhibition of cell surface receptors such as ACE2 does not prevent virus infection of Vero cells in vitro. Protease inhibitors derived from potato can fully inhibit elastin-degrading primary human neutrophil proteases. Protease inhibitor fractions can be produced at high scale (hundreds of thousands of kilograms, i.e., tons) allowing economically feasible application in lower and higher income countries.
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COVID-19 , Solanum tuberosum , Animais , Chlorocebus aethiops , Humanos , Solanum tuberosum/metabolismo , Peptídeo Hidrolases , Células Vero , Enzima de Conversão de Angiotensina 2 , Inibidores de Proteases/farmacologia , Inibidores de Proteases/metabolismo , Inibidores Enzimáticos , Inflamação , Antivirais , Elastina/metabolismoRESUMO
Understanding nanoparticle growth is crucial to increase the lifetime of supported metal catalysts. In this study, we employ in situ gas-phase transmission electron microscopy to visualize the movement and growth of ensembles of tens of nickel nanoparticles supported on carbon for CO2 hydrogenation at atmospheric pressure (H2:CO2 = 4:1) and relevant temperature (450 °C) in real time. We observe two modes of particle movement with an order of magnitude difference in velocity: fast, intermittent movement (vmax = 0.7 nm s-1) and slow, gradual movement (vaverage = 0.05 nm s-1). We visualize the two distinct particle growth mechanisms: diffusion and coalescence, and Ostwald ripening. The diffusion and coalescence mechanism dominates at small interparticle distances, whereas Ostwald ripening is driven by differences in particle size. Strikingly, we demonstrate an interplay between the two mechanisms, where first coalescence takes place, followed by fast Ostwald ripening due to the increased difference in particle size. Our direct visualization of the complex nanoparticle growth mechanisms highlights the relevance of studying nanoparticle growth in supported nanoparticle ensembles under reaction conditions and contributes to the fundamental understanding of the stability in supported metal catalysts.
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In recent years, the therapeutic (re)activation of innate anticancer immunity has gained prominence, with therapeutic blocking of the interaction of Signal Regulatory Protein (SIRP)-α with its ligand CD47 yielding complete responses in refractory and relapsed B cell lymphoma patients. SIRP-α has as crucial inhibitory role on phagocytes, with e.g., its aberrant activation enabling the escape of cancer cells from immune surveillance. SIRP-α belongs to a family of paired receptors comprised of not only immune-inhibitory, but also putative immune-stimulatory receptors. Here, we report that an as yet uninvestigated SIRP family member, SIRP-beta 2 (SIRP-ß2), is strongly expressed under normal physiological conditions in macrophages and granulocytes at protein level. Endogenous expression of SIRP-ß2 on granulocytes correlated with trogocytosis of cancer cells. Further, ectopic expression of SIRP-ß2 stimulated macrophage adhesion, differentiation and cancer cell phagocytosis as well as potentiated macrophage-mediated activation of T cell Receptor-specific T cell activation. SIRP-ß2 recruited the immune activating adaptor protein DAP12 to positively regulate innate immunity, with the charged lysine 202 of SIRP-ß2 being responsible for interaction with DAP12. Mutation of lysine 202 to leucine lead to a complete loss of the increased adhesion and phagocytosis. In conclusion, SIRP-ß2 is a novel positive regulator of innate anticancer immunity and a potential costimulatory target for innate immunotherapy.
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Antígenos de Diferenciação , Lisina , Humanos , Lisina/metabolismo , Receptores Imunológicos/metabolismo , Imunidade Inata , MacrófagosRESUMO
Acute myeloid leukemia (AML) is a malignancy still associated with poor survival rates, among others, due to frequent occurrence of therapy-resistant relapse after standard-of-care treatment with cytarabine (AraC). AraC triggers apoptotic cell death, a type of cell death to which AML cells often become resistant. Therefore, therapeutic options that trigger an alternate type of cell death are of particular interest. We previously identified that the glycan-binding protein Galectin-9 (Gal-9) has tumor-selective and non-apoptotic cytotoxicity towards various types of cancer, which depended on autophagy inhibition. Thus, Gal-9 could be of therapeutic interest for (AraC-resistant) AML. In the current study, treatment with Gal-9 was cytotoxic for AML cells, including for CD34+ patient-derived AML stem cells, but not for healthy cord blood-derived CD34+ stem cells. This Gal-9-mediated cytotoxicity did not rely on apoptosis but was negatively associated with autophagic flux. Importantly, both AraC-sensitive and -resistant AML cell lines, as well as AML patient samples, were sensitive to single-agent treatment with Gal-9. Additionally, Gal-9 potentiated the cytotoxic effect of DNA demethylase inhibitor Azacytidine (Aza), a drug that is clinically used for patients that are not eligible for intensive AraC treatment. Thus, Gal-9 is a potential therapeutic agent for the treatment of AML, including AraC-resistant AML, by inducing caspase-independent cell death.
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Purpose: Keratoconus is characterized by the progressive thinning of the cornea, which leads to a cone-like appearance of the eye over time. Although conventionally defined as a noninflammatory condition, a number of recent studies have associated keratoconus (KC) with allergic conjunctivitis (AC) based on clinical parameters. This study aimed to consolidate this association by performing a proteomic analysis of tear fluid from patients with keratoconus and/or allergic conjunctivitis. Methods: Of 51 patients, 17 were diagnosed with KC, 17 were diagnosed with AC, and 17 were diagnosed with both KC and AC (combined). Nine of 34 patients with KC had a progressive form of the disease. Tear fluid samples (n = 51, one eye per patient) were collected by the Schirmer's strips. Tear proteins were extracted from the Schirmer's strips. Proteomic profiling of 384 inflammatory proteins was assessed by a multiplex proximity extension assay (Olink Explore 384 Inflammation Panel I). Results: A total of 384 inflammatory proteins were measured. Two hundred seventy-two of the 384 proteins passed stringent data cleaning and were compared among the patient groups. Compared to the 2 other groups, LGALS9 was upregulated uniquely in KC, whereas FGF19, PDGFB, HPCAL1, OSM, and FCAR were downregulated in KC. Similarly, TNFRSF4 and CCL13 were specifically upregulated in AC, whereas ectodysplasin A receptor (EDAR) was uniquely downregulated in AC. Conclusions: High-throughput proteomic profiling of tear fluid confirms the association between KC and AC on a molecular level and raise the importance of redefining KC as an inflammatory condition.
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Conjuntivite Alérgica , Ceratocone , Humanos , Ceratocone/diagnóstico , Ceratocone/metabolismo , Conjuntivite Alérgica/diagnóstico , Conjuntivite Alérgica/metabolismo , Proteoma/metabolismo , Proteômica , Córnea/metabolismo , Lágrimas/metabolismoRESUMO
It is increasingly becoming clear that cancers are a symbiosis of diverse cell types and tumor clones. Combined single-cell RNA sequencing, flow cytometry, and immunohistochemistry studies of the innate immune compartment in the bone marrow of patients with acute myeloid leukemia (AML) reveal a shift toward a tumor-supportive M2-polarized macrophage landscape with an altered transcriptional program, with enhanced fatty acid oxidation and NAD+ generation. Functionally, these AML-associated macrophages display decreased phagocytic activity and intra-bone marrow coinjection of M2 macrophages together with leukemic blasts strongly enhances in vivo transformation potential. A 2-day in vitro exposure to M2 macrophages results in the accumulation of CALRlow leukemic blast cells, which are now protected against phagocytosis. Moreover, M2-exposed "trained" leukemic blasts display increased mitochondrial metabolism, in part mediated via mitochondrial transfer. Our study provides insight into the mechanisms by which the immune landscape contributes to aggressive leukemia development and provides alternatives for targeting strategies aimed at the tumor microenvironment.
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Leucemia Mieloide Aguda , Humanos , Leucemia Mieloide Aguda/patologia , Macrófagos/patologia , Fagocitose , Imuno-Histoquímica , Microambiente TumoralRESUMO
PURPOSE: To present two patients with residual astigmatism following toric intraocular lens (IOL) implantation. METHODS: Case reports. RESULTS: A 58-year-old woman underwent toric IOL implantation (spherical power 29.50 diopters [D], cylinder power 3.00 D; SN60T5, Alcon Laboratories Inc) to correct 2.33 D @ 80° of corneal astigmatism. Postoperatively, uncorrected distance visual acuity (UDVA) was 20/30 and corrected distance visual acuity (CDVA) was 20/22 (0 -1.75 × 95), indicating an overcorrection of astigmatism. Slit-lamp examination demonstrated no IOL misalignment. Wavefront aberrometry showed a large pupil diameter (>6 mm) and a lower corneal astigmatism in a 6-mm zone (-1.40 D @ 174°) compared to a 4-mm zone (-2.21 D @ 171°). The second patient, a 60-year-old man, underwent multifocal toric IOL implantation (spherical power 22.50 D, cylinder power 2.25 D; SND1T4, Alcon Laboratories Inc) to correct 1.51 D @ 173° of corneal astigmatism. Postoperatively, UDVA was 20/50 and CDVA was 20/20 (+0.25 -1.00 × 102), indicating an undercorrection of astigmatism. Slit-lamp examination showed no misalignment. CONCLUSIONS: Both cases indicate that unexplained residual astigmatism following toric IOL implantation may be the result of multiple factors: the effect of the spherical power and anterior chamber depth on toric IOL calculations, the effect of posterior corneal astigmatism, and the effect of a large pupil size. The first two issues may be compensated for by improving toric IOL calculations. The latter indicates that pupillometry is indicated in relatively young patients who undergo toric IOL implantation.
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Astigmatismo/etiologia , Iris/patologia , Implante de Lente Intraocular , Facoemulsificação , Complicações Pós-Operatórias , Pupila , Aberrometria , Astigmatismo/diagnóstico , Astigmatismo/cirurgia , Topografia da Córnea , Aberrações de Frente de Onda da Córnea , Feminino , Humanos , Lentes Intraoculares , Masculino , Pessoa de Meia-Idade , Acuidade Visual/fisiologiaRESUMO
Converting CO2 into value-added chemicals and fuels, such as methanol, is a promising approach to limit the environmental impact of human activities. Conventional methanol synthesis catalysts have shown limited efficiency and poor stability in a CO2/H2 mixture. To design improved catalysts, crucial for the effective utilization of CO2, an in-depth understanding of the active sites and reaction mechanism is desired. The catalytic performance of a series of carbon-supported Cu catalysts, with Cu particle sizes in the range of 5 to 20 nm, was evaluated under industrially relevant temperature and pressure, i.e. 260 °C and 40 bar(g). The CO2 hydrogenation reaction exhibited clear particle size effects up to 13 nm particles, with small nanoparticles having the lower activity, but higher methanol selectivity. MeOH and CO formation showed a different size-dependence. The TOFCO increased from 1.9 × 10-3 s-1 to 9.4 × 10-3 s-1 with Cu size increasing from 5 nm to 20 nm, while the TOFMeOH was size-independent (8.4 × 10-4 s-1 on average). The apparent activation energies for MeOH and CO formation were size-independent with values of 63 ± 7 kJ mol-1 and 118 ± 6 kJ mol-1, respectively. Hence the size dependence was ascribed to a decrease in the fraction of active sites suitable for CO formation with decreasing particle size. Theoretical models and DFT calculations showed that the origin of the particle size effect is most likely related to the differences in formate coverage for different Cu facets whose abundancy depends on particle size. Hence, the CO2 hydrogenation reaction is intrinsically sensitive to the Cu particle size.
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In this work, we discuss the role of manganese oxide as a promoter in Cu catalysts supported on graphitic carbon during hydrogenation of CO2 and CO. MnOx is a selectivity modifier in an H2/CO2 feed and is a highly effective activity promoter in an H2/CO feed. Interestingly, the presence of MnOx suppresses the methanol formation from CO2 (TOF of 0.7 â 10-3 s-1 at 533â K and 40â bar) and enhances the low-temperature reverse water-gas shift reaction (TOF of 5.7 â 10-3 s-1) with a selectivity to CO of 87 %C. Using time-resolved XAS at high temperatures and pressures, we find significant absorption of CO2 to the MnO, which is reversed if CO2 is removed from the feed. This work reveals fundamental differences in the promoting effect of MnOx and ZnOx and contributes to a better understanding of the role of reducible oxide promoters in Cu-based hydrogenation catalysts.
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Maximizing the utilization of noble metals is crucial for applications such as catalysis. We found that the minimum loading of platinum for optimal performance in the hydroconversion of n-alkanes for industrially relevant bifunctional catalysts could be reduced by a factor of 10 or more through the rational arranging of functional sites at the nanoscale. Intentionally depositing traces of platinum nanoparticles on the alumina binder or the outer surface of zeolite crystals, instead of inside the zeolite crystals, enhanced isomer selectivity without compromising activity. Separation between platinum and zeolite acid sites preserved the metal and acid functions by limiting micropore blockage by metal clusters and enhancing access to metal sites. Reduced platinum nanoparticles were more active than platinum single atoms strongly bonded to the alumina binder.
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OBJECTIVE: To compare endothelial cell (EC) loss, visual and refractive outcomes, and complications after deep anterior lamellar keratoplasty (DALK) and penetrating keratoplasty (PK). DESIGN: Randomized, multicenter clinical trial. PARTICIPANTS: Fifty-six eyes of 56 patients with a corneal stromal pathology not affecting the endothelium were randomized to DALK or PK. METHODS: The DALK procedure was performed according to Anwar's big-bubble technique. Patients underwent an ophthalmic examination preoperatively and 3, 6, and 12 months postoperatively. MAIN OUTCOME MEASURES: Endothelial cell loss, refractive and topographic astigmatism, spherical equivalent, uncorrected visual acuity, and best spectacle-corrected visual acuity (BSCVA) were measured, and complications were recorded. RESULTS: Endothelial cell loss was significantly higher after PK compared with DALK procedures performed without perforation of Descemet's membrane (12 months: 27.7% ± 11.1% vs. 12.9% ± 17.6%). The BSCVA was significantly better in the PK group at 3 and 6 months after surgery but was not significantly different 12 months after surgery (0.39 ± 0.3 logarithm of the minimum angle of resolution [logMAR] in DALK and 0.31 ± 0.3 logMAR in PK). At 12 months postoperatively, refractive and topographic astigmatism in the DALK and PK groups were -3.37 ± 2.3 diopters (D) and -3.76 ± 2.1 D (P = 0.53), and 3.57 ± 2.3 D and 4.16 ± 2.0 D (P = 0.34), respectively. (Micro)perforation of the Descemet's membrane occurred in 32% (9/28) of the DALK eyes, and 18% (5/28) of the patients required conversion to PK. Endothelial cell loss was not significantly different between DALK and PK when cases with perforation of Descemet's membrane were included in the (intention-to-treat) analysis (12 months: 19.1 ± 21.6 vs. 27.7 ± 11.1 P = 0.112). Rejection episodes were reported in 1 patient in the DALK group (epithelial rejection) and 3 patients in the PK group (all endothelial rejections). No graft failure occurred. CONCLUSIONS: One year after DALK performed without perforation of Descemet's membrane, EC loss is significantly lower, whereas the BSCVA is comparable to that in the PK group. In addition, no endothelial rejection occurred in the DALK group. However, Descemet's membrane perforation remains a major complication in DALK and warrants improvements to standardize the big-bubble technique.
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Perda de Células Endoteliais da Córnea/diagnóstico , Transplante de Córnea , Ceratoplastia Penetrante , Acuidade Visual/fisiologia , Adulto , Contagem de Células , Topografia da Córnea , Endotélio Corneano/patologia , Feminino , Seguimentos , Distrofia Endotelial de Fuchs/cirurgia , Sobrevivência de Enxerto/fisiologia , Humanos , Complicações Intraoperatórias , Ceratocone/cirurgia , Masculino , Complicações Pós-Operatórias , Refração Ocular/fisiologia , Resultado do TratamentoRESUMO
Colloidal heteronanocrystals allow for the synergistic combination of properties of different materials. For example, spatial separation of the photogenerated electron and hole can be achieved by coupling different semiconductors with suitable band offsets in one single nanocrystal, which is beneficial for improving the efficiency of photocatalysts and photovoltaic devices. From this perspective, axially segmented semiconductor heteronanorods with a type-II band alignment are particularly attractive since they ensure the accessibility of both photogenerated charge carriers. Here, a two-step synthesis route to Cu2-xS/CuInS2 Janus-type heteronanorods is presented. The heteronanorods are formed by injection of a solution of preformed Cu2-xS seed nanocrystals in 1-dodecanethiol into a solution of indium oleate in oleic acid at 240 °C. By varying the reaction time, Janus-type heteronanocrystals with different sizes, shapes, and compositions are obtained. A mechanism for the formation of the heteronanocrystals is proposed. The first step of this mechanism consists of a thiolate-mediated topotactic, partial Cu+ for In3+ cation exchange that converts one of the facets of the seed nanocrystals into CuInS2. This is followed by homoepitaxial anisotropic growth of wurtzite CuInS2. The Cu2-xS seed nanocrystals also act as sacrificial Cu+ sources, and therefore, single composition CuInS2 nanorods are eventually obtained if the reaction is allowed to proceed to completion. The two-stage seeded growth method developed in this work contributes to the rational synthesis of Cu2-xS/CuInS2 heteronanocrystals with targeted architectures by allowing one to exploit the size and faceting of premade Cu2-xS seed nanocrystals to direct the growth of the CuInS2 segment.
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PURPOSE: To investigate the economic impact of an intracameral mydriatics and anesthetic agent (ICMA), topical mydriatics, and a mydriatic ocular insert in cataract patients. SETTING: One public hospital in the Netherlands. DESIGN: Prospective cohort study. METHODS: Resource use data were collected from a healthcare and societal perspective on the day of surgery. Other outcome parameters included pupil size, surgeon satisfaction, postoperative pain, and Catquest-9SF scores. RESULTS: A total of 368 patients were included, the mean costs per patient were 506 in the ICMA group (n = 122), 474 in the ocular insert group (n = 115), and 451 in the topical group (n = 131). The acquisition cost of ICMA was highest and resulted in longer surgical time. After correction for an imbalance in the distribution of fast and slow surgeons, the mean costs in the ocular insert and topical groups were comparable (450 vs 444). There was no statistically significant difference in the use of additional mydriatics intraoperatively (P = .521). The mean ratio of pupil size to white-to-white distance was lower in the ICMA group during all intraoperative measurements (P < .001) but similar between the topical and ocular insert groups (P range .11-.82). CONCLUSIONS: In the investigated setting in the Netherlands, ICMA was the most costly strategy. In addition, pupil size was lowest in the ICMA group but did not result in more additional mydriasis measures intraoperatively. The ocular insert was comparable with topical mydriatics in costs and pupil size. Implementation of ICMA could be considered when availability of nurses or physical space for perioperative care is limited.