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HIV-induced persistent immune activation is a key mediator of inflammatory comorbidities such as cardiovascular disease (CVD) and neurocognitive disorders. While a preponderance of data indicate that gut barrier disruption and microbial translocation are drivers of chronic immune activation, the molecular mechanisms of this persistent inflammatory state remain poorly understood. Here, utilizing the nonhuman primate model of HIV infection with suppressive antiretroviral therapy (ART), we investigated activation of inflammasome pathways and their association with intestinal epithelial barrier disruption and CVD pathogenesis. Longitudinal blood samples obtained from rhesus macaques with chronic SIV infection and long-term suppressive ART were evaluated for biomarkers of intestinal epithelial barrier disruption (IEBD), inflammasome activation (IL-1ß and IL-18), inflammatory cytokines, and triglyceride (TG) levels. Activated monocyte subpopulations and glycolytic potential were investigated in peripheral blood mononuclear cells (PBMCs). Higher plasma levels of IL-1ß and IL-18 were observed following the hallmark increase in IEBD biomarkers, intestinal fatty acid-binding protein (IFABP) and LPS-binding protein (LBP), during the chronic phase of treated SIV infection. Further, significant correlations of plasma IFABP levels with IL-1ß and IL-18 were observed between 10-12 months of ART. Higher levels of sCD14, IL-6, and GM-CSF, among other inflammatory mediators, were also observed only during the long-term SIV+ART phase along with a trend of increase in frequencies of activated CD14 + CD16 + intermediate monocyte subpopulations. Lastly, we found elevated levels of blood TG and higher glycolytic capacity in PBMCs of chronic SIV-infected macaques with long-term ART. The increase in circulating IL-18 and IL-1ß following IEBD and their significant positive correlation with IFABP suggest a connection between gut barrier disruption and inflammasome activation during chronic SIV infection, despite viral suppression with ART. Additionally, the increase in markers of monocyte activation, along with elevated TG and enhanced glycolytic pathway activity, indicates metabolic remodeling that could accelerate CVD pathogenesis. Further research is needed to understand mechanisms by which gut dysfunction and inflammasome activation contribute to HIV-associated CVD and metabolic complications, enabling targeted interventions in people with HIV.
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Obesity is a risk factor for developing severe COVID-19. However, the mechanism underlying obesity-accelerated COVID-19 remains unclear. Here, we report results from a study in which 2-3-month-old K18-hACE2 (K18) mice were fed a western high-fat diet (WD) or normal chow (NC) over 3 months before intranasal infection with a sublethal dose of SARS-CoV2 WA1 (a strain ancestral to the Wuhan variant). After infection, the WD-fed K18 mice lost significantly more body weight and had more severe lung inflammation than normal chow (NC)-fed mice. Bulk RNA-seq analysis of lungs and adipose tissue revealed a diverse landscape of various immune cells, inflammatory markers, and pathways upregulated in the infected WD-fed K18 mice when compared with the infected NC-fed control mice. The transcript levels of IL-6, an important marker of COVID-19 disease severity, were upregulated in the lung at 6-9 days post-infection in the WD-fed mice when compared to NC-fed mice. Transcriptome analysis of the lung and adipose tissue obtained from deceased COVID-19 patients found that the obese patients had an increase in the expression of genes and the activation of pathways associated with inflammation as compared to normal-weight patients (n = 2). The K18 mouse model and human COVID-19 patient data support a link between inflammation and an obesity-accelerated COVID-19 disease phenotype. These results also indicate that obesity-accelerated severe COVID-19 caused by SARS-CoV-2 WA1 infection in the K18 mouse model would be a suitable model for dissecting the cellular and molecular mechanisms underlying pathogenesis.
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The gut-brain axis is essential in maintaining the homeostasis of neuronal system, endocrine system, and intestinal microbiota in both the afferent and efferent directions. This axis is considered to be a key mechanism that regulates feed efficiency (FE). This study aimed to investigate the regulatory mechanisms of gut-brain axis-related genes on the residual feed intake (RFI) in H-strain small-sized meat ducks. A total of 500 ducks with similar initial BW (635.2 ± 15.1 g) were selected and reared in the same experimental facility until slaughter at 42 d of age. RFI was calculated from the average daily gain (ADG), average daily feed intake (ADFI), and metabolic body weight (MBW0.75). Thirty high-RFI (H-RFI) and 30 low-RFI (L-RFI) birds were selected for further evaluation of growth performance, carcass characteristics, and blood biochemical parameter measurements. Six L-RFI and 6 H-RFI birds were then subjected to hypothalamic transcriptomic and cecal microbial sequencing analyses. Results indicated that L-RFI birds exhibited lower production performance (ADFI, FCR, and RFI) and blood biochemical indices (total cholesterol and ghrelin content) compared with H-RFI birds (P < 0.05). Gene expression differed significantly between the L-RFI and H-RFI birds, with 70 upregulated and 50 downregulated genes. The bacterial communities of L-RFI birds showed higher abundances of Bacteroides, Bifidobacterium, and Lactococcus, and lower abundances of Erysipelatoclostridium, Parasutterella, Fournierella, and Blautia compared with H-RFI birds (P < 0.05). Interactive analysis revealed bacterial communities associated with FE were significantly correlated with hypothalamic genes (P < 0.05), for example, Bacteroides was positively correlated with DGKH and LIPT2, while negatively correlated with CAPN9, GABRD, and PDE1A. Bifidobacterium showed significant correlations with ATP2A3, CALHM6, and TMEM121B. Overall, RFI was a crucial indicator of FE, regulated by interactions between brain gene expression and gut microbiota through cAMP signaling, neuroactive ligand-receptor interaction, and calcium signaling pathways. Notably, increased expression of hypothalamic genes and abundance of carbohydrate-utilization microbiota in L-RFI meat ducks improved FE by enhancing energy metabolism and volatile fatty acids absorption.
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Patos , Microbioma Gastrointestinal , Animales , Patos/fisiología , Patos/crecimiento & desarrollo , Patos/genética , Microbioma Gastrointestinal/fisiología , Eje Cerebro-Intestino/fisiología , Ingestión de Alimentos , MasculinoRESUMEN
Second-generation AR antagonists, such as enzalutamide, are the primary therapeutic agents for advanced prostate cancer. However, the development of both primary and secondary drug resistance leads to treatment failures and patient mortality. Bifunctional agents that simultaneously antagonize and degrade AR block the AR signaling pathway more completely and exhibit excellent antiproliferative activity against wild-type and drug-resistant prostate cancer cells. Here, we reported the discovery and optimization of a series of biphenyl derivatives as androgen receptor antagonists and degraders. These biphenyl derivatives exhibited potent antiproliferative activity against LNCaP and 22Rv1 cells. Our discoveries enrich the diversity of small molecule AR degraders and offer insights for the development of novel AR degraders for the treatment of enzalutamide-resistant prostate cancer.
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Antagonistas de Receptores Androgénicos , Antineoplásicos , Benzamidas , Compuestos de Bifenilo , Proliferación Celular , Resistencia a Antineoplásicos , Nitrilos , Feniltiohidantoína , Neoplasias de la Próstata , Receptores Androgénicos , Humanos , Masculino , Benzamidas/farmacología , Benzamidas/química , Benzamidas/síntesis química , Nitrilos/química , Nitrilos/farmacología , Feniltiohidantoína/farmacología , Feniltiohidantoína/análogos & derivados , Feniltiohidantoína/química , Compuestos de Bifenilo/farmacología , Compuestos de Bifenilo/antagonistas & inhibidores , Receptores Androgénicos/metabolismo , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/síntesis química , Proliferación Celular/efectos de los fármacos , Relación Estructura-Actividad , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/metabolismo , Resistencia a Antineoplásicos/efectos de los fármacos , Estructura Molecular , Antagonistas de Receptores Androgénicos/farmacología , Antagonistas de Receptores Androgénicos/química , Antagonistas de Receptores Androgénicos/síntesis química , Antagonistas de Receptores Androgénicos/uso terapéutico , Descubrimiento de Drogas , Ensayos de Selección de Medicamentos Antitumorales , Relación Dosis-Respuesta a Droga , Línea Celular TumoralRESUMEN
Urban waterlogging is a significant global issue. To achieve precisely control urban waterlogging and enhance our understanding of its causes, a novel study method was introduced. This method is based on a dynamic bidirectional coupling model that combines 1D-2D hydrodynamic and water quality simulations. The waterlogging phenomenon in densely populated metropolitan areas of Changzhi city, China, was studied. This study focused on investigating the process involved in waterlogging formation, particularly overflow at nodes induced by the design of the topological structure of the pipe network, constraints on the capacity of the underground drainage system, and the surface runoff accumulation. The complex interplay among these elements and their possible influences on waterlogging formation were clarified. The results indicated notable spatial and temporal variation in the waterlogging formation process in densely populated urban areas. Node overflow in the drainage system emerged as the key influencing factor in the waterlogging formation process, accounting for up to 71% of the total water accumulation at the peak time. The peak lag time of waterlogging during events with short return periods was primarily determined by the rainfall peak moment. In contrast, the peak time of waterlogging during events with long return periods was influenced by the rainfall peak moment, drainage capacity and topological structure of the pipe network. Notably, the access of inflow from both upstream and downstream segments of the pipe network drainage system significantly impacted the peak time of waterlogging, with upstream water potentially delaying the peak time substantially. This study not only provides new insights into urban waterlogging mechanisms but also provides practical guidance for optimizing urban drainage systems, urban planning, and disaster risk management.
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Modelos Teóricos , China , Movimientos del Agua , Lluvia , Ciudades , Calidad del AguaRESUMEN
This study investigates the roles of T, B, and Natural Killer (NK) cells in the pathogenesis of severe COVID-19, utilizing mouse-adapted SARS-CoV-2-MA30 (MA30). To evaluate this MA30 mouse model, we characterized MA30-infected C57BL/6 mice (B6) and compared them with SARS-CoV-2-WA1 (an original SARS-CoV-2 strain) infected K18-human ACE2 (K18-hACE2) mice. We found that the infected B6 mice developed severe peribronchial inflammation and rapid severe pulmonary edema, but less lung interstitial inflammation than the infected K18-hACE2 mice. These pathological findings recapitulate some pathological changes seen in severe COVID-19 patients. Using this MA30-infected mouse model, we further demonstrate that T and/or B cells are essential in mounting an effective immune response against SARS-CoV-2. This was evident as Rag2-/- showed heightened vulnerability to infection and inhibited viral clearance. Conversely, the depletion of NK cells did not significantly alter the disease course in Rag2-/- mice, underscoring the minimal role of NK cells in the acute phase of MA30-induced disease. Together, our results indicate that T and/or B cells, but not NK cells, mitigate MA30-induced disease in mice and the infected mouse model can be used for dissecting the pathogenesis and immunology of severe COVID-19.
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COVID-19 , Proteínas de Unión al ADN , Modelos Animales de Enfermedad , Células Asesinas Naturales , Ratones Endogámicos C57BL , SARS-CoV-2 , Animales , Células Asesinas Naturales/inmunología , COVID-19/inmunología , COVID-19/virología , Ratones , SARS-CoV-2/inmunología , SARS-CoV-2/patogenicidad , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/deficiencia , Ratones Noqueados , Humanos , Pulmón/patología , Pulmón/virología , Pulmón/inmunología , Enzima Convertidora de Angiotensina 2/genética , Enzima Convertidora de Angiotensina 2/metabolismo , Linfocitos B/inmunología , Femenino , Linfocitos T/inmunologíaRESUMEN
The methylation and demethylation of lysine and arginine side chains are fundamental processes in gene regulation and disease development. Histone lysine methylation, controlled by histone lysine methyltransferases (KMTs) and histone lysine demethylases (KDMs), plays a vital role in maintaining cellular homeostasis and has been implicated in diseases such as cancer and aging. This study focuses on two members of the lysine demethylase (KDM) family, KDM4E and KDM6B, which are significant in gene regulation and disease pathogenesis. KDM4E demonstrates selectivity for gene regulation, particularly concerning cancer, while KDM6B is implicated in inflammation and cancer. The study utilizes specific inhibitors, DA-24905 and GSK-J1, showcasing their exceptional selectivity for KDM4E and KDM6B, respectively. Employing an array of computational simulations, including sequence alignment, molecular docking, dynamics simulations, and free energy calculations, we conclude that although the binding cavities of KDM4E and KDM6B has high similarity, there are still some different crucial amino acid residues, indicating diverse binding forms between protein and ligands. Various interaction predominates when proteins are bound to different ligands, which also has significant effect on selective inhibition. These findings provide insights into potential therapeutic strategies for diseases by selectively targeting these KDM members.
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Inhibidores Enzimáticos , Histona Demetilasas con Dominio de Jumonji , Histona Demetilasas con Dominio de Jumonji/antagonistas & inhibidores , Histona Demetilasas con Dominio de Jumonji/metabolismo , Histona Demetilasas con Dominio de Jumonji/química , Humanos , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/farmacología , Simulación de Dinámica Molecular , Descubrimiento de Drogas , Simulación del Acoplamiento Molecular , Estructura Molecular , Histona Demetilasas/antagonistas & inhibidores , Histona Demetilasas/metabolismo , Histona Demetilasas/química , Relación Estructura-ActividadRESUMEN
This study demonstrates the crucial role of reduction kinetics in phase-controlled synthesis of noble-metal nanocrystals using Ru nanocrystals as a case study. We found that the reduction kinetics played a more important role than the templating effect from the preformed seed in dictating the crystal structure of the deposited overlayers despite their intertwined effects on successful epitaxial growth. By employing two different polyols, a series of Ru nanocrystals with tunable sizes of 3-7 nm and distinct patterns of crystal phase were synthesized by incorporating different types of Ru seeds. Notably, the use of ethylene glycol and triethylene glycol consistently resulted in the formation of Ru shell in natural hexagonal close-packed (hcp) and metastable face-centered cubic (fcc) phases, respectively, regardless of the size and phase of the seed. Quantitative measurements and theoretical calculations suggested that this trend was a manifestation of the different reduction kinetics associated with the precursor and the chosen polyol, which, in turn, affected the reduction pathway (solution versus surface) and packing sequence of the deposited Ru atoms. This work not only underscores the essential role of reduction kinetics in controlling the packing of atoms and thus the phase taken by Ru nanocrystals but also suggests a potential extension to other noble-metal systems.
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Introduction: Non-alcoholic fatty liver disease (NAFLD) is a global public health concern. However, limited data are available on urinary trace elements and NAFLD caused by various exposure factors. This study aimed to investigate the relationship between the presence of 16 trace elements in urine and NAFLD using data from the National Health and Nutrition Examination Survey (NHANES). Methods: By utilizing the NHANES data from 2017 to 2018, 1613 participants who fulfilled the research criteria were identified from the initial pool of 2979 participants with available urine trace element detection data. Among them, 706 individuals had been diagnosed with NAFLD based on a coefficient of attenuation parameter (CAP) value of at least 274 db/m, determined using vibration-controlled transient elastography (VCTE); whereas the remaining 907 participants were classified as non-NAFLD. The data obtained were used to construct univariate and multivariate logistic regression models and restricted cubic spline models (RCS) analyses. Results: The presence of arsenic, iodine, barium, cesium, molybdenum, lead, tin, and tungsten in the urine of individuals with NAFLD showed a positive correlation with the likelihood of developing NAFLD. The risk of NAFLD had a non-linear dose-dependent relationship with urinary iodine, molybdenum, barium, and cesium. NAFLD was also associated with elevated levels of barium and cesium in urine, which were identified as significant risk factors. Conclusion: These findings suggest a positive association between exposure to trace elements in the urine and the risk of NAFLD. Specifically, urinary barium and cesium appeared to have the greatest impact on the risk of NAFLD. These results provide novel insights into the diagnosis and treatment of NAFLD.
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Diagnóstico por Imagen de Elasticidad , Yodo , Enfermedad del Hígado Graso no Alcohólico , Oligoelementos , Humanos , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Encuestas Nutricionales , Diagnóstico por Imagen de Elasticidad/métodos , Vibración , Molibdeno , Bario , CesioRESUMEN
RESEARCH HIGHLIGHTS: Urate tophi were found in the kidneys, liver, spleen and lungs.IFA confirmed the co-expression of GoAstV-I and II antigens in the same kidney.
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Infecciones por Astroviridae , Astroviridae , Avastrovirus , Coinfección , Gota , Enfermedades de las Aves de Corral , Animales , Gansos , Infecciones por Astroviridae/veterinaria , Coinfección/veterinaria , Astroviridae/genética , Gota/veterinaria , Avastrovirus/genética , ChinaRESUMEN
SARS-CoV-2 infection can cause persistent respiratory sequelae. However, the underlying mechanisms remain unclear. Here we report that sub-lethally infected K18-human ACE2 mice show patchy pneumonia associated with histiocytic inflammation and collagen deposition at 21 and 45 days post infection (DPI). Transcriptomic analyses revealed that compared to influenza-infected mice, SARS-CoV-2-infected mice had reduced interferon-gamma/alpha responses at 4 DPI and failed to induce keratin 5 (Krt5) at 6 DPI in lung, a marker of nascent pulmonary progenitor cells. Histologically, influenza- but not SARS-CoV-2-infected mice showed extensive Krt5+ "pods" structure co-stained with stem cell markers Trp63/NGFR proliferated in the pulmonary consolidation area at both 7 and 14 DPI, with regression at 21 DPI. These Krt5+ "pods" structures were not observed in the lungs of SARS-CoV-2-infected humans or nonhuman primates. These results suggest that SARS-CoV-2 infection fails to induce nascent Krt5+ cell proliferation in consolidated regions, leading to incomplete repair of the injured lung.
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COVID-19 , Gripe Humana , Ratones , Humanos , Animales , SARS-CoV-2 , Pulmón , Perfilación de la Expresión GénicaRESUMEN
A fiber optic probe for the simultaneous measurement of chloride ions and temperature is presented. The Ag/alginate composite film is used as the reflective surface of the Fabry-Perot interferometer (FPI) and is a sensitive film for the adsorption of chloride ions. The experimental results show that the Fabry-Perot (FP) response sensitivity is approximately 1.4689 nm/µM as the chloride ion concentration changes from 1 to 9 µM, but the fiber Bragg grating (FBG) is insensitive to chloride ions. When the temperature is changed from 35°C to 80°C, the response sensitivities of the FP and the FBG are about 0.7 and 0.01115 nm/°C, respectively.
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Aims: The aim of this meta-analysis is to evaluate the potential correlation between obesity and overweight, and the vulnerability to urinary incontinence (UI) in women aged middle-aged and above. Methods: We searched PubMed, Cochrane Library, and Embase for observational studies published between the inception of the databases and April 25, 2023. A fixed-effects model was used when the P>0.1 and the I2 ≤ 50%. In cases where I2 ≥ 50% (indicating significant heterogeneity), a random-effects model was applied. For the purpose of evaluating publication bias, a funnel plot and Egger's test were used. Stata 14.0 was used for all statistical analyses. Findings: This meta-analysis includes 16 observational studies, covering29,618 individuals. The pooled analysis shows that being overweight(25 kg/m2≤BMI<30kg/m2) in middle-aged and elderly women is more likely to develop UI (OR=1.27; 95% CI: 1.17-1.37; I2 = 51.8%, P=0.013). Middle-aged and elderly women with obesity(30 kg/m2≤BMI<35 kg/m2) are significantly more likely to develop UI (OR=1.60; 95% CI: 1.42-1.81; I2 = 71.8%, P=0.000). In addition, the results indicated a higher probability of UI in middle-aged and older women with obesity class II (BMI≥35 kg/m2) (OR=1.85; 95% CI: 1.59-2.16; I2 = 48.1%, P=0.103). In subgroup analysis, there is no direct relationship between the obesity in middle-aged and elderly women and an increased risk of stress urinary incontinence (SUI) (OR=1.31; 95% CI: 0.99-1.74; I2 = 63.7%, P=0.011). In middle-aged and elderly women with obesity are more likely to develop urgent urinary incontinence (UUI) (OR=2.11; 95% CI: 1.54-2.89; I2 = 80.2%, P=0.000). Conclusion: In this meta-analysis, overweight and obesity are associated with an increased risk of UI in middle-aged and elderly women. Obesity and overweight are independent risk factors for UI, as demonstrated by this study. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023421986.
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Incontinencia Urinaria de Esfuerzo , Incontinencia Urinaria , Anciano , Persona de Mediana Edad , Humanos , Femenino , Sobrepeso/complicaciones , Sobrepeso/epidemiología , Incontinencia Urinaria/etiología , Incontinencia Urinaria/complicaciones , Obesidad/complicaciones , Obesidad/epidemiología , Estudios Epidemiológicos , Estudios Observacionales como AsuntoRESUMEN
The study investigated the effects of feed efficiency (residual feed intake, RFI and residual intake and gain, RIG) on the production performance of small-sized meat ducks. Ninety ducks with intermediate and extreme (high and low) RFI values were selected from 1,083 male ducks of similar body weight, and the 3 groups were then redivided according to RIG. For both efficiency measures, the feed conversion ratio (FCR) and average daily feed intake (ADFI) of efficient ducks were significantly lower than those of inefficient ducks (P < 0.05), while the residual body weight gain (RG) was significantly higher in efficient ducks (P < 0.05). Inefficient-RFI animals showed greater skin fat yield (P < 0.05), but no other differences in carcass traits were observed (P > 0.05). RIG had positive effects on the pH1 value of the breast muscle (P < 0.05), but feed efficiency did not affect the other meat quality traits (P > 0.05). With regard to blood biochemical parameters, efficient ducks had significantly lower triglycerides (TG) (P < 0.05). Correlation analysis demonstrated that RFI was positively correlated with average daily feed intake and feed conversion ratio (P < 0.05), while RIG exhibited a strong negative correlation with both (P < 0.05). The average daily body weight gain was positively correlated with RIG (P < 0.05). RIG had a positive effect on the pH1 value of the breast muscle (P < 0.05). Furthermore, triglyceride and high-density lipoprotein cholesterol levels correlated with both efficiency classifications (P < 0.05). Overall, the efficiency measures did not affect the carcass and meat quality of small-sized meat ducks but could identify ducks with lower feed consumption and fast growth.
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Alimentación Animal , Patos , Masculino , Animales , Patos/fisiología , Alimentación Animal/análisis , Pollos , Ingestión de Alimentos/fisiología , Carne/análisis , Fenotipo , Peso Corporal/genética , Aumento de PesoRESUMEN
With mastery over the colloidal synthesis of monometallic nanocrystals, a combination of two distinct metals with intricate architectures has emerged as a new direction of innovation. Among the diverse architectures, the one with a core-shell structure has attracted the most scientific endeavors owing to its merits of high controllability and variability. Along with the new hopes arising from the addition of a shell composed of a different metal, there comes unexpected complications for the surface composition, hindering both structural understanding and application performance. In this Focus article, we present a brief overview of the opportunities provided by the bimetallic core-shell nanocrystals, followed by a discussion of the technical challenge to elucidate the true composition of the outermost surface. Some of the promising solutions are then highlighted as well, aiming to inspire future efforts toward this frontier of research.
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ConspectusGalvanic replacement synthesis involves oxidation and dissolution of atoms from a substrate while the salt precursor to another material with a higher reduction potential is reduced and deposited on the substrate. The driving force or spontaneity of such a synthesis comes from the difference in reduction potential between the redox pairs involved. Both bulk and micro/nanostructured materials have been explored as substrates for galvanic replacement synthesis. The use of micro/nanostructured materials can significantly increase the surface area, offering immediate advantages over the conventional electrosynthesis. The micro/nanostructured materials can also be intimately mixed with the salt precursor in a solution phase, resembling the setting of a typical chemical synthesis. The reduced material tends to be directly deposited on the surface of the substrate, just like the situation in an electrosynthesis. Different from an electrosynthesis where the two electrodes are spatially separated by an electrolyte solution, the cathodes and anodes are situated on the same surface, albeit at different sites, even for a micro/nanostructured substrate. Since the oxidation and dissolution reactions occur at sites different from those for reduction and deposition reactions, one can control the growth pattern of the newly deposited atoms on the same surface of a substrate to access nanostructured materials with diverse and controllable compositions, shapes, and morphologies in a single step. Galvanic replacement synthesis has been successfully applied to different types of substrates, including those made of crystalline and amorphous materials, as well as metallic and nonmetallic materials. Depending on the substrate involved, the deposited material can take different nucleation and growth patterns, resulting in diverse but well-controlled nanomaterials sought for a variety of studies and applications.In this Account, we recapitulate our efforts over the past two decades in fabricating metal nanostructures for a broad range of applications by leveraging the unique capability of galvanic replacement synthesis. We begin with a brief introduction to the fundamentals of galvanic replacement between metal nanocrystals and salt precursors, followed by a discussion of the roles played by surface capping agents in achieving site-selected carving and deposition for the fabrication of various bimetallic nanostructures. Two examples based on the Ag-Au and Pd-Pt systems are selected to illustrate the concept and mechanism. We then highlight our recent work on the galvanic replacement synthesis involving nonmetallic substrates, with a focus on the protocol, mechanistic understanding, and experimental control for the fabrication of Au- and Pt-based nanostructures with tunable morphologies. Finally, we showcase the unique properties and applications of nanostructured materials derived from galvanic replacement reactions for biomedicine and catalysis. We also offer some perspectives on the challenges and opportunities in this emerging field of research.
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Purpose: To clarify the effects of acute hyperglycemia on the responses of choroidal structural components and vascularity index during light modulation in healthy participants using techniques including image binarization and artificial intelligence (AI) segmentation based on swept-source optical coherence tomography (SS-OCT). Methods: Twenty-four eyes of 24 healthy participants were imaged at different stages after ambient light, 40 min of dark adaptation, and 5 min of light adaptation in two imaging sessions: control and after receiving 75 g of oral glucose solution. The choroidal structural parameters, including luminal volume (LV), stromal volume (SV), total choroidal volume (TCV), and choroidal vascularity index (CVI) within a 6 mm area were determined using a custom algorithm based on image binarization and AI segmentation of SS-OCT. These measurements were compared among the conditions after adjusting for axial length, age to identify the differences. Results: In the dark, CVI decreased (-0.36 ± 0.09%) significantly in acute hyperglycemia compared to the control condition. During the transition to ambient light, there was an increasing trend in the choroidal parameters compared with the control experiment. However, only TCV (0.38 ± 0.17 mm3) and LV (0.27 ± 0.10 mm3) showed a significant increase at the time point of 5 min after ambient light. Conclusion: Analysis of choroidal structural parameters and CVI based on SS-OCT images is a potentially powerful method to objectively reflect subtle changes in neurovascular coupling between the choroid and photoreceptor during dark adaptation.
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Hiperglucemia , Tomografía de Coherencia Óptica , Humanos , Tomografía de Coherencia Óptica/métodos , Inteligencia Artificial , Coroides/diagnóstico por imagen , Coroides/irrigación sanguínea , Enfermedad Aguda , Adaptación Ocular , Hiperglucemia/diagnóstico por imagenRESUMEN
Verticillium wilt caused by Verticillium dahliae is a serious vascular disease in cotton (Gossypium spp.). V. dahliae induces the expression of the CAROTENOID CLEAVAGE DIOXYGENASE 7 (GauCCD7) gene involved in strigolactone (SL) biosynthesis in Gossypium australe, suggesting a role for SLs in Verticillium wilt resistance. We found that the SL analog rac-GR24 enhanced while the SL biosynthesis inhibitor TIS108 decreased cotton resistance to Verticillium wilt. Knock-down of GbCCD7 and GbCCD8b genes in island cotton (Gossypium barbadense) decreased resistance, whereas overexpression of GbCCD8b in upland cotton (Gossypium hirsutum) increased resistance to Verticillium wilt. Additionally, Arabidopsis (Arabidopsis thaliana) SL mutants defective in CCD7 and CCD8 putative orthologs were susceptible, whereas both Arabidopsis GbCCD7- and GbCCD8b-overexpressing plants were more resistant to Verticillium wilt than wild-type (WT) plants. Transcriptome analyses showed that several genes related to the jasmonic acid (JA)- and abscisic acid (ABA)-signaling pathways, such as MYELOCYTOMATOSIS 2 (GbMYC2) and ABA-INSENSITIVE 5, respectively, were upregulated in the roots of WT cotton plants in responses to rac-GR24 and V. dahliae infection but downregulated in the roots of both GbCCD7- and GbCCD8b-silenced cotton plants. Furthermore, GbMYC2 suppressed the expression of GbCCD7 and GbCCD8b by binding to their promoters, which might regulate the homeostasis of SLs in cotton through a negative feedback loop. We also found that GbCCD7- and GbCCD8b-silenced cotton plants were impaired in V. dahliae-induced reactive oxygen species (ROS) accumulation. Taken together, our results suggest that SLs positively regulate cotton resistance to Verticillium wilt through crosstalk with the JA- and ABA-signaling pathways and by inducing ROS accumulation.
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Arabidopsis , Verticillium , Gossypium/genética , Gossypium/metabolismo , Verticillium/fisiología , Arabidopsis/genética , Arabidopsis/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Hormonas/metabolismo , Resistencia a la Enfermedad/genética , Enfermedades de las Plantas/genética , Regulación de la Expresión Génica de las Plantas , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismoRESUMEN
We report a method to experimentally control the heterogeneous nucleation and growth of Au nanoparticles on the surface of amorphous Se (a-Se) nanospheres. When a AuIII precursor is added into a colloidal suspension of a-Se nanospheres, galvanic replacement occurs between them and the resultant Au0 atoms then heterogeneously nucleate and grow from the surface of the a-Se nanospheres. As a unique feature of this system, the Au0 atoms can only be produced on the surface of the a-Se nanospheres in the nucleation stage. Once Au nuclei are formed on the surface at the very beginning of a synthesis, they will serve as the preferential sites for further deposition of Au0 atoms, making it possible to control the number of Au nanoparticles on each nanosphere and the morphology of the final product. The dependence of the initial reduction rate on the pH can be used to obtain Se-Au hybrid nanoparticles containing one, two, three, and multiple Au nanoparticles on the surface of each a-Se nanosphere. The presence of Au patches on the hybrid nanoparticles offers an experimental handle to optimize the ligand distribution for the achievement of enhanced cellular uptake and cytotoxicity for the a-Se nanospheres.
Asunto(s)
Nanopartículas del Metal , Nanosferas , Oro , Nanopartículas del Metal/toxicidadRESUMEN
We report a robust method for the facet-controlled synthesis of nanocrystals with an ultrathin shell made of a nearly equimolar RuRhPdPt quaternary alloy. Our strategy involves the use of well-defined Rh cubic seeds, halide-free precursors, and a method for precisely controlling the reaction kinetics of different precursors. In the setting of dropwise addition, the precursors with different reactivities can be reduced at about the same pace for the generation of an alloy with a uniform and well-controlled composition. The core-shell nanocubes show greatly enhanced activity toward ethanol oxidation when benchmarked against Pd and Pt counterparts. Combining in situ and ex situ electron microscopy studies, we also demonstrate that the core-shell nanocubes possess good thermal and electrochemical stability in terms of both geometrical shape and elemental composition, with their cubic shape and alloy composition retained when annealing at 500 °C or after long-term electrochemical cycling. It is expected that the synthetic approach can be further extended to fabricate multimetallic catalysts with enhanced activities toward a variety of thermal and electrochemical reactions.