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Non-line-of-sight (NLOS) sensing is an emerging technique that is capable of detecting objects hidden behind a wall, around corners, or behind other obstacles. However, NLOS tracking of moving objects is challenging due to signal redundancy and background interference. Here, we demonstrate computational neuromorphic imaging with an event camera for NLOS tracking, unaffected by the relay surface, which can efficiently obtain non-redundant information. We show how this sensor, which responds to changes in luminance within dynamic speckle fields, allows us to capture the most relevant events for direct motion estimation. The experimental results confirm that our method has superior performance in terms of efficiency, and accuracy, which greatly benefits from focusing on well-defined NLOS object tracking.
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BACKGROUND: Conventional Mechanical ventilation modes used for individuals suffering from acute respiratory distress syndrome have the potential to exacerbate lung injury through regional alveolar overinflation and/or repetitive alveolar collapse with shearing, known as atelectrauma. Animal studies have demonstrated that airway pressure release ventilation (APRV) offers distinct advantages over conventional mechanical ventilation modes. However, the methodologies for implementing APRV vary widely, and the findings from clinical studies remain controversial. This study (APRVplus trial), aims to assess the impact of an early pathophysiology-driven APRV ventilation approach compared to a low tidal volume ventilation (LTV) strategy on the prognosis of patients with moderate to severe ARDS. METHODS: The APRVplus trial is a prospective, multicenter, randomized clinical trial, building upon our prior single-center study, to enroll 840 patients from at least 35 hospitals in China. This investigation plans to compare the early pathophysiology-driven APRV ventilation approach with the control intervention of LTV lung-protective ventilation. The primary outcome measure will be all-cause mortality at 28 days after randomization in the intensive care units (ICU). Secondary outcome measures will include assessments of oxygenation, and physiology parameters at baseline, as well as on days 1, 2, and 3. Additionally, clinical outcomes such as ventilator-free days at 28 days, duration of ICU and hospital stay, ICU and hospital mortality, and the occurrence of adverse events will be evaluated. TRIAL ETHICS AND DISSEMINATION: The research project has obtained approval from the Ethics Committee of West China Hospital of Sichuan University (2019-337). Informed consent is required. The results will be submitted for publication in a peer-reviewed journal and presented at one or more scientific conferences. TRIAL REGISTRATION: The study was registered at Clinical Trials.gov (NCT03549910) on June 8, 2018.
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Presión de las Vías Aéreas Positiva Contínua , Respiración Artificial , Síndrome de Dificultad Respiratoria , Volumen de Ventilación Pulmonar , Humanos , China , Presión de las Vías Aéreas Positiva Contínua/métodos , Unidades de Cuidados Intensivos , Estudios Multicéntricos como Asunto , Estudios Prospectivos , Ensayos Clínicos Controlados Aleatorios como Asunto , Respiración Artificial/métodos , Síndrome de Dificultad Respiratoria/terapia , Síndrome de Dificultad Respiratoria/fisiopatologíaRESUMEN
A two-photon nanoparticle probe was designed and developed based on the principle of intermolecular interaction of the aggregation-induced locally excited emission luminescence mechanism. The probe has the advantages of simple synthesis, convenient use, strong atomic economy, good biocompatibility, and photobleaching resistance. It can produce a specific and sensitive response to formaldehyde, help detect FA in normal cells and cancer cells, and is expected to become a specific detection probe for FA in vitro and in vivo.
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Materiales Biocompatibles , Formaldehído , Ensayo de Materiales , Nanopartículas , Tamaño de la Partícula , Fotones , Formaldehído/química , Formaldehído/análisis , Humanos , Nanopartículas/química , Materiales Biocompatibles/química , Materiales Biocompatibles/síntesis química , Luminiscencia , Colorantes Fluorescentes/química , Colorantes Fluorescentes/síntesis química , Estructura MolecularRESUMEN
Flaviviruses in the Japanese encephalitis virus (JEV) serogroup, such as JEV, West Nile virus, and St. Louis encephalitis virus, can cause severe neurological diseases. The nonstructural protein 1 (NS1) is a multifunctional protein of flavivirus that can be secreted by infected cells and circulate in the host bloodstream. NS1' is an additional form of NS1 protein with 52 amino acids extension at its carboxy-terminal and is produced exclusively by flaviviruses in the JEV serogroup. In this study, we demonstrated that the secreted form of both NS1 and NS1' can disrupt the blood-brain barrier (BBB) of mice, with NS1' exhibiting a stronger effect. Using the in vitro BBB model, we found that treatment of soluble recombinant JEV NS1 or NS1' protein increases the permeability of human brain microvascular endothelial cells (hBMECs) and leads to the degradation of tight junction proteins through the autophagy-lysosomal pathway. Consistently, NS1' protein exhibited a more pronounced effect compared to NS1 in these cellular processes. Further research revealed that the increased expression of macrophage migration inhibitory factor (MIF) is responsible for triggering autophagy after NS1 or NS1' treatment in hBMECs. In addition, TLR4 and NF-κB signaling was found to be involved in the activation of MIF transcription. Moreover, administering the MIF inhibitor has been shown to decrease viral loads and mitigate inflammation in the brains of mice infected with JEV. This research offers a novel perspective on the pathogenesis of JEV. In addition, the stronger effect of NS1' on disrupting the BBB compared to NS1 enhances our understanding of the mechanism by which flaviviruses in the JEV serogroup exhibit neurotropism.IMPORTANCEJapanese encephalitis (JE) is a significant viral encephalitis worldwide, caused by the JE virus (JEV). In some patients, the virus cannot be cleared in time, leading to the breach of the blood-brain barrier (BBB) and invasion of the central nervous system. This invasion may result in cognitive impairment, behavioral disturbances, and even death in both humans and animals. However, the mechanism by which JEV crosses the BBB remains unclear. Previous studies have shown that the flavivirus NS1 protein plays an important role in causing endothelial dysfunction. The NS1' protein is an elongated form of NS1 protein that is particularly produced by flaviviruses in the JEV serogroup. This study revealed that both the secreted NS1 and NS1' of JEV can disrupt the BBB by breaking down tight junction proteins through the autophagy-lysosomal pathway, and NS1' is found to have a stronger effect compared to NS1 in this process. In addition, JEV NS1 and NS1' can stimulate the expression of MIF, which triggers autophagy via the ERK signaling pathway, leading to damage to BBB. Our findings reveal a new function of JEV NS1 and NS1' in the disruption of BBB, thereby providing the potential therapeutic target for JE.
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Autofagia , Barrera Hematoencefálica , Virus de la Encefalitis Japonesa (Especie) , Encefalitis Japonesa , Proteínas no Estructurales Virales , Animales , Humanos , Ratones , Barrera Hematoencefálica/virología , Barrera Hematoencefálica/metabolismo , Encéfalo/virología , Encéfalo/metabolismo , Virus de la Encefalitis Japonesa (Especie)/fisiología , Encefalitis Japonesa/virología , Encefalitis Japonesa/metabolismo , Células Endoteliales/virología , Células Endoteliales/metabolismo , Factores Inhibidores de la Migración de Macrófagos/metabolismo , FN-kappa B/metabolismo , Proteínas no Estructurales Virales/metabolismoRESUMEN
Circular RNAs (circRNAs) exhibit essential regulation in the malignant development of hepatocellular carcinoma (HCC). This study aims to investigate the physiological mechanisms of circ_0029343 encoded by scavenger receptor class B member 1 (SCARB1) involved in the growth and metastasis of HCC. Differentially expressed mRNAs in HCC were obtained, followed by the prediction of target genes of differentially expressed miRNAs and gene ontology and kyoto encyclopedia of genes and genomes analysis on the differentially expressed mRNAs. Moreover, the regulatory relationship between circRNAs encoded by SCARB1 and differentially expressed miRNAs was predicted. In vitro cell experiments were performed to verify the effects of circ_0029343, miR-486-5p, and SRSF3 on the malignant features of HCC cells using the gain- or loss-of-function experiments. Finally, the effects of circ_0029343 on the growth and metastasis of HCC cells in xenograft mouse models were also explored. It was found that miR-486-5p might interact with seven circRNAs encoded by SCARB1, and its possible downstream target gene was SRSF3. Moreover, SRSF3 was associated with the splicing of various RNA. circ_0029343 could sponge miR-486-5p to up-regulate SRSF3 and activate PDGF-PDGFRB (platelet-derived growth factor and its receptor, receptor beta) signaling pathway by inducing p73 splicing, thus promoting the proliferation, migration, and invasion and inhibiting apoptosis of HCC cells. In vivo, animal experiments further confirmed that overexpression of circ_0029343 could promote the growth and metastasis of HCC cells in nude mice. circ_0029343 encoded by SCARB1 may induce p73 splicing and activate the PDGF-PDGFRB signaling pathway through the miR-486-5p/SRSF3 axis, thus promoting the growth and metastasis of HCC cells.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , MicroARNs , Humanos , Animales , Ratones , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patología , ARN Circular/genética , ARN Circular/metabolismo , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patología , Ratones Desnudos , Receptor beta de Factor de Crecimiento Derivado de Plaquetas/genética , Receptor beta de Factor de Crecimiento Derivado de Plaquetas/metabolismo , Línea Celular Tumoral , Proliferación Celular/genética , MicroARNs/genética , MicroARNs/metabolismo , Regulación Neoplásica de la Expresión Génica , Receptores Depuradores de Clase B/genética , Receptores Depuradores de Clase B/metabolismo , Factores de Empalme Serina-Arginina/genética , Factores de Empalme Serina-Arginina/metabolismoRESUMEN
Emerging evidence has validated that extracellular vesicles (EVs) regulate hepatocellular carcinoma (HCC) progression, while its role in HCC immune escape remains to be elucidated. This study investigates the role of EVs-encapsulated lysyl oxidase like-4 (LOXL4) derived from tumor cells in HCC immune escape. HCC-related microarray data sets GSE36376 and GSE87630 were obtained for differential analysis, followed by identifying the essential genes related to the prognosis of HCC patients. Bone marrow-derived macrophages were treated with EVs derived from mouse Hepa 1-6 cells and cocultured with CD8 + T cells to observe the CD8 + T-cell activity. At last, a mouse HCC orthotopic xenograft model was constructed to verify the effects of HCC cell-derived EVs on the immune escape of HCC cells and tumorigenicity in vivo by delivering LOXL4. It was found that ACAT1, C4BPA, EHHADH, and LOXL4 may be the essential genes related to the prognosis of HCC patients. On the basis of the TIMER database, there was a close correlation between LOXL4 and macrophage infiltration in HCC. Besides, STAT1 was closely related to LOXL4. In vitro experiments demonstrated that LOXL4 could induce programmed death-ligand 1 expression in macrophages and immunosuppression by activating STAT1. In vivo experiments also verified that HCC cell-derived EVs promoted the immune escape of HCC cells and tumorigenicity by delivering LOXL4. LOXL4 was delivered into macrophages via EVs to induce programmed death-ligand 1 by activating STAT1 and inhibiting the killing ability of CD8 + T cells to HCC cells, thus promoting immune escape in HCC.
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Carcinoma Hepatocelular , Vesículas Extracelulares , Neoplasias Hepáticas , Animales , Humanos , Ratones , Antígeno B7-H1/metabolismo , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Línea Celular Tumoral , Ligandos , Neoplasias Hepáticas/metabolismo , Proteína-Lisina 6-Oxidasa/genética , Proteína-Lisina 6-Oxidasa/metabolismo , Factor de Transcripción STAT1/genética , Factor de Transcripción STAT1/metabolismo , Escape del TumorRESUMEN
Effectively imaging through dynamic scattering media is of great importance and challenge. Some imaging methods based on physical or learning models have been designed for object reconstruction. However, with an increase in exposure time or more drastic changes in the scattering medium, the speckle pattern superimposed during camera integration time undergoes more significant changes, resulting in a modification of the collected speckle structure and increased blurring, which brings significant challenges to the reconstruction. Here, the clearer structural information of blurred speckles is unearthed with a presented speckle de-blurring algorithm, and a high-throughput imaging method through rapidly changing scattering media is proposed for reconstruction under long exposure. For the problem of varying blur degrees in different regions of the speckle, a block-based method is proposed to divide the speckle into distinct sub-speckles, which can realize the reconstruction of hidden objects. The imaging of hidden objects with different complexity through dynamic scattering media is demonstrated, and the reconstruction results are improved significantly for speckles with different blur degrees, which verifies the effectiveness of the method. This method is a high-throughput approach that enables non-invasive imaging solely through the collection of a single speckle. It directly operates on blurred speckles, making it suitable for traditional speckle-correlation methods and deep learning (DL) methods. This provides a new way of thinking about solving practical scattering imaging challenges.
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BACKGROUND: Long non-coding RNA (lncRNA) HOTAIR acts importantly in liver cancer development, but its effect on radioresistance remains poorly understood. Here, our study probed into the possible impact of HOTAIR in radioresistance in liver cancer stem cells (LCSCs) and to elucidate its molecular basis. METHODS: Following sorting of stem and non-stem liver cancer cells, LCSCs were identified and subjected to RNA-seq analysis for selecting differentially expressed genes. Expression of HOTAIR was determined in liver cancer tissues and CSCs. The stemness, proliferation, apoptosis and radioresistance of LCSCs were then detected in response to altered expression of HOTAIR-LSD1-JMJD6-BRD4. RESULTS: Ectopic HOTAIR expression was found to promote radioresistance of LCSCs by maintaining its stemness. Mechanistic investigations indicated that HOTAIR recruited LSD1 to the MAPK1 promoter region and reduced the level of H3K9me2 in the promoter region, thus elevating ERK2 (MAPK1) expression. JMJD6-BRD4 complex promoted HOTAIR transcription by forming a complex and positively regulated ERK2 (MAPK1) expression, maintaining the stemness of LCSCs, and ultimately promoting their radioresistance in vitro and in vivo. CONCLUSION: Collectively, our work highlights the promoting effect of the JMJD6-BRD4 complex on the radioresistance of LCSCs through a HOTAIR-dependent mechanism.
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Neoplasias Hepáticas , ARN Largo no Codificante , Humanos , Proteínas de Ciclo Celular/genética , Línea Celular Tumoral , Proliferación Celular/genética , Regulación Neoplásica de la Expresión Génica , Histona Demetilasas/genética , Histona Demetilasas/metabolismo , Histona Demetilasas con Dominio de Jumonji/genética , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/radioterapia , Neoplasias Hepáticas/metabolismo , Células Madre Neoplásicas/metabolismo , Proteínas Nucleares/metabolismo , Regiones Promotoras Genéticas/genética , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Factores de Transcripción/metabolismoRESUMEN
ABSTRACT: The aim of the study was to investigate ultrasound's diagnostic capabilities for infant respiratory distress syndrome. Retrospective analysis was performed on the clinical information of 96 newborns with respiratory distress syndrome who were treated at our hospital between July 2015 and October 2017. The patients were split into the mild group (n = 55) and the severe group based on the findings of the chest x-ray examinations (n = 41). All neonates underwent an ultrasound examination at baseline, 12 hours after treatment and 24 hours after treatment of pulmonary surfactant (PS). Between the 2 groups, ultrasonographic characteristics and imaging scores were compared between infants with and without PS treatment. When compared with the severe group, the ultrasound score in the mild group was lower ( P < 0.05). Before treatment, there was no statistically significant difference in ultrasound score between the PS treatment group and the non-PS treatment group ( P > 0.05). At each time point after treatment, the ultrasonography score of the non-PS treatment group was greater than that of the PS treatment group ( P < 0.05). Neonatal respiratory distress syndrome severity may be accurately assessed using ultrasound technology. Furthermore, the results of ultrasonography examinations may serve as a significant marker for assessing and measuring the severity of newborn respiratory distress syndrome.
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Surfactantes Pulmonares , Síndrome de Dificultad Respiratoria del Recién Nacido , Síndrome de Dificultad Respiratoria , Lactante , Recién Nacido , Humanos , Estudios Retrospectivos , Síndrome de Dificultad Respiratoria del Recién Nacido/diagnóstico por imagen , Síndrome de Dificultad Respiratoria del Recién Nacido/terapia , Surfactantes Pulmonares/uso terapéutico , Ultrasonografía , Síndrome de Dificultad Respiratoria/tratamiento farmacológicoRESUMEN
The "14th Five-Year Plan" period is the key stage for southern Hebei cities (Shijiazhuang, Xingtai, and Handan) to be removed from the bottom ten of the Air Quality Composite Index. The hourly ozone (O3) data of 15 country-controlled monitoring stations in the southern cities of Hebei Province from April to October 2020, hourly data of three volatile organic compound (VOCs) supersites, and the meteorological data of the same period were used for analysis, combined with the spatiotemporal succession, O3 formation potential (OFP), backward trajectory modeling, and spatial statistical modeling. The results showed the following:firstly, the temporal variations in O3 in southern cities of Hebei Province from April to October presented an inverted "U" shape, and the spatial distribution was high in the south and low in the north. O3 pollution was the most serious in June, with Xingtai (233.8 µg·m-3)>Handan (225.2 µg·m-3)>Shijiazhuang (224.8 µg·m-3). O3 was positively correlated with temperature and wind speed and negatively correlated with humidity and VOCs; furthermore, the ρ(TVOC) from April to October followed the order of Xingtai (274 µg·m-3)>Shijiazhuang (266 µg·m-3)>Handan (218 µg·m-3). The total OFP of alkenes and aromatics accounted for more than half; moreover, the trajectory of O3 pollution in southern cities of Hebei Province showed spatial directionality and relevance. The highest mass concentration of O3 (198.92 µg·m-3) was in the trajectory from Shijiazhuang to Xingtai, and the highest frequency of O3 pollution was in the trajectory from Handan to Xingtai. Moreover, the transmission contributions of O3from Xingtai to Shijiazhuang agglomerations were high (27.39%), and Handan played a significant role in the transmission contribution of O3 to Xingtai (32.76%).
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Developing green heterogeneous catalysts with excellent Fenton-like activity is critical for water remediation technologies. However, current catalysts often rely on toxic transitional metals, and their catalytic performance is far from satisfactory as alternatives of homogeneous Fenton-like catalysts. In this study, a green catalyst based on Zn single-atom was prepared in an ammonium atmosphere using ZIF-8 as a precursor. Multiple characterization analyses provided evidence that abundant intrinsic defects due to the edge sites were created, leading to the formation of a thermally stable edge-hosted Zn-N4 single-atom catalyst (ZnN4-Edge). Density functional theory calculations revealed that the edge sites equipped the single-atom Zn with a super catalytic performance, which not only promoted decomposition of peroxide molecule (HSO5-) but also greatly lowered the activation barrier for â¢OH generation. Consequently, the as-prepared ZnN4-Edge exhibited extremely high Fenton-like performance in oxidation and mineralization of phenol as a representative organic contaminant in a wide range of pH, realizing its quick detoxification. The atom-utilization efficiency of the ZnN4-Edge was ~104 higher than an equivalent amount of the control sample without edge sites (ZnN4), and the turnover frequency was ~103 times of the typical benchmark of homogeneous catalyst (Co2+). This study opens up a revolutionary way to rationally design and optimize heterogeneous catalysts to homogeneous catalytic performance for Fenton-like application.
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Histone methylation is an important epigenetic modification that affects various biological processes, including the inflammatory response. In this study, we found that infection with Japanese encephalitis virus (JEV) leads to an increase in H3K27me3 in BV2 microglial cell line, primary mouse microglia and mouse brain. Inhibition of H3K27me3 modification through EZH2 knockdown and treatment with EZH2 inhibitor significantly reduces the production of pro-inflammatory cytokines during JEV infection, which suggests that H3K27me3 modification plays a crucial role in the neuroinflammatory response caused by JEV infection. The chromatin immunoprecipitation-sequencing (ChIP-sequencing) assay revealed an increase in H3K27me3 modification of E3 ubiquitin ligases Rnf19a following JEV infection, which leads to downregulation of Rnf19a expression. Furthermore, the results showed that Rnf19a negatively regulates the neuroinflammatory response induced by JEV. This is achieved through the degradation of RIG-I by mediating its ubiquitination. In conclusion, our findings reveal a novel mechanism by which JEV triggers extensive neuroinflammation from an epigenetic perspective.
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Virus de la Encefalitis Japonesa (Especie) , Virus de la Encefalitis Japonesa (Subgrupo) , Encefalitis Japonesa , Animales , Ratones , Histonas , Encefalitis Japonesa/genética , Inflamación , Ubiquitina-Proteína Ligasas/genéticaRESUMEN
Optical imaging through scattering media is a practical challenge with crucial applications in many fields. Many computational imaging methods have been designed for object reconstruction through opaque scattering layers, and remarkable recovery results have been demonstrated in the physical models or learning models. However, most of the imaging approaches are dependent on relatively ideal states with a sufficient number of speckle grains and adequate data volume. Here, the in-depth information with limited speckle grains has been unearthed with speckle reassignment and a bootstrapped imaging method is proposed for reconstruction in complex scattering states. Benefiting from the bootstrap priors-informed data augmentation strategy with a limited training dataset, the validity of the physics-aware learning method has been demonstrated and the high-fidelity reconstruction results through unknown diffusers are obtained. This bootstrapped imaging method with limited speckle grains broadens the way to highly scalable imaging in complex scattering scenes and gives a heuristic reference to practical imaging problems.
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It is becoming increasingly evident that key mechanisms of mesenchymal stem cell (MSC) efficacy appear to associate with paracrine activities, and the delivery of cargos through extracellular vesicles (EVs) controls the mechanistic actions of MSCs. Thus, this study clarified a possible mechanism by which EV-encapsulated NEAT1 from adipose-derived mesenchymal stem cells (ADSCs) might mediate gemcitabine resistance in pancreatic cancer (PCa). Microarray profile suggested a differentially expressed lncRNA NEAT1 in PCa, and we determined its expression in PCa cells. NEAT1 was found to be upregulated in PCa. The binding affinity among NEAT1, miR-491-5p, and Snail was identified through bioinformatic analysis and experimental validation. NEAT1 competitively bound to miR-491-5p to elevate Snail expression and diminish SOCS3 expression. PCa cells were cocultured with EVs extracted from ADSCs, followed by assessment of malignant phenotypes, tumorigenesis, and gemcitabine resistance of PCa cells using gain- or loss-of-function experiments. ADSC-derived EVs carrying NEAT1 promoted PCa cell proliferation, migration, and gemcitabine resistance in vitro and enhanced tumorigenicity in vivo by inhibiting miR-491-5p and SOCS3 and upregulating Snail. Collectively, the findings from our study found a new potential strategy for gemcitabine resistance in PCa by illustrating the mechanistic insights of oncogenic ADSC-derived EVs-loaded NEAT1 via regulating the miR-491-5p/Snail/SOCS3 axis.
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Fluconazole (FLC) is widely used to prevent and treat invasive fungal infections. However, FLC is a fungistatic agent, allowing clinical FLC-susceptible isolates to tolerate FLC. Making FLC fungicidal in combination with adjuvants is a promising strategy to avoid FLC resistance and eliminate the persistence and recurrence of fungal infections. Here, we identify a new small molecule compound, CZ66, that can make FLC fungicidal. The mechanism of action of CZ66 is targeting the C-4 sterol methyl oxidase, encoded by the ERG251 gene, resulting in decreased content of sterols with the 14α-methyl group and ultimately eliminating FLC tolerance of Candida albicans. CZ66 most likely interacts with Erg251 through residues Glu195, Gly206, and Arg241. Establishing Erg251 as a synergistic lethal target protein of FLC should direct research to identify specific small molecule inhibitors of 14α-methylsterol synthesis and open the way to abolishing fungal FLC tolerance. IMPORTANCE Fluconazole (FLC) tolerance increases the frequency of acquired FLC resistance, and a high FLC tolerance level is associated with persistent candidemia. Multiple functional proteins, such as calcineurin, heat shock protein 90 (Hsp90), and ADP ribosylation factor, are essential for the survival of C. albicans exposed to FLC, but how these factors increase the fungicidal activity of FLC remains to be determined. In this study, we found that 14α-methylsterols replace ergosterol to allow C. albicans to survive FLC, but Erg251 inactivated by CZ66 results in loss of 14α-methylsterol synthesis and cell death of C. albicans treated with FLC. Establishing Erg251 as a synergistic lethal target protein of FLC should direct research to identify specific small molecule inhibitors of 14α-methylsterol synthesis and open the way to abolishing fungal FLC tolerance.
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Fluconazol , Fungicidas Industriales , Fluconazol/farmacología , Antifúngicos/farmacología , Antifúngicos/metabolismo , Candida albicans/genética , Fungicidas Industriales/farmacología , Farmacorresistencia Fúngica , Pruebas de Sensibilidad MicrobianaRESUMEN
Background Three-dimensional (3D) time-of-flight (TOF) MR angiography (MRA) at 7 T has been reported to have high image quality for visualizing small perforating vessels. However, B1 inhomogeneity and more physiologic considerations limit its applications. Angiography at 5 T may provide another choice for intracranial vascular imaging. Purpose To evaluate the image quality and cerebrovascular visualization of 5-T 3D TOF MRA for visualizing intracranial small branch arteries. Materials and Methods Participants (healthy volunteers or participants with a history of ischemic stroke undergoing intracranial CT angiography or MRA for identifying steno-occlusive disease) were prospectively included from September 2021 to November 2021. Each participant underwent 3-T, 5-T, and 7-T 3D TOF MRA with use of customized MR protocols within 48 hours. Radiologist scoring from 0 (invisible) to 3 (excellent) and quantitative assessment were obtained to evaluate the image quality. The Friedman test was used for comparison of characteristics derived from 3 T, 5 T, and 7 T. Results A total of 12 participants (mean age ± SD, 38 years ± 9; nine men) were included. Visualizations of the distal arteries and small vessels at 5-T TOF MRA were significantly higher than those at 3 T (median score: 3.0 vs 2.0, all P < .001 for distal segments and lenticulostriate artery; median score: 2.0 vs 0, P < .001 for pontine artery). The total length of small vessel branches detected at 5 T was larger than that at 3 T (5.1 m ± 0.7 vs 1.9 m ± 0.4; P < .001). However, there was no evidence of a significant difference compared with 7 T in either the depiction of distal segments and small vessel branches (average median score, 2.5; all P > .05) or the quantitative measurements (total length, 5.6 m ± 0.5; P = .41). Conclusion Three-dimensional time-of-flight MR angiography at 5 T presented the capability to provide superior visualization of distal large arteries and small vessel branches (in terms of subjective and quantitative assessment) to 3 T and had image quality similar to 7 T. © RSNA, 2022 Online supplemental material is available for this article. An earlier incorrect version appeared online. This article was corrected on September 14, 2022.
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Angiografía por Resonancia Magnética , Tomografía Computarizada por Rayos X , Masculino , Humanos , Angiografía por Resonancia Magnética/métodos , Arterias Cerebrales , Arteria Cerebral Media , Angiografía por Tomografía Computarizada , Imagenología TridimensionalRESUMEN
In our continuing efforts to discover novel triazoles with improved antifungal activity in vitro and in vivo, a series of 41 novel compounds containing 1,2,3-triazole side chains were designed and synthesized via a click reaction based on our previous work. Most of the compounds showed moderate to excellent broad-spectrum antifungal activity in vitro. Among them, the most promising compound 9A16 displayed excellent antifungal and anti-drug-resistant fungal ability (MIC80 = 0.0156-8 µg/mL). In addition, compound 9A16 showed powerful in vivo efficacy on mice systematically infected with Candida albicans SC5314, Cryptococcus neoformans H99, fluconazole-resistant C. albicans 100, and Aspergillus fumigatus 7544. Moreover, compared to fluconazole, compound 9A16 showed better in vitro anti-biofilm activity and was more difficult to induce drug resistance in a 1 month induction of resistance assay in C. albicans. With favorable pharmacokinetics, an acceptable safety profile, and high potency in vitro and in vivo, compound 9A16 is currently under preclinical investigation.