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1.
Breast Cancer Res ; 26(1): 49, 2024 Mar 21.
Artículo en Inglés | MEDLINE | ID: mdl-38515107

RESUMEN

BACKGROUND: Patient-derived xenograft (PDX) models serve as a valuable tool for the preclinical evaluation of novel therapies. They closely replicate the genetic, phenotypic, and histopathological characteristics of primary breast tumors. Despite their promise, the rate of successful PDX engraftment is various in the literature. This study aimed to identify the key factors associated with successful PDX engraftment of primary breast cancer. METHODS: We integrated clinicopathological data with morphological attributes quantified using a trained artificial intelligence (AI) model to identify the principal factors affecting PDX engraftment. RESULTS: Multivariate logistic regression analyses demonstrated that several factors, including a high Ki-67 labeling index (Ki-67LI) (p < 0.001), younger age at diagnosis (p = 0.032), post neoadjuvant chemotherapy (NAC) (p = 0.006), higher histologic grade (p = 0.039), larger tumor size (p = 0.029), and AI-assessed higher intratumoral necrosis (p = 0.027) and intratumoral invasive carcinoma (p = 0.040) proportions, were significant factors for successful PDX engraftment (area under the curve [AUC] 0.905). In the NAC group, a higher Ki-67LI (p < 0.001), lower Miller-Payne grade (p < 0.001), and reduced proportion of intratumoral normal breast glands as assessed by AI (p = 0.06) collectively provided excellent prediction accuracy for successful PDX engraftment (AUC 0.89). CONCLUSIONS: We found that high Ki-67LI, younger age, post-NAC status, higher histologic grade, larger tumor size, and specific morphological attributes were significant factors for predicting successful PDX engraftment of primary breast cancer.


Asunto(s)
Neoplasias de la Mama , Animales , Humanos , Femenino , Neoplasias de la Mama/terapia , Neoplasias de la Mama/diagnóstico , Xenoinjertos , Inteligencia Artificial , Modelos Animales de Enfermedad , Ensayos Antitumor por Modelo de Xenoinjerto
2.
Clin Proteomics ; 21(1): 17, 2024 Feb 29.
Artículo en Inglés | MEDLINE | ID: mdl-38424522

RESUMEN

BACKGROUND: Immunotherapy is applied to breast cancer to resolve the limitations of survival gain in existing treatment modalities. With immunotherapy, a tumor can be classified into immune-inflamed, excluded and desert based on the distribution of immune cells. We assessed the clinicopathological features, each subtype's prognostic value and differentially expressed proteins between immune subtypes. METHODS: Immune subtyping and proteomic analysis were performed on 56 breast cancer cases with neoadjuvant chemotherapy. The immune subtyping was based on the level of tumor-infiltrating lymphocytes (TILs) and Klintrup criteria. If the level of TILs was ≥ 10%, it was classified as immune-inflamed type without consideration of the Klintrup criteria. In cases of 1-9% TIL, Klintrup criteria 1-3 were classified as the immune-excluded subtype and Klintrup criteria not available (NA) was classified as NA. Cases of 1% TILs and Klintrup 0 were classified as the immune-desert subtype. Mass spectrometry was used to identify differentially expressed proteins in formalin-fixed paraffin-embedded biopsy tissues. RESULTS: Of the 56 cases, 31 (55%) were immune-inflamed, 21 (38%) were immune-excluded, 2 (4%) were immune-desert and 2 (4%) were NA. Welch's t-test revealed two differentially expressed proteins between immune-inflamed and immune-excluded/desert subtypes. Coronin-1A was upregulated in immune-inflamed tumors (adjusted p = 0.008) and α-1-antitrypsin was upregulated in immune-excluded/desert tumors (adjusted p = 0.008). Titin was upregulated in pathologic complete response (pCR) than non-pCR among immune-inflamed tumors (adjusted p = 0.036). CONCLUSIONS: Coronin-1A and α-1-antitrypsin were upregulated in immune-inflamed and immune-excluded/desert subtypes, respectively. Titin's elevated expression in pCR within the immune-inflamed subtype may indicate a favorable prognosis. Further studies involving large representative cohorts are necessary to validate these findings.

3.
Mol Ther ; 31(6): 1675-1687, 2023 06 07.
Artículo en Inglés | MEDLINE | ID: mdl-36945774

RESUMEN

CRISPR-Cas13-mediated viral genome targeting is a novel strategy for defending against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants. Here, we generated mRNA-encoded Cas13b targeting the open reading frame 1b (ORF1b) region to effectively degrade the RNA-dependent RNA polymerase gene. Of the 12 designed CRISPR RNAs (crRNAs), those targeting the pseudoknot site upstream of ORF1b were found to be the most effective in suppressing SARS-CoV-2 propagation. Pseudoknot-targeting Cas13b reduced expression of the spike protein and attenuated viral replication by 99%. It also inhibited the replication of multiple SARS-CoV-2 variants, exhibiting broad potency. We validated the therapeutic efficacy of this system in SARS-CoV-2-infected hACE2 transgenic mice, demonstrating that crRNA treatment significantly reduced viral titers. Our findings suggest that the pseudoknot region is a strategic site for targeted genomic degradation of SARS-CoV-2. Hence, pseudoknot-targeting Cas13b could be a breakthrough therapy for overcoming infections by SARS-CoV-2 or other RNA viruses.


Asunto(s)
COVID-19 , Animales , Ratones , SARS-CoV-2/genética , Replicación Viral , ARN Viral/genética , ARN Viral/metabolismo
4.
Sensors (Basel) ; 23(22)2023 Nov 20.
Artículo en Inglés | MEDLINE | ID: mdl-38005665

RESUMEN

Digital holographic microscopy (DHM) is a valuable technique for investigating the optical properties of samples through the measurement of intensity and phase of diffracted beams. However, DHMs are constrained by Lagrange invariance, compromising the spatial bandwidth product (SBP) which relates resolution and field of view. Synthetic aperture DHM (SA-DHM) was introduced to overcome this limitation, but it faces significant challenges such as aberrations in synthesizing the optical information corresponding to the steering angle of incident wave. This paper proposes a novel approach utilizing deep neural networks (DNNs) for compensating aberrations in SA-DHM, extending the compensation scope beyond the numerical aperture (NA) of the objective lens. The method involves training a DNN from diffraction patterns and Zernike coefficients through a circular aperture, enabling effective aberration compensation in the illumination beam. This method makes it possible to estimate aberration coefficients from the only part of the diffracted beam cutoff by the circular aperture mask. With the proposed technique, the simulation results present improved resolution and quality of sample images. The integration of deep neural networks with SA-DHM holds promise for advancing microscopy capabilities and overcoming existing limitations.

5.
Indoor Air ; 32(11): e13173, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-36437657

RESUMEN

Indoor PM2.5 in apartments must be effectively managed to minimize adverse impacts on human health. Cooking is the one of the main PM2.5 sources in apartments, and indoor air quality (IAQ) management methods (natural ventilation, mechanical ventilations, range hoods, and air purifiers) are typically used to reduce PM2.5 generated during cooking. For effective control of indoor PM2.5 , prediction of PM2.5 reduction for various IAQ management methods is necessary. This study carefully predicted indoor PM2.5 concentrations in an apartment when IAQ management methods were applied separately and/or in combination during cooking. The infiltration and exfiltration were verified by comparing the experimental results of CO2 concentration with those predicted with or without mechanical ventilation. The deposition rate for PM2.5 generated by cooking was also derived by comparing the experimental PM2.5 changes with the predicted values for PM2.5 natural decay. Through this method, effective PM2.5 control ways during cooking in apartments can be proposed, such as natural ventilation with a range hood for 30 min and then the operation of an air purifier for 30 min. Additionally, if this prediction is combined with energy consumption, it will be possible to propose the most energy-efficient indoor PM2.5 control methods for various seasons and outdoor conditions.


Asunto(s)
Contaminación del Aire Interior , Humanos , Contaminación del Aire Interior/análisis , Culinaria , Material Particulado/análisis , República de Corea
6.
Mar Drugs ; 20(5)2022 Apr 27.
Artículo en Inglés | MEDLINE | ID: mdl-35621947

RESUMEN

Crude polysaccharides, extracted from two seaweed species (Hizikia fusiforme and Sargassum horneri) and Haliotis discus hannai (abalone) viscera, were evaluated for their inhibitory effect against SARS-CoV-2 propagation. Plaque titration revealed that these crude polysaccharides efficiently inhibited SARS-CoV-2 propagation with IC50 values ranging from 0.35 to 4.37 µg/mL. The crude polysaccharide of H. fusiforme showed the strongest antiviral effect, with IC50 of 0.35 µg/mL, followed by S. horneri and abalone viscera with IC50 of 0.56 and 4.37 µg/mL, respectively. In addition, immunofluorescence assay, western blot, and quantitative RT-PCR analysis verified that these polysaccharides could inhibit SARS-CoV-2 replication. In Vero E6 cells, treatment with these crude polysaccharides before or after viral infection strongly inhibited the expression level of SARS-CoV-2 spikes, nucleocapsid proteins, and RNA copies of RNA-dependent RNA-polymerase and nucleocapsid. These results show that these crude marine polysaccharides effectively inhibit SARS-CoV-2 propagation by interference with viral entry.


Asunto(s)
Tratamiento Farmacológico de COVID-19 , Algas Marinas , Antivirales/farmacología , Humanos , Polisacáridos/farmacología , ARN , SARS-CoV-2 , Vísceras
7.
J Biol Chem ; 295(42): 14501-14509, 2020 10 16.
Artículo en Inglés | MEDLINE | ID: mdl-32816994

RESUMEN

PGAP6, also known as TMEM8A, is a phospholipase A2 with specificity to glycosylphosphatidylinositol (GPI) and expressed on the surface of various cells. CRIPTO, a GPI-anchored co-receptor for a morphogenic factor Nodal, is a sensitive substrate of PGAP6. PGAP6-mediated shedding of CRIPTO plays a critical role in an early stage of embryogenesis. In contrast, CRYPTIC, a close family member of CRIPTO, is resistant to PGAP6. In this report, chimeras between CRIPTO and CRYPTIC and truncate mutants of PGAP6 were used to demonstrate that the Cripto-1/FRL1/Cryptic domain of CRIPTO is recognized by an N-terminal domain of PGAP6 for processing. We also report that among 56 human GPI-anchored proteins tested, only glypican 3, prostasin, SPACA4, and contactin-1, in addition to CRIPTO, are sensitive to PGAP6, indicating that PGAP6 has a narrow specificity toward various GPI-anchored proteins.


Asunto(s)
Glicoproteínas de Membrana/metabolismo , Secuencia de Aminoácidos , Animales , Línea Celular , Proteínas Ligadas a GPI/química , Proteínas Ligadas a GPI/genética , Proteínas Ligadas a GPI/metabolismo , Humanos , Péptidos y Proteínas de Señalización Intercelular/química , Péptidos y Proteínas de Señalización Intercelular/genética , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Masculino , Glicoproteínas de Membrana/química , Glicoproteínas de Membrana/genética , Ratones , Mutagénesis , Proteínas de Neoplasias/química , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Unión Proteica , Dominios Proteicos , Receptores de Superficie Celular/metabolismo , Serina Endopeptidasas/metabolismo , Espermatozoides/metabolismo , Especificidad por Sustrato , Testículo/metabolismo
8.
FASEB J ; 34(8): 10316-10328, 2020 08.
Artículo en Inglés | MEDLINE | ID: mdl-32530114

RESUMEN

Cellular senescence can be triggered by various intrinsic and extrinsic stimuli. We previously reported that silencing of 3'-phosphoadenosine 5'-phosphosulfate synthetase 2 (PAPSS2) induces cellular senescence through augmented fibroblast growth factor receptor 1 (FGFR1) signaling. However, the exact molecular mechanism connecting heparan sulfation and cellular senescence remains unclear. Here, we investigated the potential involvement of heparan sulfate proteoglycans (HSPGs) in augmented FGFR1 signaling and cellular senescence. Depletion of several types of HSPGs revealed that cells depleted of syndecan 1 (SDC1) exhibited typical senescence phenotypes, and those depleted of PAPSS2-, SDC1-, or heparan sulfate 2-O sulfotransferase 1 (HS2ST1) showed decreased FGFR1 internalization along with hyperresponsiveness to and prolonged activation of fibroblast growth factor 2 (FGF2)-stimulated FGFR1- v-akt murine thymoma viral oncogene homolog (AKT) signaling. Clathrin- and caveolin-mediated FGFR1 endocytosis contributed to cellular senescence through the FGFR1-AKT-p53-p21 signaling pathway. Dynasore treatment triggered senescence phenotypes, augmented FGFR1-AKT-p53-p21 signaling, and decreased SDC1 expression. Finally, the replicatively and prematurely senescent cells were characterized by decreases of SDC1 expression and FGFR1 internalization, and an increase in FGFR1-AKT-p53-p21 signaling. Together, our results demonstrate that properly sulfated SDC1 plays a critical role in preventing cellular senescence through the regulation of FGFR1 endocytosis.


Asunto(s)
Senescencia Celular/fisiología , Endocitosis/fisiología , Receptor Tipo 1 de Factor de Crecimiento de Fibroblastos/metabolismo , Sulfatos/metabolismo , Sindecano-1/metabolismo , Caveolinas/metabolismo , Línea Celular , Línea Celular Tumoral , Clatrina/metabolismo , Factor 2 de Crecimiento de Fibroblastos/metabolismo , Heparitina Sulfato/metabolismo , Humanos , Células MCF-7 , Transducción de Señal/fisiología
9.
Inorg Chem ; 60(17): 12813-12822, 2021 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-34492761

RESUMEN

A new type of dititanium dinitrogen complex supported by a triphenolamine (TPA) ligand is reported. Analysis by single-crystal X-ray diffraction and Raman and NMR spectroscopy reveals different coordination geometries for the two titanium centers. Hence, coordination of TPA and a nitrogen ligand results in trigonal-bipyramidal geometry, while an octahedral titanium center is obtained upon additional coordination of an ethoxide generated upon C-O bond cleavage in a diethyl ether solvent molecule. The titanium complex successfully generates ammonia in the presence of an excess amount of PCy3HI and KC8 in 154% yield (per titanium atom). A titanium complex with a bulkier TPA does not form a dinitrogen complex, and mononuclear titanium dinitrogen complexes were not accessible, presumably because of the high tendency of early transition metals to form binuclear dinitrogen complexes.

10.
Int J Mol Sci ; 22(6)2021 Mar 23.
Artículo en Inglés | MEDLINE | ID: mdl-33807071

RESUMEN

Hepatocellular carcinoma (HCC), the most common malignant tumor in the liver, grows and metastasizes rapidly. Despite advances in treatment modalities, the five-year survival rate of HCC remains less than 30%. We sought genetic mutations that may affect the oncogenic properties of HCC, using The Cancer Genome Atlas (TCGA) data analysis. We found that the GNAQ T96S mutation (threonine 96 to serine alteration of the Gαq protein) was present in 12 out of 373 HCC patients (3.2%). To examine the effect of the GNAQ T96S mutation on HCC, we transfected the SK-Hep-1 cell line with the wild-type or the mutant GNAQ T96S expression vector. Transfection with the wild-type GNAQ expression vector enhanced anchorage-independent growth, migration, and the MAPK pathways in the SK-Hep-1 cells compared to control vector transfection. Moreover, cell proliferation, anchorage-independent growth, migration, and the MAPK pathways were further enhanced in the SK-Hep-1 cells transfected with the GNAQ T96S expression vector compared to the wild-type GNAQ-transfected cells. In silico structural analysis shows that the substitution of the GNAQ amino acid threonine 96 with a serine may destabilize the interaction between the regulator of G protein signaling (RGS) protein and GNAQ. This may reduce the inhibitory effect of RGS on GNAQ signaling, enhancing the GNAQ signaling pathway. Single nucleotide polymorphism (SNP) genotyping analysis for Korean HCC patients shows that the GNAQ T96S mutation was found in only one of the 456 patients (0.22%). Our data suggest that the GNAQ T96S hotspot mutation may play an oncogenic role in HCC by potentiating the GNAQ signal transduction pathway.


Asunto(s)
Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Subunidades alfa de la Proteína de Unión al GTP Gq-G11/genética , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Mutación , Transducción de Señal , Alelos , Sustitución de Aminoácidos , Carcinoma Hepatocelular/patología , Movimiento Celular/genética , Proliferación Celular , Transformación Celular Neoplásica/genética , Transformación Celular Neoplásica/metabolismo , Susceptibilidad a Enfermedades , Subunidades alfa de la Proteína de Unión al GTP Gq-G11/química , Subunidades alfa de la Proteína de Unión al GTP Gq-G11/metabolismo , Expresión Génica , Genotipo , Humanos , Neoplasias Hepáticas/patología , Sistema de Señalización de MAP Quinasas , Modelos Moleculares , Oncogenes , Conformación Proteica , Relación Estructura-Actividad
12.
Small ; 15(1): e1804005, 2019 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-30609284

RESUMEN

A simple, low-cost, large area, and continuous scalable coating method is proposed for the fabrication of hybrid organic-inorganic perovskite solar cells. A megasonic spray-coating method utilizing a 1.7 MHz megasonic nebulizer that could fabricate reproducible large-area planar efficient perovskite films is developed. The coating method fabricates uniform large-area perovskite film with large-sized grain since smaller and narrower sized mist droplets than those generated by existing ultrasonic spray methods could be generated by megasonic spraying. The volume flow rate of the CH3 NH3 PbI3 precursor solution and the reaction temperature are controlled, to obtain a high quality perovskite active layer. The devices reach a maximum efficiency of 16.9%, with an average efficiency of 16.4% from 21 samples. The applicability of megasonic spray coating to the fabrication of large-area solar cells (1 cm2 ), with a power conversion efficiency of 14.2%, is also demonstrated. This is a record high efficiency for large-area perovskite solar cells fabricated by continuous spray coating.

13.
Neural Plast ; 2016: 2123748, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27127657

RESUMEN

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive cognitive decline. Pathologic accumulation of soluble amyloid-ß (Aß) oligomers impairs synaptic plasticity and causes epileptic seizures, both of which contribute to cognitive dysfunction in AD. However, whether seizures could regulate Aß-induced synaptic weakening remains unclear. Here we show that a single episode of electroconvulsive seizures (ECS) increased protein expression of membrane-associated STriatal-Enriched protein tyrosine Phosphatase (STEP61) and decreased tyrosine-phosphorylation of its substrates N-methyl D-aspartate receptor (NMDAR) subunit GluN2B and extracellular signal regulated kinase 1/2 (ERK1/2) in the rat hippocampus at 2 days following a single ECS. Interestingly, a significant decrease in ERK1/2 expression and an increase in APP and Aß levels were observed at 3-4 days following a single ECS when STEP61 level returned to the baseline. Given that pathologic levels of Aß increase STEP61 activity and STEP61-mediated dephosphorylation of GluN2B and ERK1/2 leads to NMDAR internalization and ERK1/2 inactivation, we propose that upregulation of STEP61 and downregulation of GluN2B and ERK1/2 phosphorylation mediate compensatory weakening of synaptic strength in response to acute enhancement of hippocampal network activity, whereas delayed decrease in ERK1/2 expression and increase in APP and Aß expression may contribute to the maintenance of this synaptic weakening.


Asunto(s)
Péptidos beta-Amiloides/metabolismo , Hipocampo/metabolismo , Plasticidad Neuronal/fisiología , Proteínas Tirosina Fosfatasas/metabolismo , Convulsiones/metabolismo , Animales , Regulación hacia Abajo , Sistema de Señalización de MAP Quinasas/fisiología , Masculino , Fosforilación , Ratas , Ratas Sprague-Dawley , Receptores de N-Metil-D-Aspartato/metabolismo , Regulación hacia Arriba
14.
Neural Netw ; 169: 282-292, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37918271

RESUMEN

Existing methods for estimating human poses from video content exploit the temporal features of the video sequences and have shown impressive results. However, most methods address spatiotemporal issues separately. They compromise on accuracy to reduce jitter, or require high-resolution images to deal with occlusion, preventing full consideration of temporal features. Unfortunately, these two issues are interrelated. For example, occlusion causes uncertainty between successive frames, leading to unsmoothed results. To address these issues, we propose the Masked Kinematic Continuity-aware Hierarchical Attention Network (M-HANet) as a novel framework that exploits masked kinematic keypoint features by extending our framework HANet framework. First, we randomly select and mask a keypoint to treat the masked keypoint as it is occluded, which allows us to make the network resilient to occlusion. We also use the velocity and acceleration of each individual keypoint to effectively capture temporal features. Second, the proposed hierarchical transformer encoder refines a 2D or 3D input pose derived from existing estimators by aggregating the masked continuity of the spatiotemporal dependencies of human motion. Finally, to facilitate collaborative optimization, we perform an online cross-supervision between the final pose from our decoder and the refined input pose produced by our encoder. We validate the effectiveness of our model demonstrating that our proposed approach improves PCK@0.05 by 14.1% and MPJPE by 8.7 mm compared to the existing method on a variety of tasks, including 2D and 3D pose estimation, body mesh recovery, and sparsely annotated multi-human pose estimation.


Asunto(s)
Resiliencia Psicológica , Humanos , Fenómenos Biomecánicos , Movimiento (Física) , Incertidumbre
15.
Anticancer Res ; 44(2): 521-532, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38307549

RESUMEN

BACKGROUND/AIM: The effectiveness of adoptive T cell therapy for solid tumors remains suboptimal, partly attributed to insufficient T cell infiltration into the tumor site. A promising strategy involves directing T cells towards the tumor utilizing tumor-specific chemokine receptors. MATERIALS AND METHODS: We analyzed chemokine receptor expression in activated T cells and chemokine expression in breast and lung cancer using The Cancer Genome Atlas (TCGA) data. Subsequently, we generated 1G4 T cell receptor-engineered T (TCR-T) cells with CCR10 and performed in vitro and in vivo efficacy tests. RESULTS: CCR10 exhibited insufficient expression in various human T cells. Analysis of TCGA RNA sequencing data revealed elevated expression of the chemokine CCL28, the corresponding chemokine for CCR10, in breast and lung cancer. Consequently, we generated CCR10-1G4 TCR-T cells. CCR10-1G4 dual expressing TCR-T cells exhibited comparable cellular cytotoxicity but increased mobility compared to 1G4 TCR-T cells in vitro. Furthermore, injecting CCR10-1G4 dual expressing TCR-T cells into a xenograft tumor model demonstrated enhanced in vivo trafficking and a greater reduction of tumor burden. CONCLUSION: This study highlights the potential of CCR10 for developing efficient adoptive T-cell treatments targeting solid tumors.


Asunto(s)
Neoplasias Pulmonares , Linfocitos T , Humanos , Linfocitos T/metabolismo , Quimiocinas/metabolismo , Receptores de Quimiocina , Inmunoterapia , Neoplasias Pulmonares/terapia , Receptores de Antígenos de Linfocitos T/genética , Receptores CCR10/genética , Receptores CCR10/metabolismo
16.
RSC Adv ; 13(45): 31480-31486, 2023 Oct 26.
Artículo en Inglés | MEDLINE | ID: mdl-37901265

RESUMEN

Capacitive deionization (CDI) is an electrochemical-based water treatment technology that has attracted attention as an effective hardness-control process. However, few systematic studies have reported the criteria for the selection of suitable electrode materials for membrane capacitive deionization (MCDI) to control hardness. In this study, the effect of electrode material characteristics on the MCDI performance for hardness control was quantitatively analyzed. The results showed that the deionization capacity and the deionization rate were affected by the specific capacitance and BET-specific surface area of the activated carbon electrode. In addition, the deionization rate also showed significant relationship with the BET specific surface area. Furthermore, it was observed that the deionization capacity and the deionization rate have a highly significant relationship with the BET specific surface area divided by the wettability performance expressed as the minimum wetting rate (MWR). These findings highlighted that the electrode material should have a large surface area and good wettability to increase the deionization capacity and the deionization rate of MCDI for hardness control. The results of this study are expected to provide effective criteria for selecting MCDI electrode materials aiming hardness control.

17.
Toxics ; 11(11)2023 Nov 16.
Artículo en Inglés | MEDLINE | ID: mdl-37999583

RESUMEN

The educational and play-related activities of children proceed mainly indoors in a kindergarten. High concentrations of indoor PM2.5 and CO2 have been linked to various harmful effects on children, considerably impacting their educational outcomes in kindergarten. In this study, we explore different scenarios involving the operation of mechanical ventilation systems and air purifiers in kindergartens. Using numerical models to analyze indoor CO2 and PM2.5 concentration, we aim to optimize strategies that effectively reduce these harmful pollutants. We found that the amount of ventilation required to maintain good air quality, per child, was approximately 20.4 m3/h. However, we also found that as the amount of ventilation increased, so did the concentration of indoor PM2.5; we found that this issue can be resolved using a high-grade filter (i.e., a MERV 13 grade filter with a collection efficiency of 75%). This study provides a scientific basis for reducing PM2.5 concentrations in kindergartens, while keeping CO2 levels low.

18.
Sci Rep ; 13(1): 3303, 2023 02 27.
Artículo en Inglés | MEDLINE | ID: mdl-36849513

RESUMEN

A highly contagious virus, severe acute respiratory syndrome coronavirus 2, caused the coronavirus disease 19 (COVID-19) pandemic (SARS-CoV-2). SARS-CoV-2 genetic variants have been reported to circulate throughout the COVID-19 pandemic. COVID-19 symptoms include respiratory symptoms, fever, muscle pain, and breathing difficulty. In addition, up to 30% of COVID-19 patients experience neurological complications such as headaches, nausea, stroke, and anosmia. However, the neurotropism of SARS-CoV-2 infection remains largely unknown. This study investigated the neurotropic patterns between the B1.617.2 (Delta) and Hu-1 variants (Wuhan, early strain) in K18-hACE2 mice. Despite both the variants inducing similar pathogenic patterns in various organs, B1.617.2-infected K18-hACE2 mice demonstrated a higher range of disease phenotypes such as weight loss, lethality, and conjunctivitis when compared to those in Hu-1-infected mice. In addition, histopathological analysis revealed that B1.617.2 infects the brain of K18-hACE2 mice more rapidly and effectively than Hu-1. Finally, we discovered that, in B1.617.2-infected mice, the early activation of various signature genes involved innate cytokines and that the necrosis-related response was most pronounced than that in Hu-1-infected mice. The present findings indicate the neuroinvasive properties of SARS-CoV-2 variants in K18-hACE2 mice and link them to fatal neuro-dissemination during the disease onset.


Asunto(s)
COVID-19 , SARS-CoV-2 , Animales , Humanos , Ratones , SARS-CoV-2/genética , Pandemias
19.
Microbiol Spectr ; 11(3): e0510522, 2023 06 15.
Artículo en Inglés | MEDLINE | ID: mdl-36995225

RESUMEN

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of coronavirus disease 2019 (COVID-19). SARS-CoV-2 propagation is mediated by the protein interaction between viral proteins and host cells. Tyrosine kinase has been implicated in viral replication, and hence, it has become a target for developing antiviral drugs. We have previously reported that receptor tyrosine kinase inhibitor blocks the replication of hepatitis C virus (HCV). In the present study, we investigated two receptor tyrosine kinase-specific inhibitors, amuvatinib and imatinib, for their potential antiviral efficacies against SARS-CoV-2. Treatment with either amuvatinib or imatinib displays an effective inhibitory activity against SARS-CoV-2 propagation without an obvious cytopathic effect in Vero E6 cells. Notably, amuvatinib exerts a stronger antiviral activity than imatinib against SARS-CoV-2 infection. Amuvatinib blocks SARS-CoV-2 infection with a 50% effective concentration (EC50) value ranging from ~0.36 to 0.45 µM in Vero E6 cells. We further demonstrate that amuvatinib inhibits SARS-CoV-2 propagation in human lung Calu-3 cells. Using pseudoparticle infection assay, we verify that amuvatinib blocks SARS-CoV-2 at the entry step of the viral life cycle. More specifically, amuvatinib inhibits SARS-CoV-2 infection at the binding-attachment step. Moreover, amuvatinib exhibits highly efficient antiviral activity against emerging SARS-CoV-2 variants. Importantly, we demonstrate that amuvatinib inhibits SARS-CoV-2 infection by blocking ACE2 cleavage. Taken together, our data suggest that amuvatinib may provide a potential therapeutic agent for the treatment of COVID-19. IMPORTANCE Tyrosine kinase has been implicated in viral replication and has become an antiviral drug target. Here, we chose two well-known receptor tyrosine kinase inhibitors, amuvatinib and imatinib, and evaluated their drug potencies against SARS-CoV-2. Surprisingly, amuvatinib displays a stronger antiviral activity than imatinib against SARS-CoV-2. Amuvatinib blocks SARS-CoV-2 infection by inhibiting ACE2 cleavage and the subsequent soluble ACE2 receptor. All these data suggest that amuvatinib may be a potential therapeutic agent in SARS-CoV-2 prevention for those experiencing vaccine breakthroughs.


Asunto(s)
COVID-19 , Animales , Humanos , SARS-CoV-2 , Mesilato de Imatinib/farmacología , Mesilato de Imatinib/uso terapéutico , Enzima Convertidora de Angiotensina 2 , Antivirales/farmacología , Antivirales/uso terapéutico , Proteínas Tirosina Quinasas/farmacología , Estadios del Ciclo de Vida
20.
Toxics ; 11(11)2023 Nov 07.
Artículo en Inglés | MEDLINE | ID: mdl-37999564

RESUMEN

The mechanical ventilation systems used in houses are designed to reduce carbon dioxide emissions while minimizing the energy loss resulting from ventilation. However, the increase in indoor fine particulate (PM2.5) concentration because of external PM2.5 influx through the ventilation system poses a problem. Here, we analyzed the changes in indoor PM2.5 concentration, distinguishing between cases of high and low outdoor PM2.5 concentrations and considering the efficiency of the filters used in residential mechanical ventilation systems. When using filters with the minimum efficiency reporting value (MERV) of 10 in the ventilation system, the outdoor PM2.5 concentration was 5 µg/m³; compared to the initial concentration, the indoor PM2.5 concentration after 60 min decreased to 73%. When the outdoor PM2.5 concentration was 30-40 µg/m³, the indoor PM2.5 concentration reached 91%. However, when MERV 13 filters were used, the indoor PM2.5 concentration consistently dropped to 73-76%, regardless of the outdoor PM2.5 concentration. Furthermore, by comparing the established equation with the mass balance model, the error was confirmed to be within 5%, indicating a good fit. This allows for the prediction of indoor PM2.5 under various conditions when using mechanical ventilation systems, enabling the formulation of strategies for maintaining indoor PM2.5, as recommended by the World Health Organization.

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