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1.
Materials (Basel) ; 16(12)2023 Jun 08.
Artículo en Inglés | MEDLINE | ID: mdl-37374442

RESUMEN

Metasurface-based research with phase-change materials has been a prominent and rapidly developing research field that has drawn considerable attention in recent years. In this paper, we proposed a kind of tunable metasurface based on the simplest metal-insulator-metal structure, which can be realized by the mutual transformation of insulating and metallic states of vanadium dioxide (VO2) and can realize the functional switching of photonic spin Hall effect (PSHE), absorption and beam deflection at the same terahertz frequency. When VO2 is insulating, combined with the geometric phase, the metasurface can realize PSHE. A normal incident linear polarized wave will be split into two spin-polarized reflection beams traveling in two off-normal directions. When VO2 is in the metal state, the designed metasurface can be used as a wave absorber and a deflector, which will completely absorb LCP waves, while the reflected amplitude of RCP waves is 0.828 and deflects. Our design only consists of one layer of artificial structure with two materials and is easy to realize in the experiment compared with the metasurface of a multi-layer structure, which can provide new ideas for the research of tunable multifunctional metasurface.

3.
Opt Express ; 30(10): 16009-16019, 2022 May 09.
Artículo en Inglés | MEDLINE | ID: mdl-36221454

RESUMEN

Stealth radome (SR), especially with an ultra-broad and nearly transparent window between two absorption bands, plays a crucial role in stealth techniques, antenna radomes, and so on. However, current devices have the defects of narrow transmission bands, high insertion loss, and wide transition bands between the transmission and absorption bands, which are unfavorable for the stealth of broadband radar and communication systems. In this paper, a novel SR with an ultra-broad and high-efficiency inter-absorption band transparent window is proposed by combining broadband resonance lumped circuits with a multi-layer cascaded frequency-selective surface (FSS). The equivalent circuit model (ECM) and transmission line method (TLM) are provided and analyzed as a guideline for the SR design. The SR consists of a resistive lossy layer loaded with wide passband lumped circuits and two stacked lossless FSS layers to collectively achieve the high selectivity and ultra-broad transmission band. Simulated results indicate that the proposed SR exhibits an ultra-broad passband from 8.2 to 11.2 GHz (31%) with transmission amplitude more than 0.85 and two 90% absorption bands over 6.8-7.8 GHz and 12-13 GHz, and the transition bands at both sides are only 0.4 GHz and 0.8 GHz, respectively. Our findings can stimulate the promising applications of SR in broadband stealth devices with integrated ultra-broad communication capability or in other electromagnetic (EM) compatibility facilities.

4.
Int J Antimicrob Agents ; 60(5-6): 106684, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36279973

RESUMEN

INTRODUCTION: Antimicrobial resistance (AMR) is a global health threat; rapid and timely identification of AMR improves patient prognosis and reduces inappropriate antibiotic use. METHODS: Relevant literature in PubMed, Web of Science, Embase and Institute of Electrical and Electronics Engineers prior to 28 September 2021 was searched. Any study that deployed machine learning (ML) or a risk score as a tool to predict AMR was included in the final review; there were 25 studies that employed the ML algorithm to predict AMR. RESULTS: Extended spectrum ß-lactamases, methicillin-resistant Staphylococcus aureus (MRSA) and carbapenem resistance were the most common outcomes in studies with a specific resistance pattern. The most common algorithms in ML prediction were logistic regression (n = 14 studies), decision tree (n = 14) and random forest (n = 7). The area under the curve (AUC) range for ML prediction was 0.48-0.93. The pooled AUC for ML prediction was 0.82 (0.78-0.85). Compared with risk score, higher specificity [87% (82-91) vs. 37% (25-51)] was indicated for ML prediction, but not sensitivity [67% (62-72) vs. 73% (67-79)]. CONCLUSIONS: Machine learning might be a potential technology for AMR prediction; however, retrospective methodology for model development, nonstandard data processing and scarcity of validation in a randomised controlled trial or real-world study limit the application of these models in clinical practice.


Asunto(s)
Farmacorresistencia Bacteriana , Staphylococcus aureus Resistente a Meticilina , Humanos , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Estudios Retrospectivos , Aprendizaje Automático
5.
Adv Mater ; 34(38): e2205053, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-35926151

RESUMEN

Invisibility has been a topic of long-standing interest owing to the advent of metamaterials and transformation optics, but still faces open challenges after its tremendous development in recent decades. One of the big challenges is the narrow bandwidth, as the realization of an invisibility cloak is usually based on a metamaterial-an artificial composite material composed of subwavelength resonator structures that are always associated with dispersion. Different from previous works that have tried to eliminate the material dispersion to enhance the bandwidth of an invisibility cloak, here, it is found that by judiciously harnessing the material dispersion, the bandwidth of the cloak can still be significantly increased. Interestingly, the material dispersion does not violate the law of causality. As a proof of concept, an ultrabroadband terahertz (THz) carpet cloak is experimentally demonstrated through an array of superdispersive microparticles, rendering the target object invisible to detection by both time- and frequency-domain wideband systems. The work presents a feasible invisibility strategy that is closer to practical applications and may pave a brand-new way for the development of dispersion-dominated ultrabroadband metadevices.

6.
Opt Lett ; 47(10): 2478-2481, 2022 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-35561380

RESUMEN

Different from conventional optical waveplates, which suffer from limited functionalities and bulky configurations, metasurfaces provide full-range birefringence control along with unprecedented capabilities of wavefront shaping at any wavelength range of interest with properly designed anisotropic meta-atoms, thereby resulting in miniaturized planar meta-waveplates with excellent and fancy functionalities beyond the conventional counterparts. In this Letter, we design a set of dielectric metasurface quarter-wave plates (QWPs) that enable efficient circular-to-linear polarization conversion along with complete phase control over the converted linearly polarized beam under circularly polarized (CP) excitation. Capitalizing on this meta-QWP platform, we numerically demonstrate two advanced multifunctional meta-QWPs (i.e., a beam-steerer and a focusing metalens) to generate different wavefronts with homogeneous and inhomogeneous linear polarization distributions under CP excitation, mimicking the functionalities of cascaded multi-stage optical components. Owing to the compactness, flexibility, and versatility, such meta-QWPs are capable of integrating more advanced applications in polarization optics.

7.
Opt Express ; 30(7): 12048-12060, 2022 Mar 28.
Artículo en Inglés | MEDLINE | ID: mdl-35473134

RESUMEN

Metalenses can potentially reduce the size and complexity of existing cameras, displays, and other optical devices, owing to their capability of flexible manipulation of the polarization, amplitude, and phase of light. However, metalenses capable of maintaining polarization and broadband wavefront shaping under arbitrarily polarized excitation have not been studied. In this study, we present the first demonstration of a biomimetic moth-eye-shaped metalens for polarization-maintaining, broadband and angle-insensitive focusing under an arbitrarily polarized excitation in the mid-infrared waveband (3.1-8.0 µm). Modulation and focusing efficiencies of 92% and 90%, respectively, were achieved. Moreover, a bifocal moth-eye-shaped metalens operating at normal and oblique incidences was realized. Compared to previously reported metalenses, the one proposed in this study exhibited a better focusing under oblique incidence, ensuring light transmission as effectively as a traditional lens. This study paves the way for the development of polarization-maintaining, broadband, and angle-insensitive microscale optical devices and imaging systems.


Asunto(s)
Biomimética , Mariposas Nocturnas , Animales
8.
Opt Express ; 29(24): 39461-39472, 2021 Nov 22.
Artículo en Inglés | MEDLINE | ID: mdl-34809310

RESUMEN

Metasurfaces offer a unique platform to realize flat lenses, reducing the size and complexity of imaging systems and thus enabling new imaging modalities. In this paper, we designed a bilayer helicity-dependent continuous varifocal dielectric metalens in the near-infrared range. The first layer consists of silicon nanopillars and functions as a half-wave plate, providing the helicity-dependent metasurface by combining propagation phase and geometric phase. The second layer consists of phase-change material Sb2S3 nanopillars and provides tunable propagation phases. Upon excitation with the circularly polarized waves possessing different helicities, the metalens can generate helicity-dependent longitudinal focal spots. Under the excitation of linear polarized light, the helicity-dependent dual foci are generated. The focal lengths in this metalens can be continuously tuned by the crystallization fraction of Sb2S3. The zoom range is achieved from 32.5 µm to 37.2 µm for right circularly polarized waves and from 50.5 µm to 60.9 µm for left circularly polarized waves. The simulated focusing efficiencies are above 75% and 87% for the circularly and linearly polarized waves, respectively. The proposed metalens has potential applications in miniaturized devices, including compact optical communication systems, imaging, and medical devices.

9.
ACS Appl Mater Interfaces ; 13(19): 23081-23091, 2021 May 19.
Artículo en Inglés | MEDLINE | ID: mdl-33957757

RESUMEN

Surface-enhanced Raman scattering (SERS) substrates based on graphene and its derivatives have recently attracted attention among those interested in the detection of trace molecules; however, these substrates generally show poor uniformity, an unsatisfactory enhancement factor, and require a complex fabrication process. Herein, we design and fabricate three-dimensional (3D) graphene/silicon (3D-Gr/Si) heterojunction SERS substrates to detect various types of molecules. Notably, the detection limit of 3D-Gr/Si can reach 10-10 M for rhodamine 6G (R6G) and rhodamine B (RB), 10-7 M for crystal violet (CRV), copper(II) phthalocyanine (CuPc), and methylene blue (MB), 10-8 M for dopamine (DA), 10-6 M for bovine serum albumin (BSA), and 10-5 M for melamine (Mel), which is superior to most reported graphene-based SERS substrates. Besides, the proposed 3D-Gr/Si heterojunction SERS substrates can achieve a high uniformity with relative standard deviations (RSDs) of less than 5%. Moreover, the 3D-Gr/Si SERS substrates are reusable after washing with ethyl alcohol to remove the adsorbed molecules. These excellent SERS performances are attributed to the novel 3D structure and abundantly exposed atomically thin edges, which facilitate charge transfer between 3D-Gr and probe molecules. We believe that the 3D-Gr/Si heterojunction SERS substrates offer potential for practical applications in biochemical molecule detection and provide insight into the design of high-performance SERS substrates.

10.
J Affect Disord ; 286: 49-57, 2021 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-33676263

RESUMEN

BACKGROUND: The existing findings of the longitudinal impact of low-to-moderate drinking on symptomatic depression were controversial, as results ranged from finding no association to finding both a protective and adverse association. METHODS: The present study examined the association between low-to-moderate alcohol consumption and incident depressive symptoms by pooled analysis of three European, American and Chinese representative samples of middle-aged and older adults. RESULTS: A total of 29,506 participants (55.5% female) were included. During 278,782 person-years of follow-up, we found that subjects with low-to-moderate drinking had a significantly lower incidence of depressive symptoms compared to never-drinking subjects, with pooled hazard ratios of 0.87 (95% confidence interval [CI]: 0.79-0.96) for men and 0.87 (95% CI: 0.80-0.95) for women, whereas heavy drinkers failed to show significantly higher risk of depressive symptoms. Furthermore, a J-shaped relation between alcohol consumption and incident depressive symptoms was identified in Chinese men, US men, and UK men and women. LIMITATIONS: The classification of depressive symptoms based on the Center for Epidemiologic Studies Depression Scale may not be completely comparable to diagnosis from a clinical setting. CONCLUSIONS: Low-to-moderate alcohol consumption was significantly associated with a lower risk of depressive symptoms on a long-term basis compared to never drinking. Our results support the threshold of moderate drinking in current US guidelines. However, caution should be exercised in engaging in guideline-concordant drinking habits, for even moderate drinkers are at risk of developing heavy drinking habits and experiencing future alcohol-related problems.


Asunto(s)
Consumo de Bebidas Alcohólicas , Depresión , Anciano , Consumo de Bebidas Alcohólicas/epidemiología , Estudios de Cohortes , Depresión/epidemiología , Femenino , Conductas Relacionadas con la Salud , Humanos , Incidencia , Masculino , Persona de Mediana Edad
12.
Front Optoelectron ; 14(2): 134-147, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-36637669

RESUMEN

Manipulating circularly polarized (CP) electromagnetic (EM) waves at will is significantly important for a wide range of applications ranging from chiral-molecule manipulations to optical communication. However, conventional EM devices based on natural materials suffer from limited functionalities, bulky configurations, and low efficiencies. Recently, Pancharatnam-Berry (PB) phase metasurfaces have shown excellent capabilities in controlling CP waves in different frequency domains, thereby allowing for multi-functional PB meta-devices that integrate distinct functionalities into single and flat devices. Nevertheless, the PB phase has intrinsically opposite signs for two spins, resulting in locked and mirrored functionalities for right CP and left CP beams. Here we review the fundamentals and applications of spin-decoupled metasurfaces that release the spin-locked limitation of PB metasurfaces by combining the orientation-dependent PB phase and the dimension-dependent propagation phase. This provides a general and practical guideline toward realizing spin-decoupled functionalities with a single metasurface for orthogonal circular polarizations. Finally, we conclude this review with a short conclusion and personal outlook on the future directions of this rapidly growing research area, hoping to stimulate new research outputs that can be useful in future applications.

13.
Clin Pharmacokinet ; 60(5): 623-635, 2021 05.
Artículo en Inglés | MEDLINE | ID: mdl-33251573

RESUMEN

BACKGROUND AND OBJECTIVE: Quetiapine and aripiprazole are currently prescribed for pregnant women to treat schizophrenia and bipolar disorder. A dramlatic decline in the plasma concentrations of these two drugs was observed if the doses remained fixed throughout pregnancy. This study aims to develop physiologically based pharmacokinetic (PBPK) models to predict the pharmacokinetics of quetiapine, aripiprazole, and the active aripiprazole metabolite dehydroaripiprazole during pregnancy. METHODS: We developed models using a combined 'bottom-up' and 'top-down' strategy. Models were verified by assessing goodness-of-fit plots and ratios of predicted-to-observed pharmacokinetic parameters. To extrapolate to pregnancy, we considered anatomical, physiological, and metabolic alterations. The in silico models were applied to predict steady-state pharmacokinetics in the three stages of pregnancy and to inform dose selection. RESULTS: We successfully constructed PBPK models that accurately predicted the pharmacokinetics of drugs in the adult population. Predictions suggested that the area under the concentration-time curve at steady state in the first, second, and third trimesters, respectively, decreased by 8.7%, 35.0%, and 49.1% for quetiapine and 12.6%, 38.8%, and 60.9% for the active moiety of aripiprazole. The third-trimester plasma concentrations of quetiapine were below the lower limit of the therapeutic range (100 ng/mL) for most of the time interval, and aripiprazole was entirely unable to reach its effective concentration (150 ng/mL). CONCLUSIONS: According to PBPK predictions, the doses should be increased in the latter two trimesters. We generally recommend that women during late pregnancy take at least 2.5- and 2-times their baseline doses of quetiapine and aripiprazole, respectively.


Asunto(s)
Antipsicóticos , Mujeres Embarazadas , Aripiprazol , Simulación por Computador , Femenino , Humanos , Modelos Biológicos , Embarazo , Fumarato de Quetiapina
14.
Eur J Med Genet ; 63(11): 104021, 2020 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-32755715

RESUMEN

Spondyloepimetaphyseal dysplasias (SEMDs), which comprise a heterogeneous group of autosomal-dominant, autosomal-recessive and X-linked recessive disorders, are characterized by anomalies of the spine, the epiphyses and metaphyses of the long bones, resulting in short stature and osteoarthritic changes of the joints. UFSP2 gene encodes a highly conserved cysteine protease which cleaves two C-terminal residues from ubiquitin-fold modifier 1, an ubiquitin-like post-translational modifier protein. In 2018, Di Rocco, M reported for the first time that a novel heterozygous variant exon 11: c.1277A > C of the UFSP2 gene was the cause to spondyloepimetaphyseal dysplasia mainly manifested as: short stature, anterior vertebral dysplasia, hip dysplasia, flat vertebra, spinal metaphyseal dysplasia, irregular acetabular apex, distal femoral metaphyseal dysplasia, proximal tibial metaphyseal dysplasia, osteoarthritis and so on. In this report, we describe a boy with spondyloepimetaphyseal dysplasia due to a novel mutation exon 11: c.1283A > G (leading to p. H428R) of the UFSP2 gene. This is the second report to describe children with SEMDs associated with an UFSP2 variant. However, it is the first to describe a UFSP2 gene mutation exon 11: c.1283A > G (leading to p. H428R). Our findings of a novel heterozygous mutation of UFSP2 gene add to the list of 2 reported heterozygous mutations of UFSP2 which led to hereditary osteopathy.


Asunto(s)
Cisteína Endopeptidasas/genética , Osteocondrodisplasias/genética , Niño , Heterocigoto , Humanos , Masculino , Mutación Missense , Osteocondrodisplasias/patología
15.
ACS Appl Mater Interfaces ; 12(13): 15606-15614, 2020 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-32157866

RESUMEN

Three-dimensional graphene (3D-Gr) with excellent light absorption properties has received enormous interest, but in conventional processes to prepare 3D-Gr, amorphous carbon layers are inevitably introduced as buffer layers that may degrade the performance of graphene-based devices. Herein, 3D-Gr is prepared on germanium (Ge) using two-dimensional graphene (2D-Gr) as the buffer layer. 2D-Gr as the buffer layer facilitates the in situ synthesis of 3D-Gr on Ge by plasma-enhanced chemical vapor deposition (PECVD) by promoting 2D-Gr nucleation and reducing the barrier height. The growth mechanism is investigated and described. The enhanced light absorption as confirmed by theoretical calculation and 3D-Gr/2D-Gr/Ge with a Schottky junction improves the performance of optoelectronic devices without requiring pre- and post-transfer processes. The photodetector constructed with 3D-Gr/2D-Gr/Ge shows an excellent responsivity of 1.7 A W-1 and detectivity 3.42 × 1014 cm Hz1/2 W-1 at a wavelength of 1550 nm. This novel hybrid structure that incorporates 3D- and 2D-Gr into Ge-based integrated circuits and photodetectors delivers excellent performance and has large commercial potential.

16.
Int J Colorectal Dis ; 34(12): 2151-2159, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-31732877

RESUMEN

PURPOSE: To investigate the influence of organic cation transporter 3 (OCT3) expression on the effect of the combination regimen of 5-fluorouracil, folinic acid and oxaliplatin ((m)FOLFOX6) in colorectal cancer (CRC) patients. METHODS: This is a retrospective study conducted at a single centre (Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, China). Patients with stage IIb-IV resectable CRC who were being postoperatively treated with (m)FOLFOX6 as a first-line adjuvant chemotherapy regimen for at least 5 cycles and had resected primary tumour samples available were eligible for the study. Patients who preoperatively received chemotherapy and/or radiotherapy or were treated with targeted drugs or other anticancer drugs were excluded from the study. Immunohistochemical staining and digital image analysis were used to assess OCT3 expression in tumour samples. According to OCT3 expression level, the receiver operating characteristic curve (ROC curve) was used to divide the patients into two groups. Cox proportional risk regression was performed with the forward LR (forward stepwise regression based on maximum likelihood estimation) method using SPSS17.0 software. The primary endpoint was the 2-year progression-free survival. RESULTS: In total, 57 patients were included between 2014 and 2016 according to the inclusion and exclusion criteria (22 had low OCT3 expression, and 35 had high OCT3 expression). The mean age was 55.7 (30-74) years, and 37 of the total patients were male. According to TNM stage, 5 patients had stage IV disease, 44 patients had stage III disease, and 8 patients had stage II disease. Through Cox regression analysis, we found that among patients receiving the (m)FOLFOX6 regimen, those with higher OCT3 expression had a higher two-year progression-free survival rate than those with lower OCT3 expression (P = 0.038). The hazard ratio of patients with high OCT3 expression compared with patients with low OCT3 expression was 0.247. Besides, it was found that the age of patients was negatively correlated with expression level of OCT3, which can explain why patients over 70 years do not benefit from oxaliplatin-containing chemotherapy. CONCLUSIONS: High OCT3 expression in CRC tissues may be a protective factor for CRC patients treated with (m)FOLFOX6.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Neoplasias Colorrectales/tratamiento farmacológico , Proteínas de Transporte de Catión Orgánico/metabolismo , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Quimioterapia Adyuvante , China , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/mortalidad , Neoplasias Colorrectales/patología , Femenino , Fluorouracilo/administración & dosificación , Fluorouracilo/efectos adversos , Humanos , Leucovorina/administración & dosificación , Leucovorina/efectos adversos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Compuestos Organoplatinos/administración & dosificación , Compuestos Organoplatinos/efectos adversos , Supervivencia sin Progresión , Estudios Retrospectivos , Factores de Tiempo , Regulación hacia Arriba
17.
Pharm Res ; 36(12): 171, 2019 Oct 25.
Artículo en Inglés | MEDLINE | ID: mdl-31654287

RESUMEN

PURPOSE: Physiologically-based pharmacokinetic (PBPK) modeling offers a unique modality to predict age-specific pharmacokinetics. The objective of this study was to assess the ability of PBPK model to predict plasma exposure of oxycodone, a widely used opioid for pain management, in adults and children. METHODS: A full PBPK model of oxycodone following intravenous and oral administration was developed using a 'bottom-up' and 'top-down' combined strategy. The model was then extrapolated to pediatrics through a reasonable scaling method. The adult and pediatric model was evaluated using data from 17 clinical PK studies by testing predicted/observed goodness of fit. The mean fold error for PK parameters was calculated. Finally, we used the validated PBPK model to visualize adult-children dose conversion for oxycodone. RESULTS: The developed PBPK model successfully predicted the oxycodone disposition in adults, wherein the predicted versus observed AUC, Cmax, and tmax were within 0.90 to 1.20-fold difference. After scaling anatomy/physiology, protein binding, and clearance, the model showed satisfactory prediction performance for pediatric populations as predicted AUC were within the 1.50-fold range of the observed values. According to the application of PBPK model, we found that different intravenous doses should be given in children of different ages compared to a standard 0.1 mg/kg in adults, while a progressive increasing dose with age growth following oral administration is recommended for children. CONCLUSIONS: The current example provides the opportunity for using the PBPK model to guide dose adjustment of oxycodone in the design of future pediatric clinical studies.


Asunto(s)
Analgésicos Opioides/farmacocinética , Oxicodona/farmacocinética , Administración Intravenosa , Administración Oral , Adolescente , Adulto , Analgésicos Opioides/administración & dosificación , Niño , Preescolar , Simulación por Computador , Relación Dosis-Respuesta a Droga , Humanos , Lactante , Recién Nacido , Tasa de Depuración Metabólica , Modelos Biológicos , Oxicodona/administración & dosificación , Pediatría
18.
Oncol Rep ; 42(4): 1355-1364, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31524264

RESUMEN

Oxaliplatin (OXA) is routinely used as the first­line treatment for colorectal cancer (CRC). The addition of OXA to chemotherapy has significantly improved the prognosis of patients with CRC; however, some cases are resistant to OXA. The present study explored the influence of organic cation transporter 3 (OCT3) expression on the effects of OXA on CRC cell viability, and investigated the direct effects of OCT3 on viability, invasion and migration of CRC cells using MTT assay, wound healing assay, reverse transcription­quantitative polymerase chain reaction, inductively coupled plasma mass spectrometry and lentiviral interference. The results demonstrated that OXA cellular concentration and OXA­induced cytotoxicity were significantly increased in response to high expression of OCT3, whereas OCT3 knockdown directly increased the invasion and migration of colon cancer cells. Furthermore, upregulation of OCT3 expression in colon cancer xenografts via treatment with the DNA methyltransferase inhibitor decitabine increased cellular OXA concentration and improved the curative effect of OXA. These results collectively indicated that OCT3 may enhance the effects of OXA in CRC cells and may directly inhibit their invasion and migration. Therefore, OCT3 may be a therapeutic target in patients with CRC.

19.
mBio ; 10(5)2019 09 03.
Artículo en Inglés | MEDLINE | ID: mdl-31481383

RESUMEN

Eukaryotic cells share a basic scheme of internal organization featuring membrane-based organelles. The use of fluorescent proteins (FPs) greatly facilitated live-cell imaging of organelle dynamics and protein trafficking. One major limitation of this approach is that the fusion of an FP to a target protein can and often does compromise the function of the target protein and alter its subcellular localization. The optimization process to obtain a desirable fusion construct can be time-consuming or even unsuccessful. In this work, we set out to provide a validated set of FP-based markers for major organelles in the budding yeast (Saccharomyces cerevisiae). Out of over 160 plasmids constructed, we present a final set of 42 plasmids, the recommendations for which are backed up by meticulous evaluations. The tool set includes three colors (green, red, and blue) and covers the endoplasmic reticulum (ER), nucleus, Golgi apparatus, endosomes, vacuoles, mitochondria, peroxisomes, and lipid droplets. The fidelity of the markers was established by systematic cross-comparison and quantification. Functional assays were performed to examine the impact of marker expression on the secretory pathway, endocytic pathway, and metabolic activities of mitochondria and peroxisomes. Concomitantly, our work constitutes a reassessment of organelle identities in this model organism. Our data support the recognition that "late Golgi" and "early endosomes," two seemingly distinct terms, denote the same compartment in yeast. Conversely, all other organelles can be visually separated from each other at the resolution of conventional light microscopy, and quantification results justify their classification as distinct entities.IMPORTANCE Cells contain elaborate internal structures. For eukaryotic cells, like those in our bodies, the internal space is compartmentalized into membrane-bound organelles, each tasked with specialized functions. Oftentimes, one needs to visualize organelles to understand a complex cellular process. Here, we provide a validated set of fluorescent protein-based markers for major organelles in budding yeast. Yeast is a commonly used model when investigating basic mechanisms shared among eukaryotes. Fluorescent proteins are produced by cells themselves, avoiding the need for expensive chemical dyes. Through extensive cross-comparison, we make sure that each of our markers labels and only labels the intended organelle. We also carefully examined if the presence of our markers has any negative impact on the functionality of the cells and found none. Our work also helps answer a related question: are the structures we see really what we think they are?


Asunto(s)
Biomarcadores , Proteínas Fluorescentes Verdes , Orgánulos/ultraestructura , Saccharomyces cerevisiae/ultraestructura , Núcleo Celular , Colorantes , Endocitosis , Retículo Endoplásmico , Endosomas , Células Eucariotas , Aparato de Golgi , Gotas Lipídicas , Mitocondrias , Peroxisomas , Plásmidos , Proteínas de Saccharomyces cerevisiae/análisis , Saccharomycetales , Vacuolas
20.
Adv Ther ; 36(8): 2096-2105, 2019 08.
Artículo en Inglés | MEDLINE | ID: mdl-31148055

RESUMEN

INTRODUCTION: Factors that impact the pharmacokinetics of dapoxetine, a 5-HT selective reuptake inhibitor used for the treatment of premature ejaculation, have not been clearly identified. This study aimed to evaluate the effects of consumption of a high-fat meal and cytochrome P450 (CYP) 2D6 polymorphisms on the pharmacokinetics of dapoxetine in healthy Chinese men. METHODS: Twenty-two healthy volunteers were enrolled and classified based on their CYP2D6 genotype. A single-dose, two-treatment (fasted and fed), two-period, one-sequence pharmacokinetic study was conducted. Plasma concentrations of the drug were determined using LC-MS. Pharmacokinetic parameters were calculated by a noncompartmental analysis. RESULTS: The consumption of food significantly prolonged the time required for dapoxetine to reach its peak concentration and area under the concentration-time curve (AUC0-48) (p < 0.01). Compared with that in *1/*10 and *2/*10 genotypes, the dapoxetine plasma exposure in *10/*10 individuals was notably increased. The AUC0-48 value for *10/*10 was significantly higher than that for *1/*10 and *2/*10 (p < 0.05). CONCLUSION: The obtained results demonstrated that a high-fat meal and the CYP2D6 *10/*10 genotype influence the pharmacokinetic properties of dapoxetine and may thus have potential clinical implications. Future studies focusing on safe dapoxetine dosing based on CYP2D6 genotyping are needed. FUNDING: This study was partially sponsored by Xiamen Fuman Pharmaceutical Co., Ltd. The article processing charges were funded by The People's Hospital of Dujiangyan City.


Asunto(s)
Alelos , Bencilaminas/farmacocinética , Citocromo P-450 CYP2D6/genética , Citocromo P-450 CYP2D6/metabolismo , Dieta Alta en Grasa , Naftalenos/farmacocinética , Eyaculación Prematura/tratamiento farmacológico , Adulto , Área Bajo la Curva , Genotipo , Voluntarios Sanos , Humanos , Masculino , Persona de Mediana Edad
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