RESUMEN
Watercore is a common physiological disease of Rosaceae plants, such as apples (Malus domestica), usually occurring during fruit ripening. Apple fruit with watercore symptoms is prone to browning and rotting, thus losing commercial viability. Sorbitol and calcium ions are considered key factors affecting watercore occurrence in apples. However, the mechanism by which they affect the occurrence of watercore remains unclear. Here, we identified that the transcription factor MdWRKY9 directly binds to the promoter of MdSOT2, positively regulates the transcription of MdSOT2, increases sorbitol content in fruit, and promotes watercore occurrence. Additionally, MdCRF4 can directly bind to MdWRKY9 and MdSOT2 promoters, positively regulating their expression. Since calcium ions can induce the ubiquitination and degradation of the transcription factor MdCRF4, they can inhibit the transcription of MdWRKY9 and MdSOT2 by degrading MdCRF4, thereby reducing the sorbitol content in fruit and inhibiting the occurrence of fruit watercore disease. Our data sheds light on how calcium ions mitigate watercore in fruit, providing molecular-level insights to enhance fruit quality artificially.
Asunto(s)
Calcio , Frutas , Regulación de la Expresión Génica de las Plantas , Malus , Proteínas de Plantas , Sorbitol , Factores de Transcripción , Malus/genética , Malus/metabolismo , Frutas/genética , Frutas/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Calcio/metabolismo , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , Sorbitol/metabolismo , Regiones Promotoras Genéticas/genéticaRESUMEN
Mixed-dimensional heterostructures integrate materials of diverse dimensions with unique electronic functionalities, providing a new platform for research in electron transport and optoelectronic detection. Here, we report a novel covalently bonded one-dimensional/two-dimensional (1D/2D) homojunction structure with robust junction contacts, which exhibits wide-spectrum (from the visible to near-infrared regions), self-driven photodetection, and polarization-sensitive photodetection capabilities. Benefiting from the ultralow dark current at zero bias voltage, the on/off ratio and detectivity of the device reach 1.5 × 103 and 3.24 × 109 Jones, respectively. Furthermore, the pronounced anisotropy of the WSe2 1D/2D homojunction is attributed to its low symmetry, enabling polarization-sensitive detection. In the absence of any external bias voltage, the device exhibits strong linear dichroism for wavelengths of 638 and 808 nm, with anisotropy ratios of 2.06 and 1.96, respectively. These results indicate that such mixed-dimensional structures can serve as attractive building blocks for novel optoelectronic detectors.
RESUMEN
PURPOSE: This study was the first to evaluate the effect of CYP3A5*3 gene polymorphisms on plasma concentration of perampanel (PER) in Chinese pediatric patients with epilepsy. METHODS: We enrolled 98 patients for this investigation. Plasma PER concentrations were measured using liquid chromatography-tandem mass spectrometry. Leftover samples from standard therapeutic drug monitoring were allocated for genotyping analysis. The primary measure of efficacy was the rate of seizure reduction with PER treatment at the final checkup. RESULTS: The plasma concentration showed a linear correlation with the daily dose taken ( r â =â 0.17; P â <â 0.05). The ineffective group showed a significantly lower plasma concentration of PER (490.5â ±â 297.1 vs. 633.8â ±â 305.5â µg/ml; P â =â 0.019). For the mean concentration-to-dose (C/D) ratio, the ineffective group showed a significantly lower C/D ratio of PER (3.2â ±â 1.7 vs. 3.8â ±â 2.0; P â =â 0.040). The CYP3A5*3 CC genotype exhibited the highest average plasma concentration of PER at 562.8â ±â 293.9 ng/ml, in contrast to the CT and TT genotypes at 421.1â ±â 165.6 ng/ml and 260.0â ±â 36.1 ng/ml. The mean plasma PER concentration was significantly higher in the adverse events group (540.8â ±â 285.6 vs. 433.0â ±â 227.2 ng/ml; P â =â 0.042). CONCLUSION: The CYP3A5*3 gene's genetic polymorphisms influence plasma concentrations of PER in Chinese pediatric patients with epilepsy. Given that both efficacy and potential toxicity are closely tied to plasma PER levels, the CYP3A5*3 genetic genotype should be factored in when prescribing PER to patients with epilepsy.
Asunto(s)
Anticonvulsivantes , Citocromo P-450 CYP3A , Epilepsia , Nitrilos , Piridonas , Humanos , Citocromo P-450 CYP3A/genética , Niño , Femenino , Masculino , Epilepsia/tratamiento farmacológico , Epilepsia/genética , Nitrilos/farmacocinética , Piridonas/farmacocinética , Piridonas/administración & dosificación , Piridonas/efectos adversos , Preescolar , Anticonvulsivantes/farmacocinética , Anticonvulsivantes/administración & dosificación , Anticonvulsivantes/efectos adversos , Polimorfismo de Nucleótido Simple/genética , Genotipo , Adolescente , Pueblo Asiatico/genética , Pueblos del Este de AsiaRESUMEN
Influenza virus has the ability to circumvent host innate immune system through regulating certain host factors for its effective propagation. However, the detailed mechanism is still not fully understood. Here, we report that a host sphingolipid metabolism-related factor, sphingosine kinase 2 (SPHK2), upregulated during influenza A virus (IAV) infection, promotes IAV infection in an enzymatic independent manner. The enhancement of the virus replication is not abolished in the catalytic-incompetent SPHK2 (G212E) overexpressing cells. Intriguingly, the sphingosine-1-phosphate (S1P) related factor HDAC1 also plays a crucial role in SPHK2-mediated IAV infection. We found that SPHK2 cannot facilitate IAV infection in HDAC1 deficient cells. More importantly, SPHK2 overexpression diminishes the IFN-ß promoter activity upon IAV infection, resulting in the suppression of type I IFN signaling. Furthermore, ChIP-qPCR assay revealed that SPHK2 interacts with IFN-ß promoter through the binding of demethylase TET3, but not with the other promoters regulated by TET3, such as TGF-ß1 and IL6 promoters. The specific regulation of SPHK2 on IFN-ß promoter through TET3 can in turn recruit HDAC1 to the IFN-ß promoter, enhancing the deacetylation of IFN-ß promoter, therefore leading to the inhibition of IFN-ß transcription. These findings reveal an enzymatic independent mechanism on host SPHK2, which associates with TET3 and HDAC1 to negatively regulate type I IFN expression and thus facilitates IAV propagation.
Asunto(s)
Gripe Humana , Interferón beta , Fosfotransferasas (Aceptor de Grupo Alcohol) , Humanos , Virus de la Influenza A , Gripe Humana/enzimología , Interferón beta/genética , Interferón beta/metabolismo , Fosfotransferasas (Aceptor de Grupo Alcohol)/metabolismo , Replicación ViralRESUMEN
In the field of optics, bound states in the continuum (BICs) are of significant practical importance as they can trap electromagnetic waves spatially, even though their frequency lies within the continuous spectrum. Previous research, however, has shown that BICs localized in optical cavities are highly sensitive to geometric and environmental changes. This sensitivity implies that slight variations can lead to the loss of BICs, necessitating extreme precision in manufacturing, which poses a challenge for practical implementation. To overcome this issue, this study employs topological photonic crystals (PhCs) to engineer topological corner states (TCS) within PhCs. By doing so, it establishes a method for creating topological BICs that are inherently robust against disturbances, thereby enhancing their suitability for real-world applications.
RESUMEN
Signaling desensitization is key to limiting signal transduction duration and intensity. Signal transducer and activator of transcription 1 (STAT1) can mediate type II interferon (IFNγ)-induced immune responses, which are enhanced and inhibited by STAT1 phosphorylation and sumoylation, respectively. Here, we identified an N-MYC interacting protein, NMI, which can enhance STAT1 phosphorylation and STAT1-mediated IFNγ immune responses by binding and sequestering the E2 SUMO conjugation enzyme, UBC9, and blocking STAT1 sumoylation. NMI facilitates UBC9 nucleus-to-cytoplasm translocation in response to IFNγ, thereby inhibiting STAT1 sumoylation. STAT1 phosphorylation at Y701 and sumoylation at K703 are mutually exclusive modifications that regulate IFNγ-dependent transcriptional responses. NMI could not alter the phosphorylation level of sumoylation-deficient STAT1 after IFNγ treatment. Thus, IFNγ signaling is modulated by NMI through sequestration of UBC9 in the cytoplasm, leading to inhibition of STAT1 sumoylation. Hence, NMI functions as a switch for STAT1 activation/inactivation cycles by modulating an IFNγ-induced desensitization mechanism.
Asunto(s)
Interferón gamma , Sumoilación , Interferón gamma/metabolismo , Transducción de Señal , Fosforilación , Factor de Transcripción STAT1/genéticaRESUMEN
BACKGROUND: Information on the efficacy and plasma concentration of perampanel (PER) in Chinese pediatric patients with epilepsy is limited. Therefore, this real-world retrospective study aimed to assess the efficacy, tolerability, and plasma concentration of the maximum dose of PER for epilepsy treatment in Chinese pediatric patients. METHODS: A total of 107 pediatric patients from 2 hospitals in China were enrolled in this study. The plasma concentration of PER was determined using ultrahigh-performance liquid chromatography. The primary efficacy endpoint was the seizure reduction rate after PER treatment at the last follow-up. RESULTS: The response rate to PER therapy was 59.8% (64/107). The authors observed that patients younger than 6 years of age (n = 49) showed a significantly lower concentration-to-dose ratio than patients with ages between 6 and 14 years (n = 58) (2.2 ± 1.7 vs. 3.0 ± 1.8 mcg·mL -1 ·kg·mg -1 , respectively; P < 0.05). Patients who received enzyme-inducing antiseizure medication had significantly lower concentration-to-dose ratios than those who did not receive enzyme-inducing antiseizure medication (EIASM) (2.1 ± 1.8 vs. 3.1 ± 2.0 mcg·mL -1 ·kg·mg -1 , P < 0.05). A total of 37 patients (34.6%) reported treatment adverse events. Patients with somnolence and irritability had a significantly higher PER plasma concentration than the "no treatment-emergent adverse effect" groups ( P < 0.05). CONCLUSIONS: PER is an effective and well-tolerated treatment option for patients with epilepsy. To ensure the clinical efficacy and safety of PER in pediatric patients, it is necessary to monitor its plasma concentrations.
Asunto(s)
Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Epilepsia , Humanos , Niño , Adolescente , Anticonvulsivantes/efectos adversos , Estudios Retrospectivos , Epilepsia/tratamiento farmacológico , Nitrilos , Piridonas/efectos adversos , Resultado del Tratamiento , Quimioterapia CombinadaRESUMEN
One 3D Cd-MOF, namely, {[(HDMA)2][Cd3(L)2]·5H2O·2DMF}n (LCU-124, LCU indicates Liaocheng University), was synthesized from an ether-containing ligand 1,3-bis(3,5-dicarboxylphenoxy)benzene (H4L). Its Ln3+-postmodified samples, Eu3+@LCU-124 and Tb3+@LCU-124, were obtained through cation exchange of dimethylamine cation (HDMA) with Eu3+ and Tb3+. The successful entry of rare earth into LCU-124 by cation exchange modification was verified by IR, XRD, XPS, EDS mapping, and luminescence spectra. The proportion of Eu3+/Tb3+ was adjusted during the modification process, leading to fluorescent materials with different emissions. Luminescence measurements indicated that these complexes exhibited interesting multiresponsive sensing activities toward biomarkers urine acid (UA), quinine (QN), and quinidine (QND). First, LCU-124 has a pronounced quenching effect toward UA with the detection limit of 31.01 µM. After modification, the visualization of the detection was improved significantly and the detection limit of Eu3+@LCU-124 was reduced to 0.868 µM. Second, when QN and QND were present in the suspensions of Eu3+@LCU-124 and Tb3+@LCU-124, strong blue light emission peaks occurred, while the characteristic emission of Eu3+/Tb3+ decreased, forming ratiometric fluorescent sensors with the detection limit in the range of 0.199-9.49 µM. The fluorescent probes have high selectivity, excellent sensitivity recycling, and fast response time (less than 1 min). Besides, a simple logic gate circuit and a range of luminescent mixed matrix membranes were designed to provide simple and fast detection of above biomarkers. Our work indicated that modification of Eu3+/Tb3+ could improve the detection ability significantly.
RESUMEN
PURPOSE: We aimed to investigated the influencing risk factors of voriconazole-induced liver injury in Uygur pediatric patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT). METHODS: This was a prospective cohort design study. High-performance liquid chromatography-mass spectrometry was employed to monitor voriconazole concentration. First-generation sequencing was performed to detect gene polymorphisms. Indicators of liver function were detected at least once before and after voriconazole therapy. RESULTS: Forty-one patients were included in this study, among which, 15 patients (36.6%) had voriconazole-induced liver injury. The proportion of voriconazole trough concentration > 5.5 µg·mL-1 patients within the DILI group (40.0%) was significantly higher compared to the control group (15.4%) (p < 0.05). After administration of voriconazole, the values of ALT (103.3 ± 80.3 U/L) and AST (79.9 ± 60.6 U/L) in the DILI group were higher than that in the control group (24.3 ± 24.8 and 30.4 ± 8.6 U/L) (p < 0.05). There was no significant difference between the two groups in genotype and allele frequencies of CYP2C19*2, CYP2C19*3, CYP2C19*17, and UGT1A4 (rs2011425) (p > 0.05). CONCLUSION: There was a significant correlation between voriconazole-induced liver injury and voriconazole trough concentration in high-risk Uygur pediatric patients with allogeneic HSCT.
Asunto(s)
Antifúngicos , Enfermedad Hepática Inducida por Sustancias y Drogas , Trasplante de Células Madre Hematopoyéticas , Voriconazol , Humanos , Voriconazol/efectos adversos , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Niño , Masculino , Femenino , Estudios Prospectivos , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Enfermedad Hepática Inducida por Sustancias y Drogas/genética , Factores de Riesgo , Antifúngicos/efectos adversos , Preescolar , China , Adolescente , Citocromo P-450 CYP2C19/genética , Trasplante Homólogo/efectos adversosRESUMEN
BACKGROUND: Dual-layer spectral-detector computed tomography (DLCT) may have the potential to evaluate gastric wall thickening. PURPOSE: To evaluate the efficacy of DLCT quantitative parameters in differentiating between benign and malignant thickening of the gastric wall. MATERIAL AND METHODS: A total of 58 patients with "gastric wall thickening" who underwent multi-phase abdominal enhanced DLCT scans were included in this study. Of these patients, 33 were malignant and 25 were benign. Parameters such as iodine concentration (IC), effective atomic number (Zeff), and attenuation of the lesions were measured during the arterial phase (AP) and venous phase (VP). Binary logistic regression was employed to calculate the combined prediction probabilities. The accuracy of the DLCT parameters was assessed using receiver operating characteristic (ROC) curves. RESULTS: The values of IC, nIC, Zeff, normalized Zeff, and attenuation in the AP and VP were significantly higher (all P < 0.05) in the malignant group compared to the benign group. The ROC curves revealed that the IC, Zeff, and attenuation in the VP exhibited high diagnostic performance, with area under the ROC curve (AUC) values of 0.864, 0.862, and 0.840, respectively. The new combination of these three factors and gastric wall thickness had an AUC of 0.884, and the sensitivity and specificity were determined to be 81.8% and 92.0%, respectively. CONCLUSION: Spectral CT parameters, particularly the combination of gastric wall thickness, attenuation, IC, and Zeff in VP, have value in distinguishing between benign and malignant gastric wall thickening.
RESUMEN
Phase engineering of Pt-based intermetallic catalysts has been demonstrated as a promising strategy to optimize catalytic properties for a direct formic acid fuel cell. Pt-Bi intermetallic catalysts are attracting increasing interest due to their high catalytic activity, especially for inhibiting CO poisoning. However, the phase transformation and synthesis of intermetallic compounds usually occurring at high temperatures leads to a lack of control of the size and composition. Here, we report the synthesis of intermetallic ß-PtBi2 and γ-PtBi2 two-dimensional nanoplates with controlled sizes and compositions under mild conditions. The different phases of intermetallic PtBi2 can significantly affect the catalytic performance of the formic acid oxidation reaction (FAOR). The obtained ß-PtBi2 nanoplates exhibit an excellent mass activity of 1.1 ± 0.01 A mgPt-1 for the FAOR, which is 30-fold higher than that of commercial Pt/C catalysts. Moreover, intermetallic PtBi2 demonstrates high tolerance to CO poisoning, as confirmed by in situ infrared absorption spectroscopy.
RESUMEN
This study focused on constructing iron(III)-tetraamidomacrocyclic ligand (FeIII-TAML)-based magnetic nanostructures via a surfactant-assisted self-assembly (SAS) method to enhance the reactivity and recoverability of FeIII-TAML activators, which have been widely employed to degrade various organic contaminants. We have fabricated FeIII-TAML-based magnetic nanomaterials (FeIII-TAML/CTAB@Fe3O4, CTAB refers to cetyltrimethylammonium bromide) by adding a mixed solution of FeIII-TAML and NH3·H2O into another mixture containing CTAB, FeCl2 and FeCl3 solutions. The as-prepared FeIII-TAML/CTAB@Fe3O4 nanocomposite showed relative reactivity compared with free FeIII-TAML as indicated by decomposition of bisphenol A (BPA). Moreover, our results demonstrated that the FeIII-TAML/CTAB@Fe3O4 composite can be separated directly from reaction solutions by magnet adsorption and reused for at least four times. Therefore, the efficiency and recyclability of self-assembled FeIII-TAML/CTAB@Fe3O4 nanostructures will enable the application of FeIII-TAML-based materials with a lowered expense for environmental implication.
Asunto(s)
Compuestos de Bencidrilo , Compuestos Férricos , Nanoestructuras , Fenoles , Compuestos Férricos/química , Cetrimonio , Fenómenos MagnéticosRESUMEN
Insufficient accumulation of lipid nanoparticles (LNPs)-based mRNA vaccines in antigen presenting cells remains a key barrier to eliciting potent antitumor immune responses. Herein, we develop dendritic cells (DCs) targeting LNPs by taking advantage of mannose receptor-mediated endocytosis. Efficient delivery of mRNA to DCs is achieved in vitro and in vivo utilizing the sweet LNPs (STLNPs-Man). Intramuscular injection of mRNA vaccine (STLNPs-Man@mRNAOVA ) results in a four-fold higher uptake by DCs in comparison with commercially used LNPs. Benefiting from its DCs targeting ability, STLNPs-Man@mRNAOVA significantly promotes the antitumor performances, showing a comparable therapeutic efficacy by using one-fifth of the injection dosage as the vaccine prepared from normal LNPs, thus remarkably avoiding the side effects brought by conventional mRNA vaccines. More intriguingly, STLNPs-Man@mRNAOVA exhibits the ability to downregulate the expression of cytotoxic T-lymphocyte-associated protein 4 on T cells due to the blockade of CD206/CD45 axis, showing brilliant potentials in promoting antitumor efficacy combined with immune checkpoint blockade therapy.
Asunto(s)
Vacunas contra el Cáncer , Liposomas , Nanopartículas , Neoplasias , Humanos , Presentación de Antígeno , Vacunas de ARNm , ARN Mensajero/genética , ARN Mensajero/metabolismo , Células Dendríticas/metabolismo , Neoplasias/terapia , Neoplasias/metabolismoRESUMEN
Visual neural plasticity and V1 saliency-detection are vital for efficient-coding of dynamically changing visual inputs. However, how does neural plasticity contribute to saliency-detection of temporal-statistically distributed visual stream remains unclear. Therefore, we adopted randomly presented but unevenly distributed stimuli with multiple orientations, and examined the single-unit responses evoked by this biased orientation-adaptation protocol, by single-unit recordings in the visual thalamo-ventral pathway of cats (of either sex). We found neuronal responses potentiated when the probability of biased orientation was slightly higher than other non-biased ones, and suppressed when the probability became much higher. This single-neuronal short-term bidirectional-plasticity is selectively induced by optimal stimuli, but inter-ocularly transferable. It is inducible in LGN, Area 17 and Area 21a with distinct and hierarchically progressive patterns. With the results of latency-analysis, receptive-field structural test, cortical lesion and simulations, we suggest this bidirectional-plasticity may principally originate from the adaptation-competition between excitatory and inhibitory components of V1 neuronal receptive-field. In our simulation, above bidirectional-plasticity could achieve saliency-detection of dynamic visual inputs. These findings demonstrate a rapid probability-dependant plasticity on the neural coding of visual stream, and suggest its functional role in the efficient-coding and saliency-detection of dynamic environment.SIGNIFICANCE STATEMENTNovel elements within a dynamic visual stream can "pop-up" from the context, vital for rapid response to dynamically changing world. "Saliency-detection" is a promising bottom-up mechanism contributing to efficient selection of visual inputs, wherein visual adaptation also plays a significant role. However, the saliency-detection of dynamic visual stream is poorly understood. Here we found a novel form of visual short-term bidirectional-plasticity in multi-stages of visual system that contributes to saliency-detection of dynamic visual inputs. This bidirectional-plasticity may principally originate from the local balance of excitation-inhibition in primary visual cortex, and propagates to lower and higher visual areas with progressive pattern-change. Our findings suggest the excitation-inhibition balance within visual system contributing to visual efficient-coding.
RESUMEN
The superior performance of machine-learning scoring functions for docking has caused a series of debates on whether it is due to learning knowledge from training data that are similar in some sense to the test data. With a systematically revised methodology and a blind benchmark realistically mimicking the process of prospective prediction of binding affinity, we have evaluated three broadly used classical scoring functions and five machine-learning counterparts calibrated with both random forest and extreme gradient boosting using both solo and hybrid features, showing for the first time that machine-learning scoring functions trained exclusively on a proportion of as low as 8% complexes dissimilar to the test set already outperform classical scoring functions, a percentage that is far lower than what has been recently reported on all the three CASF benchmarks. The performance of machine-learning scoring functions is underestimated due to the absence of similar samples in some artificially created training sets that discard the full spectrum of complexes to be found in a prospective environment. Given the inevitability of any degree of similarity contained in a large dataset, the criteria for scoring function selection depend on which one can make the best use of all available materials. Software code and data are provided at https://github.com/cusdulab/MLSF for interested readers to rapidly rebuild the scoring functions and reproduce our results, even to make extended analyses on their own benchmarks.
Asunto(s)
Benchmarking/métodos , Aprendizaje Automático , Modelos Estadísticos , Algoritmos , Benchmarking/normas , Bases de Datos Factuales , Ligandos , Modelos Moleculares , Conformación Molecular , Unión Proteica , Análisis de Regresión , Reproducibilidad de los Resultados , Flujo de TrabajoRESUMEN
The study of topological photonics has gained significant attention due to its potential application for robust and efficient light manipulation. In this work, we theoretically investigate a two-dimensional photonics crystal that exhibits a topological edge state (TES) and a topological corner state (TCS). Furthermore, we also achieve a coupling between a topological corner state and a trivial cavity (TC), resulting in a phenomenon similar to the electromagnetically induced transparency (EIT) effect. To verify the stability of the EIT-like effect, disorders around TES and TCS are introduced, and the theoretical results show that this structure is immune to the disorders. The achievement of the coupling between topological states can have potential applications in the areas of waveguiding, sensing, and logic gates. It is hoped that this work will contribute to the ongoing efforts in the exploration and utilization of topological photonics.
RESUMEN
We demonstrate vertical integration of nitride-based blue/green micro-light-emitting diodes (µLEDs) stacks with independent junctions control using hybrid tunnel junction (TJ). The hybrid TJ was gown by metal organic chemical vapor deposition (p + GaN) and molecular-beam epitaxy (n + GaN). Uniform blue, green and blue/green emission can be generated from different junction diodes. The peak external quantum efficiency (EQE) of the TJ blue µLEDs and green µLEDs with indium tin oxide contact is 30% and 12%, respectively. The carrier transportation between different junction diodes was discussed. This work suggests a promising approach for vertical µLEDs integration to enhance the output power of single LEDs chip and monolithic µLEDs with different emission colors with independent junction control.
RESUMEN
AlGaN-based UV-A LEDs have wide applications in medical treatment and chemical sensing; however, their efficiencies are still far behind visible LEDs or even shorter wavelengths UV-C counterparts because of the large lattice mismatch between the low-Al-content active region and the AlN substrate. In this report, we investigated the composition and thickness of the quantum barrier in the active region in terms of LED performance. Due to the improved strain management and better carrier confinement, efficient UV-A LEDs (320 nm - 330 nm) with EQEs up to 6.8% were demonstrated, among the highest efficiencies at this wavelength range.
RESUMEN
PURPOSE: We aimed to evaluate the effect of the ABCC2 1249G>A (rs2273697) and -24C>T (rs717620) polymorphisms on lacosamide (LCM) plasma concentrations and the efficacy of LCM in Uygur pediatric patients with epilepsy. METHODS: We analyzed 231 pediatric patients with epilepsy, among which 166 were considered to be LCM responsive. For drug assays, 2-3 mL of venous blood was collected from each patient just before the morning LCM dose was administered (approximately 12 hours after the evening dose, steady-state LCM concentrations). The remaining samples after routine therapeutic drug monitoring were used for genotyping analysis. The χ 2 test and Fisher exact test were utilized for comparative analysis of the allelic and genotypic distribution of ABCC2 polymorphisms between the LCM-resistant and LCM-responsive groups. The Student t test or Mann-Whitney U test was conducted to analyze differences in plasma LCM concentration among pediatric patients with epilepsy with different genotypes. RESULTS: Patients with the ABCC2 1249G>A GA genotype (0.7 ± 0.3 mcg/mL per kg/mg) and AA genotype (0.5 ± 0.3 mcg/mL per kg/mg) showed significantly ( P < 0.001) lower LCM concentration-to-dose (CD) ratios than patients with the GG genotype (1.0 ± 0.4 mcg/mL per kg/mg). Moreover, patients with the ABCC2 -24C>T CT genotype (0.6 ± 0.2 mcg/mL per kg/mg) and TT genotype (0.6 ± 0.3 mcg/mL per kg/mg) presented a significantly ( P < 0.001) lower LCM CD ratio than patients with the CC genotype (1.1 ± 0.4 mcg/mL per kg/mg). CONCLUSIONS: The ABCC2 1249G>A (rs2273697) and ABCC2 -24C>T (rs717620) polymorphisms can affect plasma LCM concentrations and treatment efficacy among a population of Uygur pediatric patients with epilepsy, causing these patients to become resistant to LCM. In clinical practice, ABCC2 polymorphisms should be identified before LCM treatment, and then, the dosage should be adjusted for pediatric patients with epilepsy accordingly.
Asunto(s)
Epilepsia , Proteínas Asociadas a Resistencia a Múltiples Medicamentos , Humanos , Niño , Lacosamida/uso terapéutico , Proteínas Asociadas a Resistencia a Múltiples Medicamentos/genética , Proteínas Asociadas a Resistencia a Múltiples Medicamentos/uso terapéutico , Polimorfismo de Nucleótido Simple/genética , Epilepsia/tratamiento farmacológico , Epilepsia/genética , Proteína 2 Asociada a Resistencia a Múltiples Medicamentos , Genotipo , Anticonvulsivantes/uso terapéuticoRESUMEN
We theoretically realize the tunable Fano resonance in a hybrid structure that allows the coupling between Tamm plasmon-polaritons (TPPs) and graphene surface plasmon-polaritons (SPPs). In this coupling system, a distributed Bragg reflector (DBR)/Ag structure is designed to generate the TPP with a narrow resonance, and the graphene SPP is excited by grating coupling with a broad resonance. The overlap of these two kinds of resonances results in the Fano resonance with a high-quality factor close to 1500. The behaviors of the Fano resonance are discussed carefully, and the results show that both the graphene Fermi level and the incidence angle can actively tune the profile of the Fano resonance. Owing to the ultrasharp spectrum of the tunable Fano resonance, our design may offer an alternative strategy for developing various optoelectronic devices such as filters, sensors, and nonlinear and slow-light devices. Finally, as an example of the potential applications, we apply the tunable Fano resonance to the slow-light effect, a high performance slow-light effect can be achieved, and the group delay can reach up to 52 ps.