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Accurate detection and screening of Pb in biological samples is helpful to assess the risk associated with lead pollution to human health. However, conventional atomic spectroscopic instruments are bulky and cumbersome, requiring additional sample pretreatment equipment, and difficult to perform field analysis with. Herein, a portable point discharge (PD) microplasma-optical emission spectrometric (OES) device with online digestion function is designed for field and sensitive determination of lead in biological samples. With rice as a model, online digestion of a batch of six 50 mg samples can be achieved in the HNO3 and H2O2 system within 25 min by a temperature control and timing module. Compared to the conventional microwave digestion, the digestion efficiency of this device reaches 97%. Pb in digestion solution is converted into volatile species by hydride generation (HG) and directly introduced into PD-OES for excitation and detection by a self-designed rotatable and telescopic cutoff gas sampling column. Six samples can be successively detected in 2 min, and argon consumption of the whole process is only <800 mL. Under the optimized conditions, the detection limit of Pb is 0.018 mg kg-1 (0.9 µg L-1) and precision is 3.6%. The accuracy and practicability of the present device are verified by measuring several certified reference materials and real biological samples. By virtue of small size (23.5 × 17 × 8.5 cm3), lightweight (2.5 kg), and low energy consumption (24.3 W), the present device provides a convenient tool for field analysis of toxic elements in biological samples.
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Plomo , Dispositivos Ópticos , Humanos , Peróxido de Hidrógeno , Análisis Espectral/métodos , DigestiónRESUMEN
Single cell phenotypic analysis is significant for clinical diagnosis, treatment, and prognosis of cancer. Accurate differentiation of cancer stem cell (CSC) subpopulations from a large number of cancer cells may become a cancer surveillance tool and provide important implications for the development of new CSC-targeted therapy strategies. Herein, we report a new approach based on dual-isotope inductively coupled plasma quadrupole mass spectrometry (ICP-QMS) for single cell phenotypic analysis. High-throughput single cell sampling was achieved by a spiral channel microfluidic chip for cell focusing and alignment, and single cell analysis was performed with time-resolved ICP-QMS by identifying the highly specific probes. This enables the monitoring of two surface protein markers (EpCAM and MUC1) of three cell types, i.e., HeLa, MCF-7, and HepG2, at single cell level. The analysis of breast cancer stem cells further confirmed its capability in distinguishing rare cell phenotypes. The present study provides promising possibilities for adopting ICP-QMS in biomedical investigations in terms of cell typing, stemness identification of tumor cells, and cell heterogeneity analysis.
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Isótopos , Neoplasias , Humanos , Diferenciación Celular , Células HeLa , Células Madre Neoplásicas , Análisis de la Célula IndividualRESUMEN
A 2D flow cytometry platform, known as CytoLM Plus, was developed for multi-parameter single-cell analysis. Single particles or cells after hydrodynamic alignment in a microfluidic unit undergo first-dimension fluorescence and side scattering dual-channel optical detection. They were thereafter immediately directed to ICP-MS by connecting the microfluidic unit with a high-efficiency nebulizer to facilitate the second-dimension ICP-MS detection. Flow cytometry measurements of fluorescent microspheres evaluated the performance of CytoLM Plus for optical detection. 6434 fluorescence bursts were observed with a valid signal proportion as high as 99.7%. After signal unification and gating analysis, 6067 sets of single-particle signals were obtained with 6.6 and 6.2% deviations for fluorescence burst area and height, respectively. This is fairly comparable with that achieved by a commercial flow cytometer. Afterward, CytoLM Plus was evaluated by 2D flow cytometry measurement of Ag+-incubated and AO-stained MCF-7 cells. A program for 2D single-cell signal unification was developed based on the algorithm of screening in lag time window. In the present case, a lag time window of -4.2 ± 0.09 s was determined by cross-correlation analysis and two-parameter optimization, which efficiently unified the concurrent single-cell signals from fluorescence, side scattering, and ICP-MS. A total of 495 sets of concurrent 2D signals were screened out, and the statistical analysis of these single-cell signals ensured 2D multi-parameter single-cell analysis and data elucidation.
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Algoritmos , Proyectos de Investigación , Humanos , Colorantes , Citometría de Flujo , Análisis de la Célula IndividualRESUMEN
The exploration of cytology mechanisms of nanosilver uptake, toxicity, and detoxification has become an important issue due to its widespread applications. Previous studies have shown differences in the toxic response of mammalian cells to nanosilver. However, the analysis results based on cell populations ignore the impact of cell uptake heterogeneity on the expression of associated stress proteins and cellular physiological activities. In this respect, this work investigated the interaction between silver uptake and metallothionein (MT) expression in individual cells. In addition, we have also preliminarily elucidated the sensitivity variation to AgNPs by using five cell lines, e.g., LX-2, HepG-2, SK-HEP-1, Huh-7, and MDA-MB-231, by adopting a two-dimensional (2D) high-throughput single-cell analysis platform coupling laser-induced fluorescence (LIF) and inductively coupled plasma mass spectrometry (ICP-MS). We developed a 2D data analysis method for one-to-one unification of fluorescence-mass spectrometry signals corresponding to a specific single cell. It indicated that there is no obvious correlation between cellular silver uptake and cell size, and the low MT expression of cells is more sensitive to silver nanoparticles. For each cell line, significant heterogeneity in MT expression was observed. This provides important information for understanding the potential heterogeneous effects of nanosilver on mammalian biological systems. Overall, detoxified cells are more tolerant to nanosilver and normal cells are more tolerant than cancer cells.
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Nanopartículas del Metal , Plata , Animales , Plata/química , Metalotioneína/química , Mamíferos/metabolismo , Análisis de la Célula IndividualRESUMEN
BACKGROUND AND OBJECTIVES: We aimed to apply a novel nutrition screening tool to stroke patients and assess its reliability and validity. METHODS AND STUDY DESIGN: Cross-sectional data among 214 imaging-confirmed stroke patients were collected between 2015 and 2017 in two public hospitals in Hebei, China. Delphi consultation was conducted to evaluate the items in the NRS-S scale. Anthropometric indices including body mass index (BMI), triceps skin fold thickness (TSF), upper arm circumference (AMC) and mid-arm muscle circumference (MAMC) were measured. Internal consistency reliability, test-retest reliability, construct validity and content validity were assessed. In order to estimate content validity, two rounds Delphi consultation of fifteen experts were conducted to evaluate the items in the Nutrition Risk Screening Scale for Stroke (NRS-S). RESULTS: High internal consistency was indicated by Cronbach's alpha of 0.632 and a split-half reliability of 0.629; test-retest reliability of NRS-S items ranged from 0.728 to 1.000 (p<0.0001), except for loss of appetite (0.436, p<0.001) and gastrointestinal symptoms (0.213, p=0.042). Content validity index of 0.89 indicated robust validity of the items. Regarding construct validity, the Kaiser-Meyer-Olkin value was 0.579, and the result of the Bartlett test of sphericity was 166.790 (p<0.001). Three factors were extracted by exploratory factor analysis, which contributed to 63.079% of the variance. Confirmatory factor analysis was performed on the questionnaire, finding the p-value of the model to be 0.321, indicating a high model fitting index. CONCLUSIONS: A novel stroke-specific nutritional risk screening tool demonstrated a relatively high reliability and validity in its clinical application.
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Apetito , Estado Nutricional , Humanos , Reproducibilidad de los Resultados , Estudios Transversales , Índice de Masa Corporal , Encuestas y CuestionariosRESUMEN
Corona virus disease 2019 (COVID-19) is an acute respiratory infectious disease with strong contagiousness, strong variability, and long incubation period. The probability of misdiagnosis and missed diagnosis can be significantly decreased with the use of automatic segmentation of COVID-19 lesions based on computed tomography images, which helps doctors in rapid diagnosis and precise treatment. This paper introduced the level set generalized Dice loss function (LGDL) in conjunction with the level set segmentation method based on COVID-19 lesion segmentation network and proposed a dual-path COVID-19 lesion segmentation network (Dual-SAUNet++) to address the pain points such as the complex symptoms of COVID-19 and the blurred boundaries that are challenging to segment. LGDL is an adaptive weight joint loss obtained by combining the generalized Dice loss of the mask path and the mean square error of the level set path. On the test set, the model achieved Dice similarity coefficient of (87.81 ± 10.86)%, intersection over union of (79.20 ± 14.58)%, sensitivity of (94.18 ± 13.56)%, specificity of (99.83 ± 0.43)% and Hausdorff distance of 18.29 ± 31.48 mm. Studies indicated that Dual-SAUNet++ has a great anti-noise capability and it can segment multi-scale lesions while simultaneously focusing on their area and border information. The method proposed in this paper assists doctors in judging the severity of COVID-19 infection by accurately segmenting the lesion, and provides a reliable basis for subsequent clinical treatment.
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COVID-19 , Humanos , COVID-19/diagnóstico por imagen , Frecuencia Respiratoria , Tomografía Computarizada por Rayos XRESUMEN
Gliosis is a histopathological characteristic of epilepsy that comprises activated microglia and astrocytes. It is unclear whether or how crosstalk occurs between microglia and astrocytes in the evolution of epilepsy. Here, we report in a mouse model of status epilepticus, induced by intracerebroventricular injection of kainic acid (KA), sequential activation of microglia and astrocytes and their close spatial interaction in the hippocampal CA3 region. Microglial ablation reduced astrocyte activation and their upregulation of complement C3. When compared to wild-type mice, both C3-/- and C3aR-/- mice had significantly less microglia-astrocyte interaction in response to KA-induced status epilepticus. Additionally, KA-injected C3-/- mice had significantly less histochemical evidence of neurodegeneration. The results suggest that the C3-C3aR pathway contributes to KA-induced neurodegeneration by mediating microglia-astrocyte communication. The C3-C3aR pathway may prove to be a potential therapeutic target for epilepsy treatment.
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Epilepsia , Estado Epiléptico , Animales , Astrocitos , Complemento C3/genética , Ácido Kaínico/toxicidad , Ratones , Microglía , Estado Epiléptico/inducido químicamenteRESUMEN
Exploring high-efficiency and low-cost bifunctional electrodes for supercapacitors and sensors is significant but challenging. Most of the existing electrodes are mostly single-functional materials with simple structure. Herein, NiCo2O4nanowires as the core and NiMn layered double hydroxide (LDH) as the shell is directly grownin situon carbon cloth (CC) to form a heterostructure (NiMn LDH@NiCo2O4/CC). The performance in supercapacitors and enzyme-free glucose sensing has been systematically studied. Compared with a single NiCo2O4nanowire or NiMn LDH nanosheet, the heterogeneous interface produced by the unique core-shell structure has stronger electronic interaction and abundant active surface area, which shows excellent electrochemical performance. Electrochemical tests demonstrate that the NiMn LDH@NiCo2O4/CC core-shell electrode possesses an area specific capacitance of 2.40 F cm-2and a rate capability of 76.22% at 20 mA cm-2. Simultaneously, asymmetric supercapacitor is assembled with it as the positive electrode and NiFe LDH@NiCo2O4/CC as the negative electrode. The supercapacitor possesses an energy density of 47.74 Wh kg-1when the power density is 175 W kg-1, revealing excellent performance and maintains cycle stability of 93.48% after 6000 cycles at 10 mA cm-2. Additionally, the electrode applied as enzyme-free glucose sensor electrode also displays outstanding sensitivity of 2139µA mM-1cm-2, wide detection range (2µM-3mM and 4-8 mM) and low detection limit of 210 nM, representing good anti-interference performance. This work reveals the multi-metal synergy and rationally designed core-shell structure is critical to the electrochemical performance of bifunctional electrodes.
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Candida albicans is a major fungal pathogen of humans, causing both superficial and life-threatening systemic infections in immunocompromised people. The conserved Ras/cAMP/PKA pathway plays a key role in regulating multiple traits important for the virulence of C. albicans such as cell growth, yeast-hyphal transition, white-opaque switching, sexual reproduction and biofilm development. Diverse external signals influence cell physiology by activating this signaling pathway. The key components of the Ras/cAMP/PKA pathway include two Ras GTPases (Ras1 and Ras2), an adenylyl cyclase (Cyr1, also known as Cdc35), two cyclic nucleotide phosphodiesterases (Pde1 and Pde2) and the catalytic (Tpk1 and Tpk2) and regulatory (Bcy1) subunits of PKA kinase. Activation of this pathway dramatically alters the gene expression profile via several transcription factors, leading to the activation of specific biological processes. Here, we review the progress made in the past two decades to elucidate the molecular mechanisms by which the Ras/cAMP/PKA pathway senses diverse environmental cues and controls specific cellular responses and its connection with other signaling pathways in C. albicans.
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Candida albicans/crecimiento & desarrollo , Proteínas Quinasas Dependientes de AMP Cíclico/metabolismo , AMP Cíclico/metabolismo , Regulación Fúngica de la Expresión Génica , Transducción de Señal , Proteínas ras/metabolismo , Adaptación Fisiológica , Candida albicans/genética , Candida albicans/metabolismo , Candida albicans/patogenicidad , Transcripción GenéticaRESUMEN
BACKGROUND: A hallmark of temporal lobe epilepsy (TLE) is brain inflammation accompanied by neuronal demise. Accumulating evidence demonstrates that Rev-Erbα is involved in regulating neuroinflammation and determining the fate of neurons. Therefore, we studied the expression and cellular distribution of Rev-Erbα in the epileptogenic zone of TLE and the effect of treatment with the Rev-Erbα specific agonist SR9009 in the pilocarpine model. METHODS: The expression pattern of Rev-Erbα was investigated by western blotting, immunohistochemistry, and immunofluorescence labeling in patients with TLE. Next, the effects of SR9009 on neuroinflammation, neuronal apoptosis, and neuronal loss in the mouse hippocampus 7 days after status epilepticus (SE) were assessed by western blotting, immunofluorescence labeling staining, and TUNEL staining. RESULTS: The western blotting, immunohistochemistry, and immunofluorescence labeling results revealed that Rev-Erbα was downregulated in the epileptogenic zone of TLE patients and mainly localized in neurons, astrocytes, and presumably microglia. Meanwhile, the expression of Rev-Erbα was decreased in the hippocampus and temporal neocortex of mice treated with pilocarpine in the early post-SE and chronic phases. Interestingly, the expression of Rev-Erbα in the normal hippocampus showed a 24-h rhythm; however, the rhythmicity was disturbed in the early phase after SE, and this disturbance was still present in epileptic animals. Our further findings revealed that treatment with SR9009 inhibited NLRP3 inflammasome activation, inflammatory cytokine (IL-1ß, IL-18, IL-6, and TNF-α) production, astrocytosis, microgliosis, and neuronal damage in the hippocampus after SE. CONCLUSIONS: Taken together, these results suggested that a decrease in Rev-Erbα in the epileptogenic zone may contribute to the process of TLE and that the activation of Rev-Erbα may have anti-inflammatory and neuroprotective effects.
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Antiinflamatorios/farmacología , Encefalitis/genética , Encefalitis/prevención & control , Epilepsia del Lóbulo Temporal/inducido químicamente , Epilepsia del Lóbulo Temporal/metabolismo , Fármacos Neuroprotectores , Miembro 1 del Grupo D de la Subfamilia 1 de Receptores Nucleares/biosíntesis , Pirrolidinas/farmacología , Tiofenos/farmacología , Adolescente , Adulto , Animales , Convulsivantes , Citocinas/metabolismo , Encefalitis/patología , Epilepsia del Lóbulo Temporal/patología , Regulación de la Expresión Génica , Gliosis/patología , Gliosis/prevención & control , Hipocampo/patología , Humanos , Masculino , Ratones , Ratones Endogámicos C57BL , Miembro 1 del Grupo D de la Subfamilia 1 de Receptores Nucleares/agonistas , Miembro 1 del Grupo D de la Subfamilia 1 de Receptores Nucleares/genética , Pilocarpina , Estado Epiléptico/patología , Estado Epiléptico/prevención & control , Lóbulo Temporal/patología , Adulto JovenRESUMEN
Microglia are the resident immune cells of the center nervous system and participate in various neurological diseases. Here we determined the function of microglia in epileptogenesis using microglial ablation approaches. Three different microglia-specific genetic tools were used, CX3CR1CreER/+:R26iDTA/+, CX3CR1CreER/+:R26iDTR/+, and CX3CR1CreER/+:Csf1rFlox/Flox mice. We found that microglial depletion led to worse kainic acid (KA)-induced status epilepticus, higher mortality rate, and increased neuronal degeneration in the hippocampus. In KA-induced chronic spontaneous recurrent seizures, microglial depletion increased seizure frequency, interictal spiking, and seizure duration. Therefore, microglial depletion aggravates the severity of KA-induced acute and chronic seizures. Interestingly, microglial repopulation reversed the effects of depletion upon KA-induced status epilepticus. Our results demonstrate a beneficial role of microglia in suppressing both acute and chronic seizures, suggesting that microglia are a potential therapeutic target for the management of epilepsy.
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Microglía , Estado Epiléptico , Animales , Modelos Animales de Enfermedad , Hipocampo , Ácido Kaínico , Ratones , Ratones Transgénicos , ConvulsionesRESUMEN
In mammals, chicken-type (c-type) lysozymes are part of the innate immune system, killing bacteria by degrading peptidoglycan in their cell walls. Many of the studies on the evolution of c-type lysozymes have focused on its new digestive function, including the duplicated stomach lysozymes in ruminants. Similarly, in bats, gene duplications and subsequent adaptive evolution of c-type lysozyme have been reported in a clade of insectivorous species, which might have been driven by the need to digest chitin. However, no studies on the evolution of c-type lysozyme have been carried out in the second largest and dietary diverse bat family Phyllostomidae, which includes insectivorous, frugivorous, nectarivorous and sanguivorous species. Here, we sequenced and analyzed c-type lysozyme genes from four phyllostomid bats, the common vampire bat, the white-winged vampire bat, the lesser long-nosed bat and the big fruit-eating bat. Only a single lysozyme gene was identified in each of these species. Evidence for positive selection on mature lysozyme was found on lineages leading to vampire bats, but not other bats with single copy lysozyme genes. Moreover, several amino acid substitutions found in mature lysozymes from the sanguivorous clade are predicted to have functional impacts, adding further evidence for the adaptive evolution of lysozyme in vampire bats. Functional adaptation of vampire bat lysozymes could be associated with anti-microbial defense, possibly driven by the specialized sanguivory-related habits of vampire bats.
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Adaptación Fisiológica/genética , Quirópteros/genética , Muramidasa/genética , Sustitución de Aminoácidos/genética , Aminoácidos/genética , Animales , Evolución Biológica , Evolución Molecular , Duplicación de Gen/genética , Muramidasa/metabolismo , FilogeniaRESUMEN
Filamentous development is associated with the ability to cause infections and colonize the host in pathogenic Candida species. Candida tropicalis is one of the major fungal pathogens of humans. The conserved transcriptional repressor Tup1 plays a critical role in the regulation of transcription and filamentation in yeast species. Despite its central role, the full coding sequence of TUP1 has not been found in the reported genome sequence of C. tropicalis to date. In this study, we report the identification of Tup1 and characterize its role in filamentous growth in C. tropicalis. As expected, C. tropicalis Tup1 exhibits general conserved features to the orthologs of other fungi in terms of its structure and function. Deletion of TUP1 in C. tropicalis leads to increased filamentation under several culture conditions. However, Tup1 indeed exhibits species-specific roles in the regulation of filamentous development in C. tropicalis. For example, unlike the tup1/tup1 mutant of Candida albicans, the tup1/tup1 mutant of C. tropicalis is able to exist in the yeast form at low temperatures or in the presence of N-acetylglucosamine (GlcNAc). Acidic pH conditions also favor the yeast form of the tup1/tup1 mutant of C. tropicalis. Quantitative real-time PCR (qRT-PCR) assays indicate that Tup1 may regulate filamentous development through the transcriptional control of key filamentation regulators in C. tropicalis, such as Ume6, Brg1, Wor1, Sfl2, Ahr1, and Zcf3. Taken together, our findings demonstrate both conserved and species-specific roles of Tup1 in the regulation of filamentation and provide novel insights into the biology of C. tropicalis.
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Candida tropicalis/genética , Proteínas Fúngicas/genética , Regulación Fúngica de la Expresión Génica , Proteínas Represoras/genética , Acetilglucosamina/metabolismo , Candida albicans/genética , Candida albicans/metabolismo , Candida albicans/fisiología , Candida tropicalis/metabolismo , Candida tropicalis/fisiología , Candidiasis/microbiología , Proteínas Fúngicas/metabolismo , Humanos , Concentración de Iones de Hidrógeno , Mutación , Proteínas Represoras/metabolismo , Especificidad de la Especie , TemperaturaRESUMEN
Increasing evidence indicates that inflammatory processes play a crucial role in the etiopathology of epilepsy and seizure disorders. The Toll/IL-1R domain-containing adapter-inducing IFN-ß (TRIF) activated several transcriptions leading to the production of pro-inflammatory cytokines in the central nervous system, which suggests a potential role for TRIF in the epileptogenesis of epilepsy. In this study, we investigated the roles of TRIF in human and mice epileptogenic tissues. Western blot and immunohistochemistry assays showed that the expression of TRIF was significantly upregulated in neurons and glial cells in both human epileptic tissues and mouse models, and positively correlated with seizure frequency. TRIF expression positively correlated with high-mobility group box 1 (HMGB1) expression. In TRIF-deficient mice, electroencephalograms displayed a significant decrease in seizure frequency and duration time, while KA induced seizures compared with wild-type (WT) mice. The number and duration time of spontaneous seizures were also decreased in the chronic KA-induced TRIF-deficient mouse models. In TLR4-deficient hippocampal neurons and mouse models, TRIF expression was lower compared with WT mice during HMGB1 and KA stimulation. Meanwhile, in KA-induced TRIF-deficient mouse models, microglia activation was significantly suppressed; pro-inflammatory factors including IL-1ß, TNF-α, iNOS, HMGB1 and IFN-ß were reduced; and the survival of the neurons in the hippocampus increased compared with WT mice. Our findings suggested that TRIF may be involved in the epileptogenesis of temporal lobe epilepsy, which would make it a potential therapeutic target for the treatment of epilepsy.
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Proteínas Adaptadoras del Transporte Vesicular/metabolismo , Epilepsia del Lóbulo Temporal/metabolismo , Proteínas Adaptadoras del Transporte Vesicular/genética , Adolescente , Adulto , Animales , Niño , Encefalitis/metabolismo , Femenino , Proteína HMGB1/metabolismo , Hipocampo/metabolismo , Humanos , Masculino , Ratones Endogámicos C57BL , Ratones Noqueados , Microglía/metabolismo , Persona de Mediana Edad , Células Piramidales/metabolismo , Lóbulo Temporal/metabolismo , Receptor Toll-Like 4/genética , Adulto JovenRESUMEN
Quantum state transfer from flying photons to stationary matter qubits is an important element in the realization of quantum networks. Self-assembled semiconductor quantum dots provide a promising solid-state platform hosting both single photon and spin, with an inherent light-matter interface. Here, we develop a method to coherently and actively control the single-photon frequency bins in superposition using electro-optic modulators, and measure the spin-photon entanglement with a fidelity of 0.796±0.020. Further, by Greenberger-Horne-Zeilinger-type state projection on the frequency, path, and polarization degrees of freedom of a single photon, we demonstrate quantum state transfer from a single photon to a single electron spin confined in an InGaAs quantum dot, separated by 5 m. The quantum state mapping from the photon's polarization to the electron's spin is demonstrated along three different axes on the Bloch sphere, with an average fidelity of 78.5%.
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BACKGROUND: Focal cortical dysplasia type IIb (FCD IIb) and tuberous sclerosis complex (TSC) are well-recognized causes of chronic intractable epilepsy in children. Accumulating evidence suggests that activation of the microglia/macrophage and concomitant inflammatory response in FCD IIb and TSC may contribute to the initiation and recurrence of seizures. The membrane glycoproteins CD47 and CD200, which are highly expressed in neurons and other cells, mediate inhibitory signals through their receptors, signal regulatory protein α (SIRP-α) and CD200R, respectively, in microglia/macrophages. We investigate the levels and expression pattern of CD47/SIRP-α and CD200/CD200R in surgically resected brain tissues from patients with FCD IIb and TSC, and the potential effect of soluble human CD47 Fc and CD200 Fc on the inhibition of several proinflammatory cytokines associated with FCD IIb and TSC in living epileptogenic brain slices in vitro. The level of interleukin-4 (IL-4), a modulator of CD200, was also investigated. METHODS: Twelve FCD IIb (range 1.8-9.5 years), 13 TSC (range 1.5-10 years) patients, and 6 control cases (range 1.5-11 years) were enrolled. The levels of CD47/SIRP-α and CD200/CD200R were assessed by quantitative real-time polymerase chain reaction and western blot. The expression pattern of CD47/SIRP-α and CD200/CD200R was investigated by immunohistochemical analysis, and the cytokine concentrations were measured by enzyme-linked immune-sorbent assays. RESULTS: Both the messenger RNA and protein levels of CD47, SIRP-α, and CD200, as well as the mRNA level of IL-4, were downregulated in epileptogenic lesions of FCD IIb and TSC compared with the control specimens, whereas CD200R levels were not significantly changed. CD47, SIRP-α, and CD200 were decreasingly expressed in dysmorphic neuron, balloon cells, and giant cells. CD47 Fc and CD200 Fc could inhibit IL-6 release but did not suppress IL-1ß or IL-17 production. CONCLUSIONS: Our results suggest that microglial activation may be partially caused by CD47/SIRP-α- and CD200/CD200R-mediated reductions in the immune inhibitory pathways within FCD IIb and TSC cortical lesions where chronic neuroinflammation has been established. Upregulation or activation of CD47/SIRP-α and CD200/CD200R may have therapeutic potential for controlling neuroinflammation in human FCD IIb and TSC.
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Antígenos CD/biosíntesis , Encéfalo/metabolismo , Antígeno CD47/biosíntesis , Epilepsia/metabolismo , Malformaciones del Desarrollo Cortical de Grupo I/metabolismo , Esclerosis Tuberosa/metabolismo , Western Blotting , Niño , Preescolar , Regulación hacia Abajo , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Inmunohistoquímica , Lactante , Masculino , Microglía/metabolismo , Neuronas/metabolismo , Reacción en Cadena en Tiempo Real de la PolimerasaRESUMEN
Single photons are attractive candidates of quantum bits (qubits) for quantum computation and are the best messengers in quantum networks. Future scalable, fault-tolerant photonic quantum technologies demand both stringently high levels of photon indistinguishability and generation efficiency. Here, we demonstrate deterministic and robust generation of pulsed resonance fluorescence single photons from a single semiconductor quantum dot using adiabatic rapid passage, a method robust against fluctuation of driving pulse area and dipole moments of solid-state emitters. The emitted photons are background-free, have a vanishing two-photon emission probability of 0.3% and a raw (corrected) two-photon Hong-Ou-Mandel interference visibility of 97.9% (99.5%), reaching a precision that places single photons at the threshold for fault-tolerant surface-code quantum computing. This single-photon source can be readily scaled up to multiphoton entanglement and used for quantum metrology, boson sampling, and linear optical quantum computing.
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We investigate temperature-dependent resonance fluorescence spectra obtained from a single self-assembled quantum dot. A decrease of the Mollow triplet sideband splitting is observed with increasing temperature, an effect we attribute to a phonon-induced renormalization of the driven dot Rabi frequency. We also present first evidence for a nonperturbative regime of phonon coupling, in which the expected linear increase in sideband linewidth as a function of temperature is canceled by the corresponding reduction in Rabi frequency. These results indicate that dephasing in semiconductor quantum dots may be less sensitive to changes in temperature than expected from a standard weak-coupling analysis of phonon effects.
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We report a new type of single InAs quantum dot (QD) embedded at the junction of gold-free branched GaAs/AlGaAs nanowire (NW) grown on silicon substrate. The photoluminescence intensity of such QD is ~20 times stronger than that from randomly distributed QD grown on the facet of straight NW. Sharp excitonic emission is observed at 4.2 K with a line width of 101 µeV and a vanishing two-photon emission probability of g(2)(0) = 0.031(2). This new nanostructure may open new ways for designing novel quantum optoelectronic devices.
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Nanoestructuras/química , Nanotecnología , Nanocables/química , Puntos Cuánticos , Arsenicales/química , Diseño de Equipo , Galio/química , Indio/química , SilicioRESUMEN
Eosinophilic oesophagitis (EoE) is an allergen/immune-mediated chronic esophageal disease characterized by esophageal mucosal eosinophilic infiltration and esophageal dysfunction. Although the disease was originally attributed to a delayed allergic reaction to allergens and a Th2-type immune response, the exact pathogenesis is complex, and the efficacy of existing treatments is unsatisfactory. Therefore, the study of the pathophysiological process of EOE has received increasing attention. Animal models have been used extensively to study the molecular mechanism of EOE pathogenesis and also provide a preclinical platform for human clinical intervention studies of novel therapeutic agents. To maximize the use of existing animal models of EOE, it is important to understand the advantages or limitations of each modeling approach. This paper systematically describes the selection of experimental animals, types of allergens, and methods of sensitization and excitation during the preparation of animal models of EoE. It also discusses the utility and shortcomings of each model with the aim of providing the latest perspectives on EoE models and leading to better choices of animal models.