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1.
Anal Chem ; 96(29): 12112-12119, 2024 07 23.
Artículo en Inglés | MEDLINE | ID: mdl-38989957

RESUMEN

In situ sensitive detection of multiple biomarkers in a single cell was highly necessary for understanding the pathogenesis mechanism and facilitating disease diagnosis. Herein, a bipolar electrode (BPE)-electrochemiluminescence (ECL) imaging chip was designed for ultrasensitive in situ detection of multiple miRNAs in single cells based on a dual-signal amplification strategy. A single cell was trapped and lysed within the microtrap of the cathode chamber and an HCR amplification process and nanoprobes (Fc/DNA/Fe3O4) were introduced, leading to a large number of electroactive molecules (Fc) being modified on the surface. Under a suitable potential, Fc+ in the cathodic chamber was reduced to Fc and L-012 was oxidized in the anodic chamber according to the electric neutrality principle of the bipolar electrode system, resulting in the ECL signal recorded by EMCCD. Ascribed to the dual-signal amplification, sensitive visual detection of miRNA-21 and miRNA-155 in single cells was achieved. For MCF-7 cells, miRNA-21 and miRNA-155 were calculated to be 4385 and 1932 copies/cell (median), respectively. For HeLa cells, miRNA-21 and miRNA-155 were calculated to be 1843 and 1012 copies/cell (median), respectively. The comprehensive evaluation of two kinds of miRNA could effectively eliminate error signals, and the detection precision was improved by 10%.


Asunto(s)
Técnicas Electroquímicas , Electrodos , Mediciones Luminiscentes , MicroARNs , Análisis de la Célula Individual , MicroARNs/análisis , Humanos , Células HeLa , Células MCF-7 , Límite de Detección
2.
Anal Chem ; 96(22): 9218-9227, 2024 06 04.
Artículo en Inglés | MEDLINE | ID: mdl-38781682

RESUMEN

In situ monitoring of cell secretions and communications plays a fundamental role in screening of disease diagnostic biomarkers and drugs. Quantitative detection of cell secretions and monitoring of intercellular communication have been separately reported, which often rely on target labeling or complex pretreatment steps, inevitably causing damage to the target. Simultaneous in situ noninvasive detection of cell secretions and monitoring of intercellular communication are challenging and have never been reported. Herein, we smartly developed a portable device for in situ label-free monitoring of cell secretions and communications with fluorescence and ion-transport-based nanochannel electrochemistry. Based on the dual signal mode, a series of nonelectroactive secretions were sensitively and accurately quantified. The detection limits for VEGF, MUC1, and ATP were 3.84 pg/mL, 32.7 pg/mL, and 47.4 fM (3σ/S), which were 1/3.9, 1/1.1, and 1/41 of those of commercial ELISA kits, respectively. More interestingly, under the released secretions, the gradual opening of the nanochannel connected the two cells in the left and right chambers of the device; thus, the secretion mediated intercellular communication can be monitored. The proposed platform may provide a promising tool for understanding the mechanism of intercellular communication and discovering new therapeutic targets.


Asunto(s)
Técnicas Electroquímicas , Humanos , Técnicas Electroquímicas/instrumentación , Adenosina Trifosfato/análisis , Adenosina Trifosfato/metabolismo , Mucina-1/análisis , Mucina-1/metabolismo , Comunicación Celular , Factor A de Crecimiento Endotelial Vascular/análisis , Factor A de Crecimiento Endotelial Vascular/metabolismo , Fluorescencia , Límite de Detección
3.
Anal Chem ; 96(5): 2165-2172, 2024 02 06.
Artículo en Inglés | MEDLINE | ID: mdl-38284353

RESUMEN

The profiling of multiple glycans on a single cell is important for elucidating glycosylation mechanisms and accurately identifying disease states. Herein, we developed a closed bipolar electrode (BPE) array chip for live single-cell trapping and in situ galactose and sialic acid detection with the electrochemiluminescence (ECL) method. Methylene blue-DNA (MB-DNA) as well as biotin-DNA (Bio-DNA) codecorated AuNPs were prepared as nanoprobes, which were selectively labeled on the cell surface through chemoselective labeling techniques. The individual cell was captured and labeled in the microtrap of the cathodic chamber, under an appropriate potential, MB molecules on the cellular membrane underwent oxidation, triggering the reduction of [Ru(bpy)3]2+/TPA and consequently generating ECL signals in the anodic chamber. The abundance of MB groups on the single cell enabled selective monitoring of both sialic acid and galactosyl groups with high sensitivity using ECL. The sialic acid and galactosyl content per HepG2 cell were detected to be 0.66 and 0.82 fmol, respectively. Through comprehensive evaluation of these two types of glycans on a single cell, tumor cells, and normal cells could be effectively discriminated and the accuracy of single-cell heterogeneous analysis was improved. Additionally, dynamic monitoring of variations in galactosyl groups on the surface of the single cell was also achieved. This work introduced a straightforward and convenient approach for heterogeneity analysis among single cells.


Asunto(s)
Técnicas Biosensibles , Nanopartículas del Metal , Mediciones Luminiscentes/métodos , Oro , Ácido N-Acetilneuramínico , Técnicas Biosensibles/métodos , Electrodos , ADN , Técnicas Electroquímicas/métodos
4.
Opt Lett ; 49(5): 1349-1352, 2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-38427010

RESUMEN

Due to the intrinsic polarized emission property, polarized emissive materials with anisotropic nanostructures are expected to be potential substitutes for polarizers. Herein, by the template-assisted strategy, well-aligned lead-free metal halide Cs3Cu2I5 nanowire (NW) arrays are fabricated by evaporating the precursor ink in the anodic aluminum oxide (AAO) for polarized emission. The Cs3Cu2I5/AAO composite film emits highly polarized light with a degree of polarization (DOP) of 0.50. Furthermore, by changing the molar ratio of CsI/CuI, the stability of Cs3Cu2I5 precursor inks is improved. Finally, an ultraviolet (UV) light-emitting diode (LED) is adopted to pump the composite film to achieve a blue LED device. The reported Cs3Cu2I5/AAO composite film with highly polarized light emissions will have great potential for polarized emission applications such as liquid crystal display backlights, waveguides, and lasers.

5.
Sensors (Basel) ; 23(19)2023 Oct 08.
Artículo en Inglés | MEDLINE | ID: mdl-37837154

RESUMEN

Currently, the widely used blind source separation algorithm is typically associated with issues such as a sluggish rate of convergence and unstable accuracy, and it is mostly suitable for the separation of independent source signals. Nevertheless, source signals are not always independent of one another in practical applications. This paper suggests a blind source separation algorithm based on the bounded component analysis of the enhanced Beetle Antennae Search algorithm (BAS). Firstly, the restrictive assumptions of the bounded component analysis method are more relaxed and do not require the signal sources to be independent of each other, broadening the applicability of this blind source separation algorithm. Second, the objective function of bounded component analysis is optimized using the improved Beetle Antennae Search optimization algorithm. A step decay factor is introduced to ensure that the beetle does not miss the optimal point when approaching the target, improving the optimization accuracy. At the same time, since only one beetle is required, the optimization speed is also improved. Finally, simulation experiments show that the algorithm can effectively separate independent and dependent source signals and can be applied to blind source separation of images. Compared to traditional blind source separation algorithms, it has stronger universality and has faster convergence speed and higher accuracy compared to the original independent component analysis algorithm.

6.
Anal Chem ; 94(20): 7350-7357, 2022 05 24.
Artículo en Inglés | MEDLINE | ID: mdl-35543747

RESUMEN

Inspired by the promising applications of a closed bipolar electrodes (c-BPEs) system in electrochemiluminescence (ECL) detection of cell adhesion and disease-related biomarkers, here, a gold nanowires array-based c-BPEs system was constructed for cell surface protein detection. Regular and uniform gold nanowires array were prepared by intermittent potentiostatic deposition. Then, two poly(dimethylsiloxane) (PDMS) chips with a hole diameter of 2 mm as a reservoir were placed at both sides of Au nanowires array to construct c-BPEs system. Thionine-functionalized silicon dioxide nanoparticles conjugated to antibody (Ab2-Th@SiO2) were used as the electrochemical probe, while [Ru(bpy)3]2+-wrapped SiO2 nanoparticles (Ru(II)@SiO2) were employed as the ECL signal readout. Taking α-fetoprotein (AFP) as model, the gold nanowires array-based c-BPEs system allowed sensitive detection of AFP at a linear range from 0.002 to 50.0 ng/mL and at least 6 living cells ascribing to the synergetic amplification effect at both sensing and reporting chambers. Besides, the amount of AFP expressed by HepG2 cells was calculated to be 6.71 pg/cell. The presented strategy with high sensitivity provided a promising and universal platform for the detection of other cancer cells and disease-related biomarkers (such as proteins, glycan, miRNA).


Asunto(s)
Técnicas Biosensibles , Nanopartículas del Metal , Nanocables , Técnicas Electroquímicas , Oro , Límite de Detección , Mediciones Luminiscentes , Dióxido de Silicio , alfa-Fetoproteínas
7.
Small ; 18(40): e2203448, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-35980938

RESUMEN

Engineering a versatile nanocomplex integrating effective penetration of the blood-brain barrier (BBB), accurate diagnosis, and boosting therapy has always been an intractable challenge in glioblastoma multiforme (GBM). Herein, biomimetic nanocomplexes (TMPsM) for single intracellular transglutaminase 2 (TG2)-triggered self-assembly imaging and RNAi therapy for GBM are subtly developed. To prove the concept, transferrin receptor (TfR) aptamer-modified brain metastatic tumor cell membrane is prepared as the shell for dual BBB targeting capability and prolonged blood retention time. Upon targeting entering into GBM, hollow MnO2 is decomposed to release KKGKGQQ-tetraphenylethene (Pep-TPE) and siRNA. Owing to TG2 dependence, the non-emissive Pep-TPE would be self-aggregated to induce the emission turn-on in GBM that contain overexpressed TG2. The resulting aggregation-induced emission fluorescence imaging with a high signal-to-noise ratio can achieve the precise localization of the tumor and dynamic detection of TG2 activity, thereby allowing the GBM accurate diagnosis. Notably, the TG2 can be silenced by the released siRNA to cause cell apoptosis and increase chemotherapeutic sensitivity, ultimately realizing excellent antitumor efficacy. In vitro and in vivo results demonstrate that the as-prepared TMPsM indeed possess superior BBB penetration, precise diagnosis, and effective therapy of GBM. The proposed strategy may pioneer a new path for the theranostics of brain tumors.


Asunto(s)
Neoplasias Encefálicas , Glioblastoma , Glioma , Biomimética , Barrera Hematoencefálica/metabolismo , Neoplasias Encefálicas/metabolismo , Línea Celular Tumoral , Glioblastoma/patología , Glioma/diagnóstico por imagen , Glioma/metabolismo , Humanos , Compuestos de Manganeso , Óxidos/farmacología , Proteína Glutamina Gamma Glutamiltransferasa 2 , ARN Interferente Pequeño/metabolismo , Receptores de Transferrina/metabolismo
8.
Anal Chem ; 93(12): 5114-5122, 2021 03 30.
Artículo en Inglés | MEDLINE | ID: mdl-33749243

RESUMEN

The in situ glycan profiling of a single tumor cell plays an important role in personalized cancer treatment. Herein, an integrated microfluidic system was designed for living single-cell trapping and real-time monitoring of galactosyl expression on the surface, combining closed bipolar electrode (BPE) arrays and electrofluorochromic (EFC) imaging. Galactosyl groups on human liver cancer HepG2 cells were used as the model analysts, galactose oxidase (GAO) could selectively oxidize hydroxyl sites of galactosyl groups on the cell surface to aldehydes, and then biotin hydrazide (BH) was used to label the aldehydes by aniline-catalyzed hydrazone ligation. With the biotin-avidin system, nanoprobes were finally introduced to the galactosyl groups on the cell surface with avidin as a bridge, which was prepared by simultaneously assembling ferrocene-DNA (Fc-DNA) and biotin-DNA (Bio-DNA) on gold nanoparticles (AuNPs) due to their large surface area and excellent electrical conductivity. After a labeled single cell was captured in the anodic microchannel, the Fc groups attached on the cell surface were oxidized under suitable potential, and the nonfluorescent resazurin on the cathode was correspondingly reduced to produce highly fluorescent resorufin, collected by fluorescence confocal microscope. The combination of EFC imaging and BPE realized monitoring galactosyl group expression of 5.0 × 108 molecules per cell. Furthermore, the proposed platform had the ability to distinguish a single cancer cell from a normal cell according to the expression level of galactosyl groups and to dynamically monitor the galactosyl group variation on the cell surface, providing a simple and accessible method for the single-cell analysis.


Asunto(s)
Oro , Nanopartículas del Metal , Avidina , Electrodos , Humanos , Polisacáridos
9.
Med Sci Monit ; 27: e931236, 2021 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-34413280

RESUMEN

BACKGROUND This study aimed to investigate the effect of deleting the cannabinoid receptor 2 (CB2) gene on the development of hepatic fibrosis induced by carbon tetrachloride (CCl4) in mice via regulating inflammation. MATERIAL AND METHODS The DNA was extracted from the tails of mice to identify whether the cannabinoid receptor 2 gene was successfully knocked out. A liver fibrosis model was established by an intraperitoneal injection of CCl4 into mice. Hepatic damage and hepatic fibrosis were evaluated by detecting serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and staining paraffin sections of liver tissue with hematoxylin-eosin (HE). The secretion and distribution of collagen in liver tissue were observed by Masson staining. Western blot analysis was performed to detect the expression of a-smooth muscle actin (alpha-SMA), transforming growth factor-ß1 (TGF-ß1), tumor necrosis factor alpha-induced protein 3 (A20), phosphorylated nuclear factor-kB p65 (p-NF-kappaB p65), tumor necrosis factor alpha (TNF-alpha), and interleukin-6 (IL-6) in liver tissue. Reverse transcription-polymerase chain reaction (RT-PCR) was used to detect the expression of IL-6 and TNF-alpha mRNA in liver tissue. RESULTS Compared with the control mice, the mice with CB2 knockout that were exposed to CCl4 exhibited increased liver damage, liver fibrosis, and upregulated alpha-SMA, TGF-ß1, A20, and p-NF-kappaB p65 protein levels. IL-6 and TNF-alpha protein levels and mRNA levels were upregulated. CONCLUSIONS The deletion of the CB2 gene promoted the activation of hepatic stellate cells in mice with liver fibrosis and aggravated liver fibrosis by up-regulating the protein expression of A20 and p-NF-kappaB p65 and inducing inflammatory response, potentially providing new insight into the treatment of liver fibrosis.


Asunto(s)
Regulación de la Expresión Génica , Células Estrelladas Hepáticas/metabolismo , Cirrosis Hepática/etiología , Cirrosis Hepática/metabolismo , FN-kappa B/genética , Receptor Cannabinoide CB2/deficiencia , Proteína 3 Inducida por el Factor de Necrosis Tumoral alfa/genética , Animales , Biomarcadores , Tetracloruro de Carbono/efectos adversos , Colágeno/metabolismo , Modelos Animales de Enfermedad , Susceptibilidad a Enfermedades , Inmunohistoquímica , Hígado/metabolismo , Hígado/patología , Cirrosis Hepática/patología , Ratones , Ratones Noqueados , FN-kappa B/metabolismo , Proteína 3 Inducida por el Factor de Necrosis Tumoral alfa/metabolismo
10.
J Invertebr Pathol ; 184: 107643, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-34224726

RESUMEN

In November 2019, an acute disease outbreak in Australian redclaw crayfish (Cherax quadricarinatus) occurred in a farm in Hubei, China, with a cumulative mortality rate of over 80%. One of the characteristic symptoms of the disease was blisters on the tail. This symptom is also common in diseased Procambarus clarkii every year in this country, but the causative agent has not been determined. This study analyzed the etiological characteristics of this disease. Bacterial isolation and identification combined with high-throughput sequencing analysis were conducted to obtain the microbiota characteristics in the hemolymph, hepatopancreas, and intestines. Results showed that this outbreak was caused by infection from Aeromonas hydrophila and Aeromonas veronii. The underlying cause was stress imposed on crayfish during transferring from outdoor pond to indoor pond because of temperature drops. Aeromonas infection caused remarkable changes in the structure of the microbial composition in the hemolymph, hepatopancreas, and intestines of the crayfish. The abundance of Aeromonas in the hemolymph of the sick crayfish was as high as 99.33%. In particular, KEGG metabolic pathway analysis showed that some antibiotic synthesis, enterobactin biosynthesis, and myo-inositol degradation pathways were abundant in healthy crayfish hemolymphs, which may be the mechanism of maintaining crayfish health. Conversely, inhibition of these pathways led to the disorder of microbiota structure, finally leading to the occurrence of diseases. To the knowledge of the authors, this study was the first to use high-throughput amplicon sequencing targeting the 16S rRNA gene to find the causative bacteria in aquatic animals. This protocol can provide more comprehensive and reliable evidence for pathogen identification, even if the pathogenic bacteria are anaerobes or other hard-to-culture bacteria.


Asunto(s)
Aeromonas hydrophila/fisiología , Aeromonas veronii/fisiología , Astacoidea/microbiología , Animales , China , Hemolinfa/microbiología , Hepatopáncreas/microbiología , Intestinos/microbiología , Cola (estructura animal)/microbiología , Cola (estructura animal)/patología
11.
Anal Chem ; 92(1): 1574-1581, 2020 01 07.
Artículo en Inglés | MEDLINE | ID: mdl-31779307

RESUMEN

Extracellular vesicles (EVs) have the potential to be utilized as disease-specific biomarkers. Although strategies for on-chip isolation and detection of EVs have recently been developed, they need preprocessing of clinical samples and are not accurate enough for disease diagnosis just judging by EVs concentration. Here, we designed an integrated microfluidic device named a plasma separation and EV detection (PS-ED) chip for plasma separation, quantification, and high-throughput protein analysis of EVs directly from clinical whole blood samples. The device included two modules (PS and ED module): the PS module was a six-loop microchannel for rapid separation of plasma from clinical whole blood samples under inertial force; the amount of EVs in the separated plasma kept the same value as in the initial blood samples. The module reduced the mechanical damage to the blood cells and thus reduced the interference of debris or cellular contents from damaged cells during EVs detection; the ED module contained four S-channels for quantification and high-throughput protein analysis of EVs; a wide detection range from 2.5 × 102 to 2.5 × 108 particles/µL with a detection limit of 95 particles/µL was obtained. Through simultanously monitoring three proteins (CD81, CD24, and EpCAM) of EVs, the cancer type can be accurately confirmed. Furthermore, clinical blood sample analysis verified that the proposed device could be used for accurate diagnosis and therapy monitoring of ovarian cancer.


Asunto(s)
Biomarcadores de Tumor/sangre , Antígeno CD24/sangre , Molécula de Adhesión Celular Epitelial/sangre , Vesículas Extracelulares/química , Dispositivos Laboratorio en un Chip , Tetraspanina 28/sangre , Humanos
12.
Small ; 16(48): e2004492, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-33174389

RESUMEN

Exosomes are recognized as promising biomarkers for early cancer diagnosis and prognosis owing to a large amount of biological information they carried. But the key is that single type of exosomal biomarker analysis is not sufficient enough for accurate cancer diagnosis and stage monitoring due to the insufficient information and high false positive signal. To address the challenge, here simultaneous in situ detection of different types of exosomal biomarkers (surface proteins: CD81, ephrin type-A receptor 2, and carbohydrate antigen 19-9; miRNAs: miR-451a, miR-21, and miR-10b) is conducted with a 3D microfluidic chip, which works in conjunction with quantum dot (QD) labeling and vesicle fusion technology. After exosomes are efficiently captured by the microfluidic chip, the quantification of multiple exosomal proteins is achieved by using three kinds of QDs with the same excitation and different emission wavelengths, and virus-mimicking fusogenic vesicles encapsulating three exquisitely engineered molecular beacons are introduced for ultrasensitive detection of multiple exosomal miRNAs without requiring RNA extraction. Through comprehensive profiling different types of exosomal biomarkers, the false positive rate is substantially avoided and the accuracy of cancer diagnosis and stage monitoring is improved to ≈100%, which are critical to cancer effective treatment and favorable prognosis.


Asunto(s)
Exosomas , MicroARNs , Neoplasias , Biomarcadores de Tumor , Humanos , Proteínas de la Membrana , Neoplasias/diagnóstico
13.
Cardiovasc Diabetol ; 19(1): 23, 2020 02 21.
Artículo en Inglés | MEDLINE | ID: mdl-32085772

RESUMEN

BACKGROUND: Many studies have reported the predictive value of the atherogenic index of plasma (AIP) in the progression of atherosclerosis and the prognosis of percutaneous coronary intervention (PCI). However, the utility of the AIP for prediction is unknown after PCI among type 2 diabetes mellitus (T2DM). METHODS: 2356 patients with T2DM who underwent PCI were enrolled and followed up for 4 years. The primary outcome was major cardiovascular and cerebrovascular adverse events (MACCEs), considered to be a combination of cardiogenic death, myocardial infarction, repeated revascularization, and stroke. Secondary endpoints included all-cause mortality, target vessel revascularization (TVR), and non-target vessel revascularization (non-TVR). Multivariate Cox proportional hazards regression modelling found that the AIP was correlated with prognosis and verified by multiple models. According to the optimal cut-off point of the ROC curve, the population was divided into high/low-AIP groups. A total of 821 pairs were successfully matched using propensity score matching. Then, survival analysis was performed on both groups. RESULTS: The overall incidence of MACCEs was 20.50% during a median of 47.50 months of follow-up. The multivariate Cox proportional hazards regression analysis before matching suggested that the AIP was an independent risk factor for the prognosis of T2DM after PCI (hazard ratio [HR] 1.528, 95% CI 1.100-2.123, P = 0.011). According to the survival analysis of the matched population, the prognosis of the high AIP group was significantly worse than that of the low AIP group (HR (95% CI) 1.614 (1.303-2.001), P < 0.001), and the difference was mainly caused by repeat revascularization. The low-density lipoprotein-cholesterol (LDL-C) level did not affect the prognosis of patients with T2DM (P = 0.169), and the effect of the AIP on prognosis was also not affected by LDL-C level (P < 0.001). CONCLUSIONS: The AIP, a comprehensive index of lipid management in patients with T2DM, affects prognosis after PCI. The prognosis of diabetic patients with high levels of the AIP included more MACCEs and was not affected by LDL-C levels. It is recommended to monitor the AIP for lipid management in diabetic patients after PCI and ensure that the AIP is not higher than 0.318. Trial registration This is an observational cohort study that does not involve interventions. So we didn't register. We guarantee that the research is authentic and reliable, and hope that your journal can give us a chance.


Asunto(s)
Glucemia/metabolismo , Enfermedad de la Arteria Coronaria/terapia , Diabetes Mellitus Tipo 2/sangre , Dislipidemias/sangre , Lípidos/sangre , Intervención Coronaria Percutánea , Anciano , Beijing/epidemiología , Biomarcadores/sangre , Enfermedad de la Arteria Coronaria/sangre , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/mortalidad , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/mortalidad , Dislipidemias/diagnóstico , Dislipidemias/mortalidad , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Infarto del Miocardio/mortalidad , Intervención Coronaria Percutánea/efectos adversos , Intervención Coronaria Percutánea/mortalidad , Medición de Riesgo , Factores de Riesgo , Accidente Cerebrovascular/mortalidad , Factores de Tiempo , Resultado del Tratamiento
14.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 37(11): 1217-1221, 2020 Nov 10.
Artículo en Zh | MEDLINE | ID: mdl-33179224

RESUMEN

OBJECTIVE: To explore strategies of prenatal genetic testing for fetuses featuring abnormal skeletal development. METHODS: Clinical data of 17 fetuses with skeletal dysplasia was collected. The results of genetic testing and outcome of pregnancy were analyzed. RESULTS: For 12 fetuses, the femur-to-foot length ratio was less than 0.9. Thirteen fetuses had a positive finding by genetic testing. One fetus was diagnosed with chromosomal aneuploidy, three were diagnosed with microdeletion/microduplications, and nine were diagnosed with hereditary bone diseases due to pathological variants of FGFR3, COL1A2, GPX4 or ALPL genes. CONCLUSION: For fetuses with skeletal dysplasia characterized by short femur, in addition to chromosomal karyotyping and microarray analysis, sequencing of FGFR3 and other bone disease-related genes can improve the diagnostic rate.


Asunto(s)
Enfermedades del Desarrollo Óseo/diagnóstico , Enfermedades del Desarrollo Óseo/genética , Diagnóstico Prenatal , Ultrasonografía Prenatal , Femenino , Feto/diagnóstico por imagen , Pruebas Genéticas , Humanos , Cariotipificación , Embarazo , Receptor Tipo 3 de Factor de Crecimiento de Fibroblastos/genética
15.
Anal Chem ; 91(21): 14036-14042, 2019 11 05.
Artículo en Inglés | MEDLINE | ID: mdl-31603308

RESUMEN

Cancer imaging with minimal background signal and targeted intracellular drug delivery are of vital importance in clinical cancer diagnosis and therapy. Herein, we developed a biomimetic nanoprobe for activated fluorescence imaging and targeted drug delivery. pH-responsive porous coordination polymer nanoparticles (PCP NPs) were first synthesized by a codeposition method, anticancer drug doxorubicin (DOX) was then loaded into PCP NPs through physical and electrostatic adsorption (PCP-DOX), and finally the cell membranes extracted from Bel-7402 cancer cells were coated on the DOX-loaded PCP NPs (PCP-DOX-CM). The fluorescence of DOX was quenched due to the fluorescence resonance energy transfer between DOX and PCP NPs. Under acidic environment inside cancer cells, PCP NPs degraded, DOX was released from PCP-DOX-CM, and the fluorescence of DOX was activated, which was very specific for cancers with a high signal-to-noise ratio. Benefited from immune escaping and homologous targeting ability from cancer cell membranes, compared with PCP-CM and PCP-DOX, PCP-DOX-CM significantly enhanced the cellular endocytosis of DOX in Bel-7402 cancer cells and exhibited excellent cancer therapy effect in vitro. Together, our work provides a useful platform for an activated cancer imaging system and personalized cancer treatment.


Asunto(s)
Antibióticos Antineoplásicos/farmacología , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/tratamiento farmacológico , Doxorrubicina/farmacología , Sistemas de Liberación de Medicamentos , Neoplasias Hepáticas/diagnóstico por imagen , Imagen Óptica , Adsorción , Antibióticos Antineoplásicos/química , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Doxorrubicina/química , Ensayos de Selección de Medicamentos Antitumorales , Vesículas Extracelulares/química , Humanos , Neoplasias Hepáticas/tratamiento farmacológico , Estructura Molecular , Nanopartículas/química , Tamaño de la Partícula , Polímeros/química , Porosidad , Electricidad Estática , Propiedades de Superficie
16.
Anal Chem ; 91(17): 11200-11208, 2019 09 03.
Artículo en Inglés | MEDLINE | ID: mdl-31403276

RESUMEN

Multidrug resistance is a major cause of failure in the clinical cancer therapy, in which the overexpression of P-glycoprotein (P-gp) plays a crucial role. Herein, we fabricate a theranostic nanoprobe with the function of simultaneous detection and inhibition of P-gp to diagnose and combat multidrug-resistant cancer in vitro and in vivo. For constructing the nanoprobe, elacridar modified quantum dots (QDs-Ela), acting as a gatekeeper, are grafted onto the doxorubicin (DOX) loaded, folic acid (FA) decorated mesoporous silica nanoparticles (MSNs). Upon targeted uptake by multidrug-resistant cancer cells, Bel-7402/ADR are used as a model, the acidic environment results in QDs-Ela removal from the nanoprobe, and subsequent DOX release. The removed QDs-Ela could specifically combine with P-gp in the cancer cell membrane and inhibit their active sites, which prevents the efflux of intracellular DOX and increases the retention of DOX. Another way, the fluorescence intensity of the binding QDs-Ela quantifies the P-gp expression level. Subsequently, in vitro and in vivo experiments both demonstrate the enhanced multidrug-resistant cancer therapy efficacy, i.e., nanoprobe has 10 times better curative effect than free DOX. In addition, due to the conjugation of FA, the nanoprobe exhibits a selective cell targeting ability to Bel-7402/ADR cells. This nanoplatform paves a new avenue for the accurate treatment of multidrug-resistant cancers.


Asunto(s)
Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/antagonistas & inhibidores , Antibióticos Antineoplásicos/farmacología , Doxorrubicina/farmacología , Neoplasias Hepáticas/tratamiento farmacológico , Nanopartículas/química , Nanomedicina Teranóstica , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/genética , Animales , Antibióticos Antineoplásicos/química , Línea Celular Tumoral , Doxorrubicina/química , Portadores de Fármacos/química , Resistencia a Múltiples Medicamentos/efectos de los fármacos , Resistencia a Antineoplásicos/efectos de los fármacos , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas Experimentales/diagnóstico , Neoplasias Hepáticas Experimentales/tratamiento farmacológico , Ratones , Ratones Desnudos , Tamaño de la Partícula , Puntos Cuánticos/química , Propiedades de Superficie
17.
Anal Chem ; 91(12): 7902-7910, 2019 06 18.
Artículo en Inglés | MEDLINE | ID: mdl-31135138

RESUMEN

This work reports an electrofluorochromic strategy on the basis of electric field control of fluorescent signal generation on bipolar electrodes (BPEs) for visualizing cancer cell surface glycoprotein (mucin 1). The device included two separate cells: anodic sensing cell and cathodic reporting cell, which were connected by a screen-printing electrode patterned on poly(ethylene terephthalate) (PET) membrane. In the sensing cell, anti-MUC1 antibody immobilized on a chitosan-multiwalled carbon nanotube (CS-MWCNT)-modified anodic BPE channel was used for capturing mucin-1 (MUC1) or MCF-7 cancer cells. Then ferrocene (Fc)-labeled mucin 1 aptamers were introduced through hybridization. Under an applied voltage, the ferrocene was oxidized and the electroactive molecules of 1,4-benzoquinone (BQ) in the cathodic reporting cell were reduced according to electroneutrality. This produced a strongly basic 1,4-benzoquinone anion radical (BQ•-), which turned on the fluorescence of pH-responsive fluorescent molecules of (2-(2-(4-hydroxystyryl)-6-methyl-4 H-pyran-4-ylidene)malononitrile) (SPM) coexisting in the cathode reporting cell for both spectrophotometric detection and imaging. This strategy allowed sensitive detection of MUC1 at a concentration down to 10 fM and was capable of detecting a minimum of three MCF-7 cells. Furthermore, the amount of MUC1 on MCF-7 cells was calculated to be 6.02 × 104 molecules/cell. Our strategy also had the advantages of high temporal and spatial resolution, short response time, and high luminous contrast and is of great significance for human health and the promotion of life science development.


Asunto(s)
Técnicas Biosensibles/instrumentación , Mucina-1/análisis , Aptámeros de Nucleótidos/genética , Aptámeros de Nucleótidos/metabolismo , Secuencia de Bases , Electroquímica , Electrodos , Humanos , Células MCF-7 , Mucina-1/metabolismo , Oxidación-Reducción , Espectrometría de Fluorescencia
18.
Anal Chem ; 91(24): 15804-15810, 2019 12 17.
Artículo en Inglés | MEDLINE | ID: mdl-31718146

RESUMEN

Because of the extremely low solubility of gas pollution, elucidating the pathogenetic mechanism between air pollution and the lung inflammatory response has remained a significant challenge. Here, we develop a bioinspired nanoporous membrane (BNM) with a three-phase interface as a gas exposure model that mimicks the airway mechanism, gas molecules contacting with alveolar cells directly, enabling high cell viability and sensitive inflammatory response analysis. Specifically, the top side of the porous anodic alumina (PAA) membrane was in contact with the medium for cell culture, and the bottom side contacted the gas phase directly for gas exposure. Compared with the two-phase interface, the viability of cells on the BNM was enhanced up to 3-fold. Additionally, results demonstrated that the inflammatory responses of cells stimulated by gas pollution (formaldehyde and benzene as models) from the gas phase were more obvious than those induced by gas pollution from solution, especially the increment of interleukin-2 (IL-2), IL-6, and tumor necrosis factor α (TNF-α), which was almost 2 times greater than that induced by gas pollution from solution. Furthermore, an enzyme inhibitor was introduced to evaluate potential applications of the BNM.


Asunto(s)
Membranas Artificiales , Modelos Biológicos , Nanoporos , Óxido de Aluminio/química , Benceno/toxicidad , Técnicas de Cultivo de Célula , Línea Celular , Supervivencia Celular/efectos de los fármacos , Células Epiteliales/citología , Células Epiteliales/efectos de los fármacos , Células Epiteliales/metabolismo , Formaldehído/toxicidad , Gases/química , Humanos , Interacciones Hidrofóbicas e Hidrofílicas , Inflamación/metabolismo , Inflamación/patología , Interleucina-6/metabolismo , Interleucina-8/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo
19.
Sensors (Basel) ; 19(5)2019 Mar 07.
Artículo en Inglés | MEDLINE | ID: mdl-30866505

RESUMEN

To efficiently harvest environmental micro-energy from shallow soil, simulated analysis, theoretical arithmetic and experimental verification are performed to explore the spatiotemporal rules of heat transfer on a soil/finned tube interface. Simulations are carried out for 36 types of different working conditions, and the empirical formulas for temperature and heat flux are obtained. The temperature and heat flux can be calculated using the formulas if the soil temperature, soil moisture content and finned tube initial temperature are known. The simulations also show that the highest heat flux can reach approximately 0.30 mW/mm², and approximately 1507.96 mW of energy can be harvested through the finned tube. Theoretical arithmetic indicates that the heat transfer rate of the copper finned tube is 76.77% higher than that of the bare tube, the highest rate obtained in any study to date. Results also show that the finned tube should be placed where the soil moisture is greater than 30% to get more heat from the soil. A field experiment is carried out in the city of Harbin in Northeast China, where a thermoelectric power generation device has been installed and temperature data have been monitored for a certain time. The results are in good agreement with those obtained from the simulation analysis. The heat transfer processes and heat transfer steady state on the soil/finned tube interface are revealed in this work and are of great importance for the use of geothermal energy.

20.
Angew Chem Int Ed Engl ; 58(36): 12481-12485, 2019 09 02.
Artículo en Inglés | MEDLINE | ID: mdl-31317609

RESUMEN

A biomimetic conical submicrochannel (tip side ca. 400 nm) with functions of continuously tunable ion rectification and conductance based on thermoresponsive polymer layer-by-layer (LbL) self-assembly is presented. These self-assembled polymers with different layers exhibited a capability to regulate the effective channel diameter, and different ion rectifications/conductance were achieved. By controlling temperature, the conformation and wettability of the assembled polymers were reversibly transformed, thus the ion rectification/conductance could be further adjusted subtly. Owing to the synergistic effect, the ion conductance could be tuned over a wide range spanning three orders of magnitude. Moreover, the proposed system can be applied for on-demand on-off molecule delivery, which was important for disease therapy. This study opens a new door for regulating channel size according to actual demand and sensing big targets with different size with one channel.

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