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1.
Hum Mol Genet ; 29(5): 716-726, 2020 03 27.
Artículo en Inglés | MEDLINE | ID: mdl-31600775

RESUMEN

Frontotemporal dementia (FTD) is a common neurogenerative disorder characterized by progressive degeneration in the frontal and temporal lobes. Heterozygous mutations in the gene encoding progranulin (PGRN) are a common genetic cause of FTD. Recently, PGRN has emerged as an important regulator of lysosomal function. Here, we examine the impact of PGRN mutations on the processing of full-length prosaposin to individual saposins, which are critical regulators of lysosomal sphingolipid metabolism. Using FTD-PGRN patient-derived cortical neurons differentiated from induced pluripotent stem cells, as well as post-mortem tissue from patients with FTLD-PGRN, we show that PGRN haploinsufficiency results in impaired processing of prosaposin to saposin C, a critical activator of the lysosomal enzyme glucocerebrosidase (GCase). Additionally, we found that PGRN mutant neurons had reduced lysosomal GCase activity, lipid accumulation and increased insoluble α-synuclein relative to isogenic controls. Importantly, reduced GCase activity in PGRN mutant neurons is rescued by treatment with saposin C. Together, these findings suggest that reduced GCase activity due to impaired processing of prosaposin may contribute to pathogenesis of FTD resulting from PGRN mutations.


Asunto(s)
Demencia Frontotemporal/patología , Glucosilceramidasa/metabolismo , Mutación , Progranulinas/genética , Procesamiento Proteico-Postraduccional , Saposinas/metabolismo , Anciano , Anciano de 80 o más Años , Femenino , Demencia Frontotemporal/enzimología , Demencia Frontotemporal/genética , Células HEK293 , Haploinsuficiencia , Heterocigoto , Humanos , Células Madre Pluripotentes Inducidas/metabolismo , Células Madre Pluripotentes Inducidas/patología , Masculino , Persona de Mediana Edad , Neuronas/metabolismo , Neuronas/patología , Saposinas/química
2.
Mikrochim Acta ; 189(1): 20, 2021 12 08.
Artículo en Inglés | MEDLINE | ID: mdl-34878598

RESUMEN

Integrating other metal ions into mono-metallic metal-organic framework (MOF) to form bi-metallic MOF is an effective strategy to enhance the performance of MOFs from the internal structure. In this study, two-dimensional (2D) cobalt/zinc-porphyrin (Co/Zn-TCPP) MOF nanomaterials with different Co/Zn molar ratios were synthesised using a simple surfactant-assisted method, and novel dopamine (DA) sensing methods were constructed based on these materials. The characterisation results showed that all MOF with different Co/Zn molar ratios presented a nanofilm, and the Co and Zn elements were uniformly distributed. All sensors based on CoxZn100-x-TCPP had a certain catalytic performance to DA. Among them, the sensor based on CO25Zn75-TCPP showed the strongest signal response, indicating that the catalytic performance of MOF on DA can be adjusted by changing the Co/Zn molar ratio. The doping of metal ions improves the chemical environment of the pores, and increases the types and spatial arrangement of the active sites of the MOF, which is beneficial to the electron transfer and exchange with DA; Co2+ and Zn2+ active centres have a synergistic promotion effect, so the catalytic activity of MOF is significantly improved. The linear range at the potential of 0.1 V based on Co25Zn75-TCPP for DA was 5 nM-177.8 µM, with a detection limit of 1.67 nM (S/N = 3). The sensor exhibited a good selectivity for detecting DA. This research is expected to provide new ideas and references for constructing high-performance sensing interfaces and platforms.

3.
J Med Virol ; 92(8): 1059-1064, 2020 08.
Artículo en Inglés | MEDLINE | ID: mdl-31944333

RESUMEN

Enterovirus A71 (EV-A71) is one of the main pathogens causing hand, foot, and mouth disease, and often causes diseases of the central nervous system. Early diagnosis is important to prevent EV-A71 outbreaks. The detection of serum immunoglobulin M (IgM) is widely used for the early diagnosis of EV-A71 in clinics, especially in rural areas. However, this technique requires the extraction of blood from children who have thin blood vessels and who might fear the use of needles. Therefore, difficulties in the detection process are often encountered. This study developed a noninvasive method to detect EV-A71-specific immunoglobulin A (IgA) in saliva for the diagnosis of EV-A71 infection. The sensitivity and specificity of IgA detection did not differ significantly compared with IgM detection. IgA antibodies were present in saliva for a relatively shorter period than IgM antibodies were present in serum. The sensitivity of IgA detection was higher than that of IgM detection for secondary EV-A71 infections. These results suggest that the detection of EV-A71-specific IgA in the saliva allows the effective early diagnosis of EV-A71 and may be suitable for detecting EV-A71 infections in children.


Asunto(s)
Anticuerpos Antivirales/análisis , Infecciones por Enterovirus/diagnóstico , Enterovirus/inmunología , Inmunoglobulina A/análisis , Saliva/inmunología , Preescolar , Enterovirus/genética , Enterovirus/aislamiento & purificación , Infecciones por Enterovirus/inmunología , Humanos , Inmunoglobulina M/sangre , Lactante , Sensibilidad y Especificidad
4.
Nanotechnology ; 31(27): 275501, 2020 Apr 17.
Artículo en Inglés | MEDLINE | ID: mdl-32224515

RESUMEN

In this study, amorphous cobalt hydroxide/polyaniline nanofibers (Co(OH)2/PANINF) composites were successfully prepared. The formation of amorphous Co(OH)2 with irregular surface structure was confirmed by x-ray diffraction, scanning electron microscopy, and selected-area electron diffraction. The non-enzymatic electrochemical sensor for the selective and sensitive determination of dopamine (DA) has been constructed by using Co(OH)2/PANINF composites modified glassy carbon electrode (Co(OH)2/PANINF/GCE), which exhibited excellent electrocatalytic activity toward DA, in a large part owing to the advantages of large surface area of amorphous Co(OH)2 and the synergetic effect between Co(OH)2 and PANINF. The electrochemical kinetics reveal that the DA oxidation involves two electrons and two protons in a quasi-reversible electrode reaction. Differential pulse voltammetry (DPV) studies show remarkable sensing performance for the determination of DA, with a low detection limit of 0.03 µM, and a wide linear range from 0.1 to 200 µM. From a broader perspective, the present study demonstrates that Co(OH)2/PANINF composites would be promising supporting materials for novel sensing platforms.

5.
Anal Bioanal Chem ; 412(25): 6849-6858, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-32740821

RESUMEN

In this study, novel Pd nanowire networks (PdNW) grown on three-dimensional polyaniline hydrogel (3D-PANI) were prepared via a facile one-step electrodeposition approach at a constant potential of - 0.2 V and further utilized as an electrochemical sensing material for sensitive determination of glucose in alkaline medium. Compared with the sensor based on Pd nanofilm (PdNF)/3D-PANI prepared by electrodeposition at - 0.9 V, the sensor based on PdNW/3D-PANI presented substantially enhanced electrocatalytic activity towards glucose oxidation, with an excellent sensitivity of 146.6 µA mM-1 cm-2, a linear range from 5.0 to 9800 µM, and a low detection limit of 0.7 µM and was, therefore, demonstrated to be available for the determination of glucose in human serum. These findings are likely attributed to the combination of advantages of both PdNW and 3D-PANI, which outperformed most other Pd-based non-enzymatic glucose sensors reported earlier. Moreover, this non-enzymatic electrochemical sensor based on PdNW/3D-PANI may serve as an alternative tool for the assay of glucose and possibly other biomolecules. Graphical abstract.


Asunto(s)
Compuestos de Anilina/química , Glucosa/análisis , Hidrogeles/química , Nanocables/química , Paladio/química , Técnicas Biosensibles/métodos , Humanos , Límite de Detección
6.
Mikrochim Acta ; 187(7): 389, 2020 06 16.
Artículo en Inglés | MEDLINE | ID: mdl-32548762

RESUMEN

AuCu/PPy/Cu-TCPP nanocomposites were synthesized by attaching AuCu nanoparticles to a polypyrrole (PPy)-modified 2D Cu-TCPP metal-organic framework nanosheet; Cu-TCPP can exhibit catalytic activity for the reduction of H2O2. Based on the nanocomposite, a new method for the determination of H2O2 was established. The morphology of the AuCu/PPy/Cu-TCPP was analyzed by transmission electron microscopy. Cu-TCPP exhibited a 2D nanosheet with obvious wrinkles, and a large amount of AuCu was uniformly attached to PPy/Cu-TCPP. The composition and structure were studied by X-ray diffraction, FTIR, and X-ray photoelectron spectroscopy. At the optimal working potential and scan rate of - 0.55 V(vs. SCE) and 100 mV/s, respectively, electrochemical studies indicated that in N2-saturated supporting electrolyte, the method showed good catalytic performance for H2O2, with a detection limit of 6.67 nM (S/N = 3), a linear range of 7.10 µM-24.10 mM, and a sensitivity of 35.0 µA mM-1 cm2. Compared to H2O2 methods based on related materials, this method exhibits a wide linear range, and the detection limit is down to nanomolar. Graphical abstract Schematic presentation of the preparation of AuCu/PPy/Cu-TCPP nanocomposites. AuCu/PPy/Cu-TCPP nanocomposite was prepared by loading gold-copper (AuCu) bimetallic nanoparticles with good catalytic properties on two-dimensional copper (II)-porphyrin (Cu-TCPP) nanosheet metal-organic framework material, whose conductivity was improved by polypyrrole (PPy). A method for the determination of hydrogen peroxide by voltammetric was established.

7.
Mikrochim Acta ; 187(1): 89, 2020 01 02.
Artículo en Inglés | MEDLINE | ID: mdl-31897863

RESUMEN

A porous hybrid material was prepared from polydopamine-modified multiwalled carbon nanotubes and reduced graphene oxide. It was employed as a supporting material for an electrochemical hydrazine sensor. Gold nanoparticles with a size of about 13 nm were placed on the material which then was characterized by transmission electron microscopy, field emission-scanning electron microscopy, Raman spectra, FTIR and nitrogen absorption/desorption plots. The material is highly porous and has a specific surface of 290 m2 g-1, which is larger than that of P-MWCNT/rGO alone (149 m2 g-1), and an increased pore volume. It was placed on a glassy carbon electrode (GCE), and cyclic voltammetry, chronoamperometry and amperometric i-t curves were used to characterize the catalytic activity of the sensor. The kinetic parameters of the modified GCE were calculated which proved that it has a high catalytic efficiency in promoting the electron transfer kinetics of hydrazine. The amperometric signal (obtained at a typical working potential of 0.35 V vs. SCE) has two linear ranges, one from 1 µM - 3 mM and one from 3 to 55 mM, with sensitivities of 524 and 98 A mM-1 cm-2, respectively. The detection limit is 0.31 µM. Graphical abstractThe porous nanocomposite was synthesized by etching silver nanoparticles and a enhanced non-enzymatic electrochemical sensor of hydrazine was successfully designed. The electrochemical performances of the modified electrode were also examined.

8.
Anal Chem ; 91(3): 2224-2230, 2019 02 05.
Artículo en Inglés | MEDLINE | ID: mdl-30624055

RESUMEN

Colloidosome is a novel nanostructure composed of millions of colloid particles. In this work, nanosized PbS colloidosomes were initially prepared and applied as nanoprobes for an ultrasensitive immunoassay. The colloidosomes were simply prepared in mild conditions by assembling the elementary approximately 8 nm PbS nanoparticles at the water-in-oil interface of emulsion droplets. To enhance the rigidity and biocompatibility of the colloidosomes, interfacial polymer was introduced by utilizing self-polymerization of dopamine. By treating with dilute nitric acid, a bursting release of lead ions from the colloidosomes occurred and the lead ions can be detected easily by anodic stripping voltammetry. In this way, a colloidosome-based electrochemical immunoassay was developed by using the nanosized PbS colloidosomes as electroactive labels. The proposed method featured a linear calibration range from 10 fg·mL-1 to 100 ng·mL-1 with a low detection limit of 3.4 fg·mL-1 for the detection of human epididymis protein 4. This work introduced a new member for the family of colloidosomes and offered a novel perspective for the rational implementation of various colloidosomes for novel low-abundance cancer biomarkers analysis.


Asunto(s)
Coloides/química , Técnicas Electroquímicas/métodos , Inmunoensayo/métodos , Nanopartículas/química , Proteína 2 de Dominio del Núcleo de Cuatro Disulfuros WAP/análisis , Anticuerpos Inmovilizados/inmunología , Quitosano/química , Técnicas Electroquímicas/instrumentación , Electrodos , Fulerenos/química , Humanos , Indoles/química , Plomo/química , Límite de Detección , Nanocompuestos/química , Tamaño de la Partícula , Polímeros/química , Sulfuros/química , Proteína 2 de Dominio del Núcleo de Cuatro Disulfuros WAP/inmunología
9.
Anal Chem ; 91(8): 5125-5132, 2019 04 16.
Artículo en Inglés | MEDLINE | ID: mdl-30908018

RESUMEN

Label-free biosensing based on the nanoporous anodic alumina (NAA) membrane emerged as a versatile biosensing platform in the recent decade. In the present work, we developed a new immunosensing strategy based on the nanochannels of NAA and the ion pair interaction mediated by electrochemistry of C60. The NAA served as the matrix for the immobilization of the capture antibodies. The incubation of target antigens resulted in the formation of the immunocomplexes and thus an increase of the steric hindrance of the nanochannels. Therefore, the concentration of the redox probe transported through the nanochannels decreases, which can be detected at the working electrode modified with C60. Herein, we initially found that the cathodic peak ascribed to the reduction of C60 to C60- was obviously enhanced by the presence of the redox probe K3[Fe(CN)6] and which was contributed to the formation of a ternary ion association complex among C60, tetraoctylammonium bromide, and K3[Fe(CN)6]. Therefore, the transportation of K3[Fe(CN)6] though the NAA-based bionanochannels can be detected by a C60 modified electrode with an amplified signal. Choosing human epididymis protein 4 (HE4) as the model target, a linear range of 1.0 ng mL-1 to 100 ng mL-1 can be established between the peak current obtained from the differential pulse voltammetric response of the platform and the concentration of HE4. The detection limit was 0.2 ng mL-1. This study not only provides a new avenue to develop the other nanochannel-based biosensing platform for a variety of other disease biomarkers but also contributes to the electrochemistry of fullerene.


Asunto(s)
Óxido de Aluminio/química , Técnicas Biosensibles , Técnicas Electroquímicas , Ferricianuros/análisis , Fulerenos/química , Nanoporos , Nanoestructuras/química , Nanotecnología , Proteína 2 de Dominio del Núcleo de Cuatro Disulfuros WAP/análisis , Aniones/química , Electrodos , Humanos , Mediciones Luminiscentes , Oxidación-Reducción , Tamaño de la Partícula , Porosidad , Propiedades de Superficie
10.
Analyst ; 144(7): 2436-2442, 2019 Mar 25.
Artículo en Inglés | MEDLINE | ID: mdl-30820500

RESUMEN

As is known, the catalytic activity of metal nanocrystals is strongly affected by their size and shape, and the shape has a greater impact. Among them, metal nanocrystals enclosed by high-index facets have attracted significant attention due to their excellent properties. In this study, platinum concave nanocubes (Pt CNC) with different sizes and angles distributed on polyvinyl pyrrolidone-functional graphene oxide (GO) were synthesized by a one-pot hydrothermal process. The platinum concave nanocubes mainly enclosed by {410}, {510}, and {610} were prepared and used as modified glassy carbon electrodes; cyclic voltammetry and chronoamperometry were applied to investigate the difference between the catalytic activities of platinum concave nanocubes with different facets. The electrodes induced efficient electrocatalysis of hydrogen peroxide (H2O2), and the electrode modified with Pt CNC/rGO-220 showed the highest reduction current. H2O2 was detected with a detection limit of 0.7 µM over two wide linear ranges (from 3 µM to 1 mM and from 1 mM to 0.1 M) and with high sensitivities (757.4 µA mM-1 cm-2 and 315.4 µA mM-1 cm-2), respectively. The modified glassy carbon electrodes also exhibited good stability and selectivity.

11.
Analyst ; 144(2): 521-529, 2019 Jan 14.
Artículo en Inglés | MEDLINE | ID: mdl-30398238

RESUMEN

In this work, a novel non-enzymatic hydrogen peroxide sensor, Ag@zeolitic imidazolate framework-67 (Ag@ZIF-67)/glassy carbon electrode (GCE), was fabricated by a simple method at room temperature. The morphology and structure of Ag@ZIF-67 were investigated by scanning electron microscopy, transmission electron microscopy, energy dispersive spectroscopy, Fourier transform infrared spectroscopy, powder X-ray diffraction, atomic absorption spectrophotometry, and N2 absorption isotherms, which indicated that core-shell Ag@ZIF-67 was successfully synthesized with a porous rhombic dodecahedron structure. Electrochemical investigations demonstrated that the Ag@ZIF-67/GCE had strong electrocatalytic activity towards hydrogen peroxide reduction with a low detection limit of 1.5 µM (S/N = 3), a fast response time of 3 s, and three different linear relationships in the ranges of 5.0 µM-275 µM, 775 µM-2775 µM, and 4775 µM-16 775 µM with sensitivities of 27 µA mM-1 cm-2, 13 µA mM-1 cm-2, and 5.3 µA mM-1 cm-2, respectively. Moreover, the fabricated sensor exhibited an excellent recovery rate in real sample analysis of medical hydrogen peroxide disinfectant. These results proved that Ag@ZIF-67/GCE is an effective electrochemical sensor for detecting hydrogen peroxide.

12.
J Nanosci Nanotechnol ; 19(9): 5546-5553, 2019 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-30961708

RESUMEN

A nanocomposite of gold@platinum core-shell nanoparticles on reduced graphene oxide (Au@Ptgraphene) was synthesized by a one-step method and further fabricated into a nanohybrid electrode. This approach not only allows for better structural integration of different components on the electrode but also improves the electrochemical properties in terms of the electrocatalytic activity and capacitive performance. As employed in the electrochemical sensor, the Au@Pt-graphene-modified glassy carbon electrode (GCE) has a wide linear range from 0.5 µmol·L-1 to 22.3 mmol·L-1, a detection limit of 0.2 µmol·L-1, high selectivity, good reproducibility and long-term stability towards the nonenzymatic detection of hydrogen peroxide (H2O2). Furthermore, when used as a binder-free electrode in supercapacitors, this electrode exhibits a high specific capacitance of 345 F·g-1 at a current density of 1 A·g-1, and the specific capacitance retention remains at 96% after 1000 times cycles. These merits enable a versatile electrode material for electrochemical applications.

13.
Mikrochim Acta ; 186(7): 482, 2019 06 27.
Artículo en Inglés | MEDLINE | ID: mdl-31250119

RESUMEN

A non-enzymatic hydrogen peroxide (H2O2) electrochemical sensor material was prepared from silver nanoparticles and a 2D copper-porphyrin framework (MOF). The structure and morphology of the nanocomposite were characterized by scanning electron microscopy, transmission electron microscopy, X-ray diffraction, X-ray photoelectron spectroscopy and Fourier transform infrared spectroscopy. The results showed that the MOF has a two-dimensional sheet structure, and a large number of Ag NPs are uniformly attached to it. The MOF also acts as a peroxidase mimic. The sensor has excellent catalytic performance in terms of H2O2 reduction. Figures of merit include (a) an electrochemical sensitivity of 21.6 µA mM-1 cm-2 at a typical working potential of -0.25 V (vs. SCE), (b) a detection limit of 1.2 µM (at S/N = 3), and (c) a linear response range that extends from 3.7 µM to 5.8 mM. Compared to other sensors of the same type, the linear range of the sensor is extended by an order of magnitude. Graphical abstract Silver nanoparticles (Ag NPs) were reduced with sodium borohydride (NaBH4) on the surface of copper(II)-porphyrin (Cu-TCPP) nanosheets prepared with the assistance of polyvinylpyrrolidone (PVP). Their synergistic effect improved the performance of H2O2 sensor fabricated by immobilizing Ag NPs/Cu-TCPP nanocomposites on glassy carbon electrodes (GCE).

14.
Mikrochim Acta ; 186(8): 509, 2019 07 04.
Artículo en Inglés | MEDLINE | ID: mdl-31273473

RESUMEN

A voltammetric immunoassay for the carcinoembryonic antigen (CEA) was developed using silver metal-organic frameworks (Ag-MOFs) as a signal probe. The Ag-MOFs contained a substantial amount of Ag(I) whose electrochemical signal was relatively stable. Therefore, the Ag-MOFs were viable signal probes. The signal can be detected without previous acid dissolution and preconcentration steps. This simplifies the detection steps and reduces the detection time. If CEA binds to its antibody on the modified electrode, the signal for Ag(I) becomes reduced. Measurements were best performed at a potential as low as 0.07 V (vs. SCE) which made the electrode hardly sensitive to potential electroactive interferents. Under optimized conditions, the method included a wide linear response range (0.05 to 120 ng mL-1) and a low detection limit of 8.0 fg mL-1 (S/N = 3). The synthesis of Ag-MOFs is relatively simple, and Ag-MOFs are not only used as nanocarriers for immobilizing anti-CEA but also acted as electroactive materials for a signal probe. The voltammetric immunoassay is stable, inexpensive, sensitive, and selective. Based on these advantages, the method holds great promise for applications in the point-of-care disease and environmental monitoring. Graphical abstract Schematic presentation of a novel electrochemical immunoassay for the carcinoembryonic antigen (CEA) using silver metal-organic frameworks (Ag-MOFs) as a signal probe.


Asunto(s)
Antígeno Carcinoembrionario/análisis , Inmunoensayo/métodos , Nanopartículas del Metal/química , Estructuras Metalorgánicas/química , Anticuerpos Inmovilizados/química , Anticuerpos Inmovilizados/inmunología , Antígeno Carcinoembrionario/inmunología , Espectroscopía Dieléctrica , Técnicas Electroquímicas , Electrodos , Oro/química , Humanos , Límite de Detección , Ácidos Ftálicos/química , Plata/química
15.
Mikrochim Acta ; 186(4): 238, 2019 03 13.
Artículo en Inglés | MEDLINE | ID: mdl-30868260

RESUMEN

An aptamer based impedimetric assay for the mycotoxin patulin (PAT) is described. A glassy carbon electrode (GCE) was modified with black phosphorus nanosheets (BP NSs) and modified with PAT aptamer by electrostatic attraction. Detection is based on the variations of electron transfer resistance at the modified electrode surface. This assay can detect PAT over a linear range that extends from 1.0 nM to 1.0 µM with a 0.3 nM detection limit. To improve the performance of the sensor, the BP NS-GCE was further modified with gold nanoparticles and then with thiolated PAT aptamer. This modified electrode, operated at an applied potential of 0.18 V (vs. Ag/AgCl), has a wider linear range (0.1 nM to 10.0 µM) and a lower detection limits (0.03 nM). Both assays were successfully applied to the analysis of (spiked) genuine food samples. Graphical abstract Black phosphorus nanosheets (BP NSs) were used to fabricate an aptamer based assay for patulin. To further improve the performance of the electrode, gold nanoparticles (AuNP) were placed on the surface of black phosphorus nanosheets (AuNP-BP NSs) by electrostatic attraction for patulin aptasensing.

16.
Sensors (Basel) ; 19(22)2019 Nov 07.
Artículo en Inglés | MEDLINE | ID: mdl-31703448

RESUMEN

Person verification using online handwritten signatures is one of the most widely researched behavior-biometrics. Many signature verification systems typically require five, ten, or even more signatures for an enrolled user to provide an accurate verification of the claimed identity. To mitigate this drawback, this paper proposes a new elastic curve matching using only one reference signature, which we have named the curve similarity model (CSM). In the CSM, we give a new definition of curve similarity and its calculation method. We use evolutionary computation (EC) to search for the optimal matching between two curves under different similarity transformations, so as to obtain the similarity distance between two curves. Referring to the geometric similarity property, curve similarity can realize translation, stretching and rotation transformation between curves, thus adapting to the inconsistency of signature size, position and rotation angle in signature curves. In the matching process of signature curves, we design a sectional optimal matching algorithm. On this basis, for each section, we develop a new consistent and discriminative fusion feature extraction for identifying the similarity of signature curves. The experimental results show that our system achieves the same performance with five samples assessed with multiple state-of-the-art automatic signature verifiers and multiple datasets. Furthermore, it suggests that our system, with a single reference signature, is capable of achieving a similar performance to other systems with up to five signatures trained.

17.
Sensors (Basel) ; 19(14)2019 Jul 23.
Artículo en Inglés | MEDLINE | ID: mdl-31340513

RESUMEN

This paper proposed a new novel method to adaptively detect gait patterns in real time through the ground contact forces (GCFs) measured by load cell. The curve similarity model (CSM) is used to identify the division of off-ground and on-ground statuses, and differentiate gait patterns based on the detection rules. Traditionally, published threshold-based methods detect gait patterns by means of setting a fixed threshold to divide the GCFs into on-ground and off-ground statuses. However, the threshold-based methods in the literature are neither an adaptive nor a real-time approach. In this paper, the curve is composed of a series of continuous or discrete ordered GCF data points, and the CSM is built offline to obtain a training template. Then, the testing curve is compared with the training template to figure out the degree of similarity. If the computed degree of similarity is less than a given threshold, they are considered to be similar, which would lead to the division of off-ground and on-ground statuses. Finally, gait patterns could be differentiated according to the status division based on the detection rules. In order to test the detection error rate of the proposed method, a method in the literature is introduced as the reference method to obtain comparative results. The experimental results indicated that the proposed method could be used for real-time gait pattern detection, detect the gait patterns adaptively, and obtain a low error rate compared with the reference method.

18.
J Am Chem Soc ; 140(18): 5914-5924, 2018 05 09.
Artículo en Inglés | MEDLINE | ID: mdl-29676907

RESUMEN

ß-Glucocerebrosidase (GCase) mutations cause Gaucher's disease and are a high risk factor in Parkinson's disease. The implementation of a small molecule modulator is a strategy to restore proper folding and lysosome delivery of degradation-prone mutant GCase. Here, we present a potent quinazoline modulator, JZ-4109, which stabilizes wild-type and N370S mutant GCase and increases GCase abundance in patient-derived fibroblast cells. We then developed a covalent modification strategy using a lysine targeted inactivator (JZ-5029) for in vitro mechanistic studies. By using native top-down mass spectrometry, we located two potentially covalently modified lysines. We obtained the first crystal structure, at 2.2 Å resolution, of a GCase with a noniminosugar modulator covalently bound, and were able to identify the exact lysine residue modified (Lys346) and reveal an allosteric binding site. GCase dimerization was induced by our modulator binding, which was observed by native mass spectrometry, its crystal structure, and size exclusion chromatography with a multiangle light scattering detector. Finally, the dimer form was confirmed by negative staining transmission electron microscopy studies. Our newly discovered allosteric site and observed GCase dimerization provide a new mechanistic insight into GCase and its noniminosugar modulators and facilitate the rational design of novel GCase modulators for Gaucher's disease and Parkinson's disease.


Asunto(s)
Sitio Alostérico , Glucosilceramidasa/química , Glucosilceramidasa/metabolismo , Multimerización de Proteína/efectos de los fármacos , Sitio Alostérico/efectos de los fármacos , Cristalografía por Rayos X , Fibroblastos/metabolismo , Glucosilceramidasa/genética , Células HEK293 , Humanos , Espectrometría de Masas , Modelos Moleculares , Estructura Molecular , Mutación
19.
Analyst ; 144(1): 157-160, 2018 Dec 17.
Artículo en Inglés | MEDLINE | ID: mdl-30516177

RESUMEN

Ordered PdCu and Co doped PdCu nanoparticles have been synthesized on graphene oxide (GO). The obtained Co-PdCu/GO composites were used to fabricate a H2O2 electrochemical sensor which exhibits an ultralow LOD (limit of detection) of 1.2 nM and an extra broad linear range of 5 nM-5.774 mM, and has been used to detect H2O2 in living cells successfully.


Asunto(s)
Cobalto/química , Cobre/química , Grafito/química , Peróxido de Hidrógeno/análisis , Nanopartículas del Metal/química , Paladio/química , Animales , Línea Celular Tumoral , Técnicas Electroquímicas/métodos , Límite de Detección , Óxidos/química , Tamaño de la Partícula , Ratas
20.
Anal Bioanal Chem ; 410(5): 1489-1499, 2018 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-29273905

RESUMEN

A fully automated focused infrared microashing sample preparation system was proposed for preparation of biological samples with high organic matter content for the determination of multiple elements combined with inductively coupled plasma optical emission spectroscopy and inductively coupled plasma mass spectrometry. The whole ashing procedure, including sample transfer, carbonization and oxidation of the sample, dissolution of ash, constant volume control, and homogenization of the solution, was automatically controlled. Gold-plated infrared tubes were used to produce and focus infrared radiation to heat the sample. Ozone was used to accelerate the carbonization of samples at a lower temperature to avoid the production of large amounts of empyreumatic oil. In addition, the self-designed double-layer tube serves as a site for ashing and carbonization of the sample and as a container for dissolving ash, as well as for holding the solution. This is the only container in the entire system to reduce the risk of pollution. Eight biological certified reference materials were used as examples to evaluate the performance of the proposed device. A sample ashing pretreatment cycle, from solid sample to liquid solution, took only 40 min and simultaneously treated 12 samples. Except for individual results, the relative errors between the certified values and recorded values for 38 micro and trace elements, including Ca, Mg, Na, P, Li, Be, Sc, Ti, V, Mn, Co, Ni, Cu, Zn, Rb, Sr, Y, Mo, Ag, Cs, Ba, Tl, Th, U, and rare earth elements, were typically less than 30%. The relative standard deviations for five determinations were typically less than 15%. Graphical abstract Automated dry ashing sample preparation system. ICP inductively coupled plasma.


Asunto(s)
Bioensayo , Rayos Infrarrojos , Metales de Tierras Raras/análisis , Oligoelementos/análisis , Automatización , Bioensayo/métodos , Calor , Oxidación-Reducción , Factores de Tiempo
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