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The cognitive neural mechanisms by which sleep deprivation affects cognitive flexibility are poorly understood. Therefore, the study investigated the neuroelectrophysiological basis of the effect of 24 h sleep deprivation on cognitive flexibility in adolescents. 72 participants (36 females, mean age ± SD=20.46 ± 2.385 years old) participated in the study and were randomly assigned to the sleep deprivation group and control group. They were instructed to complete a task switch paradigm, during which participants' behavioral and electroencephalographic data were recorded. Behaviorally, there were significant between-group differences in accuracy. The results of event-related potential showed that the P2, N2 and P3 components had significant group effects or interaction effects. At the time-frequency level, there were statistically significant differences between the delta and theta bands. These results suggested that 24 h sleep deprivation affected problem-solving effectiveness rather than efficiency, mainly because it systematically impaired cognitive processing associated with cognitive flexibility.
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Photocatalytic synthesis of H2O2 is an advantageous and ecologically sustainable alternative to the conventional anthraquinone process. However, achieving high conversion efficiency without sacrificial agents remains a challenge. In this study, two covalent organic frameworks (COF-O and COF-C) were prepared with identical skeletal structures but with their pore walls anchored to different alkyl chains. They were used to investigate the effect of the chemical microenvironment of pores on photocatalytic H2O2 production. Experimental results reveal a change of hydrophilicity in COF-O, leading to suppressed charge recombination, diminished charge transfer resistance, and accelerated interfacial electron transfer. An apparent quantum yield as high as 10.3 % (λ=420â nm) can be achieved with H2O and O2 through oxygen reduction reaction. This is among the highest ever reported for polymer photocatalysts. This study may provide a novel avenue for optimizing photocatalytic activity and selectivity in H2O2 generation.
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Conjugated polymers (CPs) have garnered increasing attention in the field of photocatalysis due to their stability and molecular tunability. Understanding the structure-property relationship in CPs and addressing appropriate molecular design strategies are pivotal to improving the photocatalytic performance of CPs. Herein, a new efficient cyano (CN) engineering approach was proposed to promote the photocatalytic performance of CPs, and three representative CP-based photocatalysts with different CN contents were tailor-made to investigate the relationship between CN functionalization and photocatalytic activity. A series of systematically experimental and theoretical studies reveal that CN functionalization contributes to strengthening the donor-acceptor (D-A) interaction, enhancing the light absorption ability, charge separation/transfer efficiency, and hydrophilicity of CPs, and also facilitating the output of separated photoinduced electrons from CPs to Pt cocatalyst. Thus, the dicyano-functionalized polymer (P-2CN) manifests an attractive photocatalytic performance in hydrogen production. This study provides a facile strategy to develop excellent CP-based photocatalysts for solar fuel production.
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Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by heterogeneous clinical phenotypes. Patients often experience abnormal sensory perception, which may further affect the ASD core phenotype, significantly and adversely affecting their quality of life. However, biomarkers for the diagnosis of ASD sensory perception abnormality are currently elusive. We sought to identify potential biomarkers related to ASD sensory perception abnormality to construct a prediction model that could facilitate the early identification of and screening for ASD. Differentially expressed genes in ASD were obtained from the Gene Expression Omnibus database and were screened for genes related to sensory perception abnormality. After enrichment analysis, the random forest method was used to identify disease-characteristic genes. A prediction model was constructed with an artificial neural network. Finally, the results were validated using data from the dorsal root ganglion, cerebral cortex, and striatum of the BTBR T+ Itpr3tf/J (BTBR) ASD mouse model. A total of 1869 differentially expressed genes in ASD were screened, among which 16 genes related to sensory perception abnormality were identified. According to enrichment analysis, these 16 genes were mainly related to actin, cholesterol metabolism, and tight junctions. Using random forest, 15 disease-characteristic genes were screened for model construction. The area under the curve of the training set validation result was 0.999, and for the model function validation, the result was 0.711, indicating high accuracy. The validation of BTBR mice confirmed the reliability of using these disease-characteristic genes for prediction of ASD. In conclusion, we developed a highly accurate model for predicting ASD sensory perception abnormality from 15 disease-characteristic genes. This model provides a new method for the early identification and diagnosis of ASD sensory perception abnormality.
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Trastorno del Espectro Autista , Ratones , Animales , Trastorno del Espectro Autista/diagnóstico , Trastorno del Espectro Autista/genética , Trastorno del Espectro Autista/metabolismo , Calidad de Vida , Reproducibilidad de los Resultados , Ratones Endogámicos , Percepción , Modelos Animales de EnfermedadRESUMEN
Conjugated polymers (CPs) represent a promising platform for photocatalytic CO2 fixation owing to their suitable band structures that meet the requirements of the reduction potential of CO2 to value-added fuels. However, the photocatalytic performance of CPs is rather restrained by the low charge transfer efficiency. Herein, we rationally designed three CPs with a more delocalized electronic transmission channel and planar molecular structure, which are regarded to evidently reduce the exciton binding energy (Eb ) and accelerate the internal charge transfer process. Besides, the assembly of suitable electron-output "tentacles" and cocatalysts on the surface of CPs could effectively facilitate interfacial electron delivery. Accordingly, the optimal P-2CN exhibits an apparent quantum yield of 4.6 % at 420â nm for photocatalytic CO2 to CO. Further adjusting the amounts of cyano groups and cocatalysts, the CO selectivity could be obtained in the range of 0-80.5 %.
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Covalent triazine frameworks (CTFs) represent promising polymeric photocatalysts for photocatalytic hydrogen production with visible light. However, the separation and transfer of charges in CTFs are isotropic because of the uniform distribution of donor-acceptor motifs in the skeleton. Herein, to achieve the anisotropic charge carrier separation and migration, thiophene (Th) or benzothiadiazole (BT) unit is selected as the dopant to modify the molecular structure of CTF-based photocatalysts. Both theoretical and experimental studies reveal that the incorporation of Th or BT units induces the anisotropic charge carrier separation and migration at the interface of CTFs. The optimized polymer manifests a much enhanced photocatalytic activity for photocatalytic hydrogen production with visible light, and thus this study provides a useful tool to design conjugated polymer photocatalysts at the molecular level for solar energy conversion.
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Autism spectrum disorder (ASD) is a neurodevelopmental disorder. Abnormal lipid metabolism has been suggested to contribute to its pathogenesis. Further exploration of its underlying biochemical mechanisms is needed. In a search for reliable biomarkers for the pathophysiology of ASD, hippocampal tissues from the ASD model BTBR T+ Itpr3tf/J (BTBR) mice and C57BL/6J mice were analyzed, using four-dimensional (4D) label-free proteomic analysis and bioinformatics analysis. Differentially expressed proteins were significantly enriched in lipid metabolic pathways. Among them, apolipoprotein A-I (ApoA-I) is a hub protein and its expression was significantly higher in the BTBR mice. The investigation of protein levels (using Western blotting) also confirmed this observation. Furthermore, expressions of SphK2 and S1P in the ApoA-I pathway both increased. Using the SphK inhibitor (SKI-II), ASD core phenotype and phenotype-related protein levels of P-CREB, P-CaMKII, and GAD1 were improved, as shown via behavioral and molecular biology experiments. Moreover, by using SKI-II, we found proteins related to the development and function of neuron synapses, including ERK, caspase-3, Bax, Bcl-2, CDK5 and KCNQ2 in BTBR mice, whose levels were restored to protein levels comparable to those in the controls. Elucidating the possible mechanism of ApoA-I in ASD-associated phenotypes will provide new ideas for studies on the etiology of ASD.
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Trastorno del Espectro Autista , Ratones , Animales , Trastorno del Espectro Autista/metabolismo , Ratones Endogámicos C57BL , Proteómica , Apolipoproteína A-I , Ratones Endogámicos , Modelos Animales de EnfermedadRESUMEN
OBJECTIVES: To compare the diagnostic value of high frame rate contrast-enhanced ultrasound (H-CEUS) in distinguishing gallbladder adenomas from cholesterol polyp lesions with that of CEUS. METHODS: This study enrolled 94 patients with gallbladder polyp lesions (GPLs) who underwent laparoscopic cholecystectomy. CEUS and H-CEUS were performed before surgery. The perfusion features of GPLs and the final diagnosis as determined by both technologies were compared. RESULTS: There were differences in vascular types between gallbladder adenomas and cholesterol polyp lesions observed on H-CEUS (p < 0.05), while there were no differences in vascular types between gallbladder adenomas and cholesterol polyp lesions observed on CEUS (p > 0.05). In the cholesterol polyp lesion group, there were no differences in vascular types between CEUS and H-CEUS (p > 0.05), while the vascular types were different between CEUS and H-CEUS in the gallbladder adenoma group (p < 0.05). The diagnostic value of H-CEUS in distinguishing gallbladder adenomas from cholesterol polyp lesions was better than that of CEUS. CONCLUSIONS: H-CEUS improved the time resolution by increasing the frame rate, which helped to accurately reflect the difference in the microcirculation of GPLs and improved the ability of a differential diagnosis between cholesterol polyp lesions and adenomas. H-CUES may provide an effective means of imaging for patients with GPLs regarding the choice of treatment options. KEY POINTS: ⢠High frame rate CEUS improves the time resolution of CEUS by increasing the frame rate. ⢠High frame rate CEUS is helpful to accurately evaluate the microvascular morphology of a gallbladder polyp lesion in the arterial phase. ⢠High frame rate CEUS helps patients with gallbladder polyp lesions to choose the appropriate treatment means.
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Adenoma , Neoplasias de la Vesícula Biliar , Pólipos , Adenoma/diagnóstico por imagen , Adenoma/patología , Colesterol , Medios de Contraste , Diagnóstico Diferencial , Vesícula Biliar/diagnóstico por imagen , Neoplasias de la Vesícula Biliar/diagnóstico , Humanos , Pólipos/diagnóstico por imagen , UltrasonografíaRESUMEN
Semiconductor-based photocatalysts have received extensive attention for their promising capacity in confronting global energy and environmental issues. In photocatalysis, a large band gap with suitable edge-position is necessary to warrant enough driving force for reaction, whereas a much smaller band gap is needed for visible-light response and high solar energy conversion efficiency. This paradox hinders the development of photocatalysts. Via state-of-the-art first-principles calculations, we find that the transition dipole moments (TDMs) are changed significantly in O-doped partly polymerized g-C3N4, i.e., OH-terminated polymeric heptazine imide (PHI-OH), and concomitantly, an enhancement of visible-light absorption is achieved; meanwhile a large enough band gap can provide a powerful driving force in the photocatalytic watersplitting reaction. Furthermore, by using TDM analysis of the PHI-OH/BC3N heterostructure, direct light excited transition between two building layers can be confirmed, suggesting it as a candidate catalyst for hydrogen evolution. From TDM analysis of the PHI-OH/BCN heterostructure, we also verify a Z-scheme process, which involves simultaneous photoexcitations with strong reducibility and oxidizability. Thus, TDM could be a good referential descriptor for revealing photocatalytic mechanisms in semiconductor photocatalysts and interlayer photoexcitation behavior in layered heterostructures. Hopefully, more strategies via modification of TDMs would be proposed to enhance the visible-light response of a semiconductor without sacrificing its photocatalytic driving force.
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BACKGROUND/AIMS: This study aimed to investigate the effects of the VR-10 TSP-1 synthetic polypeptide on cytokines and the proliferation and migration of endothelial cells, as well as exploring a new method for anti-ocular neoangiogenesis. METHODS: We measured the proliferation of RF/6A cells by an MTT assay and investigated the migration of RF/6A cells by a Transwell chamber assay. We examined the mRNA transcript levels of TGF-ß2, VEGF, PEDF, Bcl-2 and FasL in RF/6A cells by RT-PCR and evaluated the expression of Fas and caspase-3 proteins in RF/6A cells by western blot analysis. RESULTS: 1. TSP-1 (1 µg/ml) and synthetic peptide VR-10 (0.1 µg/ml, 1 µg/ml and 10 µg/ml) inhibited the proliferation of RF/6A cells in a time and dose-dependent way. 2. TSP-1 and synthetic peptide VR-10 could inhibit the migration of RF/6A cells in a Transwell chamber (P < 0.001). It was demonstrated that 10 µg/ml synthetic peptide VR-10 had the strongest effect. 3. The expression of TGF-ß2 mRNA in RF/6A cells increased after treatment with 1 µg/ml TSP-1 (P < 0.0001). However, there was no significant difference between the synthetic peptide VR-10 and the control group (P > 0.05). Expression of PEDF mRNA in RF/6A cells was increased after treatment with 1 µg/ml TSP-1 and synthetic peptide VR-10. We demonstrated that 10 µg/ml synthetic peptide VR-10 had the strongest effect (P < 0.001). There were significant differences between groups (P < 0.001). Expression of TGF-ß2 mRNA in RF/6A cells increased after treatment with 1 µg/ml TSP-1 (P = 0.000). There was no significant difference between the synthetic peptide VR-10 and the control group (P > 0.05). PEDF mRNA expression in RF/6A cells decreased after 1 µg/ml TSP-1 and synthetic peptide VR-10 therapy, among which 10 µg/ml synthetic peptide VR-10 demonstrated the strongest effect (P < 0.001). There were significant differences between groups (P < 0.001), except for the 1 µg/ml synthetic peptide VR-10 and 1 µg/ml synthetic peptide VR-10 groups (P = 0.615). 4. Compared with the control group, FasL mRNA expression was significantly increased in the 10 µg/ml synthetic peptide VR-10 treatment group; however, Bcl-2 mRNA expression was decreased. 5. Western blotting showed that RF/6A cells in the control group mainly expressed the 32 kD procaspase-3 forms. For the 10 µg/ml synthetic peptide, VR-10 treatment group, it showed decreased expression of procaspase-3 (32 kD) and concomitant increased expression of its shorter pro apoptotic forms (20 kD). Compared with the control group, Fas protein expression significantly increased in the 10 µg/ml synthetic peptide VR-10 treatment group. CONCLUSIONS: Synthetic peptide VR-10 had an inhibitory action on the proliferation and migration of RF/6A cells. VR-10 inhibited angiogenesis by its combined actions, which included up-regulating the expression of an anti-angiogenesis gene, namely, pigment epithelium-derived factor (PEDF), down-regulating the expression of the pro-angiogenic vascular endothelial growth factor (VEGF), and mediated endothelial cell apoptosis.
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Proliferación Celular/efectos de los fármacos , Péptidos/farmacología , Trombospondina 1/farmacología , Animales , Caspasa 3/metabolismo , Línea Celular , Movimiento Celular/efectos de los fármacos , Células Endoteliales/citología , Células Endoteliales/efectos de los fármacos , Células Endoteliales/metabolismo , Proteínas del Ojo/genética , Proteínas del Ojo/metabolismo , Proteína Ligando Fas/genética , Proteína Ligando Fas/metabolismo , Macaca mulatta , Factores de Crecimiento Nervioso/genética , Factores de Crecimiento Nervioso/metabolismo , Péptidos/síntesis química , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Retina/citología , Serpinas/genética , Serpinas/metabolismo , Factor de Crecimiento Transformador beta2/genética , Factor de Crecimiento Transformador beta2/metabolismo , Regulación hacia Arriba/efectos de los fármacos , Factor A de Crecimiento Endotelial Vascular/genética , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
Here, we describe the use of DNA-conjugated antibodies for rapid and sensitive detection of whole viruses using a single-particle interferometric reflectance imaging sensor (SP-IRIS), a simple, label-free biosensor capable of imaging individual nanoparticles. First, we characterize the elevation of the antibodies conjugated to a DNA sequence on a three-dimensional (3-D) polymeric surface using a fluorescence axial localization technique, spectral self-interference fluorescence microscopy (SSFM). Our results indicate that using DNA linkers results in significant elevation of the antibodies on the 3-D polymeric surface. We subsequently show the specific detection of pseudotyped vesicular stomatitis virus (VSV) as a model virus on SP-IRIS platform. We demonstrate that DNA-conjugated antibodies improve the capture efficiency by achieving the maximal virus capture for an antibody density as low as 0.72 ng/mm(2), whereas for unmodified antibody, the optimal virus capture requires six times greater antibody density on the sensor surface. We also show that using DNA conjugated anti-EBOV GP (Ebola virus glycoprotein) improves the sensitivity of EBOV-GP carrying VSV detection compared to directly immobilized antibodies. Furthermore, utilizing a DNA surface for conversion to an antibody array offers an easier manufacturing process by replacing the antibody printing step with DNA printing. The DNA-directed immobilization technique also has the added advantages of programmable sensor surface generation based on the need and resistance to high temperatures required for microfluidic device fabrication. These capabilities improve the existing SP-IRIS technology, resulting in a more robust and versatile platform, ideal for point-of-care diagnostics applications.
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Anticuerpos Inmovilizados/química , Técnicas Biosensibles , Sondas de ADN/química , ADN/química , Vesiculovirus/aislamiento & purificación , Técnicas Biosensibles/instrumentación , Microscopía Fluorescente/instrumentación , Vesiculovirus/patogenicidadRESUMEN
Quantitative determination of the density and conformation of DNA molecules tethered to the surface can help optimize and understand DNA nanosensors and nanodevices, which use conformational or motional changes of surface-immobilized DNA for detection or actuation. We present an interferometric sensing platform that combines (i) dual-color fluorescence spectroscopy for precise axial co-localization of two fluorophores attached at different nucleotides of surface-immobilized DNA molecules and (ii) independent label-free quantification of biomolecule surface density at the same site. Using this platform, we examined the conformation of DNA molecules immobilized on a three-dimensional polymeric surface and demonstrated simultaneous detection of DNA conformational change and binding in real-time. These results demonstrate that independent quantification of both surface density and molecular nanoscale conformation constitutes a versatile approach for nanoscale solid-biochemical interface investigations and molecular binding assays.
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Técnicas Biosensibles/instrumentación , Colorantes Fluorescentes/análisis , Ácidos Nucleicos Inmovilizados/análisis , Nanoestructuras/química , Espectrometría de Fluorescencia/instrumentación , Diseño de Equipo , Fluorescencia , Conformación de Ácido Nucleico , Polímeros/químicaRESUMEN
Emulsion micro-gels exhibit significant potential as functional ingredients for modifying food texture, replacing saturated fats, or serving as templates for the controlled release of bioactive compounds. Structural design principles are being applied more frequently to develop innovative emulsion micro-gels. In this paper, whey protein concentrate (WPC), κ-carrageenan and sodium alginate (SA) were utilized for preparing emulsion micro-gels. To reveal the regulation mechanism of the structural and physicochemical properties of emulsion micro-gels on lipid digestion, the influence of SA additions on the structural, physicochemical properties and in vitro digestion behavior of κ-carrageenan/WPC-based emulsion micro-gel were explored. The FTIR results suggest that the emulsion micro-gels are formed through non-covalent interactions. With the increase of SA addition (from 0.7 g/100 mL to 1.0 g/100 mL), the decreased mean droplet size, the increased hardness, elasticity indexes, and water holding capacity, the reduced the related peak times all indicated that the emulsion micro-gels exhibit enhanced rheological, stability, and mechanical properties. It can be concluded from the microstructure, particle size distribution of the emulsion micro-gels during simulated digestion and free fatty acid release that both κ-carrageenan/WPC-based emulsion micro-gel and κ-carrageenan/WPC/SA-based emulsion micro-gel can inhibit lipid digestion due to the ability to maintain structural stability and hindering the penetration of bile salts and lipase through the hydrogel networks. And the ability is regulated by the binding properties the gel matrix and oil droplets, which determine the structure and physicochemical properties of emulsion micro-gels. The research suggested that the structure of emulsion micro-gels can be modified to produce various lipid digestion profiles. It may be significant for certain practical application in the design of low-fat food and controlled release of bioactive agents.
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Alginatos , Carragenina , Emulsiones , Proteína de Suero de Leche , Proteína de Suero de Leche/química , Carragenina/química , Alginatos/química , Emulsiones/química , Reología , Geles/química , Digestión/efectos de los fármacos , Fenómenos Químicos , Tamaño de la PartículaRESUMEN
BACKGROUND: Transgenic insect-resistant rice offers an environmentally friendly approach to mitigate yield losses caused by lepidopteran pests, such as stem borers. Bt (Bacillus thuringiensis) genes encode insecticidal proteins and are widely used to confer insect resistance to genetically modified crops. This study investigated the integration, inheritance, and expression characteristics of codon-optimised synthetic Bt genes, cry1C* and cry2A*, in transgenic early japonica rice lines. METHODS: The early japonica rice cultivar, Songgeng 9 (Oryza sativa), was transformed with cry1C* or cry2A*, which are driven by the ubi promoter via Agrobacterium tumefaciens-mediated transformation. Molecular analyses, including quantitative PCR (qPCR), enzyme-linked immunosorbent assay (ELISA), and Southern blot analysis were performed to confirm transgene integration, inheritance, transcriptional levels, and protein expression patterns across different tissues and developmental stages. RESULTS: Stable transgenic early japonica lines exhibiting single-copy transgene integration were established. Transcriptional analysis revealed variations in Bt gene expression among lines, tissues, and growth stages, with higher expression levels observed in leaves than in other organs. Notably, cry2A* exhibited consistently higher mRNA and protein levels than cry1C* across all examined tissues and developmental time points. Bt protein accumulation followed the trend of leaves > stem sheaths > young panicles > brown rice, with peak expression during the filling stage in the vegetative tissues. CONCLUSIONS: Synthetic cry2A* displayed markedly elevated transcription and translation compared to cry1C* in the transgenic early japonica rice lines examined. Distinct spatiotemporal patterns of Bt gene expression were elucidated, providing insights into the potential insect resistance conferred by these genes in rice. These findings will contribute to the development of insect-resistant japonica rice varieties and facilitate the rational deployment of Bt crops.
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Proteínas Bacterianas , Endotoxinas , Oryza , Plantas Modificadas Genéticamente , Oryza/genética , Oryza/parasitología , Plantas Modificadas Genéticamente/genética , Animales , Endotoxinas/genética , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Proteínas Hemolisinas/genética , Toxinas de Bacillus thuringiensis/genética , Bacillus thuringiensis/genética , Mariposas Nocturnas/genética , Regulación de la Expresión Génica de las Plantas , Control Biológico de Vectores/métodosRESUMEN
Protonic ceramic electrochemical cells (PCECs) have received considerable attention as they can directly generate electricity and/or produce chemicals. Development of the electrodes with the trifunctionalities of oxygen reduction/evolution and nonoxidative ethane dehydrogenation is yet challenging. Here these findings are reported in the design of trifunctional electrodes for PCECs with a detailed composition of Mn0.9Cs0.1Co2O4-δ (MCCO) and Co3O4 (CO) (MCCO-CO, 8:2 mass ratio). At 600 °C, the MCCO-CO electrode exhibits a low area-specific resistance of 0.382 Ω cm2 and reasonable stability for ≈105 h with no obvious degradation. The single cell with the MCCO-CO electrode shows an encouraging peak power density of 1.73 W cm-2 in the fuel cell (FC) mode and a current density of -3.93 A cm-2 at 1.3 V in the electrolysis cell (EC) mode at 700 °C. Moreover, the MCCO-CO cell displays promising operational stability in FC mode (223 h), EC mode (209 h), and reversible cycling stability (52 cycles, 208 h) at 650 °C. The MCCO-CO single cell shows an encouraging ethane conversion to ethylene (with a conversion of 40.3% and selectivity of 94%) and excellent H2 production rates of 4.65 mL min-1 cm-2 at 1.5 V and 700 °C, respectively, with reasonable Faradaic efficiencies.
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Asymmetrical flow field-flow fractionation (AF4), a gentle tool for the separation and characterization of particles and macromolecules, has attracted increased interest in recent years owing to its broad dynamic size range and utilization of "open channel" voids in the packing or stationary phase. A steric transition phenomenon in which the sample elution mode change from the normal mode to the steric/hyperlayer mode occurs. Accurate characterization by AF4 requires the absence of steric transition, particularly when the sample has a broad size distribution, because the effect of the combination of different modes is difficult to interpret. In this study, the relative molecular mass (M), radius of gyration (Rg), and conformation of Gastrodia elata polysaccharides (GEPs) were characterized using AF4 coupled with online multi-angle light scattering (MALS) and differential refractive index (dRI) detection (AF4-MALS-dRI). Steric transition was observed during GEP separation by AF4 owing to the broad size distribution of the molecules. This phenomenon would result in the inaccurate characterization of the GEPs in terms of M and Rg because two GEP groups of different sizes may elute together. In this study, the effects of constant and exponentially decaying cross-flow rates, sample mass concentration, and spacer thickness on steric transition were systematically investigated. The results indicated that a high GEP mass concentration (i. e., 0.75 mg/mL) can lead to steric transition. The spacer thickness affected the resolution and retention time of the GEPs and changed the steric transition point (di). An exponentially decaying cross-flow rate not only adjusted the di of the polydisperse GEP samples but also improved the GEP resolution and shortened the analysis time. The influence of steric transition was solved under the following operating conditions: injected GEP mass concentration=0.5 mg/mL; injection volume=50 µL; spacer thickness=350 µm; detector flow rate=1.0 mL/min; and cross-flow rate exponentially decayed from 0.2 to 0.05 mL/min with a half-life of 2 min. Moreover, the influence of GEP origins and ultrasound treatment time on the M and Rg distributions and conformation of GEPs were investigated under the optimized operating conditions. The results showed that the M and Rg distributions of Yunnan and Sichuan GEPs decreased with increasing ultrasound time. When the ultrasound treatment time was 15 min, the Yunnan GEPs had a loosely hyperbranched chain conformation, whereas the Sichuan GEPs had a spherical conformation. When the ultrasound treatment time was increased to 30 or 60 min, the GEPs from both Yunnan and Sichuan had a hyperbranched chain conformation, indicating that ultrasound treatment resulted in GEP degradation. Under the same extraction conditions, GEPs from Yunnan had larger M and Rg values than those from Sichuan. AF4-MALS-dRI showed good repeatability for the characterization of GEPs under the optimized operating conditions. The relative standard deviations of Rg and M were 0.5% and 1.7%, respectively. The data presented in this study can be used as a starting point for in-depth studies on the structural bioactivity of GEPs.
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Fraccionamiento de Campo-Flujo , Gastrodia , China , Polisacáridos , Fraccionamiento de Campo-Flujo/métodosRESUMEN
Hepatocellular carcinoma (HCC) is a malignant tumor leading cancer-associated high mortality worldwide. Unfortunately, the most commonly used drug therapeutics not only lack of target ability and efficiency, but also exhibit severe systemic toxicity to normal tissues. Thus, effective and targeted nanodrug of HCC therapy is emerging as a more important issue. Here, we design and develop the novel nanomicelles, namely Mannose-polyethylene glycol 600-Nitroimidazole (Man-NIT). This micelle compound with high purity comprise two parts, which can self-assemble into nanoscale micelle. The outer shell is selected mannose as hydrophilic moiety, while the inner core is nitroimidazole as hydrophobic moiety. In the cell experiment, Man-NIT was more cellular uptake by HCCLM3 cells due to the mannose modification. Mannose as a kind of glucose transporter 1 (GLUT1) substrate, can specifically recognize and bind to over-expressed GLUT1 on carcinoma cytomembrane. The nitroimidazole moiety of Man-NIT was reduced by the over-expressed nitroreductase with reduced nicotinamide adenine dinucleotide phosphate (NADPH) as the cofactor, resulting in transient deletion of NADPH and glutathione (GSH). The increase of reactive oxygen species (ROS) in HCCLM3 cells disturbed the balance of redox, and finally caused the death of tumor cells. Additional in vivo experiment was conducted using twenty-four male BALB/c nude mice to build the tumor model. The results showed that nanomicelles were accumulated in the liver of mice. The tumor size and pathological features were obviously improved after nanomicelles treatment. It indicates that namomicelles have a tumor inhibition effect, especially Man-NIT, which may be a potential nanodrug of chemotherapeutics for HCC therapy.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Masculino , Ratones , Animales , Carcinoma Hepatocelular/patología , NADP/metabolismo , Transportador de Glucosa de Tipo 1 , Neoplasias Hepáticas/patología , Micelas , Ratones Desnudos , Manosa , Línea Celular TumoralRESUMEN
INTRODUCTION: Toxoplasma gondii (T.gondii) is a widespread protozoan with significant economic losses and public health importance. But so far, the protective effect of reported DNA-based vaccines fluctuates widely, and no study has demonstrated complete protection. AREAS COVERED: This review provides an inclusive summary of T. gondii DNA vaccine antigens, adjuvants, and some other parameters. A total of 140 articles from 2000 to 2021 were collected from five databases. By contrasting the outcomes of acute and chronic challenges, we aimed to investigate and identify viable immunological strategies for optimum protection. Furthermore, we evaluated and discussed the impact of several parameters on challenge outcomes in the hopes of developing some recommendations to assist better future horizontal comparisons among research. EXPERT OPINION: In the coming five years of research, the exploration of vaccine cocktails combining invasion antigens and metabolic antigens with genetic adjuvants or novel DNA delivery methods may offer us desirable protection against this multiple stage of life parasite. In addition to finding a better immune strategy, developing better in silico prediction methods, solving problems posed by variables in practical applications, and gaining a more profound knowledge of T.gondii-host molecular interaction is also crucial towards a successful vaccine.
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Vacunas Antiprotozoos , Toxoplasma , Vacunas de ADN , Humanos , Animales , Ratones , Toxoplasma/genética , Antígenos de Protozoos/genética , Proteínas Protozoarias/genética , Vacunas Antiprotozoos/genética , Adyuvantes Inmunológicos , ADN , Anticuerpos Antiprotozoarios , Ratones Endogámicos BALB CRESUMEN
Autism spectrum disorder (ASD) is a severe neurodevelopmental disorder. Abnormal pain sensation is a common clinical symptom of ASD that seriously affects the quality of life of patients with ASD and their families. However, the underlying mechanism is unclear. It is believed to be related to the excitability of neurons and the expression of ion channels. Herein, we confirmed that baseline pain and Complete Freund's adjuvant (CFA)-induced chronic inflammatory pain were impaired in the BTBR T+ Itpr3tf/J (BTBR) mouse model of ASD. RNA sequencing (RNA-seq) analyses of the dorsal root ganglia (DRG), which are closely related to pain in ASD model mice, revealed that high expression of KCNJ10 (encoding Kir4.1) might be an important factor in ASD pain sensation abnormalities. The levels of Kir4.1 were further verified by western blotting, RT-qPCR, and immunofluorescence. By inhibiting Kir4.1, the pain insensitivity of BTBR mice improved, confirming that a high expression level of Kir4.1 was highly correlated with decreased pain sensitivity in ASD. Meanwhile, we found that the anxiety behaviours and the social novelty recognition were changed after CFA induced inflammatory pain. And after inhibiting Kir4.1, the stereotyped behaviours and social novelty recognition of BTBR mice were also improved. Further, we found that the expression levels of glutamate transporters, excitatory amino acid transporter 1 (EAAT1), and excitatory amino acid transporter 2 (EAAT2) were increased in the DRG of BTBR mice but decreased after inhibiting Kir4.1. This suggests that Kir4.1 may play a key role in the improvement of pain insensitivity in ASD by regulating glutamate transporters. In conclusion, our findings revealed the possible mechanism and role of Kir4.1 in the pain insensitivity in ASD, using bioinformatics analyses and animal experiments, and provided a theoretical basis for clinically targeted intervention in ASD.
Asunto(s)
Trastorno del Espectro Autista , Ratones , Animales , Trastorno del Espectro Autista/genética , Calidad de Vida , Ratones Endogámicos , Dolor/genética , Glutamatos , Modelos Animales de EnfermedadRESUMEN
We demonstrate an accurate, quantitative, and label-free optical technology for high-throughput studies of receptor-ligand interactions, and apply it to TATA binding protein (TBP) interactions with oligonucleotides. We present a simple method to prepare single-stranded and double-stranded DNA microarrays with comparable surface density, ensuring an accurate comparison of TBP activity with both types of DNA. In particular, we find that TBP binds tightly to single-stranded DNA, especially to stretches of polythymine (poly-T), as well as to the traditional TATA box. We further investigate the correlation of TBP activity with various lengths of DNA and find that the number of TBPs bound to DNA increases >7-fold as the oligomer length increases from 9 to 40. Finally, we perform a full human genome analysis and discover that 35.5% of human promoters have poly-T stretches. In summary, we report, for the first time to our knowledge, the activity of TBP with poly-T stretches by presenting an elegant stepwise analysis of multiple techniques: discovery by a novel quantitative detection of microarrays, confirmation by a traditional gel electrophoresis, and a full genome prediction with computational analyses.