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1.
Toxics ; 12(8)2024 Jul 31.
Artículo en Inglés | MEDLINE | ID: mdl-39195661

RESUMEN

Glyphosate is the most widely used herbicide in the world. This study aimed to evaluate the relationships among urinary glyphosate, all-cause mortality and cardiovascular diseases (CVD)-related mortality in the general US population of adults, and to determine the role of alkaline phosphatase (ALP), an inflammation marker that is associated with glyphosate exposure, in these relationships. Subjects from the National Health and Nutrition Examination Survey (NHANES) 2013-2018 cycles were included. Survey-weighted Cox regression analysis was applied to estimate the relationship of glyphosate with overall and CVD mortalities. Restricted cubic spline (RCS) analysis was utilized to detect the linearity of associations. The intermediary role of ALP was explored by mediation analysis. Our results found consistent and positive associations of glyphosate with all-cause mortality (HR: 1.29, 95%CI: 1.05-1.59) and CVD mortality (HR: 1.32, 95%CI: 1.02-1.70). RCS curves further validated linear and positive dose-dependent relationships between glyphosate and mortality-related outcomes. Moreover, serum ALP was identified as a mediator in these associations and explained 12.1% and 14.0% of the total associations between glyphosate and all-cause death and CVD death risk, respectively. Our study indicated that glyphosate was associated with increased all-cause and CVD mortality in humans. Increased ALP may play an essential role in these associations.

2.
Toxics ; 12(8)2024 Aug 18.
Artículo en Inglés | MEDLINE | ID: mdl-39195702

RESUMEN

Widespread glyphosate contamination in the environment and its endocrine-disrupting potential are concerning. However, evidence of glyphosate's effects on glycemic health is limited. To examine the association between glyphosate and glucose homeostasis in the general US population, a total of 3038 individuals were enrolled from the 2013-2016 cycles of the National Health and Nutrition Examination Survey (NHANES). Survey-weighted linear regression and restricted cubic spline curves were used to detect the associations between glyphosate and glycemic disorders. The effects of interactions between sex hormones and glyphosate on glycemic outcomes were evaluated. The results showed that glyphosate was significantly linked to increased glycated hemoglobin A1c (HbA1c) levels (ß = 0.01; 95%CI, 0.01 to 0.02; p = 0.001) and the compromised homeostatic model assessment of beta-cell function (HOMA-beta) scores (ß = -0.09; 95%CI, -0.17 to -0.01; p = 0.024). More importantly, these "glyphosate-glycemic disorder" associations were significantly modified by sex hormone-binding globulin (SHBG; P for interaction < 0.05), with more pronounced relationships being identified in individuals with low SHBG levels. Our findings indicate that glyphosate is correlated with glucose dyshomeostasis. Individuals with low SHBG levels exhibited susceptibility to glyphosate-related glycemic toxicity; therefore, it might be prudent to determine glycemic health in those subjects with glyphosate exposure.

3.
J Chem Inf Model ; 64(7): 2670-2680, 2024 04 08.
Artículo en Inglés | MEDLINE | ID: mdl-38232977

RESUMEN

Kokumi is a subtle sensation characterized by a sense of fullness, continuity, and thickness. Traditional methods of taste discovery and analysis, including those of kokumi, have been labor-intensive and costly, thus necessitating the emergence of computational methods as critical strategies in molecular taste analysis and prediction. In this study, we undertook a comprehensive analysis, prediction, and screening of the kokumi compounds. We categorized 285 kokumi compounds from a previously unreleased kokumi database into five groups based on their molecular characteristics. Moreover, we predicted kokumi/non-kokumi and multi-flavor compositions using six structure-taste relationship models: MLP-E3FP, MLP-PLIF, MLP-RDKFP, SVM-RDKFP, RF-RDKFP, and WeaveGNN feature of Atoms and Bonds. These six predictors exhibited diverse performance levels across two different models. For kokumi/non-kokumi prediction, the WeaveGNN model showed an exceptional predictive AUC value (0.94), outperforming the other models (0.87, 0.90, 0.89, 0.92, and 0.78). For multi-flavor prediction, the MLP-E3FP model demonstrated a higher predictive AUC and MCC value (0.94 and 0.74) than the others (0.73 and 0.33; 0.92 and 0.70; 0.95 and 0.73; 0.94 and 0.64; and 0.88 and 0.69). This data highlights the model's proficiency in accurately predicting kokumi molecules. As a result, we sourced kokumi active compounds through a high-throughput screening of over 100 million molecules, further refined by toxicity and similarity screening. Lastly, we launched a web platform, KokumiPD (https://www.kokumipd.com/), offering a comprehensive kokumi database and online prediction services for users.


Asunto(s)
Aprendizaje Automático , Bases de Datos Factuales
4.
Int J Mol Sci ; 24(19)2023 Sep 23.
Artículo en Inglés | MEDLINE | ID: mdl-37833919

RESUMEN

The disease of SARS-CoV-2 has caused considerable morbidity and mortality globally. Spike proteins on the surface of SARS-CoV-2 allow it to bind with human cells, leading to infection. Fullerenes and their derivatives are promising SARS-CoV-2 inhibitors and drug-delivery vehicles. In this study, Gaussian accelerated molecular dynamics simulations and the Markov state model were employed to delve into the inhibitory mechanism of Fullerene-linear-polyglycerol-b-amine sulfate (F-LGPS) on spike proteins. During the study, it was discovered that fullerene derivatives can operate at the interface of the receptor-binding domain (RBD) and the N-terminal domain (NTD), keeping structural domains in a downward conformation. It was also observed that F-LGPS demonstrated superior inhibitory effects on the XBB variant in comparison to the wild-type variant. This study yielded invaluable insights for the potential development of efficient therapeutics targeting the spike protein of SARS-CoV-2.


Asunto(s)
COVID-19 , Fulerenos , Humanos , SARS-CoV-2 , Fulerenos/farmacología , Glicoproteína de la Espiga del Coronavirus , Simulación de Dinámica Molecular , Unión Proteica
5.
Heliyon ; 9(7): e17744, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37539200

RESUMEN

The intelligent revolution caused by new digital technologies has provided new impetus to reduce carbon emissions. However, the current research on new digital technologies and carbon emissions is still in its infancy and lacks empirical conclusions between them. Therefore, this paper studies the impact of new digital technologies on carbon emissions, identifies its mechanism, and analyzes the regional heterogeneity of its effects. This research treats the National Big Data Comprehensive Pilot Zones pilot in China as a quasi-natural experiment for the development of new digital technologies along with city-level data covering from 2011 to 2019 to conduct a staggered difference-in-difference (DID) model analysis. We find that new digital technologies significantly reduce carbon emissions. This conclusion is still valid after a series of robustness tests such as heterogeneity treatment effect analysis, ex-ante trend test, spillover effect test, and placebo test. Additionally, new digital technologies can reduce carbon emissions by promoting the transformation of industrial structure, improving the level of green technology innovation, and promoting industrial agglomeration. At the same time, the heterogeneity analysis shows that new digital technologies' carbon emission reduction effect is more evident in non-western regions, southern regions, and large cities. To expand the carbon emission reduction effect of new digital technologies, the government should promote the development and application of new digital technologies, and implement differentiated policies based on regional characteristics.

6.
Poult Sci ; 102(10): 102954, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37556982

RESUMEN

Pigeons are considered less susceptible, and display few or no clinical signs to infection with avian influenza virus (AIV). Melanoma differentiation-associated gene 5 (MDA5), an important mediator in innate immunity, has been linked to the virus resistance. In this study, the pigeon MDA5 (piMDA5) was cloned. The bioinformatics analysis showed that the C-terminal domain (CTD) of MDA5 is highly conserved among species while the N-terminal caspase recruitment domain (CARD) is variable. Upon infection with Newcastle diseases virus (NDV) and AIV, piMDA5 was upregulated in both pigeons and pigeon embryonic fibroblasts (PEFs). Further study found that overexpression of piMDA5 mediated the activation of interferons (IFNs) and IFN-stimulated genes (ISGs) while inhibiting NDV replication. Conversely, the knockdown of piMDA5 promoted NDV replication. Additionally, CARD was found to be essential for the activation of IFN-ß by piMDA5. Furthermore, pigeon MDA5, chicken MDA5, and human MDA5 differ in inhibiting viral replication and inducing ISGs expression. These findings suggest that MDA5 contributes to suppressing viral replication by activating the IFN signal pathway in pigeons. This study provides valuable insight into the role of MDA5 in pigeons and a better understanding of the conserved role of MDA5 in innate immunity during evolution.


Asunto(s)
Columbidae , Virus de la Influenza A , Animales , Humanos , Columbidae/genética , Pollos/genética , Inmunidad Innata/genética , Virus de la Enfermedad de Newcastle , Replicación Viral , Antivirales
7.
Nat Commun ; 14(1): 1713, 2023 03 27.
Artículo en Inglés | MEDLINE | ID: mdl-36973294

RESUMEN

The functions of the influenza virus neuraminidase has been well documented but those of the mammalian neuraminidases remain less explored. Here, we characterize the role of neuraminidase 1 (NEU1) in unilateral ureteral obstruction (UUO) and folic acid (FA)-induced renal fibrosis mouse models. We find that NEU1 is significantly upregulated in the fibrotic kidneys of patients and mice. Functionally, tubular epithelial cell-specific NEU1 knockout inhibits epithelial-to-mesenchymal transition, inflammatory cytokines production, and collagen deposition in mice. Conversely, NEU1 overexpression exacerbates progressive renal fibrosis. Mechanistically, NEU1 interacts with TGFß type I receptor ALK5 at the 160-200aa region and stabilizes ALK5 leading to SMAD2/3 activation. Salvianolic acid B, a component of Salvia miltiorrhiza, is found to strongly bind to NEU1 and effectively protect mice from renal fibrosis in a NEU1-dependent manner. Collectively, this study characterizes a promotor role for NEU1 in renal fibrosis and suggests a potential avenue of targeting NEU1 to treat kidney diseases.


Asunto(s)
Enfermedades Renales , Neuraminidasa , Obstrucción Ureteral , Animales , Masculino , Ratones , Fibrosis , Expresión Génica , Riñón/metabolismo , Enfermedades Renales/patología , Ratones Endogámicos C57BL , Neuraminidasa/genética , Neuraminidasa/metabolismo , Obstrucción Ureteral/metabolismo
8.
Drug Dev Ind Pharm ; 49(1): 30-41, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36803327

RESUMEN

OBJECTIVE: To investigate the applicability of carboxymethyl starch (CMS) as a carrier to prepare solid dispersions (SDs) of piperine (PIP) and 18ß-glycyrrhetinic acid (ß-GA) (PIP-CMS and ß-GA-CMS SDs) and to explore the influence of drug properties on carrier selection. SIGNIFICANCE: The low oral bioavailability of natural therapeutic molecules, including PIP and ß-GA, severely restricts their pharmaceutical applications. Moreover, CMS, a natural polymer, is rarely reported as a carrier for SDs. METHODS: PIP-CMS and ß-GA-CMS SDs were prepared using the solvent evaporation method. Differential scanning calorimetry (DSC), X-ray powder diffraction (XRPD), Fourier transform infrared (FT-IR) spectroscopy, and scanning electron microscopy (SEM) were used for formulation characterization. Additionally, drug release characteristics were investigated. RESULTS: In vitro dissolution studies showed that the dissolutions of PIP-CMS and ß-GA-CMS SDs were 1.90-2.04 and 1.97-2.22 times higher than pure PIP and ß-GA, respectively, at a drug:polymer ratio of 1:6. DSC, XRPD, FT-IR, and SEM analyses confirmed the formation of SDs in their amorphous states. Significant improvements in Cmax and AUC0-24 h of PIP-CMS and ß-GA-CMS SDs (17.51 ± 8.15 µg/mL and 210.28 ± 117.13 µg·h/mL, respectively) and (32.17 ± 9.45 µg/mL and 165.36 ± 38.75 µg·h/mL, respectively) were observed in the pharmacokinetic study. Compared with weakly acidic ß-GA, loading weakly basic PIP seemed to have a profound effect on stability through intermolecular forces. CONCLUSIONS: Our findings showed CMS could be a promising carrier for SDs, and loading weakly basic drug may be more suitable, especially in binary SDs system.


Asunto(s)
Excipientes , Polímeros , Espectroscopía Infrarroja por Transformada de Fourier/métodos , Disponibilidad Biológica , Solubilidad , Excipientes/química , Rastreo Diferencial de Calorimetría
9.
Nature ; 612(7940): 503-511, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-36477535

RESUMEN

The neocortex consists of a vast number of diverse neurons that form distinct layers and intricate circuits at the single-cell resolution to support complex brain functions1. Diverse cell-surface molecules are thought to be key for defining neuronal identity, and they mediate interneuronal interactions for structural and functional organization2-6. However, the precise mechanisms that control the fine neuronal organization of the neocortex remain largely unclear. Here, by integrating in-depth single-cell RNA-sequencing analysis, progenitor lineage labelling and mosaic functional analysis, we report that the diverse yet patterned expression of clustered protocadherins (cPCDHs)-the largest subgroup of the cadherin superfamily of cell-adhesion molecules7-regulates the precise spatial arrangement and synaptic connectivity of excitatory neurons in the mouse neocortex. The expression of cPcdh genes in individual neocortical excitatory neurons is diverse yet exhibits distinct composition patterns linked to their developmental origin and spatial positioning. A reduction in functional cPCDH expression causes a lateral clustering of clonally related excitatory neurons originating from the same neural progenitor and a significant increase in synaptic connectivity. By contrast, overexpression of a single cPCDH isoform leads to a lateral dispersion of clonally related excitatory neurons and a considerable decrease in synaptic connectivity. These results suggest that patterned cPCDH expression biases fine spatial and functional organization of individual neocortical excitatory neurons in the mammalian brain.


Asunto(s)
Regulación de la Expresión Génica , Neocórtex , Protocadherinas , Animales , Ratones , Interneuronas/metabolismo , Neocórtex/anatomía & histología , Neocórtex/citología , Neocórtex/metabolismo , Neuronas/metabolismo , Protocadherinas/genética , Protocadherinas/metabolismo , Sinapsis/metabolismo , Transmisión Sináptica
10.
Materials (Basel) ; 15(23)2022 Nov 28.
Artículo en Inglés | MEDLINE | ID: mdl-36499958

RESUMEN

In this paper, warm-water flax retting was used as a pretreatment method for banana-fibre extraction. To determine the optimum conditions for flax retting, the physical properties of various parts of stems and fibres in the process of flax retting were analysed. By studying the tensile strength, elongation at break, diameter, moisture regain, and other characteristics of the fibres, the influences of bacteria and enzymes in the retting liquor on the fibre characteristics in different retting stages were determined. Through mechanical-property tests and microscopic observation of the stem skin, the change rules of the mechanical properties and degumming state of the stems were examined. The results showed that the fibre tensile strength of banana stems reached the maximum value of 45 ± 16 cN·tex-1 after 11 days of retting. As most resins had not been hydrolysed, fibre extraction was difficult. After 21-25 days of retting, the tensile strength of fibres was about 34 ± 10 cN·tex-1, elongation at break was about 1.71%, and moisture regain was about 13.56%. The fibre characteristics met the process requirements, and the tensile separation stress of the stem was small, about 0.034 MPa. This time point could be used as the optimum endpoint for retting flax in warm water, which could provide theoretical support and research basis for the recycling of banana straw. The functional groups of the extracted fibres were studied by FTIR, which confirmed the observed change rule of each component during degumming. The experimental results showed that a longer retting time corresponded with a lower content of fibre impurities, more thorough degumming, and less difficult extraction; however, strength and toughness decreased.

11.
Poult Sci ; 101(12): 102147, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36191515

RESUMEN

The mammalian-derived MDCK cells are the most widely used for avian virus vaccine production at present. The use of heterologous cell systems for avian virus preparation may cause security risks. An avian cell line is available for avian virus vaccines urgently needed. In this study, a peacock immortalized fibroblast cell line that is suitable for avian virus vaccine production was generated. The primary peacock fibroblast cells were prepared, and the immortal cells PEF-1 were obtained by transferring hTERT into the primary cells and screening with G418. The PEF-1 has high cell viability and expresses exogenous TERT protein. More importantly, the virus replication ability was stronger in PEF-1 than in MDCK cells as evaluated by virus fluorescence and TCID50, after being infected with NDV-GFP, VSV-GFP, and AIV. In conclusion, the peacock immortalized PEF cells are expected to be used for the production of peacock and other avian virus vaccines.


Asunto(s)
Gripe Aviar , Vacunas , Animales , Virus de la Enfermedad de Newcastle , Pollos , Línea Celular , Fibroblastos , Mamíferos
12.
Nat Neurosci ; 25(7): 865-875, 2022 07.
Artículo en Inglés | MEDLINE | ID: mdl-35726058

RESUMEN

Proper neural progenitor behavior in conjunction with orderly vasculature formation is fundamental to the development of the neocortex. However, the mechanisms coordinating neural progenitor behavior and vessel growth remain largely elusive. Here we show that robust metabolic production of lactate by radial glial progenitors (RGPs) co-regulates vascular development and RGP division behavior in the developing mouse neocortex. RGPs undergo a highly organized lineage progression program to produce diverse neural progeny. Systematic single-cell metabolic state analysis revealed that RGPs and their progeny exhibit distinct metabolic features associated with specific cell types and lineage progression statuses. Symmetrically dividing, proliferative RGPs preferentially express a cohort of genes that support glucose uptake and anaerobic glycolysis. Consequently, they consume glucose in anaerobic metabolism and produce a high level of lactate, which promotes vessel growth. Moreover, lactate production enhances RGP proliferation by maintaining mitochondrial length. Together, these results suggest that specific metabolic states and metabolites coordinately regulate vasculature formation and progenitor behavior in neocortical development.


Asunto(s)
Neocórtex , Animales , Células Ependimogliales/fisiología , Humanos , Ácido Láctico , Ratones , Neurogénesis/fisiología
13.
Sci Rep ; 12(1): 2159, 2022 02 09.
Artículo en Inglés | MEDLINE | ID: mdl-35140263

RESUMEN

As the demand for health grows, the increase in medical waste generation is gradually outstripping the load. In this paper, we propose a deep learning approach for identification and classification of medical waste. Deep learning is currently the most popular technique in image classification, but its need for large amounts of data limits its usage. In this scenario, we propose a deep learning-based classification method, in which ResNeXt is a suitable deep neural network for practical implementation, followed by transfer learning methods to improve classification results. We pay special attention to the problem of medical waste classification, which needs to be solved urgently in the current environmental protection context. We applied the technique to 3480 images and succeeded in correctly identifying 8 kinds of medical waste with an accuracy of 97.2%; the average F1-score of five-fold cross-validation was 97.2%. This study provided a deep learning-based method for automatic detection and classification of 8 kinds of medical waste with high accuracy and average precision. We believe that the power of artificial intelligence could be harnessed in products that would facilitate medical waste classification and could become widely available throughout China.

14.
Eur J Pharm Sci ; 168: 106071, 2022 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-34774716

RESUMEN

The oral bioavailability and efficacy of baicalein is dramatically limited by its low solubility and effect of efflux. In our study, we chose PVP-VA64 as a carrier and TPGS as a plasticizer and efflux inhibitor to prepare a solid dispersion of baicalein using hot-melt extrusion technology to improve its solubility and bioavailability. The hot-melt process and formulation were optimized, and a BAC-PVP VA64-TPGS solid dispersion (BPT-SD) was prepared. BAC exists in an amorphous or molecular state in BPT-SD. BPT-SD comprised irregular lumps and small particles without BAC or carrier characteristics. The dissolution efficiency of BPT-SD improved under sink conditions. FTIR showed a strong hydrogen bond between BAC and PVP-VA64 in BPT-SD. BPT-SD maintained good physical stability for 6 months. The apparent permeability coefficient of BAC in the Caco-2 cell model confirmed that BPT-SD had higher gastrointestinal membrane permeability. A rat pharmacokinetic study showed that BPT-SD had higher Cmax and AUC0-24h, shorter Tmax, and 2.88-fold higher bioavailability than BAC. A behavioral experiment in chronic unpredictable mild stress (CUMS) mice confirmed the antidepressant efficacy of BAC. BPT-SD reversed depression-like behavior in CUMS mice and improved BAC bioavailability. BAC preparation into a solid dispersion significantly enhanced dissolution performance and bioavailability.


Asunto(s)
Plastificantes , Animales , Disponibilidad Biológica , Células CACO-2 , Composición de Medicamentos , Flavanonas , Humanos , Ratones , Ratas , Solubilidad , Vitamina E
15.
Front Immunol ; 12: 742074, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34630423

RESUMEN

Chickens are the natural host of Newcastle disease virus (NDV) and avian influenza virus (AIV). The discovery that the RIG-I gene, the primary RNA virus pattern recognition receptor (PRR) in mammals, is naturally absent in chickens has directed attention to studies of chicken RNA PRRs and their functions in antiviral immune responses. Here, we identified Asp-Glu-Ala-Asp (DEAD)-box helicase 1 (DDX1) as an essential RNA virus PRR in chickens and investigated its functions in anti-RNA viral infections. The chDDX1 gene was cloned, and cross-species sequence alignment and phylogenetic tree analyses revealed high conservation of DDX1 among vertebrates. A quantitative RT-PCR showed that chDDX1 mRNA are widely expressed in different tissues in healthy chickens. In addition, chDDX1 was significantly upregulated after infection with AIV, NDV, or GFP-expressing vesicular stomatitis virus (VSV-GFP). Overexpression of chDDX1 in DF-1 cells induced the expression of IFN-ß, IFN-stimulated genes (ISGs), and proinflammatory cytokines; it also inhibited NDV and VSV replications. The knockdown of chDDX1 increased the viral yield of NDV and VSV and decreased the production of IFN-ß, which was induced by RNA analog polyinosinic-polycytidylic acid (poly[I:C]), by AIV, and by NDV. We used a chicken IRF7 (chIRF7) knockout DF-1 cell line in a series of experiments to demonstrate that chDDX1 activates IFN signaling via the chIRF7 pathway. Finally, an in-vitro pulldown assay showed a strong and direct interaction between poly(I:C) and the chDDX1 protein, indicating that chDDX1 may act as an RNA PRR during IFN activation. In brief, our results suggest that chDDX1 is an important mediator of IFN-ß and is involved in RNA- and RNA virus-mediated chDDX1-IRF7-IFN-ß signaling pathways.


Asunto(s)
Proteínas Aviares/inmunología , Pollos/inmunología , ARN Helicasas DEAD-box/inmunología , Inmunidad Innata/inmunología , Interferón gamma/inmunología , Animales , Infecciones por Virus ARN/inmunología , Receptores de Reconocimiento de Patrones/inmunología , Transducción de Señal/inmunología
16.
Nanomaterials (Basel) ; 11(6)2021 May 28.
Artículo en Inglés | MEDLINE | ID: mdl-34071576

RESUMEN

Aqueous zinc-ion batteries (AZIBs) are promising candidates for large-scale energy storage because of their low cost and high safety. However, their practical applications are impeded by low energy density and short service life. Here, an aqueous Zn2+/Li+ hybrid-ion battery is fabricated using the LiV3O8 nanorods as the cathode, metallic Zn as the anode, and 3 M Zn(OTf)2 + 0.5 M LiOTf aqueous solution as the electrolyte. Compared with the batteries using pure 3 M Zn(OTf)2 electrolyte, the cycle performance of the hybrid-ion battery is significantly improved. After 4000 cycles at 5 A g1, the remaining capacity is 163.9 mA h g-1 with impressive capacity retention of 87.0%. Ex-situ XRD, ex-situ XPS, and SEM tests demonstrate that the hybrid electrolyte can inhibit the formation of the irreversible Zn3(OH)2V2O7·2H2O by-product and restrict Zn dendrite growth during cycling, thereby improving the cycle performance of the batteries.

17.
Drug Dev Ind Pharm ; 47(1): 153-162, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33295808

RESUMEN

At present, saccharides as hydrophilic matrixes, have been gradually used in amorphous solid dispersions (ASD) for dispersing poorly water-soluble drugs without surfactants. In this study, an amorphous chitosan oligosaccharide (COS) was applied as a water-soluble matrix to form surfactant-free ASD via the ball milling to vitrify quercetin (QUE) and enhance the dissolution and bioavailability. Solid-state characterization (DSC, XRPD, FTIR, SEM and PLM) and physical stability assessments verified that the prepared ASDs showed excellent physical stability with complete amorphization due to potential interactions between QUE and COS. In vitro sink dissolution tests suggested all QUE-COS ASDs (w:w, 1:1, 1:2 and 1:4) significantly enhanced the dissolution rate of QUE. Meanwhile, in vitro non-sink dissolution exhibited that the maximum supersaturated concentration ranged from 112.62 to 138.00 µg/mL for all QUE-COS ASDs, which was much higher than that of pure QUE. Besides, the supersaturation of QUE-COS ASD kept for at least 24 h. In rat pharmacokinetics, the oral bioavailability of QUE-COS ASDs showed 1.64 ∼ 2.25 times increase compared to the pure QUE (p < .01). Hence, the present study confirms the amorphous COS could be applied as a promising hydrophilic matrix in QUE-COS ASDs for enhancing dissolution performance and bioavailability of QUE.


Asunto(s)
Quercetina , Tensoactivos , Animales , Disponibilidad Biológica , Interacciones Hidrofóbicas e Hidrofílicas , Ratas , Solubilidad
18.
Chempluschem ; 85(9): 2129-2135, 2020 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-32844598

RESUMEN

Controlling morphology, adopting metal cations and introducing crystal water are three effective strategies to improve the electrochemical performance of various battery electrodes. However, the effects of simultaneously applying these three strategies to aqueous rechargeable zinc batteries (ARZBs) are rarely demonstrated. Herein, hierarchical H11 Al2 V6 O23.2 (HAVO) microspheres were successfully prepared using a simple hydrothermal method, and used as cathode material for ARZBs. The as-prepared HAVO microspheres exhibited superior electrochemical performance than the dehydrated AlV3 O9 (AVO) microspheres, i. e. they have a larger specific capacity of 390.4 mA h g-1 at 100 mA g-1 , a better rate capability of 191.4 mA h g-1 at 5000 mA g-1 and a higher cycling stability of up to 1000 cycles with a capacity retention of 80.9 %. The excellent electrochemical performance of HAVO is due to the synergistic effects of the shortened ion diffusion distance in primary HAVO nanosheets, the improved electronic conductivity, and structural stability by adopting Al3+ into the lattice, the enhanced charge transfer properties and ion diffusion coefficient of the electrode due to the existence of crystal water. Therefore, this work may offer a new route for the design and synthesis of more advanced electrode materials for ARZBs.

19.
Nature ; 580(7801): 106-112, 2020 04.
Artículo en Inglés | MEDLINE | ID: mdl-32238932

RESUMEN

Radial glial progenitor cells (RGPs) are the major neural progenitor cells that generate neurons and glia in the developing mammalian cerebral cortex1-4. In RGPs, the centrosome is positioned away from the nucleus at the apical surface of the ventricular zone of the cerebral cortex5-8. However, the molecular basis and precise function of this distinctive subcellular organization of the centrosome are largely unknown. Here we show in mice that anchoring of the centrosome to the apical membrane controls the mechanical properties of cortical RGPs, and consequently their mitotic behaviour and the size and formation of the cortex. The mother centriole in RGPs develops distal appendages that anchor it to the apical membrane. Selective removal of centrosomal protein 83 (CEP83) eliminates these distal appendages and disrupts the anchorage of the centrosome to the apical membrane, resulting in the disorganization of microtubules and stretching and stiffening of the apical membrane. The elimination of CEP83 also activates the mechanically sensitive yes-associated protein (YAP) and promotes the excessive proliferation of RGPs, together with a subsequent overproduction of intermediate progenitor cells, which leads to the formation of an enlarged cortex with abnormal folding. Simultaneous elimination of YAP suppresses the cortical enlargement and folding that is induced by the removal of CEP83. Together, these results indicate a previously unknown role of the centrosome in regulating the mechanical features of neural progenitor cells and the size and configuration of the mammalian cerebral cortex.


Asunto(s)
Centrosoma/metabolismo , Corteza Cerebral/citología , Corteza Cerebral/embriología , Células Ependimogliales/citología , Células-Madre Neurales/citología , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Animales , Proteínas de Ciclo Celular/metabolismo , Membrana Celular/metabolismo , Membrana Celular/patología , Proliferación Celular , Centriolos/metabolismo , Corteza Cerebral/patología , Femenino , Masculino , Ratones , Proteínas Asociadas a Microtúbulos/deficiencia , Proteínas Asociadas a Microtúbulos/genética , Proteínas Asociadas a Microtúbulos/metabolismo , Microtúbulos/metabolismo , Microtúbulos/patología , Neurogénesis , Proteínas Señalizadoras YAP
20.
PeerJ ; 7: e6346, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-30775171

RESUMEN

INTRODUCTION: Rice bean (Phaseolus calcaltus), as an annual summer legume, is always subjected to acid soils in tropical to subtropical regions, limiting its growth and nodulation. However, little is known about its responses to lime and biochar addition, the two in improving soil fertility in acid soils. MATERIALS AND METHODS: In the current study, a pot experiment was conducted using rice bean on a sandy yellow soil (Orthic Acrisol) with a pH of 5.5. The experiment included three lime rates (0, 0.75 and 1.5 g kg-1) and three biochar rates (0, 5 and 10 g kg-1). The biochar was produced from aboveground parts of Solanum tuberosum using a home-made device with temperature of pyrolysis about 500 °C. RESULTS AND DISCUSSION: The results indicated that both lime and biochar could reduce soil exchange Al concentration, increase soil pH and the contents of soil microbial biomass carbon and microbial biomass nitrogen, and enhance urease and dehydrogenase activities, benefiting P. calcaltus growth and nodulation in acid soils. Lime application did decrease the concentrations of soil available phosphorus (AP) and alkali dispelled nitrogen (AN), whereas biochar application increased the concentrations of soil AP, AN and available potassium (AK). However, sole biochar application could not achieve as much yield increase as lime application did. High lime rate (1.5 g lime kg-1) incorporated with low biochar rate (5 g biochar kg-1) could obtain higher shoot biomass, nutrient uptake, and nodule number when compared with high lime rate and high biochar rate. CONCLUSION: Lime incorporated with biochar application could achieve optimum improvement for P. calcaltus growing in acid soils when compared with sole lime or biochar addition.

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