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1.
Sensors (Basel) ; 24(7)2024 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-38610274

RESUMO

Batteries play a crucial role as energy storage devices across various industries. However, achieving high performance often comes at the cost of safety. Continuous monitoring is essential to ensure the safety and reliability of batteries. This paper investigates the advancements in battery monitoring technology, focusing on fiber Bragg gratings (FBGs). By examining the factors contributing to battery degradation and the principles of FBGs, this study discusses key aspects of FBG sensing, including mounting locations, monitoring targets, and their correlation with optical signals. While current FBG battery sensing can achieve high measurement accuracies for temperature (0.1 °C), strain (0.1 µÎµ), pressure (0.14 bar), and refractive index (6 × 10-5 RIU), with corresponding sensitivities of 40 pm/°C, 2.2 pm/µÎµ, -0.3 pm/bar, and -18 nm/RIU, respectively, accurately assessing battery health in real time remains a challenge. Traditional methods struggle to provide real-time and precise evaluations by analyzing the microstructure of battery materials or physical phenomena during chemical reactions. Therefore, by summarizing the current state of FBG battery sensing research, it is evident that monitoring battery material properties (e.g., refractive index and gas properties) through FBGs offers a promising solution for real-time and accurate battery health assessment. This paper also delves into the obstacles of battery monitoring, such as standardizing the FBG encapsulation process, decoupling multiple parameters, and controlling costs. Ultimately, the paper highlights the potential of FBG monitoring technology in driving advancements in battery development.

2.
Cancer Cell Int ; 23(1): 223, 2023 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-37777759

RESUMO

BACKGROUND: High-grade serous ovarian cancer (HGSOC) is a challenging malignancy characterized by complex interactions between tumor cells and the surrounding microenvironment. Understanding the immune landscape of HGSOC, particularly the role of the extracellular matrix (ECM), is crucial for improving prognosis and guiding therapeutic interventions. METHODS AND RESULTS: Using univariate Cox regression analysis, we identified 71 ECM genes associated with prognosis in seven HGSOC populations. The ECMscore signature, consisting of 14 genes, was validated using Cox proportional hazards regression with a lasso penalty. Cox regression analyses demonstrated that ECMscore is an excellent indicator for prognostic classification in prevalent malignancies, including HGSOC. Moreover, patients with higher ECMscores exhibited more active stromal and carcinogenic activation pathways, including apical surface signaling, Notch signaling, apical junctions, Wnt signaling, epithelial-mesenchymal transition, TGF-beta signaling, and angiogenesis. In contrast, patients with relatively low ECMscores showed more active immune-related pathways, such as interferon alpha response, interferon-gamma response, and inflammatory response. The relationship between the ECMscore and genomic anomalies was further examined. Additionally, the correlation between ECMscore and immune microenvironment components and signals in HGSOC was examined in greater detail. Moreover, the expression of MGP, COL8A2, and PAPPA and its correlation with FAP were validated using qRT-PCR on samples from HGSOC. The utility of ECMscore in predicting the prospective clinical success of immunotherapy and its potential in guiding the selection of chemotherapeutic agents were also explored. Similar results were obtained from pan-cancer research. CONCLUSION: The comprehensive evaluation of the ECM may help identify immune activation and assist patients in HGSOC and even pan-cancer in receiving proper therapy.

3.
Proc Natl Acad Sci U S A ; 117(43): 26985-26995, 2020 10 27.
Artigo em Inglês | MEDLINE | ID: mdl-33046653

RESUMO

Current models emphasize that membrane voltage (Vm) depolarization-induced Ca2+ influx triggers the fusion of vesicles to the plasma membrane. In sympathetic adrenal chromaffin cells, activation of a variety of G protein coupled receptors (GPCRs) can inhibit quantal size (QS) through the direct interaction of G protein Gißγ subunits with exocytosis fusion proteins. Here we report that, independently from Ca2+, Vm (action potential) per se regulates the amount of catecholamine released from each vesicle, the QS. The Vm regulation of QS was through ATP-activated GPCR-P2Y12 receptors. D76 and D127 in P2Y12 were the voltage-sensing sites. Finally, we revealed the relevance of the Vm dependence of QS for tuning autoinhibition and target cell functions. Together, membrane voltage per se increases the quantal size of dense-core vesicle release of catecholamine via Vm → P2Y12(D76/D127) → Gißγ → QS → myocyte contractility, offering a universal Vm-GPCR signaling pathway for its functions in the nervous system and other systems containing GPCRs.


Assuntos
Catecolaminas/metabolismo , Células Cromafins/fisiologia , Proteínas Heterotriméricas de Ligação ao GTP/metabolismo , Vesículas Secretórias/fisiologia , Potenciais de Ação , Animais , Feminino , Células HEK293 , Humanos , Masculino , Camundongos Knockout , Cultura Primária de Células , Ratos Sprague-Dawley , Receptores Purinérgicos P2Y12/metabolismo , Transdução de Sinais
4.
Molecules ; 28(21)2023 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-37959733

RESUMO

Sodium-ion batteries (SIBs) are promising alternatives to replace lithium-ion batteries as future energy storage batteries because of their abundant sodium resources, low cost, and high charging efficiency. In order to match the high energy capacity and density, designing an atomically doped carbonous material as the anode is presently one of the important strategies to commercialize SIBs. In this work, we report the preparation of high-performance dual-atom-doped carbon (C) materials using low-cost corn starch and thiourea (CH4N2S) as the precursors. The electronegativity and radii of the doped atoms and C are different, which can vary the embedding properties of sodium ions (Na+) into/on C. As sulfur (S) can effectively expand the layer spacing, it provides more channels for embedding and de-embedding Na+. The synergistic effect of N and S co-doping can remarkably boost the performance of SIBs. The capacity is preserved at 400 mAh g -1 after 200 cycles at 500 mA g-1; more notably, the initial Coulombic efficiency is 81%. Even at a high rate of high current of 10 A g-1, the cell capacity can still reach 170 mAh g-1. More importantly, after 3000 cycles at 1 A g-1, the capacity decay is less than 0.003% per cycle, which demonstrates its excellent electrochemical performance. These results indicate that high-performance carbon materials can be prepared using low-cost corn starch and thiourea.

5.
Molecules ; 28(10)2023 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-37241775

RESUMO

With the development of high-performance electrode materials, sodium-ion batteries have been extensively studied and could potentially be applied in various fields to replace the lithium-ion cells, owing to the low cost and natural abundance. As the key anode materials of sodium-ion batteries, hard carbons still face problems, such as poor cycling performance and low initial Coulombic efficiency. Owning to the low synthesis cost and the natural presence of heteroatoms of biomasses, biomasses have positive implications for synthesizing the hard carbons for sodium-ion batteries. This minireview mainly explains the research progress of biomasses used as the precursors to prepare the hard-carbon materials. The storage mechanism of hard carbons, comparisons of the structural properties of hard carbons prepared from different biomasses, and the influence of the preparation conditions on the electrochemical properties of hard carbons are introduced. In addition, the effect of doping atoms is also summarized to provide an in-depth understanding and guidance for the design of high-performance hard carbons for sodium-ion batteries.

6.
Mol Med ; 28(1): 2, 2022 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-34983361

RESUMO

BACKGROUND: Although long noncoding RNA HLA complex group 18 (lncRNA HCG18) has been suggested to regulate cell growth in several tumours, the function of HCG18 in epithelial ovarian cancer (EOC) and its mechanism are still unclear. METHODS: shRNAs were applied to reduce HCG18 and related genes. For overexpression of miRNA, a miRNA mimic was transfected into cells. Quantitative real-time PCR (qRT-PCR) was used to detect levels of HCG18, miR-29a/b, and mRNAs. MTT, colony formation, wound healing and Transwell assays were used to evaluate cell proliferation, migration and invasion, respectively. A luciferase reporter assay was utilized to evaluate NF-κB activity and the binding of miRNAs with HCG18 or TRAF4/5. BALB nude mice injected with cells stably expressing shHCG18 or shNC were used for in vivo modelling. Subcutaneous tumour growth was monitored in nude mice, and immunohistochemistry (IHC) was used to determine expression of the proliferation marker Ki67. RESULTS: Abnormal expression of HCG18 and miR-29a/b was observed in EOC tissues. Knockdown of HCG18 using shRNA inhibited proliferation, migration, EMT and the proinflammatory pathway in EOC cells. miR-29a/b mimics and TRAF4/5 knockdown exhibited effects similar to HCG18 knockdown. Further experiments suggested that HCG18 directly targets miR-29a/b and upregulates TRAF4/5 expression, which are inhibited by targeting miR-29a/b. Moreover, overexpression of TRAF4/5 antagonized the inhibitory effect of HCG18 knockdown, suggesting that they are involved in HCG18-mediated oncogenic effects. Silencing HCG18 reduced tumour size and levels of Ki67 and TRAF4/5 while increasing miR-29a/b levels in vivo. CONCLUSIONS: Taken together, our data revealed an oncogenic signalling pathway mediated by HCG18 in ovarian cell lines, which functions as a ceRNA of miR-29a/b and thus derepresses expression levels of TRAF4/5, facilitating NF-κB pathway-mediated promotion of EOC cell proliferation and migration.


Assuntos
Carcinoma Epitelial do Ovário/genética , Antígenos HLA/genética , Antígenos de Histocompatibilidade Classe I/genética , MicroRNAs/genética , RNA Longo não Codificante/genética , Fator 4 Associado a Receptor de TNF/genética , Fator 5 Associado a Receptor de TNF/genética , Regiões 3' não Traduzidas , Adulto , Idoso , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Biologia Computacional/métodos , Feminino , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Humanos , Pessoa de Meia-Idade , Gradação de Tumores , Metástase Neoplásica , Estadiamento de Neoplasias , Interferência de RNA , Transdução de Sinais
7.
Faraday Discuss ; 233(0): 190-205, 2022 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-34889342

RESUMO

Copper is the most widely used substrate for Li deposition and dissolution in lithium metal anodes, which is complicated by the formation of solid electrolyte interphases (SEIs), whose physical and chemical properties can affect Li deposition and dissolution significantly. However, initial Li nucleation and growth on bare Cu creates Li nuclei that only partially cover the Cu surface so that SEI formation could proceed not only on Li nuclei but also on the bare region of the Cu surface with different kinetics, which may affect the follow-up processes distinctively. In this paper, we employ in situ atomic force microscopy (AFM), together with X-ray photoelectron spectroscopy (XPS), to investigate how SEIs formed on a Cu surface, without Li participation, and on the surface of growing Li nuclei, with Li participation, affect the components and structures of the SEIs, and how the formation sequence of the two kinds of SEIs, along with Li deposition, affect subsequent dissolution and re-deposition processes in a pyrrolidinium-based ionic liquid electrolyte containing a small amount of water. Nanoscale in situ AFM observations show that sphere-like Li deposits may have differently conditioned SEI-shells, depending on whether Li nucleation is preceded by the formation of the SEI on Cu. Models of integrated-SEI shells and segmented-SEI shells are proposed to describe SEI shells formed on Li nuclei and SEI shells sequentially formed on Cu and then on Li nuclei, respectively. "Top-dissolution" is observed for both types of shelled Li deposits, but the integrated-SEI shells only show wrinkles, which can be recovered upon Li re-deposition, while the segmented-SEI shells are apparently top-opened due to mechanical stresses introduced at the junctions of the top regions and become "dead" SEIs, which forces subsequent Li nucleation and growth in the interstice of the dead SEIs. Our work provides insights into the impact mechanism of SEIs on the initial stage Li deposition and dissolution on foreign substrates, revealing that SEIs could be more influential on Li dissolution and that the spatial integration of SEI shells on Li deposits is important to improving the reversibility of deposition and dissolution cycling.

8.
J Neurosci ; 39(26): 5080-5094, 2019 06 26.
Artigo em Inglês | MEDLINE | ID: mdl-31036761

RESUMO

Synucleinopathies are characterized by the accumulation of insoluble α-synuclein (αSyn). To test whether αSyn aggregates modulate synaptic activity, we used a recently developed model in primary neurons for inducing αSyn pathology. We demonstrated that preformed fibrils (PFFs) generated with recombinant human αSyn compromised synaptic activity in a time- and dose-dependent manner and that the magnitude of these deficits correlated with the formation of αSyn pathology in cultured excitatory hippocampal neurons from both sexes of mice. Remarkably, acute passive infusion of αSyn PFFs from whole-cell patch-clamp pipette decreased mEPSC frequency within 10 min followed by induction of αSyn pathology within 1 d. Moreover, by direct addition of αSyn PFFs into culture medium, the formation of misfolded αSyn inclusions dramatically compromised the colocalization of synaptic markers and altered dynamic changes of dendritic spines, but the viability of neurons was not affected up to 7 d post-treatment with αSyn PFFs. Our data indicate that intraneuronal αSyn fibrils impaired the initiation of synaptogenesis and their physiological functions, thereby suggesting that targeting synaptic dysfunction in synucleinopathies may provide a promising therapeutic direction.SIGNIFICANCE STATEMENT Under pathological conditions, the presynaptic protein α-synuclein (αSyn) aggregates to form intraneuronal inclusions. To understand how and to what extent αSyn aggregates modulate synaptic activity before neuron loss, we demonstrate that αSyn preformed fibrils (PFFs) reduced synaptic activity in a dose- and time-dependent manner. The magnitude of these deficits correlated with the deposition of αSyn pathology, which dramatically compromised the colocalization of synaptic markers and altered the dendritic spine dynamics. The present work further highlights the impact of αSyn PFFs on synaptogenesis and physiological function, which may be applicable to other types of synucleinopathies.


Assuntos
Hipocampo/metabolismo , Neurônios/metabolismo , Agregados Proteicos/fisiologia , Sinapses/metabolismo , alfa-Sinucleína/metabolismo , Animais , Sobrevivência Celular , Hipocampo/patologia , Camundongos , Camundongos Knockout , Neurônios/patologia , Agregação Patológica de Proteínas/metabolismo , Agregação Patológica de Proteínas/patologia , Sinapses/patologia
9.
J Neurosci ; 39(2): 199-211, 2019 01 09.
Artigo em Inglês | MEDLINE | ID: mdl-30381405

RESUMO

Dynamin 1 (dyn1) is required for clathrin-mediated endocytosis in most secretory (neuronal and neuroendocrine) cells. There are two modes of Ca2+-dependent catecholamine release from single dense-core vesicles: full-quantal (quantal) and subquantal in adrenal chromaffin cells, but their relative occurrences and impacts on total secretion remain unclear. To address this fundamental question in neurotransmission area using both sexes of animals, here we report the following: (1) dyn1-KO increased quantal size (QS, but not vesicle size/content) by ≥250% in dyn1-KO mice; (2) the KO-increased QS was rescued by dyn1 (but not its deficient mutant or dyn2); (3) the ratio of quantal versus subquantal events was increased by KO; (4) following a release event, more protein contents were retained in WT versus KO vesicles; and (5) the fusion pore size (dp) was increased from ≤9 to ≥9 nm by KO. Therefore, Ca2+-induced exocytosis is generally a subquantal release in sympathetic adrenal chromaffin cells, implying that neurotransmitter release is generally regulated by dynamin in neuronal cells.SIGNIFICANCE STATEMENT Ca2+-dependent neurotransmitter release from a single vesicle is the primary event in all neurotransmission, including synaptic/neuroendocrine forms. To determine whether Ca2+-dependent vesicular neurotransmitter release is "all-or-none" (quantal), we provide compelling evidence that most Ca2+-induced secretory events occur via the subquantal mode in native adrenal chromaffin cells. This subquantal release mode is promoted by dynamin 1, which is universally required for most secretory cells, including neurons and neuroendocrine cells. The present work with dyn1-KO mice further confirms that Ca2+-dependent transmitter release is mainly via subquantal mode, suggesting that subquantal release could be also important in other types of cells.


Assuntos
Glândulas Suprarrenais/metabolismo , Células Cromafins/metabolismo , Dinamina I/fisiologia , Neurotransmissores/metabolismo , Transmissão Sináptica/fisiologia , Vesículas Sinápticas/metabolismo , Glândulas Suprarrenais/citologia , Animais , Cálcio/farmacologia , Catecolaminas/metabolismo , Dinamina I/genética , Endocitose/fisiologia , Exocitose/efeitos dos fármacos , Feminino , Técnicas In Vitro , Masculino , Camundongos , Camundongos Knockout , Mutação/genética , Vesículas Secretórias/metabolismo
10.
Acta Neuropathol ; 140(6): 831-849, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33021680

RESUMO

Alpha-synuclein (αSyn) preformed fibrils (PFF) induce endogenous αSyn aggregation leading to reduced synaptic transmission. Neuronal activity modulates release of αSyn; however, whether neuronal activity regulates the spreading of αSyn pathology remains elusive. Here, we established a hippocampal slice culture system from wild-type (WT) mice and found that both Ca2+ influx and the uptake of αSyn PFF were higher in the CA3 than in the CA1 sub-region. Pharmacologically enhancing neuronal activity substantially increased αSyn pathology in αSyn PFF-treated hippocampal or midbrain slice cultures and accelerated dopaminergic neuron degeneration. Consistently, neuronal hyperactivity promoted PFF trafficking along axons/dendrites within microfluidic chambers. Unexpectedly, enhancing neuronal activity in LRRK2 G2019S mutant slice cultures further increased αSyn pathology, especially with more Lewy body (LB) forming than in WT slice cultures. Finally, following injection of αSyn PFF and chemogenetic modulators into the dorsal striatum of WT mice, both motor behavior and αSyn pathology were exacerbated likely by enhancing neuronal activity, since they were ameliorated by reducing neuronal activity. Thus, a greater understanding of the impact of neuronal activity on αSyn aggregation and spreading, as well as dopaminergic neuronal vulnerability, may provide new therapeutic strategies for patients with LB disease (LBD).


Assuntos
Encéfalo/patologia , Degeneração Neural/patologia , Neurônios/fisiologia , Sinucleinopatias/patologia , alfa-Sinucleína/metabolismo , Animais , Axônios/patologia , Dopamina/metabolismo , Neurônios Dopaminérgicos/metabolismo , Humanos , Doença por Corpos de Lewy/patologia , Camundongos , Sinucleinopatias/metabolismo
11.
Environ Res ; 184: 109323, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32145552

RESUMO

Volatile organic compounds (VOCs) are perceived as serious pollutants due to their great threat to both environment and human health. Recovery and removal of VOCs is of great significance. Herein, novel MOF-199 derived porous carbon materials (MC-T-n) were prepared by using MOF-199 as precursor, glucose as additional carbon source and KOH as activator, and then characterized. Adsorption performance of MC-T-n materials for benzene vapor was investigated. Isotherms of MC-T-n samples towards benzene and water vapor were measured. The adsorption selectivities of benzene/water were estimated by DIH (difference of the isosteric heats) equation. Results indicated that BET surface area and pore volume of MC-T-n materials reached separately 2320 m2/g and 1.05 m3/g. Benzene adsorption capacity of MC-T-n materials reached as high as 12.8 mmol/g at 25 °C, outperforming MOF-199 and some conventional adsorbents. Moreover, MC-T-n materials presented type-V isotherms of water vapor, suggesting their excellent water resistance. The isosteric heats of benzene adsorption on MC-500-6 were much greater than that of water adsorption, leading to a preferential adsorption for C6H6 over H2O. The adsorption selectivity of C6H6/H2O on MC-500-6 reached up to 16.3 superior to some previously reported MOFs. Therefore, MC-500-6 was a promising candidate for VOC adsorption and seperation. This study provides a strong foundation for MOF derived porous carbons as adsorbents for VOC removal.


Assuntos
Poluição do Ar , Benzeno , Carbono , Adsorção , Poluição do Ar/prevenção & controle , Benzeno/química , Gases , Porosidade
12.
Opt Lett ; 44(4): 931-934, 2019 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-30768023

RESUMO

We realized an efficient spectra-stable tandem white organic light-emitting device (WOLED) with pleasurable warm white emission and an extremely high color-rendering index (CRI) simultaneously by connecting a fluorescent blue unit and a phosphorescent dual-color unit via an easy-fabrication charge generation unit (CGU). Over a wide range of driving current density, the tandem warm white OLED exhibited general CRI (Ra) value exceeding 85 and special CRI (R9) value close to 57. In addition, Duvs are within the tolerance for CRI measurements, ensuring validity and logicality of the calculated results concerning Ra and R9. The obtained tandem OLED showed the maximum efficiencies of 38 cd/A and 22.9 lm/W, and still maintained high efficiencies of 35.5 cd/A and 17.2 lm/W at the luminance of 1000 cd/m2. Moreover, we studied the origins of both extreme color stability in dual-color OLED and extremely efficient electron injection within the CGU. To the best of our knowledge, this is the first report regarding quantitative values of both R9 and the Duv for a high-Ra tandem WOLED.

13.
Biochem Biophys Res Commun ; 497(4): 1162-1170, 2018 03 18.
Artigo em Inglês | MEDLINE | ID: mdl-28057486

RESUMO

Epithelial ovarian cancer (EOC) is the most lethal gynecologic cancer. Although molecular diagnostic tools and targeted therapies have been developed over the past few decades, the survival rate is still rather low. Numerous researches suggest that some microRNAs (miRNAs) are key regulators of tumor progression. Among those miRNAs that has attracted much attention for their multiple roles in human cancers, the function of miR-221-3p in EOC has not been elucidated. Herein, we examined the expression of miR-221-3p in EOC patients and cell lines. Our data revealed that higher expression of miR-221-3p was linked to better overall survival in EOC patients. In-vitro experiments indicated that miR-221-3p inhibited EOC cell proliferation and migration. By performing subsequent systematic molecular biological and bioinformatic analyses, we found ADP-ribosylation factor (ARF) 4 is one of the putative target genes, the direct binding relationship was further confirmed by dual-luciferase reporter assay. Finally, a distinct gene expression between miR-221-3p and ARF4 in EOC group and normal group was identified, and the negative correlation between their expression levels in EOC specimens was further confirmed. Taken together, our research uncovered the tumor suppressive role of miR-221-3p in EOC and directly targeted ARF4, suggesting that miR-221-3p might be a novel potential candidate for clinical prognosis and therapeutics of EOC.


Assuntos
Fatores de Ribosilação do ADP/antagonistas & inibidores , MicroRNAs/fisiologia , Neoplasias Epiteliais e Glandulares/patologia , Neoplasias Ovarianas/patologia , Fatores de Ribosilação do ADP/genética , Adulto , Carcinoma Epitelial do Ovário , Linhagem Celular , Movimento Celular , Proliferação de Células , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Epiteliais e Glandulares/tratamento farmacológico , Neoplasias Epiteliais e Glandulares/mortalidade , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/mortalidade , Taxa de Sobrevida
14.
EMBO Rep ; 17(1): 47-63, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26589353

RESUMO

Precise and efficient endocytosis is essential for vesicle recycling during a sustained neurotransmission. The regulation of endocytosis has been extensively studied, but inhibitors have rarely been found. Here, we show that synaptotagmin-11 (Syt11), a non-Ca(2+)-binding Syt implicated in schizophrenia and Parkinson's disease, inhibits clathrin-mediated endocytosis (CME) and bulk endocytosis in dorsal root ganglion neurons. The frequency of both types of endocytic event increases in Syt11 knockdown neurons, while the sizes of endocytosed vesicles and the kinetics of individual bulk endocytotic events remain unaffected. Specifically, clathrin-coated pits and bulk endocytosis-like structures increase on the plasma membrane in Syt11-knockdown neurons. Structural-functional analysis reveals distinct domain requirements for Syt11 function in CME and bulk endocytosis. Importantly, Syt11 also inhibits endocytosis in hippocampal neurons, implying a general role of Syt11 in neurons. Taken together, we propose that Syt11 functions to ensure precision in vesicle retrieval, mainly by limiting the sites of membrane invagination at the early stage of endocytosis.


Assuntos
Vesículas Revestidas por Clatrina/fisiologia , Clatrina/metabolismo , Endocitose , Neurônios/metabolismo , Sinaptotagminas/genética , Sinaptotagminas/metabolismo , Animais , Exocitose , Gânglios Espinais/citologia , Técnicas de Silenciamento de Genes , Neurônios/ultraestrutura , Ratos , Transmissão Sináptica/genética , Transmissão Sináptica/fisiologia
15.
Nanotechnology ; 28(6): 065401, 2017 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-28045009

RESUMO

Nanostructured fluorine-doped α-Fe2O3 nanorods were synthesized based on a one-step low temperature hydrothermal method. The XPS results verified that fluorine has been successfully incorporated into the hematite lattice. The delivered lithium capacity was effectively improved owing to the fluorine doping comparing with the pristine α-Fe2O3. The increase in electrochemical capacity of fluorine-doped α-Fe2O3 was then studied from the pointviews of nanostructure, electronic properties, and magnetic characteristics.

16.
Biol Pharm Bull ; 40(4): 435-443, 2017 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-28111380

RESUMO

Tumor necrosis factor-alpha (TNF-α) plays an important role in the developing process of inflammatory bowel disease. Tight junction protein zonula occludens-1 (ZO-1), one of epithelial junctional proteins, maintains the permeability of intestinal barrier. The objective of this study was to investigate the mechanism of the protective effect of baicalin on TNF-α-induced injury and ZO-1 expression in intestinal epithelial cells (IECs). We found that baicalin pretreatment significantly improved cell viability and cell migration following TNF-α stimulation. miR-191a inhibitor increased the protective effect of baicalin on cell motility injured by TNF-α. In addition, miR-191a down-regulated the mRNA and protein level of its target gene ZO-1. TNF-α stimulation increased miR-191a expression, leading to the decline of ZO-1 mRNA and protein. Moreover, pretreatment with baicalin reversed TNF-α induced decrease of ZO-1 and increase of miR-191a, miR-191a inhibitor significantly enhanced ZO-1 protein expression restored by baicalin. These results indicate that baicalin exerts a protective effect on IEC-6 (rat small intestinal epithelial cells) cells against TNF-α-induced injury, which is at least partly via inhibiting the expression of miR-191a, thus increasing ZO-1 mRNA and protein levels.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Flavonoides/farmacologia , MicroRNAs/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Proteína da Zônula de Oclusão-1/genética , Animais , Linhagem Celular , Movimento Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Regulação para Baixo , Medicamentos de Ervas Chinesas/farmacologia , Humanos , Doenças Inflamatórias Intestinais/metabolismo , Mucosa Intestinal/metabolismo , Intestino Delgado/metabolismo , MicroRNAs/antagonistas & inibidores , Permeabilidade/efeitos dos fármacos , Substâncias Protetoras/farmacologia , RNA Mensageiro/metabolismo , Ratos , Scutellaria baicalensis/química , Junções Íntimas/efeitos dos fármacos , Junções Íntimas/metabolismo , Proteína da Zônula de Oclusão-1/metabolismo
17.
Mol Divers ; 21(4): 791-807, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28770474

RESUMO

ROCK II is an important pharmacological target linked to central nervous system disorders such as Alzheimer's disease. The purpose of this research is to generate ROCK II inhibitor prediction models by machine learning approaches. Firstly, four sets of descriptors were calculated with MOE 2010 and PaDEL-Descriptor, and optimized by F-score and linear forward selection methods. In addition, four classification algorithms were used to initially build 16 classifiers with k-nearest neighbors [Formula: see text], naïve Bayes, Random forest, and support vector machine. Furthermore, three sets of structural fingerprint descriptors were introduced to enhance the predictive capacity of classifiers, which were assessed with fivefold cross-validation, test set validation and external test set validation. The best two models, MFK + MACCS and MLR + SubFP, have both MCC values of 0.925 for external test set. After that, a privileged substructure analysis was performed to reveal common chemical features of ROCK II inhibitors. Finally, binding modes were analyzed to identify relationships between molecular descriptors and activity, while main interactions were revealed by comparing the docking interaction of the most potent and the weakest ROCK II inhibitors. To the best of our knowledge, this is the first report on ROCK II inhibitors utilizing machine learning approaches that provides a new method for discovering novel ROCK II inhibitors.


Assuntos
Simulação por Computador , Inibidores de Proteínas Quinases/farmacologia , Quinases Associadas a rho/antagonistas & inibidores , Descoberta de Drogas , Simulação de Acoplamento Molecular , Conformação Proteica , Inibidores de Proteínas Quinases/química , Inibidores de Proteínas Quinases/metabolismo , Quinases Associadas a rho/química , Quinases Associadas a rho/metabolismo
18.
Proc Natl Acad Sci U S A ; 111(44): 15804-9, 2014 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-25331880

RESUMO

Embryonic stem cell-based therapies exhibit great potential for the treatment of Parkinson's disease (PD) because they can significantly rescue PD-like behaviors. However, whether the transplanted cells themselves release dopamine in vivo remains elusive. We and others have recently induced human embryonic stem cells into primitive neural stem cells (pNSCs) that are self-renewable for massive/transplantable production and can efficiently differentiate into dopamine-like neurons (pNSC-DAn) in culture. Here, we showed that after the striatal transplantation of pNSC-DAn, (i) pNSC-DAn retained tyrosine hydroxylase expression and reduced PD-like asymmetric rotation; (ii) depolarization-evoked dopamine release and reuptake were significantly rescued in the striatum both in vitro (brain slices) and in vivo, as determined jointly by microdialysis-based HPLC and electrochemical carbon fiber electrodes; and (iii) the rescued dopamine was released directly from the grafted pNSC-DAn (and not from injured original cells). Thus, pNSC-DAn grafts release and reuptake dopamine in the striatum in vivo and alleviate PD symptoms in rats, providing proof-of-concept for human clinical translation.


Assuntos
Corpo Estriado/metabolismo , Dopamina/metabolismo , Células-Tronco Neurais/metabolismo , Doença de Parkinson/metabolismo , Doença de Parkinson/terapia , Transplante de Células-Tronco , Animais , Diferenciação Celular , Corpo Estriado/patologia , Neurônios Dopaminérgicos/metabolismo , Neurônios Dopaminérgicos/patologia , Xenoenxertos , Humanos , Masculino , Células-Tronco Neurais/transplante , Doença de Parkinson/patologia , Ratos , Ratos Sprague-Dawley , Tirosina 3-Mono-Oxigenase/metabolismo
19.
Nanotechnology ; 27(36): 365702, 2016 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-27479275

RESUMO

Atomic-level substitutional doping can significantly tune the electronic properties of graphene. Using low-temperature scanning tunneling microscopy and spectroscopy, the atomic-scale crystalline structure of graphene grown on polycrystalline Cu, the distribution of nitrogen dopants and their effect on the electronic properties of graphene were investigated. Both the graphene sheet growth and nitrogen doping were performed using microwave plasma-enhanced chemical vapor deposition. The results indicated that the nitrogen dopants preferentially sit at the grain boundaries of the graphene sheets and confirmed that plasma treatment is a potential method to incorporate foreign atoms into the graphene lattice to tailor the graphene's electronic properties.

20.
Diabetologia ; 58(2): 324-33, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25381556

RESUMO

AIMS/HYPOTHESIS: Insulin is a key metabolic regulator in health and diabetes. In pancreatic beta cells, insulin release is regulated by the major second messengers Ca(2+) and cAMP: exocytosis is triggered by Ca(2+) and mediated by the cAMP/protein kinase A (PKA) signalling pathway. However, the causal link between these two processes in primary beta cells remains undefined. METHODS: Time-resolved confocal imaging of fluorescence resonance energy transfer signals was performed to visualise PKA activity, and combined membrane capacitance recordings were used to monitor insulin secretion from patch-clamped rat beta cells. RESULTS: Membrane depolarisation-induced Ca(2+) influx caused an increase in cytosolic PKA activity via activating a Ca(2+)-sensitive adenylyl cyclase 8 (ADCY8) subpool. Glucose stimulation triggered coupled Ca(2+) oscillations and PKA activation. ADCY8 knockdown significantly reduced the level of depolarisation-evoked PKA activation and impaired replenishment of the readily releasable vesicle pool. Pharmacological inhibition of PKA by two inhibitors reduced depolarisation-induced PKA activation to a similar extent and reduced the capacity for sustained vesicle exocytosis and insulin release. CONCLUSIONS/INTERPRETATION: Our findings suggest that depolarisation-induced Ca(2+) influx plays dual roles in regulating exocytosis in rat pancreatic beta cells by triggering vesicle fusion and replenishing the vesicle pool to support sustained insulin release. Therefore, Ca(2+) influx may be important for glucose-stimulated insulin secretion.


Assuntos
Adenilil Ciclases/metabolismo , Cálcio/metabolismo , Células Secretoras de Insulina/metabolismo , Animais , Células Cultivadas , AMP Cíclico/metabolismo , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Modelos Animais de Doenças , Técnicas de Patch-Clamp , Ratos , Ratos Wistar , Transdução de Sinais
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