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1.
Genomics ; 2020 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-32027955

RESUMO

Myostatin (MSTN) was previously shown to differentially regulate the adipogenesis of adipose-derived stem cells (ADSCs) and muscle satellite cells (MSCs), both of which can serve as progenitor cells for intramuscular adipocytes. We previously showed that MSTN mediates the differential regulation of MyoD and PPARγ in ADSCs and MSCs. Here, we analyzed the effects of MSTN on whole-transcriptome expression profiles of ADSCs and MSCs, revealing that MSTN differentially regulates ADSCs and MSCs, with MSCs being more responsive to MSTN treatment. More genes and pathways were altered in MSCs than in ADSCs. These changes may be responsible for the differences in the adipogenesis potential of ADSCs and MSCs after MSTN treatment. Analysis of the functions of genes that are differentially expressed in ADSCs and MSCs showed that KLF6 is a positive regulator of adipogenesis. In conclusion, the results provide important molecular insights into the regulatory mechanisms of MSTN in ADSCs and MSCs.

2.
Mar Pollut Bull ; 151: 110818, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32056610

RESUMO

To evaluate changes in the source of sedimentary organic matter (OM) in the Yellow River estuary, a sediment core collected in eastern Laizhou Bay was analyzed for total organic carbon (TOC), stable carbon isotopes of TOC, and biomarkers. The results showed a decreasing trend in terrestrial OM (TOM), but an increasing trend in marine OM (MOM) over the past 60 years. TOM was subdivided into soil OM and plant OM in a three end-member mixing model. The soil OM gradually decreased over the past 60 years, with a significant decline since the 1980s, while the plant OM gradually increased. This reveals that the reduction in TOM was caused mainly by the decreased input of soil OM. The reduced TOM contribution can be attributed primarily to dam construction and a decline in precipitation, whereas the elevated MOM contribution was caused by enhanced marine productivity driven by a rise in nutrient inputs.


Assuntos
Monitoramento Ambiental , Estuários , Rios , Poluentes da Água/análise , China , Sedimentos Geológicos , Solo
3.
ACS Nano ; 2020 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-31961130

RESUMO

Stacking order has a strong influence on the coupling between the two layers of twisted bilayer graphene (BLG), which in turn determines its physical properties. Here, we report the investigation of the interlayer coupling of the epitaxially grown single-crystal 30°-twisted BLG on Cu(111) at the atomic scale. The stacking order and morphology of BLG is controlled by a rationally designed two-step growth process, that is, the thermodynamically controlled nucleation and kinetically controlled growth. The crystal structure of the 30°-twisted bilayer graphene (30°-tBLG) is determined to have quasicrystal-like symmetry. The electronic properties and interlayer coupling of the 30°-tBLG are investigated using scanning tunneling microscopy and spectroscopy. The energy-dependent local density of states with in situ electrostatic doping shows that the electronic states in two graphene layers are decoupled near the Dirac point. A linear dispersion originated from the constituent graphene monolayers is discovered with doubled degeneracy. This study contributes to controlled growth of twist-angle-defined BLG and provides insights on the electronic properties and interlayer coupling in this intriguing system.

4.
Nat Commun ; 11(1): 541, 2020 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-31992713

RESUMO

The fast development of high-resolution electron microscopy (EM) demands a background-noise-free substrate to support the specimens, where atomically thin graphene membranes can serve as an ideal candidate. Yet the preparation of robust and ultraclean graphene EM grids remains challenging. Here we present a polymer- and transfer-free direct-etching method for batch fabrication of robust ultraclean graphene grids through membrane tension modulation. Loading samples on such graphene grids enables the detection of single metal atoms and atomic-resolution imaging of the iron core of ferritin molecules at both room- and cryo-temperature. The same kind of hydrophilic graphene grid allows the formation of ultrathin vitrified ice layer embedded most protein particles at the graphene-water interface, which facilitates cryo-EM 3D reconstruction of archaea 20S proteasomes at a record high resolution of ~2.36 Å. Our results demonstrate the significant improvements in image quality using the graphene grids and expand the scope of EM imaging.


Assuntos
Grafite/química , Microscopia Eletrônica/instrumentação , Microscopia Eletrônica/métodos , Fenômenos Químicos , Microscopia Crioeletrônica/métodos , Elétrons , Desenho de Equipamento , Processamento de Imagem Assistida por Computador , Membranas , Polímeros , Proteínas
5.
Life Sci ; 240: 117069, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31751582

RESUMO

AIM: Intraluminal thrombus (ILT) is presented in most abdominal aortic aneurysms (AAAs) and is suggested to promote AAA expansion. D-dimer, a breakdown product in the thrombus remodeling, may have prognostic value for AAA. This study investigated the interrelation between plasma D-dimer level, ILT volume, AAA size and progression. MAIN METHODS: This was a retrospective observational study that involved 181 patients with infra-renal AAA. They were divided into small and large AAA groups according to AAA diameter. 24 of them had repeated abdominal computed tomography angiography (CTA) scan and were divided into slow-growing and fast-growing AAA groups according to the median value of AAA growth rate. Baseline and follow-up plasma D-dimer level, maximum diameter of AAA, total infra-renal aortic volume and ILT volume were analyzed. KEY FINDINGS: Plasma D-dimer level was positively correlated with ILT volume (R = 0.382, P < 0.001) and maximum diameter of AAA (R = 0.442, P < 0.001). Increasing value of plasma D-dimer was positively associated with the accelerated growth rate of AAA (R = 0.720, P < 0.01). ILT volume showed positive correlation with maximum diameter (R = 0.859, P < 0.001) and growth rate of AAA (R = 0.490, P < 0.05). After adjusting the baseline ILT volume, the positive correlations remained to be statistically significant between plasma D-dimer level and AAA size (R = 0.200, P < 0.05), as well as increasing value of plasma D-dimer and growth rate of AAA (R = 0.642, P < 0.05). SIGNIFICANCE: Plasma D-dimer level reflected ILT burden in AAAs. Plasma D-dimer level and ILT volume were positively correlated with AAA size. Increasing value of plasma D-dimer and baseline ILT volume could be predictors of AAA progression.


Assuntos
Aneurisma da Aorta Abdominal/diagnóstico , Aneurisma da Aorta Abdominal/etiologia , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Trombose/complicações , Trombose/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Aneurisma da Aorta Abdominal/sangue , Efeitos Psicossociais da Doença , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Estudos Retrospectivos , Fumar/epidemiologia , Trombose/sangue , Tomografia Computadorizada por Raios X
6.
BMC Bioinformatics ; 20(1): 469, 2019 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-31519146

RESUMO

BACKGROUND: Long-chain non-coding RNA (lncRNA) is closely related to many biological activities. Since its sequence structure is similar to that of messenger RNA (mRNA), it is difficult to distinguish between the two based only on sequence biometrics. Therefore, it is particularly important to construct a model that can effectively identify lncRNA and mRNA. RESULTS: First, the difference in the k-mer frequency distribution between lncRNA and mRNA sequences is considered in this paper, and they are transformed into the k-mer frequency matrix. Moreover, k-mers with more species are screened by relative entropy. The classification model of the lncRNA and mRNA sequences is then proposed by inputting the k-mer frequency matrix and training the convolutional neural network. Finally, the optimal k-mer combination of the classification model is determined and compared with other machine learning methods in humans, mice and chickens. The results indicate that the proposed model has the highest classification accuracy. Furthermore, the recognition ability of this model is verified to a single sequence. CONCLUSION: We established a classification model for lncRNA and mRNA based on k-mers and the convolutional neural network. The classification accuracy of the model with 1-mers, 2-mers and 3-mers was the highest, with an accuracy of 0.9872 in humans, 0.8797 in mice and 0.9963 in chickens, which is better than those of the random forest, logistic regression, decision tree and support vector machine.


Assuntos
RNA Longo não Codificante/genética , RNA Mensageiro/genética , Animais , Galinhas , Humanos , Camundongos
7.
Adv Mater ; 31(43): e1902978, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31502709

RESUMO

Contamination is a major concern in surface and interface technologies. Given that graphene is a 2D monolayer material with an extremely large surface area, surface contamination may seriously degrade its intrinsic properties and strongly hinder its applicability in surface and interfacial regions. However, large-scale and facile treatment methods for producing clean graphene films that preserve its excellent properties have not yet been achieved. Herein, an efficient postgrowth treatment method for selectively removing surface contamination to achieve a large-area superclean graphene surface is reported. The as-obtained superclean graphene, with surface cleanness exceeding 99%, can be transferred to dielectric substrates with significantly reduced polymer residues, yielding ultrahigh carrier mobility of 500 000 cm2 V-1 s-1 and low contact resistance of 118 Ω µm. The successful removal of contamination is enabled by the strong adhesive force of the activated-carbon-based lint roller on graphene contaminants.

8.
EMBO Rep ; 20(11): e47650, 2019 11 05.
Artigo em Inglês | MEDLINE | ID: mdl-31486214

RESUMO

LTR retrotransposons are abundant repetitive elements in the human genome, but their functions remain poorly understood. Here, we report the function and regulatory mechanism of an ERV-9 LTR retrotransposon-derived lncRNA called p53-regulated lncRNA for homologous recombination (HR) repair 1 (PRLH1) in human cells. PRLH1 is highly expressed in p53-mutated hepatocellular carcinoma (HCC) samples and promotes cell proliferation in p53-mutated HCC cells, and its transcription is promoted by NF-Y and suppressed by p53. Mechanistically, PRLH1 specifically binds to an uncharacterized domain of RNF169 through two GCUUCA boxes in its 5' terminal region to form a DNA repair complex that supplants 53BP1 at double-strand break (DSB) sites and then promotes the initiation of HR repair. Notably, PRLH1 is essential for the stabilization of RNF169, acting as an RNA platform to recruit and assemble HR protein factors. This study characterizes PRLH1 as a novel HR-promoting factor and provides new insights into the function and mechanism of LTR retrotransposon-derived lncRNAs.

9.
Nanoscale ; 11(27): 13117-13125, 2019 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-31268079

RESUMO

Using graphene as electrodes provides an opportunity for fabricating stable single-molecule field-effect transistors (FETs) operating at room temperature. However, the role of the unique graphene band structure in charge transport of single-molecule devices is still not clear. Here we report the Dirac-cone induced electrostatic gating effects in single-molecule FETs with graphene electrodes and a solid-state local bottom gate. With the highest occupied molecular orbital (HOMO) as the dominating conduction channel and the graphene leads remaining intrinsic at zero gate voltage, electrostatic gating on the HOMO and the density of states of graphene at the negative gate polarity reinforces each other, resulting in an enhanced conductance modulation. In contrast, gating effects on the HOMO and the graphene states at the positive gate polarity are opposite. Depending on the gating efficiencies, the conductance can decrease, increase or remain almost unchanged when a more positive gate voltage is applied. Our observations can be well understood by a modified single-level model taking into account the linear dispersion of graphene near the Dirac point. Single-molecule FETs with Dirac-cone enhanced gating have shown high performances, with the modulation of a wide range of current over one order of magnitude. Our studies highlight the advantages of using graphene as an electrode material for molecular devices and pave the way for single-molecule FETs toward circuitry applications.

10.
Pathol Oncol Res ; 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31264122

RESUMO

Colorectal cancer (CRC) is one of the most aggressive tumours in the human digestive system. Most CRC patients have poor prognosis due to metastasis and recurrence. Angiopoietin-like 4 (ANGPTL4) is involved in tumour development. Regulatory T (Treg) cells and M2 macrophages promote tumour growth and metastasis. Herein, we explored the changes of ANGPTL4 expression in CRC patients at different stages and observed whether in situ tumour-Treg and -M2 macrophages are correlated with ANGPTL4 expression. Serum ANGPTL4 (sANGPTL4) levels of 70 CRC patients and 10 healthy controls were detected by ELISA. ANGPTL4, Foxp3 and CD163 expression levels in CRC tissues were measured by immunohistochemistry. Recombinant ANGPTL4 (rANGPTL4) proteins were further added into cell-culture systems for induction of Treg cells and M2 macrophages. The results showed both sANGPTL4 and in situ tumour-ANGPTL4 expression levels increased in Dukes C-D stage CRC patients. Foxp3+ and CD163+ cells in tumour tissue sections were also more intensive in Dukes C-D stage patients than in Dukes A-B stage patients. Foxp3+ and CD163+ cells in tumour tissues were positively correlated with both tissue and sANGPTL4 expression (P < 0.01). Recombinant ANGPTL4 promoted the induction of murine Treg cells and M2 macrophages ex vivo. Therefore, elevated ANGPTL4 expression could be a marker for advanced CRC. Treg cell and M2 macrophage induction could be one of the mechanisms of tumour promotion mediated by ANGPTL4.

11.
Toxicol In Vitro ; 61: 104608, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31348984

RESUMO

Tritium is an important radioactive waste which needs to be monitored for radiation protection. Due to long biological half-life of organically bound tritium (OBT), the adverse consequence caused by chronic exposure of tritiated water (HTO) attracts concern. In this study, fibroblast cells were exposed to 2 × 106 Bq/ml HTO to investigate the cellular behaviors. The dose relationship of survival fraction and γH2AX foci was a "U-shaped" curve. And the results of γH2AX intensity produced by ICCM, which was obtained from different doses, demonstrated bystander signal accounted for the protective effects induced by intermediate dose of 100 mGy. The comparison of temporal kinetics and spatial dynamics of DNA repair between tritium ß-rays and γ-rays showed longer time was need for the dephosphorylation of H2AX protein after HTO exposure. It indicated complex cluster DSBs induced by tritium ß-rays at the low dose impaired efficient recovery of DNA damage, which bear responsibility for the persistence of residual foci after low dose expsoure. It suggests after exposed to low dose radiation cells prefer to eliminate damage population to avoid DNA damage increasing the mutation potential.

12.
Sci China Life Sci ; 2019 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-31240521

RESUMO

The roles of concealed microproteins encoded by long noncoding RNAs (lncRNAs) are gradually being exposed, but their functions in tumorigenesis are still largely unclear. Here, we identify and characterize a conserved 99-amino acid microprotein named KRASIM that is encoded by the putative lncRNA NCBP2-AS2. KRASIM is differentially expressed in normal hepatocytes and hepatocellular carcinoma (HCC) cells and can suppress HCC cell growth and proliferation. Mechanistically, KRASIM interacts and colocalizes with the KRAS protein in the cytoplasm of human HuH-7 hepatoma cells. More importantly, the overexpression of KRASIM decreases the KRAS protein level, leading to the inhibition of ERK signaling activity in HCC cells. These results demonstrate a novel microprotein repressor of the KRAS pathway for the first time and provide new insights into the regulatory mechanisms of oncogenic signaling and HCC therapy.

13.
Micromachines (Basel) ; 10(6)2019 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-31248148

RESUMO

The single-cell capture microfluidic chip has many advantages, including low cost, high throughput, easy manufacturing, integration, non-toxicity and good stability. Because of these characteristics, the cell capture microfluidic chip is increasingly becoming an important carrier on the study of life science and pharmaceutical analysis. Important promises of single-cell analysis are the paring, fusion, disruption and analysis of intracellular components for capturing a single cell. The capture, which is based on the fluid dynamics method in the field of micro fluidic chips is an important way to achieve and realize the operations mentioned above. The aim of this study was to compare the ability of three fluid dynamics-based microfluidic chip structures to capture cells. The effects of cell growth and distribution after being captured by different structural chips and the subsequent observation and analysis of single cells on the chip were compared. It can be seen from the experimental results that the microfluidic chip structure most suitable for single-cell capture is a U-shaped structure. It enables single-cell capture as well as long-term continuous culture and the single-cell observation of captured cells. Compared to the U-shaped structure, the cells captured by the microcavity structure easily overlapped during the culture process and affected the subsequent analysis of single cells. The flow shortcut structure can also be used to capture and observe single cells, however, the shearing force of the fluid caused by the chip structure is likely to cause deformation of the cultured cells. By comparing the cell capture efficiency of the three chips, the reagent loss during the culture process and the cell growth state of the captured cells, we are provided with a theoretical support for the design of a single-cell capture microfluidic chip and a reference for the study of single-cell capture in the future.

14.
J Radiat Res ; 60(4): 476-482, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31165153

RESUMO

There is no doubt that estimating the exposure risk of external and internal low-dose radiation is an imperative issue in radiobiological study. Human mesenchymal stem cells (hMSCs) are multipotent and self-renewing, supporting the regeneration of damaged tissue, including tissue damaged by radiation. However, the responses of hMSCs to internal exposure to radionuclides are still insufficiently understood. In order to evaluate the adverse effects produced by internal exposure to tritiated water (HTO) at a low dose, hMSCs were exposed to 2 × 107 Bq/ml HTO, and the biological effects after the exposure were examined. Apoptosis and DNA double-strand breaks (DSBs) were assayed to analyze the cellular response to the damage induced by HTO. Slight enhancement of apoptosis was found after treatment, except at the dose of 9 mGy. The number of DSBs at 24 h post-irradiation showed that the DNA damage was able to be efficiently repaired by the hMSCs. Moreover, the increasing proportion of the cell population in S phase proved that the persistence of residual γH2AX foci at lower concentrations of HTO was attributable to the secondary production of DSBs in DNA replication. Our work adds to the available data, helping us understand the risk of stem cell transformation due to internal exposure and its correlation with low-dose radiation-induced carcinogenesis.


Assuntos
Células-Tronco Mesenquimais/efeitos da radiação , Trítio/química , Apoptose/efeitos da radiação , Partículas beta , Ciclo Celular/efeitos da radiação , Células Cultivadas , Quebras de DNA de Cadeia Dupla/efeitos da radiação , Replicação do DNA/efeitos da radiação , Histonas/metabolismo , Humanos , Radioisótopos , Água
15.
Biomed Pharmacother ; 113: 108773, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30889484

RESUMO

OBJECTIVES: This study was to evaluate platelet reactivity over time among patients with chronic kidney disease (CKD) receiving standard dose of clopidogrel after percutaneous coronary intervention (PCI). The effect of CYP2C19 loss-of-function genotypes on platelet reactivity was also determined. METHODS: Patients with CKD (n = 138) on maintenance dose of clopidogrel after PCI were enrolled. Platelet reactivity was assessed by measuring P2Y12 reaction units (PRU) with VerifyNow P2Y12 assay, and platelet reactivity index (PRI) with flow cytometric using vasodilator-stimulated phosphoprotein (VASP) at baseline and 2 weeks later, respectively. The genotypes of CYP2C19 were also measured concurrently. RESULTS: The proportion of patients with high platelet reactivity (HPR) ranged from 23.2% to 59.4%, and almost 1 in 5 patients had a dual conversion between HPR and non-HPR status. Patients carrying CYP2C19 loss-of-function genotypes showed a higher platelet reactivity than non-carriers, but with an undetermined HPR status between the first and second visits. The individual switch of HPR to non-HPR status existed in both loss-of-function genotype carriers and non-carriers. CONCLUSIONS: HPR conversions occur in a significant proportion of CKD patients with maintenance doses of clopidogrel treatment post-PCI, and this conversion was not confined to CYP2C19 loss-of-function genotype carriers. Risk stratification for treatment adjustment in personalized antiplatelet therapy should be investigated in future research.


Assuntos
Plaquetas/efeitos dos fármacos , Doença da Artéria Coronariana/terapia , Inibidores da Agregação de Plaquetas/farmacologia , Insuficiência Renal Crônica/fisiopatologia , Idoso , Plaquetas/metabolismo , Clopidogrel/farmacologia , Citocromo P-450 CYP2C19/genética , Feminino , Citometria de Fluxo , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Intervenção Coronária Percutânea/métodos , Stents , Fatores de Tempo
16.
Environ Pollut ; 249: 225-235, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30893635

RESUMO

High resolution sediment records in the Yangtze Delta front were constructed to reveal recent environmental changes in response to river basin human activities. Increases in nutrient and organic C influxes that began in the 1950s, together with elevated primary productivity and increased chemical fertilizer application, suggested a shift toward anthropogenic-predominated environmental changes during this period. The depletion of total organic C (TOC), total N (TN), and biogenic Si (BSi), along with the decline in sedimentation rate and coarsening of sediment coincided with the development of hydrological engineering in the river basin from the 1980s. Reservoir Si retention substantially altered river mouth primary productivity community composition from diatoms to non-diatoms, thereby changing the BSi/TOC molar ratio in the sediment profile. Estimation of biogenic component burial fluxes was conducted to assess the variation and potential impacts. A recent dramatic decline in biogenic component burial in the delta area suggested a low nutrient removal efficiency in this region, due to the decrease in sediment discharge. Consequently, more nutrients have been further transported to the inner shelf and open waters instead of being buried in the delta sediment, thereby increasing the environmental pressure in the Yangtze Delta and adjoining coastal area.


Assuntos
Monitoramento Ambiental , Sepultamento , China , Diatomáceas , Fertilizantes , Sedimentos Geológicos/química , Atividades Humanas , Humanos , Nitrogênio/análise , Fósforo/análise , Rios/química , Poluentes da Água/análise
17.
Nano Lett ; 19(3): 2148-2153, 2019 03 13.
Artigo em Inglês | MEDLINE | ID: mdl-30835131

RESUMO

Emerging two-dimensional (2D) semiconducting materials serve as promising alternatives for next-generation digital electronics and optoelectronics. However, large-scale 2D semiconductor films synthesized so far are typically polycrystalline with defective grain boundaries that could degrade their performance. Here, for the first time, wafer-size growth of a single-crystal Bi2O2Se film, which is a novel air-stable 2D semiconductor with high mobility, was achieved on insulating perovskite oxide substrates [SrTiO3, LaAlO3, (La, Sr)(Al, Ta)O3]. The layered Bi2O2Se epilayer exhibits perfect lattice matching and strong interaction with perovskite oxide substrates, which enable unidirectional alignment and seamless mergence of multiple seeds into single-crystal continuous films free of detrimental grain boundaries. The single-crystal Bi2O2Se thin films show excellent spatial homogeneity over the entire wafer and allow for the batch fabrication of high-performance field-effect devices with high mobilities of ∼150 cm2 V-1 s-1 at room temperature, excellent switching behavior with large on/off ratio of >105, and high drive current of ∼45 µA µm-1 at a channel length of ∼5 µm. Our work makes a step toward the practical applications of high-mobility semiconducting 2D layered materials and provides an alternative platform of oxide heterostructure to investigate novel physical phenomena.

18.
Proc Natl Acad Sci U S A ; 116(11): 5154-5159, 2019 03 12.
Artigo em Inglês | MEDLINE | ID: mdl-30804206

RESUMO

A high-fat diet (HFD) causes obesity-associated morbidities involved in macroautophagy and chaperone-mediated autophagy (CMA). AMPK, the mediator of macroautophage, has been reported to be inactivated in HFD-caused renal injury. However, PAX2, the mediator for CMA, has not been reported in HFD-caused renal injury. Here we report that HFD-caused renal injury involved the inactivation of Pax2 and Ampk, and the activation of soluble epoxide hydrolase (sEH), in a murine model. Specifically, mice fed on an HFD for 2, 4, and 8 wk showed time-dependent renal injury, the significant decrease in renal Pax2 and Ampk at both mRNA and protein levels, and a significant increase in renal sEH at mRNA, protein, and molecular levels. Also, administration of an sEH inhibitor, 1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl)urea, significantly attenuated the HFD-caused renal injury, decreased renal sEH consistently at mRNA and protein levels, modified the renal levels of sEH-mediated epoxyeicosatrienoic acids (EETs) and dihydroxyeicosatrienoic acids (DHETs) as expected, and increased renal Pax2 and Ampk at mRNA and/or protein levels. Furthermore, palmitic acid (PA) treatment caused significant increase in Mcp-1, and decrease in both Pax2 and Ampk in murine renal mesangial cells (mRMCs) time- and dose-dependently. Also, 14(15)-EET (a major substrate of sEH), but not its sEH-mediated metabolite 14,15-DHET, significantly reversed PA-induced increase in Mcp-1, and PA-induced decrease in Pax2 and Ampk. In addition, plasmid construction revealed that Pax2 may positively regulate Ampk transcriptionally in mRMCs. This study provides insights into and therapeutic target for the HFD-mediated renal injury.


Assuntos
Adenilato Quinase/metabolismo , Dieta Hiperlipídica , Epóxido Hidrolases/antagonistas & inibidores , Rim/lesões , Fator de Transcrição PAX2/metabolismo , Animais , Sistema Enzimático do Citocromo P-450/metabolismo , Modelos Animais de Doenças , Eicosanoides/metabolismo , Inibidores Enzimáticos/farmacologia , Epóxido Hidrolases/metabolismo , Hipertrofia , Rim/patologia , Células Mesangiais/efeitos dos fármacos , Células Mesangiais/metabolismo , Células Mesangiais/patologia , Camundongos , Ácido Palmítico , Compostos de Fenilureia/farmacologia , Piperidinas/farmacologia , Solubilidade , Fatores de Tempo , Ganho de Peso
19.
FASEB J ; 33(1): 1389-1400, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30133326

RESUMO

Cholesterol is an important component of plasma membranes (PMs) and the precursor of all steroid hormones. In steroidogenic tissues, upon hormone stimulation, there is a rapid transfer of cholesterol to the mitochondria, which is the site of the initial step in steroidogenesis. In the current study, we examined PM cholesterol trafficking for steroidogenesis. In a mitochondrial reconstitution assay, adrenal PMs supported steroidogenesis in the absence of additional transport proteins. Depletion of cholesterol in PMs by 50% eliminated the membranes' ability to support steroidogenesis in vitro and reduced steroid production in intact Y1 adrenocortical cells. Syntaxin (STX)-5 and α-soluble N-ethylmaleimide-sensitive factor attachment protein (α-SNAP) are enriched in adrenal PMs, and adrenocorticotropic hormone treatment of rats recruited STX5 and α-SNAP to adrenal PMs and mitochondria. Immunodepletion of STX5 and α-SNAP from PMs decreased steroidogenesis supported by PMs in vitro. Protease digestion of PMs decreased, whereas recombinant STX5 or α-SNAP restored, the PMs' ability to support steroidogenesis. Knockdown of either STX5 or α-SNAP in Y1 cells decreased stimulated steroidogenesis. These results indicate that STX5 and α-SNAP facilitate cholesterol trafficking from PMs to mitochondria for adrenal steroid synthesis and underscore the importance of vesicular trafficking of PM cholesterol for steroidogenesis.-Deng, B., Shen, W.-J., Dong, D., Azhar, S., Kraemer, F. B. Plasma membrane cholesterol trafficking in steroidogenesis.


Assuntos
Lipídeos de Membrana/metabolismo , Esteroides/biossíntese , Animais , Transporte Biológico , Células Cultivadas , Gotículas Lipídicas/metabolismo , Masculino , Camundongos , Ratos , Ratos Sprague-Dawley , Proteínas SNARE/metabolismo
20.
Adv Mater ; 31(9): e1800996, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30277604

RESUMO

Chemical vapor deposition (CVD) is considered to be an efficient method for fabricating large-area and high-quality graphene films due to its excellent controllability and scalability. Great efforts have been made to control the growth of graphene to achieve large domain sizes, uniform layers, fast growth, and low synthesis temperatures. Some attempts have been made by both the scientific community and startup companies to mass produce graphene films; however, there is a large difference in the quality of graphene synthesized on a laboratory scale and an industrial scale. Here, recent progress toward the mass production of CVD graphene films is summarized, including the manufacturing process, equipment, and critical process parameters. Moreover, the large-scale homogeneity of graphene films and fast characterization methods are also discussed, which are crucial for quality control in mass production.

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