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1.
Artigo em Inglês | MEDLINE | ID: mdl-31944535

RESUMO

The incidence of melanoma is rising globally including China. Comparing to Caucasians, the incidence of non-cutaneous melanomas is significantly higher in Chinese. Herein, we performed genomic profiling of 89 Chinese surgically resected primary melanomas, including acral (n = 54), cutaneous (n = 22), and mucosal (n = 13), by hybrid capture-based next-generation sequencing. We show that mucosal melanomas tended to harbor more pathogenic mutations than other types of melanoma, though the biological significance of this finding remains uncertain. Chromosomal arm-level alterations including 6q, 9p, and 10p/q loss were highly recurrent in all subtypes, but mucosal melanoma was significantly associated with increased genomic instability. Importantly, 7p gain significantly correlated with unfavorable clinical outcomes in non-cutaneous melanomas, representing an intriguing prognostic biomarker of those subtypes. Furthermore, focal amplification of 4q12 (KIT, KDR, and PDGFRα) and RAD51 deletion were more abundant in mucosal melanoma, while NOTCH2 amplification was enriched in acral melanoma. Additionally, cutaneous melanomas had higher mutation load than acral melanomas, while mucosal melanomas did not differ from other subtypes in mutation burden. Together, our data revealed important features of acral and mucosal melanomas in Chinese including distinctive driver mutation pattern and increased genomic instability. These findings highlight the possibilities of combination therapies in the clinical management of melanoma.

2.
Int J Nurs Pract ; : e12817, 2020 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-31985129

RESUMO

BACKGROUND AND AIM: To our knowledge, the practice of transitional care was not common in mainland China. This study was designed to test the intervention effects of a specific dose (4 weeks) of an Omaha-based system transitional care programme for Chinese patients suffering from rheumatoid arthritis. METHODS: The intervention group adopted a 4-week nurse-led transitional care intervention based on the Omaha System. The control group used a comparable length of routine care. The outcome indexes were a Chinese version of the Arthritis Self-Efficacy Scale-8, Health Assessment Questionnaire-Disability Index, and hospital readmission rates. Data were collected from June 2018 to December 2018. RESULTS: Finally, 88 patients (44 in the intervention group and 44 in the control group) entered the data analysis. Baseline sociodemographic data for both groups were not found to be statistically significant. The self-efficacy and HAQ-DI of the intervention group were significantly different from the control group. Although the readmission rates of the intervention group were lower than that of the control group, it was not statistically significant. CONCLUSIONS: This 4-week transitional care intervention dose is sufficient to provide evidence for improving self-efficacy to implement disease management and enhancing physical function of patients diagnosed with rheumatoid arthritis.

3.
J Cell Biochem ; 121(2): 996-1004, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31452254

RESUMO

The aim is to investigate the mechanism of miR-499a-5p on the damage of cardiomyocyte induced by hypoxia/reoxygenation. The activity of lactate dehydrogenase (LDH), apoptosis rate and the expression of miR-499a-5p and cluster of differentiation 38 (CD38) in hypoxia-reoxygenation model cells were detected by LDH Cytotoxicity Assay Kit, flow cytometry, real-time polymerase chain reaction, and Western blot analysis, respectively. Apoptosis, the activity of LDH was detected after overexpression of miR-499a-5p or silencing of CD38 in H9c2 cells. The target relationship between miR-499a-5p and CD38 was verified by Targetscan online prediction and dual-luciferase assay. Apoptosis, the activity of LDH was detected after overexpression of miR-499a-5p and CD38. Apoptosis, the activity of LDH and the expression of CD38 were increased (P < .05) while expression of miR-499a-5p was decreased (P < .05) in hypoxia/reoxygenation model cells. Apoptosis and the activity of LDH in H9c2 cells after overexpression of miR-499a-5p or silence of CD38 were decreased (P < .05). The results of Targetscan online prediction and dual-luciferase assay indicated that CD38 was a potential target gene of miR-499a-5p. Overexpression of CD38 could reverse the inhibition of miR-499a-5p on LDH activity and apoptosis in H9c2 cells. miR-499a-5p could relief the injury of cardiomyocytes induced by hypoxia/reoxygenation via targeting CD38.

4.
Mol Immunol ; 117: 201-215, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31835202

RESUMO

Myeloid-derived suppressor cells (MDSCs) expand in tumor-bearing host. They suppress anti-tumor immune response and promote tumor growth. Chemokines play a vital role in recruiting MDSCs into tumor tissue. They can also induce the generation of MDSCs in the bone marrow, maintain their suppressive activity, and promote their proliferation and differentiation. Here, we review CCL2/CCL12-CCR2, CCL3/4/5-CCR5, CCL15-CCR1, CX3CL1/CCL26-CX3CR1, CXCL5/2/1-CXCR2, CXCL8-CXCR1/2, CCL21-CCR7, CXCL13-CXCR5 signaling pathways, their role in MDSCs recruitment to tumor tissue, and their correlation with tumor development, metastasis and prognosis. Targeting chemokines and their receptors may serve as a promising strategy in immunotherapy, especially combined with other strategies such as chemotherapy, cyclin-dependent kinase or immune checkpoints inhibitors.

5.
Int J Biol Macromol ; 2019 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-31786299

RESUMO

The objective of this work was to fabricate and characterize food-grade pea protein isolate (PPI) and carbohydrate polymer pullulan (PUL) nanofiber films by using green electrospinning technology. The effect of the blend ratios on the PPI/PUL solution properties (e.g. viscosity, surface tension and electrical conductivity) and morphology of the resulting electrospun nanofibers was investigated. The presence of PUL in the blends resulted in decreased apparent viscosity (P < 0.05), stable surface tension (42.09-46.26 mN/m) (P < 0.05) and lower conductivity of the solutions (P < 0.05), which were due to a better chain entanglement and decrease in the polyelectrolyte protein character, respectively, both factors were needed for uniform nanofiber (around 203 nm) formation. Rheological evaluation indicated a pseudoplastic behavior for all formulations. The Fourier transform infrared spectral changes and XRD patterns indicated that the protein and polysaccharide were well tangled in nanofibers. The results of the differential scanning calorimetry (DSC) indicate that thermal stability of the electrospun nanofiber films were improved in comparison to pure PUL. Finally, in order to expand the application range of the electrospun nanofiber films in future, thermal crosslinking method was conducted and water contact angles (WCAs) of the thermal treated nanofiber films exhibited better hydrophobic properties compared to the un-crosslinking samples.

6.
Shanghai Kou Qiang Yi Xue ; 28(4): 408-411, 2019 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-31792483

RESUMO

PURPOSE: To detect the gene expression of miRNAs in patients with periodontitis and to explore their biological functions and involved signaling pathways. METHODS: Bioinformatics analysis of gene chip data from 158 periodontitis patients and 40 healthy controls of the microarray database GSE54710 were performed. The expression changes of miRNAs were analyzed. The involved biological function and signal path was predicted. SPSS 19.0 software package was used for statistical analysis. RESULTS: Five miRNAs (hsa-miR-451, hsa-miR-223, hsa-miR-486-5p, hsa-miR-3917, hsa-miR-671-5p) were significantly up-regulated, and 4 miRNAs (hsa-miR-203, hsa-miR-210, hsa-miR-1246, hsa-miR-1260) were significantly down-regulated. Among them, there were 584 target genes of hsa-miR-1260 and 139 target genes of hsa-miR-451. KEGG pathway enrichment analysis showed that hsa-miR-1260 target gene was significantly enriched into 12 signaling pathways such as TGF-beta, and hsa-miR-451 target gene was significantly enriched into 17 signaling pathways. CONCLUSIONS: miRNAs expression profiles were obtained in periodontitis tissues, periodontitis-induced hsa-miR-1260 and hsa-miR-451 may play a key role in the pathophysiology of periodontitis.


Assuntos
MicroRNAs , Periodontite , Biologia Computacional , Perfilação da Expressão Gênica , Humanos , Análise de Sequência com Séries de Oligonucleotídeos
7.
Oncogene ; 2019 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-31831835

RESUMO

The original version of this Article omitted the following from the Acknowledgements: Professor Stebbing sits on SABs for Celltrion, Singapore Biotech, Vor Biopharma, TLC Biopharmaceuticals and Benevolent AI, has consulted with Lansdowne partners, Vitruvian and Social Impact Capital and Chairs the Board of Directors for BB Biotech Healthcare Trust and Xerion Healthcare. This has now been corrected in both the PDF and HTML versions of the Article.

8.
J Chem Phys ; 151(23): 234105, 2019 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-31864248

RESUMO

Nonequilibrium molecular dynamics (NEMD) has been extensively used to study thermal transport at various length scales in many materials. In this method, two local thermostats at different temperatures are used to generate a nonequilibrium steady state with a constant heat flux. Conventionally, the thermal conductivity of a finite system is calculated as the ratio between the heat flux and the temperature gradient extracted from the linear part of the temperature profile away from the local thermostats. Here, we show that, with a proper choice of the thermostat, the nonlinear part of the temperature profile should actually not be excluded in thermal transport calculations. We compare NEMD results against those from the atomistic Green's function method in the ballistic regime and those from the homogeneous nonequilibrium molecular dynamics method in the ballistic-to-diffusive regime. These comparisons suggest that in all the transport regimes, one should directly calculate the thermal conductance from the temperature difference between the heat source and sink and, if needed, convert it into the thermal conductivity by multiplying it with the system length. Furthermore, we find that the Langevin thermostat outperforms the Nosé-Hoover (chain) thermostat in NEMD simulations because of its stochastic and local nature. We show that this is particularly important for studying asymmetric carbon-based nanostructures, for which the Nosé-Hoover thermostat can produce artifacts leading to unphysical thermal rectification.

9.
Huan Jing Ke Xue ; 40(12): 5503-5514, 2019 Dec 08.
Artigo em Chinês | MEDLINE | ID: mdl-31854623

RESUMO

Eutrophic aquaculture ponds are important methane (CH4) sources. In order to quantify CH4 emission characteristics and its influencing factors over aquaculture ponds, we conducted several intensive observations over two ponds located in Quanjiao County, Anhui Province, in 2018. The ebullition and diffusion flux of CH4 were measured in two seasons (winter and spring) using the inverted-funnel and bulk diffusion model, respectively. In winter, the CH4 ebullition flux during the daytime was higher than that at night (almost zero), whereas the diurnal pattern was found to be reversed in spring. Seasonally, the CH4 ebullition flux over the ponds was significantly lower in winter[3.92 mg·(m2·d)-1] than in spring[106.94 mg·(m2·d)-1], while the diffusion flux in winter[2.81 mg·(m2·d)-1] was slightly higher than in spring[0.87 mg·(m2·d)-1]. The CH4 ebullition and diffusion flux can be significantly controlled by natural factors such as water temperature and air pressure. It was revealed that the CH4ebullition flux in the studied ponds increased exponentially with increasing water temperature, and increased linearly with decreasing air pressure. Furthermore, we found that artificial management measures (i.e., winter drainage and spring manure treatment) could significantly enhance the CH4 ebullition flux rather than diffusion flux. For instance, the CH4 ebullition flux was found to increase with water depth decrease during the winter drainage period, while in the spring, the CH4 ebullition flux could reach as high as 1002.30 mg·(m2·d)-1 with chicken manure applicated. This study can provide data support for assessing the contribution of small ponds to the global carbon cycle.


Assuntos
Aquicultura , Metano , Tanques , Dióxido de Carbono , Estações do Ano , Temperatura Ambiente
10.
Pest Manag Sci ; 2019 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-31696614

RESUMO

BACKGROUND: Pydiflumetofen is a new generation succinate dehydrogenase inhibitor currently undergoing the process of registration in China for the control of Fusarium head blight in wheat. A resistance risk assessment of Fusarium graminearum to pydiflumetofen was undertaken in this study. RESULTS: A total of 75 pydiflumetofen-resistant mutants were generated through spontaneous selection and displayed high resistance with an average resistance factor (RF) value of 78. Four mutants were generated through UV mutagenesis and displayed very high resistance with an RF value >1000. The sequence analysis results for Sdh genes and fitness studies revealed the existence of four types of mutations. In particular, 32 spontaneous selection mutants (SP mutants) had an arginine (R) to histidine (H) transition at position 86 in FGSdhC, resulting in seriously reduced fitness. Seven SP mutants had an R to cysteine (C) transition at position 86 in FGSdhC, resulting in reduced fitness. Thirty-six SP mutants had an alanine (A) to valine (V) transition at position 83 in FGSdhC and had no fitness penalties. The efficacy of pydiflumetofen towards a mutant carrying A83V in FGSdhC in vivo was significantly decreased at 42.7%. Four UV mutants had no mutations on all Sdh genes and no fitness penalties. Cross-resistance among boscalid, fluopyram and pydiflumetofen was observed. CONCLUSION: Sdhc mutations were found and other target site resistance may be present in laboratory PR mutants of F. graminearum. An overall moderate risk of resistance development in F. graminearum was recommended for pydiflumetofen. © 2019 Society of Chemical Industry.

11.
Int J Mol Sci ; 20(22)2019 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-31739570

RESUMO

The WRKY transcription factor superfamily is known to participate in plant growth and stress response. However, the role of this family in wheat (Triticum aestivum L.) is largely unknown. Here, a salt-induced gene TaWRKY13 was identified in an RNA-Seq data set from salt-treated wheat. The results of RT-qPCR analysis showed that TaWRKY13 was significantly induced in NaCl-treated wheat and reached an expression level of about 22-fold of the untreated wheat. Then, a further functional identification was performed in both Arabidopsis thaliana and Oryza sativa L. Subcellular localization analysis indicated that TaWRKY13 is a nuclear-localized protein. Moreover, various stress-related regulatory elements were predicted in the promoter. Expression pattern analysis revealed that TaWRKY13 can also be induced by polyethylene glycol (PEG), exogenous abscisic acid (ABA), and cold stress. After NaCl treatment, overexpressed Arabidopsis lines of TaWRKY13 have a longer root and a larger root surface area than the control (Columbia-0). Furthermore, TaWRKY13 overexpression rice lines exhibited salt tolerance compared with the control, as evidenced by increased proline (Pro) and decreased malondialdehyde (MDA) contents under salt treatment. The roots of overexpression lines were also more developed. These results demonstrate that TaWRKY13 plays a positive role in salt stress.

12.
Oncogene ; 2019 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-31754213

RESUMO

EGFR-mutant non-small-cell lung cancer (NSCLC) patients inevitably develop drug resistance when treated with EGFR tyrosine kinase inhibitors (TKIs). Systematic genetic analysis is important to understand drug-resistant mechanisms; however, the clinical significance of co-occurring genetic alterations at baseline, co-acquired mutations at progressive disease (PD), and the clonal evolution remain underinvestigated. We performed targeted sequencing of pre-treatment and PD tumor samples from 54 EGFR-mutant NSCLC patients. Ten additional patients were sequenced using whole-exome sequencing to infer the clonal evolution patterns. We observed a domain-dependent effect of PIK3CA mutation at baseline on patient progression-free survival (PFS). In addition, at baseline, 9q34.3/19p13.3 (NOTCH1/STK11/GNA11) showed a co-deletion pattern, which was associated with a significantly worse PFS (p = 0.00079). T790M-postive patients with other concurrent acquired oncogenic mutations had a significantly shorter PFS (p = 0.005). Besides acquired T790M mutation, chromosomal instability (CIN) related genes, including AURKA and TP53 alterations, were the most frequently acquired events. CIN significantly increased during TKI treatment in T790M-negative patients and is a candidate resistance mechanism to the first-generation TKIs. Clonal evolution analyses suggest that the composition and relationship among resistant subclones, particularly relationship with T790M subclone, affect patients' outcomes. Overall, our findings of novel co-occurring alterations and clonal evolution patterns can be served as predictive biomarkers to stratify patients and help to better understand the drug-resistant mechanism to TKIs.

13.
Adv Mater ; 31(49): e1905099, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31621971

RESUMO

Efficient thermal energy harvesting using phase-change materials (PCMs) has great potential for cost-effective thermal management and energy storage applications. However, the low thermal conductivity of PCMs (KPCM ) is a long-standing bottleneck for high-power-density energy harvesting. Although PCM-based nanocomposites with an enhanced thermal conductivity can address this issue, achieving a higher K (>10 W m-1 K-1 ) at filler loadings below 50 wt% remains challenging. A strategy for synthesizing highly thermally conductive phase-change composites (PCCs) by compression-induced construction of large aligned graphite sheets inside PCCs is demonstrated. The millimeter-sized graphite sheet consists of lateral van-der-Waals-bonded and oriented graphite nanoplatelets at the micro/nanoscale, which together with a thin PCM layer between the sheets synergistically enhance KPCM in the range of 4.4-35.0 W m-1 K-1 at graphite loadings below 40.0 wt%. The resulting PCCs also demonstrate homogeneity, no leakage, and superior phase change behavior, which can be easily engineered into devices for efficient thermal energy harvesting by coordinating the sheet orientation with the thermal transport direction. This method offers a promising route to high-power-density and low-cost applications of PCMs in large-scale thermal energy storage, thermal management of electronics, etc.

14.
J Am Heart Assoc ; 8(20): e012338, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31576776

RESUMO

Background Heart failure (HF) is one of the most significant causes of morbidity and mortality for the cardiovascular risk population. We found previously that extracellular HSP70 (heat shock protein) is an important trigger in cardiac hypertrophy and fibrosis, which are associated with the development of heart dysfunction. However, the potential role of HSP70 in response to HF and whether it could be a target for the therapy of HF remain unknown. Methods and Results An HF mouse model was generated by a single IP injection of doxorubicin at a dose of 15 mg/kg. Ten days later, these mice were treated with an HSP70 neutralizing antibody for 5 times. We observed that doxorubicin treatment increased circulating HSP70 and expression of HSP70 in myocardium and promoted its extracellular release in the heart. Blocking extracellular HSP70 activity by its antibody significantly ameliorated doxorubicin-induced left ventricular dilation and dysfunction, which was accompanied by a significant inhibition of cardiac fibrosis. The cardioprotective effect of the anti-HSP70 antibody was largely attributed to its ability to promote the resolution of myocardial inflammation, as evidenced by its suppression of the toll-like receptor 2-associated signaling cascade and modulation of the intracellular distribution of the p50 and p65 subunits of nuclear factor-κB. Conclusions Extracellular HSP70 serves as a noninfectious inflammatory factor in the development of HF, and blocking extracellular HSP70 activity may provide potential therapeutic benefits for the treatment of HF.

15.
Mater Sci Eng C Mater Biol Appl ; 105: 110042, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31546440

RESUMO

Influences of proteins on degradation of magnesium alloys are of great significance but not well understood. In particular the roles of amino acids, the basic unit of proteins in regulating the progress of biodegradation of magnesium based materials remain unclear. This study aims to investigate the impacts of alanine, glutamic acid and lysine on degradation of pure magnesium in phosphate buffer solution through SEM, XPS, FTIR, potentiodynamic polarisation curves, electrochemical impedance spectroscopy and immersion tests. The changed contents of amino acids in solutions were detected by UV-vis spectrophotometer. Results demonstrate that the charges of the selected amino acids imposed significant contribution to suppressing the degradation of pure magnesium in phosphate buffer solution. The presence of amino acids led to the formation of phosphate-based corrosion products, increasing free corrosion potential, and reduction in corrosion current density and solution pH depending on their isoelectric points and molecular structures. A plausible corrosion mechanism organised by amino acids on pure magnesium was proposed.

16.
Materials (Basel) ; 12(18)2019 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-31546884

RESUMO

In this work, a miniaturized bandpass filter (BPF) constructed of two spiral intertwined inductors and a central capacitor, with several interdigital structures, was designed and fabricated using integrated passive device (IPD) technology on a GaAs wafer. Five air-bridge structures were introduced to enhance the mutual inductive effect and form the differential geometry of the outer inductors. In addition, the design of the differential inductor combined with the centrally embedded capacitor results in a compact construction with the overall size of 0.037λ0 × 0.019λ0 (1537.7 × 800 µm2) where λ0 is the wavelength of the central frequency. For the accuracy evolution of the equivalent circuit, the frequency-dependent lumped elements of the proposed BPF was analyzed and modeled through the segment method, mutual inductance approach, and simulated scattering parameters (S-parameters). Afterward, the BPF was fabricated using GaAs-based IPD technology and a 16-step manufacture flow was accounted for in detail. Finally, the fabricated BPF was wire-bonded with Au wires and packaged onto a printed circuit board for radio-frequency performance measurements. The measured results indicate that the implemented BPF possesses a center frequency operating at 2 GHz with the insertion losses of 0.38 dB and the return losses of 40 dB, respectively, and an ultrawide passband was achieved with a 3-dB fraction bandwidth of 72.53%, as well. In addition, a transmission zero is located at 5.32 GHz. Moreover, the variation of the resonant frequency with different inductor turns and metal thicknesses was analyzed through the simulation results, demonstrating good controllability of the proposed BPF.

17.
Transl Stroke Res ; 2019 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-31494833

RESUMO

The aim of this study was to assess the association between admission to stroke centers for acute ischemic stroke and complications and mortality during hospitalization in a Chinese population by means of an observational study using data from the China Stroke Center Data-Sharing Platform. We compared in-hospital complications and mortality for patients admitted with acute ischemic stroke (N = 13,236) between November 1, 2018 and December 31, 2018 at stroke center (SH) and non-stroke center (CH) hospitals using distance to hospitals as an instrumental variable to adjust for potential prehospital selection bias. The results showed that complication rates during hospitalization among ischemic stroke patients who received thrombolytic therapy (n = 11,203) were lower in the SH group than in the CH group: 11.1% vs 15.7% (absolute difference, - 5.11% [95% CI, - 6.05 to - 3.99%], odds ratio [OR] 0.85 [95% CI, 0.74 to 0.92]). The incidence of intracranial hemorrhage was reduced from 4.2 to 3.2%: SH group vs CH group, 3.2% vs 4.2% (absolute difference, - 1.24% [95% CI, - 1.65 to - 0.82%], OR 0.83 [95% CI, 0.69 to 0.0.98]). Furthermore, the total mortality rate in the SH group was also lower than in the CH group: SH group vs CH group, 2.2% vs 3.0% (absolute difference, - 0.92% [95% CI, - 1.48 to - 0.53%], OR 0.85 [95% CI, 0.73 to 0.96]). The data showed that admission to SH hospitals was associated with a lower risk of treatment complications and death for patients with an acute ischemic stroke receiving thrombolytic therapy.

18.
Adv Mater ; 31(40): e1903125, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31402540

RESUMO

Hard carbon is regarded as a promising anode material for sodium-ion batteries (SIBs). However, it usually suffers from the issues of low initial Coulombic efficiency (ICE) and poor rate performance, severely hindering its practical application. Herein, a flexible, self-supporting, and scalable hard carbon paper (HCP) derived from scalable and renewable tissue is rationally designed and prepared as practical additive-free anode for room/low-temperature SIBs with high ICE. In ether electrolyte, such HCP achieves an ICE of up to 91.2% with superior high-rate capability, ultralong cycle life (e.g., 93% capacity retention over 1000 cycles at 200 mA g-1 ) and outstanding low-temperature performance. Working mechanism analyses reveal that the plateau region is the rate-determining step for HCP with a lower electrochemical reaction kinetics, which can be significantly improved in ether electrolyte.

19.
Biochem Biophys Res Commun ; 518(1): 120-126, 2019 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-31405565

RESUMO

Type 2 diabetes (T2D) is characterized by lack of insulin, insulin resistance and high blood sugar. However, the underlying mechanisms of insulin resistance during T2D development remains unclear. As the most common mRNAs modification, N6-Methyladenosine (m6A) is involved in many of pathological processes in aging disease. However, it remains unclear whether m6A is involved in T2D development and what is the regulatory mechanism. This study is aimed to illustrate the roles of m6A and its methyltransferase METTL3 in the regulation of blood glucose homeostasis and insulin sensitivity. The results showed that m6A methylated RNA level and its N6-methyladenosine methylase METTL3 were consistently up-regulated in the liver tissues from patients with T2D. Moreover, both m6A methylated RNA and METTL3 levels showed positive correlation with HOMA-IR and negative correlation with HOMA-ß. The m6A methylated RNA and METTL3 levels were also up-regulated in mouse with 16 weeks high-fat diet (HFD), compared with mice fed a standard chow diet (CD). Hepatocyte-specific knockout of METTL3 in mice fed a HFD improved insulin sensitivity and decreased fatty acid synthesis. Furthermore, mechanism analysis demonstrates that METTL3 silence decreased the m6A methylated and total mRNA level of Fatty acid synthase (Fasn), subsequently inhibited fatty acid metabolism. Adeno-associated virus mediated Fasn overexpression in METTL3 knockout mice abrogates the improved insulin sensitivity and decreased fatty acid synthesis. Collectively, these results reveal that RNA N6-methyladenosine methylase METTL3 inhibits hepatic insulin sensitivity via N6-methylation of Fasn mRNA and promoting fatty acid metabolism.

20.
ACS Appl Mater Interfaces ; 11(34): 31402-31410, 2019 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-31381291

RESUMO

Increasing power density makes modern electronic devices and power equipment generate excess heat, which greatly restricts the applications of polymeric materials because of their poor thermal conductivity. In the present work, inspired by the structure and production process of millefeuille cakes, we show that electrostatic spraying of boron nitride nanosheets (BNNSs) onto electrospun poly(vinyl alcohol) (PVA) nanofibers can produce highly thermally conductive, electrically insulating, flexible, and lightweight nanocomposites via a scalable method of building a multilayer PVA/BNNS nanonetwork structure. The PVA/BNNS nanocomposites exhibit an ultrahigh in-plane thermal conductivity of 21.4 W/(m·K) at 22.2 vol % BNNS addition, realized by an orientated BNNS network structure with overlapping interconnections. The BNNS networks exhibit low thermal resistance and interfacial heat scattering between BNNSs. Moreover, for heat dissipation applications, the nanocomposites with an overlapping BNNS network show higher efficiency in dissipating hot spots than randomly dispersed BNNS or directly hot-pressed BNNS composites. These PVA/BNNS nanocomposites can be used as high-performance lateral heat spreaders in next-generation thermal management systems.

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