m6A mRNA demethylase FTO regulates melanoma tumorigenicity and response to anti-PD-1 blockade

Melanoma is one of the most deadly and therapy-resistant cancers. Here we show that N6-methyladenosine (m6A) mRNA demethylation by fat mass and obesity-associated protein (FTO) increases melanoma growth and decreases response to anti-PD-1 blockade immunotherapy. FTO level is increased in human melanoma and enhances melanoma tumorigenesis in mice. FTO is induced by metabolic starvation stress through the autophagy and NF-κB pathway. Knockdown of FTO increases m6A methylation in the critical protumorigenic melanoma cell-intrinsic genes including PD-1 (PDCD1), CXCR4, and SOX10, leading to increased RNA decay through the m6A reader YTHDF2. Knockdown of FTO sensitizes melanoma cells to interferon gamma (IFNγ) and sensitizes melanoma to anti-PD-1 treatment in mice, depending on adaptive immunity. Our findings demonstrate a crucial role of FTO as an m6A demethylase in promoting melanoma tumorigenesis and anti-PD-1 resistance, and suggest that the combination of FTO inhibition with anti-PD-1 blockade may reduce the resistance to immunotherapy in melanoma. © 2019, The Author(s)

Prenatal diagnosis of micrognathia: a systematic review

PurposeThis systematic review aimed to analyze the characteristics of different diagnostic techniques for micrognathia, summarize the consistent diagnostic criteria of each technique, and provide a simple and convenient prenatal diagnosis strategy for micrognathia.MethodsIn accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, the search was undertaken in three international databases (PubMed, Scopus, and Web of Science). The three reviewers assessed all papers and extracted the following variables: author's name and year of publication, country, study design, number of participants, gestational age, equipment for prenatal examination, biometric parameters related to micrognathia, main results.ResultsA total of 25 articles included in the analysis. Nineteen articles described cross-sectional studies (76 percent), 4 (16 percent) were case-control studies, and 2 (8 percent) were cohort studies. Fifteen studies (60 percent) had a prospective design, 9 (36 percent) had a retrospective design, and one (4 percent) had both prospective and retrospective design. Thirty-two percent of the studies (n = 8) were performed in USA, and the remaining studies were performed in China (n = 4), Israel (n = 3), Netherlands (n = 3), UK (n = 1), France (n = 1), Italy (n = 1), Belgium(n = 1), Germany (n = 1), Spain (n = 1), and Austria (n = 1). The prenatal diagnosis of micrognathia can be performed as early as possible in the first trimester, while the second and third trimester of pregnancy were the main prenatal diagnosis period. The articles that were included in the qualitative synthesis describe 30 biometric parameters related to the mandible.ConclusionOf the 30 biometric parameters related to the mandible, 15 can obtain the simple and convenient diagnostic criteria or warning value for micrognathia. Based on these diagnostic criteria or warning value, clinicians can quickly make a preliminary judgment on facial deformities, to carry out cytologic examination to further clarify the diagnosis of micrognathia

Effect of metal additives on the catalytic performance of Ni/Al2O3 catalyst in thermocatalytic decomposition of methane

Thermocatalytic decomposition of methane is proposed to be an economical and green method to produce COx-free hydrogen and carbon nanomaterial. In present work, 60 wt% Ni/Al2O3 catalysts with different additives (Cu, Mn, Pd, Co, Zn, Fe, Mg) were prepared by co-impregnation method to investigate promotional effects of these metal additives on the activity and stability of 60 wt% Ni/Al2O3 and find out a really effective promoter for decomposition of methane. The catalyst was characterized by N-2 adsorption/desorption, X-ray diffraction, scanning electron microscopy, inductively coupled plasma optical emission spectrometer and hydrogen temperature programmed reduction. While metal additives (5 wt%) were added into 60 wt% Ni/Al2O3, the activity stability of 60 wt% Ni/Al2O3 was improved and the CH4 conversion of 60 wt% Ni/Al2O3 was also improved except Zn addition. Mn addition was found to improve the catalytic activity of 60 wt% Ni/Al2O3 significantly and the CH4 conversion of 5 wt% Mn-60 wt% Ni/Al2O3 was -80%. Cu addition was found to remarkably improve the catalytic stability of 60 wt% Ni/Al2O3 and the CH4 conversion of 5 wt% Cu-60 wt% Ni/Al2O3 decreased from 61% to 45% after 250 min of reaction time. Carbon nanomaterials formed in the thermocatalytic decomposition process were characterized by X-ray diffraction, scanning electron microscopy, thermal gravimetric analyzer and Raman spectroscopy. Carbon deposits consist of amorphous carbon and carbon nanofibers. (C) 2019 Hydrogen Energy Publications LLC. Published by Elsevier Ltd. All rights reserved

Electrochemical capacitive properties of all-solid-state supercapacitors based on ternary MoS2/CNTs-MnO2 hybrids and ionic mixture electrolyte

All-solid-state supercapacitors constructed with effectively composited materials are required urgently for the next generation of portable electronic devices. Herein, two dimensions of materials (carbon nanotubes and exfoliated MoS2) are used as basic building blocks for deposition of zero-dimensional birnessite-MnO2 nanoparticles. The obtained ternary hybrids with open conducting nanoarchitecture can provide multiple accessible electroactive sites to minimize the ion-diffusion distances. In a three-electrode aqueous system, the MoS2/CNITs-MnO2 exhibits high specific capacitance (365.6 F/g) and excellent rate capability (76.5% capacity retention at 8 A/g). The advantages of MoS2/CNITs-MnO2 hybrids are evaluated by investigating symmetric and asymmetric supercapacitor using PVDF-HFP/EMIMBF4/ EMIMTFSI gel electrolyte. The potential window of both symmetric and asymmetric supercapacitor can be enlarged to 4 V. In particular, the asymmetric device provides a maximum energy of 124 Wh/kg at a specific power of 916 kW/kg. It is prospected that such novel hybrids can offer potential promise in energy storage device applications. (C) 2018 Elsevier B.V. All rights reserved

Synthesis, Crystal Structure and Optical Properties of Europium Trifluoroacetate Complexes with 1,10-Phenanthroline and 2,2 '-Bipyridine

<p>Two europium trifluoroacetate complexes, Eu(CF3COO)(3)center dot phen (1) and Eu(CF3COO)(3)center dot bpy (2) (where phen=1,10-phenanthroline, bpy=2,2&#39;-bipyridine), were synthesized and characterized by elemental analysis, Fourier transform infrared spectroscopy (FT-IR), photoluminescence (PL) spectroscopy and thermogravimetric analysis (TA). Single-crystal X-ray structure has been determined for the complex [Eu-2(CF3COO)(6)center dot(phen)(3)center dot(H2O)(2)]center dot EtOH. The crystal structure of [Eu-2(CF3COO)(6)center dot(phen)(3)center dot(H2O)(2)]center dot EtOH shows that two different coordination styles with europium ions coexist in the same crystal and have entirely different coordination geometries and numbers. This crystal can be considered as an 1 : 1 adduct of [Eu(CF3COO)(3)center dot(Phen)(2)center dot H2O]center dot EtOH (9-coordination part) and Eu(CF3COO)(3)center dot phen center dot H2O (8-coordination part). The excitation spectra of the two complexes demonstrate that the energy collected by &quot;antenna ligands&quot; is transferred to Eu3+ ions efficiently. The room-temperature PL spectra of the complexes are composed of the typical Eu3+ ions red emission, due to transitions between D-5(0) -&gt; F-7(J(J=0 -&gt; 4)). The lifetimes of D-5(0) of Eu3+ in the complexes were examined using time-resolved spectroscopic analysis, and the lifetime values of Eu(CF3COO)(3)center dot phen and Eu(CF3COO)(3)center dot bpy were fitting with bi-exponential (2987 and 353 mu s) and monoexponential (3191 mu s) curves, respectively. In order to elucidate the energy transfer process of the europium complexes, the energy levels of the relevant electronic states had been estimated. The thermal analyses indicate that they are all quite stable to heat.</p

Hierarchical MnO2/activated carbon cloth electrode prepared by synchronized electrochemical activation and oxidation for flexible asymmetric supercapacitors

Despite appealing supercapacitive properties, the flexible asymmetric supercapacitor devices (FASCs) are still suffering from low mass loading and limited operating voltage, leading to unsatisfactory energy densities. Herein, we introduced a high-voltage anodic electro-deposition process (AED) which is a novel avenue enabling the synthesis of hierarchical MnO2 on activated carbon cloth (H-MnO2/ACC). Interestingly, the concomitant activation of carbon cloth substrate is found to be beneficial to improve the conductivity and hydrophilic nature of our novel electrode. A FASC based on H-MnO2/ACC-300 and reduced carbon cloth (RCC) was assembled using a mixed ionic liquid gel (ionogel) electrolyte. Benefiting from highly conductive paths derived from intimately attached fiber-MnO2 interfaces, hierarchically interpenetrated lamella MnO2 porosity and concentric MnO2 interlayer voids, as well as the merits of ionic liquid, the resultant FASC delivers an output voltage as high as 4 V and an impressive volumetric energy density of 3.82 mWh/cm(3). Furthermore, the optimized H-MnO2/ACC-300 electrode with high mass loading can even retain 94.2% of initial capacitance upon 5000 cycles in 1 M Na2SO4. The unique H-MnO2/ACC can aid in the rational design towards flexible electronic devices with high mass loading and this synthetic strategy opens up enormous possibilities for the fabrication of electrodeposited materials

Hierarchical porous carbon foam supported on carbon cloth as high-performance anodes for aqueous supercapacitors

Carbon anodes have been widely utilized for the fabrication of high-performance asymmetric supercapacitors. However, they generally suffer from unsatisfactory energy density due to low specific capacitance arising from inferior conductivity and insufficient ionic diffusion rate. Here a surface modification method is conducted after the annealing of ZIF-67 precursor to produce hydrophilic, porous and heteroatom-doped carbon foam. On top of enhanced area capacitance, widened voltage window of -1.3-0V (vs saturated calomel electrode) can be achieved through electrochemical reduction to suppress the hydrogen evolution reaction. The optimized reduced porous carbon foam on carbon cloth exhibits a maximum area capacitance of 1049 mF/cm(2) at an applied current density of 12 mA/cm(2) with excellent capacitance retention of 98.4% after 6000 charge-discharge cycles at 15 mA/cm(2). By well pairing with hierarchical MnO2/CC cathode, a 2.3 V asymmetric supercapacitor in neutral aqueous Na2SO4 electrolyte is assembled, which delivers an exceptional energy density of up to 10.07 mWh/cm(3). The procedure in this paper for carbonaceous material to simultaneously achieve considerable capacitance and enlarged voltage window can open up a wider prospect toward design of anodes for high-performance aqueous supercapacitor

Urchin-like NiCo2S4 structures synthesized through a one-step solvothermal process for high-performance supercapacitors

Nickel cobalt sulfides (MCo2S4) have attracted considerable attention as electrode materials for supercapacitors. Herein, a sea-urchin-like NiCo2S4 material was synthesized through a one-step solvothermal process. Polyethylene glycol (PEG) 200 and thiourea were used as a shape-control age nt and sulfur source for in-s让u sulfuration, respectively. The urchin-like NiC02S4 was characterized by X-ray powder diffraction, scanning electron microscopy, Brunauer-Emmett-Teller surface area, and electrochemical measurements. The resulting NiCo2S4 with ion diffusion-favored structure demonstrated remarkable electrochemical characteristics for supercapacitor with a high specific capacitance (1334F/g at 0.5 A/g) and superior rate capability (78.1% of the original capacity from 0.5 to 20 A/g) in 6M KOH aqueous solution. Furthermore, an asymmetric supercapacitor was assembled using NiCo2S4 as a positive electrode and activated carb on (AC) as a n egative electrode. A NiCo2Sj/AC device exhibited a high energy density of 37.32 Wh/kg at a power density of 317.8 W/kg with capacity retention of 91.9% and up to 2000 charge/discharge cycles at 3 A/g. The results demonstrate that the sea-urchin-like NiCo2S4 has potential applications in supercapacitors

Reconstruction of the labia majora using a neurovascular pedicled pudendal thigh flap after extensive vulvectomy for primary extramammary Paget's disease: A case report

Key Clinical Message A neurovascular pedicled pudendal thigh flap was used to reconstruct labial defect after extensive vulvectomy for primary extramammary Paget's disease. The flap was reliable for the superior skin and ideal for large labial defect reconstruction. Abstract Extramammary Paget's disease (EMPD), a rare type of intraepidermal carcinoma, predominantly affects the genitalia. Generally, the treatment for primary EMPD is wide surgical excision; however, large tissue defects after resection necessitate customized reconstruction. Previously, several reconstruction techniques have been outlined, such as local skin flaps (V‐Y flaps), skin grafts, pedicled flaps, and free flaps. However, the complexity of EMPD management is due to the multiple flaps and techniques. In this case report, we applied a neurovascular pedicled pudendal thigh flap to reconstruct a labial defect in a 68‐year‐old woman using the technique of elevation and particularly the insetting of the flap. This pedicled flap was robust and reliable, producing a labium that was natural in appearance with good‐quality skin cover and a protective sensation. The patient was satisfied with both the cosmetic appearance and normal sensation of the reconstructed labia. Additionally, the linear scar at the donor site was located along the inguinal fold, and the flap was accepted by the patient as an ideal tissue for reconstruction of the large labial defect

Urchin-like NiCo2S4 structures synthesized through a one-step solvothermal process for high-performance supercapacitors

Nickel cobalt sulfides (NiCo2S4) have attracted considerable attention as electrode materials for super capacitors. Herein, a sea-urchin-like NiCo2S4 material was synthesized through a one-step solvothermal process. Polyethylene glycol (PEG) 200 and thiourea were used as a shape-control agent and sulfur source for in-situ sulfuration, respectively. The urchin-like NiCo2S4 was characterized by X-ray powder diffraction, scanning electron microscopy, Brunauer-Emmett-Teller surface area, and electrochemical measurements. The resulting NiCo2S4 with ion diffusion-favored structure demonstrated remarkable electrochemical characteristics for supercapacitor with a high specific capacitance (1334 F/g at 0.5 A/g) and superior rate capability (78.1% of the original capacity from 0.5 to 20 A/g) in 6 M KOH aqueous solution. Furthermore, an asymmetric supercapacitor was assembled using NiCo2S4 as a positive electrode and activated carbon (AC) as a negative electrode. A NiCo2S4//AC device exhibited a high energy density of 37.32 Wh/kg at a power density of 317.8 W/kg with capacity retention of 91.9% and up to 2000 charge/discharge cycles at 3 A/g. The results demonstrate that the sea-urchin-like NiCo2S4 has potential applications in supercapacitors. (C) 2018 Chinese Society of Particuology and Institute of Process Engineering, Chinese Academy of Sciences. Published by Elsevier B.V. All rights reserved