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The silver-promoted reaction of tertiary cyclobutanols with N-methoxypyridinium salts enables the efficient synthesis of a range of C2-substituted pyridines. The overall process likely occurs by ring-opening (via ß-scission) of the cyclobutoxy radical to generate the corresponding γ-keto alkyl radical that itself adds to the pyridinium salt. A wide range of tertiary cyclobutanols and N-methoxypyridinium salts are compatible with the reaction conditions.
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Ciclobutanos , Compuestos de Piridinio , Sales (Química) , PlataRESUMEN
Grandparents caring for grandchildren has become a common experience in China. However, the health implications of grandparenting, especially for health self-management, remain unclear. A cross-sectional study was conducted to investigate the effects of grandparenting on health self-management in older adults in China. Information on socioeconomic characteristics, grandparenting, and health self-management was collected through interviewer-administered questionnaires. Age less than 50, male gender, higher education level, being a local resident, having a chronic illness, and supporting themselves financially were all factors that were significantly positively associated with health self-management (P < .05) in grandparents. Grandparenting characteristics, including caring for grandchildren at night, a caregiving burden of more than 50%, poorly behaved grandchildren, caring for grandchildren more than 6 hours per day, and caring for grandchildren less than 1 year in age were significantly negatively associated with health self-management in grandparents (P < .05). Multiple regression analyses indicated that grandparent age, receiving financial support from children, being a local resident, education level, grandchild behavior and age, and being an urban resident were all statistically significant factors associated with health self-management in grandparents involved in grandparenting. Taken together, these results suggested that financial condition and caregiving burden might be the major factors affecting health self-management in grandparents involved in grandparenting.
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Cuidado del Niño , Abuelos , Automanejo , Factores de Edad , Anciano , Niño , Cuidado del Niño/métodos , Cuidado del Niño/psicología , Cuidado del Niño/estadística & datos numéricos , Preescolar , China , Escolaridad , Femenino , Abuelos/psicología , Humanos , Lactante , Masculino , Persona de Mediana Edad , Factores Socioeconómicos , Encuestas y CuestionariosRESUMEN
Protein arginine methyltransferase 5 (PRMT5) is a member of the arginine methyltransferase protein family that critically mediates the symmetric dimethylation of Arg-3 at histone H4 (H4R3me2s) and is involved in many key cellular processes, including hematopoiesis. However, the post-translational modifications (PTMs) of PRMT5 that may affect its biological functions remain less well-understood. In this study, using MS analyses, we found that PRMT5 itself is methylated in human erythroleukemia Lys-562 cells. Biochemical assays revealed that coactivator-associated arginine methyltransferase 1 (CARM1) interacts directly with and methylates PRMT5 at Arg-505 both in vivo and in vitro. Substitutions at Arg-505 significantly reduced PRMT5's methyltransferase activity, decreased H4R3me2s enrichment at the γ-globin gene promoter, and increased the expression of the γ-globin gene in Lys-562 cells. Moreover, CARM1 knockdown consistently reduced PRMT5 activity and activated γ-globin gene expression. Importantly, we show that CARM1-mediated methylation of PRMT5 is essential for the intracellular homodimerization of PRMT5 to its active form. These results thus reveal a critical PTM of PRMT5 that represses human γ-globin gene expression. We conclude that CARM1-mediated asymmetric methylation of PRMT5 is critical for its dimerization and methyltransferase activity leading to the repression of γ-globin expression. Given PRMT5's crucial role in diverse cellular processes, these findings may inform strategies for manipulating its methyltransferase activity for managing hemoglobinopathy or cancer.
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Regulación Neoplásica de la Expresión Génica , Leucemia Eritroblástica Aguda/metabolismo , Proteínas de Neoplasias/metabolismo , Proteína-Arginina N-Metiltransferasas/metabolismo , gamma-Globinas/biosíntesis , Línea Celular Tumoral , Metilación de ADN/genética , ADN de Neoplasias/genética , ADN de Neoplasias/metabolismo , Técnicas de Silenciamiento del Gen , Células HEK293 , Humanos , Leucemia Eritroblástica Aguda/genética , Leucemia Eritroblástica Aguda/patología , Proteínas de Neoplasias/genética , Proteína-Arginina N-Metiltransferasas/genética , gamma-Globinas/genéticaRESUMEN
Objective To explore the clinical value of one-step visualization loop-mediated isothermal amplification(LAMP)in the detection of Mycoplasma pneumoniae(Mp). Methods One-step visualized LAMP,polymerase chain reaction(PCR),and enzyme-linked immunosorbent assay(ELISA)were used to simultaneously detect 108 clinical Mp specimens in children,which included 73 cases of Mp infection diagnosed by PCR and 35 cases of other chronic/acute respiratory tract infections.On the first day of admission,one-step visualization LAMP,PCR(fluorimetric method),and ELISA were used to test the throat swab and serum sample obtained from the same patient,and the Kappa value was calculated.The consistence between LAMP and PCR and that between LAMP and ELISA were compared.On the fifth day of admission,40 patients were resampled and the findings of these three tests on the first day and on the fifth day were compared. Results One-step visualization LAMP had a sensitivity of 100% and a specificity of 94.3%,whereas ELISA had a sensitivity of 65.8% and a specificity of 82.9%.The ratio of Kappa camparing one-step visualization LAMP and PCR was 0.956 and the ratio of Kappa camparing one-step visualization LAMP and ELISA was 0.38.The number of positive specimens detected by LAMP was higher than that by ELISA on the first day. Conclusions One-step visualization LAMP has excellent sensitivity and specificity in detecting early acute Mp infection.It has high consistency with PCR and can be applied to detect Mp.
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Mycoplasma pneumoniae/aislamiento & purificación , Técnicas de Amplificación de Ácido Nucleico , Neumonía por Mycoplasma/diagnóstico , Niño , Ensayo de Inmunoadsorción Enzimática , Humanos , Reacción en Cadena de la Polimerasa , Sensibilidad y EspecificidadRESUMEN
Production of hemoglobin during development is tightly regulated. For example, expression from the human ß-globin gene locus, comprising ß-, δ-, ϵ-, and γ-globin genes, switches from ϵ-globin to γ-globin during embryonic development and then from γ-globin to ß-globin after birth. Expression of human ϵ-globin in mice has been shown to ameliorate anemia caused by ß-globin mutations, including those causing ß-thalassemia and sickle cell disease, raising the prospect that reactivation of ϵ-globin expression could be used in managing these conditions in humans. Although the human globin genes are known to be regulated by a variety of multiprotein complexes containing enzymes that catalyze epigenetic modifications, the exact mechanisms controlling ϵ-globin gene silencing remain elusive. Here we found that the heterochromatin protein HP1γ, a multifunctional chromatin- and DNA-binding protein with roles in transcriptional activation and elongation, represses ϵ-globin expression by interacting with a histone-modifying enzyme, lysine methyltransferase SUV4-20h2. Silencing of HP1γ expression markedly decreased repressive histone marks and the multimethylation of histone H3 lysine 9 and H4 lysine 20, leading to a significant decrease in DNA methylation at the proximal promoter of the ϵ-globin gene and greatly increased ϵ-globin expression. In addition, using chromatin immunoprecipitation, we showed that SUV4-20h2 facilitates the deposition of HP1γ on the ϵ-globin-proximal promoter. Thus, these data indicate that HP1γ is a novel epigenetic repressor of ϵ-globin gene expression and provide a potential strategy for targeted therapies for ß-thalassemia and sickle cell disease.
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Proteínas Cromosómicas no Histona/metabolismo , Represión Epigenética , Globinas épsilon/genética , Línea Celular , Homólogo de la Proteína Chromobox 5 , Metilación de ADN , N-Metiltransferasa de Histona-Lisina/metabolismo , Humanos , Regiones Promotoras Genéticas , Activación TranscripcionalRESUMEN
A sub-eutectic high-entropy alloy composed of CoCrFeNiNb0.25 was prepared using a combination of mechanical powder mixing and selective laser melting (SLM). The mechanical properties of the alloy were enhanced by employing an interlayer laser remelting process. This study demonstrates the feasibility of using mechanical mixing and SLM to form an CoCrFeNiNb0.25 alloy. The interlayer laser remelting process can effectively promote the melting of Nb particles introduced by mechanical mixing, release the stresses near the unfused Nb particles, and reduce their degradation of the specimen properties. The results indicate that the CoCrFeNiNb0.25 alloy, prepared using the interlayer laser remelting process, had an average microhardness of 376 HV, a tensile strength of 974 MPa, and an elongation at break of 10.51%. This process offers a viable approach for rapidly adjusting the composition of high-entropy alloys for SLM forming.
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With the continuous reduction of chip size, fluxless soldering has brought attention to high-density, three-dimensional packaging. Although fluxless soldering technology with formic acid (FA) atmosphere has been presented, few studies have examined the effect of the Pt catalytic, preheating time, and soldering pad on FA soldering for the Sn-58Bi solder. The results have shown that the Pt catalytic can promote oxidation-reduction and the formation of a large pore in the Sn-58Bi/Cu solder joint, which causes a decrease in shear strength. ENIG (electroless nickel immersion gold) improves soldering strength. The shear strength of Sn-58Bi/ENIG increases under the Pt catalytic FA atmosphere process due to the isolation of the Au layer on ENIG. The Au layer protects metal from corrosion and provides a good contact surface for the Sn-58Bi solder. The shear strength of the Sn-58Bi/ENIG joints under a Pt catalytic atmosphere improved by 44.7% compared to using a Cu pad. These findings reveal the improvement of the shear strength of solder joints bonded at low temperatures under the FA atmosphere.
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Developing large-scale hydrogels with high tensile strength and robust mechanical properties is an intricate challenge of great industrial significance. In this study, we demonstrate an efficient method for producing nanocomposite hydrogels with extraordinary mechanical properties. Our approach involves a two-step process: an initial stage of pre-cross-linking boron nitride (BN)-enriched pre-gel sodium alginate, followed by cross-linking with metal ions. In stark contrast to conventional sodium alginate hydrogels (SA), our newly formulated 'BS hydrogel' exhibited an impressive tensile strength exceeding 41 MPa and improved thermal resistance. Moreover, the reconstituted BS hydrogel exhibited tensile strengths ranging from 47 to 96 MPa and elastic moduli ranging from 199 to 1184 MPa, depending on the cross-linking metal ions. These findings indicate the multifaceted potential of the BS hydrogel, which is poised to revolutionize many applications and represents a significant step forward in hydrogel technology for industrial applications.
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Aerogel-based composites, renowned for their three-dimensional (3D) network architecture, are gaining increasing attention as lightweight electromagnetic (EM) wave absorbers. However, attaining high reflection loss, broad effective absorption bandwidth (EAB), and ultrathin thickness concurrently presents a formidable challenge, owing to the stringent demands for precise structural regulation and incorporation of magnetic/dielectric multicomponents with synergistic loss mechanisms within the 3D networks. In this study, we successfully synthesized a 3D hierarchical porous Fe3O4/MoS2/rGO/Ti3C2Tx MXene (FMGM) composite aerogel via directional freezing and subsequent heat treatment processes. Owing to their ingenious structure and multicomponent design, the FMGM aerogels, featured with abundant heterogeneous interface structure and magnetic/dielectric synergism, show exceptional impedance matching characteristics and diverse EM wave absorption mechanisms. After optimization, the prepared ultralight (6.4 mg cm-3) FMGM-2 aerogel exhibits outstanding EM wave absorption performance, achieving a minimal reflection loss of -66.92 dB at a thickness of 3.61 mm and an EAB of 6.08 GHz corresponding to the thickness of 2.3 mm, outperforming most of the previously reported aerogel-based absorbing materials. This research presents an effective strategy for fabricating lightweight, ultrathin, highly efficient, and broad band EM wave absorption materials.
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Bimetallic alloy nanoparticles have garnered substantial attention for diverse catalytic applications owing to their abundant active sites and tunable electronic structures, whereas the synthesis of ultrafine alloy nanoparticles with atomic-level homogeneity for bulk-state immiscible couples remains a formidable challenge. Herein, we present the synthesis of RuxCo1-x solid-solution alloy nanoparticles (ca. 2 nm) across the entire composition range, for highly efficient, durable, and selective CO2 hydrogenation to CH4 under mild conditions. Notably, Ru0.88Co0.12/TiO2 and Ru0.74Co0.26/TiO2 catalysts, with 12 and 26 atom % of Ru being substituted by Co, exhibit enhanced catalytic activity compared with the monometallic Ru/TiO2 counterparts both in dark and under light irradiation. The comprehensive experimental investigations and density functional theory calculations unveil that the electronic state of Ru is subtly modulated owing to the intimate interaction between Ru and Co in the alloy nanoparticles, and this effect results in the decline in the CO2 conversion energy barrier, thus ultimately culminating in an elevated catalytic performance relative to monometallic Ru and Co catalysts. In the photopromoted thermocatalytic process, the photoinduced charge carriers and localized photothermal effect play a pivotal role in facilitating the chemical reaction process, which accounts for the further boosted CO2 methanation performance.
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OBJECTIVE: To observe the clinical efficacy of combination of traditional Chinese medicine and western medicine in the treatment of patient bitten by agkistrodon halys pallas, and the changes in peripheral blood inflammatory factors (hs-PCR, IL-6, TNF-alpha). METHOD: Ninty-eight patients were divided into three groups according to their hospitalization dates: the western medicine group, in which 32 patients were treated with antivenom serum (6 000 U) for five days, once every day; the traditional Chinese medicine group, in which 32 patients were treated with anti pit viper No. 2 concentrated decoction (300 mL), twice to three times every day, for five days; and the combined traditional Chinese medicine and western medicine group, in which 35 patients were treated with the combination of Chinese and Western medicine treatment described above. Then blood samples of all of patients were obtained, and serum factors (hs-PCR, IL-6, TNF-alpha) in peripheral blood were measured by Elisa assay. Another 30 health volunteers were chosen as the normal control group. RESULT: The serum inflammatory factors were significantly higher in all patients of the three groups than that in healthy control before treatment (P < 0.01), and decreased significantly after treatment. In particular, the more remarkable reduction was found in the combined traditional Chinese medicine and western medicine group compared with the western medicine group and the traditional medicine group (P < 0.01). Symptom elimination in the three groups was superior to the western medicine group and the traditional medicine group at the first day and the third day of treatment (P < 0.05, P < 0.01). Total clinical effective rate was 100% in the combined traditional Chinese medicine and western medicine group, 84. 37% in the traditional medicine group and 65.62% in the western medicine group, the clinical effective rate of the combined traditional Chinese medicine and western medicine group was notably superior to that of the western medicine group and the traditional medicine group (P < 0.01). CONCLUSION: The serum inflammatory factors increased significantly in patients bitten by agkistrodon halys pallas. Treatment with the combined traditional Chinese medicine and western medicine can significantly decrease the serum inflammatory factors, and increase clinical effect, with more obvious clinical efficacy compared with the western medicine group and the traditional medicine group.
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Antivenenos/administración & dosificación , Medicamentos Herbarios Chinos/administración & dosificación , Mordeduras de Serpientes/tratamiento farmacológico , Adolescente , Adulto , Anciano , Niño , Quimioterapia Combinada , Femenino , Humanos , Interleucina-6/sangre , Interleucina-6/inmunología , Masculino , Persona de Mediana Edad , Mordeduras de Serpientes/sangre , Mordeduras de Serpientes/inmunología , Resultado del Tratamiento , Factor de Necrosis Tumoral alfa/sangre , Factor de Necrosis Tumoral alfa/inmunología , Adulto JovenRESUMEN
Carbon dioxide (CO2) hydrogenation to methane (CH4) is regarded as a promising approach for CO2 utilization, whereas achieving desirable conversion efficiency under mild conditions remains a significant challenge. Herein, we have identified ultrasmall Ru nanoparticles (â¼2.5 nm) anchored on MnCo2O4 nanosheets as prospective photothermal catalysts for CO2 methanation at ambient pressure with light irradiation. Our findings revealed that MnCo2O4 nanosheets exhibit dual functionality as photothermal substrates for localized temperature enhancement and photocatalysts for electron donation. As such, the optimized Ru/MnCo2O4-2 gave a high CH4 production rate of 66.3 mmol gcat-1 h-1 (corresponding to 5.1 mol gRu-1 h-1) with 96% CH4 selectivity at 230 °C under ambient pressure and light irradiation (420-780 nm, 1.25 W cm-2), outperforming most reported plasmonic metal-based catalysts. The mechanisms behind the intriguing photothermal catalytic performance improvement were substantiated through a comprehensive investigation involving experimental characterizations, numerical simulations and density functional theory (DFT) calculations, which unveiled the synergistic effects of enhanced charge separation efficiency, improved reaction kinetics, facilitated reactant adsorption/activation and accelerated intermediate conversion under light irradiation over Ru/MnCo2O4. A comparison study showed that, with identical external input energy during the reaction, Ru/MnCo2O4-2 had a much higher catalytic efficiency compared to Ru/TiO2 and Ru/Al2O3. This study underscores the pivotal role played by photothermal supports and is believed to engender a heightened interest in plasmonic metal nanoparticles anchored on photothermal substrates for CO2 methanation under mild conditions.
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Two-dimensional nanomaterial-based membranes have earned broad attention because of their excellent capability of separation performance in a mixture that can challenge the conventional membrane materials utilized in the organic solvent nanofiltration (OSN) field. Boron nitride (BN) nanosheet membranes have displayed superb stability and separation ability in aqueous and organic solutions compared to the widely researched analogous graphene-based membranes; nevertheless, the concentration polarization of organic dye pollutants fades their separation performance and eclipses their potential adoption as a feasible technology. Herein, PDDA-modified BN (PBN) and sodium alginate-modified BN (SBN) nanosheet membranes with a thinner laminar structure are facially fabricated to improve the molecule separation performance compared to that of the pristine BN membrane. In aqueous separation application, the SBN membranes (2 µm) can reject positively charged dyes up to 100% and the PBN membrane (2 µm) could reject negatively charged dyes up to 100%. Impressively, the PBN membranes (3 µm) and SBN membranes (3 µm) demonstrate record high performances in OSN, with a permeance of 809 L m-2 h-1 bar-1 and 97.71% rejection to acid fuchsin in acetonitrile and 290 L m-2 h-1 bar-1 and 94.94% rejection to Azure B in dimethyl sulfoxide, respectively. The charged PBN and SBN nanosheet membranes demonstrate stable separation capability, exhibiting their potential for practical water and organic solvent purification processes.
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Achieving scalable synthesis of nanoscale transition-metal carbides (TMCs), regarded as substitutes for platinum-group noble metals, remains an ongoing challenge. Herein, a 100-g scale synthesis of single-phased cobalt carbide (Co2 C) through carburization of Co-based Prussian Blue Analog (Co-PBA) is reported in CO2 /H2 atmosphere under mild conditions (230 °C, ambient pressure). Textural property investigations indicate a successful preparation of orthorhombic-phased Co2 C nanomaterials with Pt-group-like electronic properties. As a demonstration, Co2 C achieves landmark photo-assisted thermal catalytic CO2 conversion rates with photo-switched product selectivity, which far exceeds the representative Pt-group-metal-based catalysts. This impressive result is attributed to the excellent activation of reactants, colorific light absorption, and photo-to-thermal conversion capacities. In addition to CO2 hydrogenation, the versatile Co2 C materials show huge prospects in antibacterial therapy, interfacial water evaporation, electrochemical hydrogen evolution reaction, and battery technologies. This study paves the way toward unlocking the potential of multi-functional Co2 C nanomaterials.
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Human demand for food has been increasing as population grows around the world. Meanwhile, global temperature has been rising with the increase of greenhouse gas (GHG) emissions. Although soil mulching (SM) is an effective method to increase crop yield because it could conserve soil moisture and temperature, it is also an important factor affecting GHG productions and emissions. At present, research results in terms of the impact of SM on agricultural GHG emissions are still inconsistent. Therefore, a meta-analysis was used to quantitatively analyze the impact of SM on crop yield and GHG emissions in China. Overall, SM significantly enhanced not only crop yield, but also GHG emissions. Compared with no soil mulching (NSM), SM improved crop yield by 21.84%, while increased global warming potential (GWP) by 11.38%. To minimize the negative impact of SM on GHG, for maize and wheat in arid, semi-arid and semi-humid zones, it is recommended to use flat full mulching with grave or straw plus drip irrigation under neutral or weakly alkaline soil with bulk density <1.3g cm-3. For rice in humid regions, it is advisable to apply SM to minimize GHG emissions by significantly decreasing CH4 emissions.
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Producción de Cultivos , Gases de Efecto Invernadero/análisis , Suelo/química , China , Calentamiento Global , Metano/análisis , Óxidos de Nitrógeno/análisis , Oryza/crecimiento & desarrolloRESUMEN
Nitrogen fertilization (NF) is one of the common practices to increase crop production worldwide over the past several decades. Nevertheless, unreasonable NF results in massive greenhouse gas (GHG) emissions, leading to climate change and global warming. Many studies have already reported the impact of NF on crop yield, global warming potential (GWP) and greenhouse gas intensity (GHGI), but the studies were limited to only some parameters. In this study, a total of 174 studies from 16 countries were collected and then a regression analysis was conducted to obtain the appropriate N fertilization rates that enhance crop yield while reducing GWP and GHGI. After that, a meta-analysis was performed to evaluate the effects of NF on crop yield, GHGI, GWP and GHG emissions and identify NF management strategies that benefit crop yield and maintain GWP. The results showed that the suitable N fertilization rate was 180, 150, 130 and 200 kg ha-1 for wheat, maize, rice and vegetables or industrial crops, respectively. Overall, NF resulted in positive effect size in crop yield (0.56) and negative effect size in GHGI (-0.14) compared to NNF. GWP showed positive effect size (0.37) due to an increase in N2O emissions (0.91) relative to NNF, which is higher than the increase of CH4 emissions (0.01) and CO2 emissions (0.22). It was recommended that split and banded application of urea or urea plus manure is employed for cereals (especially wheat) in the arid and semi-arid regions with medium-textured and neutral or alkaline soil.
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Gases de Efecto Invernadero , Oryza , Agricultura/métodos , Fertilizantes/análisis , Calentamiento Global , Gases de Efecto Invernadero/análisis , Metano/análisis , Nitrógeno , Óxido Nitroso/análisis , Suelo , Triticum , UreaRESUMEN
A key common problem for vertical few-layer graphene (VFLG) applications in electronic devices is the solution to grow on substrates. In this study, four kinds of substrates (silicon, stainless-steel, quartz and carbon-cloth) were examined to understand the mechanism of the nucleation and growth of VFLG by using the inductively-coupled plasma-enhanced chemical vapor deposition (ICPCVD) method. The theoretical and experimental results show that the initial nucleation of VFLG was influenced by the properties of the substrates. Surface energy and catalysis of substrates had a significant effect on controlling nucleation density and nucleation rate of VFLG at the initial growth stage. The quality of the VFLG sheet rarely had a relationship with this kind of substrate and was prone to being influenced by growth conditions. The characterization of conductivity and field emissions for a single VFLG were examined in order to understand the influence of substrates on the electrical property. The results showed that there was little difference in the conductivity of the VFLG sheet grown on the four substrates, while the interfacial contact resistance of VFLG on the four substrates showed a tremendous difference due to the different properties of said substrates. Therefore, the field emission characterization of the VFLG sheet grown on stainless-steel substrate was the best, with the maximum emission current of 35 µA at a 160 V/µm electrostatic field. This finding highlights the controllable interface of between VFLG and substrates as an important issue for electrical application.
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In this work, we performed a systematic study of the physical properties of amorphous Indium-Gallium-Zinc Oxide (a-IGZO) films prepared under various deposition pressures, O2/(Ar+O2) flow ratios, and annealing temperatures. X-ray reflectivity (XRR) and microwave photoconductivity decay (µ-PCD) measurements were conducted to evaluate the quality of a-IGZO films. The results showed that the process conditions have a substantial impact on the film densities and defect states, which in turn affect the performance of the final thin-film transistors (TFT) device. By optimizing the IGZO film deposition conditions, high-performance TFT was able to be demonstrated, with a saturation mobility of 8.4 cm2/Vs, a threshold voltage of 0.9 V, and a subthreshold swing of 0.16 V/dec.
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The proto-oncogene c-Myc regulates multiple biological processes mainly through selectively activating gene expression. However, the mechanisms underlying c-Myc-mediated gene repression in the context of cancer remain less clear. This study aimed to clarify the role of PRMT5 in the transcriptional repression of c-Myc target genes in gastric cancer. Methods: Immunohistochemistry was used to evaluate the expression of PRMT5, c-Myc and target genes in gastric cancer patients. PRMT5 and c-Myc interaction was assessed by immunofluorescence, co-immunoprecipitation and GST pull-down assays. Bioinformatics analysis, immunoblotting, real-time PCR, chromatin immunoprecipitation, and rescue experiments were used to evaluate the mechanism. Results: We found that c-Myc directly interacts with protein arginine methyltransferase 5 (PRMT5) to transcriptionally repress the expression of a cohort of genes, including PTEN, CDKN2C (p18INK4C), CDKN1A (p21CIP1/WAF1), CDKN1C (p57KIP2) and p63, to promote gastric cancer cell growth. Specifically, we found that PRMT5 was required to promote gastric cancer cell growth in vitro and in vivo, and for transcriptional repression of this cohort of genes, which was dependent on its methyltransferase activity. Consistently, the promoters of this gene cohort were enriched for both PRMT5-mediated symmetric di-methylation of histone H4 on Arg 3 (H4R3me2s) and c-Myc, and c-Myc depletion also upregulated their expression. H4R3me2s also colocalized with the c-Myc-binding E-box motif (CANNTG) on these genes. We show that PRMT5 directly binds to c-Myc, and this binding is required for transcriptional repression of the target genes. Both c-Myc and PRMT5 expression levels were upregulated in primary human gastric cancer tissues, and their expression levels inversely correlated with clinical outcomes. Conclusions: Taken together, our study reveals a novel mechanism by which PRMT5-dependent transcriptional repression of c-Myc target genes is required for gastric cancer progression, and provides a potential new strategy for therapeutic targeting of gastric cancer.
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Adenocarcinoma/metabolismo , Histonas/metabolismo , Proteína-Arginina N-Metiltransferasas/metabolismo , Proteínas Proto-Oncogénicas c-myc/metabolismo , Neoplasias Gástricas/metabolismo , Adenocarcinoma/patología , Línea Celular Tumoral , Progresión de la Enfermedad , Expresión Génica , Regulación Neoplásica de la Expresión Génica , Humanos , Metilación , Regiones Promotoras Genéticas , Proto-Oncogenes Mas , Neoplasias Gástricas/patologíaRESUMEN
The development of wearable strain sensors for the human-machine interface has attracted considerable research interest. Most existing wearable strain sensors were incapable of simultaneously detecting strain amplitudes and directions, and they failed to fully record stretching vectors that occurred on the body. Graphene and graphene-derived materials have been utilized to construct wearable strain sensors with excellent electrical sensitivities. Although the growth techniques of planar graphene and vertical graphene (VG) have been established, the fabrication of VG aligned in parallel within a larger area has not been previously achieved. Here, parallelly aligned VG (PAVG) in a large area was successfully fabricated and constructed as a wearable strain vector sensor. The PAVG was fabricated via inductively coupled plasma chemical vapor deposition assisted by metal inducers. The as-fabricated sensor was electrically anisotropic because of the profiles of the VG nanosheets aligned in parallel. Therefore, the sensor could simultaneously and sensitively detect the direction and the amplitude of the strain vectors with excellent accuracy. Application of this strain vector sensor for the human-sensor interface to identify the stretching directions and amplitudes of finger joints was also demonstrated. This work established the fabrication methodology of graphene with unique vertical and parallel alignment morphology. This study introduced a new opportunity of developing wearable sensors that could fully detect multidirectional human actions.