RESUMEN
The mechanism by which interferon regulatory factor 8 (IRF8) mutation contributes to lymphomagenesis is unknown. We modeled IRF8 variants in B cell lymphomas and found that they affected the expression of regulators of antigen presentation. Expression of IRF8 mutants in murine B cell lymphomas suppressed CD4, but not CD8, activation elicited by antigen presentation and downmodulated CD74 and human leukocyte antigen (HLA) DM, intracellular regulators of antigen peptide processing/loading in the major histocompatibility complex (MHC) II. Concordantly, mutant IRF8 bound less efficiently to the promoters of these genes. Mice harboring IRF8 mutant lymphomas displayed higher tumor burden and remodeling of the tumor microenvironment, typified by depletion of CD4, CD8, and natural killer cells, increase in regulatory T cells and T follicular helper cells. Deconvolution of bulk RNA sequencing data from IRF8-mutant human diffuse large B cell lymphoma (DLBCL) recapitulated part of the immune remodeling detected in mice. We concluded that IRF8 mutations contribute to DLBCL biology by facilitating immune escape.
Asunto(s)
Presentación de Antígeno , Antígenos de Diferenciación de Linfocitos B , Antígenos de Histocompatibilidad Clase II , Factores Reguladores del Interferón , Mutación , Factores Reguladores del Interferón/genética , Factores Reguladores del Interferón/metabolismo , Animales , Presentación de Antígeno/inmunología , Presentación de Antígeno/genética , Humanos , Ratones , Antígenos de Histocompatibilidad Clase II/genética , Antígenos de Histocompatibilidad Clase II/inmunología , Antígenos de Histocompatibilidad Clase II/metabolismo , Antígenos de Diferenciación de Linfocitos B/genética , Antígenos de Diferenciación de Linfocitos B/metabolismo , Linfoma de Células B/genética , Linfoma de Células B/inmunología , Microambiente Tumoral/inmunología , Linfoma de Células B Grandes Difuso/genética , Linfoma de Células B Grandes Difuso/inmunología , Linfoma de Células B Grandes Difuso/patología , Línea Celular Tumoral , Escape del Tumor/genética , Regulación Neoplásica de la Expresión GénicaRESUMEN
Two-dimensional (2D) transitional metal dichalcogenides (TMDs) have garnered significant attention due to their potential for next-generation electronics, which require device scaling. However, the performance of TMD-based field-effect transistors (FETs) is greatly limited by the contact resistance. This study develops an effective strategy to optimize the contact resistance of WSe2 FETs by combining contact doping and 2D metallic electrode materials. The contact regions were doped using a laser, and the metallic TaSe2 flakes were stacked on doped WSe2 as electrodes. Doping the contact areas decreases the depletion width, while introducing the TaSe2 contact results in a lower Schottky barrier. This method significantly improves the electrical performance of the WSe2 FETs. The doped WSe2/TaSe2 contact exhibits an ultralow Schottky barrier height of 65 meV and a contact resistance of 11 kΩ·µm, which is a 50-fold reduction compared to the conventional Cr/Au contact. Our method offers a way on fabricating high-performance 2D FETs.
RESUMEN
In diffuse large B-cell lymphoma (DLBCL), the transcription factor IRF8 is the target of a series of potentially oncogenic events, including, chromosomal translocation, focal amplification, and super-enhancer perturbations. IRF8 is also frequently mutant in DLBCL, but how these variants contribute to lymphomagenesis is unknown. We modeled IRF8 mutations in DLBCL and found that they did not meaningfully impact cell fitness. Instead, IRF8 mutants, mapping either to the DNA-binding domain (DBD) or c-terminal tail, displayed diminished transcription activity towards CIITA, a direct IRF8 target. In primary DLBCL, IRF8 mutations were mutually exclusive with mutations in genes involved in antigen presentation. Concordantly, expression of IRF8 mutants in murine B cell lymphomas uniformly suppressed CD4, but not CD8, activation elicited by antigen presentation. Unexpectedly, IRF8 mutation did not modify MHC CII expression on the cell surface, rather it downmodulated CD74 and HLA- DM, intracellular regulators of antigen peptide processing/loading in the MHC CII complex. These changes were functionally relevant as, in comparison to IRF8 WT, mice harboring IRF8 mutant lymphomas displayed a significantly higher tumor burden, in association with a substantial remodeling of the tumor microenvironment (TME), typified by depletion of CD4, CD8, Th1 and NK cells, and increase in T-regs and Tfh cells. Importantly, the clinical and immune phenotypes of IRF8-mutant lymphomas were rescued in vivo by ectopic expression of CD74. Deconvolution of bulk RNAseq data from primary human DLBCL recapitulated part of the immune remodeling detected in mice and pointed to depletion of dendritic cells as another feature of IRF8 mutant TME. We concluded that IRF8 mutations contribute to DLBCL biology by facilitating immune escape.
RESUMEN
Two-dimensional transition metal dichalcogenides (TMDs), as flexible and stretchable materials, have attracted considerable attention in the field of novel flexible electronics due to their excellent mechanical, optical, and electronic properties. Among the various TMD materials, atomically thin MoS2has become the most widely used material due to its advantageous properties, such as its adjustable bandgap, excellent performance, and ease of preparation. In this work, we demonstrated the practicality of a stacked wafer-scale two-layer MoS2film obtained by transferring multiple single-layer films grown using chemical vapor deposition. The MoS2field-effect transistor cell had a top-gated device structure with a (PI) film as the substrate, which exhibited a high on/off ratio (108), large average mobility (â¼8.56 cm2V-1s-1), and exceptional uniformity. Furthermore, a range of flexible integrated logic devices, including inverters, NOR gates, and NAND gates, were successfully implemented via traditional lithography. These results highlight the immense potential of TMD materials, particularly MoS2, in enabling advanced flexible electronic and optoelectronic devices, which pave the way for transformative applications in future-generation electronics.
RESUMEN
The TMEM127 gene encodes a transmembrane protein of poorly known function that is mutated in pheochromocytomas, neural crest-derived tumors of adrenomedullary cells. Here, we report that, at single-nucleus resolution, TMEM127-mutant tumors share precursor cells and transcription regulatory elements with pheochromocytomas carrying mutations of the tyrosine kinase receptor RET. Additionally, TMEM127-mutant pheochromocytomas, human cells, and mouse knockout models of TMEM127 accumulate RET and increase its signaling. TMEM127 contributes to RET cellular positioning, trafficking, and lysosome-mediated degradation. Mechanistically, TMEM127 binds to RET and recruits the NEDD4 E3 ubiquitin ligase for RET ubiquitination and degradation via TMEM127 C-terminal PxxY motifs. Lastly, increased cell proliferation and tumor burden after TMEM127 loss can be reversed by selective RET inhibitors in vitro and in vivo. Our results define TMEM127 as a component of the ubiquitin system and identify aberrant RET stabilization as a likely mechanism through which TMEM127 loss-of-function mutations cause pheochromocytoma.
Asunto(s)
Neoplasias de las Glándulas Suprarrenales , Feocromocitoma , Humanos , Animales , Ratones , Feocromocitoma/genética , Feocromocitoma/metabolismo , Feocromocitoma/patología , Mutación de Línea Germinal , Neoplasias de las Glándulas Suprarrenales/genética , Neoplasias de las Glándulas Suprarrenales/metabolismo , Neoplasias de las Glándulas Suprarrenales/patología , Mutación/genética , Ubiquitinación , Proteínas Proto-Oncogénicas c-ret/genética , Proteínas Proto-Oncogénicas c-ret/metabolismo , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismoRESUMEN
Interlayer excitons (ILEs) in the van der Waals (vdW) heterostructures of type-II band alignment transition metal dichalcogenides (TMDCs) have attracted significant interest owing to their unique exciton properties and potential in quantum information applications. However, the new dimension that emerges with the stacking of structures with a twist angle leads to a more complex fine structure of ILEs, presenting both an opportunity and a challenge for the regulation of the interlayer excitons. In this study, we report the evolution of interlayer excitons with the twist angle in the WSe2/WS2 heterostructure and identify the direct (indirect) interlayer excitons by combining photoluminescence (PL) and density functional theory (DFT) calculations. Two interlayer excitons with opposite circular polarization assigned to the different transition paths of K-K and Q-K were observed. The nature of the direct (indirect) interlayer exciton was confirmed by circular polarization PL measurement, excitation power-dependent PL measurement and DFT calculations. Furthermore, by applying an external electric field to regulate the band structure of the WSe2/WS2 heterostructure and control the transition path of the interlayer excitons, we could successfully realize the regulation of interlayer exciton emission. This study provides more evidence for the twist-angle-based control of heterostructure properties.
RESUMEN
Two-dimensional (2D) materials and their van der Waals stacked heterostructures (vdWH) are becoming the rising and glowing candidates in the emerging flexible nanoelectronics and optoelectronic industry. Strain engineering proves to be an efficient way to modulate the band structure of 2D materials and their vdWH, which will broaden understanding and practical applications of the material. Therefore, how to apply desired strain to 2D materials and their vdWH is of great importance to get the intrinsic understanding of 2D materials and their vdWH with strain modulation. Here, systematic and comparative studies of strain engineering on monolayer WSe2 and graphene/WSe2 heterostructure are studied by photoluminescence (PL) measurements under uniaxial tensile strain. It is found that contacts between graphene and WSe2 interface are improved, and the residual strain is relieved through the pre-strain process, which thus results in the comparable shift rate of the neutral exciton (A) and trion (AT) of monolayer WSe2 and graphene/WSe2 heterostructure under the subsequent strain release process. Furthermore, the PL quenching occurred when the strain is restored to the original position also indicates the pre-strain process to 2D materials, and their vdWH is important and necessary for improving the interface contacts and reducing the residual strain. Thus, the intrinsic response of the 2D material and their vdWH under strain can be obtained after the pre-strain treatment. These findings provide a quick, fast and efficient way to apply desired strain and also have important significance in guiding the use of 2D materials and their vdWH in the field of flexible and wearable devices.
RESUMEN
Two-dimensional InSe has been considered as a promising candidate for novel optoelectronic devices owing to large electron mobility and a near-infrared optical band gap. However, its widespread applications suffer from environmental instability. A lot of theoretical studies on the degradation mechanism of InSe have been reported whereas the experimental proofs are few. Meanwhile, the role of the extrinsic environment is still obscure during the degradation. As a common technique of studying the degradation mechanism of 2D materials, laser irradiation exhibits many unique advantages, such as being fast, convenient, and offering in situ compatibility. Here, we have developed a laser-treated method, which involves performing repeated measurements at the same point while monitoring the evolution of the resulting PL, to systematically study the photo-induced degradation process of InSe. Interestingly, we observe different evolution behavior of PL intensity under weak irradiation and strong irradiation. Our experimental results indicate the vacancy passivation and degrading effect simultaneously occurring in InSe under a weak laser irradiation, resulting in the PL increasing first and then decreasing during the measurement. Meanwhile we also notice that the passivation has a stronger effect on the PL than the degrading effect of weak oxidation. In contrast, under a strong laser irradiation, the InSe suffers serious destruction caused by excess heating and intense oxidation. This leads to a direct decrease of PL and corresponding oxidative products. Our work provides a reliable experimental supplement to the photo oxidation study of InSe and opens up a new avenue to regulate the PL of InSe.
RESUMEN
Epidermal growth factor receptor variant III (EGFRvIII) is a mutant isoform of EGFR with a deletion of exons 2-7 making it insensitive to EGF stimulation and downstream signal constitutive activation. However, the mechanism underlying the stability of EGFRvIII remains unclear. Based on CRISPR-Cas9 library screening, we found that mucin1 (MUC1) is essential for EGFRvIII glioma cell survival and temozolomide (TMZ) resistance. We revealed that MUC1-C was upregulated in EGFRvIII-positive cells, where it enhanced the stability of EGFRvIII. Knockdown of MUC1-C increased the colocalization of EGFRvIII and lysosomes. Upregulation of MUC1 occurred in an NF-κB dependent manner, and inhibition of the NF-κB pathway could interrupt the EGFRvIII-MUC1 feedback loop by inhibiting MUC1-C. In a previous report, we identified AC1Q3QWB (AQB), a small molecule that could inhibit the phosphorylation of NF-κB. By screening the structural analogs of AQB, we obtained EPIC-1027, which could inhibit the NF-κB pathway more effectively. EPIC-1027 disrupted the EGFRvIII-MUC1-C positive feedback loop in vitro and in vivo, inhibited glioma progression, and promoted sensitization to TMZ. In conclusion, we revealed the pivotal role of MUC1-C in stabilizing EGFRvIII in glioblastoma (GBM) and identified a small molecule, EPIC-1027, with great potential in GBM treatment.
Asunto(s)
Neoplasias Encefálicas , Glioblastoma , Glioma , Humanos , Temozolomida/farmacología , Glioblastoma/tratamiento farmacológico , Glioblastoma/genética , Glioblastoma/metabolismo , FN-kappa B/metabolismo , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Línea Celular Tumoral , Mucina-1/genéticaRESUMEN
Molecular ferroelectrics (MFs) have been proven to demonstrate excellent properties even comparable to those of inorganic counterparts usually with heavy metals. However, the validation of their device applications is still at the infant stage. The polycrystalline feature of conventionally obtained MF films, the patterning challenges for microelectronics and the brittleness of crystalline films significantly hinder their development for organic integrated circuits, as well as emerging flexible electronics. Here, a large-area flexible memory array is demonstrated of oriented molecular ferroelectric single crystals (MFSCs) with nearly saturated polarization. Highly-uniform MFSC arrays are prepared on large-scale substrates including Si wafers and flexible substrates using an asymmetric-wetting and microgroove-assisted coating (AWMAC) strategy. Resultant flexible memory arrays exhibit excellent nonvolatile memory properties with a low-operating voltage of <5 V, i.e., nearly saturated ferroelectric polarization (6.5 µC cm-2 ), and long bending endurance (>103 ) under various bending radii. These results may open an avenue for scalable flexible MF electronics with high performance.
RESUMEN
Organic-inorganic hybrid semiconducting (OIHS) materials, which can detect broader spectral regions, are highly desired in several applications including biomedical imaging, night vision, and optical communications. Although lead (Pb)-halide perovskites have reached a mature research stage, high toxicity of Pb hinders their large-scale viability. Tin (Sn)-based perovskites are the most common OIHS broadband light absorbers that replace toxic Pb; however, they are extremely unstable due to the notorious Sn2+ oxidation. Herein, a novel, non-toxic, and solution-processed millimeter-sized OIHS single crystal [Ga(C3H7NO)6](I3)3 has been grown at room temperature. Both the absorption measurement and density functional theory calculations have confirmed a narrow indirect band gap of 1.32 eV. The corresponding photodetector based on this single crystal demonstrated excellent performance including an ultraviolet-visible-near infrared (UV-vis-NIR) response between 325 and 1064 nm, fast response time (trise/tdecay = 3.8 ms/5.4 ms), and profound air storage stability (41 h), thus outperforming most common photodetectors based on Sn-based perovskites. This work not only provides a profound understanding of this novel organic-inorganic single-crystal material but also demonstrates its great potential to realize the high-performance UV-vis-NIR broadband photodetectors.
RESUMEN
2D semiconductors, such as molybdenum disulfide (MoS2 ), have attracted tremendous attention in constructing advanced monolithic integrated circuits (ICs) for future flexible and energy-efficient electronics. However, the development of large-scale ICs based on 2D materials is still in its early stage, mainly due to the non-uniformity of the individual devices and little investigation of device and circuit-level optimization. Herein, a 4-inch high-quality monolayer MoS2 film is successfully synthesized, which is then used to fabricate top-gated (TG) MoS2 field-effect transistors with wafer-scale uniformity. Some basic circuits such as static random access memory and ring oscillators are examined. A pass-transistor logic configuration based on pseudo-NMOS is then employed to design more complex MoS2 logic circuits, which are successfully fabricated with proper logic functions tested. These preliminary integration efforts show the promising potential of wafer-scale 2D semiconductors for application in complex ICs.
RESUMEN
Technostress as an antecedent factor exploring knowledge hiding continues to be seldomly discussed in the digital era. Based on the job demand-resource theory, this article introduces work exhaustion as a mediator variable and constructs a model that the five sub-dimensions of technostress (i.e., overload, invasion, complexity, insecurity, and uncertainty) affect knowledge hiding for R&D employees. Similarly, this study analyzes the moderation of workplace friendship as the resource buffering effect. Based on data from the 254 questionnaires of the two-stage survey, empirical results show that: (1) Techno-invasion, techno-insecurity, and techno-complexity have significant positive effects on work exhaustion, and techno-invasion has the greatest effect. However, techno-overload and techno-uncertainty have no significant relationship with work exhaustion. (2) Work exhaustion plays a mediating role in the relationships between the three aspects of technostress (techno-invasion, techno-insecurity, techno-complexity) and knowledge hiding; However, its mediating effects are insignificant in the relationships between the two aspects of technostress (techno-overload and techno-uncertainty) and knowledge hiding. (3) Workplace friendship negatively moderates the relationships between the two aspects of technostress (techno-invasion and techno-insecurity) and work exhaustion, leading to less knowledge hiding. Nonetheless, its negative moderation for the relationships between the two aspects of technostress (techno-overload and techno-uncertainty) and work exhaustion are insignificant. Empirical results further show that workplace friendship positively moderates the relationship between techno-complexity and work exhaustion.
RESUMEN
Hydraulic redistribution (HR), which is the passive movement of water through plant roots from wet to dry soil due to the water gradient, is important for plant physiology and ecohydrological processes. However, our poor knowledge on HR in the humid monsoon climate zone hampers the understanding of the interactions between vegetation and soil water during frequent droughts in evergreen forests. Thus, 5 years (2011-2015) of data, including meteorological parameters and soil moisture content at depths of 10, 30, 50, and 100 cm in soil profiles, were compared at one evergreen broad-leaved forest and at one clear-cutting forest site in south China. Analyses of soil moisture dynamics show that HR was frequently triggered within the depth of 30 cm at the evergreen broad-leaved forest, while (if any) was less visible at the clear-cutting forest site. The daily averaged magnitude of redistributed soil water reached the maximum of 0.81 mm/d. The HR mainly occurred during the monsoon dry season (i.e., from October to March of the following year), possibly indicating a different cause, i.e., asynchronous variations in rainfall and plant water use shape the seasonal patterns of soil water HR, compared to other humid zones. During the study period when HR occurred, the average daily HR in the soil profiles replenished approximately 34-50% of the water consumption in the 0-30 cm soil layer. The simulation results of a distributed hydrology-soil-vegetation model incorporating a HR scheme indicate that evapotranspiration enhanced during drought periods when HR occurred. In the future climate change context, comprehensive investigations on the water fluxes in the atmosphere-vegetation-soil continuum are needed to fully understand the effects of HR on the physiological responses of plants and on the water cycle.
Asunto(s)
Suelo , Agua , China , Bosques , Árboles/fisiología , Agua/fisiologíaRESUMEN
Angiogenesis and MYC expression associate with poor outcome in diffuse large B-cell lymphoma (DLBCL). MYC promotes neo-vasculature development but whether its deregulation in DLBCL contributes to angiogenesis is unclear. Examination of this relationship may uncover novel pathogenic regulatory circuitry as well as anti-angiogenic strategies in DLBCL. Here, we show that MYC expression positively correlates with vascular endothelial growth factor (VEGF) expression and angiogenesis in primary DLBCL biopsies, independently of dual expressor status or cell-of-origin classification. We found that MYC promotes VEGFA expression, a correlation that was validated in large datasets of mature B-cell tumours. Using DLBCL cell lines and patient-derived xenograft models, we identified the second messenger cyclic-AMP (cAMP) as a potent suppressor of MYC expression, VEGFA secretion and angiogenesis in DLBCL in normoxia. In hypoxia, cAMP switched targets and suppressed hypoxia-inducible factor 1α, a master regulator of VEGFA/angiogenesis in low oxygen environments. Lastly, we used the phosphodiesterase 4b (Pde4b) knockout mouse to demonstrate that the cAMP/PDE4 axis exercises additional anti-angiogenesis by directly targeting the lymphoma microenvironment. In conclusion, MYC could play a direct role in DLBCL angiogenesis, and modulation of cAMP levels, which can be achieved with clinical grade PDE4 inhibitors, has cell and non-cell autonomous anti-angiogenic activity in DLBCL.
Asunto(s)
AMP Cíclico , Subunidad alfa del Factor 1 Inducible por Hipoxia , Linfoma de Células B Grandes Difuso , Proteínas Proto-Oncogénicas c-myc , Adenosina Monofosfato , Animales , Línea Celular Tumoral , AMP Cíclico/metabolismo , Humanos , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Linfoma de Células B Grandes Difuso/patología , Ratones , Neovascularización Patológica/genética , Proteínas Proto-Oncogénicas c-myc/metabolismo , Microambiente Tumoral , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
In this study, a novel peptide GPPGPA was screened from the collagen hydrolysates of Chinese giant salamander (Andrias davidianus) skin, and its anti-diabetes mechanism was predicted by network pharmacology, and an inhibitory effect on α-glycosidase and protective effect on IR (insulin resistance) and oxidative stress of IR-HepG2 cells were detected. Through network pharmacology screening, GPPGPA was found to have good drug-like properties, and 103 targets of GPPGPA overlap with T2DM targets. These targets were mainly enriched in the PI3K-Akt signaling pathway associated with T2DM, the AGE-RAGE signaling pathway in diabetic complications, the TNF signaling pathway, insulin resistance and so on. The core targets were identified as AKT1, MAPK8, MAPK10 and JUN by constructing a "peptide-target-pathway" network. The molecular docking results showed that GPPGPA was well bound to the core targets. These results suggested that GPPGPA had the potential to reduce T2DM. Further in vitro experiments showed that GPPGPA as a competitive inhibitor could effectively inhibit the activity of α-glucosidase. The results of the IR-HepG2 cell model experiments showed that GPPGPA was not toxic to HepG2 cells, and could reduce IR of HepG2 cells induced by high-glucose and high-insulin, improve glucose consumption, increase the activity of superoxide dismutase (SOD), and reduce the content of malondialdehyde (MDA). The above results suggested that GPPGPA could improve T2DM by reducing insulin resistance through a multi-target and multi-pathway mechanism. GPPGPA could be developed and utilized as a novel hyperglycemic inhibitor in functional food.
Asunto(s)
Colágeno/química , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Hipoglucemiantes/farmacología , Fragmentos de Péptidos/farmacología , Piel/química , Urodelos , Animales , Glucosa/metabolismo , Glucógeno/metabolismo , Inhibidores de Glicósido Hidrolasas , Células Hep G2 , Humanos , Hipoglucemiantes/metabolismo , Resistencia a la Insulina , Cinética , Malondialdehído/metabolismo , Simulación del Acoplamiento Molecular , Farmacología en Red , Estrés Oxidativo , Fragmentos de Péptidos/metabolismo , Hidrolisados de Proteína , Superóxido Dismutasa/metabolismo , alfa-Glucosidasas/metabolismoRESUMEN
The emergence of near-eye displays, such as head-mounted displays, is triggering a requirement for highly enhanced display resolution. High-resolution micro-displays with micro-organic light-emitting diodes (micro-OLEDs) can be a preferential candidate, owing to the mature industrialization of OLEDs along with the advantages of flexibility, light weight, and ease of processing. However, micro-OLEDs with pixel sizes down to micrometers are difficult to be achieved using conventional techniques such as fine metal mask evaporation and lithography. Here, a solution-processing approach to pattern organic semiconductors (OSCs) for micro-OLED arrays with the assistance of templated dewetting is demonstrated. Solvents containing organic functional materials are dewetted on the surface with hydrophobic/hydrophilic patterns to form ordered droplet arrays using dip-coating. Subsequently, patterned OSC films are produced by effectively controlling solvent evaporation. Micro-OLED arrays with a pixel size down to 1 µm are successfully fabricated by further deposition of emitting/electron transport layers and top electrodes. This approach can open an avenue for low-cost manufacturing of flexible and high-resolution micro-displays.
Asunto(s)
Metales , Semiconductores , Electrodos , Diseño de EquipoRESUMEN
Mitochondria can function as signaling organelles, and part of this output leads to epigenetic remodeling. The full extent of this far-reaching interplay remains undefined. Here, we show that MYC transcriptionally activates IDH2 and increases alpha-ketoglutarate (αKG) levels. This regulatory step induces the activity of αKG-dependent DNA hydroxylases and RNA demethylases, thus reducing global DNA and RNA methylation. MYC, in a IDH2-dependent manner, also promotes the nuclear accumulation of TET1-TET2-TET3, FTO and ALKBH5. Notably, this subcellular movement correlated with the ability of MYC, in an IDH2-dependent manner, and, unexpectedly, of αKG to directly induce O-GlcNAcylation. Concordantly, modulation of the activity of OGT and OGA, enzymes that control the cycling of this non-canonical mono-glycosylation, largely recapitulated the effects of the MYC-IDH2-αKG axis on the subcellular movement of DNA and RNA demethylases. Together, we uncovered a hitherto unsuspected crosstalk between MYC, αKG and O-GlcNAcylation which could influence the epigenome and epitranscriptome homeostasis.
Asunto(s)
Metilación de ADN , ARN , Dioxigenasa FTO Dependiente de Alfa-Cetoglutarato/genética , Dioxigenasa FTO Dependiente de Alfa-Cetoglutarato/metabolismo , ADN/metabolismo , Proteínas de Unión al ADN/metabolismo , Humanos , Mitocondrias/metabolismo , Oxigenasas de Función Mixta/genética , Oxigenasas de Función Mixta/metabolismo , Proteínas Proto-Oncogénicas/metabolismoRESUMEN
Aiming at laser powder bed fusion of GH3536 nickel base alloy, the effects of different scanning strategies on microstructure, porosity and mechanical properties were explored. In the aspect of microstructure and micro hardness of the sample, three scanning strategies had little difference; in the aspect of macro mechanical properties of the sample, the slope subarea scanning was better than the helix and island scanning. On this basis, the slope subarea scanning was selected as the optimal scanning strategy to form the G-surface structure, and the compression performance of G-surface was studied. The results showed that: (1) the compression performance of G-surface structure was smaller than that of solid structure, The compression strength of G-surface can only reach about 20% of solid structure: the average strength value of G-surface is 220 MPa, solid structure is 1.1 GMpa; while G-surface structure had a smooth compression curve, which indicated the good energy absorption characteristics; (2) with the increase of wall thickness, the mechanical performance of G-surface structure was also enhanced, while the energy absorption capacity was constantly reduced; (3) with the same wall thickness, the compression performance of sample in building direction (BD) is higher than that in horizontal direction (HD).
RESUMEN
High-quality homogeneous junctions are of great significance for developing transition metal dichalcogenides (TMDs) based electronic and optoelectronic devices. Here, we demonstrate a lateral p-type/intrinsic/n-type (p-i-n) homojunction based multilayer WSe2 diode. The photodiode is formed through selective doping, more specifically by utilizing self-aligning surface plasma treatment at the contact regions, while keeping the WSe2 channel intrinsic. Electrical measurements of such a diode reveal an ideal rectifying behavior with a current on/off ratio as high as 1.2 × 106 and an ideality factor of 1.14. While operating in the photovoltaic mode, the diode presents an excellent photodetecting performance under 450 nm light illumination, including an open-circuit voltage of 340 mV, a responsivity of 0.1 A W-1, and a specific detectivity of 2.2 × 1013 Jones. Furthermore, benefiting from the lateral p-i-n configuration, the slow photoresponse dynamics including the photocarrier diffusion in undepleted regions and photocarrier trapping/detrapping due to dopants or doping process induced defect states are significantly suppressed. Consequently, a record-breaking response time of 264 ns and a 3 dB bandwidth of 1.9 MHz are realized, compared with the previously reported TMDs based photodetectors. The above-mentioned desirable properties, together with CMOS compatible processes, make this WSe2 p-i-n junction diode promising for future applications in self-powered high-frequency weak signal photodetection.