Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 109
Filtrar
1.
Small ; : e2404087, 2024 Jul 19.
Artículo en Inglés | MEDLINE | ID: mdl-39031097

RESUMEN

Membrane separation stands as an environmentally friendly, high permeance and selectivity, low energy demand process that deserves scientific investigation and industrialization. To address intensive demand, seeking appropriate membrane materials to surpass trade-off between permeability and selectivity and improve stability is on the schedule. 2D materials offer transformational opportunities and a revolutionary platform for researching membrane separation process. Especially, the atomically thin graphene with controllable porosity and structure, as well as unique properties, is widely considered as a candidate for membrane materials aiming to provide extreme stability, exponentially large selectivity combined with high permeability. Currently, it has shown promising opportunities to develop separation membranes to tackle bottlenecks of traditional membranes, and it has been of great interest for tremendously versatile applications such as separation, energy harvesting, and sensing. In this review, starting from transport mechanisms of separation, the material selection bank is narrowed down to nanoporous graphene. The study presents an enlightening overview of very recent developments in the preparation of atomically thin nanoporous graphene and correlates surface properties of such 2D nanoporous materials to their performance in critical separation applications. Finally, challenges related to modulation and manufacturing as well as potential avenues for performance improvements are also pointed out.

3.
Hortic Res ; 11(2): uhad295, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38404593

RESUMEN

Powdery mildew (PM) is one of the most destructive diseases that threaten cucumber production globally. Efficient breeding of novel PM-resistant cultivars will require a robust understanding of the molecular mechanisms of cucumber resistance against PM. Using a genome-wide association study, we detected a locus significantly correlated with PM resistance in cucumber stem, pm-s5.1. A 1449-bp insertion in the CsMLO8 coding region at the pm-s5.1 locus resulted in enhanced stem PM resistance. Knockout mutants of CsMLO8 and CsMLO11 generated by CRISPR/Cas9 both showed improved PM resistance in the stem, hypocotyl, and leaves, and the double mutant mlo8mlo11 displayed even stronger resistance. We found that reactive oxygen species (ROS) accumulation was higher in the stem of these mutants. Protein interaction assays suggested that CsMLO8 and CsMLO11 could physically interact with CsRbohD and CsCRK2, respectively. Further, we showed that CsMLO8 and CsCRK2 competitively interact with the C-terminus of CsRbohD to affect CsCRK2-CsRbohD module-mediated ROS production during PM defense. These findings provide new insights into the understanding of CsMLO proteins during PM defense responses.

4.
Pestic Biochem Physiol ; 198: 105760, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38225067

RESUMEN

Corynespora leaf spot, caused by Corynespora cassiicola, is a foliar disease in cucumber. While the application of quinone outside inhibitors (QoIs) is an effective measure for disease control, it carries the risk of resistance development. In our monitoring of trifloxystrobin resistance from 2008 to 2020, C. cassiicola isolates were categorized into three populations: sensitive isolates (S, 0.01 < EC50 < 0.83 µg/mL), moderately resistant isolates (MR, 1.18 < EC50 < 55.67 µg/mL), and highly resistant isolates (HR, EC50 > 56.98 µg/mL). The resistance frequency reached up to 90% during this period, with an increasing trend observed in the annual average EC50 values of all the isolates. Analysis of the CcCytb gene revealed that both MR and HR populations carried the G143A mutation. Additionally, we identified mitochondrial heterogeneity, with three isolates carrying both G143 and A143 in MR and HR populations. Interestingly, isolates with the G143A mutation (G143A-MR and G143A-HR) displayed differential sensitivity to QoIs. Further experiments involving gene knockout and complementation demonstrated that the major facilitator superfamily (MFS) transporter (CcMfs1) may contribute to the disparity in sensitivity to QoIs between the G143A-MR and G143A-HR populations. However, the difference in sensitivity caused by the CcMfs1 transporter is significantly lower than the differences observed between the two populations. This suggests additional mechanisms contributing to the variation in resistance levels among C. cassiicola isolates. Our study highlights the alarming level of trifloxystrobin resistance in C. cassiicola in China, emphasizing the need for strict prohibition of QoIs use. Furthermore, our findings shed light on the occurrence of both target and non-target resistance mechanisms associated with QoIs in C. cassiicola.


Asunto(s)
Acetatos , Ascomicetos , Fungicidas Industriales , Iminas , Estrobilurinas/farmacología , Fungicidas Industriales/farmacología , Farmacorresistencia Fúngica/genética , Enfermedades de las Plantas
5.
IEEE Trans Pattern Anal Mach Intell ; 46(7): 4850-4865, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38261483

RESUMEN

Although stereo image restoration has been extensively studied, most existing work focuses on restoring stereo images with limited horizontal parallax due to the binocular symmetry constraint. Stereo images with unlimited parallax (e.g., large ranges and asymmetrical types) are more challenging in real-world applications and have rarely been explored so far. To restore high-quality stereo images with unlimited parallax, this paper proposes an attention-guided correspondence learning method, which learns both self- and cross-views feature correspondence guided by parallax and omnidirectional attention. To learn cross-view feature correspondence, a Selective Parallax Attention Module (SPAM) is proposed to interact with cross-view features under the guidance of parallax attention that adaptively selects receptive fields for different parallax ranges. Furthermore, to handle asymmetrical parallax, we propose a Non-local Omnidirectional Attention Module (NOAM) to learn the non-local correlation of both self- and cross-view contexts, which guides the aggregation of global contextual features. Finally, we propose an Attention-guided Correspondence Learning Restoration Network (ACLRNet) upon SPAMs and NOAMs to restore stereo images by associating the features of two views based on the learned correspondence. Extensive experiments on five benchmark datasets demonstrate the effectiveness and generalization of the proposed method on three stereo image restoration tasks including super-resolution, denoising, and compression artifact reduction.

6.
Adv Mater ; 36(1): e2307242, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37717168

RESUMEN

Biological ion channels possess prominent ion transport performances attributed to their critical chemical groups across the continuous nanoscale filters. However, it is still a challenge to imitate these sophisticated performances in artificial nanoscale systems. Herein, this work develops the strategy to fabricate functionalized graphene nanopores in pioneer based on the synergistic regulation of the pore size and chemical properties of atomically thin confined structure through decoupling etching combined with in situ covalent modification. The modified graphene nanopores possess asymmetric ion transport behaviors and efficient monovalent metal ions sieving (K+ /Li+ selectivity ≈48.6). Meanwhile, it also allows preferential transport for cations, the resulting membranes exhibit a K+ /Cl- selectivity of 76 and a H+ /Cl- selectivity of 59.3. The synergistic effects of steric hindrance and electrostatic interactions imposing a higher energy barrier for Cl- or Li+ across nanopores lead to ultra-selective H+ or K+ transport. Further, the functionalized graphene nanopores generate a power density of 25.3 W m-2 and a conversion efficiency of 33.9%, showing potential application prospects in energy conversion. The theoretical studies quantitatively match well with the experimental results. The feasible preparation of functionalized graphene nanopores paves the way toward direct investigation on ion transport mechanism and advanced design in devices.

7.
J Colloid Interface Sci ; 657: 428-437, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38056047

RESUMEN

The proton exchange membrane (PEM) fuel cell is a device that demonstrates a significant potential for environmental sustainability, since it efficiently converts chemical energy into electrical energy. The microporous layer (MPL) in PEM fuel cells promotes gas transport and eliminates water. Nevertheless, the power density of PEM fuel cells is restricted by ohmic losses and mass transport losses in conventional MPLs. In this study, we enhanced the power density of proton exchange membrane (PEM) fuel cells through the identification of appropriate materials and the mitigation of mass transport losses occurring at the interface between the microporous layer and the catalyst layer. The incorporation of high electron conductivity, slip behavior at the interface between graphene and water, and rapid water evaporation facilitated by nanoporous graphene effectively address transport-related challenges. We evaluated two types of graphene as potential substitutes for carbon black in the microporous layer (MPL). The enhanced power density (up to 1.1 W cm-2) under all humidity conditions and reduced mass transport resistance (a 75 % reduction compared to carbon black MPL) make them promising candidates for next-generation PEM fuel cells. Furthermore, these findings provide guidance for controlling interfacial mass transport in colloidal systems.

8.
Nano Lett ; 24(1): 26-34, 2024 Jan 10.
Artículo en Inglés | MEDLINE | ID: mdl-38117701

RESUMEN

Salinity gradient energy is an environmentally friendly energy source that possesses potential to meet the growing global energy demand. Although covalently modified nanoporous graphene membranes are prospective candidates to break the trade-off between ion selectivity and permeability, the random reaction sites and inevitable defects during modification reduce the reaction efficiency and energy conversion performance. Here, we developed a preanchoring method to achieve directional modification near the graphene nanopores periphery. Numerical simulation revealed that the improved surface charge density around nanopores results in exceptional K+/Cl- selectivity and osmotic energy conversion performance, which agreed well with experimental results. Ionic transport measurements showed that the directionally modified graphene membranes achieved an outstanding power density of 81.6 W m-2 with an energy conversion efficiency of 35.4% under a 100-fold salinity gradient, outperforming state-of-the-art graphene-based nanoporous membranes. This work provided a facile approach for precise modification of nanoporous graphene membranes and opened up new ways for osmotic power harvesting.

9.
Int Rev Neurobiol ; 172: 321-331, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37833017

RESUMEN

Intraoperative seizure is the most prevalent and serious complication of awake craniotomy in functional areas, which may not only trigger complications of the surgical procedure or even the failure of awake craniotomy but also may result in adverse consequences to patients. The influencing factors of intraoperative seizures are unclear, and only the possible influencing factors can be acquired from the examination and summary of existing cases to offer guidance for the seizure prevention of intraoperative epilepsy.


Asunto(s)
Neoplasias Encefálicas , Epilepsia , Glioma , Humanos , Neoplasias Encefálicas/cirugía , Neoplasias Encefálicas/complicaciones , Vigilia , Monitoreo Intraoperatorio/efectos adversos , Monitoreo Intraoperatorio/métodos , Glioma/cirugía , Convulsiones/etiología , Convulsiones/cirugía , Epilepsia/cirugía , Craneotomía/efectos adversos , Craneotomía/métodos , Mapeo Encefálico/efectos adversos
10.
J Integr Plant Biol ; 65(12): 2552-2568, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37811725

RESUMEN

Low-temperature (LT) stress threatens cucumber production globally; however, the molecular mechanisms underlying LT tolerance in cucumber remain largely unknown. Here, using a genome-wide association study (GWAS), we found a naturally occurring single nucleotide polymorphism (SNP) in the STAYGREEN (CsSGR) coding region at the gLTT5.1 locus associated with LT tolerance. Knockout mutants of CsSGR generated by clustered regularly interspaced palindromic repeats (CRISPR)/CRISPR-associated nuclease 9 exhibit enhanced LT tolerance, in particularly, increased chlorophyll (Chl) content and reduced reactive oxygen species (ROS) accumulation in response to LT. Moreover, the C-repeat Binding Factor 1 (CsCBF1) transcription factor can directly activate the expression of CsSGR. We demonstrate that the LT-sensitive haplotype CsSGRHapA , but not the LT-tolerant haplotype CsSGRHapG could interact with NON-YELLOW COLORING 1 (CsNYC1) to mediate Chl degradation. Geographic distribution of the CsSGR haplotypes indicated that the CsSGRHapG was selected in cucumber accessions from high latitudes, potentially contributing to LT tolerance during cucumber cold-adaptation in these regions. CsSGR mutants also showed enhanced tolerance to salinity, water deficit, and Pseudoperonospora cubensis, thus CsSGR is an elite target gene for breeding cucumber varieties with broad-spectrum stress tolerance. Collectively, our findings provide new insights into LT tolerance and will ultimately facilitate cucumber molecular breeding.


Asunto(s)
Cucumis sativus , Cucumis sativus/genética , Temperatura , Estudio de Asociación del Genoma Completo , Fitomejoramiento , Frío
11.
J Phys Chem Lett ; 14(35): 7883-7891, 2023 Sep 07.
Artículo en Inglés | MEDLINE | ID: mdl-37639374

RESUMEN

Proton exchange membrane (PEM) fuel cells are a promising and environmentally friendly device to directly convert hydrogen energy into electric energy. However, water flooding and gas transport losses degrade its power density owing to structural issues (cracks, roughness, etc.) of the microporous layer (MPL). Here, we introduce a green material, supercritical fluid exfoliated graphene (s-Gr), to act as a network to effectively improve gas transport and water management. The assembled PEM fuel cell achieves a power density of 1.12 W cm-2. This improved performance is attributed to the reduction of cracks and the slip of water and gas on the s-Gr surface, in great contrast to the nonslip behavior on carbon black (CB). These findings open up an avenue to solve the water and gas transport problem in porous media by materials design with low friction and provide a new opportunity to boost high power density PEM fuel cells.

12.
IEEE Trans Image Process ; 32: 4701-4715, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37549080

RESUMEN

Existing low-light video enhancement methods are dominated by Convolution Neural Networks (CNNs) that are trained in a supervised manner. Due to the difficulty of collecting paired dynamic low/normal-light videos in real-world scenes, they are usually trained on synthetic, static, and uniform motion videos, which undermines their generalization to real-world scenes. Additionally, these methods typically suffer from temporal inconsistency (e.g., flickering artifacts and motion blurs) when handling large-scale motions since the local perception property of CNNs limits them to model long-range dependencies in both spatial and temporal domains. To address these problems, we propose the first unsupervised method for low-light video enhancement to our best knowledge, named LightenFormer, which models long-range intra- and inter-frame dependencies with a spatial-temporal co-attention transformer to enhance brightness while maintaining temporal consistency. Specifically, an effective but lightweight S-curve Estimation Network (SCENet) is first proposed to estimate pixel-wise S-shaped non-linear curves (S-curves) to adaptively adjust the dynamic range of an input video. Next, to model the temporal consistency of the video, we present a Spatial-Temporal Refinement Network (STRNet) to refine the enhanced video. The core module of STRNet is a novel Spatial-Temporal Co-attention Transformer (STCAT), which exploits multi-scale self- and cross-attention interactions to capture long-range correlations in both spatial and temporal domains among frames for implicit motion estimation. To achieve unsupervised training, we further propose two non-reference loss functions based on the invertibility of the S-curve and the noise independence among frames. Extensive experiments on the SDSD and LLIV-Phone datasets demonstrate that our LightenFormer outperforms state-of-the-art methods.

13.
Chem Sci ; 14(29): 7782-7817, 2023 Jul 26.
Artículo en Inglés | MEDLINE | ID: mdl-37502317

RESUMEN

Peptide and protein selective modification at tyrosine residues has become an exploding field of research as tyrosine constitutes a robust alternative to lysine and cysteine-targeted traditional peptide/protein modification protocols. This review offers a comprehensive summary of the latest advances in tyrosine-selective cleavage, functionalization, and conjugation of peptides and proteins from the past three years. This updated overview complements the extensive body of work on site-selective modification of peptides and proteins, which holds significant relevance across various disciplines, including chemical, biological, medical, and material sciences.

14.
Artículo en Inglés | MEDLINE | ID: mdl-37339043

RESUMEN

The knee has gradually become an important research target for the lower extremity exoskeleton. However, the issue that whether the flexion-assisted profile based on the contractile element (CE) is effective throughout the gait is still a research gap. In this study, we first analyze the effective flexion-assisted method through the passive element's (PE) energy storage and release mechanism. Specifically, ensuring assisting within an entire joint power period and the human's active movement is a prerequisite for the CE-based flexion-assisted method. Second, we design the enhanced adaptive oscillator (EAO) to ensure the human's active movement and the integrity of the assistance profile. Third, a fundamental frequency estimation based on discrete Fourier transform (DFT) is proposed to shorten the convergence time of EAO significantly. The finite state machine (FSM) is designed to improve the stability and practicality of EAO. Finally, we demonstrate the effectiveness of the prerequisite condition for the CE-based flexion-assisted method by using electromyography (EMG) and metabolic indicators in experiments. In particular, for the knee joint, CE-based flexion assistance should be within an entire joint power period rather than just in the negative power phase. Ensuring the human's active movement will also significantly reduce the activation of antagonistic muscles. This study will aid in designing assistive methods from the perspective of natural human actuation and apply the EAO to the human-exoskeleton system.


Asunto(s)
Dispositivo Exoesqueleto , Humanos , Extremidad Inferior , Marcha/fisiología , Electromiografía/métodos , Articulación de la Rodilla/fisiología , Fenómenos Biomecánicos/fisiología
15.
Front Plant Sci ; 14: 1116214, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37235012

RESUMEN

Low temperatures (LTs) negatively affect the percentage and rate of cucumber (Cucumis sativus L.) seed germination, which has deleterious effects on yield. Here, a genome-wide association study (GWAS) was used to identify the genetic loci underlying low temperature germination (LTG) in 151 cucumber accessions that represented seven diverse ecotypes. Over two years, phenotypic data for LTG i.e., relative germination rate (RGR), relative germination energy (RGE), relative germination index (RGI) and relative radical length (RRL), were collected in two environments, and 17 of the 151 accessions were found to be highly cold tolerant using cluster analysis. A total of 1,522,847 significantly associated single-nucleotide polymorphism (SNP) were identified, and seven loci associated with LTG, on four chromosomes, were detected: gLTG1.1, gLTG1.2, gLTG1.3, gLTG4.1, gLTG5.1, gLTG5.2, and gLTG6.1 after resequencing of the accessions. Of the seven loci, three, i.e., gLTG1.2, gLTG4.1, and gLTG5.2, showed strong signals that were consistent over two years using the four germination indices, and are thus strong and stable for LTG. Eight candidate genes associated with abiotic stress were identified, and three of them were potentially causal to LTG: CsaV3_1G044080 (a pentatricopeptide repeat-containing protein) for gLTG1.2, CsaV3_4G013480 (a RING-type E3 ubiquitin transferase) for gLTG4.1, and CsaV3_5G029350 (a serine/threonine-protein kinase) for gLTG5.2. The function for CsPPR (CsaV3_1G044080) in regulating LTG was confirmed, as Arabidopsis lines ectopically expressing CsPPR showed higher germination and survival rates at 4°C compared to the wild-type, which preliminarily illustrates that CsPPR positively regulates cucumber cold tolerance at the germination stage. This study will provide insights into cucumber LT-tolerance mechanisms and further promote cucumber breeding development.

16.
Aging (Albany NY) ; 15(6): 2208-2220, 2023 03 25.
Artículo en Inglés | MEDLINE | ID: mdl-37000153

RESUMEN

Glioblastoma (GBM) is the most prevalent and malignant brain tumor and is highly resistant to currently available treatment. In this study, we reveal that polypeptide N-acetylgalactosaminyltransferase 5 (GALNT2) expression level was elevated in GBM, IDH1 wildtype glioma, and GBM stem cells (GSCs). GALNT2 increased expression correlated with GBM patients' unfavorable clinical outcomes. Functionally, targeting GALNT2 blocks GSCs cell proliferation, self-renewal, and malignant invasion through repressing CD44 expression. Most importantly, we first provide evidence suggesting that STAT3 activates GALNT2 expression at the transcriptional level by directly binding to the GALNT2 promoter. Through a rational screening, we found a GALNT2 inhibitor that dramatically suppresses GSCs self-maintenance in vitro and in vivo. Collectively, we uncovered the critical function of GALNT2 in promoting GSCs self-maintenance and GBM progression and may provide a new potential drug for GBM clinical therapy.


Asunto(s)
Neoplasias Encefálicas , Glioblastoma , Glioma , Humanos , Neoplasias Encefálicas/patología , Línea Celular Tumoral , Proliferación Celular , Glioblastoma/metabolismo , Glioma/patología , Receptores de Hialuranos/genética , Receptores de Hialuranos/metabolismo , Células Madre Neoplásicas/metabolismo , Polipéptido N-Acetilgalactosaminiltransferasa
17.
ACS Nano ; 17(1): 421-436, 2023 01 10.
Artículo en Inglés | MEDLINE | ID: mdl-36573683

RESUMEN

Glioblastoma (GBM) is the most devastating brain tumor and highly resistant to conventional chemotherapy. Herein, we introduce biomimetic nanosonosensitizer systems (MDNPs) combined with noninvasive ultrasound (US) actuation for orthotopic GBM-targeted delivery and sonodynamic-enhanced chemotherapy. MDNPs were fabricated with biodegradable and pH-sensitive polyglutamic acid (PGA) and the chemotherapeutic agent and sonosensitizer doxorubicin (DOX), camouflaged with human GBM U87 cell membranes. MDNPs presented homologous targeting accumulation and in vivo long-term circulation ability. They effectively passed through the blood-brain barrier (BBB) under US assistance and reached the orthotopic GBM site. MDNPs exhibited controllable US-elicited sonodynamic effect by generation of reactive oxygen species (ROS). ROS not only induced cancer cell apoptosis but also downregulated drug-resistance-related factors to disrupt chemoresistance and increase sensitivity to chemotherapy. The in vivo study of orthotopic GBM treatments further proved that MDNPs exhibited US-augmented synergistic antitumor efficacy and strongly prolonged the survival rate of mice. The use of low-dose DOX and the safety of US enabled repeated treatment (4 times) without obvious cardiotoxicity. This effective and safe US-enhanced chemotherapy strategy with the advantages of noninvasive brain delivery and high drug sensitivity holds great promise for deep-seated and drug-resistant tumors.


Asunto(s)
Glioblastoma , Nanopartículas , Humanos , Ratones , Animales , Glioblastoma/tratamiento farmacológico , Glioblastoma/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Biomimética , Ultrasonografía , Doxorrubicina/farmacología , Doxorrubicina/uso terapéutico , Resistencia a Medicamentos , Línea Celular Tumoral
18.
IEEE Trans Pattern Anal Mach Intell ; 45(4): 5158-5173, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-35917573

RESUMEN

Variation of scales or aspect ratios has been one of the main challenges for tracking. To overcome this challenge, most existing methods adopt either multi-scale search or anchor-based schemes, which use a predefined search space in a handcrafted way and therefore limit their performance in complicated scenes. To address this problem, recent anchor-free based trackers have been proposed without using prior scale or anchor information. However, an inconsistency problem between classification and regression degrades the tracking performance. To address the above issues, we propose a simple yet effective tracker (named Siamese Box Adaptive Network, SiamBAN) to learn a target-aware scale handling schema in a data-driven manner. Our basic idea is to predict the target boxes in a per-pixel fashion through a fully convolutional network, which is anchor-free. Specifically, SiamBAN divides the tracking problem into classification and regression tasks, which directly predict objectiveness and regress bounding boxes, respectively. A no-prior box design is proposed to avoid tuning hyper-parameters related to candidate boxes, which makes SiamBAN more flexible. SiamBAN further uses a target-aware branch to address the inconsistency problem. Experiments on benchmarks including VOT2018, VOT2019, OTB100, UAV123, LaSOT and TrackingNet show that SiamBAN achieves promising performance and runs at 35 FPS.

19.
Nat Commun ; 13(1): 6548, 2022 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-36319643

RESUMEN

Aberrant expression of the Forkhead box transcription factor, FOXQ1, is a prevalent mechanism of epithelial-mesenchymal transition (EMT) and metastasis in multiple carcinoma types. However, it remains unknown how FOXQ1 regulates gene expression. Here, we report that FOXQ1 initiates EMT by recruiting the MLL/KMT2 histone methyltransferase complex as a transcriptional coactivator. We first establish that FOXQ1 promoter recognition precedes MLL complex assembly and histone-3 lysine-4 trimethylation within the promoter regions of critical genes in the EMT program. Mechanistically, we identify that the Forkhead box in FOXQ1 functions as a transactivation domain directly binding the MLL core complex subunit RbBP5 without interrupting FOXQ1 DNA binding activity. Moreover, genetic disruption of the FOXQ1-RbBP5 interaction or pharmacologic targeting of KMT2/MLL recruitment inhibits FOXQ1-dependent gene expression, EMT, and in vivo tumor progression. Our study suggests that targeting the FOXQ1-MLL epigenetic axis could be a promising strategy to combat triple-negative breast cancer metastatic progression.


Asunto(s)
Neoplasias de la Mama , Neoplasias Primarias Secundarias , Femenino , Humanos , Neoplasias de la Mama/genética , Línea Celular Tumoral , Transición Epitelial-Mesenquimal/fisiología , Factores de Transcripción Forkhead/metabolismo , Regulación Neoplásica de la Expresión Génica , Neoplasias Primarias Secundarias/genética , Proteína de la Leucemia Mieloide-Linfoide/metabolismo , Melanoma Cutáneo Maligno
20.
Nat Commun ; 13(1): 6350, 2022 10 26.
Artículo en Inglés | MEDLINE | ID: mdl-36289222

RESUMEN

The methyltransferase like 3 (METTL3) has been generally recognized as a nuclear protein bearing oncogenic properties. We find predominantly cytoplasmic METTL3 expression inversely correlates with node metastasis in human cancers. It remains unclear if nuclear METTL3 is functionally distinct from cytosolic METTL3 in driving tumorigenesis and, if any, how tumor cells sense oncogenic insults to coordinate METTL3 functions within these intracellular compartments. Here, we report an acetylation-dependent regulation of METTL3 localization that impacts on metastatic dissemination. We identify an IL-6-dependent positive feedback axis to facilitate nuclear METTL3 functions, eliciting breast cancer metastasis. IL-6, whose mRNA transcript is subjected to METTL3-mediated m6A modification, promotes METTL3 deacetylation and nuclear translocation, thereby inducing global m6A abundance. This deacetylation-mediated nuclear shift of METTL3 can be counterbalanced by SIRT1 inhibition, a process that is further enforced by aspirin treatment, leading to ablated lung metastasis via impaired m6A methylation. Intriguingly, acetylation-mimetic METTL3 mutant reconstitution results in enhanced translation and compromised metastatic potential. Our study identifies an acetylation-dependent regulatory mechanism determining the subcellular localization of METTL3, which may provide mechanistic clues for developing therapeutic strategies to combat breast cancer metastasis.


Asunto(s)
Neoplasias de la Mama , Metiltransferasas , Humanos , Femenino , Metiltransferasas/metabolismo , Acetilación , Sirtuina 1/metabolismo , Interleucina-6/metabolismo , ARN Mensajero/metabolismo , Carcinogénesis , Neoplasias de la Mama/genética , Proteínas Nucleares/metabolismo , Aspirina
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA