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1.
Rev Sci Instrum ; 95(9)2024 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-39283182

RESUMEN

We have developed a cryogen-free, low-temperature terahertz scanning tunneling microscope (THz-STM). This system utilizes a continuous-flow cryogen-free cooler to achieve low temperatures of ∼25 K. Meanwhile, an ultra-small ultra-high vacuum chamber results in the reduction of the distance from sample to viewport to only 4 cm. NA = 0.6 can be achieved while placing the entire optical component, including a large parabolic mirror, outside the vacuum chamber. Thus, the convenience of optical coupling is much improved without compromising the performance of STM. Based on this, we introduced THz pulses into the tunnel junction and constructed the THz-STM, achieving atomic-level spatial resolution in THz-driven current imaging and sub-picosecond (sub-ps) time resolution in autocorrelation signals during pump-probe measurements. Experimental data from various representative samples are presented to showcase the performance of the instrument, establishing it as an ideal platform for studying non-equilibrium dynamic processes at nanoscale.

2.
Nano Lett ; 24(35): 11075-11081, 2024 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-39177195

RESUMEN

The ruby lattice is one of the tight-binding models which hosts a flat band in its electronic structure and has potential applications in future spintronics and quantum devices. However, the experimental realization of a ruby lattice in realistic materials remains elusive. Here, we have experimentally realized an atomic ruby lattice by fabricating monolayer CuCl1+x on a Au(111) substrate. Scanning tunneling microscopy/spectra (STM/STS) measurements combined with density-functional theory (DFT) calculations reveal that the Cu atoms are arranged in a ruby lattice in this monolayer. Moreover, a significant density of states (DOS) peak corresponding to the characteristic of a ruby system is observed, consistent with both the tight-binding model and first-principles calculations on the band structure. Our work provides a promising platform to explore the physics of the ruby model.

3.
Small Methods ; : e2400463, 2024 May 17.
Artículo en Inglés | MEDLINE | ID: mdl-38757540

RESUMEN

Metal zinc (Zn) is being explored as a possible anode for aqueous zinc ion batteries (AZIBs). However, unrestrained Zn dendrite caused by "tip effect" and chemical corrosion continue to plague the Zn deposition process, limiting the functionality of AZIBs and prohibiting their use at high current densities. This work presents an in situ approach for introducing homogeneous ZnO nanoarrays onto the surface of Zn foil (Zn@ZnO NAs) as a functional protective interphase. On the one hand, well-distributed ZnO NAs protection layer can regulate the "tip effect" and confine the growth of Zn dendrite. On the other hand, the ZnO NAs layer can enhance the desolvation and diffusion process of Zn2+ on the surface of anode, attributing to low voltage hysteresis and exceptional electrochemical performance at high current densities. As a result, the Zn@ZnO NAs exhibits a low voltage hysteresis of 50.8 mV with a superb lifespan of 1200 h at a current density of 5 mA cm-2. Moreover, Zn@ZnO NAs||α-MnO2 full-cell shows a superior cycling performance after 500 cycles at 0.5 A g-1 with a capacity of 216.69 mAh g-1. This work is expected to provide ideas for designing other reversible zinc anode chemical systems, especially under a high current density.

4.
ACS Appl Mater Interfaces ; 16(19): 24494-24501, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38703109

RESUMEN

For many years, humans have been relentlessly focused on enhancing battery longevity and boosting energy storage capacities. The performance and durability of a battery depend significantly on the material used for its electrodes. In this context, merging machine learning with density functional theory (DFT) calculations has emerged as a pivotal approach to advancing the exploration of battery crystal structures. We present a new method that combines a graph convolutional neural network (GNN) with a Transformer convolutional layer, which we call Transformer-GNN. To underscore its efficacy, we benchmarked Transformer-GNN against three established statistical machine learning models: Support Vector Machine, Random Forest, and XGBoost. We also developed a standard GNN, which we refer to as Basic-GNN. Additionally, we compared Basic-GNN with Transformer-GNN to highlight the improvements brought about by incorporating the Transformer convolutional layer. The Transformer-GNN model outperforms the other models, achieving the highest R2 value of 0.82 and the lowest mean squared error of 0.3161. Our findings demonstrate that the Transformer-GNN can profoundly understand battery crystal structures, thus forging the path toward more sophisticated and durable battery systems. Leveraging the GNN model's voltage predictions in tandem with the capacity data sourced from the database, we screened and pinpointed Na(NiO2)2 as a high-voltage (higher than 5 V), high-capacity sodium cathode material. We conducted DFT calculations on Na(NiO2)2 and revealed the migration mechanism of the Na ions.

5.
New Phytol ; 241(4): 1794-1812, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38135652

RESUMEN

The SWI/SNF complex is guided to the promoters of designated genes by its co-operator to activate transcription in a timely and appropriate manner to govern development, pathogenesis, and stress responses in fungi. Nevertheless, knowledge of the complexes and their co-operator in phytopathogenic fungi is still fragmented. We demonstrate that the heat shock transcription factor SsHsf1 guides the SWI/SNF complex to promoters of heat shock protein (hsp) genes and antioxidant enzyme genes using biochemistry and pharmacology. This is accomplished through direct interaction with the complex subunit SsSnf5 under heat shock and oxidative stress. This results in the activation of their transcription and mediates histone displacement to maintain reactive oxygen species (ROS) homeostasis. Genetic results demonstrate that the transcription module formed by SsSnf5 and SsHsf1 is responsible for regulating morphogenesis, stress tolerance, and pathogenicity in Sclerotinia sclerotiorum, especially by directly activating the transcription of hsp genes and antioxidant enzyme genes counteracting plant-derived ROS. Furthermore, we show that stress-induced phosphorylation of SsSnf5 is necessary for the formation of the transcription module. This study establishes that the SWI/SNF complex and its co-operator cooperatively regulate the transcription of hsp genes and antioxidant enzyme genes to respond to host and environmental stress in the devastating phytopathogenic fungi.


Asunto(s)
Ascomicetos , Proteínas de Unión al ADN , Factores de Transcripción , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Proteínas de Unión al ADN/metabolismo , Especies Reactivas de Oxígeno , Antioxidantes , Virulencia , Proteínas de Choque Térmico/metabolismo , Homeostasis
6.
ACS Nano ; 17(21): 21317-21327, 2023 Nov 14.
Artículo en Inglés | MEDLINE | ID: mdl-37862706

RESUMEN

The emerging two-dimensional (2D) van der Waals (vdW) materials and their heterostructures hold great promise for optoelectronics and photonic applications beyond strictly lattice-matching constraints and grade interfaces. However, previous photodetectors and optoelectronic devices rely on relatively simple vdW heterostructures with one or two blocks. The realization of high-order heterostructures has been exponentially challenging due to conventional layer-by-layer arduous restacking or sequential synthesis. In this study, we present an approach involving the direct exfoliation of high-quality BiI3-BiI heterostructure nanosheets with alternating blocks, derived from solution-grown binary heterocrystals. These heterostructure-based photodetectors offer several notable advantages. Leveraging the "active layer energetics" of BiI layers and the establishment of a significant depletion region, our photodetector demonstrates a significant reduction in dark current compared with pure BiI3 devices. Specifically, the photodetector achieves an extraordinarily low dark current (<9.2 × 10-14 A at 5 V bias voltage), an impressive detectivity of 8.8 × 1012 Jones at 638 nm, and a rapid response time of 3.82 µs. These characteristics surpass the performance of other metal-semiconductor-metal (MSM) photodetectors based on various 2D materials and structures at visible wavelengths. Moreover, our heterostructure exhibits a broad-band photoresponse, covering the visible, near-infrared (NIR)-I, and NIR-II regions. In addition to these promising results, our heterostructure also demonstrated the potential for flexible and imaging applications. Overall, our study highlights the potential of alternating vdW heterostructures for future optoelectronics with low power consumption, fast response, and flexible requirements.

7.
Nano Lett ; 23(17): 7838-7844, 2023 Sep 13.
Artículo en Inglés | MEDLINE | ID: mdl-37590032

RESUMEN

Retaining ferroelectricity in ultrathin films or nanostructures is crucial for miniaturizing ferroelectric devices, but it is a challenging task due to intrinsic depolarization and size effects. In this study, we have shown that it is possible to stably maintain in-plane polarization in an extremely thin, one-unit-cell thick epitaxial Bi2WO6 film. The use of a perfectly lattice-matched NdGaO3 (110) substrate for the Bi2WO6 film minimizes strain and enhances stability. We attribute the residual polarization in this ultrathin film to the crystal stability of the Bi-O octahedral framework against structural distortions. Our findings suggest that ferroelectricity can surpass the critical thickness limit through proper strain engineering, and the Bi2WO6/NdGaO3 (110) system presents a potential platform for designing low-energy consumption, nonvolatile ferroelectric memories.

8.
Small ; 19(35): e2301986, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37096917

RESUMEN

Glycerol-assisted hybrid water electrolysis is a potential strategy to achieve energy-efficient hydrogen production. However, the design of an efficient catalyst for the specific reaction is still a key challenge, which suffers from the barrier of regulating the adsorption characteristics of distinctive intermediates in different reactions. Herein, a novel rationale that achieves selective adsorption behavior modulation for self-supported nickel selenide electrode by heteroatom implantation and heterointerface construction through electrodeposition is developed, which can realize nichetargeting optimization on hydrogen evolution reaction (HER) and glycerol oxidation reaction (GOR), respectively. Specifically, the prepared Mo-doped Ni3 Se2 electrode exhibits superior catalytic activity for HER, while the NiSe-Ni3 Se2 electrode exhibits high Faradaic efficiency (FE) towards formate production for GOR. A two-electrode electrolyzer exhibits superb activity that only needs an ultralow cell voltage of 1.40 V to achieve 40 mA cm-2 with a high FE (97%) for formate production. Theoretical calculation unravels that the introduction of molybdenum contributes to the deviation of the d-band center of Ni3 Se2 from the Fermi level, which is conducive to hydrogen desorption. Meanwhile, the construction of the heterojunction induces the distortion of the surface structure of nickel selenide, which exposes highly active nickel sites for glycerol adsorption, thus contributing to the excellent electrocatalytic performance.

9.
World J Hepatol ; 15(3): 386-392, 2023 Mar 27.
Artículo en Inglés | MEDLINE | ID: mdl-37034232

RESUMEN

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide. NAFLD comprises a continuum of liver abnormalities from nonalcoholic fatty liver to nonalcoholic steatohepatitis, and can even lead to cirrhosis and liver cancer. However, a well-established treatment for NAFLD has yet to be identified. Exosomes have become an ideal drug delivery tool because of their high transmissibility, low immunogenicity, easy accessibility and targeting. Exosomes with specific modifications, known as engineered exosomes, have the potential to treat a variety of diseases. Here, we review the treatment of NAFLD with engineered exosomes and the potential use of exosomes as biomarkers and therapeutic targets for NAFLD.

10.
Adv Mater ; 35(25): e2300935, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-36964932

RESUMEN

As promising hydrogen energy carrier, formic acid (HCOOH) plays an indispensable role in building a complete industry chain of a hydrogen economy. Currently, the biomass upgrading assisted water electrolysis has emerged as an attractive alternative for co-producing green HCOOH and H2 in a cost-effective manner, yet simultaneously affording high current density and Faradaic efficiency (FE) still remains a big challenge. Here, the ternary NiVRu-layered double hydroxides (LDHs) nanosheet arrays for selective glycerol oxidation and hydrogen evolution catalysis are reported, which yield an industry-level 1 A cm-2 at voltage of 1.933 V, meanwhile showing considerable HCOOH and H2 productivities of 12.5 and 17.9 mmol cm-2  h-1 , with FEs of almost 80% and 96%, respectively. Experimental and theoretical results reveal that the introduced Ru atoms can tune the local electronic structure of Ni-based LDHs, which not only optimizes hydrogen adsorption kinetics for HER, but also reduces the reaction energy barriers for both the conversion of NiII into GOR-active NiIII and carboncarbon (CC) bond cleavage. In short, this work highlights the potential of large-scale H2 and HCOOH productions from integrated electrocatalytic system and provides new insights for designing advanced electrocatalyst for low-cost and sustainable energy conversion.

11.
Int J Biol Sci ; 19(2): 377-392, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36632463

RESUMEN

HER2 is a transmembrane receptor with intrinsic tyrosine kinase activity that is overexpressed in almost 25% of human breast cancers. Here, we report that the neddylation of HER2 is a new post-translational modification that controls its expression and oncogenic activity in human breast cancer. Two critical members in the neddylation pathway, NEDD8 and NEDD8-activating enzyme E1 subunit 1 (NAE1), are detected in human breast specimens. Overexpressed NEDD8 and NAE1 are positively correlated with HER2 expression in human breast cancer. Subsequent structure and function experiments show that HER2 directly interacts with NEDD8 and NAE1, whereas HER2 protein expression is decreased by neddylation depletion. Mechanistically, neddylation inhibition promotes the degradation of HER2 protein by improving its ubiquitination. HER2 overexpression abrogates neddylation depletion-triggered cell growth suppression. The inhibition of neddylation synergized with trastuzumab significantly suppresses growth of HER2 positive breast cancer. Collectively, this study demonstrates a previously undiscovered role of NEDD8-dependent HER2 neddylation promotes tumor growth in breast cancer.


Asunto(s)
Neoplasias de la Mama , Proteína NEDD8 , Proteolisis , Receptor ErbB-2 , Ubiquitinación , Femenino , Humanos , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Procesamiento Proteico-Postraduccional , Receptor ErbB-2/metabolismo , Proteína NEDD8/metabolismo , Progresión de la Enfermedad
12.
Small ; 19(17): e2207425, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36703521

RESUMEN

Urea-assisted hybrid water splitting is a promising technology for hydrogen (H2 ) production, but the lack of cost-effective electrocatalysts hinders its extensive application. Herein, it is reported that Nitrogen-doped Co9 S8 /Ni3 S2 hybrid nanosheet arrays on nickel foam (N-Co9 S8 /Ni3 S2 /NF) can act as an active and robust bifunctional catalyst for both urea oxidation reaction (UOR) and hydrogen evolution reaction (HER), which could drive an ultrahigh current density of 400 mA cm-2 at a low working potential of 1.47 V versus RHE for UOR, and gives a low overpotential of 111 mV to reach 10 mA cm-2 toward HER. Further, a hybrid water electrolysis cell utilizing the synthesized N-Co9 S8 /Ni3 S2 /NF electrode as both the cathode and anode displays a low cell voltage of 1.40 V to reach 10 mA cm-2 , which can be powered by an AA battery with a nominal voltage of 1.5 V. The density functional theory (DFT) calculations decipher that N-doped heterointerfaces can synergistically optimize Gibbs free energy of hydrogen and urea, thus accelerating the catalytic kinetics of HER and UOR. This work significantly advances the development of the promising cobalt-nickel-based sulfide as a bifunctional electrocatalyst for energy-saving electrolytic H2 production and urea-rich innocent wastewater treatment.

13.
Small ; 18(30): e2203288, 2022 07.
Artículo en Inglés | MEDLINE | ID: mdl-35780484

RESUMEN

Carbon materials, as promising anode candidates for K+ storage due to their low cost, abundant sources, and high physicochemical stability, however, encounter limited specific capacity and unfavorable cycling stability that seriously hinder their practical applications. Herein, a feasible strategy to tailor and stabilize the nitrogen species in unique P/N co-doped disk-like carbon through the Sn incorporation (P/NSn -CD) is presented, which can largely enhance the specific capacity and cycling capability for K+ storage. Specifically, it delivers a high specific capacity of 439.3 mAh g-1 at 0.1 A g-1 and ultra-stable cycling capability with a capacity retention of 93.5% at 5000 mA g-1 over 5000 cycles for K+ storage. The underlying mechanism for the superior K+ storage performance is investigated by systematical experimental data combined with theoretical simulation results, which can be derived from the increased edge-nitrogen species, improved content and stability of P/N heteroatoms, and enhanced ionic/electronic kinetics. After coupling P/NSn -CD anode with activated carbon cathode, the KIHCs can deliver a high energy density of 171.7 Wh kg-1 at 106.8 W kg-1 , a superior power density (14027.0 W kg-1 with 31.2 Wh kg-1 retained), and ultra-stable lifespan (89.7% retention after 30 K cycles with cycled at 2 A g-1 ).


Asunto(s)
Nitrógeno , Potasio , Electrodos , Iones , Cinética
14.
ACS Nano ; 16(8): 12922-12929, 2022 Aug 23.
Artículo en Inglés | MEDLINE | ID: mdl-35904281

RESUMEN

Type-II Dirac semimetal platinum ditelluride (PtTe2) is a promising functional material for photodetectors because of its specially tilted Dirac cones, strong light absorption, and high carrier mobilities. The stack of two-dimensional (2D) Dirac heterostructures consisting of PtTe2 and graphene could overcome the limit of detection range and response time occurring in the heterostructures of graphene and other low-mobility and large-gap transition metal dichalcogenides (TMDs). Here, we report an approach for achieving highly controllable, wafer-scale production of 2D Dirac heterostructures of PtTe2/graphene with tunable thickness, variable size, and CMOS compatibility. More importantly, the optimized recipes achieve the exact stoichiometric ratio of 1:2 for Pt and Te elements without contaminating the underlayer graphene film. Because of the built-in electric field at the junction area, the photodetectors based on the PtTe2/graphene heterostructure are self-driven with a broadband photodetection from 405 to 1850 nm. In particular, the photodetectors have a high responsivity of up to ∼0.52 AW-1 (without bias) and a fast response time of ∼8.4 µs. Our work demonstrated an approach to synthesizing hybrid 2D Dirac heterostructures, which can be applied in the integration of on-chip, CMOS-compatible photodetectors with near-infrared detection, high sensitivity, and low energy consumption.

15.
Small ; 18(20): e2200242, 2022 05.
Artículo en Inglés | MEDLINE | ID: mdl-35434924

RESUMEN

Hydrazine-assisted hybrid water electrolysis is an energy-saving approach to produce high-purity hydrogen, whereas the development of pH-universal bifunctional catalysts encounters a grand challenge. Herein, a phase-selective synthesis of ruthenium phosphide compounds hybrid with carbon forming pancake-like particles (denoted as Rux P/C-PAN, x = 1 or 2) is presented. The obtained RuP/C-PAN exhibits the highest catalytic activity among the control samples, delivering ultralow cell voltages of 0.03, 0.27, and 0.65 V to drive 10 mA cm-2 using hybrid water electrolysis corresponding to pH values of 14, 7, and 0, respectively. Theoretical calculation deciphers that the RuP phase displays optimized free energy for hydrogen adsorption and reduced energy barrier for hydrazine dehydrogenation. This work may not only open up a new avenue in exploring universally compatible catalyst to transcend the limitation on the pH value of electrolytes, but also push forward the development of an energy-saving hydrogen generation technique based on emerging hybrid water electrolysis.


Asunto(s)
Rutenio , Agua , Electrólisis , Hidrazinas , Hidrógeno , Concentración de Iones de Hidrógeno
16.
Nanotechnology ; 33(17)2022 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-35008075

RESUMEN

WTe2nanostructures have intrigued much attention due to their unique properties, such as large non-saturating magnetoresistance, quantum spin Hall effect and topological surface state. However, the controllable growth of large-area atomically thin WTe2nanostructures remains a significant challenge. In the present work, we demonstrate the controllable synthesis of 1T' atomically thin WTe2nanoflakes (NFs) by water-assisted ambient pressure chemical vapor deposition method based on precursor design and substrate engineering strategies. The introduction of water during the growth process can generate a new synthesized route by reacting with WO3to form intermediate volatile metal oxyhydroxide. Using WO3foil as the growth precursor can drastically enhance the uniformity of as-prepared large-area 1T' WTe2NFs compared to WO3powders. Moreover, highly oriented WTe2NFs with distinct orientations can be obtained by using a-plane and c-plane sapphire substrates, respectively. Corresponding precursor design and substrate engineering strategies are expected to be applicable to other low dimensional transition metal dichalcogenides, which are crucial for the design of novel electronic and optoelectronic devices.

17.
ACS Nano ; 16(1): 783-791, 2022 Jan 25.
Artículo en Inglés | MEDLINE | ID: mdl-34931805

RESUMEN

Thinning crystalline materials to two dimensions (2D) creates a rich playground for electronic phases, including charge, spin, superconducting, and topological order. Bulk materials hosting charge density waves (CDWs), when reduced to ultrathin films, have shown CDW enhancement and tunability. However, charge order confined to only 2D remains elusive. Here we report a distinct charge ordered state emerging in the monolayer limit of 1T-VSe2. Systematic scanning tunneling microscopy experiments reveal that bilayer VSe2 largely retains the bulk electronic structure, hosting a tridirectional CDW. However, monolayer VSe2 ─consistently across distinct substrates─exhibits a dimensional crossover, hosting two CDWs with distinct wavelengths and transition temperatures. Electronic structure calculations reveal that while one CDW is bulk-like and arises from the well-known Peierls mechanism, the other is decidedly unconventional. The observed CDW-lattice decoupling and the emergence of a flat band suggest that the second CDW could arise from enhanced electron-electron interactions in the 2D limit. These findings establish monolayer-VSe2 as a host of coexisting charge orders with distinct origins, and enable the tailoring of electronic phenomena via emergent interactions in 2D materials.

18.
ACS Nano ; 15(12): 20403-20413, 2021 Dec 28.
Artículo en Inglés | MEDLINE | ID: mdl-34780146

RESUMEN

The noble transition metal dichalcogenide palladium diselenide (PdSe2) is an ideal candidate material for broad-spectrum photodetection owing to the large bandgap tunability, high mobility, low thermal conductivity, and large Seebeck coefficient. In this study, self-powered ultrabroadband PdSe2 photodetectors from the visible-infrared to terahertz (THz) region driven by a mutiphysical mechanism are reported. In the visible-infrared region, the photogenerated electron-hole pairs in the PdSe2 body are quickly separated by the built-in electric field at the metal-semiconductor interface and achieve a photoresponsivity of 28 A·W-1 at 405 nm and 0.4 A·W-1 at 1850 nm. In the THz region, PdSe2 photodetectors display a room-temperature responsivity of 20 mA·W-1 at 0.10 THz and 5 mA·W-1 at 0.24 THz based on efficient production of hot carriers in an antenna-assisted structure. Owing to the fast response speed of ∼7.5 µs and low noise equivalent power of ∼900 pW·Hz-1/2, high-resolution transmission THz imaging is demonstrated under an ambient environment at room temperature. Our research validates the great potential of PdSe2 for broadband photodetection and provides a possibility for future optoelectronic applications.

19.
ACS Appl Mater Interfaces ; 13(48): 57822-57830, 2021 Dec 08.
Artículo en Inglés | MEDLINE | ID: mdl-34797636

RESUMEN

Interlayer charge transfer (CT) between PtSe2 and WS2 is studied experimentally. Layer-selective pump-probe and photoluminescence quenching measurements reveal ultrafast interlayer CT in the heterostructure formed by bilayer PtSe2 and monolayer WS2, confirming its type-II band alignment. The CT facilitates the formation of the interlayer excitons with a lifetime of several hundred ps to 1 ns, a diffusion coefficient of 0.9 cm2 s-1, and a diffusion length reaching 200 nm. These results demonstrate the integration of PtSe2 with other materials in van der Waals heterostructures with novel charge-transfer properties and help develop fundamental understanding on the performance of various optoelectronic devices based on heterostructures involving PtSe2.

20.
Cell Death Dis ; 12(10): 857, 2021 09 21.
Artículo en Inglés | MEDLINE | ID: mdl-34548474

RESUMEN

Androgen receptor splice variant 7 (AR-V7), a form of ligand-independent and constitutively activating variant of androgen receptor (AR), is considered as the key driver to initiate castration-resistant prostate cancer (CRPC). Because AR-V7 lacks ligand-binding domain, the AR-targeted therapies that aim to inactivate AR signaling through disrupting the interaction between AR and androgen are limited in CRPC. Thus, the emergence of AR-V7 has become the greatest challenge for treating CRPC. Targeting protein degradation is a recently proposed novel avenue for cancer treatment. Our previous studies have been shown that the oncoprotein AR-V7 is a substrate of the proteasome. Identifying novel drugs that can trigger the degradation of AR-V7 is therefore critical to cure CRPC. Here we show that nobiletin, a polymethoxylated flavonoid derived from the peel of Citrus fruits, exerts a potent anticancer activity via inducing G0/G1 phase arrest and enhancing the sensitivity of cells to enzalutamide in AR-V7 positive PC cells. Mechanically, we unravel that nobiletin selectively induces proteasomal degradation of AR-V7 (but not AR). This effect relies on its selective inhibition of the interactions between AR-V7 and two deubiquitinases USP14 and USP22. These findings not only enrich our understanding on the mechanism of AR-V7 degradation, but also provide an efficient and druggable target for overcoming CRPC through interfering the stability of AR-V7 mediated by the interaction between AR-V7 and deubiquitinase.


Asunto(s)
Neoplasias de la Próstata Resistentes a la Castración/metabolismo , Proteolisis , Receptores Androgénicos/metabolismo , Animales , Benzamidas/farmacología , Puntos de Control del Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Flavonas/farmacología , Humanos , Lisina/metabolismo , Masculino , Ratones Endogámicos BALB C , Ratones Desnudos , Modelos Biológicos , Nitrilos/farmacología , Feniltiohidantoína/farmacología , Neoplasias de la Próstata Resistentes a la Castración/patología , Complejo de la Endopetidasa Proteasomal/metabolismo , Proteolisis/efectos de los fármacos , Ubiquitina Tiolesterasa/metabolismo , Ubiquitinación
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