Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 31
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Circulation ; 141(3): 217-233, 2020 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-31801360

RESUMO

BACKGROUND: Heart failure is a leading cause of death worldwide. Cyclic nucleotide phosphodiesterases (PDEs), through degradation of cyclic nucleotides, play critical roles in cardiovascular biology and disease. Our preliminary screening studies have revealed PDE10A upregulation in the diseased heart. However, the roles of PDE10A in cardiovascular biology and disease are largely uncharacterized. The current study is aimed to investigate the regulation and function of PDE10A in cardiac cells and in the progression of cardiac remodeling and dysfunction. METHODS: We used isolated adult mouse cardiac myocytes and fibroblasts, as well as preclinical mouse models of hypertrophy and heart failure. The PDE10A selective inhibitor TP-10, and global PDE10A knock out mice were used. RESULTS: We found that PDE10A expression remains relatively low in normal and exercised heart tissues. However, PDE10A is significantly upregulated in mouse and human failing hearts. In vitro, PDE10A deficiency or inhibiting PDE10A with selective inhibitor TP-10, attenuated cardiac myocyte pathological hypertrophy induced by Angiotensin II, phenylephrine, and isoproterenol, but did not affect cardiac myocyte physiological hypertrophy induced by IGF-1 (insulin-like growth factor 1). TP-10 also reduced TGF-ß (transforming growth factor-ß)-stimulated cardiac fibroblast activation, proliferation, migration and extracellular matrix synthesis. TP-10 treatment elevated both cAMP and cGMP levels in cardiac myocytes and cardiac fibroblasts, consistent with PDE10A as a cAMP/cGMP dual-specific PDE. In vivo, global PDE10A deficiency significantly attenuated myocardial hypertrophy, cardiac fibrosis, and dysfunction induced by chronic pressure overload via transverse aorta constriction or chronic neurohormonal stimulation via Angiotensin II infusion. Importantly, we demonstrated that the pharmacological effect of TP-10 is specifically through PDE10A inhibition. In addition, TP-10 is able to reverse pre-established cardiac hypertrophy and dysfunction. RNA-Sequencing and bioinformatics analysis further identified a PDE10A-regualted transcriptome involved in cardiac hypertrophy, fibrosis, and cardiomyopathy. CONCLUSIONS: Taken together, our study elucidates a novel role for PDE10A in the regulation of pathological cardiac remodeling and development of heart failure. Given that PDE10A has been proven to be a safe drug target, PDE10A inhibition may represent a novel therapeutic strategy for preventing and treating cardiac diseases associated with cardiac remodeling.

2.
ACS Nano ; 14(1): 303-310, 2020 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-31860271

RESUMO

Two-dimensional (2D) semiconductors have been extensively explored as a new class of materials with great potential. In particular, black phosphorus (BP) has been considered to be a strong candidate for applications such as high-performance infrared photodetectors. However, the scalability of BP thin film is still a challenge, and its poor stability in the air has hampered the progress of the commercialization of BP devices. Herein, we report the use of hydrothermal-synthesized and air-stable 2D tellurene nanoflakes for broadband and ultrasensitive photodetection. The tellurene nanoflakes show high hole mobilities up to 458 cm2/V·s at ambient conditions, and the tellurene photodetector presents peak extrinsic responsivity of 383 A/W, 19.2 mA/W, and 18.9 mA/W at 520 nm, 1.55 µm, and 3.39 µm light wavelength, respectively. Because of the photogating effect, high gains up to 1.9 × 103 and 3.15 × 104 are obtained at 520 nm and 3.39 µm wavelength, respectively. At the communication wavelength of 1.55 µm, the tellurene photodetector exhibits an exceptionally high anisotropic behavior, and a large bandwidth of 37 MHz is obtained. The photodetection performance at different wavelength is further supported by the corresponding quantum molecular dynamics (QMD) simulations. Our approach has demonstrated the air-stable tellurene photodetectors that fully cover the short-wave infrared band with ultrafast photoresponse.

3.
Nat Commun ; 10(1): 5544, 2019 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-31804496

RESUMO

Defects can induce drastic changes of the electronic properties of two-dimensional transition metal dichalcogenides and influence their applications. It is still a great challenge to characterize small defects and correlate their structures with properties. Here, we show that tip-enhanced Raman spectroscopy (TERS) can obtain distinctly different Raman features of edge defects in atomically thin MoS2, which allows us to probe their unique electronic properties and identify defect types (e.g., armchair and zigzag edges) in ambient. We observed an edge-induced Raman peak (396 cm-1) activated by the double resonance Raman scattering (DRRS) process and revealed electron-phonon interaction in edges. We further visualize the edge-induced band bending region by using this DRRS peak and electronic transition region using the electron density-sensitive Raman peak at 406 cm-1. The power of TERS demonstrated in MoS2 can also be extended to other 2D materials, which may guide the defect engineering for desired properties.

4.
Comput Struct Biotechnol J ; 17: 1326-1338, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31741723

RESUMO

Alteration of RNA structure by environmental signals is a fundamental mechanism of gene regulation. For example, the riboswitch is a noncoding RNA regulatory element that binds a small molecule and causes a structural change in the RNA, thereby regulating transcription, splicing, or translation of an mRNA. The role of riboswitches in metabolite sensing and gene regulation in bacteria and other lower species was reported almost two decades ago, but riboswitches have not yet been discovered in mammals. An analog of the riboswitch, the protein-directed RNA switch (PDRS), has been identified as an important regulatory mechanism of gene expression in mammalian cells. RNA-binding proteins and microRNAs are two major executors of PDRS via their interaction with target transcripts in mammals. These protein-RNA interactions influence cellular functions by integrating environmental signals and intracellular pathways from disparate stimuli to modulate stability or translation of specific mRNAs. The discovery of a riboswitch in eukaryotes that is composed of a single class of thiamine pyrophosphate (TPP) suggests that additional ligand-sensing RNAs may be present to control eukaryotic or mammalian gene expression. In this review, we focus on protein-directed RNA switch mechanisms in mammals. We offer perspectives on the potential discovery of mammalian protein-directed and compound-dependent RNA switches that are related to human disease and medicine.

5.
Biochem Biophys Res Commun ; 516(3): 753-759, 2019 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-31255281

RESUMO

The GAIT (gamma-interferon-activated inhibitor of translation) complex or miR-297-RISC (RNA-induced silencing complex), together with hnRNP L or hnRNP L-bearing complex, operates an RNA switch in myeloid cells that regulates stress-dependent expression of vascular endothelial growth factor-A (VEGFA). Here, we have shown that hnRNP L directs multiple hypoxia-inducible RNA switches simultaneously and regulates expression of these oncogenic genes in addition to VEGFA. Bioinformatic and polysome profiling-microarray screens have identified DNM1L (Dynamin 1-like) and PHF21A (PHD finger protein 21A) mRNAs as regulated at the translational level by GAIT-dependent, hnRNP L-directed RNA switches. We have also uncovered CDK6 (Cyclin dependent kinase 6), MKLN1 (Muskelin 1) and EIF5 (Eukaryotic initiation factor 5) as novel miR-297-dependent, hnRNP L-directed RNA switch transcripts. Src Kinase is required for the phosphorylation of hnRNP L and activation of the RNA switch pathway. Knockdown of hnRNP L sensitizes the human U937 monocytic cells under hypoxia stress but not in normoxia via inducing cell apoptosis partially due to the reduced translation of hnRNP L target mRNAs. Collectively, our findings suggest that commonly controlled genes by the hnRNP L-directed RNA switches form a translational regulon that promotes hypoxia resistance and cell survival.

6.
Nat Commun ; 10(1): 2419, 2019 06 03.
Artigo em Inglês | MEDLINE | ID: mdl-31160599

RESUMO

The electron-phonon coupling (EPC) in a material is at the frontier of the fundamental research, underlying many quantum behaviors. van der Waals heterostructures (vdWHs) provide an ideal platform to reveal the intrinsic interaction between their electrons and phonons. In particular, the flexible van der Waals stacking of different atomic crystals leads to multiple opportunities to engineer the interlayer phonon modes for EPC. Here, in hBN/WS2 vdWH, we report the strong cross-dimensional coupling between the layer-breathing phonons well extended over tens to hundreds of layer thick vdWH and the electrons localized within the few-layer WS2 constituent. The strength of such cross-dimensional EPC can be well reproduced by a microscopic picture through the mediation by the interfacial coupling and also the interlayer bond polarizability model in vdWHs. The study on cross-dimensional EPC paves the way to manipulate the interaction between electrons and phonons in various vdWHs by interfacial engineering for possible interesting physical phenomena.

7.
Adv Mater ; 31(33): e1902118, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31237378

RESUMO

Anisotropic photonic materials with linear dichroism are crucial components in many sensing, imaging, and communication applications. Such materials play an important role as polarizers, filters, and waveplates in photonic devices and circuits. Conventional crystalline materials with optical anisotropy typically show unidirectional linear dichroism over a broad wavelength range. The linear dichroism conversion phenomenon has not been observed in crystalline materials. The investigation of the unique linear dichroism conversion phenomenon in quasi-1D hexagonal perovskite chalcogenide BaTiS3 is reported. This material shows a record level of optical anisotropy within the visible wavelength range. In contrast to conventional anisotropic optical materials, the linear dichroism polarity in BaTiS3 makes an orthogonal change at an optical wavelength corresponding to the photon energy of 1.78 eV. First-principles calculations reveal that this anomalous linear dichroism conversion behavior originates from the different selection rules of the parallel energy bands in the BaTiS3 material. Wavelength-dependent polarized Raman spectroscopy further confirms this phenomenon. Such a material, with linear dichroism conversion properties, could facilitate the sensing and control of the energy and polarization of light, and lead to novel photonic devices such as polarization-wavelength selective detectors and lasers for multispectral imaging, sensing, and optical communication applications.

8.
ACS Nano ; 13(4): 4133-4139, 2019 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-30913391

RESUMO

The successful fabrication of a two-dimensional boron sheet, which features a triangular lattice with periodic hole arrays, has stimulated great interest in its specific structure as well as properties such as possible superconductivity. Here, we report a study on the vibrational spectra and electron-phonon coupling (EPC) in monolayer boron sheets by in situ Raman and tip-enhanced Raman spectroscopy (TERS) at low temperature and ultrahigh vacuum. The gap-mode TERS gives a 3 × 109 selective enhancement on vertical vibrational Raman modes. A spatial resolution of 1 nm is achieved in this system. Combined with first-principle calculations, the vibrational properties as well as EPC in borophene are determined. The results are helpful for further study on the mechanical, electronic, and possible superconducting properties of two-dimensional boron.

9.
Adv Mater ; 31(17): e1806562, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30861234

RESUMO

To explore new constituents in two-dimensional (2D) materials and to combine their best in van der Waals heterostructures is in great demand as being a unique platform to discover new physical phenomena and to design novel functionalities in interface-based devices. Herein, PbI2 crystals as thin as a few layers are synthesized, particularly through a facile low-temperature solution approach with crystals of large size, regular shape, different thicknesses, and high yields. As a prototypical demonstration of band engineering of PbI2 -based interfacial semiconductors, PbI2 crystals are assembled with several transition metal dichalcogenide monolayers. The photoluminescence of MoS2 is enhanced in MoS2 /PbI2 stacks, while a dramatic photoluminescence quenching of WS2 and WSe2 is revealed in WS2 /PbI2 and WSe2 /PbI2 stacks. This is attributed to the effective heterojunction formation between PbI2 and these monolayers; type I band alignment in MoS2 /PbI2 stacks, where fast-transferred charge carriers accumulate in MoS2 with high emission efficiency, results in photoluminescence enhancement, and type II in WS2 /PbI2 and WSe2 /PbI2 stacks, with separated electrons and holes suitable for light harvesting, results in photoluminescence quenching. The results demonstrate that MoS2 , WS2 , and WSe2 monolayers with similar electronic structures show completely distinct light-matter interactions when interfacing with PbI2 , providing unprecedented capabilities to engineer the device performance of 2D heterostructures.

10.
ACS Nano ; 12(8): 8770-8780, 2018 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-30086224

RESUMO

The material choice, layer thickness, and twist angle widely enrich the family of van der Waals heterostructures (vdWHs), providing multiple degrees of freedom to engineer their optical and electronic properties. The moiré patterns in vdWHs create a periodic potential for electrons and excitons to yield many interesting phenomena, such as Hofstadter butterfly spectrum and moiré excitons. Here, in the as-grown/transferred twisted bilayer MoS2 (tBLMs), one of the simplest prototypes of vdWHs, we show that the periodic potentials of moiré patterns also modify the properties of phonons of its monolayer MoS2 constituent to generate Raman modes related to moiré phonons. These Raman modes correspond to zone-center phonons in tBLMs, which are folded from the off-center phonons in monolayer MoS2. However, the folded phonons related to crystallographic superlattices are not observed in the Raman spectra. By varying the twist angle, the moiré phonons of tBLM can be exploited to map the phonon dispersions of the monolayer constituent. The lattice dynamics of the moiré phonons are modulated by the patterned interlayer coupling resulting from periodic potential of moiré patterns, as confirmed by density functional theory calculations. The Raman intensity related to moiré phonons in all tBLMs are strongly enhanced when the excitation energy approaches the C exciton energy. This study can be extended to various vdWHs to deeply understand their Raman spectra, moiré phonons, lattice dynamics, excitonic effects, and interlayer coupling.

11.
Nanoscale ; 10(34): 16138-16144, 2018 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-30117506

RESUMO

Stokes and anti-Stokes Raman spectroscopy associated with the intervalley double resonance process in carbon materials is a unique technique to reveal the relationship between their characteristic electronic band structures and phonon dispersion. In graphene, the dominant resonant behavior for its 2D mode is an intervalley triple resonance Raman process. In this paper, we report the Stokes and anti-Stokes Raman scattering of the 2D mode in pristine graphene. The excitation energy (Eex)-dependent frequency discrepancy between anti-Stokes and Stokes components of the 2D mode (Δω(2D)) is observed, which is in good agreement with the theoretical results. This is attributed to the nonlinear dispersion of the in-plane transverse optical (iTO) phonon branch near the K point, confirmed by the nonlinear Eex-dependent frequency of the 2D mode (ω(2D)) in the range of 1.58-3.81 eV. The wavevector-dependent phonon group velocity of the iTO phonon branch is directly derived from Δω(2D). The Stokes and anti-Stokes Raman scattering of the D mode in defected graphene and the 2D mode in bilayer graphene associated with intervalley double resonance Raman processes is also reported.

12.
Nano Lett ; 18(5): 2937-2942, 2018 05 09.
Artigo em Inglês | MEDLINE | ID: mdl-29601201

RESUMO

The atomic structures of self-assembled silicon nanoribbons and magic clusters on Ag(110) substrate have been studied by high-resolution noncontact atomic force microscopy (nc-AFM) and tip-enhanced Raman spectroscopy (TERS). Pentagon-ring structures in Si nanoribbons and clusters have been directly visualized. Moreover, the vibrational fingerprints of individual Si nanoribbon and cluster retrieved by subnanometer resolution TERS confirm the pentagonal nature of both Si nanoribbons and clusters. This work demonstrates that Si pentagon can be an important element in building silicon nanostructures, which may find important applications for future nanoelectronic devices based on silicon.

13.
Chem Soc Rev ; 47(5): 1822-1873, 2018 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-29368764

RESUMO

Graphene-based materials exhibit remarkable electronic, optical, and mechanical properties, which has resulted in both high scientific interest and huge potential for a variety of applications. Furthermore, the family of graphene-based materials is growing because of developments in preparation methods. Raman spectroscopy is a versatile tool to identify and characterize the chemical and physical properties of these materials, both at the laboratory and mass-production scale. This technique is so important that most of the papers published concerning these materials contain at least one Raman spectrum. Thus, here, we systematically review the developments in Raman spectroscopy of graphene-based materials from both fundamental research and practical (i.e., device applications) perspectives. We describe the essential Raman scattering processes of the entire first- and second-order modes in intrinsic graphene. Furthermore, the shear, layer-breathing, G and 2D modes of multilayer graphene with different stacking orders are discussed. Techniques to determine the number of graphene layers, to probe resonance Raman spectra of monolayer and multilayer graphenes and to obtain Raman images of graphene-based materials are also presented. The extensive capabilities of Raman spectroscopy for the investigation of the fundamental properties of graphene under external perturbations are described, which have also been extended to other graphene-based materials, such as graphene quantum dots, carbon dots, graphene oxide, nanoribbons, chemical vapor deposition-grown and SiC epitaxially grown graphene flakes, composites, and graphene-based van der Waals heterostructures. These fundamental properties have been used to probe the states, effects, and mechanisms of graphene materials present in the related heterostructures and devices. We hope that this review will be beneficial in all the aspects of graphene investigations, from basic research to material synthesis and device applications.

14.
Phys Rev Lett ; 119(19): 196803, 2017 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-29219519

RESUMO

Combining ultrahigh sensitivity, spatial resolution, and the capability to resolve chemical information, tip-enhanced Raman spectroscopy (TERS) is a powerful tool to study molecules or nanoscale objects. Here we show that TERS can also be a powerful tool in studying two-dimensional materials. We have achieved a 10^{9} Raman signal enhancement and a 0.5 nm spatial resolution using monolayer silicene on Ag(111) as a prototypical 2D material system. Because of the selective enhancement on Raman modes with vertical vibrational components in TERS, our experiment provides direct evidence of the origination of Raman modes in silicene. Furthermore, the ultrahigh sensitivity of TERS allows us to identify different vibrational properties of silicene phases, which differ only in the bucking direction of the Si-Si bonds. Local vibrational features from defects and domain boundaries in silicene can also be identified.

15.
ACS Nano ; 11(11): 11714-11723, 2017 11 28.
Artigo em Inglês | MEDLINE | ID: mdl-29068659

RESUMO

Interfacial coupling between neighboring layers of van der Waals heterostructures (vdWHs), formed by vertically stacking more than two types of two-dimensional materials (2DMs), greatly affects their physical properties and device performance. Although high-resolution cross-sectional scanning tunneling electron microscopy can directly image the atomically sharp interfaces in the vdWHs, the interfacial coupling and lattice dynamics of vdWHs formed by two different types of 2DMs, such as semimetal and semiconductor, are not clear so far. Here, we report the ultralow-frequency Raman spectroscopy investigation on interfacial couplings in the vdWHs formed by graphene and MoS2 flakes. Because of the significant interfacial layer-breathing couplings between MoS2 and graphene flakes, a series of layer-breathing modes with frequencies dependent on their layer numbers are observed in the vdWHs, which can be described by the linear chain model. It is found that the interfacial layer-breathing force constant between MoS2 and graphene, α0⊥(I) = 60 × 1018 N/m3, is comparable with the layer-breathing force constant of multilayer MoS2 and graphene. The results suggest that the interfacial layer-breathing couplings in the vdWHs formed by MoS2 and graphene flakes are not sensitive to their stacking order and twist angle between the two constituents. Our results demonstrate that the interfacial interlayer coupling in vdWHs formed by two-dimensional semimetals and semiconductors can lead to new lattice vibration modes, which not only can be used to measure the interfacial interactions in vdWHs but also is beneficial to fundamentally understand the properties of vdWHs for further engineering the vdWHs-based electronic and photonic devices.

16.
Nat Commun ; 8(1): 278, 2017 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-28819184

RESUMO

Black phosphorus is a two-dimensional material of great interest, in part because of its high carrier mobility and thickness dependent direct bandgap. However, its instability under ambient conditions limits material deposition options for device fabrication. Here we show a black phosphorus ink that can be reliably inkjet printed, enabling scalable development of optoelectronic and photonic devices. Our binder-free ink suppresses coffee ring formation through induced recirculating Marangoni flow, and supports excellent consistency (< 2% variation) and spatial uniformity (< 3.4% variation), without substrate pre-treatment. Due to rapid ink drying (< 10 s at < 60 °C), printing causes minimal oxidation. Following encapsulation, the printed black phosphorus is stable against long-term (> 30 days) oxidation. We demonstrate printed black phosphorus as a passive switch for ultrafast lasers, stable against intense irradiation, and as a visible to near-infrared photodetector with high responsivities. Our work highlights the promise of this material as a functional ink platform for printed devices.Atomically thin black phosphorus shows promise for optoelectronics and photonics, yet its instability under environmental conditions and the lack of well-established large-area synthesis protocols hinder its applications. Here, the authors demonstrate a stable black phosphorus ink suitable for printed ultrafast lasers and photodetectors.

17.
Rev Sci Instrum ; 88(5): 053110, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28571441

RESUMO

Simultaneous Stokes and anti-Stokes ultralow-frequency (ULF) Raman measurement down to ∼2 cm-1 or 60 GHz is realized by a single-stage spectrometer in combination with volume-Bragg-grating-based notch filters. This system reveals its excellent performance by probing Brillouin signal of acoustic phonons in silicon, germanium, gallium arsenide, and gallium nitride. The deduced sound velocity and elastic constants are in good accordance with previous results determined by various methods. This system can shorten the integration time of the Brillouin signal with a good signal-to-noise ratio by more than 2000-fold compared to a Fabry-Perot interferometer (FPI). This study shows how a filter-based ULF Raman system can be used to reliably achieve Brillouin spectroscopy for condensed materials with high sensitivity and high signal-to-noise ratio, stimulating fast Brillouin spectrum measurements to probe acoustic phonons in semiconductors.

18.
Nucleic Acids Res ; 45(13): 7950-7964, 2017 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-28520992

RESUMO

MicroRNAs (miRNAs) and heterogeneous nuclear ribonucleoproteins (hnRNPs) are families of sequence-specific, posttranscriptional modulators of gene expression. Despite extensive mechanistic and functional studies on both regulatory classes, the interactions and crosstalk between them are largely unexplored. We have reported that competition between miR-297 and hnRNP L to bind a 3΄UTR-localized CA-rich element (CARE) of VEGFA mRNA regulates its translation. Here, we show that translation of VEGFA mRNA in human myeloid cells is dictated by a bi-directional interaction between miR-574-3p, a CA-rich microRNA, and hnRNP L. In normoxia, miR-574-3p, acting as a decoy, binds cytoplasmic hnRNP L and prevents its binding to the CARE and stimulation of VEGFA mRNA translation, simultaneously permitting miR-297-mediated translational silencing. However, in hypoxia, cytoplasmic accumulation of Tyr359-phosphorylated hnRNP L sequesters miR-574-3p, overcoming its decoy activity and seed sequence-dependent gene silencing activity. Ectopically expressed miR-574-3p binds multiple RNA recognition motif (RRM) domains of hnRNP L, synergizes with miR-297, reduces VEGFA mRNA translation, and triggers apoptosis, thereby suppressing tumorigenesis. Our studies establish a novel condition-dependent interplay between a miRNA and an hnRNP that regulates their functions in a bidirectional manner.


Assuntos
Ribonucleoproteínas Nucleares Heterogêneas Grupo L/genética , Ribonucleoproteínas Nucleares Heterogêneas Grupo L/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Fator A de Crescimento do Endotélio Vascular/biossíntese , Fator A de Crescimento do Endotélio Vascular/genética , Regiões 3' não Traduzidas , Carboxipeptidases/antagonistas & inibidores , Carboxipeptidases/metabolismo , Carcinogênese/genética , Carcinogênese/metabolismo , Hipóxia Celular/genética , Hipóxia Celular/fisiologia , Transformação Celular Neoplásica/genética , Humanos , Mutagênese Sítio-Dirigida , Células Mieloides/citologia , Células Mieloides/metabolismo , Biossíntese de Proteínas , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Células U937
19.
Oncotarget ; 7(27): 42274-42287, 2016 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-27281615

RESUMO

Damage to mitochondria often results in the activation of both mitophagy and mitochondrial apoptosis. The elimination of dysfunctional mitochondria is necessary for mitochondrial quality maintenance and efficient energy supply. Here we report that miR-181a is a novel inhibitor of mitophagy. miR-181a is downregulated by mitochondrial uncouplers in human neuroblastoma SH-SY5Y cells. Overexpression of miR-181a inhibits mitochondrial uncoupling agents-induced mitophagy by inhibiting the degradation of mitochondrial proteins without affecting global autophagy. Knock down of endogenous miR-181a accelerates the autophagic degradation of damaged mitochondria. miR-181a directly targets Parkin E3 ubiquitin ligase and partially blocks the colocalization of mitochondria and autophagosomes/lysosomes. Re-expression of exogenous Parkin restores the inhibitory effect of miR-181a on mitophagy. Furthermore, miR-181a increases the sensitivity of neuroblastoma cells to mitochondrial uncoupler-induced apoptosis, whereas miR-181a antagomir prevents cell death. Because mitophagy defects are associated with a variety of human disorders, these findings indicate an important link between microRNA and Parkin-mediated mitophagy and highlights a potential therapeutic strategy for human diseases.


Assuntos
Apoptose , Regulação Neoplásica da Expressão Gênica , MicroRNAs/metabolismo , Mitocôndrias/patologia , Neuroblastoma/patologia , Ubiquitina-Proteína Ligases/metabolismo , Linhagem Celular Tumoral , DNA Mitocondrial/metabolismo , Perfilação da Expressão Gênica , Humanos , Lisossomos/metabolismo , Proteínas de Desacoplamento Mitocondrial/metabolismo , Neuroblastoma/metabolismo
20.
Nanoscale ; 8(15): 8324-32, 2016 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-27035503

RESUMO

Anisotropic two-dimensional (2D) van der Waals (vdW) layered materials, with both scientific interest and application potential, offer one more dimension than isotropic 2D materials to tune their physical properties. Various physical properties of 2D multi-layer materials are modulated by varying their stacking orders owing to significant interlayer vdW coupling. Multilayer rhenium disulfide (ReS2), a representative anisotropic 2D material, was expected to be randomly stacked and lack interlayer coupling. Here, we demonstrate two stable stacking orders, namely isotropic-like (IS) and anisotropic-like (AI) N layer (NL, N > 1) ReS2 are revealed by ultralow- and high-frequency Raman spectroscopy, photoluminescence and first-principles density functional theory calculation. Two interlayer shear modes are observed in AI-NL-ReS2 while only one shear mode appears in IS-NL-ReS2, suggesting anisotropic- and isotropic-like stacking orders in IS- and AI-NL-ReS2, respectively. This explicit difference in the observed frequencies identifies an unexpected strong interlayer coupling in IS- and AI-NL-ReS2. Quantitatively, the force constants of them are found to be around 55-90% of those of multilayer MoS2. The revealed strong interlayer coupling and polytypism in multi-layer ReS2 may stimulate future studies on engineering physical properties of other anisotropic 2D materials by stacking orders.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA