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1.
Nature ; 593(7857): 56-60, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33953409

RESUMO

Exciting phenomena may emerge in non-centrosymmetric two-dimensional electronic systems when spin-orbit coupling (SOC)1 interplays dynamically with Coulomb interactions2,3, band topology4,5 and external modulating forces6-8. Here we report synergetic effects between SOC and the Stark effect in centrosymmetric few-layer black arsenic, which manifest as particle-hole asymmetric Rashba valley formation and exotic quantum Hall states that are reversibly controlled by electrostatic gating. The unusual findings are rooted in the puckering square lattice of black arsenic, in which heavy 4p orbitals form a Brillouin zone-centred Γ valley with pz symmetry, coexisting with doubly degenerate D valleys of px origin near the time-reversal-invariant momenta of the X points. When a perpendicular electric field breaks the structure inversion symmetry, strong Rashba SOC is activated for the px bands, which produces spin-valley-flavoured D± valleys paired by time-reversal symmetry, whereas Rashba splitting of the Γ valley is constrained by the pz symmetry. Intriguingly, the giant Stark effect shows the same px-orbital selectiveness, collectively shifting the valence band maximum of the D± Rashba valleys to exceed the Γ Rashba top. Such an orchestrating effect allows us to realize gate-tunable Rashba valley manipulations for two-dimensional hole gases, hallmarked by unconventional even-to-odd transitions in quantum Hall states due to the formation of a flavour-dependent Landau level spectrum. For two-dimensional electron gases, the quantization of the Γ Rashba valley is characterized by peculiar density-dependent transitions in the band topology from trivial parabolic pockets to helical Dirac fermions.

2.
Small ; 19(33): e2300964, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37066740

RESUMO

The long-range magnetic ordering in frustrated magnetic systems is stabilized by coupling magnetic moments to various degrees of freedom, for example, by enhancing magnetic anisotropy via lattice distortion. Here, the unconventional spin-lattice coupled metamagnetic properties of atomically-thin CrOCl, a van der Waals antiferromagnet with inherent magnetic frustration rooted in the staggered square lattice, are reported. Using temperature- and angle-dependent tunneling magnetoconductance (TMC), in complementary with magnetic torque and first-principles calculations, the antiferromagnetic (AFM)-to-ferrimagnetic (FiM) metamagnetic transitions (MTs) of few-layer CrOCl are revealed to be triggered by collective magnetic moment flipping rather than the established spin-flop mechanism, when external magnetic field (H) enforces a lattice reconstruction interlocked with the five-fold periodicity of the FiM phase. The spin-lattice coupled MTs are manifested by drastic jumps in TMC, which show anomalous upshifts at the transition thresholds and persist much higher above the AFM Néel temperature. While the MTs exhibit distinctive triaxial anisotropy, reflecting divergent magnetocrystalline anisotropy of the c-axis AFM ground state, the resulting FiM phase has an a-c easy plane in which the magnetization axis is freely rotated by H. At the 2D limit, such a field-tunable FiM phase may provide unique opportunities to explore exotic emergent phenomena and novel spintronics devices.

3.
Cell Commun Signal ; 19(1): 24, 2021 02 24.
Artigo em Inglês | MEDLINE | ID: mdl-33627137

RESUMO

BACKGROUND: The oncogenic transcript factor c-Maf is stabilized by the deubiquitinase Otub1 and promotes myeloma cell proliferation and confers to chemoresistance. Inhibition of the Otub1/c-Maf axis is a promising therapeutic target, but there are no inhibitors reported on this specific axis. METHODS: A luciferase assay was applied to screen potential inhibitors of Otub1/c-Maf. Annexin V staining/flow cytometry was applied to evaluate cell apoptosis. Immunoprecipitation was applied to examine protein ubiquitination and interaction. Xenograft models in nude mice were used to evaluate anti-myeloma activity of AVT. RESULTS: Acevaltrate (AVT), isolated from Valeriana glechomifolia, was identified based on a bioactive screen against the Otub1/c-Maf/luciferase system. AVT disrupts the interaction of Otub1/c-Maf thus inhibiting Otub1 activity and leading to c-Maf polyubiquitination and subsequent degradation in proteasomes. Consistently, AVT inhibits c-Maf transcriptional activity and downregulates the expression of its target genes key for myeloma growth and survival. Moreover, AVT displays potent anti-myeloma activity by triggering myeloma cell apoptosis in vitro and impairing myeloma xenograft growth in vivo but presents no marked toxicity. CONCLUSIONS: The natural product AVT inhibits the Otub1/c-Maf axis and displays potent anti-myeloma activity. Given its great safety and efficacy, AVT could be further developed for MM treatment. Video Abstract.


Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Cisteína Endopeptidases/metabolismo , Inibidores de Cisteína Proteinase/uso terapêutico , Iridoides/uso terapêutico , Mieloma Múltiplo/tratamento farmacológico , Proteínas Proto-Oncogênicas c-maf/antagonistas & inibidores , Animais , Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Cisteína Endopeptidases/genética , Inibidores de Cisteína Proteinase/farmacologia , Feminino , Humanos , Iridoides/farmacologia , Camundongos Endogâmicos BALB C , Camundongos Nus , Mieloma Múltiplo/metabolismo , Mieloma Múltiplo/patologia , Proteínas Proto-Oncogênicas c-maf/genética , Proteínas Proto-Oncogênicas c-maf/metabolismo
4.
Acta Pharmacol Sin ; 42(8): 1338-1346, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33184448

RESUMO

Recent studies show that the expression of CCND1, a key factor in cell cycle control, is increased following the progress and deteriotation of glioma and predicts poor outcomes. On the other hand, dysregulated deubiquitinase USP10 also predicts poor prognosis for patients with glioblastoma (GBM). In the present study, we investigated the interplay between CCND1 protein and USP10 in GBM cells. We showed that the expression of CCND1 was significantly higher in both GBM tissues and GBM-derived stem cells. USP10 interacted with CCND1 and prevented its K48- but not K63-linked polyubiquitination in GBM U251 and HS683 cells, which led to increased CCND1 stability. Consistent with the action of USP10 on CCND1, knockdown of USP10 by single-guided RNA downregulated CCND1 and caused GBM cell cycle arrest at the G1 phase and induced GBM cell apoptosis. To implement this finding in the treatment of GBMs, we screened a natural product library and found that acevaltrate (AVT), an active component derived from the herbal plant Valeriana jatamansi Jones was strikingly potent to induce GBM cell apoptosis, which was confirmed by the Annexin V staining and activation of the apoptotic signals. Furthermore, we revealed that AVT concentration-dependently suppressed USP10-mediated deubiquitination on CCND1 therefore inducing CCND1 protein degradation. Collectively, the present study demonstrates that the USP10/CCND1 axis could be a promising therapeutic target for patients with GBMs.


Assuntos
Ciclina D1/metabolismo , Glioblastoma/metabolismo , Iridoides/farmacologia , Ubiquitina Tiolesterase/metabolismo , Ubiquitinação/fisiologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/fisiologia , Glioblastoma/tratamento farmacológico , Células HEK293 , Humanos , Ubiquitina Tiolesterase/antagonistas & inibidores , Ubiquitinação/efeitos dos fármacos
5.
Neurol Sci ; 42(9): 3605-3613, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34236554

RESUMO

BACKGROUND: Atherosclerosis is the most common cause of ischemia stroke. Computed tomographic angiography (CTA) and digital subtraction angiography (DSA) are used to evaluate the degree of lumen stenosis. However, these examinations are invasive and can only reveal mild to moderate stenosis. High-resolution magnetic resonance imaging (HRMRI) seems a more intuitive way to show the pathological changes of vascular wall. Hence, we conducted a systematic retrospective study to determine the characteristics of symptomatic plaques in patients with intracranial atherosclerosis on HRMRI and their association with the occurrence and recurrence of ischemic stroke events. METHODS: The PubMed database was searched for relevant studies reported from January 31, 2010, to October 31, 2020. RESULTS: We selected 14 clinical outcome studies. We found that plaque enhancement and positive remodeling on HRMRI indicate symptomatic plaques. Besides, intraplaque hemorrhage and positive remodeling index are closely related to the occurrence of stroke. However, it is still controversial whether the initial enhancement of plaque and the occurrence and recurrence of stroke are related. There is also no significant correlation between vascular stenosis and symptomatic plaque or the occurrence and recurrence of ischemic stroke. CONCLUSION: High-resolution magnetic resonance imaging can be used as an assessment tool to predict the risk of stroke onset and recurrence in patients with atherosclerosis, but further research is also needed.


Assuntos
Isquemia Encefálica , Arteriosclerose Intracraniana , AVC Isquêmico , Placa Aterosclerótica , Acidente Vascular Cerebral , Isquemia Encefálica/complicações , Isquemia Encefálica/diagnóstico por imagem , Isquemia Encefálica/epidemiologia , Humanos , Arteriosclerose Intracraniana/complicações , Arteriosclerose Intracraniana/diagnóstico por imagem , Angiografia por Ressonância Magnética , Imageamento por Ressonância Magnética , Placa Aterosclerótica/diagnóstico por imagem , Estudos Retrospectivos , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/epidemiologia
6.
Neurol Sci ; 42(10): 4139-4148, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33528671

RESUMO

BACKGROUND: In recent years, the implantable cardiac monitors (ICM) have enhanced the recognition ability of atrial fibrillation (AF), which makes ICM have a new application in AF detection. We conducted a meta-analysis to determine the total incidence of newly found AF detected by ICM after cryptogenic stroke and to evaluate the factors related to the detection of AF. METHODS: A literature search was conducted in the PubMed, EMBASE, Web of Science, and Cochrane library databases until March 1, 2020. Studies that reported the detection rate of AF using ICM in cryptogenic stroke patients with negative initial AF screening were analyzed. RESULTS: A total of 23 studies were included. The overall proportion of AF detected by ICM in cryptogenic stroke patients was 25% (95% confidence interval [CI], 22-29%). The rate of AF detected by ICM was independently related to both cardiac monitoring time (coefficient = 0.0003; 95% CI, 0.0001-0.0005; P = 0.0001) and CHA2DS2-VASc score (coefficient = 0.0834; 95% CI, 0.0339-0.1329; P = 0.001). In subgroup analysis, we found a significant difference in the detection rate of AF for monitoring duration (< 6 months: 9.6% [95% CI, 4.4-16.4%]; ≥ 6 and ≤ 12 months: 19.3% [95% CI, 15.9-23.0%]; > 12 and ≤ 24 months: 23.6% [95% CI, 19.9-27.5%]; > 24 months and ≤ 36 months: 36.5% [95% CI, 24.2-49.9%]; P < 0.001), and continent (Europe: 26.5% [95% CI, 22.2-31.0%]; North America: 16.0% [95% CI, 10.3-22.6%]; Asia: 17.4% [95% CI, 12.4-23.0%]; P = 0.005). CONCLUSIONS: The longer the time of ICM monitoring after cryptogenic stroke, the higher the detection rate of AF. Further research is still needed to determine the optimal duration of long-term cardiac monitoring.


Assuntos
Fibrilação Atrial , AVC Isquêmico , Acidente Vascular Cerebral , Fibrilação Atrial/complicações , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/epidemiologia , Eletrocardiografia Ambulatorial , Humanos , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/epidemiologia , Fatores de Tempo
7.
Neurol Sci ; 42(7): 2645-2651, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33954827

RESUMO

OBJECTIVE: We aim to determine the risk of acute ischemic stroke in patients with severe and non-severe coronavirus disease 2019 (COVID-19). METHODS: A literature search was conducted in the PubMed, Embase, Web of Science, and Cochrane Library databases until October 28, 2020. Studies covering COVID-19's severity classification data and COVID-19 patients with acute ischemic stroke were included. Two independent evaluators extracted data, and the random effects model was used to calculate the risk ratios (RR) and 95% confidence interval (95% CI) of acute ischemic stroke associated with COVID-19's severity. RESULTS: A total of 8 studies were included, involving 5266 patients. Among all COVID-19 patients, the total incidence of ischemic stroke was 1.76% (95% CI: 0.82-3.01). Severe patients have an increased risk of acute ischemic stroke compared with non-severe patients (RR = 3.53, 95% CI: 2.06-6.07, P < 0.0001; I2 = 12%). This association was also observed when COVID-19's severity was defined by clinical parameters (RR 2.91, 95% CI: 1.17-7.26, P = 0.02; I2 = 29%) and the need for intensive care (RR 4.47, 95% CI: 2.40-8.31, P < 0.0001; I2 = 0%). CONCLUSIONS: This meta-analysis shows that the severe course of COVID-19 is associated with an increased risk of acute ischemic stroke.


Assuntos
Isquemia Encefálica , COVID-19 , AVC Isquêmico , Acidente Vascular Cerebral , Isquemia Encefálica/complicações , Isquemia Encefálica/epidemiologia , Humanos , SARS-CoV-2 , Acidente Vascular Cerebral/epidemiologia
8.
Neurol Sci ; 41(6): 1451-1458, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32086687

RESUMO

BACKGROUND: Acute ischemic stroke leads to serious long-term disability and high mortality, especially in patients with large-vessel occlusive strokes. Nowadays, endovascular therapy is considered as an alternative treatment for these patients. Several studies have used thrombus characteristics based on non-contrast computed tomography (NCCT) and computed tomography angiography (CTA) to predict prognosis in ischemic stroke. We conducted a systematic review to identify potential imaging predictive factors for successful recanalization and improved clinical outcome after endovascular therapy in patients with large-vessel occlusion (LVO) in anterior arterial circulation. METHODS: The PubMed databases were searched for related studies reported between September 18, 2009, and September 18, 2019. RESULTS: We selected 11 studies on revascularization and 12 studies on clinical outcome. Patients with thrombus of higher Hounsfield unit (HU), shorter length, higher clot burden score, and increased thrombus permeability may achieve higher recanalization and improved clinical outcome, but the matter is still under debate. CONCLUSION: Imaging of thrombus can be used as an aseessment tool to predict the outcomes and it needs further studies in the future.


Assuntos
Arteriopatias Oclusivas/diagnóstico por imagem , Doenças Arteriais Cerebrais/diagnóstico por imagem , AVC Isquêmico/diagnóstico por imagem , Neuroimagem/normas , Avaliação de Resultados em Cuidados de Saúde/normas , Trombose/diagnóstico por imagem , Doenças Arteriais Cerebrais/complicações , Humanos , AVC Isquêmico/etiologia , Trombose/complicações
9.
Nano Lett ; 19(6): 4126-4133, 2019 06 12.
Artigo em Inglês | MEDLINE | ID: mdl-31082262

RESUMO

The details of the superconducting to quantum metal transition (SQMT) at T = 0 are an open problem that invokes great interest in the nature of this exotic and unexpected ground state (Ephron et al., 1996; Mason and Kapitulnik, 1999; Chervenak and Valles, 2000). However, the SQMT was not yet investigated in a crystalline 2D superconductor with coexisting and fluctuating quantum orders. Here, we report the observation of a SQMT in 2D ion-gel-gated 1T-TiSe2 (Li et al., 2016) driven by a magnetic field. A field-induced crossover between Bose quantum metal and vortex quantum creeping with an increasing field is observed. We discuss the interplay between superconducting and CDW fluctuations (discommensurations) and their relation to the anomalous quantum metal (AQM) phase. From our findings, gate-tunable 1T-TiSe2 emerges as a privileged platform to scrutinize, in a controlled way, the details of the SQMT, the role of coexisting fluctuating orders and, ultimately, to obtain a deeper understanding of the fate of superconductivity in strictly two-dimensional crystals near zero temperature.

10.
J Biol Chem ; 293(16): 5847-5859, 2018 04 20.
Artigo em Inglês | MEDLINE | ID: mdl-29467225

RESUMO

TMEPAI (transmembrane prostate androgen-induced protein, also called prostate transmembrane protein, androgen-induced 1 (PMEPA1)) is a type I transmembrane (TM) protein, but its cellular function is largely unknown. Here, studying factors influencing the stability of c-Maf, a critical transcription factor in multiple myeloma (MM), we found that TMEPAI induced c-Maf degradation. We observed that TMEPAI recruited NEDD4 (neural precursor cell expressed, developmentally down-regulated 4), a WW domain-containing ubiquitin ligase, to c-Maf, leading to its degradation through the proteasomal pathway. Further investigation revealed that TMEPAI interacts with NEDD4 via its conserved PY motifs. Alanine substitution or deletion of these motifs abrogated the TMEPAI complex formation with NEDD4, resulting in failed c-Maf degradation. Functionally, TMEPAI suppressed the transcriptional activity of c-Maf. Of note, increased TMEPAI expression was positively associated with the overall survival of MM patients. Moreover, TMEPAI was down-regulated in MM cells, and re-expression of TMEPAI induced MM cell apoptosis. In conclusion, this study highlights that TMEPAI decreases c-Maf stability by recruiting the ubiquitin ligase NEDD4 to c-Maf for proteasomal degradation. Our findings suggest that the restoration of functional TMEPA1 expression may represent a promising complementary therapeutic strategy for treating patients with MM.


Assuntos
Apoptose , Proteínas de Membrana/metabolismo , Mieloma Múltiplo/metabolismo , Proteólise , Proteínas Proto-Oncogênicas c-maf/metabolismo , Humanos , Mieloma Múltiplo/patologia , Ubiquitina-Proteína Ligases Nedd4/metabolismo , Mapas de Interação de Proteínas , Ubiquitinação
11.
J Am Chem Soc ; 141(6): 2288-2298, 2019 02 13.
Artigo em Inglês | MEDLINE | ID: mdl-30649864

RESUMO

Mn2+-doped ZnSe nanocrystals (Mn:ZnSe d-dots) with high optical quality-high dopant emission quantum yield with monoexponential dopant-emission decay dynamics-enable systematic and quantitative studies of temperature- and Mn2+ concentration-dependent optical properties of the dopant emission, especially its relationship with magnetic coupling. While temperature-dependent steady-state and transient dopant emission of d-dots with dilute Mn2+ concentrations originated from isolated Mn2+ ions, and can be quantitatively treated as a result of exciton-phonon coupling of isolated paramagnetic emission centers. Dopant emission of d-dots with high Mn2+ concentrations (up to 50% of Zn2+ ions being replaced by Mn2+ ions in the core nanocrystals) are found solely related to magnetically coupled Mn2+ emission. Magnetic coupling effects on steady-state dopant emission of d-dots with high Mn2+ concentrations are much stronger than those observed for doped bulk semiconductors, which is found to follow a strong and universe shell-thickness dependence for the epitaxial ZnSe and/or ZnS shells of the d-dots. By exciting the magnetically coupled Mn2+ ions directly, dopant-emission of d-dots with high Mn2+ concentrations exhibit monoexponential decay dynamics. In addition to this emission channel, a minor channel with slightly longer decay lifetime appears when the host nanocrystals with high Mn2+ concentrations are excited, which is barely visible at room temperature and increases its fraction by decreasing temperature.

12.
J Am Chem Soc ; 140(12): 4391-4400, 2018 03 28.
Artigo em Inglês | MEDLINE | ID: mdl-29494136

RESUMO

We report a new quasi-one-dimensional compound KMn6Bi5 composed of parallel nanowires crystallizing in a monoclinic space group C2/ m with a = 22.994(2) Å, b = 4.6128(3) Å, c = 13.3830(13) Å and ß = 124.578(6)°. The nanowires are infinite [Mn6Bi5]- columns each of which is composed of a nanotube of Bi atoms acting as the cladding with a nanorod of Mn atoms located in the central axis of the nanotubes. The nanorods of Mn atoms inside the Bi cladding are stabilized by Mn-Mn bonding and are defined by distorted Mn-centered cluster icosahedra of Mn13 sharing their vertices along the b axis. The [Mn6Bi5]- nanowires are linked with weak internanowire Bi-Bi bonds and charge balanced with K+ ions. The [Mn6Bi5]- nanowires were directly imaged by high-resolution transmission electron microscopy and scanning transmission electron microscopy. Magnetic susceptibility studies show one-dimensional characteristics with an antiferromagnetic transition at ∼75 K and a small average effective magnetic moment (1.56 µB/Mn for H ∥ b and 1.37 µB/Mn for H ⊥ b) of Mn from Curie-Weiss fits above 150 K. Specific heat measurements reveal an electronic specific heat coefficient γ of 6.5(2) mJ K-2(mol-Mn)-1 and a small magnetic entropy change Δ Smag ≈ 1.6 J K-1 (mol-Mn)-1 across the antiferromagnetic transition. In contrast to a metallic resistivity along the column, the resistivity perpendicular to the column shows a change from a semiconducting behavior at high temperatures to a metallic one at low temperatures, indicating an incoherent-to-coherent crossover of the intercolumn tunneling of electrons.

13.
Nano Lett ; 17(5): 3035-3039, 2017 05 10.
Artigo em Inglês | MEDLINE | ID: mdl-28415840

RESUMO

Ultrathin freestanding bismuth film is theoretically predicted to be one kind of two-dimensional topological insulators. Experimentally, the topological nature of bismuth strongly depends on the situations of the Bi films. Film thickness and interaction with the substrate often change the topological properties of Bi films. Using angle-resolved photoemission spectroscopy, scanning tunneling microscopy or spectroscopy and first-principle calculation, the properties of Bi(111) ultrathin film grown on the NbSe2 superconducting substrate have been studied. We find the band structures of the ultrathin film is quasi-freestanding, and one-dimensional edge state exists on Bi(111) film as thin as three bilayers. Superconductivity is also detected on different layers of the film and the pairing potential exhibits an exponential decay with the layer thicknesses. Thus, the topological edge state can coexist with superconductivity, which makes the system a promising platform for exploring Majorana Fermions.

14.
J Pharmacol Sci ; 134(4): 197-202, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28779993

RESUMO

S14161 is a pan-Class I PI3K inhibitor that induces blood cancer cell death, but its mechanism is largely unknown. In the present study, we evaluated the role of S14161 in autophagy, an emerging event in cell destination. Multiple myeloma cell lines RPMI-8226, OPM2, KMS11 and leukemia cell line K562 were treated with S14161. The results showed that S14161 induced autophagy as demonstrated by increased LC3-II and decreased p62, which were prevented by autophagy inhibitors including 3-methyladenine and bafilomycin A1. Mechanistic studies showed that S14161 had no effects on Vps34 expression, but increased Beclin 1 and decreased Bcl-2, two major regulators of autophagy. Furthermore, S14161 dissociated the Beclin 1/Bcl-2 complex and enhanced the formation of Beclin 1/Vps34 complex. Moreover, S14161 inhibited the mTORC1 signaling transduction. S14161 downregulated activation of mTOR and its two critical targets 4E-BP1 and p70S6K, suggesting S14161 inhibited protein synthesis. Taken together, these results demonstrated that Class I PI3K regulates autophagy by modulating protein synthesis and the Beclin 1 signaling pathway. This finding helps understanding the roles of PI3K in autophagy and cancer treatment.


Assuntos
Autofagia/efeitos dos fármacos , Proteína Beclina-1/metabolismo , Benzopiranos/farmacologia , Classe III de Fosfatidilinositol 3-Quinases/metabolismo , Neoplasias Hematológicas/patologia , Leucemia/patologia , Mieloma Múltiplo/patologia , Inibidores de Fosfoinositídeo-3 Quinase , Proteína Beclina-1/genética , Linhagem Celular Tumoral , Classe III de Fosfatidilinositol 3-Quinases/genética , Expressão Gênica/efeitos dos fármacos , Humanos , Células K562 , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Proteínas Associadas aos Microtúbulos/metabolismo , Fosfatidilinositol 3-Quinases/fisiologia , Proteínas de Ligação a RNA/metabolismo , Transdução de Sinais/efeitos dos fármacos
15.
Acta Pharmacol Sin ; 38(5): 651-659, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28260800

RESUMO

The signal transducer and activator of transcription 3 (STAT3) plays a critical role in platelet functions. This study sought to understand the effects of the STAT3 inhibitor SC99 on platelet activation and aggregation. Immunoblotting assays were applied to measure the effects of SC99 on the STAT3 signaling pathway. A ChronoLog aggregometer was used to evaluate platelet aggregation. A flow cytometer was used to evaluate P-selectin expression in the presence of SC99. AlamarBlue and Annexin-V staining were used to evaluate platelet viability and apoptosis, respectively. A fluorescence microscope was applied to analyze platelet spreading. SC99 inhibited the phosphorylation of JAK2 and STAT3 in human platelets but had no effects on the phosphorylation of AKT, p65 or Src, all of which are involved in platelet activation. Further studies revealed that SC99 inhibited human platelet aggregation induced by collagen and thrombin in a dose-dependent manner. SC99 inhibited thrombin-induced P-selectin expression and fibrinogen binding to single platelets. Moreover, SC99 inhibited platelet spreading on fibrinogen and clot retraction mediated by outside-in signaling. SC99 inhibited platelet aggregation in mice but it did not significantly prolong the bleeding time. Taken together, the present study revealed that SC99 inhibited platelet activation and aggregation as a STAT3 inhibitor. This agent can be developed as a promising treatment for thrombotic disorders.


Assuntos
Hidrazonas/farmacologia , Ativação Plaquetária/efeitos dos fármacos , Inibidores da Agregação Plaquetária/farmacologia , Agregação Plaquetária/efeitos dos fármacos , Fator de Transcrição STAT3/antagonistas & inibidores , Animais , Tempo de Sangramento , Retração do Coágulo/efeitos dos fármacos , Humanos , Hidrazonas/toxicidade , Camundongos Endogâmicos C57BL , Inibidores da Agregação Plaquetária/toxicidade , Transdução de Sinais
16.
J Am Chem Soc ; 138(7): 2170-3, 2016 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-26853632

RESUMO

We report the first nitrogen-containing iron-pnictide superconductor ThFeAsN, which is synthesized by a solid-state reaction in an evacuated container. The compound crystallizes in a ZrCuSiAs-type structure with the space group P4/nmm and lattice parameters a = 4.0367(1) Å and c = 8.5262(2) Å at 300 K. The electrical resistivity and dc magnetic susceptibility measurements indicate superconductivity at 30 K for the nominally undoped ThFeAsN.

17.
Phys Rev Lett ; 116(25): 257003, 2016 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-27391745

RESUMO

Recently, theory has predicted a Majorana zero mode (MZM) to induce spin selective Andreev reflection (SSAR), a novel magnetic property which can be used to detect the MZM. Here, spin-polarized scanning tunneling microscopy or spectroscopy has been applied to probe SSAR of MZMs in a topological superconductor of the Bi_{2}Te_{3}/NbSe_{2} heterostructure. The zero-bias peak of the tunneling differential conductance at the vortex center is observed substantially higher when the tip polarization and the external magnetic field are parallel rather than antiparallel to each other. This spin dependent tunneling effect provides direct evidence of MZM and reveals its magnetic property in addition to the zero energy modes. Our work will stimulate MZM research on these novel physical properties and, hence, is a step towards experimental study of their statistics and application in quantum computing.

18.
Nat Mater ; 13(8): 777-81, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24859644

RESUMO

A quantum critical point arises at a continuous transformation between distinct phases of matter at zero temperature. Studies in antiferromagnetic heavy-fermion materials have revealed that quantum criticality has several classes, with an unconventional type that involves a critical destruction of the Kondo entanglement. To understand such varieties, it is important to extend the materials basis beyond the usual setting of intermetallic compounds. Here we show that a nickel oxypnictide, CeNiAsO, exhibits a heavy-fermion antiferromagnetic quantum critical point as a function of either pressure or P/As substitution. At the quantum critical point, non-Fermi-liquid behaviour appears, which is accompanied by a divergent effective carrier mass. Across the quantum critical point, the low-temperature Hall coefficient undergoes a rapid sign change, suggesting a sudden jump of the Fermi surface and a destruction of the Kondo effect. Our results imply that the enormous materials basis for the oxypnictides, which has been so crucial in the search for high-temperature superconductivity, will also play a vital role in the effort to establish the universality classes of quantum criticality in strongly correlated electron systems.

19.
J Am Chem Soc ; 136(4): 1284-7, 2014 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-24428401

RESUMO

Superconductivity in low-dimensional compounds has long attracted much interest. Here we report superconductivity in a low-dimensional ternary telluride Ta4Pd3Te16 in which the repeating layers contain edge-sharing octahedrally coordinated PdTe2 chains along the crystallographic b axis. Measurements of electrical resistivity, magnetic susceptibility and specific heat on the Ta4Pd3Te16 crystals, grown via a self-flux method, consistently demonstrate bulk superconductivity at 4.6 K. Further analyses of the data indicate significant electron-electron interaction, which allows electronic Cooper pairing in the present system.

20.
J Am Chem Soc ; 136(43): 15386-93, 2014 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-25314008

RESUMO

We have synthesized a novel europium bismuth sulfofluoride, Eu3Bi2S4F4, by solid-state reactions in sealed evacuated quartz ampules. The compound crystallizes in a tetragonal lattice (space group I4/mmm, a = 4.0771(1) Å, c = 32.4330(6) Å, and Z = 2), in which CaF2-type Eu3F4 layers and NaCl-like BiS2 bilayers stack alternately along the crystallographic c axis. There are two crystallographically distinct Eu sites, Eu(1) and Eu(2) at the Wyckoff positions 4e and 2a, respectively. Our bond valence sum calculation, based on the refined structural data, indicates that Eu(1) is essentially divalent, while Eu(2) has an average valence of ∼ +2.64(5). This anomalous Eu valence state is further confirmed and supported, respectively, by Mössbauer and magnetization measurements. The Eu(3+) components donate electrons into the conduction bands that are mainly composed of Bi 6px and 6py states. Consequently, the material itself shows metallic conduction and superconducts at 1.5 K without extrinsic chemical doping.

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