Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 51
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Sci Adv ; 8(19): eabm6638, 2022 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-35559673

RESUMO

Exploiting cancer vulnerabilities is critical for the discovery of anticancer drugs. However, tumor suppressors cannot be directly targeted because of their loss of function. To uncover specific vulnerabilities for cells with deficiency in any given tumor suppressor(s), we performed genome-scale CRISPR loss-of-function screens using a panel of isogenic knockout cells we generated for 12 common tumor suppressors. Here, we provide a comprehensive and comparative dataset for genetic interactions between the whole-genome protein-coding genes and a panel of tumor suppressor genes, which allows us to uncover known and new high-confidence synthetic lethal interactions. Mining this dataset, we uncover essential paralog gene pairs, which could be a common mechanism for interpreting synthetic lethality. Moreover, we propose that some tumor suppressors could be targeted to suppress proliferation of cells with deficiency in other tumor suppressors. This dataset provides valuable information that can be further exploited for targeted cancer therapy.

2.
ACS Appl Mater Interfaces ; 14(3): 4132-4143, 2022 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-35019270

RESUMO

Efficient and long-term stable triplet-triplet annihilation upconversion (TTA-UC) can be achieved by effectively protecting the excited organic triplet ensembles from photoinduced oxygen quenching, and discovery of a new material platform that promotes TTA-UC in ambient conditions is of paramount importance for practical applications. In this study, we present the first demonstration of an organic nonparaffin phase-change material (PCM) as an air-tolerant medium for TTA-UC with a unique solid-liquid phase transition in response to temperature variation. For the proposed concept, 2,4-hexadien-1-ol is used and extensively characterized with several key features, including good solvation capacity, mild melting point (30.5 °C), and exclusive antioxidant property, enabling a high-efficiency, low-threshold, and photostable TTA-UC system without energy-intensive degassing processes. In-depth characterization reveals that the triplet diffusion among the transient species, i.e., 3sensitizer* and 3acceptor*, is efficient and well protected from oxygen quenching in both aerated liquid- and solid-phase 2,4-hexadien-1-ol. We also propose a new strategy for the nanoencapsulation of PCM by employing hollow mesoporous silica nanoparticles as vehicles. This scheme is applicable to both aqueous- and solid-phase TTA-UC systems as well as suitable for various applications, such as thermal energy storage and smart drug delivery.

3.
Kidney Res Clin Pract ; 41(2): 188-199, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34974653

RESUMO

BACKGROUND: Organ crosstalk between the kidney and the heart has been suggested. Acute kidney injury (AKI) and acute heart failure (AHF) are well-known independent risk factors for mortality in hospitalized patients. This study aimed to investigate if these conditions have an additive effect on mortality in hospitalized patients, as this has not been explored in previous studies. METHODS: We retrospectively reviewed the records of 101,804 hospitalized patients who visited two tertiary hospitals in the Republic of Korea over a period of 5 years. AKI was diagnosed using serum creatinine-based criteria, and AHF was classified using International Classification of Diseases codes within 2 weeks after admission. Patients were divided into four groups according to the two conditions. The primary outcome was all-cause mortality. RESULTS: AKI occurred in 6.8% of all patients (n = 6,920) and AHF in 1.2% (n = 1,244). Three hundred thirty-one patients (0.3%) developed both conditions while AKI alone was present in 6,589 patients (6.5%) and AHF alone in 913 patients (0.9%). Among the 5,181 patients (5.1%) who died, 20.8% died within 1 month. The hazard ratio for 1-month mortality was 29.23 in patients with both conditions, 15.00 for AKI only, and 3.39 for AHF only. The relative excess risk of interaction was 11.85 (95% confidence interval, 2.43-21.27), and was more prominent in patients aged <75 years and those without chronic heart failure. CONCLUSION: AKI and AHF have a detrimental additive effect on short-term mortality in hospitalized patients.

4.
Nature ; 600(7889): 439-443, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34912084

RESUMO

Fractional Chern insulators (FCIs) are lattice analogues of fractional quantum Hall states that may provide a new avenue towards manipulating non-Abelian excitations. Early theoretical studies1-7 have predicted their existence in systems with flat Chern bands and highlighted the critical role of a particular quantum geometry. However, FCI states have been observed only in Bernal-stacked bilayer graphene (BLG) aligned with hexagonal boron nitride (hBN)8, in which a very large magnetic field is responsible for the existence of the Chern bands, precluding the realization of FCIs at zero field. By contrast, magic-angle twisted BLG9-12 supports flat Chern bands at zero magnetic field13-17, and therefore offers a promising route towards stabilizing zero-field FCIs. Here we report the observation of eight FCI states at low magnetic field in magic-angle twisted BLG enabled by high-resolution local compressibility measurements. The first of these states emerge at 5 T, and their appearance is accompanied by the simultaneous disappearance of nearby topologically trivial charge density wave states. We demonstrate that, unlike the case of the BLG/hBN platform, the principal role of the weak magnetic field is merely to redistribute the Berry curvature of the native Chern bands and thereby realize a quantum geometry favourable for the emergence of FCIs. Our findings strongly suggest that FCIs may be realized at zero magnetic field and pave the way for the exploration and manipulation of anyonic excitations in flat moiré Chern bands.

5.
Nucleic Acids Res ; 49(14): 8214-8231, 2021 08 20.
Artigo em Inglês | MEDLINE | ID: mdl-34320214

RESUMO

Because of essential roles of DNA damage response (DDR) in the maintenance of genomic integrity, cellular homeostasis, and tumor suppression, targeting DDR has become a promising therapeutic strategy for cancer treatment. However, the benefits of cancer therapy targeting DDR are limited mainly due to the lack of predictive biomarkers. To address this challenge, we performed CRISPR screens to search for genetic vulnerabilities that affect cells' response to DDR inhibition. By undertaking CRISPR screens with inhibitors targeting key DDR mediators, i.e. ATR, ATM, DNAPK and CHK1, we obtained a global and unbiased view of genetic interactions with DDR inhibition. Specifically, we identified YWHAE loss as a key determinant of sensitivity to CHK1 inhibition. We showed that KLHL15 loss protects cells from DNA damage induced by ATM inhibition. Moreover, we validated that APEX1 loss sensitizes cells to DNAPK inhibition. Additionally, we compared the synergistic effects of combining different DDR inhibitors and found that an ATM inhibitor plus a PARP inhibitor induced dramatic levels of cell death, probably through promoting apoptosis. Our results enhance the understanding of DDR pathways and will facilitate the use of DDR-targeting agents in cancer therapy.


Assuntos
Proteínas 14-3-3/genética , Proteínas Mutadas de Ataxia Telangiectasia/genética , Quinase 1 do Ponto de Checagem/genética , Dano ao DNA/genética , Proteína Quinase Ativada por DNA/genética , Apoptose/efeitos dos fármacos , Proteínas Mutadas de Ataxia Telangiectasia/antagonistas & inibidores , Sistemas CRISPR-Cas/genética , Quinase 1 do Ponto de Checagem/antagonistas & inibidores , Instabilidade Genômica/genética , Humanos , Proteínas dos Microfilamentos/genética , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia
6.
Nature ; 595(7868): 526-531, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34290431

RESUMO

Moiré quantum matter has emerged as a materials platform in which correlated and topological phases can be explored with unprecedented control. Among them, magic-angle systems constructed from two or three layers of graphene have shown robust superconducting phases with unconventional characteristics1-5. However, direct evidence of unconventional pairing remains to be experimentally demonstrated. Here we show that magic-angle twisted trilayer graphene exhibits superconductivity up to in-plane magnetic fields in excess of 10 T, which represents a large (2-3 times) violation of the Pauli limit for conventional spin-singlet superconductors6,7. This is an unexpected observation for a system that is not predicted to have strong spin-orbit coupling. The Pauli-limit violation is observed over the entire superconducting phase, which indicates that it is not related to a possible pseudogap phase with large superconducting amplitude pairing. Notably, we observe re-entrant superconductivity at large magnetic fields, which is present over a narrower range of carrier densities and displacement fields. These findings suggest that the superconductivity in magic-angle twisted trilayer graphene is likely to be driven by a mechanism that results in non-spin-singlet Cooper pairs, and that the external magnetic field can cause transitions between phases with potentially different order parameters. Our results demonstrate the richness of moiré superconductivity and could lead to the design of next-generation exotic quantum matter.

7.
Front Chem ; 9: 699284, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34169061

RESUMO

The localized surface plasmon resonance of metallic nanoparticles has attracted much attention owing to its unique characteristics, including the enhancement of signals in sensors and photothermal effects. In particular, hollow gold nanostructures are highly promising for practical applications, with significant advantages being found in their material properties and structures: 1) the interaction between the outer surface plasmon mode and inner cavity mode leads to a greater resonance, allowing it to absorb near-infrared light, which can readily penetrate tissue; 2) it has anti-corrosiveness and good biocompatibility, which makes it suitable for biomedical applications; 3) it shows a reduced net density and large surface area, allowing the possibility of nanocarriers for drug delivery. In this review, we present information on the classification, characteristics, and synthetic methods of hollow gold nanostructures; discuss the recent advances in hollow gold nanostructures in biomedical applications, including biosensing, bioimaging, photothermal therapy, and drug delivery; and report on the existing challenges and prospects for hollow gold nanostructures.

8.
Nat Nanotechnol ; 16(7): 769-775, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33941915

RESUMO

Magic-angle twisted bilayer graphene (MATBG) has recently emerged as a highly tunable two-dimensional material platform exhibiting a wide range of phases, such as metal, insulator and superconductor states. Local electrostatic control over these phases may enable the creation of versatile quantum devices that were previously not achievable in other single-material platforms. Here we engineer Josephson junctions and tunnelling transistors in MATBG, solely defined by electrostatic gates. Our multi-gated device geometry offers independent control of the weak link, barriers and tunnelling electrodes. These purely two-dimensional MATBG Josephson junctions exhibit non-local electrodynamics in a magnetic field, in agreement with the Pearl theory for ultrathin superconductors. Utilizing the intrinsic bandgaps of MATBG, we also demonstrate monolithic edge tunnelling spectroscopy within the same MATBG devices and measure the energy spectrum of MATBG in the superconducting phase. Furthermore, by inducing a double-barrier geometry, the devices can be operated as a single-electron transistor, exhibiting Coulomb blockade. With versatile functionality encompassed within a single material, these MATBG tunnelling devices may find applications in graphene-based tunable superconducting qubits, on-chip superconducting circuits and electromagnetic sensing.

9.
Science ; 372(6539): 264-271, 2021 04 16.
Artigo em Inglês | MEDLINE | ID: mdl-33859029

RESUMO

Strongly interacting electrons in solid-state systems often display multiple broken symmetries in the ground state. The interplay between different order parameters can give rise to a rich phase diagram. We report on the identification of intertwined phases with broken rotational symmetry in magic-angle twisted bilayer graphene (TBG). Using transverse resistance measurements, we find a strongly anisotropic phase located in a "wedge" above the underdoped region of the superconducting dome. Upon its crossing with the superconducting dome, a reduction of the critical temperature is observed. Furthermore, the superconducting state exhibits an anisotropic response to a direction-dependent in-plane magnetic field, revealing nematic ordering across the entire superconducting dome. These results indicate that nematic fluctuations might play an important role in the low-temperature phases of magic-angle TBG.

10.
Nature ; 592(7852): 43-48, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33790447

RESUMO

Interaction-driven spontaneous symmetry breaking lies at the heart of many quantum phases of matter. In moiré systems, broken spin/valley 'flavour' symmetry in flat bands underlies the parent state from which correlated and topological ground states ultimately emerge1-10. However, the microscopic mechanism of such flavour symmetry breaking and its connection to the low-temperature phases are not yet understood. Here we investigate the broken-symmetry many-body ground state of magic-angle twisted bilayer graphene (MATBG) and its nontrivial topology using simultaneous thermodynamic and transport measurements. We directly observe flavour symmetry breaking as pinning of the chemical potential at all integer fillings of the moiré superlattice, demonstrating the importance of flavour Hund's coupling in the many-body ground state. The topological nature of the underlying flat bands is manifested upon breaking time-reversal symmetry, where we measure energy gaps corresponding to Chern insulator states with Chern numbers 3, 2, 1 at filling factors 1, 2, 3, respectively, consistent with flavour symmetry breaking in the Hofstadter butterfly spectrum of MATBG. Moreover, concurrent measurements of resistivity and chemical potential provide the temperature-dependent charge diffusivity of MATBG in the strange-metal regime11-a quantity previously explored only in ultracold atoms12. Our results bring us one step closer to a unified framework for understanding interactions in the topological bands of MATBG, with and without a magnetic field.

11.
Nature ; 592(7853): 214-219, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33828314

RESUMO

In the 1950s, Pomeranchuk1 predicted that, counterintuitively, liquid 3He may solidify on heating. This effect arises owing to high excess nuclear spin entropy in the solid phase, where the atoms are spatially localized. Here we find that an analogous effect occurs in magic-angle twisted bilayer graphene2-6. Using both local and global electronic entropy measurements, we show that near a filling of one electron per moiré unit cell, there is a marked increase in the electronic entropy to about 1kB per unit cell (kB is the Boltzmann constant). This large excess entropy is quenched by an in-plane magnetic field, pointing to its magnetic origin. A sharp drop in the compressibility as a function of the electron density, associated with a reset of the Fermi level back to the vicinity of the Dirac point, marks a clear boundary between two phases. We map this jump as a function of electron density, temperature and magnetic field. This reveals a phase diagram that is consistent with a Pomeranchuk-like temperature- and field-driven transition from a low-entropy electronic liquid to a high-entropy correlated state with nearly free magnetic moments. The correlated state features an unusual combination of seemingly contradictory properties, some associated with itinerant electrons-such as the absence of a thermodynamic gap, metallicity and a Dirac-like compressibility-and others associated with localized moments, such as a large entropy and its disappearance under a magnetic field. Moreover, the energy scales characterizing these two sets of properties are very different: whereas the compressibility jump has an onset at a temperature of about 30 kelvin, the bandwidth of magnetic excitations is about 3 kelvin or smaller. The hybrid nature of the present correlated state and the large separation of energy scales have implications for the thermodynamic and transport properties of the correlated states in twisted bilayer graphene.

12.
Nature ; 590(7845): 249-255, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33526935

RESUMO

Moiré superlattices1,2 have recently emerged as a platform upon which correlated physics and superconductivity can be studied with unprecedented tunability3-6. Although correlated effects have been observed in several other moiré systems7-17, magic-angle twisted bilayer graphene remains the only one in which robust superconductivity has been reproducibly measured4-6. Here we realize a moiré superconductor in magic-angle twisted trilayer graphene (MATTG)18, which has better tunability of its electronic structure and superconducting properties than magic-angle twisted bilayer graphene. Measurements of the Hall effect and quantum oscillations as a function of density and electric field enable us to determine the tunable phase boundaries of the system in the normal metallic state. Zero-magnetic-field resistivity measurements reveal that the existence of superconductivity is intimately connected to the broken-symmetry phase that emerges from two carriers per moiré unit cell. We find that the superconducting phase is suppressed and bounded at the Van Hove singularities that partially surround the broken-symmetry phase, which is difficult to reconcile with weak-coupling Bardeen-Cooper-Schrieffer theory. Moreover, the extensive in situ tunability of our system allows us to reach the ultrastrong-coupling regime, characterized by a Ginzburg-Landau coherence length that reaches the average inter-particle distance, and very large TBKT/TF values, in excess of 0.1 (where TBKT and TF are the Berezinskii-Kosterlitz-Thouless transition and Fermi temperatures, respectively). These observations suggest that MATTG can be electrically tuned close to the crossover to a two-dimensional Bose-Einstein condensate. Our results establish a family of tunable moiré superconductors that have the potential to revolutionize our fundamental understanding of and the applications for strongly coupled superconductivity.

13.
Alzheimers Dement ; 17 Suppl 7: e049487, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35109531

RESUMO

BACKGROUND: Family caregivers of dementia patient are at higher risk for perceived burden of caregiving and stress from COVID-19 than general population. The current study examines the current status COVID-19-specific stress, anxiety, burden of caregiving and health related- quality of life that may be significantly deteriorated for family caregivers in understanding cargiver burden and their stress experienced due to the COVID-19 pandemic. METHOD: About two hundred family caregivers aged 20-79 years in the South Korea will be recruited to collect the data on their stress, anxiety related to ongoing COVID-19, burden of caregiving, and health-related Quality of life in an online or telephone survey. RESULT: The present study will show that the current status of perceived stress, anxiety, burden of cargiving of person with dementia associated with COVID-19 pandemic. The increased stress, anixety, and burden of cargiving could negatively affect their health-related quality of life. The specific study findings will be demonstrated in poster presentation of the conference. CONCLUSION: The present study will be demonstrated that the association between COVID-19-specific stress, burden of caregiving, and health related quality of life for family caregivers of dementia patient. This study findings will encourage future development of public interventions to address burden of caregiving in family caregivers with COVID-19 pandemic.

14.
Oncogenesis ; 9(9): 85, 2020 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-32989218

RESUMO

The ERK1/2 pathway is one of the most commonly dysregulated pathways in human cancers and controls many vital cellular processes. Although many ERK1/2 kinase substrates have been identified, the diversity of ERK1/2 mediated processes suggests the existence of additional targets. Here, we identified Deoxyhypusine synthase (DHPS), an essential hypusination enzyme regulating protein translation, as a major and direct-binding protein of ERK1/2. Further experiments showed that ERK1/2 phosphorylate DHPS at Ser-233 site. The Ser-233 phosphorylation of DHPS by ERK1/2 is important for its function in cell proliferation. Moreover, we found that higher DHPS expression correlated with poor prognosis in lung adenocarcinoma and increased resistance to inhibitors of the ERK1/2 pathway. In summary, our results suggest that ERK1/2-mediated DHPS phosphorylation is an important mechanism that underlies protein translation and that DHPS expression is a potent biomarker of response to therapies targeting ERK1/2-pathway.

15.
Nanoscale ; 12(32): 16895-16900, 2020 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-32766647

RESUMO

In this study, we propose a rational route to create wrinkling patterns with individually controllable location and direction in thin polymer films. Optical and atomic force microscopy analysis confirmed the formation of straight wrinkles with a typical width of 1.51 to 1.55 µm and a height of 60 to 65 nm. Confocal fluorescence microscopy revealed that each wrinkle produces a continuous hollow channel that interconnects neighboring holes in the polymer film, demonstrating potential applications as nanoscale fluidic channel and reactor. Moreover, we propose a mechanism that considers the elastic deformation energy and interface energies as crucial parameters that govern the mechanical instabilities, which provides scaling relationships between the height, width, and thickness of the wrinkles. This offers additional opportunities for control over the size and aspect ratio of the wrinkles and channels.

16.
Nature ; 583(7816): E27, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32612239

RESUMO

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

17.
J Exerc Rehabil ; 16(3): 279-285, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32724786

RESUMO

This study aimed to provide fundamental data of core balance training (CBT) on Cobb angle and isokinetic torque and balance in unilateral exercised athletes. Forty-eight subjects were divided by control group (CON; n=16), non-CBT exercised group in unilateral handed athletes (NEG, n=16), and CBT exercised group in unilateral handed athletes (EG, n=16), respectively. Although the group by time interaction in the Cobb angle and in the isokinetic torque were not significantly changed in the EG, the balance of the EG showed significantly improved. As conclusions, these results informed that the 16-week CBT would provide a positive effect on the balance except for the Cobb angle and the isokinetic torque.

18.
Nature ; 583(7815): 215-220, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32499644

RESUMO

The recent discovery of correlated insulator states and superconductivity in magic-angle twisted bilayer graphene1,2 has enabled the experimental investigation of electronic correlations in tunable flat-band systems realized in twisted van der Waals heterostructures3-6. This novel twist angle degree of freedom and control should be generalizable to other two-dimensional systems, which may exhibit similar correlated physics behaviour, and could enable techniques to tune and control the strength of electron-electron interactions. Here we report a highly tunable correlated system based on small-angle twisted bilayer-bilayer graphene (TBBG), consisting of two rotated sheets of Bernal-stacked bilayer graphene. We find that TBBG exhibits a rich phase diagram, with tunable correlated insulator states that are highly sensitive to both the twist angle and the application of an electric displacement field, the latter reflecting the inherent polarizability of Bernal-stacked bilayer graphene7,8. The correlated insulator states can be switched on and off by the displacement field at all integer electron fillings of the moiré unit cell. The response of these correlated states to magnetic fields suggests evidence of spin-polarized ground states, in stark contrast to magic-angle twisted bilayer graphene. Furthermore, in the regime of lower twist angles, TBBG shows multiple sets of flat bands near charge neutrality, resulting in numerous correlated states corresponding to half-filling of each of these flat bands, all of which are tunable by the displacement field as well. Our results could enable the exploration of twist-angle- and electric-field-controlled correlated phases of matter in multi-flat-band twisted superlattices.

20.
Oncogene ; 39(16): 3245-3257, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32086441

RESUMO

ATR and CHK1 play key roles in the protection and recovery of the stalled replication forks. Claspin, an adaptor for CHK1 activation, is essential for DNA damage signaling and efficient replication fork progression. Here, we show that tristetraprolin (TTP), an mRNA-binding protein, can modulate the replication stress response via stabilization of Claspin mRNA. TTP depletion compromised specifically in the phosphorylation of CHK1, but not p53 or H2AX among other ATR substrates, and produced CHK1-defective replication phenotypes including accumulation of stalled replication forks. Importantly, the expression of siRNA-resistant TTP in TTP-deficient cells restored CHK1 phosphorylation and reduced the number of stalled replication forks as close to the control cells. Besides, we found that TTP was required for efficient replication fork progression even in the absence of exogenous DNA damage in a Claspin-dependent manner. Mechanistically, TTP was able to bind to the 3'-untranslated region of Claspin mRNA to increase the stability of Claspin mRNA which eventually contributed to the subsequent ATR-CHK1 activation upon DNA damage. Taken together, our results revealed an intimate link between TTP-dependent Claspin mRNA stability and ATR-CHK1-dependent replication fork stability to maintain replication fork integrity and chromosomal stability.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Replicação do DNA/genética , Estabilidade de RNA/genética , Tristetraprolina/genética , Regiões 3' não Traduzidas/genética , Células A549 , Proteínas Mutadas de Ataxia Telangiectasia/genética , Quinase 1 do Ponto de Checagem/genética , Instabilidade Cromossômica/genética , Proteínas de Ligação a DNA/genética , Células Epiteliais/metabolismo , Células HCT116 , Histonas/genética , Humanos , RNA Mensageiro/genética , Estresse Fisiológico/genética , Proteína Supressora de Tumor p53/genética
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...