An electric molecular motor Zhang, Long; Qiu, Yunyan; Liu, Wei-Guang ...
Nature (London),
01/2023, Letnik:
613, Številka:
7943
Journal Article
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Macroscopic electric motors continue to have a large impact on almost every aspect of modern society. Consequently, the effort towards developing molecular motors
that can be driven by electricity ...could not be more timely. Here we describe an electric molecular motor based on a 3catenane
, in which two cyclobis(paraquat-p-phenylene)
(CBPQT
) rings are powered by electricity in solution to circumrotate unidirectionally around a 50-membered loop. The constitution of the loop ensures that both rings undergo highly (85%) unidirectional movement under the guidance of a flashing energy ratchet
, whereas the interactions between the two rings give rise to a two-dimensional potential energy surface (PES) similar to that shown by F
F
ATP synthase
. The unidirectionality is powered by an oscillating
voltage
or external modulation of the redox potential
. Initially, we focused our attention on the homologous 2catenane, only to find that the kinetic asymmetry was insufficient to support unidirectional movement of the sole ring. Accordingly, we incorporated a second CBPQT
ring to provide further symmetry breaking by interactions between the two mobile rings. This demonstration of electrically driven continual circumrotatory motion of two rings around a loop in a 3catenane is free from the production of waste products and represents an important step towards surface-bound
electric molecular motors.
2D layered materials with broken inversion symmetry are being extensively pursued as spin source layers to realize high‐efficiency magnetic switching. Such low‐symmetry layered systems are, however, ...scarce. In addition, most layered magnets with perpendicular magnetic anisotropy show a low Curie temperature. Here, the experimental observation of spin–orbit torque magnetization self‐switching at room temperature in a layered polar ferromagnetic metal, Fe2.5Co2.5GeTe2 is reported. The spin–orbit torque is generated from the broken inversion symmetry along the c‐axis of the crystal. These results provide a direct pathway toward applicable 2D spintronic devices.
In conventional switching heterostructures based on spin‐orbit torque (SOT), a spin source material with strong spin‐orbit coupling or broken inversion symmetry is typically required to generate SOT when a charge current is applied. In this study, we achieved current‐induced self‐switching of magnetization at room temperature using a layered polar magnetic metal, Fe2.5Co2.5GeTe2, thereby greatly simplifying the structure for magnetization switching.
The BET family of proteins consists of BRD2, BRD3, BRD4, and BRDt. Each protein contains two distinct bromodomains (BD1 and BD2). BET family bromodomain inhibitors under clinical development for ...oncology bind to each of the eight bromodomains with similar affinities. We hypothesized that it may be possible to achieve an improved therapeutic index by selectively targeting subsets of the BET bromodomains. Both BD1 and BD2 are highly conserved across family members (>70% identity), whereas BD1 and BD2 from the same protein exhibit a larger degree of divergence (∼40% identity), suggesting selectivity between BD1 and BD2 of all family members would be more straightforward to achieve. Exploiting the Asp144/His437 and Ile146/Val439 sequence differences (BRD4 BD1/BD2 numbering) allowed the identification of compound 27 demonstrating greater than 100-fold selectivity for BRD4 BD2 over BRD4 BD1. Further optimization to improve BD2 selectivity and oral bioavailability resulted in the clinical development compound 46 (ABBV-744).
The BET family of proteins consists of BRD2, BRD3, BRD4, and BRDt. Each protein contains two distinct bromodomains (BD1 and BD2). BET family bromodomain inhibitors under clinical development for ...oncology bind to each of the eight bromodomains with similar affinities. We hypothesized that it may be possible to achieve an improved therapeutic index by selectively targeting subsets of the BET bromodomains. Both BD1 and BD2 are highly conserved across family members (>70% identity), whereas BD1 and BD2 from the same protein exhibit a larger degree of divergence (∼40% identity), suggesting selectivity between BD1 and BD2 of all family members would be more straightforward to achieve. Exploiting the Asp144/His437 and Ile146/Val439 sequence differences (BRD4 BD1/BD2 numbering) allowed the identification of compound
demonstrating greater than 100-fold selectivity for BRD4 BD2 over BRD4 BD1. Further optimization to improve BD2 selectivity and oral bioavailability resulted in the clinical development compound
(ABBV-744).
Recent J-TEXT research has highlighted the significance of the role that non-axisymmetric magnetic perturbations, so called three-dimensional (3D) magnetic perturbation (MP) fields, play in a ...fundamentally 2D concept, i.e. tokamaks. This paper presents the J-TEXT results achieved over the last two years, especially on the impacts of 3D MP fields on magnetohydrodynamic instabilities, plasma disruptions and plasma turbulence transport. On J-TEXT, the resonant MP (RMP) system, capable of providing either a static or a high frequency (up to 8 kHz) rotating RMP field, has been upgraded by adding a new set of 12 in-vessel saddle coils. The shattered pellet injection system was built in J-TEXT in the spring of 2018. The new capabilities advance J-TEXT to be at the forefront of international magnetic fusion facilities, allowing flexible study of 3D effects and disruption mitigation in a tokamak. The fast rotating RMP field has been successfully applied for avoidance of mode locking and the prevention of plasma disruption. A new control strategy, which applies pulsed RMP to the tearing mode only during the accelerating phase region, was proved by nonlinear numerical modelling to be efficient in accelerating mode rotation and even completely suppresses the mode. Remarkably, the rotating tearing mode was completely suppressed by the electrode biasing. The impacts of 3D magnetic topology on the turbulence has been investigated on J-TEXT. It is found that the fluctuations of electron density, electron temperature and plasma potential can be significantly modulated by the island structure, and a larger fluctuation level appears at the X-point of islands. The suppression of runaway electrons during disruptions is essential to the operation of ITER, and it has been reached by utilizing the 3D magnetic perturbations on J-TEXT. This may provide an alternative mechanism of runaway suppression for large-scale tokamaks and ITER.
Tumor necrosis factor-alpha (TNF-alpha) is a cytokine that has an important role in immunity and inflammation by inducing cellular responses such as apoptosis. The transcription factor nuclear ...factor-kappaB (NF-kappaB) can paradoxically suppress and promote apoptosis in response to TNF-alpha. In this study, we found that p53 upregulated modulator of apoptosis (PUMA), a p53 downstream target and a BH3-only Bcl-2 family member, is directly regulated by NF-kappaB in response to TNF-alpha. TNF-alpha treatment led to increases in PUMA mRNA and protein levels in human colon cancer cells. The induction of PUMA was p53 independent, and mediated by the p65 component of NF-kappaB through a kappaB site in the PUMA promoter. The apoptotic effect of PUMA induction by TNF-alpha was unmasked by depleting the antiapoptotic protein Bcl-X(L). In mice, PUMA was also induced by TNF-alpha in an NF-kappaB-dependent manner. TNF-alpha-induced apoptosis in a variety of tissues and cell types, including small intestinal epithelial cells, hepatocytes, and thymocytes, was markedly reduced in PUMA-deficient mice. Collectively, these results demonstrated that PUMA is a direct target of NF-kappaB and mediates TNF-alpha-induced apoptosis in vitro and in vivo.
The aim of this study was to investigate the mechanism of linezolid resistance and evaluate the risk factors for linezolid-resistant
(LZR-Efa) infections.
A total of 730
isolates were collected, and ...whole-genome sequencing and bioinformatics analysis were performed. Meanwhile, risk factors related to linezolid resistance were analyzed by binary logistic regression.
Twenty-six LZR-Efa were isolated from various clinical samples, and 24 isolates were multidrug resistant. Four isolates were daptomycin nonsusceptible, while all LZR-Efa were susceptible to vancomycin. Thirteen different sequence types (STs) were identified, and the most prevalent type was ST16 (23.1%). The genes
,
, and
were identified in all isolates. A total of 23
were positive for
gene, and six amino acids mutations were identified among 18 LZR-Efa in OptrA. The 23S rRNA mutation was found in 16 LZR-Efa isolates. However, the presence of
was not identified. Furthermore, there were 41 virulence genes detected, and 10 genes (
,
,
,
,
,
,
,
,
, and
) were found in all isolates. A total of nine isolates were positive for multiple virulent factors (
,
,
,
,
, and
). There was no difference in the number of virulence factors among different specimens (
=0.825). It is of note that all patients had not been prescribed linezolid or traveled abroad previously. Moreover, previous use of carbapenems was a risk factor for LZR-Efa infections.
The main trends of LZR-Efa, with lower level of resistance, were sporadic mainly in the department of surgery.
and 23S rRNA were the main resistance mechanisms. In addition, carbapenems use was an independent predictor of LZR-Efa infections.
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