Although the conventional activities of p53 such as cell cycle arrest, senescence, and apoptosis are well accepted as the major checkpoints in stress responses, accumulating evidence implicates the ...importance of other tumor suppression mechanisms. Among these unconventional activities, an iron-dependent form of non-apoptotic cell death, termed ferroptosis, attracts great interest. Unlike apoptotic cell death, activation of p53 alone is not sufficient to induce ferroptosis directly; instead, through its metabolic targets, p53 is able to modulate the ferroptosis response in the presence of ferroptosis inducers such as GPX4 inhibitors or high levels of ROS. Here, we review the role of ferroptosis in p53-mediated tumor suppression, with a focus on what cellular factors are critical for p53-dependent ferroptosis during tumor suppression and how p53 modulates both the canonical (GPX4-dependent) and the non-canonical (GPX4-independent) ferroptosis pathways. We also discuss the possibility of targeting p53-mediated ferroptotic responses for the treatment of human cancers and potentially, other diseases.
A
bstract
In this paper we discuss correlation function computations in massive topological Landau-Ginzburg orbifolds, extending old results of Vafa 1. We then apply these computations to provide ...further tests of the nonabelian mirrors proposal and two-dimensional Hori-Seiberg dualities with (
S
)
O
±
gauge groups and their mirrors.
Although cell-cycle arrest, senescence, and apoptosis are established mechanisms of tumor suppression, accumulating evidence reveals that ferroptosis, an iron-dependent, nonapoptotic form of cell ...death, represents a new regulatory pathway in suppressing tumor development. Ferroptosis is triggered by lipid peroxidation and is tightly regulated by SLC7A11, a key component of the cystine-glutamate antiporter. Although many studies demonstrate the importance of transcriptional regulation of SLC7A11 in ferroptotic responses, it remains largely unknown how the stability of SLC7A11 is controlled in human cancers. In this study, we utilized biochemial purification to identify the ubiquitin hydrolase OTUB1 as a key factor in modulating SLC7A11 stability. OTUB1 directly interacted with and stabilized SLC7A11; conversely, OTUB1 knockdown diminished SLC7A11 levels in cancer cells. OTUB1 was overexpressed in human cancers, and inactivation of OTUB1 destabilized SLC7A11 and led to growth suppression of tumor xenografts in mice, which was associated with reduced activation of ferroptosis. Notably, overexpression of the cancer stem cell marker CD44 enhanced the stability of SLC7A11 by promoting the interaction between SLC7A11 and OTUB1; depletion of CD44 partially abrogated this interaction. CD44 expression suppressed ferroptosis in cancer cells in an OTUB1-dependent manner. Together, these results show that OTUB1 plays an essential role in controlling the stability of SLC7A11 and the CD44-mediated effects on ferroptosis in human cancers. SIGNIFICANCE: This study identifies OTUB1 as a key regulator of ferroptosis and implicates it as a potential target in cancer therapy.
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Inorganic cesium lead iodide perovskite CsPbI3 is attracting great attention as a light absorber for single or multi‐junction photovoltaics due to its outstanding thermal stability and proper band ...gap. However, the device performance of CsPbI3‐based perovskite solar cells (PSCs) is limited by the unsatisfactory crystal quality and thus severe non‐radiative recombination. Here, vacuum‐assisted thermal annealing (VATA) is demonstrated as an effective approach for controlling the morphology and crystallinity of the CsPbI3 perovskite films formed from the precursors of PbI2, CsI, and dimethylammonium iodide (DMAI). By this method, a large‐area and high‐quality CsPbI3 film is obtained, exhibiting a much reduced trap‐state density with prolonged charge lifetime. Consequently, the solar cell efficiency is raised from 17.26 to 20.06 %, along with enhanced stability. The VATA would be an effective approach for fabricating high‐performance thin‐film CsPbI3 perovskite optoelectronics.
A vacuum‐assisted thermal annealing approach is employed for the fabrication of CsPbI3 perovskite films with full surface coverage and enhanced crystallization. The resultant CsPbI3 perovskite solar cells exhibit a power conversion efficiency (PCE) as high as 20.06 %, along with enhanced long‐term stability.
Based on the no-outflow assumption, we investigate steady-state, axisymmetric, optically thin accretion flows in spherical coordinates. By comparing the vertically integrated advective cooling rate ...with the viscous heating rate, we find that the former is generally less than 30% of the latter, which indicates that the advective cooling itself cannot balance the viscous heating. As a consequence, for radiatively inefficient flows with low accretion rates such as M <, ~ 10 super(-3) M sub(Edd), where M sub(Edd) is the Eddington accretion rate, the viscous heating rate will be larger than the sum of the advective cooling rate and the radiative cooling one. Thus, no thermal equilibrium can be established under the no-outflow assumption. We therefore argue that in such cases outflows ought to occur and take away more than 70% of the thermal energy generated by viscous dissipation. Similarly, for optically thick flows with extremely large accretion rates such as M > ~ 10 M sub(Edd), outflows should also occur owing to the limited advection and the low efficiency of radiative cooling. Our results may help to understand the mechanism of outflows found in observations and numerical simulations.
Nearly all infectious agents contain DNA or RNA genomes, making sequencing an attractive approach for pathogen detection. The cost of high-throughput or next-generation sequencing has been reduced by ...several orders of magnitude since its advent in 2004, and it has emerged as an enabling technological platform for the detection and taxonomic characterization of microorganisms in clinical samples from patients. This review focuses on the application of untargeted metagenomic next-generation sequencing to the clinical diagnosis of infectious diseases, particularly in areas in which conventional diagnostic approaches have limitations. The review covers (
a
) next-generation sequencing technologies and common platforms, (
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) next-generation sequencing assay workflows in the clinical microbiology laboratory, (
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) bioinformatics analysis of metagenomic next-generation sequencing data, (
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) validation and use of metagenomic next-generation sequencing for diagnosing infectious diseases, and (
e
) significant case reports and studies in this area. Next-generation sequencing is a new technology that has the promise to enhance our ability to diagnose, interrogate, and track infectious diseases.
ABSTRACT
We propose a compact binary model with an eccentric orbit to explain periodically active fast radio burst (FRB) sources, where the system consists of a neutron star (NS) with strong dipolar ...magnetic fields and a magnetic white dwarf (WD). In our model, the WD fills its Roche lobe at periastron, and mass transfer occurs from the WD to the NS around this point. The accreted material may be fragmented into a number of parts, which arrive at the NS at different times. The fragmented magnetized material may trigger magnetic reconnection near the NS surface. The electrons can be accelerated to an ultrarelativistic speed, and therefore the curvature radiation of the electrons can account for the burst activity. In this scenario, the duty cycle of burst activity is related to the orbital period of the binary. We show that such a model may work for duty cycles roughly from 10 min to 2 d. For the recently reported 16.35-d periodicity of FRB 180916.J0158 + 65, our model does not naturally explain such a long duty cycle, since an extremely high eccentricity (e > 0.95) is required.
A nickel‐catalyzed three‐component reaction for the synthesis of difluoroalkylated compounds through tandem difluoroalkylation‐arylation of enamides has been developed. The reaction tolerates a ...variety of arylboronic acids and widely available difluoroalkyl bromides, and even the relatively inert substrate chlorodifluoroacetate. The significant advantages of this protocol are the low‐cost nickel catalyst, synthetic convenience, excellent functional‐group compatibility and high reaction efficiency.
All about efficiency: The title reaction tolerates a variety of arylboronic acids and widely available difluoroalkyl bromides, and even the relatively inert substrate chlorodifluoroacetate. The protocol provides a highly efficient method for the catalytic synthesis of difluoroalkylated compounds.
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