Although ARF can suppress tumor growth by activating p53 function, the mechanisms by which it suppresses tumor growth independently of p53 are not well understood. Here, we identified ARF as a key ...regulator of nuclear factor E2-related factor 2 (NRF2) through complex purification. ARF inhibits the ability of NRF2 to transcriptionally activate its target genes, including SLC7A11, a component of the cystine/glutamate antiporter that regulates reactive oxygen species (ROS)-induced ferroptosis. As a consequence, ARF expression sensitizes cells to ferroptosis in a p53-independent manner while ARF depletion induces NRF2 activation and promotes cancer cell survival in response to oxidative stress. Moreover, the ability of ARF to induce p53-independent tumor growth suppression in mouse xenograft models is significantly abrogated upon NRF2 overexpression. These results demonstrate that NRF2 is a major target of p53-independent tumor suppression by ARF and also suggest that the ARF-NRF2 interaction acts as a new checkpoint for oxidative stress responses.
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•ARF interacts with NRF2 both in vitro and in vivo•ARF inhibits the ability of NRF2 to activate its target genes•The ARF-NRF2 interaction is critical for ferroptosis in p53 null cells•NRF2 is a major target for p53-independent tumor suppression by ARF
Chen et al. identified ARF as a key regulator of NRF2-mediated activation of SLC7A11, a component of the cystine/glutamate antiporter that regulates reactive oxygen species (ROS)-induced ferroptosis. They showed that the ARF-NRF2 interaction is critical for p53-independent ferroptosis and tumor suppression induced by ARF.
Herein, we developed a new procedure on 1,2‐dicarbonylative cyclization of 4‐aryl‐1‐butenes with alkyl bromides. Using simple copper catalyst, two molecules of carbon monoxide were introduced into ...the double bond with the formation of four new C−C bonds and a new ring. Various α‐tetralones and 2,3‐dihydroquinolin‐4‐ones were formed in moderate to good yields.
Here, we have described a new copper‐catalyzed 1,2‐dicarbonylative cyclization of 4‐aryl‐1‐butenes with unactivated alkyl bromides. In this reaction, two carbonyl groups were introduced into the double bond by the insertion of two molecules of carbon monoxide, and four new C−C bonds could be constructed in one reaction. At the same time, the corresponding skeletons of α‐tetralones as well as 2,3‐dihydroquinolin‐4‐one were obtained smoothly, which could also be transformed into three consecutive ring structures via subsequent derivatizations.
Abstract
According to the number of detected bursts, fast radio bursts (FRBs) can be classified into two categories, i.e., one-off FRBs and repeating ones. We make a statistical comparison of these ...two categories based on the first FRB catalog of the Canadian Hydrogen Intensity Mapping Experiment Fast Radio Burst Project. Using the Anderson–Darling, Kolmogorov–Smirnov, and Energy statistic tests, we find significant statistical differences (
p
-value < 0.001) in the burst properties between the one-off FRBs and the repeating ones. More specifically, after controlling for distance, we find that the peak luminosities of one-off FRBs are, on average, higher than the repeating ones; the pulse temporal widths of repeating FRBs are, on average, longer than the one-off ones. The differences indicate that these two categories could have distinct physical origins. Moreover, we discuss the subpopulations of FRBs and provide statistical evidence to support the existence of subpopulations in one-off FRBs and in repeating ones.
Long-duration gamma-ray bursts (LGRBs) and ultra-LGRBs (ULGRBs) originate from collapsars, in the center of which a newborn rotating stellar-mass black hole (BH) surrounded by a massive accretion ...disk may form. In the scenario of the BH hyperaccretion inflow-outflow model and Blandford-Znajek (BZ) mechanism to trigger gamma-ray bursts (GRBs), the real accretion rate to power a BZ jet is far lower than the mass supply rate from the progenitor star. The characteristics of the progenitor stars can be constrained by GRB luminosity observations, and the results exceed usual expectations. LGRBs lasting from several seconds to tens of seconds in the rest frame may originate from solar-metallicity ( , where Z and are the metallicities of progenitor stars and the Sun), massive ( , where M and are the masses of progenitor stars and the Sun) stars or some zero-metallicity ( ) stars. A fraction of low-metallicity ( ) stars, including Population III stars, can produce ULGRBs such as GRB 111209A. The fraction of LGRBs lasting less than tens of seconds in the rest frame is more than 40%, which cannot conform to the fraction of the demanded type of progenitor star. It possibly implies that the activity timescale of the central engine may be much longer than the observed timescale of prompt emission phase, as indicated by X-ray late-time activities. Alternatively, LGRBs and ULGRBs may be powered by a millisecond magnetar central engine.
It is well established that both p53 and MDM2 are short-lived proteins whose stabilities are tightly controlled through ubiquitination-mediated degradation. Although numerous studies indicate that ...the MDM2 E3 ligase activity, as well as the protein-protein interaction between p53 and MDM2, is the major focus for this regulation, emerging evidence suggests that the deu- biquitinase herpesvirus-associated ubiquitin-specific protease （HAUSP, also known as USP7） plays a critical role. Furthermore, HAUSP inhibition elevates p53 stability and might be beneficial for therapeutic purposes. In this review, we discuss the advances of this dynamic pathway and the contributions of positive and negative regulators affecting HAUSP activity. We also highlight the roles of HAUSP in cancer justifying the production of the first generation of HAUSP inhibitors.
In this study, we propose a novel distributed secondary control scheme for both voltage and frequency in autonomous microgrids. By incorporating predictive mechanisms into distributed generations, ...the secondary voltage control is converted to a tracker consensus problem of distributed model predictive control, with the synchronous convergence procedure for voltage magnitudes to the reference value drastically accelerated at a low communication cost. A sufficient local stability condition with the parameter analysis is established. Thus, a distributed proportional integral method combined with a finite-time observer to estimate the global reference information is presented in the frequency restoration while maintaining accurate active power sharing. Our approach accommodates model uncertainty, plug-and-play capability, and especially robustness against information update intervals, which is essential when the conventional method probably yields toward a poor performance. Meanwhile, the distributed architecture implemented on the local and neighboring information allows for a sparse communication network and eliminates the requirement for a centralized controller. Simulation results are provided to verify the effectiveness of the proposed control methodology.
This paper proposes an optimal distributed control strategy for the coordination of multiple distributed generators in an islanded microgrid (MG). A finite-time secondary frequency control approach ...is developed to eliminate the frequency deviation and maintain accurate active power sharing in a finite-time manner. It is demonstrated that the traditional distributed control approach with asymptotical convergence is just a special case of the proposed finite-time control strategy under the specific control parameter settings. Then, a secondary voltage control approach is presented to regulate the average voltage magnitude of all distributed generators to the desired value and achieve accurate reactive power sharing. The implementation of the proposed distributed control strategy only requires information exchange among neighboring local controllers through a sparse communication network. Simulations with an islanded MG testbed built in MATLAB/Simulink are conducted to validate the effectiveness of the proposed distributed control strategy.
Liver transplantation, the only proven treatment for end‐stage liver disease and acute liver failure, is hampered by the scarcity of donors. Regenerative medicine provides an alternative therapeutic ...approach. Tremendous efforts dedicated to liver regenerative medicine include the delivery of transplantable cells, microtissues, and bioengineered whole livers via tissue engineering and the maintenance of partial liver function via extracorporeal support. This brief review summarizes the current status of regenerative medicine for the hepatobiliary system. For liver regenerative medicine, the focus is on strategies for expansion of transplantable hepatocytes, generation of hepatocyte‐like cells, and therapeutic potential of engineered tissues in liver disease models. For biliary regenerative medicine, the discussion concentrates on the methods for generation of cholangiocyte‐like cells and strategies in the treatment of biliary disease. Significant advances have been made in large‐scale and long‐term expansion of liver cells. The development of tissue engineering and stem cell induction technology holds great promise for the future treatment of hepatobiliary diseases. The application of regenerative medicine in liver still lacks extensive animal experiments. Therefore, a large number of preclinical studies are necessary to provide sufficient evidence for their therapeutic effectiveness. Much remains to be done for the treatment of hepatobiliary diseases with regenerative medicine.
Highlight
Huang and colleagues summarized the current status of regenerative medicine research on the liver and bile ducts, covering stem cell culture techniques, small molecule cocktail medium, and tissue engineering. Although there are still many challenges, the development of these technologies holds great promise for the future treatment of hepatobiliary diseases.
This study proposes a fully decentralized secondary voltage control scheme which employs the state estimation method in autonomous microgrids. Based on a large-signal dynamic model of a microgrid, a ...linear parameter varying based state estimator that is localized in each distributed generation (DG) unit serves as an alternative communication role and obtains the dynamics of the other DG units independently. A linear matrix inequality formulation for pole placement condition is derived for the state estimator design. A decentralized secondary voltage controller is, thus, able to achieve accurate reactive power sharing and average voltage restoration without any additional communication links. Our approach offers superior reliability, flexibility, and economic efficiency because of the irrelevance of communications to its performance, which is essential when conventional centralized or distributed methods are likely to yield towards poor performance or even instability under communication latency or data drop-out conditions. Simulation results that verify the effectiveness of the proposed methodology are provided.
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