Constructing responsive and adaptive materials by dynamic covalent bonds is an attractive strategy in material design. Here, we present a kind of dynamic covalent polyureas which can be prepared from ...the highly efficient polyaddition reaction of pyrazoles and diisocyanates at ambient temperature in the absence of a catalyst. Owing to multiphase structural design, poly(pyrazole-ureas) (PPzUs) show excellent mechanical properties and unique crystallization behavior. Besides, the crosslinked PPzUs can be successfully recycled upon heating (~130 °C) and the molecular-level blending of polyurea and polyurethane is realized. Theoretical studies prove that the reversibility of pyrazole-urea bonds (PzUBs) arises from the unique aromatic nature of pyrazole and the N-assisting intramolecular hydrogen transfer process. The PzUBs could further broaden the scope of dynamic covalent bonds and are very promising in the fields of dynamic materials.
Acetaminophen (APAP)-induced liver injury is an important clinical and toxicological problem. Understanding the mechanisms and modes of cell death are vital for the development of therapeutic ...interventions. The histological and clinical features of APAP hepatotoxicity including cell and organelle swelling, karyolysis, and extensive cell contents release lead to the characterization of the cell death as oncotic necrosis. However, the more recent identification of detailed signaling mechanisms of mitochondrial dysfunction, the amplification mechanisms of mitochondrial oxidant stress and peroxynitrite formation by a mitogen-activated protein kinase cascade, mechanisms of the mitochondrial permeability transition pore opening and nuclear DNA fragmentation as well as the characterization of the sterile inflammatory response suggested that the mode of cell death is better termed programmed necrosis. Additional features like mitochondrial Bax translocation and cytochrome c release, mobilization of lysosomal iron and the activation of receptor-interacting protein kinases and the inflammasome raised the question whether other emerging modes of cell death such as apoptosis, necroptosis, ferroptosis and pyroptosis could also play a role. The current review summarizes the key mechanisms of APAP-induced liver injury and compares these with key features of the newly described modes of cell death. Based on the preponderance of experimental and clinical evidence, the mode of APAP-induced cell death should be termed programmed necrosis; despite some overlap with other modes of cell death, APAP hepatotoxicity does not fulfill the characteristics of either apoptosis, necroptosis, ferroptosis, pyroptosis or autophagic cell death.
Abstract Mitochondria are essential organelles that regulate cellular energy homeostasis and cell death. The removal of damaged mitochondria through autophagy, a process called mitophagy, is thus ...critical for maintaining proper cellular functions. Indeed, mitophagy has been recently proposed to play critical roles in terminal differentiation of red blood cells, paternal mitochondrial degradation, neurodegenerative diseases, and ischemia or drug-induced tissue injury. Removal of damaged mitochondria through autophagy requires two steps: induction of general autophagy and priming of damaged mitochondria for selective autophagic recognition. Recent progress in mitophagy studies reveals that mitochondrial priming is mediated either by the Pink1-Parkin signaling pathway or the mitophagic receptors Nix and Bnip3. In this review, we summarize our current knowledge on the mechanisms of mitophagy. We also discuss the pathophysiological roles of mitophagy and current assays used to monitor mitophagy.
Organic–inorganic hybrid perovskite solar cells (PSCs) are currently attracting significant interest owing to their promising outdoor performance. However, the ability of indoor light harvesting of ...the perovskites and corresponding device performance are rarely reported. Here, the potential of planar PSCs in harvesting indoor light for low‐power consumption devices is investigated. Ionic liquid of 1‐butyl‐3‐methylimidazolium tetrafluoroborate (BMIMBF4) is employed as a modification layer of 6,6‐phenyl‐C61‐butyric acid methyl ester) (PCBM) in the inverted PSCs. The incorporation of BMIMBF4 not only paves the interface contact between PCBM and electrode, but also facilitates the electron transport and extraction owing to the efficient passivation of the surface trap states. Moreover, BMIMBF4 with excellent thermal stability can act as a protective layer by preventing the erosion of moisture and oxygen into the perovskite layer. The resulting devices present a record indoor power conversion efficiency (PCE) of 35.20% under fluorescent lamps of 1000 lux, and an impressive PCE of 19.30% under 1 sun illumination. The finding in this work verifies the excellent indoor performance of PSCs to meet the requirements of eco‐friendly economy.
Ionic liquid of 1‐butyl‐3‐methylimidazolium tetrafluoroborate (BMIMBF4) is employed as a cathode modification and a protective layer to fabricate indoor perovskite solar cells. The resulting devices deliver an impressive power conversion efficiency (PCE) of 19.30% at 1 sun illumination, and a record indoor PCE of 35.20% under fluorescent lamp with 1000 lux, which is the highest value reported so far for indoor solar cells.
The mitochondrion is an organelle that plays a vital role in the regulation of hepatic cellular redox, lipid metabolism, and cell death. Mitochondrial dysfunction is associated with both acute and ...chronic liver diseases with emerging evidence indicating that mitophagy, a selective form of autophagy for damaged/excessive mitochondria, plays a key role in the liver's physiology and pathophysiology. This review will focus on mitochondrial dynamics, mitophagy regulation, and their roles in various liver diseases (alcoholic liver disease, non-alcoholic fatty liver disease, drug-induced liver injury, hepatic ischemia-reperfusion injury, viral hepatitis, and cancer) with the hope that a better understanding of the molecular events and signaling pathways in mitophagy regulation will help identify promising targets for the future treatment of liver diseases.
Combined with backstepping techniques, an observer-based adaptive consensus tracking control strategy is developed for a class of high-order nonlinear multiagent systems, of which each follower agent ...is modeled in a semi-strict-feedback form. By constructing the neural network-based state observer for each follower, the proposed consensus control method solves the unmeasurable state problem of high-order nonlinear multiagent systems. The control algorithm can guarantee that all signals of the multiagent system are semi-globally uniformly ultimately bounded and all outputs can synchronously track a reference signal to a desired accuracy. A simulation example is carried out to further demonstrate the effectiveness of the proposed consensus control method.
Autophagy can selectively remove damaged organelles, including mitochondria, and, in turn, protect against mitochondria‐damage–induced cell death. Acetaminophen (APAP) overdose can cause liver injury ...in animals and humans by inducing mitochondria damage and subsequent necrosis in hepatocytes. Although many detrimental mechanisms have been reported to be responsible for APAP‐induced hepatotoxicity, it is not known whether APAP can modulate autophagy to regulate hepatotoxicity in hepatocytes. To test the hypothesis that autophagy may play a critical protective role against APAP‐induced hepatotoxicity, primary cultured mouse hepatocytes and green fluorescent protein/light chain 3 transgenic mice were treated with APAP. By using a series of morphological and biochemical autophagic flux assays, we found that APAP induced autophagy both in the in vivo mouse liver and in primary cultured hepatocytes. We also found that APAP treatment might suppress mammalian target of rapamycin in hepatocytes and that APAP‐induced autophagy was suppressed by N‐acetylcysteine, suggesting APAP mitochondrial protein binding and the subsequent production of reactive oxygen species may play an important role in APAP‐induced autophagy. Pharmacological inhibition of autophagy by 3‐methyladenine or chloroquine further exacerbated APAP‐induced hepatotoxicity. In contrast, induction of autophagy by rapamycin inhibited APAP‐induced hepatotoxicity. Conclusion: APAP overdose induces autophagy, which attenuates APAP‐induced liver cell death by removing damaged mitochondria. (HEPATOLOGY 2012)
We investigated the mixed traffic flow with human-driving and autonomous cars. A new mathematical model with adjustable sensitivity and smooth factor was proposed to describe the autonomous car’s ...moving behavior in which smooth factor is used to balance the front and back headway in a flow. A lemma and a theorem were proved to support the stability criteria in traffic flow. A series of simulations were carried out to analyze the mixed traffic flow. The fundamental diagrams were obtained from the numerical simulation results. The varying sensitivity and smooth factor of autonomous cars affect traffic flux, which exhibits opposite varying tendency with increasing parameters before and after the critical density. Moreover, the sensitivity of sensors and smooth factors play an important role in stabilizing the mixed traffic flow and suppressing the traffic jam.
•A mixed traffic flow was investigated based on car-following model.•One theorem were proven as criteria for judging stability of traffic flow.•Fundamental diagrams were examined with different parameters in simulations.
Acetaminophen (APAP) overdose is the most frequent cause of acute liver failure in the USA and many other countries. Although the metabolism and pathogenesis of APAP has been extensively investigated ...for decades, the mechanisms by which APAP induces liver injury are incompletely known, which hampers the development of effective therapeutic approaches to tackle this important clinical problem. Autophagy is a highly conserved intracellular degradation pathway, which aims at recycling cellular components and damaged organelles in response to adverse environmental conditions and stresses as a survival mechanism. There is accumulating evidence indicating that autophagy is activated in response to APAP overdose in specific liver zone areas, and pharmacological activation of autophagy protects against APAP‐induced liver injury. Increasing evidence also suggests that hepatic autophagy is impaired in nonalcoholic fatty livers (NAFLD), and NAFLD patients are more susceptible to APAP‐induced liver injury. Here, we summarized the current progress on the role and mechanisms of autophagy in protecting against APAP‐induced liver injury.
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