Phosphoenolpyruvate carboxykinase (PEPCK or PCK) catalyzes the first rate-limiting step in hepatic gluconeogenesis pathway to maintain blood glucose levels. Mammalian cells express two PCK genes, ...encoding for a cytoplasmic (PCPEK-C or PCK1) and a mitochondrial (PEPCK-M or PCK2) isoforms, respectively. Increased expressions of both PCK genes are found in cancer of several organs, including colon, lung, and skin, and linked to increased anabolic metabolism and cell proliferation. Here, we report that the expressions of both PCK1 and PCK2 genes are downregulated in primary hepatocellular carcinoma (HCC) and low PCK expression was associated with poor prognosis in patients with HCC. Forced expression of either PCK1 or PCK2 in liver cancer cell lines results in severe apoptosis under the condition of glucose deprivation and suppressed liver tumorigenesis in mice. Mechanistically, we show that the pro-apoptotic effect of PCK1 requires its catalytic activity. We demonstrate that forced PCK1 expression in glucose-starved liver cancer cells induced TCA cataplerosis, leading to energy crisis and oxidative stress. Replenishing TCA intermediate α-ketoglutarate or inhibition of reactive oxygen species production blocked the cell death caused by PCK expression. Taken together, our data reveal that PCK1 is detrimental to malignant hepatocytes and suggest activating PCK1 expression as a potential treatment strategy for patients with HCC.
Highly selective and direct electroreductive ring‐opening carboxylation of epoxides with CO2 in an undivided cell is reported. This reaction shows broad substrate scopes within styrene oxides under ...mild conditions, providing practical and scalable access to important synthetic intermediate β‐hydroxy acids. Mechanistic studies show that CO2 functions not only as a carboxylative reagent in this reaction but also as a promoter to enable efficient and chemoselective transformation of epoxides under additive‐free electrochemical conditions. Cathodically generated α‐radical and α‐carbanion intermediates lead to the regioselective formation of α‐carboxylation products.
Highly selective and direct electroreductive ring‐opening carboxylation of epoxides with CO2 in an undivided cell to yield synthetically important β‐hydroxy acids is described. CO2 functions not only as a carboxylative reagent in this reaction but also as a promoter to enable efficient and chemoselective transformation of epoxides under additive‐free electrochemical conditions.
This technical brief considers the distributed consensus problems for multi-agent systems with general linear and Lipschitz nonlinear dynamics. Distributed relative-state consensus protocols with an ...adaptive law for adjusting the coupling weights between neighboring agents are designed for both the linear and nonlinear cases, under which consensus is reached for all undirected connected communication graphs. Extensions to the case with a leader-follower communication graph are further studied. In contrast to the existing results in the literature, the adaptive consensus protocols here can be implemented by each agent in a fully distributed fashion without using any global information.
Peroxisomes account for ~35% of total H2O2 generation in mammalian tissues. Peroxisomal ACOX1 (acyl‐CoA oxidase 1) is the first and rate‐limiting enzyme in fatty acid β‐oxidation and a major producer ...of H2O2. ACOX1 dysfunction is linked to peroxisomal disorders and hepatocarcinogenesis. Here, we show that the deacetylase sirtuin 5 (SIRT5) is present in peroxisomes and that ACOX1 is a physiological substrate of SIRT5. Mechanistically, SIRT5‐mediated desuccinylation inhibits ACOX1 activity by suppressing its active dimer formation in both cultured cells and mouse livers. Deletion of SIRT5 increases H2O2 production and oxidative DNA damage, which can be alleviated by ACOX1 knockdown. We show that SIRT5 downregulation is associated with increased succinylation and activity of ACOX1 and oxidative DNA damage response in hepatocellular carcinoma (HCC). Our study reveals a novel role of SIRT5 in inhibiting peroxisome‐induced oxidative stress, in liver protection, and in suppressing HCC development.
Synopsis
This study reveals a role for SIRT5 in regulating peroxisomal H2O2 and ROS homeostasis and indicates its potential function in liver protection and hepatocellular carcinoma suppression.
SIRT5 is localized in peroxisomes where it controls H2O2 metabolism.
SIRT5‐mediated desuccinylation inhibits ACOX1 activity by suppressing its active dimer formation.
SIRT5 downregulation increases ACOX1 activity and oxidative DNA damage response in HCC.
This study reveals a role for SIRT5 in regulating peroxisomal H2O2 and ROS homeostasis and indicates its potential function in liver protection and hepatocellular carcinoma suppression.
This technical note considers the distributed tracking control problem of multiagent systems with general linear dynamics and a leader whose control input is nonzero and not available to any ...follower. Based on the relative states of neighboring agents, two distributed discontinuous controllers with, respectively, static and adaptive coupling gains, are designed for each follower to ensure that the states of the followers converge to the state of the leader, if the interaction graph among the followers is undirected, the leader has directed paths to all followers, and the leader's control input is bounded. A sufficient condition for the existence of the distributed controllers is that each agent is stabilizable. Simulation examples are given to illustrate the theoretical results.
It is of great significance to depolymerize used or waste polymers to recover the starting monomers suitable for repolymerization reactions that reform recycled materials no different from the virgin ...polymer. Herein, we report a novel recyclable plastic: degradable polycarbonate synthesized by dinuclear chromium‐complex‐mediated copolymerization of CO2 with 1‐benzyloxycarbonyl‐3,4‐epoxy pyrrolidine, a meso‐epoxide. Notably, the novel polycarbonate with more than 99 % carbonate linkages could be recycled back into the epoxide monomer in quantitative yield under mild reaction conditions. Remarkably, the copolymerization/depolymerization processes can be achieved by the ON/OFF reversible temperature switch, and recycled several times without any change in the epoxide monomer and copolymer. These characteristics accord well with the concept of perfectly sustainable polymers.
A sustainable plastic was synthesized by dinuclear chromium‐complex‐mediated copolymerization of CO2 with an epoxide that could be recycled back into the monomer in quantitative yield under mild conditions. Temperature was used as a reversible switch in the recycle process. These characteristics are in accordance with the concept of perfectly sustainable polymers.
Summary
Polyethylene terephthalate (PET) is a mass‐produced synthetic polyester contributing remarkably to the accumulation of solid plastics waste and plastics pollution in the natural environments. ...Recently, bioremediation of plastics waste using engineered enzymes has emerged as an eco‐friendly alternative approach for the future plastic circular economy. Here we genetically engineered a thermophilic anaerobic bacterium, Clostridium thermocellum, to enable the secretory expression of a thermophilic cutinase (LCC), which was originally isolated from a plant compost metagenome and can degrade PET at up to 70°C. This engineered whole‐cell biocatalyst allowed a simultaneous high‐level expression of LCC and conspicuous degradation of commercial PET films at 60°C. After 14 days incubation of a batch culture, more than 60% of the initial mass of a PET film (approximately 50 mg) was converted into soluble monomer feedstocks, indicating a markedly higher degradation performance than previously reported whole‐cell‐based PET biodegradation systems using mesophilic bacteria or microalgae. Our findings provide clear evidence that, compared to mesophilic species, thermophilic microbes are a more promising synthetic microbial chassis for developing future biodegradation processes of PET waste.
Promising bioremediation strategies for plastics waste are of great importance and requirements. In our study, we constructed a recombinant Clostridium thermocellum strain expressing a secretory cutinase (LCC) as a thermophilic whole‐cell biocatalyst to degrade PET under high‐temperature condition (60°C). To our knowledge, this biocatalysis system demonstrates the highest PET degradation efficiency compared to reported whole‐cell‐based systems and also enjoys a low‐cost advantage over the free enzyme‐based process.
This paper considers the distributed consensus problem of multi-agent systems with general continuous-time linear dynamics for both the cases without and with a leader whose control input might be ...nonzero and time varying. For the case without a leader, based on the relative output information of neighboring agents, two types of distributed adaptive dynamic consensus protocols are proposed, namely, the edge-based adaptive protocol which assigns a time-varying coupling weight to each edge in the communication graph and the node-based adaptive protocol which uses a time-varying coupling weight for each node. These two adaptive protocols are designed to ensure that consensus is reached in a fully distributed fashion for all undirected connected communication graphs. It is shown that the edge-based adaptive consensus protocol is applicable to arbitrary switching connected graphs. For the case where there exists a leader whose control input is possibly nonzero and bounded, a distributed continuous adaptive protocol is designed to guarantee the ultimate boundedness of the consensus error with respect to any communication graph which contains a directed spanning tree with the leader as the root and whose subgraph associated with the followers is undirected, requiring neither global information of the communication graph nor the upper bound of the leader’s control input. A distributed discontinuous protocol is also discussed as a special case. Simulation examples are finally given to illustrate the theoretical results.
Unprecedented enantioselectivity and catalytic activity was observed in the asymmetric copolymerization of CO2 with meso‐epoxides (including the less reactive cyclopentene oxide) mediated by the ...dinuclear CoIII complex (S,S,S,S)‐1 under mild conditions. The resultant copolymers possess more than 99 % carbonate linkages and a perfectly isotactic structure.
•N and S doped hard carbon anode (NS-MPC) derived from mango-peels biowastes for Na ion batteries is firstly demonstrated.•In-situ monitoring surface functional of mango-peel wastages via FT-IR ...analysis.•Heteroatoms doped-hard carbon anode exhibits superior electrochemical performance than un-doped sample.•The NS-MPC anode delivers a reversible discharge capacity of 400 mAh/g at 100 mA/g for 2500 cycles.
Electrochemical energy storage devices, namely batteries are vital role to cut greenhouse gas secretions and reliable alternative of fossil fuel-used various electrical energy storage systems. Thus, the hard carbon is one of the promising cheapest sustainable material for energy storage sectors. In this study, we assemble the sodium-ion cell via renewable biomass-waste resource of mango-peels derived hard carbon (MPC) used as an anode electrode for Na-ion storage for the first-time. Furthermore, the hard carbon is modified with N, and S (NS-MPC) through a facile carbonization route. The structural, functional, morphological and chemical characteristics are systematically studied in details through spectroscopic techniques. The NS-MPC electrode consisted sodium-ion storage delivers a reversible discharge capacity of 400 mAh/g at a current density of 100 mA/g and exposed a reversible capacity of 155 mAh/g over 2500 cycles at 2 A/g. The Na-ion charge storage behavior reveals through the different rate controlled cyclic voltammetry (CV) analysis, which result exposed increasing contribution percentage of surface-controlled capacity with increment of current rates. Overall, this work signifies to protecting the environment by employed the bio-wastage to wealth applications, especially cost-effective fabrication of batteries for future pioneering grid energy storage applications.
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