Humans are inevitably exposed to ethyl carbamate (EC) via consumption of fermented food and beverages. EC, known as an environmental toxin, can cause oxidative stress-mediated severe toxicity, but ...the underlying mechanisms remain unveiled. Ferroptosis is a newly identified ROS-mediated non-apoptotic cell death characterized by iron accumulation and excessive lipid oxidation. In this study, we first found that EC triggered ferroptosis in liver cells by detection of decreased cell viability, GSH, GPX4 and Ferritin levels, as well as increased iron and MDA contents. Ferroptosis inhibitor ferrostatin-1 (Fer-1) pretreatment rescued ferroptotic damage, indicating that ferroptosis was critical for EC-caused cell death. Furthermore, GSH synthesis precursor N-acetylcysteine displayed significant anti-ferroptotic properties and we suggested that GSH depletion might be the main cause of ferroptosis under EC exposure. EC-triggered GSH depletion mainly depended on suppressed GSH synthesis via inhibition of SLC7A11 and GCLC expressions. Notably, EC blocked Nrf2 activation by repression of phosphorylation modification and nuclear translocation, which further resulted in ferroptosis occurrence. We also observed EC-induced liver dysfunction and inflammation, accompanied with oxidative stress, ferroptosis and downregulated Nrf2 signaling in Balb/c mice, which could be effectively reversed by Fer-1 and tBHQ pretreatment. Together, our study indicated that ferroptosis is a new mechanism for EC-caused toxicity, which was attributed to Nrf2 inactivation and GSH depletion.
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•Ethyl carbamate (EC) caused ferroptosis in L02 cells and liver tissues.•GSH depletion was critical for EC-induced ferroptotic cell death.•EC exposure blocked GSH synthesis-related pathways.•Inactivation of Nrf2 signaling was involved in EC-triggered ferroptosis.
In order to improve the visual communication effect of the 3D image visual communication system, this article combines the automatic reconstruction technology of digital images to design the 3D image ...visual communication system. Moreover, this article studies the shock stability of the shock capture scheme by combining entropy generation analysis, linear disturbance analysis, and numerical experiments. In addition to this, this article presents a general method that can be used to suppress numerical shock instabilities in various Godunov-type schemes. It can be seen from the experimental results that the proposed 3D image visual communication system for the automatic reconstruction of digital images has a good visual communication effect.
Abstract
Background
The effect of the timing of norepinephrine initiation on clinical outcomes in patients with septic shock is uncertain. A systematic review and meta-analysis was performed to ...evaluate the impact of early and late start of norepinephrine support on clinical outcomes in patients with septic shock.
Methods
We searched the PubMed, Cochrane, and Embase databases for randomized controlled trials (RCTs) and cohort studies from inception to the 1st of March 2020. We included studies involving adult patients (> 18 years) with septic shock. All authors reported our primary outcome of short-term mortality and clearly comparing early versus late norepinephrine initiation with clinically relevant secondary outcomes (ICU length of stay, time to achieved target mean arterial pressure (≥ 65 mmHg), and volume of intravenous fluids within 6 h). Results were expressed as odds ratio (OR) and mean difference (MD) with accompanying 95% confidence interval (CI).
Results
Five studies including 929 patients were included. The primary outcome of this meta-analysis showed that the short-term mortality of the early group was lower than that of the late group (odds ratio OR = 0.45; 95% CI, 0.34 to 0.61;
P
< 0.00001;
χ
2
= 3.74;
I
2
= 0%). Secondary outcomes demonstrated that the time to achieved target MAP of the early group was shorter than that of the late group (mean difference = − 1.39; 95% CI, − 1.81 to − 0.96;
P
< 0.00001;
χ
2
= 1.03;
I
2
= 0%). The volume of intravenous fluids within 6 h of the early group was less than that of the late group (mean difference = − 0.50; 95% CI, − 0.68 to − 0.32;
P
< 0.00001;
χ
2
= 33.76;
I
2
= 94%). There was no statistically significant difference in the ICU length of stay between the two groups (mean difference = − 0.11; 95% CI, − 1.27 to 1.05;
P
= 0.86;
χ
2
= 0.85;
I
2
= 0%).
Conclusions
Early initiation of norepinephrine in patients with septic shock was associated with decreased short-term mortality, shorter time to achieved target MAP, and less volume of intravenous fluids within 6 h. There was no significant difference in ICU length of stay between early and late groups. Further large-scale RCTs are still required to confirm these results.
This paper concerns robust stabilization of nonlinear fractional order interconnected systems. Based on uncertain fractional order Takagi–Sugeno fuzzy model and the fractional order extension of ...lyapunov direct method, a parallel distributed compensate controller is designed to asymptotically stabilize the fractional order interconnected systems. Then, a sufficient condition is given in the format of linear matrix inequalities. Simulation example is given to validate the effectiveness of the approach.
Size control: Sterically stabilized methacrylic nanolatexes are readily prepared by aqueous dispersion polymerization using RAFT reactions (see scheme; CTA=chain transfer agent). Varying the length ...of the poly(HPMA) chains allows precise size control of the nanolatex particles.
Equal equity is not a suitable pathway to control the corporations. For Apple Company, due to Jobs’ equal equity, the most important reason that he quitted his company is that at the first step of ...the company, he had the same shares as other members of the board, but he did not have the absolute control of his company. Also, after the corporation was listed, the shares have been diluted gradually. Losing the control right, Jobs cannot make wise decisions or seek for strategic chances to make a huge profit, when members of the board held diverse opinions. Therefore dual-class share structure and ownership systems are the better choice for founders and entrepreneurs to operate and control the company. Managers have absolute control of the corporations so that they could make intellectual decisions without disturbance and intervention. Companies, accumulating a large amount of money, could pay dividends to shareholders and buy stocks.
Non-equilibrium phase separating systems with reactions, such as biomolecular condensates and bacteria colonies, can break time-reversal symmetry (TRS) in two distinct ways. Firstly, the conservative ...and non-conservative sectors of the dynamics can be governed by incompatible free energies; when both sectors are present, this is the leading-order TRS violation, captured in its simplest form by ‘Model AB’. Second, the diffusive dynamics can break TRS in its own right. This happens only at higher order in the gradient expansion (but is the leading behaviour without reactions present) and is captured by ‘Active Model B+’ (AMB+). Each of the two mechanisms can lead to microphase separation, by quite different routes. Here we introduce Model AB+, for which both mechanisms are simultaneously present, and show that for slow reaction rates the system can undergo a new type of hierarchical microphase separation, which we call ‘bubbly microphase separation’. In this state, small droplets of one fluid are continuously created and absorbed into large droplets, whose length-scales are controlled by the competing reactive and diffusive dynamics.
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