The homeostatic link between oxidative stress and autophagy plays an important role in cellular responses to a wide variety of physiological and pathological conditions. However, the regulatory ...pathway and outcomes remain incompletely understood. Here, we show that reactive oxygen species (ROS) function as signaling molecules that regulate autophagy through ataxia‐telangiectasia mutated (ATM) and cell cycle checkpoint kinase 2 (CHK2), a DNA damage response (DDR) pathway activated during metabolic and hypoxic stress. We report that CHK2 binds to and phosphorylates Beclin 1 at Ser90/Ser93, thereby impairing Beclin 1‐Bcl‐2 autophagy‐regulatory complex formation in a ROS‐dependent fashion. We further demonstrate that CHK2‐mediated autophagy has an unexpected role in reducing ROS levels via the removal of damaged mitochondria, which is required for cell survival under stress conditions. Finally, CHK2−/− mice display aggravated infarct phenotypes and reduced Beclin 1 p‐Ser90/Ser93 in a cerebral stroke model, suggesting an in vivo role of CHK2‐induced autophagy in cell survival. Taken together, these results indicate that the ROS‐ATM‐CHK2‐Beclin 1‐autophagy axis serves as a physiological adaptation pathway that protects cells exposed to pathological conditions from stress‐induced tissue damage.
Synopsis
Whether hypoxia and nutrient starvation are coupled to cellular autophagy remains unclear. Here, DNA damage response kinases ATM and CHK2 are shown to trigger autophagy in response to reactive oxygen species (ROS) accumulation, suggesting a novel physiological adaptation pathway toward metabolic stress.
Depletion of CHK2 or ATM impairs oxidative stress‐induced autophagy in MEFs.
CHK2 binds and phosphorylates Beclin1 at Ser90/Ser93, suppressing Beclin1‐Bcl‐2 autophagy regulatory complex formation.
CHK2‐induced autophagy limits intracellular ROS levels by clearing damaged mitochondria.
CHK2‐induced autophagy protects against cell death and tissue damage following cerebral ischemia.
ROS accumulation activates protective autophagy to prevent stress‐induced tissue damage.
A novel Na0.70Fe0.10Ni0.05Cu0.20Mn0.65O2 cathode material shows excellent cycling stability and can remain P2 phase during whole electrochemical reaction process.
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Fe-Mn based layer ...oxides cathode materials have attracted widespread attention as a potential candidate for sodium-ion batteries (SIBs) owing to the earth abundance, cost-effectiveness and acceptable specific capacity. However, the irreversible phase transition often brings rapid capacity decay, which seriously hinders the practical application in large-scale energy storage. Herein, we design a nickel-doped Na0.70Fe0.10Cu0.20Ni0.05Mn0.65O2 (NFCNM-0.05) cathode material of SIBs with activated anionic redox reaction, and then inhibit the harmful phase transition. The ex-situ X-ray diffraction patterns demonstrate the NFCNM-0.05 always keeps the P2 phase during the sodiation/desodiation process, indicating a high structure stability. The ex-situ X-ray photoelectron spectroscopy implies the redox reactions between O2− and O− occur in the charging process, which offers extra specific capacity. Thus, the NFCNM-0.05 electrode delivers a high initial discharge capacity of 148 mA h g−1 and remains a prominent cycling stability with an excellent capacity retention of 95.9% after 200 cycles at 1 C. In addition, the electrochemical impedance spectroscopy and galvanostatic intermittent titration technique show the NFCNM-0.05 electrode possesses fast ion diffusion ability, which is beneficial for the enhancement of rate performance. Even at 10 C, the NFCNM-0.05 can offer a reversible discharge capacity of 81 mA h g−1. DFT calculation demonstrates the doping of appropriate amount of Ni ions is benefit for the enhancement of the electrochemical performance of the layer oxides. This work provides an effective strategy to enhance the electrochemical performance of Fe-Mn based cathode materials of SIBs.
The study of topological phases with unconventional bulk‐boundary correspondences and nontrivial real Chern number has garnered significant attention in the topological states of matter. Using the ...first‐principle calculations and theoretical analysis, a high‐throughput material screening of the 3D obstructed atomic insulators (OAIs) and 3D real Chern insulators (RCIs) based on the Samara Carbon Allotrope Database (SACADA) are performed. Results show that 422 out of 703 3D carbon allotropes are 3D OAIs with multiple bulk‐boundary correspondences, including 2D obstructed surface states (OSSs) and 1D hinge states, which are in 1D and 2Ds lower than the 3D bulk, respectively. The 2D OSSs in these OAIs can be modified when subjected to appropriate boundaries, which benefits the investigation of surface engineering and the development of efficient topological catalysts. These 422 OAIs, which have 2D and 1D boundary states, are excellent platforms for multi‐dimensional topological boundaries research. Remarkably, 138 of 422 OAIs are also 3D RCIs, which show a nontrivial real topology in the protection of spacetime inversion symmetry. This work not only provides a comprehensive list of 3D carbon‐based OAIs and RCIs, but also guides their application in various aspects based on multiple bulk‐boundary correspondences and real topological phases.
A high‐throughput material screening of the 3D obstructed atomic insulators (OAIs) and 3D real Chern insulators (RCIs) based on the Samara Carbon Allotrope Database (SACADA) is performed. Results show 422 out of 703 3D carbon allotropes are 3D OAIs with multiple bulk‐boundary correspondences. Remarkably, 138 of 422 OAIs are also 3D RCIs with a nontrivial real topology.
Two cycles in one pot! The synthesis of biologically important phenanthridinones has been achieved by the one‐pot formation of CC and CN bonds through a palladium‐catalyzed dual CH activation, ...which involves four bond ruptures and two bond formations (see scheme). The conversion of phenanthridinones into natural product like derivatives further demonstrates the utility of this synthetic achievement.
Neural networks are frequently employed to model species distribution through backpropagation methods, known as backpropagation neural networks (BPNN). However, the complex structure of BPNN ...introduces parameter settings challenges, such as the determination of connection weights, which can affect the accuracy of model simulation. In this paper, we integrated the Grey Wolf Optimizer (GWO) algorithm, renowned for its excellent global search capacity and rapid convergence, to enhance the performance of BPNN. Then we obtained a novel hybrid algorithm, the Grey Wolf Optimizer algorithm optimized backpropagation neural networks algorithm (GNNA), designed for predicting species' potential distribution. We also compared the GNNA with four prevalent species distribution models (SDMs), namely the generalized boosting model (GBM), generalized linear model (GLM), maximum entropy (MaxEnt), and random forest (RF). These models were evaluated using three evaluation metrics: the area under the receiver operating characteristic curve, Cohen's kappa, and the true skill statistic, across 23 varied species. Additionally, we examined the predictive accuracy concerning spatial distribution. The results showed that the predictive performance of GNNA was significantly improved compared to BPNN, was significantly better than that of GLM and GBM, and was even comparable to that of MaxEnt and RF in predicting species distributions with small sample sizes. Furthermore, the GNNA demonstrates exceptional powers in forecasting the potential non-native distribution of invasive plant species.
BackgroundPast studies have found a strong relationship between alcohol drinking and human health.MethodsIn this study, we first tested the association of rs671 with alcohol use in 2349 participants ...in southeast China. We then evaluated the causal impact between alcohol use and cardiovascular traits through a Mendelian randomisation (MR) analysis.ResultsWe found strong evidence for the association of rs671 in the ALDH2 gene with alcohol drinking (p=6.08×10-47; ORadj G=4.50, 95% CI 3.67 to 5.52). We found that female G carriers of rs671 had a higher proportion of non-drinkers than male G carriers (88.01% vs 38.70%). In non-drinkers, the female G allele frequency was higher than the male G allele frequency (71.1% vs 55.2%). MR analysis suggested that alcohol use had a causal effect on blood pressure (increasing 9.46 mm Hg for systolic blood pressure (p=9.67×10-4) and 7.50 mm Hg for diastolic blood pressure (p=9.62×10-5)), and on hypertension in men (p=0.011; OR =1.19, 95% CI 1.04 to 1.36) and in pooled samples (p=0.013; OR =1.20, 95% CI 1.04 to 1.39), but not in women. We did not observe a causal effect of alcohol use on body mass index and lipid levels; further studies are needed to clarify the non-causal relationship.ConclusionsCompared to never-drinkers, current and previous alcohol use had a causal effect on blood pressure and hypertension in pooled samples and in men. These results reflect Chinese culture which does not encourage women to drink.
Autoimmune factor was regarded as one of the risk factors in the pathogenesis of chronic pancreatitis (CP), especially for autoimmune pancreatitis (AIP). However, whether autoimmune factor plays a ...role in non-AIP CP or not was unknown.
Hospitalized patients with non-AIP CP from January 2010 to October 2016 were detected for 22 autoantibodies at the time of hospital admission. Autoantibodies with frequency > 0.5% were enrolled to calculate the frequency in historial healthy controls through literature search in PubMed. Differentially expressed autoantibodies were determined between patients and historial healthy controls, and related factors were identified by multivariate logistic regression analysis.
In a total of 557 patients, 113 cases were detected with 19 kinds of positive autoantibodies, among them anti-β2-glycoprotein I (β2-GPI) antibody was most frequent (9.16%). Compared with historial healthy controls, the frequencies of serum β2-GPI and anti SS-B antibody in patients were significantly higher, while frequencies of anti-smooth muscle antibody and anticardiolipin antibody were significantly lower (all P < 0.05). Multivariate logistic regression analysis result showed that diabetes mellitus (OR = 2.515) and common bile duct stricture (OR = 2.844) were the risk factors of positive β2-GPI antibody in patients while diabetes mellitus in first-/second-/third-degree relatives (OR = 0.266) was the protective factor. There were no related factors for other three differentially expressed autoantibodies.
Four autoantibodies were expressed differentially between patients with non-AIP CP and historial healthy controls. Due to limited significance for diagnosis and treatment of chronic pancreatitis, autoantibodies detection is not recommended conventionally unless suspected of AIP.
Adolescent idiopathic scoliosis (AIS) is the most common spinal deformity during adolescence, leading to altered postural control with compromised stability. To identify the effects of AIS on ...whole-body balance control during obstacle-crossing, 14 adolescents with Lenke 1 thoracic AIS and 14 healthy controls were compared in terms of the inclination angle (IA) of the body's center of mass (COM) relative to the center of pressure (COP), the rate of change of IA (RCIA) and the jerk index of IA. Between-side comparisons were also performed for the AIS group. The patients showed less smooth COM-COP motion in the sagittal plane with significantly increased anterior RCIA and IA jerk index during crossing with either the concave side (p = 0.001) or the convex side (p = 0.001) leading when compared to healthy controls. In the frontal plane, the patients showed close-to-zero RCIA (p = 0.002) while crossing with the leading limb, with an increased IA magnitude (p = 0.039) only while crossing with the concave-side limb leading. The patients with Lenke 1 thoracic AIS were found to cross obstacles with altered, compromised COM-COP control in both sagittal and frontal planes when compared to healthy controls. The results suggest that the thoracic spinal deformity in Lenke 1 AIS affects the whole-body balance control during obstacle-crossing, which should be monitored for signs of increased risk of loss of balance in the management of such patient groups.
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