NRF2 activation suppresses motor neuron ferroptosis induced by the SOD1G93A mutation and exerts neuroprotection in amyotrophic lateral sclerosis.

The progressive neurodegenerative disease amyotrophic lateral sclerosis (ALS) is caused by a decline in motor neuron function, resulting in worsened motor impairments, malnutrition, respiratory failure and mortality, and there is a lack of effective clinical treatments. The exact mechanism of motor neuronal degeneration remains unclear. Previously, we reported that ferroptosis, which is characterized by the accumulation of lipid peroxide and glutathione depletion in an iron-dependent manner, contributed to motor neuronal death in ALS cell models with the hSOD1G93A (human Cu/Zn-superoxide dismutase) gene mutation. In this study, we further explored the role of ferroptosis in motor neurons and its regulation in mutant hSOD1G93A cell and mouse models. Our results showed that ferroptosis was activated in hSOD1G93A NSC-34 cells and mouse models, which was accompanied by decreased nuclear retention of nuclear factor erythroid 2-related factor 2 (NRF2) and downregulation of solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4) levels. Moreover, RTA-408, an NRF2 activator, inhibited ferroptosis in hSOD1G93A NSC-34 cells by upregulating the protein expression of SLC7A11 and GPX4. Moreover, hSOD1G93A mice treated with RTA-408 showed obvious improvements in body weight and motor function. Our study demonstrated that ferroptosis contributed to the toxicity of motor neurons and that activating NRF2 could alleviate neuronal degeneration in ALS with the hSOD1G93A mutation.

Friction effect of stator in a multi-walled CNT-based rotation transmission system.

The rotation transmission system (RTS) made from co-axial multi-walled nanotubes (MWNTs) has the function of regulating the input rotation from a nanomotor. The mechanism for the regulation is that the friction among the tubes during rotation governs the rotation of the rotors in the nanosystem. By integrating a rotary nanomotor and a nanobearing into an MWNT-based RTS, it is discovered that the stator (outer tube) provides relatively greater friction on the rotors by penetrating the motor tube, which has a higher stable rotational frequency. And the output rotation of the rotors in the system depends significantly on the temperature of the system, as the rotor tubes are slightly longer than the motor tube. Briefly, at low temperatures, say 8 K, the rotors rotate synchronously with the motor. However, at high temperatures, the rotors rotate slower than the motor with a bigger difference between their rotational frequencies. Hence, the output rotational frequencies can be adjusted by changing the temperature as well as the input rotational frequency.

Genomic data and ecological niche modeling reveal an unusually slow rate of molecular evolution in the Cretaceous Eupteleaceae.

Living fossils are evidence of long-term sustained ecological success. However, whether living fossils have little molecular changes remains poorly known, particularly in plants. Here, we have introduced a novel method that integrates phylogenomic, comparative genomic, and ecological niche modeling analyses to investigate the rate of molecular evolution of Eupteleaceae, a Cretaceous relict angiosperm family endemic to East Asia. We assembled a high-quality chromosome-level nuclear genome, and the chloroplast and mitochondrial genomes of a member of Eupteleaceae (Euptelea pleiosperma). Our results show that Eupteleaceae is most basal in Ranunculales, the earliest-diverging order in eudicots, and shares an ancient whole-genome duplication event with the other Ranunculales. We document that Eupteleaceae has the slowest rate of molecular changes in the observed angiosperms. The unusually low rate of molecular evolution of Eupteleaceae across all three independent inherited genomes and genes within each of the three genomes is in association with its conserved genome architecture, ancestral woody habit, and conserved niche requirements. Our findings reveal the evolution and adaptation of living fossil plants through large-scale environmental change and also provide new insights into early eudicot diversification.

Feature Sequencing Method of Industrial Control Data Set Based on Multidimensional Evaluation Parameters.

The industrial control data set has many features and large redundancy, which has a certain impact on the training speed and classification results of the neural network anomaly detection algorithm. However, features are independent of each other, and dimension reduction often increases the false positive rate and false negative rate. The feature sequencing algorithm can reduce this effect. In order to select the appropriate feature sequencing algorithm for different data sets, this paper proposes an adaptive feature sequencing method based on data set evaluation index parameters. Firstly, the evaluation index system is constructed by the basic information of the data set, the mathematical characteristics of the data set, and the association degree of the data set. Then, the selection model is obtained by the decision tree training with the data label and the evaluation index, and the suitable feature sequencing algorithm is selected. Experiments were conducted on 11 data sets, including Batadal data set, CICIDS 2017, and Mississippi data set. The sequenced data sets are classified by ResNet. The accuracy of the sequenced data sets increases by 2.568% on average in 30 generations, and the average time reduction per epoch is 24.143%. Experiments show that this method can effectively select the feature sequencing algorithm with the best comprehensive performance.

ACT-6, a novel plasmid-encoded class C ß-lactamase in a Klebsiella pneumoniae isolate from China.

The purpose of this study was to investigate the phenotypic and molecular characterization of a novel plasmid-mediated AmpC-type ß-lactamase in Klebsiella pneumoniae E701 isolated from Anhui province in China. In comparison with the ACT-1, sequence analysis revealed that there were 43 point mutations in the coding gene, and 10 of which led to amino-acid substitution. Resistance could be transferred by conjugation or transformation with plasmid DNA into E. coli JM109, which was due to the production of a ß-lactamase with an isoelectric point of 8.4 named ACT-6. Cloning, expression, purification and kinetics were carried out to study the characterization of the novel AmpC-type ß-lactamase. The results of MIC determinations and substrate profiles showed there was no significant difference in the activities of the novel enzyme and ACT-1. Moreover, the class 1 integron and the whole open reading frame of the novel AmpC-type ß-lactamase from K.pneumoniae E701 were detectable in the same size plasmid. This is the first report on the emergence of the novel ACT-6 type ß-lactamases in K. pneumoniae.