Ferroptosis is an iron-dependent form of regulated necrosis. It is implicated in various human diseases, including ischemic organ damage and cancer. Here, we report the crucial role of autophagy, ...particularly autophagic degradation of cellular iron storage proteins （a process known as ferritinophagy）, in ferroptosis. Using RNAi screening coupled with subsequent genetic analysis, we identified multiple autophagy-related genes as positive regulators of ferroptosis. Ferroptosis induction led to autophagy activation and consequent degradation of ferritin and ferritino- phagy cargo receptor NCOA4. Consistently, inhibition of ferritinophagy by blockage of autophagy or knockdown of NCOA4 abrogated the accumulation of ferroptosis-associated cellular labile iron and reactive oxygen species, as well as eventual ferroptotic cell death. Therefore, ferroptosis is an autophagic cell death process, and NCOA4-mediated ferritinophagy supports ferroptosis by controlling cellular iron homeostasis.
In recent years, the integration of digital technology development and the traditional financial service industry has generated a new financial service model, that is, digital finance, which has ...exerted a certain impact on various industries. This paper selects the panel data of 30 provinces in China from 2011 to 2020 to explore how digital finance will affect the agglomeration development of the logistics industry. The two-way fixed model is used for empirical analysis and the results show that digital finance has a significant role in promoting the agglomeration development of the logistics industry. From different perspectives, the coverage breadth, depth of use, and digitalization finance greatly promote the logistics industry, while digitalization development has no such impact on the logistics industry. The positive impact of digital finance on logistics industry agglomeration has clear regional heterogeneity. Specifically speaking, the impact of digital finance in central and western regions is significant on logistics industry agglomeration, while that in the eastern region is not. Therefore, in order to further expand the role of digital finance in promoting the agglomeration development of the logistics industry, we should spare no efforts to develop digital finance, strengthen regional cooperation, and improve the coordinated development of digital finance and logistics industry agglomeration.
Mitogen-activated protein kinase (MAPK) cascades play important roles in regulating plant innate immune responses. In a genetic screen to search for mutants with constitutive defense responses, we ...identified multiple alleles of mpk4 and mekk1 that exhibit cell death and constitutive defense responses. Bimolecular fluorescence complementation (BiFC) analysis showed that both MPK4 and MEKK1 interact with MKK1 and MKK2, two closely related MAPK kinases. mkk1 and mkk2 single mutant plants do not have obvious mutant phenotypes. To test whether MKK1 and MKK2 function redundantly, mkk1 mkk2 double mutants were generated. The mkk1 mkk2 double mutant plants die at seedling stage and the seedling-lethality phenotype is temperature-dependent. Similar to the mpk4 and mekk1 mutants, the mkk1 mkk2 double mutant seedlings accumulate high levels of H2O2, display spontaneous cell death, constitutively express Pathogenesis Related (PR) genes and exhibit pathogen resistance. In addition, activation of MPK4 by flg22 is impaired in the mkk1 mkk2 double mutants, suggesting that MKK1 and MKK2 function together with MPK4 and MEKK1 in a MAP kinase cascade to negatively regulate innate immune responses in plants.
Pathogen-associated molecular pattern (PAMP)-triggered immunity (PTI) serves as a primary plant defense response against microbial pathogens, with MEKK1, MKK1/MKK2, and MPK4 functioning as a MAP ...kinase cascade downstream of PAMP receptors. Plant Resistance (R) proteins sense specific pathogen effectors to initiate a second defense mechanism, termed effector-triggered immunity (ETI). In a screen for suppressors of the mkk1 mkk2 autoimmune phenotype, we identify the nucleotide-binding leucine-rich repeat (NB-LRR) protein SUMM2 and find that the MEKK1-MKK1/MKK2-MPK4 cascade negatively regulates SUMM2-mediated immunity. Further, the MEKK1-MKK1/MKK2-MPK4 cascade positively regulates basal defense targeted by the Pseudomonas syringae pathogenic effector HopAI1, which inhibits MPK4 kinase activity. Inactivation of MPK4 by HopAI1 results in activation of SUMM2-mediated defense responses. Our data suggest that SUMM2 is an R protein that becomes active when the MEKK1-MKK1/MKK2-MPK4 cascade is disrupted by pathogens, supporting the hypothesis that R proteins evolved to protect plants when microbial effectors suppress basal resistance.
► The MEKK1-MKK1/MKK2-MPK4 kinase cascade is required for basal defense ► MEKK1-MKK1/MKK2-MPK4 cascade negatively regulates NB-LRR protein SUMM2-mediated immunity ► The bacterial pathogenic effector HopAI1 targets MPK4 kinase activity ► Inactivation of MPK4 by HopAI1 activates SUMM2-mediated immune responses
Anomaly detection systems can accurately identify malicious network traffic, providing network security. With the development of internet technology, network attacks are becoming more and more ...sourced and complicated, making it difficult for traditional anomaly detection systems to effectively analyze and identify abnormal traffic. At present, deep neural network (DNN) technology achieved great results in terms of anomaly detection, and it can achieve automatic detection. However, there still exists misclassified traffic in the prediction results of deep neural networks, resulting in redundant alarm information. This paper designs a two-level anomaly detection system based on deep neural network and association analysis. We made a comprehensive evaluation of experiments using DNNs and other neural networks based on publicly available datasets. Through the experiments, we chose DNN-4 as an important part of our system, which has high precision and accuracy in identifying malicious traffic. The Apriori algorithm can mine rules between various discretized features and normal labels, which can be used to filter the classified traffic and reduce the false positive rate. Finally, we designed an intrusion detection system based on DNN-4 and association rules. We conducted experiments on the public training set NSL-KDD, which is considered as a modified dataset for the KDDCup 1999. The results show that our detection system has great precision in malicious traffic detection, and it achieves the effect of reducing the number of false alarms.
The identification of ecological security pattern(ESP) is of great significance in solving regional ecological security problems. The study proposes two new perspectives for the study of ESP Firstly, ...a new method for identifying ecological supply and demand areas based on the ratio of ecosystem service supply and demand is proposed; The second is to combine socioeconomic pathways and representative concentration pathways (SSP-RCP) scenarios to predict the future supply and demand of regional ecosystem services under different climate scenarios, and to further predict the future regional ESPs under different climate scenarios. Finally, A planning proposal based on ESP of the Yangtze River Delta(YRD) based on the supply and demand perspective was put forward, with 'two belts-four zones'. The results show that the ESP changes significantly under different climate scenarios, and the ecological demands under the three scenarios continue to increase during the study period.
Cell-surface-localized plant immune receptors, such as FLS2, detect pathogen-associated molecular patterns (PAMPs) and initiate PAMP-triggered immunity (PTI) through poorly understood ...signal-transduction pathways. The pathogenic Pseudomonas syringae effector AvrPphB, a cysteine protease, cleaves the Arabidopsis receptor-like cytoplasmic kinase PBS1 to trigger cytoplasmic immune receptor RPS5-specified effector-triggered immunity (ETI). Analyzing the function of AvrPphB in plants lacking RPS5, we find that AvrPphB can inhibit PTI by cleaving additional PBS1-like (PBL) kinases, including BIK1, PBL1, and PBL2. In unstimulated plants, BIK1 and PBL1 interact with FLS2 and are rapidly phosphorylated upon FLS2 activation by its ligand flg22. Genetic and molecular analyses indicate that BIK1, and possibly PBL1, PBL2, and PBS1, integrate immune signaling from multiple immune receptors. Whereas AvrPphB-mediated degradation of one of these kinases, PBS1, is monitored by RPS5 to initiate ETI, this pathogenic effector targets other PBL kinases for PTI inhibition.
► Pseudomonas syringae effector AvrPphB inhibits PAMP-triggered immunity (PTI) ► PBS1-like kinases required for PTI are AvrPphB protease substrates ► The PBS1-like kinase BIK1 interacts with the PTI receptor FLS2 ► PBS1-like kinases integrate signaling from multiple immune receptors
Salicylic acid (SA) is a defense hormone required for both local and systemic acquired resistance (SAR) in plants. Pathogen infections induce SA synthesis through up-regulating the expression of ...Isochorismate Synthase 1 (ICS1), which encodes a key enzyme in SA production. Here we report that both SAR Deficient 1 (SARD1) and CBP60g are key regulators for ICS1 induction and SA synthesis. Whereas knocking out SARD1 compromises basal resistance and SAR, overexpression of SARD1 constitutively activates defense responses. In the sard1-1 cbp60g-1 double mutant, pathogen-induced ICS1 upregulation and SA synthesis are blocked in both local and systemic leaves, resulting in compromised basal resistance and loss of SAR. Electrophoretic mobility shift assays showed that SARD1 and CBP60g represent a plant-specific family of DNA-binding proteins. Both proteins are recruited to the promoter of ICS1 in response to pathogen infections, suggesting that they control SA synthesis by regulating ICS1 at the transcriptional level.
In Arabidopsis thaliana, the MEKK1-MKK1/MKK2-MPK4 mitogen-activated protein (MAP) kinase cascade represses cell death and immune responses. In mekk1, mkk1 mkk2, and mpk4 mutants, programmed cell ...death and defense responses are constitutively activated, but the mechanism by which MEKK1, MKK1/MKK2, and MPK4 negatively regulate cell death and immunity was unknown. From a screen for suppressors of mkk1 mkk2, we found that mutations in suppressor of mkk1 mkk2 1 (summ1) suppress the cell death and defense responses not only in mkk1 mkk2 but also in mekk1 and mpk4. SUMM1 encodes the MAP kinase kinase kinase MEKK2. It interacts with MPK4 and is phosphorylated by MPK4 in vitro. Overexpression of SUMM1 activates cell death and defense responses that are dependent on the nucleotide bindingleucine-rich repeat protein SUMM2. Taken together, our data suggest that the MEKK1-MKK1/MKK2-MPK4 kinase cascade negatively regulates MEKK2 and activation of MEKK2 triggers SUMM2-mediated immune responses.
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