Cucumber (Cucumis sativus L.) translationally controlled tumor protein interacts with CsRab11A and promotes activation of target of rapamycin in response to Podosphaera xanthii.

The target of rapamycin (TOR) kinase serves as a central regulator that integrates nutrient and energy signals to orchestrate cellular and organismal physiology in both animals and plants. Despite significant advancements having been made in understanding the molecular and cellular functions of plant TOR kinases, the upstream regulators that modulate TOR activity are not yet fully elucidated. In animals, the translationally controlled tumor protein (TCTP) is recognized as a key player in TOR signaling. This study reveals that two TCTP isoforms from Cucumis sativus, when introduced into Arabidopsis, are instrumental in balancing growth and defense mechanisms against the fungal pathogen Golovinomyces cichoracearum. We hypothesize that plant TCTPs act as upstream regulators of TOR in response to powdery mildew caused by Podosphaera xanthii in Cucumis. Our research further uncovers a stable interaction between CsTCTP and a small GTPase, CsRab11A. Transient transformation assays indicate that CsRab11A is involved in the defense against P. xanthii and promotes the activation of TOR signaling through CsTCTP. Moreover, our findings demonstrate that the critical role of TOR in plant disease resistance is contingent upon its regulated activity; pretreatment with a TOR inhibitor (AZD-8055) enhances cucumber plant resistance to P. xanthii, while pretreatment with a TOR activator (MHY-1485) increases susceptibility. These results suggest a sophisticated adaptive response mechanism in which upstream regulators, CsTCTP and CsRab11A, coordinate to modulate TOR function in response to P. xanthii, highlighting a novel aspect of plant-pathogen interactions.

Target of rapamycin (TOR) plays a role in regulating ROS-induced chloroplast damage during cucumber (Cucumis sativus) leaf senescence.

In cucumber production, delaying leaf senescence is crucial for improving cucumber yield and quality. Target of rapamycin (TOR) is a highly conserved serine/threonine protein kinase in eukaryotes, which can integrate exogenous and endogenous signals (such as cell energy state levels) to stimulate cell growth, proliferation, and differentiation. However, no studies have yet examined the regulatory role of TOR signalling in cucumber leaf senescence. In this study, the effects of TOR signalling on dark-induced cucumber leaf senescence were investigated using the TOR activator MHY1485 and inhibitor AZD8055 combined with transient transformation techniques. The results indicate that TOR responds to dark-induced leaf senescence, and alterations in TOR activity/expression influence cucumber leaf resistance to dark-induced senescence. Specifically, in plants with elevated TOR activity/expression, we observed reduced expression of senescence-related genes, less membrane lipid damage, decreased cell apoptosis, lower levels of reactive oxygen species production, and less damage to the photosynthetic system compared to the control. In contrast, in plants with reduced TOR activity/expression, we observed higher expression of senescence-related genes, increased membrane lipid damage, enhanced cell apoptosis, elevated levels of reactive oxygen species production, and more damage to the photosynthetic system. These comprehensive results underscore the critical role of TOR in regulating dark-induced cucumber leaf senescence. These findings provide a foundation for controlling premature leaf senescence in cucumber production and offer insights for further exploration of leaf senescence mechanisms and the development of more effective control methods.

Global research evolution and frontier analysis of artificial intelligence in brain injury: A bibliometric analysis.

Research on artificial intelligence for brain injury is currently a prominent area of scientific research. A significant amount of related literature has been accumulated in this field. This study aims to identify hotspots and clarify research resources by conducting literature metrology visualization analysis, providing valuable ideas and references for related fields. The research object of this paper consists of 3000 articles cited in the core database of Web of Science from 1998 to 2023. These articles are visualized and analyzed using VOSviewer and CiteSpace. The bibliometric analysis reveals a continuous increase in the number of articles published on this topic, particularly since 2016, indicating significant growth. The United States stands out as the leading country in artificial intelligence for brain injury, followed by China, which tends to catch up. The core research institutions are primarily universities in developed countries, but there is a lack of cooperation and communication between research groups. With the development of computer technology, the research in this field has shown strong wave characteristics, experiencing the early stage of applied research based on expert systems, the middle stage of prediction research based on machine learning, and the current phase of diversified research focused on deep learning. Artificial intelligence has innovative development prospects in brain injury, providing a new orientation for the treatment and auxiliary diagnosis in this field.

Epidemiological and transcriptome data identify association between iron overload and metabolic dysfunction-associated steatotic liver disease and hepatic fibrosis.

The primary objective of this study was to examine the association between iron overload (IO), metabolic dysfunction-associated steatotic liver disease (MASLD), and hepatic fibrosis. We hypothesized that there is a significant association. Data from the NHANES (2017-2020) were analyzed to explore IO's impact on MASLD and hepatic fibrosis in U.S. adults. We assessed serum ferritin, controlled attenuation parameter (CAP), liver stiffness measurement (LSM), and various covariates. Gene expression data were sourced from the FerrDb V2 and GEO databases. Differential gene expression analysis, Protein-Protein Interaction (PPI) Network construction, and Gene Ontology (GO) and KEGG pathway enrichment analyses were performed. The study verified the link between MASLD, hepatic fibrosis, and iron overload hub genes. This study of 5927 participants, averaging 46.78 years of age, revealed significant correlations between serum ferritin and CAP, LSM, after adjusting for covariates. Threshold effect analysis indicated nonlinear associations between serum ferritin and CAP, LSM, with distinct patterns observed by age and gender. Moreover, the area under the ROC curve for serum ferritin with MASLD and hepatic fibrosis was 0.8272 and 0.8376, respectively, demonstrating its performance in assessing these conditions. Additionally, molecular analyses identified potential hub genes associated with iron overload and MASLD, and hepatic fibrosis, revealing the underlying mechanisms. Our study findings reveal an association between iron overload, MASLD, and hepatic fibrosis. Additionally, the hub genes may be implicated in iron overload and subsequently contribute to the progression of MASLD and hepatic fibrosis. These findings support precision nutrition strategies.

Phosphoproteomics analysis of the effect of target of rapamycin kinase inhibition on Cucumis sativus in response to Podosphaera xanthii.

Target of rapamycin (TOR) kinase is a conserved sensor of cell growth in yeasts, plants, and mammals. Despite the extensive research on the TOR complex in various biological processes, large-scale phosphoproteomics analysis of TOR phosphorylation events upon environmental stress are scarce. Powdery mildew caused by Podosphaera xanthii poses a major threat to the quality and yield of cucumber (Cucumis sativus L.). Previous studies concluded that TOR participated in abiotic and biotic stress responses. Hence, studying the underlying mechanism of TOR-P. xanthii infection is particularly important. In this study, we performed a quantitative phosphoproteomics studies of Cucumis against P. xanthii attack under AZD-8055 (TOR inhibitor) pretreatment. A total of 3384 phosphopeptides were identified from the 1699 phosphoproteins. The Motif-X analysis showed high sensitivity and specificity of serine sites under AZD-8055-treatment or P. xanthii stress, and TOR exhibited a unique preference for proline at +1 position and glycine at -1 position to enhance the phosphorylation response to P. xanthii. The functional analysis suggested that the unique responses were attributed to proteins related to plant hormone signaling, mitogen-activated protein kinase cascade signaling, phosphatidylinositol signaling system, and circadian rhythm; and calcium signaling- and defense response-related proteins. Our results provided rich resources for understanding the molecular mechanism of how the TOR kinase controlled plant growth and stress adaptation.

Pharmacological Mechanism of Sancao Yuyang Decoction in the Treatment of Oral Mucositis Based on Network Pharmacology and Experimental Validation.

Purpose: The network pharmacology analysis, molecular docking and experimental verification were performed to explore the pharmacological mechanisms of Sancao Yuyang Decoction (SCYYD) in the treatment of oral mucositis (OM). Methods: Active ingredients in SCYYD and their potential targets, as well as OM-related targets were screened from public databases. The core targets and signaling pathways of SCYYD against OM were determined by protein-protein interaction (PPI) network, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. The ingredient-target-disease network and target-pathway network were constructed. Subsequently, molecular docking was carried out to predict the binding activity between active ingredients and key targets. Moreover, in vivo experiment was conducted to further verify the core targets predicted by network pharmacology analysis. Results: A total of 119 bioactive ingredients were screened from the corresponding databases. One hundred and eighty-six putative targets were retrieved and bioinformatics analysis was performed to reveal the top 5 potential candidate agents and 10 core targets. GO and KEGG enrichment analysis showed that SCYYD exerted excellent therapeutic effects on OM through several pathways, such as HIF-1 and Ras signaling pathway. Subsequently, molecular docking showed that main ingredients in SCYYD had optimal binding activities to the key protein targets. Moreover, the result of in vivo experiment indicated that SCYYD not only inhibited inflammation response and promoted wound healing of oral mucosa in OM rats, but also reversed high expressions of SRC, HSP90AA1, STAT3, HIF1α, mTOR, TLR4, MMP9, and low expression of ESR1. Conclusion: This study preliminarily uncovered the multiple compounds and multiple targets of SCYYD against OM using network pharmacology, molecular docking and in vivo verification, which provided a new insight of the pharmacological mechanisms of SCYYD in treatment of OM.