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Autophagy in eukaryotes functions to maintain homeostasis by degradation and recycling of long-lived and unwanted cellular materials. Autophagy plays important roles in pathogenicity of various fungal pathogens, suggesting that autophagy is a novel target for development of antifungal compounds. Here, we describe bioluminescence resonance energy transfer (BRET)-based high-throughput screening (HTS) strategy to identify compounds that inhibit fungal ATG4 cysteine protease-mediated cleavage of ATG8 that is critical for autophagosome formation. We identified ebselen (EB) and its analogs ebselen oxide (EO) and 2-(4-methylphenyl)-1,2-benzisothiazol-3(2H)-one (PT) as inhibitors of fungal pathogens Botrytis cinerea and Magnaporthe oryzae ATG4-mediated ATG8 processing. The EB and its analogs inhibit spore germination, hyphal development, and appressorium formation in Ascomycota pathogens, B. cinerea, M. oryzae, Sclerotinia sclerotiorum and Monilinia fructicola. Treatment with EB and its analogs significantly reduced fungal pathogenicity. Our findings provide molecular insights to develop the next generation of antifungal compounds by targeting autophagy in important fungal pathogens.

Abstract We measured the levels of High‐Mobility Group Box 1 (HMGB1), Receptor for Advanced Glycation Endproducts (RAGE), T Helper 17 cells (Th17), Regulatory T cells (Treg), and related cytokines in the peripheral blood of patients with severe preeclampsia (SPE) complicated with acute heart failure (AHF) to explore the expression changes in these indicators. In total, 96 patients with SPE admitted to Gansu Provincial Maternity and Child‐care Hospital between June 2020 and June 2022 were included in the study. The patients were divided into SPE+AHF (40 patients) and SPE (56 patients) groups based on whether they suffered from AHF. Additionally, 56 healthy pregnant women who either received prenatal examinations or were admitted to our hospital for delivery during the same period were selected as the healthy control group. An enzyme‐linked immunosorbent assay was performed to detect the expression levels of HMGB1, RAGE, interleukin (IL)‐17, IL‐6, transforming growth factor β (TGF‐β), IL‐10, and NT‐proBNP in plasma. Flow cytometry was employed to determine the percentages of Th17 and Treg cells. Compared to the healthy control group, the SPE+AHF and SPE groups had higher plasma levels of HMGB1 and RAGE expression, higher Th17 percentage and Th17/Treg ratio, and lower Treg percentage. Compared to the SPE group, the SPE+AHF group had higher plasma levels of HMGB1 and RAGE expression, higher Th17 percentage and Th17/Treg ratio, and lower Treg percentage (P

Accumulating evidence has shown that the apoptosis of trophoblast cells plays an important role in the pathogenesis of preeclampsia, and an intricate interplay between DNA methylation and polycomb group (PcG) protein-mediated gene silencing has been highlighted recently. Here, we provide evidence that the expression of nervous system polycomb 1 (NSPc1), a BMI1 homologous polycomb protein, is significantly elevated in trophoblast cells during preeclampsia, which accelerates trophoblast cell apoptosis. Since NSPc1 acts predominantly as a transcriptional inactivator that specifically represses HOXA11 expression in trophoblast cells during preeclampsia, we further show that NSPc1 is required for DNMT3a recruitment and maintenance of the DNA methylation in the HOXA11 promoter in trophoblast cells during preeclampsia. In addition, we find that the interplay of DNMT3a and NSPc1 represses the expression of HOXA11 and promotes trophoblast cell apoptosis. Taken together, these results indicate that the cooperation between NSPc1 and DNMT3a reduces HOXA11 expression in preeclampsia pathophysiology, which provides novel therapeutic approaches for targeted inhibition of trophoblast cell apoptosis during preeclampsia pathogenesis.

Aim and background: Tertiary lymphoid structures (TLS) are increasingly recognized for their role in immunity. Despite growing interest, a systematic bibliometric analysis of TLS-related research has been lacking. To provide a comprehensive overview of current research trends and hotspots, we conducted a bibliometric analysis using data from the Web of Science Core Collection. Methods: We retrieved TLS-related publications from the Science Citation Index Expanded within the Web of Science Core Collection from January 2014 to December 2023. Co-occurrence analysis with "VOSviewer" identified current status and research hotspots, while "CiteSpace" was used for co-citation analysis to assess knowledge evolution and bursts. Thematic evolution was explored using bibliometrics to identify emerging keyword trends. Additionally, we examined country/region, institutional, and author contributions and collaborations. Tables were created using Microsoft Word. Results: A total of 785 publications were analyzed, showing a continuous growth trend from 2017 to 2023, indicating escalating interest in TLS among researchers. Leading countries in TLS research were China (231 publications), the United States (212 publications), and France (89 publications). The most productive institution and author were the "Institut national de la santé et de la recherche médicale" (70 publications) and Catherine Sautes-Fridman (21 publications), respectively. Key topics included TLS, B cells, and immunotherapy. Recent research has focused on mechanisms linking TLS with cancers, such as immunotherapy, tumor microenvironment, tumor-infiltrating lymphocytes, prognosis, and immune checkpoint inhibitors, highlighting an expanding area of study. Additionally, TLS' potential as a biomarker for predicting immunotherapy efficacy across different cancer types remains a burgeoning research direction. Conclusions: This study provides a comprehensive analysis of global TLS-related publications, revealing key literature metrics and identifying influential articles and emerging research concerns. These findings contribute valuable insights into the role of TLS in immunotherapy and suggest future directions for this dynamic field. [ABSTRACT FROM AUTHOR]

Background: Excessive oxidative stress is known to cause endothelial dysfunction and drive cardiovascular diseases (CVD). While telomerase reverse transcriptase (TERT) shows protective effects against oxidative stress in rodents and is associated to human flow-mediated dilation in CVD, its regulatory mechanisms in human vascular systems under pathological oxidative stress require further investigation. Methods: Human induced pluripotent stem cells (hiPSCs) were used to create vascular organoids (VOs). These VOs and human umbilical vein endothelial cells (HUVECs) were subjected to oxidative stress through both hydrogen peroxide (H2O2) and oxidized low-density lipoprotein (oxLDL) models. The effects of TERT overexpression by inhibition of the ubiquitin protein ligase E3 component N-recognin 5 (UBR5) on reactive oxygen species (ROS)-induced vascular injury and cellular senescence were assessed using neovascular sprouting assays, senescence-associated β-galactosidase (SA-β-Gal) staining, and senescence-associated secretory phenotype (SASP) assays. Results: ROS significantly impaired VO development and endothelial progenitor cell (EPC) angiogenesis, evidenced by reduced neovascular sprouting and increased senescence markers, including elevated SA-β-Gal activity and SASP-related cytokine levels. Overexpression of TERT counteracted these effects, restoring VO development and EPC function. Immunoprecipitation-mass spectrometry identified UBR5 as a critical TERT regulator, facilitating its degradation. Inhibition of UBR5 stabilized TERT, improving VO angiogenic capacity, and reducing SA-β-Gal activity and SASP cytokine levels. Conclusions: Inhibiting UBR5 stabilizes TERT, which preserves EPC angiogenic capacity, reduces VO impairment, and delays endothelial cell senescence under oxidative stress. These findings highlight the potential of targeting UBR5 to enhance vascular health in oxidative stress-related conditions. [ABSTRACT FROM AUTHOR]

Autonomous path planning of UAV is a key technical problem for future UAV operation. In view of the shortcomings of traditional route planning methods,such as low efficiency,poor real-time performance,easy to fall into local optimum,an improved heuristic ant colony algorithm for UAV route planning is proposed. In the early stage of the algorithm,Dijkstra algorithm is used to initialize the track,and heuristic information is introduced to improve the search efficiency. Logistic chaotic map is used to initialize pheromone,so that the diversity of solutions can be increased and the convergence speed of the algorithm can be improved. In the middle and late stage of the algorithm,multi-track selection strategy and simulated annealing mechanism are used to improve the global search ability of the algorithm,which avoid falling into local optimum due to too fast convergence speed solution. The simulation results show that,compared with the basic ant colony algorithm,the improved ant colony algorithm can plan a path from the start to the end effectively in the complex environment with threats and obstacles. It also has higher optimization accuracy and faster convergence speed,which is of applicable value.

Along with the advancement of low-altitude airspace reform, it has become a developing trend that UAV leaves the isolation airspace and gets into the fusion low-altitude airspace to perform diverse missions. A serious threat is brought to UAV in the low dynamic complex fusion airspace, so the obstacle avoidance technology has become a key process in UAV mission decision-making system, to ensure the safe operation of the UAV and to improve working efficiency. Firstly, the relevant concepts, path evaluation indexes and key technologies of UAV obstacle avoidance are described. Then, the concepts of obstacle avoidance algorithms based on optimization, potential field and machine learning are described, and the advantages and disadvantages of these algorithms are compared. Finally, the current challenges that restrict the development of UAV obstacle avoidance and the future research directions are proposed.