Asexual reproduction strategies in the moon jellyfish Aurelia (Cnidaria: Scyphozoa)

The genus Aurelia is one of the major contributors to jellyfish blooms in coastal waters, possibly due to its adaptive reproduction strategies. Different Aurelia lineages have adapted their reproduction modes to varying environmental conditions in their respective habitats. To understand the successful adaptation strategies, three strains of Aurelia coerulea and two strains of Aurelia solida polyps from different geographical areas were exposed to a range of temperatures and two food regimes, and the effects on reproduction rates were assessed. Asexual reproduction was significantly affected by the changes in these factors. The highest reproduction rate under sufficient food conditions was observed in the United States strain and the lowest was observed in the Israel strain, regardless of temperature, indicating the differences in the blooming potential. Six asexual reproduction modes were observed, of which lateral budding, lateral budding by means of stolons, and reproduction from parts of stolons were the main modes used by all Aurelia strains, except Aurelia solidaISR, for which reproduction by stolons was the main mode. The capability to switch reproductive strategies in response to environmental cues depending on the lineage predetermines the highly frequent blooming events of Aurelia.Fil: Wang, Fanghan. Chinese Academy of Sciences; República de ChinaFil: Schiariti, Agustin. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones Marinas y Costeras. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Instituto de Investigaciones Marinas y Costeras; Argentina. Instituto Nacional de Investigaciones y Desarrollo Pesquero; ArgentinaFil: Xu, Shengnan. Chinese Academy of Sciences; República de ChinaFil: Ma, Yuanqing. Shandong Marine Resource And Environment Research Institute; ChinaFil: Sun, Tingting. Chinese Academy of Sciences; República de ChinaFil: Wang, Lei. Chinese Academy of Sciences; República de ChinaFil: Zhao, Jianmin. Chinese Academy of Sciences; República de ChinaFil: Dong, Zhijun. Chinese Academy of Sciences; República de Chin

Renshen Yangrong decoction for secondary malaise and fatigue: network pharmacology and Mendelian randomization study

BackgroundRenshen Yangrong decoction (RSYRD) has been shown therapeutic effects on secondary malaise and fatigue (SMF). However, to date, its bioactive ingredients and potential targets remain unclear.PurposeThe purpose of this study is to assess the potential ingredients and targets of RSYRD on SMF through a comprehensive strategy integrating network pharmacology, Mendelian randomization as well as molecular docking verification.MethodsSearch for potential active ingredients and corresponding protein targets of RSYRD on TCMSP and BATMAN-TCM for network pharmacology analysis. Mendelian randomization (MR) was performed to find therapeutic targets for SMF. The eQTLGen Consortium (sample sizes: 31,684) provided data on cis-expression quantitative trait loci (cis-eQTL, exposure). The summary data on SMF (outcome) from genome-wide association studies (GWAS) were gathered from the MRC-IEU Consortium (sample sizes: 463,010). We built a target interaction network between the probable active ingredient targets of RSYRD and the therapeutic targets of SMF. We next used drug prediction and molecular docking to confirm the therapeutic value of the therapeutic targets.ResultsIn RSYRD, network pharmacology investigations revealed 193 possible active compounds and 234 associated protein targets. The genetically predicted amounts of 176 proteins were related to SMF risk in the MR analysis. Thirty-seven overlapping targets for RSYRD in treating SMF, among which six (NOS3, GAA, IMPA1, P4HTM, RB1, and SLC16A1) were prioritized with the most convincing evidence. Finally, the 14 active ingredients of RSYRD were identified as potential drug molecules. The strong affinity between active components and putative protein targets was established by molecular docking.ConclusionThis study revealed several active components and possible RSYRD protein targets for the therapy of SMF and provided novel insights into the feasibility of using Mendelian randomization for causal inference between Chinese medical formula and disease

PML-ED : A method of partial multi-label learning by using encoder-decoder framework and exploring label correlation

Partial multi-label learning (PML) addresses problems where each instance is assigned a candidate label set and only a subset of these candidate labels is correct. The major challenge of PML is that the training procedure can be easily misguided by noisy labels. Current studies on PML have revealed two significant drawbacks. First, most of them do not sufficiently explore complex label correlations, which could improve the effectiveness of label disambiguation. Second, PML models heavily rely on prior assumptions, limiting their applicability to specific scenarios. In this work, we propose a novel method of PML based on the Encoder-Decoder Framework (PML-ED) to address the drawbacks. PML-ED initially achieves the distribution of label probability through a KNN label attention mechanism. It then adopts Conditional Layer Normalization (CLN) to extract the high-order label correlation and relaxes the prior assumption of label noise by introducing a universal Encoder-Decoder framework. This approach makes PML-ED not only more efficient compared to the state-of-the-art methods, but also capable of handling the data with large noisy labels across different domains. Experimental results on 28 benchmark datasets demonstrate that the proposed PML-ED model, when benchmarked against nine leading-edge PML algorithms, achieves the highest average ranking across five evaluation criteria

Asexual reproduction strategies in the moon jellyfish Aurelia (Cnidaria: Scyphozoa)

The genus Aurelia is one of the major contributors to jellyfish blooms in coastal waters, possibly due to its adaptive reproduction strategies. Different Aurelia lineages have adapted their reproduction modes to varying environmental conditions in their respective habitats. To understand the successful adaptation strategies, three strains of Aurelia coerulea and two strains of Aurelia solida polyps from different geographical areas were exposed to a range of temperatures and two food regimes, and the effects on reproduction rates were assessed. Asexual reproduction was significantly affected by the changes in these factors. The highest reproduction rate under sufficient food conditions was observed in the United States strain and the lowest was observed in the Israel strain, regardless of temperature, indicating the differences in the blooming potential. Six asexual reproduction modes were observed, of which lateral budding, lateral budding by means of stolons, and reproduction from parts of stolons were the main modes used by all Aurelia strains, except Aurelia solida(ISR), for which reproduction by stolons was the main mode. The capability to switch reproductive strategies in response to environmental cues depending on the lineage predetermines the highly frequent blooming events of Aurelia

Environmental and molecular regulation of diapause formation in a scyphozoan jellyfish

Understanding the mechanisms underlying diapause formation is crucial for gaining insight into adaptive survival strategies across various species. In this study, we aimed to uncover the pivotal role of temperature and food availability in regulating diapausing podocyst formation in the jellyfish Aurelia coerulea. Furthermore, we explored the cellular and molecular basis of diapause formation using single-cell RNA sequencing. Our results showed cell-type-specific transcriptional landscapes during podocyst formation, which were underscored by the activation of specific transcription factors and signalling pathways. In addition, we found that the heat shock protein-coding genes HSC70 and HSP90a potentially act as hub genes that regulate podocyst formation. Finally, we mapped the single-cell atlas of diapausing podocysts and identified cell types involved in metabolism, environmental sensing, defence and development that may collectively contribute to the long-term survival and regulated excystment of diapausing podocysts. Taken together, the findings of this study provide novel insights into the molecular mechanisms that regulate diapause formation and contributes to a better understanding of adaptive survival strategies in a variety of ecological contexts

Design and Synthesis of Novel Ultralong-Acting Peptides as EDP-EBP Interaction Inhibitors for Pulmonary Fibrosis Treatment

The increased remodeling of the extracellular matrix (ECM) in pulmonary fibrosis (PF) generates bioactive ECM fragments called matricryptins, which include elastin-derived peptides (EDPs). The interaction between EDPs and their receptors, including elastin-binding protein (EBP), plays a crucial role in exacerbating fibrosis. Here, we present LXJ‑02 for the first time, a novel ultralong-acting inhibitor that disrupts the EDPs/EBP peptide–protein interaction, promoting macrophages to secrete matrix metalloproteinase-12 (MMP-12), and showing great promise as a stable peptide. MMP-12 has traditionally been implicated in promoting inflammation and fibrosis in various acute and chronic diseases. However, we reveal a novel role of LXJ‑02 that activates the macrophage-MMP-12 axis to increase MMP-12 expression and degrade ECM components like elastin. This leads to the preventing of PF while also improving EDP-EBP interaction. LXJ‑02 effectively reverses PF in mouse models with minimal side effects, holding great promise as an excellent therapeutic agent for lung fibrosis

Design and Synthesis of Novel Ultralong-Acting Peptides as EDP-EBP Interaction Inhibitors for Pulmonary Fibrosis Treatment

The increased remodeling of the extracellular matrix (ECM) in pulmonary fibrosis (PF) generates bioactive ECM fragments called matricryptins, which include elastin-derived peptides (EDPs). The interaction between EDPs and their receptors, including elastin-binding protein (EBP), plays a crucial role in exacerbating fibrosis. Here, we present LXJ‑02 for the first time, a novel ultralong-acting inhibitor that disrupts the EDPs/EBP peptide–protein interaction, promoting macrophages to secrete matrix metalloproteinase-12 (MMP-12), and showing great promise as a stable peptide. MMP-12 has traditionally been implicated in promoting inflammation and fibrosis in various acute and chronic diseases. However, we reveal a novel role of LXJ‑02 that activates the macrophage-MMP-12 axis to increase MMP-12 expression and degrade ECM components like elastin. This leads to the preventing of PF while also improving EDP-EBP interaction. LXJ‑02 effectively reverses PF in mouse models with minimal side effects, holding great promise as an excellent therapeutic agent for lung fibrosis

Design and Synthesis of Novel Ultralong-Acting Peptides as EDP-EBP Interaction Inhibitors for Pulmonary Fibrosis Treatment

The increased remodeling of the extracellular matrix (ECM) in pulmonary fibrosis (PF) generates bioactive ECM fragments called matricryptins, which include elastin-derived peptides (EDPs). The interaction between EDPs and their receptors, including elastin-binding protein (EBP), plays a crucial role in exacerbating fibrosis. Here, we present LXJ‑02 for the first time, a novel ultralong-acting inhibitor that disrupts the EDPs/EBP peptide–protein interaction, promoting macrophages to secrete matrix metalloproteinase-12 (MMP-12), and showing great promise as a stable peptide. MMP-12 has traditionally been implicated in promoting inflammation and fibrosis in various acute and chronic diseases. However, we reveal a novel role of LXJ‑02 that activates the macrophage-MMP-12 axis to increase MMP-12 expression and degrade ECM components like elastin. This leads to the preventing of PF while also improving EDP-EBP interaction. LXJ‑02 effectively reverses PF in mouse models with minimal side effects, holding great promise as an excellent therapeutic agent for lung fibrosis

Design and Synthesis of Novel Ultralong-Acting Peptides as EDP-EBP Interaction Inhibitors for Pulmonary Fibrosis Treatment

The increased remodeling of the extracellular matrix (ECM) in pulmonary fibrosis (PF) generates bioactive ECM fragments called matricryptins, which include elastin-derived peptides (EDPs). The interaction between EDPs and their receptors, including elastin-binding protein (EBP), plays a crucial role in exacerbating fibrosis. Here, we present LXJ‑02 for the first time, a novel ultralong-acting inhibitor that disrupts the EDPs/EBP peptide–protein interaction, promoting macrophages to secrete matrix metalloproteinase-12 (MMP-12), and showing great promise as a stable peptide. MMP-12 has traditionally been implicated in promoting inflammation and fibrosis in various acute and chronic diseases. However, we reveal a novel role of LXJ‑02 that activates the macrophage-MMP-12 axis to increase MMP-12 expression and degrade ECM components like elastin. This leads to the preventing of PF while also improving EDP-EBP interaction. LXJ‑02 effectively reverses PF in mouse models with minimal side effects, holding great promise as an excellent therapeutic agent for lung fibrosis

Design and Synthesis of Novel Ultralong-Acting Peptides as EDP-EBP Interaction Inhibitors for Pulmonary Fibrosis Treatment

The increased remodeling of the extracellular matrix (ECM) in pulmonary fibrosis (PF) generates bioactive ECM fragments called matricryptins, which include elastin-derived peptides (EDPs). The interaction between EDPs and their receptors, including elastin-binding protein (EBP), plays a crucial role in exacerbating fibrosis. Here, we present LXJ‑02 for the first time, a novel ultralong-acting inhibitor that disrupts the EDPs/EBP peptide–protein interaction, promoting macrophages to secrete matrix metalloproteinase-12 (MMP-12), and showing great promise as a stable peptide. MMP-12 has traditionally been implicated in promoting inflammation and fibrosis in various acute and chronic diseases. However, we reveal a novel role of LXJ‑02 that activates the macrophage-MMP-12 axis to increase MMP-12 expression and degrade ECM components like elastin. This leads to the preventing of PF while also improving EDP-EBP interaction. LXJ‑02 effectively reverses PF in mouse models with minimal side effects, holding great promise as an excellent therapeutic agent for lung fibrosis