Pub Date : 2025-03-25DOI: 10.1016/j.jare.2025.03.022
Zuodong Zhou, Jiawei E, Qianwen Shi, Wenjun Zhang, Liyun Sun, Jianhua Fan
Introduction
Tetraselmis helgolandica is a marine microalga belonging to the Chlorophyta phylum. It is widely distributed in the coastal waters of Asia and is commonly used as aquatic feed. T. helgolandica is characterized by its large size, preference for starch accumulation, low temperature tolerance, presence of flagella, and strong motility. However, research on T. helgolandica is limited, and its genome data remains unavailable.
Objective
We generated a high-quality, chromosome-scale genome of T. helgolandica. Through comparative genomics, we uncovered the genome characteristics and evolutionary history of T. helgolandica. Additionally, by integrating transcriptome data, we elucidated how the light–dark rhythm enhances the high starch production.
Methods
We utilized long-read sequencing data and high-throughput chromosome conformation capture data from the Oxford Nanopore platform to construct a high-quality genome of T. helgolandica. Genome annotation was performed using multiple databases, and comparative genomic analysis was conducted with nine species, including Arabidopsis thaliana, to reveal the evolutionary history. Finally, we combined transcriptome data to elucidate the molecular mechanisms underlying the high starch yield.
Results
Circadian rhythm significantly promote starch accumulation and increase amylose content. The chromosome-scale genome revealed it shares a common ancestor with other green algae approximately 1,017 million years ago. This relatively ancient divergence underscores its evolutionary distinction within the green lineage. It may possess a more complex protein modification mechanism and a more fully developed Golgi apparatus. Circadian rhythm broadly up-regulates key enzymes involved in starch synthesis, including GBSS and Starch Synthase, while down-regulating SS Ⅲa. This regulation enhances starch accumulation and increases the amylose content.
Conclusion
This study provided a high-quality genome of T. helgolandica and revealed the potential mechanism by which the circadian rhythm promotes starch accumulation and increases the amylose ratio. The genome of T. helgolandica will serve as an important resource for evolutionary research and transgenic platform development.
{"title":"Chromosome-level genome provides novel insights into the starch metabolism regulation and evolutionary history of Tetraselmis helgolandica","authors":"Zuodong Zhou, Jiawei E, Qianwen Shi, Wenjun Zhang, Liyun Sun, Jianhua Fan","doi":"10.1016/j.jare.2025.03.022","DOIUrl":"https://doi.org/10.1016/j.jare.2025.03.022","url":null,"abstract":"<h3>Introduction</h3>Tetraselmis helgolandica is a marine microalga belonging to the Chlorophyta phylum. It is widely distributed in the coastal waters of Asia and is commonly used as aquatic feed. T. helgolandica is characterized by its large size, preference for starch accumulation, low temperature tolerance, presence of flagella, and strong motility. However, research on T. helgolandica is limited, and its genome data remains unavailable.<h3>Objective</h3>We generated a high-quality, chromosome-scale genome of T. helgolandica. Through comparative genomics, we uncovered the genome characteristics and evolutionary history of T. helgolandica. Additionally, by integrating transcriptome data, we elucidated how the light–dark rhythm enhances the high starch production.<h3>Methods</h3>We utilized long-read sequencing data and high-throughput chromosome conformation capture data from the Oxford Nanopore platform to construct a high-quality genome of <em>T. helgolandica.</em> Genome annotation was performed using multiple databases, and comparative genomic analysis was conducted with nine species, including <em>Arabidopsis thaliana</em>, to reveal the evolutionary history. Finally, we combined transcriptome data to elucidate the molecular mechanisms underlying the high starch yield.<h3>Results</h3>Circadian rhythm significantly promote starch accumulation and increase amylose content. The chromosome-scale genome revealed it shares a common ancestor with other green algae approximately 1,017 million years ago. This relatively ancient divergence underscores its evolutionary distinction within the green lineage. It may possess a more complex protein modification mechanism and a more fully developed Golgi apparatus. Circadian rhythm broadly up-regulates key enzymes involved in starch synthesis, including GBSS and Starch Synthase, while down-regulating SS Ⅲa. This regulation enhances starch accumulation and increases the amylose content.<h3>Conclusion</h3>This study provided a high-quality genome of <em>T. helgolandica</em> and revealed the potential mechanism by which the circadian rhythm promotes starch accumulation and increases the amylose ratio. The genome of <em>T. helgolandica</em> will serve as an important resource for evolutionary research and transgenic platform development.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"21 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143702939","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-25DOI: 10.1016/j.jare.2025.03.025
Ye Wang, Pengyan Wu, Zhanchao Chen, Zhaoying Li, Yini Wang, Miao Yan, Yiying Zhang, Shanjie Wang, Shaohong Fang, Bo Yu
Aims
Tryptophan catabolism is implicated in the progression of cardiovascular disease. We sought to investigate the prognostic value of tryptophan catabolism-related features in patients with acute myocardial infarction (AMI).
Methods and Results
A prospective cohort of 4071 patients (mean age: 60.7 years; 69.1 % men) with AMI between February 2017 and June 2019 was included and followed up for a median of 5.6 years (IQR 5.1–6.2). There were 666 all-cause deaths, 365 cardiovascular deaths, and 559 HF events. Plasma levels of tryptophan-related metabolites were measured using liquid chromatography tandem mass spectrometry (LC-MS/MS), and were repeatedly determined in 1044 patients after discharge. Tryptophan, kynurenine, indole-3-propionic acid, and indole-3-lactic acid were screened to construct tryptophan metabolites combination (TMC) score using coefficients from predictive models for MACE. Patients were divided into 3 groups by TMC tertiles. Patients with higher TMC score were older, more likely to be male and have hypertension. Compared to those with TMC tertile 1, patients in TMC tertile 3 had significant associations with the risk of all-cause death (HR: 1.90; 95 %CI: 1.54–2.34), cardiovascular death (HR: 2.32; 95 %CI: 1.71–3.15) and incident HF (HR: 1.77; 95 %CI: 1.40–2.24). The incremental prognostic value of TMC score over the Grace score was measured by the likelihood ratio, C-statistic, continuous net reclassification improvement (NRI), and integrated discrimination improvement (IDI) for prediction, discrimination, and reclassification of outcomes.
Conclusions
In this hospital-based AMI cohort, the TMC score was significantly associated with all-cause mortality, cardiovascular mortality, and incident HF, and improved risk stratification beyond established clinical risk factors. The TMC score provided a novel tool for assessment of Trp catabolism dysfunction and outcomes risk.
{"title":"Prognostic value of tryptophan catabolism-base scores in acute myocardial infarction patients","authors":"Ye Wang, Pengyan Wu, Zhanchao Chen, Zhaoying Li, Yini Wang, Miao Yan, Yiying Zhang, Shanjie Wang, Shaohong Fang, Bo Yu","doi":"10.1016/j.jare.2025.03.025","DOIUrl":"https://doi.org/10.1016/j.jare.2025.03.025","url":null,"abstract":"<h3>Aims</h3>Tryptophan catabolism is implicated in the progression of cardiovascular disease. We sought to investigate the prognostic value of tryptophan catabolism-related features in patients with acute myocardial infarction (AMI).<h3>Methods and Results</h3>A prospective cohort of 4071 patients (mean age: 60.7 years; 69.1 % men) with AMI between February 2017 and June 2019 was included and followed up for a median of 5.6 years (IQR 5.1–6.2). There were 666 all-cause deaths, 365 cardiovascular deaths, and 559 HF events. Plasma levels of tryptophan-related metabolites were measured using liquid chromatography tandem mass spectrometry (LC-MS/MS), and were repeatedly determined in 1044 patients after discharge. Tryptophan, kynurenine, indole-3-propionic acid, and indole-3-lactic acid were screened to construct tryptophan metabolites combination (TMC) score using coefficients from predictive models for MACE. Patients were divided into 3 groups by TMC tertiles. Patients with higher TMC score were older, more likely to be male and have hypertension. Compared to those with TMC tertile 1, patients in TMC tertile 3 had significant associations with the risk of all-cause death (HR: 1.90; 95 %CI: 1.54–2.34), cardiovascular death (HR: 2.32; 95 %CI: 1.71–3.15) and incident HF (HR: 1.77; 95 %CI: 1.40–2.24). The incremental prognostic value of TMC score over the Grace score was measured by the likelihood ratio, C-statistic, continuous net reclassification improvement (NRI), and integrated discrimination improvement (IDI) for prediction, discrimination, and reclassification of outcomes.<h3>Conclusions</h3>In this hospital-based AMI cohort, the TMC score was significantly associated with all-cause mortality, cardiovascular mortality, and incident HF, and improved risk stratification beyond established clinical risk factors. The TMC score provided a novel tool for assessment of Trp catabolism dysfunction and outcomes risk.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"35 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143695580","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The authors regret the oversight in Figs. 6 and S6. While subsequently organizing the experimental data for this article, they unexpectedly found that some images in these two figures were presented incorrectly.
{"title":"Corrigendum to “Hsa_circ_0001402 alleviates vascular neointimal hyperplasia through a miR-183-5p-dependent regulation of vascular smooth muscle cell proliferation, migration, and autophagy” [Journal of Advanced Research, Volume 60, June (2024) Pages 93–110]","authors":"Jia-Jie Lin, Rui Chen, Li-Yun Yang, Miao Gong, Mei-Yang Du, Shi-Qing Mu, Ze-An Jiang, Huan-Huan Li, Yang Yang, Xing-Hui Wang, Si-Fan Wang, Ke-Xin Liu, Shan-Hu Cao, Zhao-Yi Wang, An-Qi Zhao, Shu-Yan Yang, Cheng Li, Shao-Guang Sun","doi":"10.1016/j.jare.2025.03.048","DOIUrl":"https://doi.org/10.1016/j.jare.2025.03.048","url":null,"abstract":"The authors regret the oversight in Figs. 6 and S6. While subsequently organizing the experimental data for this article, they unexpectedly found that some images in these two figures were presented incorrectly.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"11 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143702888","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Traditionally, Silicon (Si) fertilizers are applied externally to the soil or sprayed on the leaves to reduce rice’s arsenic (As) accumulation. However, in practical agricultural production, the economic benefits of lowering As in rice grains often fail to outweigh the production costs.
Objectives
This study investigated an innovative technology—Si-rich seedlings (endogenous Si)—that is simple to implement, cost-effective, and highly effective in reducing As accumulation in rice grains.
Methods
The effects of exogenous and endogenous Si supplementation on As dynamics in rice were investigated in hydroponics in field experiments.
Results
Both methods significantly reduced As accumulation in the rice grains (22.23 % and 17.70 %, respectively). There was no significant difference in the treatment effects. However, endogenous Si supplementation demonstrated a significantly lower cost per unit of As reduction (88.61 % decrease), and it was easier to implement when compared with exogenous Si supplementation. The main processes by which various Si treatment techniques decrease As accumulation in rice differed, even though Si was crucial to As absorption in rice through a combination of mechanisms, such as gene regulation, iron plaque inhibition, and node I sequestration. The fundamental mechanism was Si/As antagonism, which regulated Si absorption through gene regulation in both methods. Interestingly, the exogenous Si treatment improved the barrier function of the root surface iron plaque against As. At the same time, laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) demonstrated that endogenous Si had a more pronounced impact on rice node I. Furthermore, experiments conducted at multiple scales (including variety, pot, and field experiments) validated the stability and reliability of the Si-rich seedling technology under complex environmental conditions.
Conclusion
Si-rich seedlings provide a cost-effective, stable, and practical solution for mitigating As contamination in paddy fields. This approach holds significant potential for enhancing soil health and improving food safety, contributing to the sustainable development of rice cultivation.
{"title":"Exploring the role of endogenous and exogenous silicon in reducing arsenic accumulation in rice: A multi-scale hydroponic to field study","authors":"Yuepeng Yin, Mengfan Jia, Ping Li, Kaiwen Zhu, Min Nie, Xin Tang, Liqin He, Ting Li, Zhihong Guo, Zhigao Zhou, Lirong Li, Taolin Zhang, Xingxiang Wang, Changfeng Ding","doi":"10.1016/j.jare.2025.03.028","DOIUrl":"https://doi.org/10.1016/j.jare.2025.03.028","url":null,"abstract":"<h3>Introduction</h3>Traditionally, Silicon (Si) fertilizers are applied externally to the soil or sprayed on the leaves to reduce rice’s arsenic (As) accumulation. However, in practical agricultural production, the economic benefits of lowering As in rice grains often fail to outweigh the production costs.<h3>Objectives</h3>This study investigated an innovative technology—Si-rich seedlings (endogenous Si)—that is simple to implement, cost-effective, and highly effective in reducing As accumulation in rice grains.<h3>Methods</h3>The effects of exogenous and endogenous Si supplementation on As dynamics in rice were investigated in hydroponics in field experiments.<h3>Results</h3>Both methods significantly reduced As accumulation in the rice grains (22.23 % and 17.70 %, respectively). There was no significant difference in the treatment effects. However, endogenous Si supplementation demonstrated a significantly lower cost per unit of As reduction (88.61 % decrease), and it was easier to implement when compared with exogenous Si supplementation. The main processes by which various Si treatment techniques decrease As accumulation in rice differed, even though Si was crucial to As absorption in rice through a combination of mechanisms, such as gene regulation, iron plaque inhibition, and node I sequestration. The fundamental mechanism was Si/As antagonism, which regulated Si absorption through gene regulation in both methods. Interestingly, the exogenous Si treatment improved the barrier function of the root surface iron plaque against As. At the same time, laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) demonstrated that endogenous Si had a more pronounced impact on rice node I. Furthermore, experiments conducted at multiple scales (including variety, pot, and field experiments) validated the stability and reliability of the Si-rich seedling technology under complex environmental conditions.<h3>Conclusion</h3>Si-rich seedlings provide a cost-effective, stable, and practical solution for mitigating As contamination in paddy fields. This approach holds significant potential for enhancing soil health and improving food safety, contributing to the sustainable development of rice cultivation.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"71 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143677938","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The rise of antibiotic-resistant bacteria, particularly those harboring mcr-1 and blaNDM-1, threatens public health by reducing the efficacy of colistin and carbapenems. Recently, the co-spread of mcr-1 and blaNDM-1 has been reported, and the emergence of dual-resistant Enterobacteriaceae severely exacerbates antimicrobial resistance.
Objectives
This study aims to investigate the impact of mcr-1 and blaNDM-1 expression on metabolism in Escherichia coli and to identify potential antimicrobial agents capable of overcoming the resistance conferred by these genes.
Methods
We employed non-targeted metabolomics to profile the metabolic perturbations of E. coli strains harboring mcr-1 and blaNDM-1. The bactericidal effects of the differential metabolite, inosine monophosphate (IMP), were assessed both in vitro using time-killing assays and in vivo using a mouse infection model. The antimicrobial mechanism of IMP was elucidated through transcriptomic analysis and biochemical approaches.
Results
Metabolic profiling revealed significant alterations in the purine pathway, with IMP demonstrating potent bactericidal activity against E. coli strains carrying both resistance genes. IMP increased membrane permeability, disrupted proton motive force, reduced ATP levels, induced oxidative damage by promoting reactive oxygen species and inhibiting bacterial antioxidant defenses, and improved the survival rate of infected mice.
Conclusion
Our findings suggest that IMP could be a promising candidate for combating mcr-1 and blaNDM-1-mediated resistance and provide a novel approach for discovering antimicrobial agents against colistin- and carbapenem-resistant bacteria.
{"title":"Inosine monophosphate overcomes the coexisting resistance of mcr-1 and blaNDM-1 in Escherichia coli","authors":"Liang Zhao, Jian Xu, Saiwa Liu, Jingjing Du, Xixi Jia, Zhinan Wang, Lirui Ge, Kexin Cui, Yu Ga, Xiaowei Li, Xi Xia","doi":"10.1016/j.jare.2025.03.043","DOIUrl":"https://doi.org/10.1016/j.jare.2025.03.043","url":null,"abstract":"<h3>Introduction</h3>The rise of antibiotic-resistant bacteria, particularly those harboring <em>mcr-1</em> and <em>bla</em><sub>NDM-1</sub>, threatens public health by reducing the efficacy of colistin and carbapenems. Recently, the co-spread of <em>mcr-1</em> and <em>bla</em><sub>NDM-1</sub> has been reported, and the emergence of dual-resistant Enterobacteriaceae severely exacerbates antimicrobial resistance.<h3>Objectives</h3>This study aims to investigate the impact of <em>mcr-1</em> and <em>bla</em><sub>NDM-1</sub> expression on metabolism in <em>Escherichia coli</em> and to identify potential antimicrobial agents capable of overcoming the resistance conferred by these genes.<h3>Methods</h3>We employed non-targeted metabolomics to profile the metabolic perturbations of <em>E. coli</em> strains harboring <em>mcr-1</em> and <em>bla</em><sub>NDM-1</sub>. The bactericidal effects of the differential metabolite, inosine monophosphate (IMP), were assessed both <em>in vitro</em> using time-killing assays and <em>in vivo</em> using a mouse infection model. The antimicrobial mechanism of IMP was elucidated through transcriptomic analysis and biochemical approaches.<h3>Results</h3>Metabolic profiling revealed significant alterations in the purine pathway, with IMP demonstrating potent bactericidal activity against <em>E. coli</em> strains carrying both resistance genes. IMP increased membrane permeability, disrupted proton motive force, reduced ATP levels, induced oxidative damage by promoting reactive oxygen species and inhibiting bacterial antioxidant defenses, and improved the survival rate of infected mice.<h3>Conclusion</h3>Our findings suggest that IMP could be a promising candidate for combating <em>mcr-1</em> and <em>bla</em><sub>NDM-1</sub>-mediated resistance and provide a novel approach for discovering antimicrobial agents against colistin- and carbapenem-resistant bacteria.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"17 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143677937","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Soil salinity is an important limiting factor for plant growth. As a RING-type E3 ubiquitin ligase, MdXERICO is highly responsive to salt stress and can enhance the salt tolerance of plants. However, the molecular mechanism for the response of MdXERICO to salt stress remains unclear.
Objectives
This study aims to dissect the molecular mechanisms for MdXERICO to regulate plant response to salt stress.
Methods
Transcriptome data were compared to obtain the salt stress-induced gene MdXERICO. Transgenic apple seedlings, apple calli, Arabidopsis, and tomato material were obtained using Agrobacterium-mediated transformation assays. Semiendogenous co-immunoprecipitation analysis, yeast two-hybrid, pull-down and dual-luciferase reporter system were used to detect the protein–protein interactions. Electrophoretic mobility shift assay, yeast one-hybrids, dual luciferase and Gus staining assay were employed to verify the protein-DNA interactions.
Results
The results revealed that MdXERICO interacted with MdNRP and improved salt tolerance of apple by ubiquitinating and degrading MdNRP via the 26S proteasome pathway. Moreover, the HMG box-containing transcription factor MdHMGB15 interacted with the MdXERICO promoter, thereby activating its expression and enhancing the salt tolerance of apple.
Conclusion
This study explores the apple’s tolerance to salt stress through the MdHMGB15-MdXERICO-MdNRP module, and provides potential targets for engineering salt-tolerant varieties.
{"title":"MdHMGB15-MdXERICO-MdNRP module mediates salt tolerance of apple by regulating the expression of salt stress-related genes","authors":"Ran-Xin Liu, Shan-Shan Li, Qian-Yu Yue, Hong-Liang Li, Jie Lu, Wan-Cong Li, Yue-Ning Wang, Jia-Xing Liu, Xin-Long Guo, Xiang Wu, Ying-Xue Lv, Xiao-Fei Wang, Chun-Xiang You","doi":"10.1016/j.jare.2025.03.040","DOIUrl":"https://doi.org/10.1016/j.jare.2025.03.040","url":null,"abstract":"<h3>Introduction</h3>Soil salinity is an important limiting factor for plant growth. As a RING-type E3 ubiquitin ligase, <em>MdXERICO</em> is highly responsive to salt stress and can enhance the salt tolerance of plants. However, the molecular mechanism for the response of <em>MdXERICO</em> to salt stress remains unclear.<h3>Objectives</h3>This study aims to dissect the molecular mechanisms for MdXERICO to regulate plant response to salt stress.<h3>Methods</h3>Transcriptome data were compared to obtain the salt stress-induced gene <em>MdXERICO</em>. Transgenic apple seedlings, apple calli, <em>Arabidopsis</em>, and tomato material were obtained using <em>Agrobacterium-</em>mediated transformation assays. Semiendogenous co-immunoprecipitation analysis, yeast two-hybrid, pull-down and dual-luciferase reporter system were used to detect the protein–protein interactions. Electrophoretic mobility shift assay, yeast one-hybrids, dual luciferase and Gus staining assay were employed to verify the protein-DNA interactions.<h3>Results</h3>The results revealed that MdXERICO interacted with MdNRP and improved salt tolerance of apple by ubiquitinating and degrading MdNRP via the 26S proteasome pathway. Moreover, the HMG box-containing transcription factor MdHMGB15 interacted with the <em>MdXERICO</em> promoter, thereby activating its expression and enhancing the salt tolerance of apple.<h3>Conclusion</h3>This study explores the apple’s tolerance to salt stress through the MdHMGB15-MdXERICO-MdNRP module, and provides potential targets for engineering salt-tolerant varieties.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"1 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143678059","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Emerging evidence indicates a notable connection between gut microbiota and Vascular Calcification (VC). Gut microbiota influences various disease processes through host metabolic pathways; however, the causative link between gut microbiota and VC, along with the potential mediating role of metabolites, is still not well understood.
Methods
We leveraged data from the largest Genome-Wide Association Studies (GWAS) concerning gut microbiota, blood metabolites, and VC. To explore the causal relationships among these variables, we conducted two-sample bidirectional Mendelian Randomization (MR) analyses. Furthermore, mediation analyses were conducted to determine if metabolites act as an intermediary in the impact of gut microbiota on VC. In addition, we recruited CKD patients for mass spectrometry and CT examination, and performed a correlation analysis between the expression of blood metabolites and VC score. Finally, we experimentally validated the effects of intermediate metabolites on VC.
Results
We identified 19 positive gut microbiota species and 52 positive blood metabolites with causal effects on VC. Additionally, the onset of VC was found to induce changes in the abundance of 24 gut microbiota species and 56 metabolites. Further analyses revealed that up to 13 positive gut microbiota species regulate the expression of 20 positive metabolites. Mediation analysis suggests that the gut microbiota g_KLE1615 promotes VC by downregulating the methionine-to-phosphate ratio. Mass spectrometry results indicate that over half of the metabolites identified through MR analysis show altered expression during CKD progression. Among them, 7 metabolites were significantly associated with the progression of VC. Further in vitro experiments confirmed the inhibitory effect of the intermediate metabolite methionine on VC.
Conclusion
Gut microbiota and blood metabolites are causally linked to VC. These findings provide a theoretical basis for microbiome- and metabolome-based therapeutic strategies for targeting VC and enhances our comprehension of the gut-vascular axis.
{"title":"Blood metabolites mediate causal inference studies on the effect of gut microbiota on the risk of vascular calcification","authors":"Aoran Huang, Jianshuai Ma, Huijin Zhu, Yanli Qi, Yang Jin, Mingxuan Zhang, Li Yin, Minhong Luo, Sifan Chen, Chen Xie, Hui Huang","doi":"10.1016/j.jare.2025.03.038","DOIUrl":"https://doi.org/10.1016/j.jare.2025.03.038","url":null,"abstract":"<h3>Background</h3>Emerging evidence indicates a notable connection between gut microbiota and Vascular Calcification (VC). Gut microbiota influences various disease processes through host metabolic pathways; however, the causative link between gut microbiota and VC, along with the potential mediating role of metabolites, is still not well understood.<h3>Methods</h3>We leveraged data from the largest Genome-Wide Association Studies (GWAS) concerning gut microbiota, blood metabolites, and VC. To explore the causal relationships among these variables, we conducted two-sample bidirectional Mendelian Randomization (MR) analyses. Furthermore, mediation analyses were conducted to determine if metabolites act as an intermediary in the impact of gut microbiota on VC. In addition, we recruited CKD patients for mass spectrometry and CT examination, and performed a correlation analysis between the expression of blood metabolites and VC score. Finally, we experimentally validated the effects of intermediate metabolites on VC.<h3>Results</h3>We identified 19 positive gut microbiota species and 52 positive blood metabolites with causal effects on VC. Additionally, the onset of VC was found to induce changes in the abundance of 24 gut microbiota species and 56 metabolites. Further analyses revealed that up to 13 positive gut microbiota species regulate the expression of 20 positive metabolites. Mediation analysis suggests that the gut microbiota g_KLE1615 promotes VC by downregulating the methionine-to-phosphate ratio. Mass spectrometry results indicate that over half of the metabolites identified through MR analysis show altered expression during CKD progression. Among them, 7 metabolites were significantly associated with the progression of VC. Further in vitro experiments confirmed the inhibitory effect of the intermediate metabolite methionine on VC.<h3>Conclusion</h3>Gut microbiota and blood metabolites are causally linked to VC. These findings provide a theoretical basis for microbiome- and metabolome-based therapeutic strategies for targeting VC and enhances our comprehension of the gut-vascular axis.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"94 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143677939","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-24DOI: 10.1016/j.jare.2025.03.042
Yuanyuan Yu, Zhifeng Xu, Le Xu, Dan Lu, Yamei Tang, Hongcheng Mai
Background
Plant extracellular vesicles (PEVs) have emerged important roles in central nervous system (CNS) disorders. PEVs are nanoscale vesicles (30–150 nm) that mediate intercellular communication and exhibit unique therapeutic potential due to their natural biocompatibility, minimal immunogenicity, and ability to cross the blood–brain barrier (BBB). With increasing interest in neurotherapeutics, PEVs offer promising applications for CNS disorders by overcoming delivery barriers and reducing adverse effects associated with synthetic nanoparticles.
Aim of review
This review provides a comprehensive analysis of the role of PEVs in CNS disorders, focusing on their mechanisms of action, therapeutic potential, and advantages over mammalian extracellular vesicles (MEVs) and synthetic delivery systems. It also highlights emerging research, challenges, and future directions for their clinical translation.
Key scientific concepts of review
PEVs, derived from fruits, vegetables, and medicinal plants, contain bioactive molecules such as proteins, lipids, microRNAs (miRNAs) and nucleic acids. These vesicles demonstrate the ability to traverse the BBB through receptor-mediated transport and membrane fusion, delivering therapeutic effects for CNS disorders, including neuroinflammation, ischemic stroke, and gliomas. Their pharmacological benefits stem from active metabolites, such as gingerols, alkaloids, and flavonoids, which modulate immune responses, maintain BBB integrity, and reduce neuronal apoptosis. Despite their advantages, challenges such as efficient extraction methods, standardization, and scalability remain obstacles to clinical application. Addressing these issues through advanced extraction techniques, improved characterization, and optimized drug loading strategies can enhance the clinical utility of PEVs.
{"title":"Plant extracellular vesicles as emerging neuroprotective agents for central nervous system disorders","authors":"Yuanyuan Yu, Zhifeng Xu, Le Xu, Dan Lu, Yamei Tang, Hongcheng Mai","doi":"10.1016/j.jare.2025.03.042","DOIUrl":"https://doi.org/10.1016/j.jare.2025.03.042","url":null,"abstract":"<h3>Background</h3>Plant extracellular vesicles (PEVs) have emerged important roles in central nervous system (CNS) disorders. PEVs are nanoscale vesicles (30–150 nm) that mediate intercellular communication and exhibit unique therapeutic potential due to their natural biocompatibility, minimal immunogenicity, and ability to cross the blood–brain barrier (BBB). With increasing interest in neurotherapeutics, PEVs offer promising applications for CNS disorders by overcoming delivery barriers and reducing adverse effects associated with synthetic nanoparticles.<h3>Aim of review</h3>This review provides a comprehensive analysis of the role of PEVs in CNS disorders, focusing on their mechanisms of action, therapeutic potential, and advantages over mammalian extracellular vesicles (MEVs) and synthetic delivery systems. It also highlights emerging research, challenges, and future directions for their clinical translation.<h3>Key scientific concepts of review</h3>PEVs, derived from fruits, vegetables, and medicinal plants, contain bioactive molecules such as proteins, lipids, microRNAs (miRNAs) and nucleic acids. These vesicles demonstrate the ability to traverse the BBB through receptor-mediated transport and membrane fusion, delivering therapeutic effects for CNS disorders, including neuroinflammation, ischemic stroke, and gliomas. Their pharmacological benefits stem from active metabolites, such as gingerols, alkaloids, and flavonoids, which modulate immune responses, maintain BBB integrity, and reduce neuronal apoptosis. Despite their advantages, challenges such as efficient extraction methods, standardization, and scalability remain obstacles to clinical application. Addressing these issues through advanced extraction techniques, improved characterization, and optimized drug loading strategies can enhance the clinical utility of PEVs.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"93 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143695581","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-23DOI: 10.1016/j.jare.2025.03.041
Di Fan, Yi Zhong, Yin Dong, Meng Du, Kai Huang, Xiaoguang Li
Introduction
Sepsis consists of life-threatening multi-organ dysfunction caused by an excessive systemic inflammatory response to infection. Therefore, identifying negative regulators of innate inflammation is crucial for treating this condition.
Objectives
In this study, we aimed to understand how transducin-like enhancer of split 3 (TLE3) regulates inflammatory responses.
Methods
We detected Tle3 changes in sepsis patients by analyzing public databases, which were confirmed in septic survivors, septic mouse models, and inflammatory macrophages using Western blotting, qRT-PCR, and immunohistochemistry staining. We investigated the role and mechanism of TLE3 in sepsis by utilizing bone marrow-transplantation (BMT) and adenovirus-infected mice. Furthermore, Protein-Protein Docking, BiFC, LC-MS/MS analysis, CUT & Tag-seq, and CHIP experiments were utilized to disclose the mechanism underlying TLE3 involving macrophage inflammation.
Results
In this study, we found that Tle3 transcript is upregulated in peripheral blood samples of sepsis survivors and is decreased in non-survivors, suggesting the critical role of TLE3 in sepsis outcomes. TLE3 is also upregulated in lipopolysaccharide (LPS)-stimulated human monocyte-derived macrophages (MDMs), murine bone marrow-derived macrophages (BMDMs), and septic mice. Gain-of- and loss-of-function of TLE3 in LPS-stimulated murine BMDMs, human MDMs, and mouse models of sepsis showed that TLE3 alleviates LPS-induced cytokine production, as well as nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and mitogen-activated protein kinase (MAPK) activation in macrophages, which protects against LPS-induced acute systemic inflammation, multi-organ injury, and death caused by sepsis. Mechanistically, upregulated TLE3 interacts with the transcriptional coactivator, DEAD-box helicase 5 (DDX5), promoting its retention in the cytoplasm and ultimately decreasing transcription of the DDX5/ activating transcription factor 1 (ATF1)-targeted gene Ppp2r5a. Furthermore, the TLE3-DDX5-ATF1 axis downregulates PPP2R5A, a negative regulatory subunit of protein phosphatase 2A (PP2A), thereby increasing PP2A activity and promoting the dephosphorylation of NF-κB and MAPK.
Conclusion
Our study shows that TLE3 represents a novel suppressor of LPS-induced inflammatory signaling in macrophages.
{"title":"Transducin-like enhancer of split 3 protects against lipopolysaccharide-induced inflammation through DDX5-ATF1-PPP2R5A signaling","authors":"Di Fan, Yi Zhong, Yin Dong, Meng Du, Kai Huang, Xiaoguang Li","doi":"10.1016/j.jare.2025.03.041","DOIUrl":"https://doi.org/10.1016/j.jare.2025.03.041","url":null,"abstract":"<h3>Introduction</h3>Sepsis consists of life-threatening multi-organ dysfunction caused by an excessive systemic inflammatory response to infection. Therefore, identifying negative regulators of innate inflammation is crucial for treating this condition.<h3>Objectives</h3>In this study, we aimed to understand how transducin-like enhancer of split 3 (TLE3) regulates inflammatory responses.<h3>Methods</h3>We detected <em>Tle3</em> changes in sepsis patients by analyzing public databases, which were confirmed in septic survivors, septic mouse models, and inflammatory macrophages using Western blotting, qRT-PCR, and immunohistochemistry staining. We investigated the role and mechanism of TLE3 in sepsis by utilizing bone marrow-transplantation (BMT) and adenovirus-infected mice. Furthermore, Protein-Protein Docking, BiFC, LC-MS/MS analysis, CUT & Tag-seq, and CHIP experiments were utilized to disclose the mechanism underlying TLE3 involving macrophage inflammation.<h3>Results</h3>In this study, we found that <em>Tle3</em> transcript is upregulated in peripheral blood samples of sepsis survivors and is decreased in non-survivors, suggesting the critical role of TLE3 in sepsis outcomes. TLE3 is also upregulated in lipopolysaccharide (LPS)-stimulated human monocyte-derived macrophages (MDMs), murine bone marrow-derived macrophages (BMDMs), and septic mice. Gain-of- and loss-of-function of TLE3 in LPS-stimulated murine BMDMs, human MDMs, and mouse models of sepsis showed that TLE3 alleviates LPS-induced cytokine production, as well as nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and mitogen-activated protein kinase (MAPK) activation in macrophages, which protects against LPS-induced acute systemic inflammation, multi-organ injury, and death caused by sepsis. Mechanistically, upregulated TLE3 interacts with the transcriptional coactivator, DEAD-box helicase 5 (DDX5), promoting its retention in the cytoplasm and ultimately decreasing transcription of the DDX5/ activating transcription factor 1 (ATF1)-targeted gene <em>Ppp2r5a</em>. Furthermore, the TLE3-DDX5-ATF1 axis downregulates PPP2R5A, a negative regulatory subunit of protein phosphatase 2A (PP2A), thereby increasing PP2A activity and promoting the dephosphorylation of NF-κB and MAPK.<h3>Conclusion</h3>Our study shows that TLE3 represents a novel suppressor of LPS-induced inflammatory signaling in macrophages.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"28 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143675432","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Early life bone accumulation, which predicts future fragility fracture risk, is intimately associated with sex hormones. N, N-diethyl-3-methylbenzamide (DEET) is the primary and most effective active ingredient widely used globally, especially among children and adolescents. However, the effects of DEET on sex hormones and bone mass remain unclear.
Objective
We aimed to explore the adverse effects of DEET exposure on bone mass and to elucidate the potential mediating roles of sex hormones in children and adolescents.
Methods
This cross-sectional study analyzed 864 children and adolescents from NHANES 2013–2016. Urinary 3-diethyl-carbamoyl benzoic acid (DCBA) was employed as a biomarker for DEET exposure. The study examined the relationships between DCBA, sex hormones, and bone mass, with a particular focus on evaluating the independent and serial mediation effects of sex hormones on DEET-bone mass associations.
Results
Increased DCBA was associated with decreased testosterone (TT), estrogen (E2), and free androgen index (FAI), alongside an increase in sex hormone-binding globulin (SHBG) levels, particularly pronounced among subjects < 12 years [β% (95 % CI) = -0.081 (−0.144, −0.017), −0.064 (−0.114, −0.013), −0.101 (−0.177, −0.024), and 0.020 (−0.009, 0.048), respectively] and non-overweight subjects [β% (95 % CI) = -0.160 (−0.234, −0.086), −0.103 (−0.158, −0.048), −0.195 (−0.282, −0.107), and 0.035 (0.012, 0.058), respectively]. Negative dose–response relationships between DCBA and bone mass were observed in non-overweight participants [β% (95 % CI) = -0.011 (−0.018, −0.005) and −0.027 (−0.041, −0.013) for total bone mineral density (BMD) and total bone mineral content (BMC), respectively], and in children < 12 years for total BMC [β% (95 % CI) = -0.012 (−0.024, 0.000)]. Additionally, TT, E2, and SHBG were found to significantly and independently mediate 15.41 % to 79.84 % of the relationship between DCBA and bone mass. Furthermore, serial mediation effects among sex hormones were detected between TT, E2, and SHBG.
Conclusions
DEET exerts a detrimental effect on bone health by interfering with sex hormones in children and adolescents, warranting heightened public concern.
{"title":"From repellent to risk: DEET’s adverse effects on hormones and bone health in kids","authors":"Xinyu Zhu, Wanlu Liu, Baihao Lin, Haixia Qian, Mengya Xu, Yuyu Zheng, Yansen Bai","doi":"10.1016/j.jare.2025.03.037","DOIUrl":"https://doi.org/10.1016/j.jare.2025.03.037","url":null,"abstract":"<h3>Introduction</h3>Early life bone accumulation, which predicts future fragility fracture risk, is intimately associated with sex hormones. N, N-diethyl-3-methylbenzamide (DEET) is the primary and most effective active ingredient widely used globally, especially among children and adolescents. However, the effects of DEET on sex hormones and bone mass remain unclear.<h3>Objective</h3>We aimed to explore the adverse effects of DEET exposure on bone mass and to elucidate the potential mediating roles of sex hormones in children and adolescents.<h3>Methods</h3>This cross-sectional study analyzed 864 children and adolescents from NHANES 2013–2016. Urinary 3-diethyl-carbamoyl benzoic acid (DCBA) was employed as a biomarker for DEET exposure. The study examined the relationships between DCBA, sex hormones, and bone mass, with a particular focus on evaluating the independent and serial mediation effects of sex hormones on DEET-bone mass associations.<h3>Results</h3>Increased DCBA was associated with decreased testosterone (TT), estrogen (E2), and free androgen index (FAI), alongside an increase in sex hormone-binding globulin (SHBG) levels, particularly pronounced among subjects < 12 years [β% (95 % CI) = -0.081 (−0.144, −0.017), −0.064 (−0.114, −0.013), −0.101 (−0.177, −0.024), and 0.020 (−0.009, 0.048), respectively] and non-overweight subjects [β% (95 % CI) = -0.160 (−0.234, −0.086), −0.103 (−0.158, −0.048), −0.195 (−0.282, −0.107), and 0.035 (0.012, 0.058), respectively]. Negative dose–response relationships between DCBA and bone mass were observed in non-overweight participants [β% (95 % CI) = -0.011 (−0.018, −0.005) and −0.027 (−0.041, −0.013) for total bone mineral density (BMD) and total bone mineral content (BMC), respectively], and in children < 12 years for total BMC [β% (95 % CI) = -0.012 (−0.024, 0.000)]. Additionally, TT, E2, and SHBG were found to significantly and independently mediate 15.41 % to 79.84 % of the relationship between DCBA and bone mass. Furthermore, serial mediation effects among sex hormones were detected between TT, E2, and SHBG.<h3>Conclusions</h3>DEET exerts a detrimental effect on bone health by interfering with sex hormones in children and adolescents, warranting heightened public concern.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"8 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143666483","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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