Journal of Advanced Research最新文献

{"title":"The Application of artificial intelligence in periprosthetic joint infection","authors":"Pengcheng Li, Yan Wang, Runkai Zhao, Lin Hao, Wei Chai, Chen Jiying, Zeyu Feng, Quanbo Ji, Guoqiang Zhang","doi":"10.1016/j.jare.2025.03.039","DOIUrl":"https://doi.org/10.1016/j.jare.2025.03.039","url":null,"abstract":"Periprosthetic joint infection (PJI) represents one of the most devastating complications following total joint arthroplasty, often necessitating additional surgeries and antimicrobial therapy, and potentially leading to disability. This significantly increases the burden on both patients and the healthcare system. Given the considerable suffering caused by PJI, its prevention and treatment have long been focal points of concern. However, challenges remain in accurately assessing individual risk, preventing the infection, improving diagnostic methods, and enhancing treatment outcomes. The development and application of artificial intelligence (AI) technologies have introduced new, more efficient possibilities for the management of many diseases. In this article, we review the applications of AI in the prevention, diagnosis, and treatment of PJI, and explore how AI methodologies might achieve individualized risk prediction, improve diagnostic algorithms through biomarkers and pathology, and enhance the efficacy of antimicrobial and surgical treatments. We hope that through multimodal AI applications, intelligent management of PJI can be realized in the future.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"21 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143734404","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}

{"title":"Prediction of influenza virus infection based on deep learning and peripheral blood proteomics: A diagnostic study","authors":"Yumei Zhou, Pengbo Wang, Haiyun Zhang, Taihao Wang, Shuai Han, Xin Ma, Shuang Liang, Minghua Bai, Pengbei Fan, Lei Wang, Ji Wang, Qi Wang","doi":"10.1016/j.jare.2025.03.051","DOIUrl":"https://doi.org/10.1016/j.jare.2025.03.051","url":null,"abstract":"Isntroduction.Influenza viruses cause seasonal epidemics almost every year, and it is difficult to diagnose quickly and accurately. Machine learning and peripheral blood protein omics have brought new ideas to the research of clinical markers.<h3>Objectives</h3>Prediction of key molecular marker of influenza virus infection by the established machine learning model and peripheral blood protein omics.<h3>Methods</h3>This study used the testing data of 850 patients (including influenza, COVID-19 and mixed infections) and 265 healthy individuals, to establish and validate a diagnostic prediction model for influenza infection and verified the potential value of this model in the differential diagnosis of influenza, COVID-19 and healthy people.<h3>Results</h3>The overall analysis showed that there were significant differences in 9 clinical features in the influenza group. Principal component analysis can effectively group samples based on these clinical features. Based on the random forest model and LASSO regression model found that the selected features are clinical indicators that can accurately distinguish influenza patients. We performed proteome sequencing combined with machine learning and found a total of 26 DEPs. Through PPI and WGCNA analysis, we identified several genes related to the proportion of monocytes. We then analyzed the correlation of these factors with immune cell proportions and found that SAA1 and SAA2 were highly correlated with various vital immunocyte. ROC curve analysis shows that SERPINA3 can distinguish influenza, COVID-19, mixed infection and healthy people; SAA1 can distinguish COVID-19, mixed infection and healthy people; SAA2 can distinguish influenza and healthy people. In influenza, high expression of SERPINA3, SAA1, and SAA2 is associated with higher risk. Finally, we used the ELISA method to confirm that SAA2 protein can be used as an auxiliary diagnostic indicator for influenza infection.<h3>Conclusions</h3>Preliminary results showed that SAA2 is an important molecular marker specific to influenza infection.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"47 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143723823","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}

{"title":"Fasting influences the muscle quality of fish during transportation by regulating the balance between energy metabolism and ammonia nitrogen stress","authors":"Ling Peng, Juan You, Ru Liu, Yong Long, Guili Song, Soottawat Benjakul, Shanbai Xiong, Ziaur Rahman, Qiling Huang, Sheng Chen, Tao Yin","doi":"10.1016/j.jare.2025.03.047","DOIUrl":"https://doi.org/10.1016/j.jare.2025.03.047","url":null,"abstract":"<h3>Introduction</h3>Fasting has been widely applied in aquaculture to improve the welfare of fish. However, fasting regulate the interplay of energy metabolism and ammonia nitrogen stress on the muscle quality unclear.<h3>Objectives</h3>To clarify the impact of fasting on the energy metabolism, ammonia nitrogen stress, and muscle quality.<h3>Methods</h3>Blunt snout bream (<em>Megalobrama amblycephala</em>) were fasted for different days before transportation. Then changes in energy metabolism, stress response, cell apoptosis, and muscle quality were assessed using UPLC-QTOF-MS untargeted metabolomics along with classical molecular biology techniques.<h3>Results</h3>Our findings revealed that short-term fasting (2–3 d) effectively alleviated ammonia nitrogen stress. The cortisol and superoxide dismutase decreased gradually as the fasting time was extended from 0 to 3 d, with decreased of 28.60 % and 55.39 %. Regarding the energy reserves, a reduction in muscle glycogen, protein, and lipid content was observed after fasting. These changes were attributed to the intensified tricarboxylic acid cycle, amino acid metabolism, and lipid metabolism. Furthermore, fasting enhanced the glycolysis of glycogen, and the gluconeogenesis of glutamic acid and aspartic acid to generate adenosine triphosphate. Notably, short-term fasting alleviated muscle cell apoptosis <em>via</em> down-regulating expression of Caspase 9 and Bax. Moreover, the water holding capacity, shear force, and springiness were better improved after fasting 3 d, reaching 79.88 %, 407.11 g, and 0.73 g, respectively. However, when fasting was extended to 4 d, there was a decrease in energy substances in the fish muscle and an increase in oxidative stress and apoptosis, thereby inducing a decrease in the muscle quality.<h3>Conclusion</h3>Our data concluded that fasting affects cell apoptosis by regulating the balance between energy metabolism and stress, ultimately impacting muscle quality. For long-distance transportation, a fasting period of 2–3 d is optimal.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"29 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143713693","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}

{"title":"Sex-specific proteomic signatures improve cardiovascular risk prediction for the general population without cardiovascular disease or diabetes","authors":"Ruijie Xie, Tomislav Vlaski, Sha Sha, Hermann Brenner, Ben Schöttker","doi":"10.1016/j.jare.2025.03.034","DOIUrl":"https://doi.org/10.1016/j.jare.2025.03.034","url":null,"abstract":"<h3>Introduction</h3>Accurate prediction of 10-year major adverse cardiovascular events (MACE) is critical for effective disease prevention and management. Although the SCORE2 model introduced sex-specific algorithms, opportunities remain to further refine prediction.<h3>Objectives</h3>To evaluate whether adding sex-specific proteomic profiles to the SCORE2 model enhances 10-year MACE risk prediction in the large UK Biobank (UKB) cohort.<h3>Methods</h3>Data from 47,382 UKB participants, aged 40 to 69 years without prior cardiovascular disease or diabetes, were utilized. Proteomic profiling of plasma samples was conducted using the Olink Explore 3072 platform, measuring 2,923 unique proteins, of which 2,085 could be used. Sex-specific Least Absolute Shrinkage and Selection Operator (LASSO) regression was used for biomarker selection. Model performance was assessed by changes in Harrell’s C-index (a measure of discrimination), net reclassification index (NRI), and integrated discrimination index (IDI).<h3>Results</h3>During 10-year follow-up, 2,163 participants experienced MACE. Overall, 18 proteins were selected by LASSO regression, with 5 of them identified in both sexes, 7 only in males, and 6 only in females. Incorporating these proteins significantly improved the C-index of the SCORE2 model from 0.713 to 0.778 (<em>P</em> &lt; 0.001) in the total population. The improvement was greater in males (C-index increase from 0.684 to 0.771; Δ = +0.087) than in females (from 0.720 to 0.769; Δ = +0.049). The WAP four-disulfide core domain protein (WFDC2) and the growth/differentiation factor 15 (GDF15) were the proteins contributing the strongest C-index increase in both sexes, even more than the N-terminal prohormone of brain natriuretic peptide (NTproBNP).<h3>Conclusion</h3>The derived sex-specific 10-year MACE risk prediction models, combining 12 protein concentrations among men and 11 protein concentrations among women with the SCORE2 model, significantly improved the discriminative abilities of the SCORE2 model. This study shows the potential of sex-specific proteomic profiles for enhanced cardiovascular risk stratification and personalized prevention strategies.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"30 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143713694","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}

{"title":"Carbon dot superoxide dismutase nanozyme enhances reactive oxygen species scavenging in diabetic skin wound repair","authors":"Zhu Yan, Yufei Zhang, Qin Chen, Jing Li, Xiaoying Ning, Fan Bai, Yaqi Wang, Xiaoming Liu, Yale Liu, Mingzhen Zhang, Cui Liu, Yumin Xia","doi":"10.1016/j.jare.2025.03.049","DOIUrl":"https://doi.org/10.1016/j.jare.2025.03.049","url":null,"abstract":"<h3>Introduction</h3>The accumulation of reactive oxygen species (ROS) in diabetic wounds leads to inflammation and impaired neovascularization. Recent studies have indicated that carbon dot nanozymes (C-dots) exhibiting superoxide dismutase (SOD)-like activity can neutralize excessive ROS and mitigate diseases associated with oxidative stress.<h3>Objectives</h3>Our study was designed to evaluate the therapeutic impact of C-dots on the healing of diabetic wounds and to unravel the complex molecular mechanisms through which these nanozymes modulate oxidative stress and inflammatory responses within the wound microenvironment.<h3>Methods and results</h3>We synthesized C-dots from carbon fiber and confirmed their structure using transmission electron microscopy. The presence of carbon–carbon double bonds on the C-dots was verified with X-ray photoelectron spectroscopy. We assessed the scavenging capacity of C-dots for superoxide anion, hydroxyl radical, and nitric oxide radical using electron spin resonance spectroscopy. Their SOD-like activity and total antioxidant capacity were evaluated with commercial assay kits. <em>In vitro</em> experiments showed that C-dots effectively scavenged excessive ROS, protecting human keratinocytes, vascular endothelial cells, and fibroblasts from oxidative stress-induced damage. Concurrently, C-dots increased the migratory capacity of fibroblasts. In an streptozocin-induced diabetic mice model, C-dots application enhanced skin wound healing, evidenced by accelerated re-epithelialization and orderly collagen matrix assembly. Mechanistic investigations indicated that C-dots markedly suppressed ROS generation and diminished the levels of inflammatory cytokines in the wound environment. Additionally, C-dots induced a M2 polarization phenotype in macrophages and promoted neovascularization, indicating a transition from the inflammatory to the proliferative phase. Quantitative proteomic analysis was conducted to further clarify the underlying mechanisms of C-dots in ameliorating diabetic wounds.<h3>Conclusion</h3>C-dots represent a robust nanomaterial-based strategy for treating diabetic wounds, with the ability to accelerate healing by alleviating oxidative stress, mitigating harmful inflammatory responses, and fostering angiogenesis. This highlights their significant therapeutic potential in the field of biomedicine.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"104 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143713695","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}

{"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}

{"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}

{"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}

{"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}

{"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>_NDM-1, threatens public health by reducing the efficacy of colistin and carbapenems. Recently, the co-spread of <em>mcr-1</em> and <em>bla</em>_NDM-1 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>_NDM-1 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>_NDM-1. 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>_NDM-1-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}