Ferroptosis significantly compromises diabetic wound healing and represents a promising therapeutic target for clinical intervention. Baicalein (Bai), a natural flavonoid, has been considered to own ferroptosis-regulating properties, while the underlying mechanisms remain understood.
Pseudomonas syringae pv. tabaci, a Gram-negative bacterial pathogen, causes devastating tobacco wildfire disease with global economic impacts. While its pathogenicity is well documented, the dynamic defense mechanisms of tobacco against infection remain poorly understood.
{"title":"Time-series transcriptome and metabolome profiling Uncovers WRKY6 and WRKY23 as critical regulators in tobacco response to Pseudomonas syringae infection","authors":"Xinhua Tian, Peng Lu, Zechao Qu, Huan Su, Qiao Wang, Jiemeng Tao, Qian Sun, Shuaibin Wang, Lijun Meng, Peijian Cao, Yuanhu Xuan, Jingjing Jin","doi":"10.1016/j.jare.2026.01.036","DOIUrl":"https://doi.org/10.1016/j.jare.2026.01.036","url":null,"abstract":"<ce:italic>Pseudomonas syringae</ce:italic> pv. <ce:italic>tabaci</ce:italic>, a Gram-negative bacterial pathogen, causes devastating tobacco wildfire disease with global economic impacts. While its pathogenicity is well documented, the dynamic defense mechanisms of tobacco against infection remain poorly understood.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"11 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2026-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145956609","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}
Intracerebral hemorrhage (ICH) is a devastating stroke subtype, yet the intrinsic mechanisms conferring genetic protection against it remain poorly understood. While risk-associated loci have been identified, the cell-type-specific pathways that actively preserve cerebrovascular stability remain largely unmapped.
{"title":"Astrocyte-derived LAMC1 protects against intracerebral hemorrhage: A novel genetic mechanism maintaining neurovascular integrity","authors":"Liang Cao, Yanjun Zhang, Wenjun Pi, Rui Zhang, Yi Zhang, V.Wee Yong, Mengzhou Xue","doi":"10.1016/j.jare.2026.01.028","DOIUrl":"https://doi.org/10.1016/j.jare.2026.01.028","url":null,"abstract":"Intracerebral hemorrhage (ICH) is a devastating stroke subtype, yet the intrinsic mechanisms conferring genetic protection against it remain poorly understood. While risk-associated loci have been identified, the cell-type-specific pathways that actively preserve cerebrovascular stability remain largely unmapped.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"31 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2026-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145956610","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 : 2026-01-12DOI: 10.1016/j.jare.2026.01.023
Na Young Choi, Seokbeom Ham, Dahee Jeong, Jihye Ryu, Minseong Lee, Abida Raheem, Suk-Won Ahn, Yukyeong Lee, Yerin Kim, Han Sung Hwang, Gwang Jun Kim, Kisung Ko, Chaeyoung Lee, Kinarm Ko
Genomic imprinting is an epigenetic mechanism in which gene expression is determined by the parent of origin. Imprinted genes are crucial for mammalian growth and development, and mutations at imprinting sites can lead to developmental disorders and diseases. Therefore, identifying novel imprinted differentially methylated regions (DMRs) is essential for understanding imprinting mechanisms and their implications in human biology. This study aimed to identify new imprinted DMRs using parthenogenetic and androgenetic human induced pluripotent stem cells (PgHiPSCs and AgHiPSCs), derived from mature cystic teratomas and complete hydatidiform moles, respectively. Genome-wide DNA methylation profiling via DNA methyl-capture sequencing (MethylCap-seq) was used to identify candidate imprinted DMRs. Subsequent bisulfite sequencing validated the methylation status, and comparative analyses confirmed pluripotency-specific imprinting. We identified 26 novel imprinted DMRs and excluded 6 that exhibited the absence of allelic imbalance or the presence of potential confounding by expression quantitative trait locus. Among the remaining 20, the DMRs in DOCK4 and LYNX1 were validated. They had distinct imprinted methylation and expression patterns unique to pluripotent stem cells and absent in fibroblasts and normal adult tissues. These findings highlight the utility of uniparental iPSCs for discovering imprinted genes specific to the pluripotent state and provide insights into the epigenetic regulation of early human development.
{"title":"Pluripotent stem cell–specific imprinted genes identified using human Uniparental-Induced pluripotent stem cells","authors":"Na Young Choi, Seokbeom Ham, Dahee Jeong, Jihye Ryu, Minseong Lee, Abida Raheem, Suk-Won Ahn, Yukyeong Lee, Yerin Kim, Han Sung Hwang, Gwang Jun Kim, Kisung Ko, Chaeyoung Lee, Kinarm Ko","doi":"10.1016/j.jare.2026.01.023","DOIUrl":"https://doi.org/10.1016/j.jare.2026.01.023","url":null,"abstract":"Genomic imprinting is an epigenetic mechanism in which gene expression is determined by the parent of origin. Imprinted genes are crucial for mammalian growth and development, and mutations at imprinting sites can lead to developmental disorders and diseases. Therefore, identifying novel imprinted differentially methylated regions (DMRs) is essential for understanding imprinting mechanisms and their implications in human biology. This study aimed to identify new imprinted DMRs using parthenogenetic and androgenetic human induced pluripotent stem cells (PgHiPSCs and AgHiPSCs), derived from mature cystic teratomas and complete hydatidiform moles, respectively. Genome-wide DNA methylation profiling via DNA methyl-capture sequencing (MethylCap-seq) was used to identify candidate imprinted DMRs. Subsequent bisulfite sequencing validated the methylation status, and comparative analyses confirmed pluripotency-specific imprinting. We identified 26 novel imprinted DMRs and excluded 6 that exhibited the absence of allelic imbalance or the presence of potential confounding by expression quantitative trait locus. Among the remaining 20, the DMRs in <ce:italic>DOCK4</ce:italic> and <ce:italic>LYNX1</ce:italic> were validated. They had distinct imprinted methylation and expression patterns unique to pluripotent stem cells and absent in fibroblasts and normal adult tissues. These findings highlight the utility of uniparental iPSCs for discovering imprinted genes specific to the pluripotent state and provide insights into the epigenetic regulation of early human development.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"15 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2026-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145956614","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 detection and identification of various phosphates are crucial in disease diagnostics. However, traditional detection techniques often require the development of multi-ion systems, and the complexity of sensor unit fabrication has limited the broad applications of sensor arrays. In this study, we report for the first-time the design of a colorimetric sensor using oxygen vacancy-regulated MoOx(2 ≤ x ≤ 3) nanosheets. By precisely modulating the concentration of introduced oxygen vacancies, the plasmonic resonance absorption peak of the MoOx nanosheets exhibited tunable shifts, thereby influencing their optical properties. The addition of phosphate ions with different configurations influenced the light absorption range and the plasmonic peak values of the oxygen vacancy-rich MoOx sensor array to various extents. Through statistical analysis methods, this sensing array effectively identified ten types of phosphates (i.e., ATP, ADP, AMP, PPi, Pi, UTP, GTP, GDP, GMP, and CTP). The sensor demonstrated excellent detection and discrimination capabilities in both quantitative identification and the recognition of mixed phosphates. The practical application of this sensor array was validated by precisely detecting phosphates in complex systems such as serum. Compared to the previous reports, the fabrication process of the oxygen vacancy-regulated MoOx nanosheets is simple, the discrimination detection effect is good, and it provides a new approach and method for the design and fabrication of highly efficient sensor arrays.
各种磷酸盐的检测和鉴定在疾病诊断中至关重要。然而，传统的检测技术往往需要开发多离子系统，并且传感器单元制造的复杂性限制了传感器阵列的广泛应用。在这项研究中，我们首次报道了使用氧空位调节的MoOx（2 ≤ x ≤ 3）纳米片设计的比色传感器。通过精确调制引入氧空位的浓度，MoOx纳米片的等离子共振吸收峰发生可调位移，从而影响其光学性质。不同构型磷酸盐离子的加入对富氧空位MoOx传感器阵列的光吸收范围和等离子体峰值有不同程度的影响。通过统计分析方法，该传感阵列有效识别出ATP、ADP、AMP、PPi、Pi、UTP、GTP、GDP、GMP、CTP等十种磷酸。该传感器在定量识别和混合磷酸盐识别方面均表现出优异的检测和识别能力。通过对血清等复杂系统中磷酸盐的精确检测，验证了该传感器阵列的实际应用。与以往报道相比，氧空位调节MoOx纳米片的制备工艺简单，识别检测效果好，为高效传感器阵列的设计和制造提供了新的途径和方法。
{"title":"Oxygen-Vacancy-Regulated Molybdenum oxide nanosheets for a Multi-Phosphate Discriminative colorimetric sensor array","authors":"Cheng Cheng, Xingying Li, Zhiwei Chen, Aiwu Wang, Fucong Lyu, Muhammad Humayun, Mohamed Bououdina","doi":"10.1016/j.jare.2026.01.025","DOIUrl":"https://doi.org/10.1016/j.jare.2026.01.025","url":null,"abstract":"The detection and identification of various phosphates are crucial in disease diagnostics. However, traditional detection techniques often require the development of multi-ion systems, and the complexity of sensor unit fabrication has limited the broad applications of sensor arrays. In this study, we report for the first-time the design of a colorimetric sensor using oxygen vacancy-regulated MoO<ce:inf loc=\"post\">x</ce:inf>(2 ≤ x ≤ 3) nanosheets. By precisely modulating the concentration of introduced oxygen vacancies, the plasmonic resonance absorption peak of the MoO<ce:inf loc=\"post\">x</ce:inf> nanosheets exhibited tunable shifts, thereby influencing their optical properties. The addition of phosphate ions with different configurations influenced the light absorption range and the plasmonic peak values of the oxygen vacancy-rich MoO<ce:inf loc=\"post\">x</ce:inf> sensor array to various extents. Through statistical analysis methods, this sensing array effectively identified ten types of phosphates (i.e., ATP, ADP, AMP, PPi, Pi, UTP, GTP, GDP, GMP, and CTP). The sensor demonstrated excellent detection and discrimination capabilities in both quantitative identification and the recognition of mixed phosphates. The practical application of this sensor array was validated by precisely detecting phosphates in complex systems such as serum. Compared to the previous reports, the fabrication process of the oxygen vacancy-regulated MoO<ce:inf loc=\"post\">x</ce:inf> nanosheets is simple, the discrimination detection effect is good, and it provides a new approach and method for the design and fabrication of highly efficient sensor arrays.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"1 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2026-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145956612","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 : 2026-01-11DOI: 10.1016/j.jare.2026.01.021
Chaoying Wen, Yi Jiao, Zhaoran Wang, Tong Shi, Yan Wang, Jiahe Xu, Tiantian Deng, Guoqiang Zhang, Cheng Xiao
The dynamic crosstalk between N6-methyladenosine (m6A) RNA methylation and ferroptosis is pivotal for understanding disease pathogenesis. As the most abundant form of eukaryotic mRNA modification, m6A methylation guides RNA metabolism through writers, erasers, and readers. Ferroptosis, an iron-dependent and lipid peroxidation-driven form of cell death, occurs under conditions including dysregulated iron metabolism, compromised antioxidant defences, and lipid peroxidation.
{"title":"m6A methylation in ferroptosis regulation: mechanisms, targets, and therapeutic interventions","authors":"Chaoying Wen, Yi Jiao, Zhaoran Wang, Tong Shi, Yan Wang, Jiahe Xu, Tiantian Deng, Guoqiang Zhang, Cheng Xiao","doi":"10.1016/j.jare.2026.01.021","DOIUrl":"https://doi.org/10.1016/j.jare.2026.01.021","url":null,"abstract":"The dynamic crosstalk between N6-methyladenosine (m6A) RNA methylation and ferroptosis is pivotal for understanding disease pathogenesis. As the most abundant form of eukaryotic mRNA modification, m6A methylation guides RNA metabolism through writers, erasers, and readers. Ferroptosis, an iron-dependent and lipid peroxidation-driven form of cell death, occurs under conditions including dysregulated iron metabolism, compromised antioxidant defences, and lipid peroxidation.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"7 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2026-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145956615","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 : 2026-01-10DOI: 10.1016/j.jare.2026.01.019
Bing Zhang, Wanida Phetsang, Sanjaya Kc, Mark S. Butler, Ruby Pelingon, Alysha G. Elliott, Maite Amado, Alejandra Gallardo-Godoy, Matthew A. Cooper, Mark A.T. Blaskovich
Introduction
Polymyxins are considered last-resort antibiotics for treating Gram-negative bacterial infections. The alarming global rise in polymyxin-resistant bacteria coupled with the slowness of conventional antimicrobial susceptibility testing methods leads to an unmet need for rapid susceptibility testing to facilitate timely and targeted therapeutic interventions.
Objectives
In this study, we aimed to develop novel polymyxin-derived fluorescent probes and improve the identification of polymyxin resistance by using these pathway-specific tools.
Methods
We designed, synthesized, and profiled a polymyxin-fluorophore derivative (PMX-NBD) with the small fluorophore NBD attached the central cyclic core of polymyxin via a triazole linker. We then applied PMX-NBD to develop RAPIDFC, a flow cytometry method that can rapidly and accurately profile polymyxin susceptibility of various Gram-negative pathogens.
Results
In contrast to many previously reported polymyxin probes, the fluorescent PMX-NBD retains the antimicrobial activity and profile of the parent polymyxin. Furthermore, we tested probe uptake in 49 strains encompassing E. coli, K. pneumoniae, P. aeruginosa, A. baumannii and S. aureus with a range of polymyxin sensitivity, leading to a susceptibility testing method RAPIDFC. Susceptibility to PMXB was defined by the difference between the Geometric Mean (GMean) of PMX-NBD fluorescence intensity at the two concentrations, with sensitive strains showing a greater variation compared to resistant strains. The RAPIDFC method is easy to implement and only requires 45 min compared to the broth microdilution method, which requires at least 24 h. However, the standard protocol failed to provide clear discrimination for A. baumannii, a key WHO-priority pathogen, necessitating a modified, species-specific approach for this organism.
Conclusions
The RAPIDFC method, based on the polymyxin-derived fluorescent probe, is fast and applicable to multiple species, making it a promising antimicrobial susceptibility method to guide appropriate therapy in the clinic. The case of A. baumannii demonstrates that species-specific resistance mechanisms may require tailored optimization of detection protocols.
{"title":"Rapid profiling of polymyxin B susceptibility in gram-negative bacteria with a novel polymyxin-derived fluorescent probe","authors":"Bing Zhang, Wanida Phetsang, Sanjaya Kc, Mark S. Butler, Ruby Pelingon, Alysha G. Elliott, Maite Amado, Alejandra Gallardo-Godoy, Matthew A. Cooper, Mark A.T. Blaskovich","doi":"10.1016/j.jare.2026.01.019","DOIUrl":"https://doi.org/10.1016/j.jare.2026.01.019","url":null,"abstract":"<h3>Introduction</h3>Polymyxins are considered last-resort antibiotics for treating Gram-negative bacterial infections. The alarming global rise in polymyxin-resistant bacteria coupled with the slowness of conventional antimicrobial susceptibility testing methods leads to an unmet need for rapid susceptibility testing to facilitate timely and targeted therapeutic interventions.<h3>Objectives</h3>In this study, we aimed to develop novel polymyxin-derived fluorescent probes and improve the identification of polymyxin resistance by using these pathway-specific tools.<h3>Methods</h3>We designed, synthesized, and profiled a polymyxin-fluorophore derivative (PMX-NBD) with the small fluorophore NBD attached the central cyclic core of polymyxin via a triazole linker. We then applied PMX-NBD to develop RAPID<sub>FC</sub>, a flow cytometry method that can rapidly and accurately profile polymyxin susceptibility of various Gram-negative pathogens.<h3>Results</h3>In contrast to many previously reported polymyxin probes, the fluorescent PMX-NBD retains the antimicrobial activity and profile of the parent polymyxin. Furthermore, we tested probe uptake in 49 strains encompassing <em>E. coli</em>, <em>K. pneumoniae</em>, <em>P. aeruginosa</em>, <em>A. baumannii</em> and <em>S. aureus</em> with a range of polymyxin sensitivity, leading to a susceptibility testing method RAPID<sub>FC</sub>. Susceptibility to PMXB was defined by the difference between the Geometric Mean (GMean) of PMX-NBD fluorescence intensity at the two concentrations, with sensitive strains showing a greater variation compared to resistant strains. The RAPID<sub>FC</sub> method is easy to implement and only requires 45 min compared to the broth microdilution method, which requires at least 24 h. However, the standard protocol failed to provide clear discrimination for<!-- --> <em>A. baumannii</em>, a key WHO-priority pathogen, necessitating a modified, species-specific approach for this organism.<h3>Conclusions</h3>The RAPID<sub>FC</sub> method, based on the polymyxin-derived fluorescent probe, is fast and applicable to multiple species, making it a promising antimicrobial susceptibility method to guide appropriate therapy in the clinic. The case of<!-- --> <em>A. baumannii</em> <!-- -->demonstrates that species-specific resistance mechanisms may require tailored optimization of detection protocols.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"1 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2026-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145949918","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}
Hepatocellular carcinoma (HCC) is a major cause of cancer-related mortality. Epigenetic dysregulation, particularly through methyltransferase METTL4, plays a critical role in HCC progression. METTL4 is known to catalyze m6Am methylation of mRNA, yet its pathological significance in liver cancer remains unclear.
Objective
This study aims to firstly investigate the role of METTL4 in the pathogenesis of HCC, and then to evaluate the antitumor efficacy of targeting METTL4 in inhibiting HCC growth and metastasis.
Methods
In a total of 802 postoperative HCC patients from four independent cohorts, we analyzed METTL4 expression in HCC tissues and its correlation with tumor staging and survival rates. Functional assays assessed the impact of METTL4 knockdown on HCC cell proliferation and metastasis, and patient-derived organoids (PDO) were used to evaluate the therapeutic efficacy of targeting METTL4. m6A-seq analyses identified GLI1 as a direct target of METTL4, investigating how METTL4-mediated m6Am modification affects GLI1 mRNA translation. Finally, we developed a siMETTL4-carrying nanoparticle and explored their efficacy in treating HCC in orthotopic and spontaneous liver tumor models.
Results
METTL4 was significantly upregulated in HCC tissues, correlating with higher tumor staging and poorer survival. Knockdown of METTL4 significantly inhibited HCC cell proliferation, migration, tumor growth, and lung metastasis. Meanwhile, targeting METTL4 effectively inhibited the growth of HCC PDO. METTL4-mediated m6Am modification enhanced GLI1 mRNA translation, with recognized target sites confirmed. Finally, siMETTL4-encapsulated nanoparticles effectively inhibited the growth and metastasis of orthotopic and spontaneous liver tumors.
Conclusions
Our findings highlight the role of METTL4-mediated m6Am modification in promoting HCC progression by enhancing GLI1 translation. Targeting METTL4 with siMETTL4-Nanoparticles represents a novel therapeutic strategy, bridging molecular insights in RNA epitranscriptomics with translational applications for HCC treatment.
{"title":"METTL4 enhances GLI1 translation through m6Am modification to promote tumor progression as a therapeutic target for hepatocellular carcinoma","authors":"Weijie Sun, Weiqi Dai, Chaobo Chen, Qian Qiu, Jianqing Chen, Jiaojiao Chen, Yueyue Li, Yuqi Liu, Dengyu Han, Wenhui Mo, Zishu Wang, Yihang Yuan, Xuanfu Xu","doi":"10.1016/j.jare.2026.01.009","DOIUrl":"https://doi.org/10.1016/j.jare.2026.01.009","url":null,"abstract":"<h3>Introduction</h3>Hepatocellular carcinoma (HCC) is a major cause of cancer-related mortality. Epigenetic dysregulation, particularly through methyltransferase METTL4, plays a critical role in HCC progression. METTL4 is known to catalyze m<sup>6</sup>Am methylation of mRNA, yet its pathological significance in liver cancer remains unclear.<h3>Objective</h3>This study aims to firstly investigate the role of METTL4 in the pathogenesis of HCC, and then to evaluate the antitumor efficacy of targeting METTL4 in inhibiting HCC growth and metastasis.<h3>Methods</h3>In a total of 802 postoperative HCC patients from four independent cohorts, we analyzed METTL4 expression in HCC tissues and its correlation with tumor staging and survival rates. Functional assays assessed the impact of METTL4 knockdown on HCC cell proliferation and metastasis, and patient-derived organoids (PDO) were used to evaluate the therapeutic efficacy of targeting METTL4. m<sup>6</sup>A-seq analyses identified GLI1 as a direct target of METTL4, investigating how METTL4-mediated m<sup>6</sup>Am modification affects GLI1 mRNA translation. Finally, we developed a siMETTL4-carrying nanoparticle and explored their efficacy in treating HCC in orthotopic and spontaneous liver tumor models.<h3>Results</h3>METTL4 was significantly upregulated in HCC tissues, correlating with higher tumor staging and poorer survival. Knockdown of METTL4 significantly inhibited HCC cell proliferation, migration, tumor growth, and lung metastasis. Meanwhile, targeting METTL4 effectively inhibited the growth of HCC PDO. METTL4-mediated m<sup>6</sup>Am modification enhanced GLI1 mRNA translation, with recognized target sites confirmed. Finally, siMETTL4-encapsulated nanoparticles effectively inhibited the growth and metastasis of orthotopic and spontaneous liver tumors.<h3>Conclusions</h3>Our findings highlight the role of METTL4-mediated m<sup>6</sup>Am modification in promoting HCC progression by enhancing GLI1 translation. Targeting METTL4 with siMETTL4-Nanoparticles represents a novel therapeutic strategy, bridging molecular insights in RNA epitranscriptomics with translational applications for HCC treatment.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"19 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2026-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145937556","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 : 2026-01-06DOI: 10.1016/j.jare.2026.01.017
Laiming Zhang, Zengliang Jiang, Donghong Liu, Chengxiao Yu, Yi Wang, Haozhen Zhang, Jiaxiong Wu, Haibo Pan, Xingqian Ye, Shiguo Chen
Introduction
Sarcopenia, characterized by the progressive loss of muscle mass and function, may be alleviated by ellagic acid (EA) through its microbial metabolite urolithin A (Uro-A). However, the low in vivo conversion efficiency of EA to Uro-A limits its clinical utility.
Objectives
This study aimed to develop a gut microbiota-targeted dietary strategy to enhance Uro-A biosynthesis and improve muscle performance.
Methods
A combinatorial approach using EA and fructooligosaccharides (FOS) was applied in vivo to modulate microbial metabolism. Gut microbiota composition, urolithin profiles, and muscle performance were assessed. Mechanistic roles of key bacterial species were further explored.
Results
EA and FOS synergistically improved muscle endurance and strength by enhancing Uro-A production, compared with either intervention alone. Mechanistically, we identified a previously unrecognized two-step cooperative pathway: Bifidobacterium pseudolongum initiated EA metabolism by converting it to urolithin C (Uro-C), and while Enterococcus faecalis, identified here for the first time, catalyzed the conversion of Uro-C to Uro-A. This newly uncovered cross-feeding partnership between the two species proved essential for maximizing Uro-A biosynthesis and mediating the physiological benefits.
Conclusion
This study demonstrates a proof-of-concept strategy to boost gut microbial Uro-A biosynthesis through dietary modulation, providing a novel and cost-effective approach for sarcopenia prevention and management.
{"title":"Fructooligosaccharides and ellagic acid synergistically enhance muscular endurance via targeting gut microbial urolithin A biosynthesis","authors":"Laiming Zhang, Zengliang Jiang, Donghong Liu, Chengxiao Yu, Yi Wang, Haozhen Zhang, Jiaxiong Wu, Haibo Pan, Xingqian Ye, Shiguo Chen","doi":"10.1016/j.jare.2026.01.017","DOIUrl":"https://doi.org/10.1016/j.jare.2026.01.017","url":null,"abstract":"<h3>Introduction</h3>Sarcopenia, characterized by the progressive loss of muscle mass and function, may be alleviated by ellagic acid (EA) through its microbial metabolite urolithin A (Uro-A). However, the low <em>in vivo</em> conversion efficiency of EA to Uro-A limits its clinical utility.<h3>Objectives</h3>This study aimed to develop a gut microbiota-targeted dietary strategy to enhance Uro-A biosynthesis and improve muscle performance.<h3>Methods</h3>A combinatorial approach using EA and fructooligosaccharides (FOS) was applied <em>in vivo</em> to modulate microbial metabolism. Gut microbiota composition, urolithin profiles, and muscle performance were assessed. Mechanistic roles of key bacterial species were further explored.<h3>Results</h3>EA and FOS synergistically improved muscle endurance and strength by enhancing Uro-A production, compared with either intervention alone. Mechanistically, we identified a previously unrecognized two-step cooperative pathway: <em>Bifidobacterium pseudolongum</em> initiated EA metabolism by converting it to urolithin C (Uro-C), and while <em>Enterococcus faecalis,</em> identified here for the first time, catalyzed the conversion of Uro-C to Uro-A. This newly uncovered cross-feeding partnership between the two species proved essential for maximizing Uro-A biosynthesis and mediating the physiological benefits.<h3>Conclusion</h3>This study demonstrates a proof-of-concept strategy to boost gut microbial Uro-A biosynthesis through dietary modulation, providing a novel and cost-effective approach for sarcopenia prevention and management.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"44 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145907652","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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