iMeta最新文献

{"title":"Non-differential gut microbes contribute to hypertension and its severity through co-abundances: A multi-regional prospective cohort study","authors":"Lu Liu,&nbsp;Qianyi Zhou,&nbsp;Tianbao Xu,&nbsp;Qiufeng Deng,&nbsp;Yuhao Sun,&nbsp;Jingxiang Fu,&nbsp;Muxuan Chen,&nbsp;Xiaojiao Chen,&nbsp;Zhenchao Ma,&nbsp;Quanbin Dong,&nbsp;Beining Ma,&nbsp;Yuwen Jiao,&nbsp;Yan Zhou,&nbsp;Tingting Wu,&nbsp;Huayiyang Zou,&nbsp;Jing Shi,&nbsp;Yifeng Wang,&nbsp;Yanhui Sheng,&nbsp;Liming Tang,&nbsp;Chao Zheng,&nbsp;Wei Wu,&nbsp;Wenjun Ma,&nbsp;Wei Sun,&nbsp;Shixian Hu,&nbsp;Hongwei Zhou,&nbsp;Yan He,&nbsp;Xiangqing Kong,&nbsp;Lianmin Chen","doi":"10.1002/imt2.268","DOIUrl":"https://doi.org/10.1002/imt2.268","url":null,"abstract":"<p>Microbial dysbiosis, characterized by an imbalanced microbial community structure and function, has been linked to hypertension. While prior research has primarily focused on differential abundances, our study highlights the role of non-differential microbes in hypertension. We propose that non-differential microbes contribute to hypertension through their ecological interactions, as defined by co-abundances (pairs of microbes exhibiting correlated abundance patterns). Using gut microbiome data from the Guangdong Gut Microbiome Project, which includes 2355 hypertensive and 4644 non-hypertensive participants across 14 regions, we identified replicable hypertension-related microbial interactions. Notably, most co-abundances involved non-differential microbes, which were found to correlate with both hypertension severity and hypertension-related microbial metabolic pathways. These findings emphasize the importance of microbial interactions in hypertension pathogenesis and propose a novel perspective for microbiome-based therapeutic strategies.</p>","PeriodicalId":73342,"journal":{"name":"iMeta","volume":"4 1","pages":""},"PeriodicalIF":23.7,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/imt2.268","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143497205","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The prognostic and therapeutic significance of polyunsaturated fatty acid-derived oxylipins in ST-segment elevation myocardial infarction","authors":"Zhiyong Du,&nbsp;Yingyuan Lu,&nbsp;Ying Ma,&nbsp;Yunxiao Yang,&nbsp;Wei Luo,&nbsp;Sheng Liu,&nbsp;Ming Zhang,&nbsp;Yong Wang,&nbsp;Lei Li,&nbsp;Chun Li,&nbsp;Wei Wang,&nbsp;Hai Gao","doi":"10.1002/imt2.266","DOIUrl":"https://doi.org/10.1002/imt2.266","url":null,"abstract":"<p>Polyunsaturated fatty acid-derived oxylipins regulate systemic inflammation and exert cardiovascular effects, yet their role in ST-segment elevation myocardial infarction (STEMI) remains unclear. Herein, we used targeted metabolomics and machine learning algorithms to develop an oxylipin-based risk model to accurately predict recurrent major adverse cardiovascular events (MACE) after STEMI in two independent prospective cohorts with 2 years of follow-up. The in vivo effects of significant oxylipin predictors were explored via a murine myocardial ischemia‒reperfusion model and functional metabolomics. Among the 130 plasma oxylipins detected in discovery cohort (<i>n</i> = 645), patients with and without recurrent MACE exhibited significant differences in a variety of oxylipin subclasses. We constructed an oxylipin-based prediction model that showed powerful performance in predicting recurrent MACE in the discovery cohort (predictive accuracy: 91.5%). The predictive value of the oxylipin marker panel was confirmed in an independent external validation cohort (predictive accuracy: 89.9%; <i>n</i> = 401). Furthermore, we found that the anti-inflammatory/pro-resolving oxylipin (ARO) predictor panel showed better prognostic performance than the pro-inflammatory oxylipin predictor panel in both cohorts. Compared with the treatment of pro-inflammatory oxylipin predictor panel, combined treatment of six ARO predictors, including 14,15 epoxy-eicosatrienoic acid, 14(15)-epoxy-eicosatetraenoic acid, 12,13-epoxy-octadecenoic acid, lipoxin A4, resolving D1, and 6 keto-prostaglandin F1 showed significant cardiac activities and synergistic metabolic actions in myocardial infarction‒reperfusion model mice. We also mechanistically identified an important role of ARO predictors in restraining ceramide/lysophosphatidylcholine synthesis and inhibiting inflammatory responses. Overall, the present study depicted the landscape of oxylipin profiles in the largest panel of STEMI patients worldwide. Our results also highlight the great potential of bioactive oxylipins in prognostic prediction and therapeutics after STEMI.</p>","PeriodicalId":73342,"journal":{"name":"iMeta","volume":"4 1","pages":""},"PeriodicalIF":23.7,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/imt2.266","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143497204","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gut microbiota in treating inflammatory digestive diseases: Current challenges and therapeutic opportunities","authors":"Yongpeng Shi,&nbsp;Zeran Chen,&nbsp;Tingyu Fang,&nbsp;Xingyao Chen,&nbsp;Youpeng Deng,&nbsp;Hao Qin,&nbsp;Min Lian,&nbsp;Juntao Shen,&nbsp;Yuru Zong,&nbsp;Huikuan Chu,&nbsp;Constanze Hoebinger,&nbsp;Hao Guo,&nbsp;Zhongshang Yuan,&nbsp;Jie Zheng,&nbsp;Yongjian Zhou,&nbsp;Yue Pan,&nbsp;Beatriz G. Mendes,&nbsp;Sonja Lang,&nbsp;Tim Hendrikx,&nbsp;Suling Zeng,&nbsp;Hailong Cao,&nbsp;Ling Yang,&nbsp;Lianmin Chen,&nbsp;Peng Chen,&nbsp;Lei Dai,&nbsp;Hua Wang,&nbsp;Shi Yin,&nbsp;Shu Zhu,&nbsp;Xiong Ma,&nbsp;Bernd Schnabl,&nbsp;Hanqing Chen,&nbsp;Yi Duan","doi":"10.1002/imt2.265","DOIUrl":"https://doi.org/10.1002/imt2.265","url":null,"abstract":"<p>Accumulating evidence indicates that the gut microbiota is intricately involved in the initiation and progression of human diseases, forming a multidirectional regulatory axis centered on intestinal microbiota. This article illustrates the challenges in exploring the role of the gut microbiota in inflammatory digestive diseases, such as metabolic dysfunction-associated steatotic liver disease (MASLD) and inflammatory bowel disease (IBD), and summarizes the existing microbiome-focused treatment strategies (probiotics, prebiotics, symbiotics, fecal microbiota transplantation, and bacteriophages therapy), emerging technologies (gut microbiome-on-a-chip and artificial intelligence), as well as possible future research directions. Taken together, these therapeutic strategies and technologies present both opportunities and challenges, which require researchers and clinicians to test the rationality and feasibility of various therapeutic modalities in continuous practice.\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":73342,"journal":{"name":"iMeta","volume":"4 1","pages":""},"PeriodicalIF":23.7,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/imt2.265","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143497167","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gut Bifidobacterium pseudocatenulatum protects against fat deposition by enhancing secondary bile acid biosynthesis","authors":"Andong Zha,&nbsp;Ming Qi,&nbsp;Yuankun Deng,&nbsp;Hao Li,&nbsp;Nan Wang,&nbsp;Chengming Wang,&nbsp;Simeng Liao,&nbsp;Dan Wan,&nbsp;Xia Xiong,&nbsp;Peng Liao,&nbsp;Jing Wang,&nbsp;Yulong Yin,&nbsp;Bi'e Tan","doi":"10.1002/imt2.261","DOIUrl":"10.1002/imt2.261","url":null,"abstract":"<p>Gut microbiome is crucial for lipid metabolism in humans and animals. However, how specific gut microbiota and their associated metabolites impact fat deposition remains unclear. In this study, we demonstrated that the colonic microbiome of lean and obese pigs differentially contributes to fat deposition, as evidenced by colonic microbiota transplantation experiments. Notably, the higher abundance of <i>Bifidobacterium pseudocatenulatum</i> was significantly associated with lower backfat thickness in lean pigs. Microbial-derived lithocholic acid (LCA) species were also significantly enriched in lean pigs and positively correlated with the abundance of <i>B. pseudocatenulatum</i>. In a high-fat diet (HFD)-fed mice model, administration of live <i>B. pseudocatenulatum</i> decreased fat deposition and enhances colonic secondary bile acid biosynthesis. Importantly, pharmacological inhibition of the bile salt hydrolase (BSH), which mediates secondary bile acid biosynthesis, impaired the anti-fat deposition effect of <i>B. pseudocatenulatum</i> in antibiotic-pretreated, HFD-fed mice. Furthermore, dietary LCA also decreased fat deposition in HFD-fed rats and obese pig models. These findings provide mechanistic insights into the anti-fat deposition role of <i>B. pseudocatenulatum</i> and identify BSH as a potential target for preventing excessive fat deposition in humans and animals.</p>","PeriodicalId":73342,"journal":{"name":"iMeta","volume":"3 6","pages":""},"PeriodicalIF":23.7,"publicationDate":"2024-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11683477/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142916340","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"EGDB: A comprehensive multi-omics database for energy grasses and the epigenomic atlas of pearl millet","authors":"Lin Luo,&nbsp;Dongmei Lin,&nbsp;Jinhui Li,&nbsp;Hao Chen,&nbsp;Qi Qu,&nbsp;Lin Zhang,&nbsp;Yuan Luo,&nbsp;Jiaming Chen,&nbsp;Dingkun Jiang,&nbsp;Peitao Lü,&nbsp;Wenjun Zhu,&nbsp;Hui Lin,&nbsp;Ensi Shao,&nbsp;Haidong Yan,&nbsp;Yarong Jin,&nbsp;Guodong Lu,&nbsp;Zhanxi Lin,&nbsp;LuLu Xun,&nbsp;Fangjie Zhu,&nbsp;Linkai Huang,&nbsp;Jiajing Xiao","doi":"10.1002/imt2.263","DOIUrl":"https://doi.org/10.1002/imt2.263","url":null,"abstract":"<p>Given the key role of energy grasses in biomass energy, electricity, biofuels, and carbon sequestration, the Energy Grass Omics Database (EGDB) integrates germplasm data with genomics, transcriptomics, epigenomics, and phenomics data to support functional genomic research on diverse energy grass species. EGDB also currently supplies the largest epigenetic data set of energy grasses: a high-resolution chromatin modification, chromatin accessibility, and gene expression landscape of pearl millet to provide insights into regulatory traits essential for sustainable energy production.\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":73342,"journal":{"name":"iMeta","volume":"4 1","pages":""},"PeriodicalIF":23.7,"publicationDate":"2024-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/imt2.263","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143497413","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pangenome and genome variation analyses of pigs unveil genomic facets for their adaptation and agronomic characteristics","authors":"Dong Li,&nbsp;Yulong Wang,&nbsp;Tiantian Yuan,&nbsp;Minghao Cao,&nbsp;Yulin He,&nbsp;Lin Zhang,&nbsp;Xiang Li,&nbsp;Yifan Jiang,&nbsp;Ke Li,&nbsp;Jingchun Sun,&nbsp;Guangquan Lv,&nbsp;Guosheng Su,&nbsp;Qishan Wang,&nbsp;Yuchun Pan,&nbsp;Xinjian Li,&nbsp;Yu Jiang,&nbsp;Gongshe Yang,&nbsp;Martien A. M. Groenen,&nbsp;Martijn F. L. Derks,&nbsp;Rongrong Ding,&nbsp;Xiangdong Ding,&nbsp;Taiyong Yu","doi":"10.1002/imt2.257","DOIUrl":"10.1002/imt2.257","url":null,"abstract":"<p>The development of a comprehensive pig graph pangenome assembly encompassing 27 genomes represents the most extensive collection of pig genomic data to date. Analysis of this pangenome reveals the critical role of structural variations in driving adaptation and defining breed-specific traits. Notably, the study identifies <i>BTF3</i> as a key candidate gene governing intramuscular fat deposition and meat quality in pigs. These findings underscore the power of pangenome approaches in uncovering novel genomic features underlying economically important agricultural traits. Collectively, these results demonstrate the value of leveraging large-scale, multi-genome analyses for advancing our understanding of livestock genomes and accelerating genetic improvement.\u0000\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":73342,"journal":{"name":"iMeta","volume":"3 6","pages":""},"PeriodicalIF":23.7,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11683468/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142916343","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comprehensive lung microbial gene and genome catalogs assist the mechanism survey of Mesomycoplasma hyopneumoniae strains causing pig lung lesions","authors":"Jingquan Li,&nbsp;Fei Huang,&nbsp;Yunyan Zhou,&nbsp;Tao Huang,&nbsp;Xinkai Tong,&nbsp;Mingpeng Zhang,&nbsp;Jiaqi Chen,&nbsp;Zhou Zhang,&nbsp;Huipeng Du,&nbsp;Zifeng Liu,&nbsp;Meng Zhou,&nbsp;Yiwen Xiahou,&nbsp;Huashui Ai,&nbsp;Congying Chen,&nbsp;Lusheng Huang","doi":"10.1002/imt2.258","DOIUrl":"10.1002/imt2.258","url":null,"abstract":"<p>Understanding the community structure of the lower respiratory tract microbiome is crucial for elucidating its roles in respiratory tract diseases. However, there are few studies about this topic due to the difficulty in obtaining microbial samples from both healthy and disease individuals. Here, using 744 high-depth metagenomic sequencing data of lower respiratory tract microbial samples from 675 well-phenotyped pigs, we constructed a lung microbial gene catalog containing the largest scale of 10,031,593 nonredundant genes to date, 44.8% of which are novel. We obtained 356 metagenome-assembled genomes (MAGs) which were further clustered into 256 species-level genome bins with 41.8% being first reported in the current databases. Based on these data sets and through integrated analysis of the isolation of the related bacterial strains, in vitro infection, and RNA sequencing, we identified and confirmed that <i>Mesomycoplasma hyopneumoniae</i> (<i>M. hyopneumoniae</i>) MAG_47 and its adhesion-related virulence factors (VFs) were associated with lung lesions in pigs. Differential expression levels of adhesion- and immunomodulation-related VFs likely determined the heterogenicity of adhesion and pathogenicity among <i>M. hyopneumoniae</i> strains. <i>M. hyopneumoniae</i> adhesion activated several pathways, including nuclear factor kappa-light-chain-enhancer of activated B, mitogen-activated protein kinase, cell apoptosis, T helper 1 and T helper 2 cell differentiation, tumor necrosis factor signaling, interleukin-6/janus kinase 2/signal transducer and activator of transcription signaling, and response to reactive oxygen species, leading to cilium loss, epithelial cell‒cell barrier disruption, and lung tissue lesions. Finally, we observed the similar phylogenetic compositions of the lung microbiome between humans with <i>Mycoplasma pneumoniae</i> and pigs infected with <i>M. hyopneumoniae</i>. The results provided important insights into pig lower respiratory tract microbiome and its relationship with lung health.</p>","PeriodicalId":73342,"journal":{"name":"iMeta","volume":"3 6","pages":""},"PeriodicalIF":23.7,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11683470/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142916224","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrating gut and IgA-coated microbiota to identify Blautia as a probiotic for enhancing feed efficiency in chickens","authors":"Chunlin Xie,&nbsp;Jiaheng Cheng,&nbsp;Peng Chen,&nbsp;Xia Yan,&nbsp;Chenglong Luo,&nbsp;Hao Qu,&nbsp;Dingming Shu,&nbsp;Jian Ji","doi":"10.1002/imt2.264","DOIUrl":"https://doi.org/10.1002/imt2.264","url":null,"abstract":"<p>This study explores the role of IgA-coated bacteria in improving feed efficiency in chickens, offering a novel perspective for probiotic screening. Chickens with high feed efficiency were found to have a greater abundance of Gram-positive bacteria, while low feed efficiency chickens exhibited higher levels of Gram-negative bacteria and potential pathogens. Through fecal microbiota transplantation (FMT) and integrating analysis of cecal and IgA-coated microbiota, we precisely identified <i>Blautia</i> as a key genus linked to improved feed efficiency. Further validation demonstrated that <i>Blautia coccoides</i>, a representative species of this genus, enhances feed efficiency and activates B cells to produce Immunoglobulin A (IgA), both in vivo and in vitro. Our findings provide new insights into the potential of IgA-coated bacteria as functional probiotics, offering a promising strategy for enhancing feed efficiency in animal production.\u0000\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":73342,"journal":{"name":"iMeta","volume":"4 1","pages":""},"PeriodicalIF":23.7,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/imt2.264","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143497210","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unraveling the diversity dynamics and network stability of alkaline phosphomonoesterase-producing bacteria in modulating maize yield","authors":"Lijun Chen,&nbsp;Guofan Zhu,&nbsp;Alberto Pascual-Garcia,&nbsp;Francisco Dini-Andreote,&nbsp;Jie zheng,&nbsp;Xiaoyue Wang,&nbsp;Shungui Zhou,&nbsp;Yuji Jiang","doi":"10.1002/imt2.260","DOIUrl":"10.1002/imt2.260","url":null,"abstract":"<p>Phosphorus, as a nonrenewable resource, plays a crucial role in crop development and productivity. However, the extent to which straw amendments contribute to the dynamics of soil alkaline phosphomonoesterase (ALP)-producing bacterial community and functionality over an extended period remains elusive. Here, we conducted a 7-year long-term field experiment consisting of a no-fertilizer control, a chemical fertilizer treatment, and three straw (straw, straw combined with manure, and straw biochar) treatments. Our results indicated that straw amendments significantly improved the succession patterns of the ALP-producing bacterial diversity. Simultaneously, straw amendments significantly increased the network stability of the ALP-producing bacteria over time, as evidenced by higher network robustness, a higher ratio of negative to positive cohesion, and lower network vulnerability. High dynamic and stability of ALP-producing bacterial community generated high ALP activity which further increased soil Phosphorus (P) availability as well as maize productivity.\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":73342,"journal":{"name":"iMeta","volume":"3 6","pages":""},"PeriodicalIF":23.7,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11683463/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142916423","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transcriptome-wide association identifies KLC1 as a regulator of mitophagy in non-syndromic cleft lip with or without palate","authors":"Shu Lou,&nbsp;Guirong Zhu,&nbsp;Changyue Xing,&nbsp;Shushu Hao,&nbsp;Junyan Lin,&nbsp;Jiayi Xu,&nbsp;Dandan Li,&nbsp;Yifei Du,&nbsp;Congbo Mi,&nbsp;Lian Sun,&nbsp;Lin Wang,&nbsp;Meilin Wang,&nbsp;Mulong Du,&nbsp;Yongchu Pan","doi":"10.1002/imt2.262","DOIUrl":"10.1002/imt2.262","url":null,"abstract":"<p>This study investigated pathogenic genes associated with non-syndromic cleft lip with or without cleft palate (NSCL/P) through transcriptome-wide association studies (TWAS). By integrating expression quantitative trait loci (eQTL) data with genome-wide association study (GWAS) data, we identified key susceptibility genes, including <i>KLC1</i>. Notably, the variant rs12884809 G&gt;A was associated with an increased risk of NSCL/P by enhancing the binding of the transcription factor ELK1 to the <i>KLC1</i> promoter, thereby activating its expression. This alteration in <i>KLC1</i> expression subsequently impacted mitophagy, leading to significant changes in cellular behavior and zebrafish morphology. Our findings illuminate the genetic mechanisms underlying NSCL/P and provide valuable insights for future prevention strategies and a deeper understanding of this condition.\u0000\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":73342,"journal":{"name":"iMeta","volume":"3 6","pages":""},"PeriodicalIF":23.7,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11683466/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142916420","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}