Journal of advanced research最新文献

{"title":"Extracellular vesicle-derived miR-146a as a novel crosstalk mechanism for high-fat induced atherosclerosis by targeting SMAD4.","authors":"Kefeng Zhai, Liangle Deng, Yuxuan Wu, Han Li, Jing Zhou, Ying Shi, Jianhu Jia, Wei Wang, Sihui Nian, Ghulam Jilany Khan, Hesham R El-Seedi, Hong Duan, Lili Li, Zhaojun Wei","doi":"10.1016/j.jare.2024.08.012","DOIUrl":"10.1016/j.jare.2024.08.012","url":null,"abstract":"<p><strong>Introduction: </strong>Exosome-miR-146a is significantly increased in patients with Atherosclerosis (AS), but its mechanism and effect on AS have not been fully elucidated.</p><p><strong>Objectives: </strong>To explore the change rule and mechanism of exosomes release, and the role and molecular mechanism of exosome-miR-146a in AS.</p><p><strong>Methods: </strong>We isolated and identified exosomes from THP-1 macrophages after treating them with ox-LDL. Then used co-immunoprecipitation and silver staining to identify the proteins involved in regulating exosome release. PKH67 was used to label exosomes to confirm that cells can absorb them, and then co-culture with HVSMCs for cell proliferation and migration detection. The target genes of miR-146a were screened and identified through bioinformatics and luciferase activity assay, and the expression of miR-146a and related proteins was detected through qRT-PCR and Western blot in HUVECs. An AS model in LDLR^-/- mice induced by a high-fat diet was developed to investigate the impact of exosome-miR-146a on AS.</p><p><strong>Results: </strong>The results showed that experimental foam cells from AS showed higher expression of miR-146a. It was observed that NMMHC IIA and HSP70 interacted to regulate the release of exosomes. And HUVECs can absorb exosomes derived from macrophages. In addition, we also found that miR-146a directly targeted the SMAD4 gene to modulate the p38 MAPK signaling pathway, thereby mediating HUVECs damage. Furthermore, exosome-miR-146a induced abnormal proliferation and migration of HVSMCs. The expression of miR-146a was significantly reduced in miR-146a-mimics mice and increased in miR-146a inhibitor mice whereas the inhibition of miR-146a effectively reduced while increasing miR-146a worsened AS in mice.</p><p><strong>Conclusion: </strong>Our findings expressed the potential of miR-146a as a favorable therapeutic target for AS, however, further exploration is suggestive for deep understanding of the mechanisms regulating exosome-miR-146a release in vivo and to develop effective therapeutic strategies involving miR-146a.</p>","PeriodicalId":94063,"journal":{"name":"Journal of advanced research","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141914915","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Design and construction of light-regulated gene transcription and protein translation systems in yeast P. Pastoris.","authors":"Siyu Zhang, Jiazhen Zhang, Ru Lin, Chaoyu Lu, Bohao Fang, Jiacheng Shi, Tianyi Jiang, Mian Zhou","doi":"10.1016/j.jare.2024.08.008","DOIUrl":"10.1016/j.jare.2024.08.008","url":null,"abstract":"<p><strong>Introduction: </strong>P. pastoris is a common host for effective biosynthesis of heterologous proteins as well as small molecules. Accurate regulation of gene transcription and protein synthesis is necessary to coordinate synthetic gene circuits and optimize cellular energy distribution. Traditional methanol or other inducible promoters, natural or engineered, have defects in either fermentation safety or expression capacity. The utilization of chemical inducers typically adds complexity to the product purification process, but there is no other well-controlled protein synthesis system than promoters yet.</p><p><strong>Objective: </strong>The study aimed to address the aforementioned challenges by constructing light-regulated gene transcription and protein translation systems with excellent expression capacity and light sensitivity.</p><p><strong>Methods: </strong>Trans-acting factors were designed by linking the N. crassa blue-light sensor WC-1 with the activation domain of endogenous transcription factors. Light inducible or repressive promoters were then constructed through chimeric design of cis-elements (light-responsive elements, LREs) and endogenous promoters. Various configurations of trans-acting factor/LRE pairs, along with different LRE positions and copy numbers were tested for optimal promoter performance. In addition to transcription, a light-repressive translation system was constructed through the \"rare codon brake\" design. Rare codons were deliberately utilized to serve as brakes during protein synthesis, which were switched on and off through the light-regulated changes in the expression of the corresponding pLRE-tRNA.</p><p><strong>Results: </strong>As demonstrated with GFP, the light-inducible promoter 4pLRE-cP_AOX1 was 70 % stronger than the constitutive promoter P_GAP, with L/D ratio = 77. The light-repressive promoter P_GAP-pLRE was strictly suppressed by light, with expression capacity comparable with P_GAP in darkness. As for the light-repressive translation system, the \"triple brake\" design successfully eliminated leakage and achieved light repression on protein synthesis without any impact on mRNA expression.</p><p><strong>Conclusion: </strong>The newly designed light-regulated transcription and translation systems offer innovative tools that optimize the application of P. pastoris in biotechnology and synthetic biology.</p>","PeriodicalId":94063,"journal":{"name":"Journal of advanced research","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141908711","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impacts of parental genomic divergence in non-syntenic regions on cotton heterosis.","authors":"Chujun Huang, Yu Cheng, Yan Hu, Xuemei Zhang, Jinwen Chen, Ting Zhao, Zhanfeng Si, Yiwen Cao, Yiqian Li, Lei Fang, Xueying Guan, Tianzhen Zhang","doi":"10.1016/j.jare.2024.08.010","DOIUrl":"10.1016/j.jare.2024.08.010","url":null,"abstract":"<p><strong>Introduction: </strong>Heterosis has revolutionized crop breeding, enhancing global agricultural production. However, the mechanisms underlying heterosis remain obscure. Xiangzamian 2# (XZM2), a super hybrid upland cotton (Gossypium hirsutum L.) characterized by high-yield heterosis, has been developed and extensively planted in China.</p><p><strong>Objectives: </strong>We conducted a systematic analysis of CRI12 and J8891, two parents of XZM2. We aimed to reveal the precise genetic information and the role of non-syntenic divergence in shaping heterosis, laying a foundation for advancing understanding of heterosis.</p><p><strong>Methods: </strong>We de novo assembled high-quality genomes of CRI12 and J8891, and further uncovered abundant genetic variations and non-syntenic regions between the parents. Whole-genome comparison, association analysis, transcriptomic analysis and relative identity-by-descent (rIBD) estimation were conducted to identify structural variations (SVs) and introgressions within non-syntenic blocks and to analyze their impacts on promoting heterosis.</p><p><strong>Results: </strong>Parental genetic divergence increased in non-syntenic regions. Furthermore, these regions, accounting for only 16.71% of the total genome, contained more loci with significantly higher heterotic effects, far exceeding the syntenic background. SVs covered 97.26% of non-syntenic sequences and caused widespread gene expression differences in these regions, driving dynamic complementation of gene expression in the hybrid. A set of SVs were responsible for trait improvement and had positive effects on heterosis, contributing larger heritability than short variations. We characterized numerous parental-specific introgressions from G. barbadense. Specifically, a functional introgression segment within non-syntenic blocks introduced an elite haplotype, which significantly increased lint yield and enhanced heterosis.</p><p><strong>Conclusion: </strong>Our study clarified non-syntenic regions to harbor more loci with higher heterotic effects, revealed their importance in promoting heterosis and supported the crucial role of genetic complementation in heterosis. SVs and introgressions were identified as key factors responsible for non-syntenic divergence between the parents. They had important effects on gene expression and trait improvement, positively contributing to heterosis.</p>","PeriodicalId":94063,"journal":{"name":"Journal of advanced research","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141903965","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Short-chain fatty acid butyrate against TMAO activating endoplasmic-reticulum stress and PERK/IRE1-axis with reducing atrial arrhythmia.","authors":"Tzu-Yu Cheng, Ting-Wei Lee, Shao-Jung Li, Ting-I Lee, Yao-Chang Chen, Yu-Hsun Kao, Satoshi Higa, Pao-Huan Chen, Yi-Jen Chen","doi":"10.1016/j.jare.2024.08.009","DOIUrl":"10.1016/j.jare.2024.08.009","url":null,"abstract":"<p><strong>Introduction: </strong>The accumulation of microbiota-derived trimethylamine N-oxide (TMAO) in the atrium is linked to the development and progression of atrial arrhythmia. Butyrate, a major short-chain fatty acid, plays a crucial role in sustaining intestinal homeostasis and alleviating systemic inflammation, which may reduce atrial arrhythmogenesis.</p><p><strong>Objectives: </strong>This study explored the roles of butyrate in regulating TMAO-mediated atrial remodeling and arrhythmia.</p><p><strong>Methods: </strong>Whole-cell patch clamp experiments, Western blotting, and immunocytochemistry were used to analyze electrical activity and signaling, respectively, in TMAO-treated HL-1 atrial myocytes with or without sodium butyrate (SB) administration. Telemetry electrocardiographic recording and echocardiography and Masson's trichrome staining and immunohistochemistry were employed to examine atrial function and histopathology, respectively, in mice treated with TMAO with and without SB administration.</p><p><strong>Results: </strong>Compared with control cells, TMAO-treated HL-1 myocytes exhibited reduced action potential duration (APD), elevated sarcoplasmic reticulum (SR) calcium content, larger L-type calcium current (I_Ca-L), increased Na⁺/Ca²⁺ exchanger (NCX) current, and increased potassium current. However, the combination of SB and TMAO resulted in similar APD, SR calcium content, I_Ca-L, transient outward potassium current (I_to), and ultrarapid delayed rectifier potassium current (I_Kur) compared with controls. Additionally, TMAO-treated HL-1 myocytes exhibited increased activation of endoplasmic reticulum (ER) stress signaling, along with increased PKR-like ER stress kinase (PERK)/IRE1α axis activation and expression of phospho-IP3R, NCX, and Kv1.5, compared with controls or HL-1 cells treated with the combination of TMAO and SB. TMAO-treated mice exhibited atrial ectopic beats, impaired atrial function, increased atrial fibrosis, and greater activation of ER stress signaling with PERK/IRE1α axis activation compared with controls and mice treated with TMAO combined with SB.</p><p><strong>Conclusion: </strong>TMAO administration led to PERK/IRE1α axis activation, which may increase atrial remodeling and arrhythmogenesis. SB treatment mitigated TMAO-elicited ER stress. This finding suggests that SB administration is a valuable strategy for treating TMAO-induced atrial arrhythmia.</p>","PeriodicalId":94063,"journal":{"name":"Journal of advanced research","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141903968","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Loss of Nup155 promotes high fructose-driven podocyte senescence by inhibiting INO80 mRNA nuclear export.","authors":"Li Chen, Tangdi Xu, Zixuan Wang, Chengzhi Wang, Lei Fang, Lingdong Kong","doi":"10.1016/j.jare.2024.08.007","DOIUrl":"10.1016/j.jare.2024.08.007","url":null,"abstract":"<p><strong>Introduction: </strong>Podocyte senescence causes podocyte loss and glomerulopathy. Excessive fructose intake is a risk factor for podocyte injury. However, whether high fructose promotes podocyte senescence remains unknown.</p><p><strong>Objectives: </strong>To explore the pathological mechanism by which high fructose drives podocyte senescence and find natural compounds to alleviate podocyte senescence.</p><p><strong>Methods: </strong>Podocyte senescence was characterized with senescence-associated beta-galactosidase (SA-β-gal) staining, Western blot, real-time quantitative polymerase chain reaction (qRT-PCR), comet assay and immunofluorescence. Proteomics analysis was performed to identify differentially expressed proteins in high fructose-exposed podocytes. Podocyte nuclear pore complexes (NPCs) and foot processes were observed by transmission electron microscopy. The mRNA and protein levels of nucleoporin 155 (Nup155) and inositol requiring mutant 80 (INO80) were detected by qRT-PCR, Western blot and immunofluorescence. Virtual screening was conducted to find natural compounds that target Nup155.</p><p><strong>Results: </strong>High fructose increased SA-β-gal activity, protein level of p53, p21, p16 and phosphorylated histone H2AX (γ-H2AX), as well as mRNA expression of interleukin-1β (IL-1β), IL-6 and tumor necrosis factor α (TNF-α) in rat glomeruli and podocytes. Proteomic analysis unraveled a crucial molecule Nup155, which was decreased in high fructose-induced podocyte senescence. Meanwhile, the number of podocyte NPCs was also decreased in vivo and in vitro. Consistently, high fructose suppressed nuclear export of INO80 mRNA, thereby down-regulated INO80 protein expression in podocyte senescence. Deletion of Nup155 inhibited INO80 mRNA nuclear export to induce podocyte senescence, whereas overexpression of Nup155 or INO80 alleviated high fructose-induced podocyte senescence. Ferulic acid was found to up-regulate Nup155 by both direct binding to stabilize Nup155 protein and enhancing its transcription, to promote INO80 mRNA nuclear export in the mitigation of high fructose-caused podocyte senescence.</p><p><strong>Conclusion: </strong>High fructose induces podocyte senescence by decreasing Nup155 to inhibit INO80 mRNA nuclear export. Ferulic acid targeting Nup155 may be a potential strategy to prevent high fructose-induced podocyte senescence.</p>","PeriodicalId":94063,"journal":{"name":"Journal of advanced research","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141903966","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DeepB³P: A transformer-based model for identifying blood-brain barrier penetrating peptides with data augmentation using feedback GAN.","authors":"Qiang Tang, Wei Chen","doi":"10.1016/j.jare.2024.08.002","DOIUrl":"https://doi.org/10.1016/j.jare.2024.08.002","url":null,"abstract":"<p><strong>Introduction: </strong>The blood-brain barrier (BBB) serves as a critical structural barrier and impedes the entry of most neurotherapeutic drugs into the brain. This poses substantial challenges for central nervous system (CNS) drug development, as there is a lack of efficient drug delivery technologies to overcome this obstacle. BBB penetrating peptides (BBBPs) hold promise in overcoming the BBB and facilitating the delivery of drug molecules to the brain. Therefore, precise identification of BBBPs has become a crucial step in CNS drug development. However, most computational methods are designed based on conventional models that inadequately capture the intricate interaction between BBBPs and the BBB. Moreover, the performance of these methods was further hampered by unbalanced datasets.</p><p><strong>Objectives: </strong>This study addresses the problem of unbalanced datasets in BBBP prediction and proposes a powerful predictor for efficiently and accurately identifying BBBPs, as well as generating analogous BBBPs.</p><p><strong>Methods: </strong>A transformer-based deep learning model, DeepB³P, was proposed for predicting BBBP. The feedback generative adversarial network (FBGAN) model was employed to effectively generate analogous BBBPs, addressing data imbalance.</p><p><strong>Results: </strong>The FBGAN model possesses the ability to generate novel BBBP-like peptides, effectively mitigating the data imbalance in BBBP prediction. Extensive experiments on benchmarking datasets demonstrated that DeepB³P outperforms other BBBP prediction models by approximately 9.09%, 4.55% and 9.41% in terms of specificity, accuracy, and Matthew's correlation coefficient, respectively. For accelerating the progress in BBBP identification and CNS drug design, the proposed DeepB³P was implemented as a webserver, which is accessible at http://cbcb.cdutcm.edu.cn/deepb3p/.</p><p><strong>Conclusion: </strong>The interpretable analyses provided by DeepB³P offer valuable insights and enhance downstream analyses for BBBP identification. Moreover, the BBBP-like peptides generated by FBGAN hold potential as candidates for CNS drug development.</p>","PeriodicalId":94063,"journal":{"name":"Journal of advanced research","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141903954","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of modern Chinese medicine guided by molecular compatibility theory.","authors":"Lifeng Luo, Jieru Zhou, Xiaonan Liu, Yanyu Chen, Xiao Du, Lili Gao, Yunting Sun, Shuling Wang","doi":"10.1016/j.jare.2024.08.005","DOIUrl":"https://doi.org/10.1016/j.jare.2024.08.005","url":null,"abstract":"<p><strong>Background: </strong>Traditional Chinese Medicine (TCM) has gained global attention, particularly after Professor Youyou Tu was awarded the Nobel Prize for her discovery of artemisinin as a treatment for malaria. However, the theory behind TCM is often perceived as a \"black-box\" with complex components and an unclear structure and mechanism of action. This had hindered the development of TCM within the framework of modern medicine.</p><p><strong>Aim of review: </strong>The molecular compatibility theory proposed by Professor Tian Xie's team integrates TCM with Western medicine in clinical practice, and provide a feasible direction for TCM modernization. It is necessary to summarize and popularize this theory. This review aims to systematically introduce this theory to provide some new insight for development of TCM.</p><p><strong>Key scientific concepts of review: </strong>According to the molecular compatibility theory, the desired effects can be achieved by organically combining multiple active molecules from TCM. These TCM molecular compounds have specific ingredients, precise mechanisms, and controllable quality that meet the standards of modern medicine. The molecular compatibility theory has guided the development of antitumor new drug elemene emulsions, and has also revealed extensive compatibility between TCM-derived active molecules and other TCM, Western medicine, or biomaterials. This discovery opens up potential TCM-based treatment options. In conclusion, the molecular compatibility theory holds promise as a strategy for modernizing TCM.</p>","PeriodicalId":94063,"journal":{"name":"Journal of advanced research","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141903964","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacological inhibition of Septins with Forchlorfenuron attenuates thrombus formation in experimental thrombotic mice models with modulating multiple signaling pathways in platelets.","authors":"Zhen Hao, Minghui Yan, Reyisha Tuerhong, Luying Zhang, Zhen Zhang, Habib Alam, Jun Wu, Yuanhua Qin, Feng Zhao, Lei Shi","doi":"10.1016/j.jare.2024.08.006","DOIUrl":"https://doi.org/10.1016/j.jare.2024.08.006","url":null,"abstract":"<p><strong>Introduction: </strong>The Septin family of cytoskeletal proteins is abundant in platelets. When these proteins are functionally blocked using the compound forchlorfenuron (FCF), it hampers the normal activation processes of purified human platelets.</p><p><strong>Objectives: </strong>To evaluate the in vivo effects of FCF on physiological haemostasis and pathological thrombosis in mice and to investigate possible molecular mechanisms.</p><p><strong>Methods: </strong>The impact of FCF on haemorrhage risk in the brain, liver, and tail of mice was investigated. Using several experimental models, thrombus development in the lung, mesenteric arteries, and postcava was studied. Functional assays were performed on mice and human platelets, both with and without FCF pretreatment. These tests included aggregation, granule release, ROS production, integrin αIIbβ3 activation, cytoskeletal remodeling imaging, and clot retraction.</p><p><strong>Results: </strong>Neither oral nor intravenous administration of FCF showed any apparent impairment of haemostasis in the tissues studied, but only later administration resulted in a significant reduction in thrombus formation in different mice vessel types. FCF generally inhibited agonist-induced platelet aggregation, degranulation, ROS burst, morphological expansion on the fibrinogen matrix with completely disordered dynamic organizations of the cytoskeleton for septin, tubulin and actin. In addition, FCF was found to antagonise agonist-induced dephosphorylation of VASP (Ser239) and PI3K/AKT and ERK1/2 phosphorylation.</p><p><strong>Conclusion: </strong>FCF showed preferences in attenuating pathological thrombus formation, apart from physiological haemostasis, with possible mechanisms to prevent cytoskeletal remodelling and signal transduction of AKT, ERK1/2 and VASP signalling pathways, suggesting that Septin may serve as a promising target for the prevention and treatment of thrombotic diseases.</p>","PeriodicalId":94063,"journal":{"name":"Journal of advanced research","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141903967","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deciphering the dynamic expression network of fiber elongation and the functional role of the GhTUB5 gene for fiber length in cotton based on an introgression population of upland cotton.","authors":"Jianjiang Ma, Liupeng Yang, Yuanyue Dang, Kashif Shahzad, Jikun Song, Bing Jia, Li Wang, Juanjuan Feng, Nuohan Wang, Wenfeng Pei, Man Wu, Xuexian Zhang, Jinfa Zhang, Jianyong Wu, Jiwen Yu","doi":"10.1016/j.jare.2024.08.004","DOIUrl":"10.1016/j.jare.2024.08.004","url":null,"abstract":"<p><strong>Introduction: </strong>Interspecific introgression between Gossypium hirsutum and G. barbadense allows breeding cotton with outstanding fiber length (FL). However, the dynamic gene regulatory network of FL-related genes has not been characterized, and the functional mechanism through which the hub gene GhTUB5 mediates fiber elongation has yet to be determined.</p><p><strong>Methods: </strong>Coexpression analyses of 277 developing fiber transcriptomes integrated with QTL mapping using 250 introgression lines of different FL phenotypes were conducted to identify genes related to fiber elongation. The function of GhTUB5 was determined by ectopic expression of two TUB5 alleles in Arabidopsis and knockout of GhTUB5 in upland cotton. Yeast two-hybrid, split-luciferase and pull-down assays were conducted to screen for interacting proteins, and upstream genes were identified by yeast one-hybrid, dual-LUC and electrophoretic mobility shift assays.</p><p><strong>Results: </strong>The 32,612, 30,837 and 30,277 genes expressed at 5, 10 and 15 days postanthesis (dpa) were grouped into 19 distinct coexpression modules, and 988 genes in the MEblack module were enriched in the cell wall process and exhibited significant associations with FL. A total of 20 FL-QTLs were identified, each explaining 3.34-16.04 % of the phenotypic variance in the FL. Furthermore, several FL-QTLs contained 15 genes that were differentially expressed in the MEblack module including the tubulin beta gene (TUB5). Compared with the wild type, the overexpression of GhTUB5 and GbTUB5 in Arabidopsis suppressed root cell length but promoted cellulose synthesis. Knockout of GhTUB5 resulted in longer fiber lines. Protein-based experiments revealed that GhTUB5 interacts with GhZFP6. Additionally, GhTUB5 was directly activated by GhHD-ZIP7, a homeobox-leucine zipper transcription factor, and its paralogous gene was previously reported to mediate fiber elongation.</p><p><strong>Conclusion: </strong>This study opens a new avenue to dissect functional mechanism of cotton fiber elongation. Our findings provide some molecular details on how GhTUB5 mediates the FL phenotype in cotton.</p>","PeriodicalId":94063,"journal":{"name":"Journal of advanced research","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141899247","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GDF11 protects against mitochondrial-dysfunction-dependent NLRP3 inflammasome activation to attenuate osteoarthritis.","authors":"Pengfei Zhang, Haoxin Zhai, Shuai Zhang, Xiaojie Ma, Ao Gong, Zhaoning Xu, Wei Zhao, Hui Song, Shufeng Li, Tengfei Zheng, Zhendong Ying, Lei Cheng, Yunpeng Zhao, Lei Zhang","doi":"10.1016/j.jare.2024.08.001","DOIUrl":"10.1016/j.jare.2024.08.001","url":null,"abstract":"<p><strong>Introduction: </strong>Osteoarthritis (OA) is a highly prevalent degenerative disease worldwide, and tumor necrosis factor (TNF-α) is closely associated with its development. Growth differentiation factor 11 (GDF11) has demonstrated anti-injury and anti-aging abilities in certain tissues; however, its regulatory role in OA remains unclear and requires further investigation.</p><p><strong>Objectives: </strong>To identify whether GDF11 can attenuate osteoarthritis. To exploring the the potential mechanism of GDF11 in alleviating osteoarthritis.</p><p><strong>Methods: </strong>In this study, we cultured and stimulated mouse primary chondrocytes with or without TNF-α, analyzing the resulting damage phenotype through microarray analysis. Additionally, we employed GDF11 conditional knockout mice OA model to examine the relationship between GDF11 and OA. To investigate the target of GDF11's function, we utilized NLRP3 knockout mice and its inhibitor to verify the potential involvement of the NLRP3 inflammasome.</p><p><strong>Results: </strong>Our in vitro experiments demonstrated that endogenous overexpression of GDF11 significantly inhibited TNF-α-induced cartilage matrix degradation and inflammatory expression in chondrocytes. Furthermore, loss of GDF11 led to NLRP3 inflammasome activation, inflammation, and metabolic dysfunction. In an in vivo surgically induced mouse model, intraarticular administration of recombinant human GDF11 alleviated OA pathogenesis, whereas GDF11 conditional knockout reversed this effect. Additionally, findings from the NLRP3-knockout DMM mouse model revealed that GDF11 exerted its protective effect by inhibiting NLRP3.</p><p><strong>Conclusion: </strong>These findings demonstrate the ability of GDF11 to suppress TNF-α-induced inflammation and cartilage degeneration by preventing mitochondrial dysfunction and inhibiting NLRP3 inflammasome activation, suggesting its potential as a promising therapeutic drug for osteoarthritis.</p>","PeriodicalId":94063,"journal":{"name":"Journal of advanced research","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141895076","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}