Journal of Advanced Research最新文献

{"title":"Design of highly leaf-adhesive and anti-UV herbicide nanoformulation for enhanced herbicidal activity","authors":"Dongdong Li, Jianan Li, Hao Li, Zhendong Bai, Chujian Ma, Haodong Bai, Dingfeng Luo, Zuren Li, Lianyang Bai","doi":"10.1016/j.jare.2024.12.034","DOIUrl":"https://doi.org/10.1016/j.jare.2024.12.034","url":null,"abstract":"<h3>Introduction</h3>Conventional pesticide formulations have been widely used to boost agricultural productivity, but their weak foliar adhesion and instability under UV light during spraying lead to low utilization rates and potential environmental and health hazards. To counter these challenges, the development of nanoformulations represents a pivotal strategy. These advanced formulations are designed to enhance the efficacy of active ingredients (AIs) and reduce ecological impacts, thereby addressing the need for sustainable agricultural development.<h3>Objectives</h3>The study aims to fabricate a highly leaf-adhesive and anti-UV herbicide nanoformulation, designed to enhance the herbicidal activity and utilization rates of AIs.<h3>Methods</h3>Herein, the herbicide nanoformulations (Called CB@MSNs-TA-Fe) are synthesized by incorporating cyhalofop-butyl into tannic acid-Fe (III) ions-coated functionalized mesoporous silica. The foliar retention performance of the samples was assessed integrating SEM observation and HPLC analysis.<h3>Results</h3>The CB@MSNs-TA-Fe with rough outer surface displays typical core–shell structure featuring an average diameter of about 118 nm. After amino modification, the CB@MSNs-TA-Fe shows enhanced loading rate for CB (14.4 ± 0.2 %) and superior thermal stability. The release rate of CB within CB@MSNs-TA-Fe under acidic conditions is higher compared to that under alkaline and neutral conditions. Upon UV irradiation, the half-life of CB within CB@MSNs-TA-Fe nanoparticles is 12.4 times higher than that of CB technical (CB TC). Enhanced foliar adhesion of CB@MSNs-TA-Fe on hydrophobic leaf surfaces is observed, which can effectively mitigate the risk of wash-off by rainfall. The CB@MSNs-TA-Fe displays enhanced herbicidal efficacies against barnyard grass under UV irradiation or simulated rainwater scouring, compared with CB TC and CB oil dispersion. Furthermore, the TA-Fe-coated MSNs-NH₂ nano-carrier (MSNs-TA-Fe) reveals excellent biosafety on rice, zebrafish, and earthworms.<h3>Conclusion</h3>The developed TA-Fe-functionalized herbicide nanoformulations, with high foliar adhesion and anti-UV properties, effectively improve the utilization efficiency of AIs, thus offering innovative solutions for the development of efficient pesticide formulations.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"11 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2024-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142874688","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":"Absence of gut microbiota alleviates iron overload-induced colitis by modulating ferroptosis in mice","authors":"Ke Gu, Aimin Wu, Chen Liu, Bing Yu, Jun He, Xin Lai, Junzhou Chen, Yuheng Luo, Hui Yan, Ping Zheng, Junqiu Luo, Junning Pu, Quyuan Wang, Huifen Wang, Daiwen Chen","doi":"10.1016/j.jare.2024.12.030","DOIUrl":"https://doi.org/10.1016/j.jare.2024.12.030","url":null,"abstract":"<h3>Introduction</h3>Iron overload disrupts gut microbiota and induces ferroptosis, contributing to colitis. However, whether gut microbiota directly drives iron overload-induced colitis and its underlying mechanism remain unclear.<h3>Objectives</h3>The study aimed to explore whether gut microbiota can directly regulate iron overload-induced colitis and its underling mechanism.<h3>Methods</h3>Male C57BL/6N mice were fed with ferrous sulfate to establish an iron overload model. Antibiotics and DSS were used to create germ-free and colitis models, respectively.<h3>Results</h3>Results showed that iron overload caused disruption of systemic iron homeostasis via activating pro-inflammation response, which caused induction of ferroptosis and eventually resulted in colitis in mice. Notably, iron overload inhibited System Xc- and activated the nuclear factor E2-related factor 2/heme oxygenase-1 pathway, driving ferroptosis and colitis progression. Similar results were observed in mouse colon epithelial cells, which were treated with high doses ferric ammonium citrate. Additionally, iron overload exacerbated DSS-induced colitis by activating the ferroptosis and increasing harmful bacteria (e.g., <em>Mucispirillum</em>) abundance. Interestingly, eliminating gut microbiota attenuated iron overload-induced colitis, without affecting systemic inflammation through inhibiting ferroptosis of mice. Depletion of the gut microbiota partially mitigated the exacerbating effect of iron overload on DSS-induced colitis through inhibiting ferroptosis of mice.<h3>Conclusion</h3>Iron overload activates ferroptosis in colonic cells, increases the relative abundance of harmful bacteria, and exacerbates DSS-induced colitis in mice. Iron overload exacerbates DSS-induced ferroptosis and colitis in a microbiota-dependent manner. Targeting gut microbiota may offer new strategies for managing iron overload-induced colitis.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"27 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142867557","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":"The role of cGAS-STING signaling pathway in ferroptosis","authors":"Lina Ding, Ruicheng Zhang, Wenqi Du, Qingling Wang, Dongsheng Pei","doi":"10.1016/j.jare.2024.12.028","DOIUrl":"https://doi.org/10.1016/j.jare.2024.12.028","url":null,"abstract":"The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling pathway has been identified as a crucial mechanism in antiviral defense and innate immunity pathway. Ferroptosis, characterized by iron dependence and lipid peroxidation, represents a specialized form of cell death. A burgeoning collection of studies has demonstrated that the cGAS-STING signaling pathway participates in the homeostatic regulation of the organism by modulating ferroptosis-associated enzyme activity or gene expression. Consequently, elucidating the specific roles of the STING signaling pathway and ferroptosis in vivo is vital for targeted disease intervention. This review systematically examines the interactions between the cGAS-STING signaling pathway and ferroptosis, highlighting their influence on disease progression in the contexts of inflammation, injury, and cancerous cell dynamics. Understanding these interactions may provide novel therapeutic strategies. The STING pathway has been implicated in the regulation of various cell death mechanisms, including apoptosis, pyroptosis, necroptosis, autophagy, and ferroptosis. Our focus primarily addresses the role and mechanism of the cGAS-STING signaling pathway and ferroptosis in diseases, limiting discussion of other cell death modalities and precluding a comprehensive overview of the pathway’s additional functions.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"55 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142867558","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":"Targeting ATM enhances radiation sensitivity of colorectal cancer by Potentiating radiation-induced cell death and antitumor immunity","authors":"Yuwen Xie, Yang Liu, Mingdao Lin, Zhenkang Li, Zhiyong Shen, Shengqi Yin, Yilin Zheng, Yishu Zou, Yaowei Zhang, Yizhi Zhan, Yuan Fang, Yi Ding","doi":"10.1016/j.jare.2024.12.023","DOIUrl":"https://doi.org/10.1016/j.jare.2024.12.023","url":null,"abstract":"<h3>Introduction</h3>The efficacy of radiotherapy in colorectal cancer (CRC) is often limited by radiation resistance. Ataxia telangiectasia mutated (ATM) is well known for its role in repairing double-strand DNA breaks within the DNA damage response (DDR) pathway. However, whether ATM mediates other mechanisms contributing to radiation resistance remains insufficiently investigated.<h3>Objectives</h3>This study investigates how targeting ATM enhances CRC radiation sensitivity and evaluates combination strategies to improve radiotherapy outcomes.<h3>Methods</h3>Clinical specimens were analyzed to correlate ATM activation with radiotherapy response. Functional assays, including EdU, cell viability, clonogenic survival, and apoptosis assays, were used to assess the impact of ATM inhibition on radiation sensitivity. Mechanistic insights were gained through RNA-seq, RT-qPCR, western blotting, ELISA, immunofluorescence, flow cytometry, ChIP-qPCR, and co-immunoprecipitation. In vivo efficacy was evaluated using subcutaneous tumor models in nude, BALB/c, and C57BL/6J mice.<h3>Results</h3>High ATM phosphorylation levels correlated with poor radiotherapy response in CRC patients. ATM inhibition enhanced radiation sensitivity in both in vitro and in vivo models. Mechanistically, ATM inhibition increased radiation-induced ROS accumulation and mitochondrial damage, leading to the release of mitochondrial DNA (mtDNA) into the cytosol and activation of the STING-type I interferon pathway. This enhanced CD8+ T cell infiltration and boosted antitumor immunity. Additionally, ATM inhibition partially alleviated the radiation-induced upregulation of PD-L1, likely through the ATM/NEMO/NF-κB pathway. Notably, triple therapy combining radiotherapy, an ATM inhibitor, and anti-PD-L1 achieved superior tumor control and remission in mouse models, including large, treatment-resistant tumors.<h3>Conclusion</h3>Targeting ATM enhances radiation-induced tumor cell death and boosts antitumor immune responses, offering a promising strategy to overcome CRC radiation resistance. The synergy of radiotherapy, ATM inhibitior, and immune checkpoint blockade highlights a novel therapeutic approach for CRC management.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"96 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142849804","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":"The role of trehalose metabolism in plant stress tolerance","authors":"Tong-Ju Eh, Yaxuan Jiang, Mingquan Jiang, Jianxin Li, Pei Lei, Ximei Ji, Hyon-Il Kim, Xiyang Zhao, Fanjuan Meng","doi":"10.1016/j.jare.2024.12.025","DOIUrl":"https://doi.org/10.1016/j.jare.2024.12.025","url":null,"abstract":"<h3>Background</h3>Trehalose is a nonreducing disaccharide containing two glucose molecules linked through an α,α-1,1-glycosidic bond. This unique chemical structure causes trehalose levels to fluctuate significantly in plants under stress, where it functions as an osmoprotectant, enhancing plant resistance to stress. Previous studies have confirmed that the trehalose synthesis pathway is widely conserved across most plants. However, the protective role of trehalose is limited only to organelles or tissues where the concentration is sufficiently high.<h3>Aim of review</h3>In this review, we summarize previous reports on improving plant stress tolerance (drought, cold, heat, salt, pathogen, etc.) by applying trehalose-6-phosphate (T6P) or trehalose and manipulating the expression of trehalose metabolism-related genes. The molecular mechanisms underlying T6P, trehalose, and their related genes that regulate plant stress resistance are reviewed. More progressive studies on the spatiotemporal control of trehalose metabolism will provide a novel tool that allows for the simultaneous enhancement of crop yield and stress tolerance.<h3>Key scientific concepts of review</h3>We introduce the history of trehalose and discuss the possibility of trehalose and its metabolity-related genes binding to T6P to participate in stress response through unknown signaling pathways. In addition, the effects of trehalose metabolism regulation on plant growth and stress resistance were reviewed, and the molecular mechanism was fully discussed. In particular, we came up with new insights that the molecular mechanism of trehalose metabolism to enhance plant stress resistance in the future and we propose the need to use biotechnology methods to cultivate crops with stress resistance and high yield potential.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"40 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142857865","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":"Maternal fish oil supplementation enhances placental nutrient transport and mammary gland secretion via the GPR120 signaling pathway","authors":"Qihui Li, Qianzi Zhang, Senlin Su, Siwang Yang, Jiayuan Shao, Wutai Guan, Shihai Zhang","doi":"10.1016/j.jare.2024.12.029","DOIUrl":"https://doi.org/10.1016/j.jare.2024.12.029","url":null,"abstract":"<h3>Introduction</h3>Maternal fish oil (FO) supplementation during pregnancy has been shown to improve pregnancy outcomes. FO is recognized as dietary source for n-3 polyunsaturated fatty acids (n-3 PUFAs). While early research has focused on the benefits of n-3 polyunsaturated fatty acids n-3 PUFAs for fetal neurodevelopment, retinal maturation and neonatal behavior, their roles in the placenta during late pregnancy and in the mammary gland during lactation still remain unknow.<h3>Objectives</h3>Here, we aim to clarify the mechanisms by which maternal supplementation with FO during pregnancy and lactation affects placental and mammary gland function.<h3>Methods</h3>We evaluated the effects of FO on maternal placental nutrient transport, mammary gland milk synthesis and offspring growth. We then explored the molecular mechanisms by which docosahexaenoic acid (DHA) affects the function of placental trophoblast cells and nutrient secretion of mammary epithelial cells through <em>in vitro</em> experiments. Finally, a lipopolysaccharide-challenged experiment was performed to access the potential of maternal FO supplementation in alleviating offspring intestinal inflammation.<h3>Results</h3>Maternal supplementation with FO during late pregnancy increased offspring birth weight, associated with enhanced maternal placental vascularization and nutrient transporter abundance. Additionally, maternal FO supplementation during lactation improved mammary gland secretion, increasing the fat, protein, and non-fat solids content in both colostrum and mature milk, thereby promoting offspring growth. The stimulatory effects of DHA on placental trophoblast cell function and nutrient secretion in mammary gland epithelial cells were mediated by GPR120 signaling pathways. Furthermore, maternal FO supplementation strengthened the placental barrier, reduced placental inflammation, oxidative stress and alleviated lipopolysaccharide-induced intestinal inflammation in offspring.<h3>Conclusion</h3>Maternal FO supplementation during late pregnancy and lactation enhances offspring growth by increasing placental nutrient transport and mammary gland secretion function, mediated by GPR120. Additionally, maternal FO supplementation reduces the susceptibility of offspring to intestinal inflammation.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"62 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142849349","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 mediating roles of depression and cognitive function in the association between sarcopenia and frailty: A Cox survival analysis approach","authors":"Yan Zhu, Haojie Yin, Xianli Zhong, Qin Zhang, Li Wang, Rong Lu, Ping Jia","doi":"10.1016/j.jare.2024.12.021","DOIUrl":"https://doi.org/10.1016/j.jare.2024.12.021","url":null,"abstract":"<h3>Background</h3>Despite earlier research indicating a potential link between the development of sarcopenia and an elevated risk of frailty, the lack of comprehensive prospective data on the correlation between sarcopenia and frailty incidence leaves open the question of whether depression and cognitive function mediate this association.<h3>Objective</h3>The principal aim of the current investigation was to evaluate the intricate interplay among sarcopenia, depression, and cognitive function collectively influence the risk of developing frailty.<h3>Methods</h3>The participants included in this study were obtained from three waves of the China Health and Retirement Longitudinal Study (CHARLS), which collectively encompassed a total of 3,108 participants. To examine the interrelationships among sarcopenia, depression, cognitive function, and the incidence of frailty, we employed Cox regression models along with structural equation modelling, while making necessary adjustments for baseline demographic characteristics and various lifestyle factors.<h3>Results</h3>During a 4-year follow-up, we documented 753 frailty events. Compared to those with nonsarcopenia, those with possible sarcopenia and sarcopenia presented risk ratios for frailty events of 1.354 (95 % CI: 1.156, 1.586) and 1.514 (95 % CI: 1.203, 1.907), respectively. Stratified analyses by different statuses of sarcopenia further revealed that the significant effect of depression on frailty was present across all groups (nonsarcopenia, possible sarcopenia and sarcopenia), whereas the effect of cognitive function on frailty was limited to the non-sarcopenia and possible sarcopenia groups. Mediation analysis showed that sarcopenia was correlated not only with frailty through depression and cognitive function separately but also through a chain-mediated effect of depression and cognitive function together.<h3>Conclusions</h3>Sarcopenia is associated with frailty, depression and cognitive function playing partial, mediating roles. Frailty’s susceptibility to depression and cognitive function differs based on sarcopenia status. Therefore, comprehensive interventions that include sarcopenia screening, interventions, improvements in depression, the promotion of mental health, and delays in cognitive decline will be more effective in preventing and delaying frailty. This effectiveness is particularly relevant for middle-aged and older adults who reside in China.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"10 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142833066","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":"An AP2/ERF transcription factor controls generation of the twin-seedling rice","authors":"Kaichong Teng, Neng Zhao, Yonghong Xie, Rongbai Li, Jianxiong Li","doi":"10.1016/j.jare.2024.12.013","DOIUrl":"https://doi.org/10.1016/j.jare.2024.12.013","url":null,"abstract":"<h3>Introduction</h3>The floret of rice is a main component of the spikelet, and the ovule of pistil is a critical organ for successful reproduction and determines the number of seeds. However, the molecular mechanisms underlying the ovule development remain elusive.<h3>Objective</h3>Twin-seedling rice has great potential for application in rice production. The study was to isolate the gene that controls twin-seedling in rice and explore the molecular function of the gene in floret development.<h3>Methods</h3>We discovered a twin-seedling rice (<em>tsr</em>) mutant and constructed different segregating populations to clone <em>TSR</em> gene using map-based cloning method. To explore the molecular functions of <em>TSR</em> in determination of the ovary number and development, we applied molecular technologies such as yeast two-hybrid assay, electrophoretic mobility shift assay (EMSA), and dual-LUC transient expression assay to search for the TSR-interacting proteins and the target genes regulated by <em>TSR</em>.<h3>Results</h3>We report here the map-based cloning of <em>TSR</em> which encodes an AP2/ERF transcription factor. Mutations in <em>TSR</em> lead to occurrence of the twin-seedling rice. The <em>tsr</em> mutant showed open hulls of the spikelets and displayed changes in the number of stamens and ovules of the florets. The ovary of <em>tsr</em> mutant contained two conjugated ovules which developed into a mature seed with two viable embryos. Mechanistic studies revealed that <em>TSR</em> regulates the expression levels of genes related to spikelet determination and ovule identity by binding to their promoters. Furthermore, TSR interacted with OsMADS1 and this interaction allowed OsMADS1 to modulate the transcriptional activities of TSR on gene expression. The molecular study of <em>TSR</em> provides new insights into the formation and development of rice floret and helps breeders generate twin-seedling rice in production.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"77 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142833065","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":"FTO activates PD-L1 promotes immunosuppression in breast cancer via the m6A/YTHDF3/PDK1 axis under hypoxic conditions","authors":"Siyu Wang, Xingda Zhang, Quanrun Chen, Hao Wu, Shihan Cao, Shilu Zhao, Guozheng Li, Jianyu Wang, Yajie Gong, Xinheng Wang, Da Pang, Song Gao","doi":"10.1016/j.jare.2024.12.026","DOIUrl":"https://doi.org/10.1016/j.jare.2024.12.026","url":null,"abstract":"<h3>Introduction</h3>Altered epigenetic reprogramming enables breast cancer cells to adapt to hypoxic stress. Hypoxic microenvironment can alter immune cell infiltration and function, limiting the effectiveness of immunotherapy.<h3>Objectives</h3>The study aimed to identify how fat mass and obesity-associated protein (FTO) helps breast cancer cells cope with the hypoxic microenvironment and the mechanisms behind breast cancer cell resistance to tumor immunity.<h3>Methods</h3>Clinical samples were utilized to analyze the impact of FTO on breast cancer progression and the effect of programmed cell death protein 1/ programmed cell death 1 ligand 1(PD-1/PD-L1) immune checkpoint inhibitor treatment. Utilized MeRIP-seq and mRNA-seq to analyze the downstream genes regulated by FTO under hypoxia. Methylation modification regulation of PDK1 by FTO was clarified using RIP. Then mouse models were utilized to analyze the efficacy of inhibiting FTO and 3-Phosphoinositide-dependent protein kinase 1(PDK1) in combination with PD-1/PD-L1 immune checkpoint inhibitor treatment.<h3>Result</h3>N6-Methyladenosine(m⁶A) demethylase FTO was transcriptionally activated by hypoxia inducible factor 1α(HIF-1α). PDK1 was identified as a potential target of FTO under hypoxic conditions through high-throughput sequencing. Mechanistically, overexpression of FTO decreases m⁶A modification sites on PDK1 mRNA, preventing YTH domain family 3(YTHDF3) from recognizing and binding to these sites, thereby inhibiting the degradation of PDK1 mRNA. Overexpression of PDK1 activates the AKT/STAT3 pathway, leading to enhanced PD-L1 expression. Targeting the FTO and PDK1-AKT pathways with FB23 and BX-912 inhibit breast cancer growth, enhance cytotoxic T lymphocyte (CTL) activity, and enhance the effectiveness of the PD-1/PD-L1 checkpoint inhibitor Atezolizumab.<h3>Conclusion</h3>This study reveals that HIF-1α promotes FTO transcription under hypoxic conditions, thereby increasing PD-L1 expression through the PDK1/AKT/STAT3 axis. Inhibition of FTO and PDK1 under hypoxic conditions could serve as a promising immunotherapeutic strategy for breast cancer.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"48 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142841526","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":"Biomechanical research using advanced micro-nano devices: In-Vitro cell Characterization focus","authors":"Shiqiang Yan, Yan Lu, Changming An, Wanglai Hu, Yaofeng Chen, Ziwen Li, Wenbo Wei, Zongzheng Chen, Xianhai Zeng, Wei Xu, Zhenghua Lv, Fan Pan, Wei Gao, Yongyan Wu","doi":"10.1016/j.jare.2024.12.024","DOIUrl":"https://doi.org/10.1016/j.jare.2024.12.024","url":null,"abstract":"<h3>Background</h3>Cells in the body reside in a dynamic microenvironment subjected to various physical stimuli, where mechanical stimulation plays a crucial role in regulating cellular physiological behaviors and functions.<h3>Aim of Review</h3>Investigating the mechanisms and interactions of mechanical transmission is essential for understanding the physiological and functional interplay between cells and physical stimuli. Therefore, establishing an in vitro biomechanical stimulation cell culture system holds significant importance for research related to cellular biomechanics.<h3>Key Scientific Concepts of Review</h3>In this review, we primarily focused on various biomechanically relevant cell culture systems and highlighted the advancements and prospects in their preparation processes. Firstly, we discussed the types and characteristics of biomechanics present in the microenvironment within the human body. Subsequently, we introduced the research progress, working principles, preparation processes, potential advantages, applications, and challenges of various biomechanically relevant in vitro cell culture systems. Additionally, we summarized and categorized currently commercialized biomechanically relevant cell culture systems, offering a comprehensive reference for researchers in related fields.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"30 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142841483","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}