Research最新文献

Ly6G⁺ Neutrophils and Interleukin-17 Are Essential in Protection against Rodent Malaria Caused by Plasmodium berghei ANKA.

IF 11 1区综合性期刊

Research Pub Date : 2024-12-19 eCollection Date: 2024-01-01 DOI: 10.34133/research.0559

Ziwei Su, Qilong Li, Yiwei Zhang, Tong Liu, Kunying Lv, Anni Feng, Yixin Yang, Yanxin Zhang, Zhiming Wei, Xiaoyu Sang, Ying Feng, Ran Chen, Ning Jiang, Qijun Chen

{"title":"Ly6G+ Neutrophils and Interleukin-17 Are Essential in Protection against Rodent Malaria Caused by Plasmodium berghei ANKA.","authors":"Ziwei Su, Qilong Li, Yiwei Zhang, Tong Liu, Kunying Lv, Anni Feng, Yixin Yang, Yanxin Zhang, Zhiming Wei, Xiaoyu Sang, Ying Feng, Ran Chen, Ning Jiang, Qijun Chen","doi":"10.34133/research.0559","DOIUrl":"https://doi.org/10.34133/research.0559","url":null,"abstract":"Neutrophils are essential in combating invading pathogens such as Plasmodium parasites, but the participation of their subpopulations and mechanisms in resistance to parasite infection are not fully understood. Our study identified a marked increase in Ly6G+ neutrophils in response to P. berghei ANKA infection. Depletion of these cells rendered mice more susceptible to infection. Elevated interleukin-17 (IL-17) levels, which increased the Ly6G+ neutrophil population, were also found to contribute to this protective effect. IL-17 depletion led to reduced neutrophil numbers and increased susceptibility. Furthermore, dihydroartemisinin (DHA) treatment enhanced neutrophil-mediated immune responses through up-regulation of CD18 and CXCR4 factors. These findings revealed key mechanisms of neutrophil and IL-17 interactions in malaria protection and highlighted DHA's potential to promote neutrophil function in combating malaria.","PeriodicalId":21120,"journal":{"name":"Research","volume":"7 ","pages":"0559"},"PeriodicalIF":11.0,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11658117/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142865523","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Two-Dimensional MXenes: Innovative Materials for Efficient Thermal Management and Safety Solutions.

IF 11 1区综合性期刊

Research Pub Date : 2024-12-19 eCollection Date: 2024-01-01 DOI: 10.34133/research.0542

XiaoYan Hu, Qi Fan, Shengchao Wang, Yanxin Chen, Degao Wang, Ke Chen, Fangfang Ge, Wenhu Zhou, Kun Liang

{"title":"Two-Dimensional MXenes: Innovative Materials for Efficient Thermal Management and Safety Solutions.","authors":"XiaoYan Hu, Qi Fan, Shengchao Wang, Yanxin Chen, Degao Wang, Ke Chen, Fangfang Ge, Wenhu Zhou, Kun Liang","doi":"10.34133/research.0542","DOIUrl":"https://doi.org/10.34133/research.0542","url":null,"abstract":"MXenes, a class of 2-dimensional transition metal carbides and nitrides, have garnered important attention due to their remarkable electrical and thermal conductivity, high photothermal conversion efficiency, and multifunctionality. This review explores the potential of MXene materials in various thermal applications, including thermal energy storage, heat dissipation in electronic devices, and the mitigation of electromagnetic interference in wearable technologies. Recent advancements in MXene composites, such as MXene/bacterial cellulose aerogel films and MXene/polymer composites, have demonstrated enhanced performance in phase change thermal storage and electromagnetic interference shielding, underscoring their versatility and effectiveness. Although notable progress has been made, challenges remain, including the need for a deeper understanding of photothermal conversion mechanisms, improvements in mechanical properties, exploration of diverse MXene types, and the development of sustainable synthesis methods. This paper discusses these aspects and outlines future research directions, emphasizing the growing importance of MXenes in addressing energy efficiency, health, and safety concerns in modern applications.","PeriodicalId":21120,"journal":{"name":"Research","volume":"7 ","pages":"0542"},"PeriodicalIF":11.0,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11658421/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142865527","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Discovery of Staircase Chirality through the Design of Unnatural Amino Acid Derivatives.

IF 11 1区综合性期刊

Research Pub Date : 2024-12-19 eCollection Date: 2024-01-01 DOI: 10.34133/research.0550

Anis U Rahman, Yu Wang, Ting Xu, Kambham Devendra Reddy, Shengzhou Jin, Jasmine X Yan, Qingkai Yuan, Daniel Unruh, Ruibin Liang, Guigen Li

{"title":"Discovery of Staircase Chirality through the Design of Unnatural Amino Acid Derivatives.","authors":"Anis U Rahman, Yu Wang, Ting Xu, Kambham Devendra Reddy, Shengzhou Jin, Jasmine X Yan, Qingkai Yuan, Daniel Unruh, Ruibin Liang, Guigen Li","doi":"10.34133/research.0550","DOIUrl":"https://doi.org/10.34133/research.0550","url":null,"abstract":"Chirality has garnered significant attention in the scientific community since its discovery by Louis Pasteur over a century ago. It has been showing a profound impact on chemical, biomedical, and materials sciences. Significant progress has been made in controlling molecular chirality, as evidenced by the several Nobel Prizes in chemistry awarded in this area, particularly for advancements in the asymmetric catalytic synthesis of molecules with central and axial chirality. However, the exploration of new types of chirality has been largely stagnant for more than half a century, likely due to the complexity and challenges inherent in this field. In this work, we present the discovery of a novel type of chirality-staircase chirality as inspired by the design and synthesis of unnatural amino acid derivatives. The architecture of staircase chirality is characterized by 2 symmetrical phenyl rings anchored by a naphthyl pier, with the rings asymmetrically displaced due to the influence of chiral auxiliaries at their para positions. This unique staircase chiral framework has been thoroughly characterized using spectroscopic techniques, with its absolute configuration definitively confirmed by x-ray diffraction analysis. Remarkably, one of the staircase molecules exhibits 4 distinct types of chirality: central, orientational, turbo, and staircase chirality, a combination that has not been previously documented in the literature. Computational studies using density functional theory (DFT) calculations were conducted to analyze the relative energies of individual staircase isomers, and the results are in agreement with our experimental findings. We believe that this discovery will open up a new research frontier in asymmetric synthesis and catalysis, with the potential to make a substantial impact on the fields of chemistry, medicine, and materials science.","PeriodicalId":21120,"journal":{"name":"Research","volume":"7 ","pages":"0550"},"PeriodicalIF":11.0,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11658802/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142865521","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Sensitivity Challenge of the Next-Generation Bolometric Double-Beta Decay Experiment.

IF 11 1区综合性期刊

Research Pub Date : 2024-12-19 eCollection Date: 2024-01-01 DOI: 10.34133/research.0569

Long Ma, Huan-Zhong Huang, Yu-Gang Ma

{"title":"Sensitivity Challenge of the Next-Generation Bolometric Double-Beta Decay Experiment.","authors":"Long Ma, Huan-Zhong Huang, Yu-Gang Ma","doi":"10.34133/research.0569","DOIUrl":"https://doi.org/10.34133/research.0569","url":null,"abstract":"Cryogenic crystal bolometer plays a crucial role in searching for neutrinoless double-beta (0νββ) decay, which is a rare process that could determine the Majorana nature of neutrinos. The flagship bolometer experiment-CUORE (Cryogenic Underground Observatory for Rare Events)-operating at the Gran Sasso underground laboratory [Laboratori Nazionali del Gran Sasso (LNGS)] as the world's first ton-scale bolometric detector has achieved great success and well demonstrated advantages of the bolometric technology for the 0νββ study. The proposed upgrade of CUORE-the CUPID project-aims to achieve higher sensitivity with orders of magnitude background reduction by utilizing scintillating crystals and dual readout technology to exclude most of the background events dominated by alpha particles. Although CUPID has outstanding advantages over CUORE, further increasing the detection capability to fully explore the effective neutrino mass region for the inverted neutrino mass hierarchy and possibly to discover Majorana neutrinos remains a technical challenge ahead. In this prospective, we discuss strategies toward future technology development to further enhance the experimental sensitivity.","PeriodicalId":21120,"journal":{"name":"Research","volume":"7 ","pages":"0569"},"PeriodicalIF":11.0,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11658775/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142865525","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Pyruvate Abundance Confounds Aminoglycoside Killing of Multidrug-Resistant Bacteria via Glutathione Metabolism.

IF 11 1区综合性期刊

Research Pub Date : 2024-12-18 eCollection Date: 2024-01-01 DOI: 10.34133/research.0554

Jiao Xiang, Si-Qi Tian, Shi-Wen Wang, Ying-Li Liu, Hui Li, Bo Peng

{"title":"Pyruvate Abundance Confounds Aminoglycoside Killing of Multidrug-Resistant Bacteria via Glutathione Metabolism.","authors":"Jiao Xiang, Si-Qi Tian, Shi-Wen Wang, Ying-Li Liu, Hui Li, Bo Peng","doi":"10.34133/research.0554","DOIUrl":"https://doi.org/10.34133/research.0554","url":null,"abstract":"To explore whether the metabolic state reprogramming approach may be used to explore previously unknown metabolic pathways that contribute to antibiotic resistance, especially those that have been neglected in previous studies, pyruvate reprogramming was performed to reverse the resistance of multidrug-resistant Edwardsiella tarda. Surprisingly, we identified a pyruvate-regulated glutathione system that occurs by boosting glycine, serine, and threonine metabolism. Moreover, cysteine and methionine metabolism played a key role in this reversal. This process involved pyruvate-depressed glutathione and pyruvate-promoted glutathione oxidation, which was attributed to the elevated glutathione peroxidase and depressed glutathione reductase that was inhibited by glycine. This regulation inhibited reactive oxygen species (ROS) degradation and thereby elevated ROS to eliminate E. tarda. Loss of metB, gpx, and gor of the metabolic pathways increased and decreased resistance, respectively, both in vitro and in vivo, thereby supporting the hypothesis of a pyruvate-cysteine-glutathione system/glycine-ROS metabolic pathway. The role of this metabolic pathway in drug resistance and reprogramming reversal was demonstrated in laboratory-evolved gentamicin-resistant E. tarda and other clinically isolated multidrug- and carbapenem-resistant pathogens. Thus, we reveal a less studied antibiotic resistance metabolic pathway along with the mechanisms involved in its reversal.","PeriodicalId":21120,"journal":{"name":"Research","volume":"7 ","pages":"0554"},"PeriodicalIF":11.0,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11654824/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142855282","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Palladium-Based Nanocomposites Remodel Osteoporotic Microenvironment by Bone-Targeted Hydrogen Enrichment and Zincum Repletion.

IF 11 1区综合性期刊

Research Pub Date : 2024-12-17 eCollection Date: 2024-01-01 DOI: 10.34133/research.0540

Lubing Liu, Huiying Liu, Xiaoya Lu, Zhengshuai Yin, Wei Zhang, Jing Ye, Yingying Xu, Zhenzhen Weng, Jun Luo, Xiaolei Wang

{"title":"Palladium-Based Nanocomposites Remodel Osteoporotic Microenvironment by Bone-Targeted Hydrogen Enrichment and Zincum Repletion.","authors":"Lubing Liu, Huiying Liu, Xiaoya Lu, Zhengshuai Yin, Wei Zhang, Jing Ye, Yingying Xu, Zhenzhen Weng, Jun Luo, Xiaolei Wang","doi":"10.34133/research.0540","DOIUrl":"https://doi.org/10.34133/research.0540","url":null,"abstract":"Osteoporosis presents a marked global public health challenge, characterized by deficient osteogenesis and a deteriorating immune microenvironment. Conventional clinical interventions primarily target osteoclast-mediated bone damage, yet lack a comprehensive therapeutic approach that balances bone formation and resorption. Herein, we introduce a bone-targeted nanocomposite, A-Z@Pd(H), designed to address these challenges by integrating diverse functional components. The nanocomposite incorporates internal hydrogen-carrying nanozymes, which effectively scavenge multiple reactive oxygen species (ROS) and synergistically engage the autophagy-lysosome pathway to accelerate endogenous ROS degradation in macrophages. This mechanism disrupts the vicious cycle of autophagic dysfunction-ROS accumulation-macrophage inflammation. In addition, external metal-organic frameworks release zinc ions (Zn2+) in response to the acidic osteoporotic environment, thereby promoting osteogenesis. In a murine model of osteoporosis, intravenous administration of A-Z@Pd(H) leads to preferential accumulation in the femur, thereby remodeling the osteoporotic microenvironment through immune regulation, osteogenesis promotion, and osteoclast inhibition. These findings suggest that this system composed of hydrogen therapy and ion therapy may be a promising candidate for bone-targeted comprehensive therapy in osteoporosis.","PeriodicalId":21120,"journal":{"name":"Research","volume":"7 ","pages":"0540"},"PeriodicalIF":11.0,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11651528/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142847689","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Polydatin-Mediated Inhibition of HSP90α Disrupts NLRP3 Complexes and Alleviates Acute Pancreatitis.

IF 11 1区综合性期刊

Research Pub Date : 2024-12-17 eCollection Date: 2024-01-01 DOI: 10.34133/research.0551

Jiashu Yang, Chenyang Jiao, Nannan Liu, Wen Liu, Yueyao Wang, Ying Pan, Lingdong Kong, Wenjie Guo, Qiang Xu

{"title":"Polydatin-Mediated Inhibition of HSP90α Disrupts NLRP3 Complexes and Alleviates Acute Pancreatitis.","authors":"Jiashu Yang, Chenyang Jiao, Nannan Liu, Wen Liu, Yueyao Wang, Ying Pan, Lingdong Kong, Wenjie Guo, Qiang Xu","doi":"10.34133/research.0551","DOIUrl":"https://doi.org/10.34133/research.0551","url":null,"abstract":"The NLRP3 inflammasome plays a critical role in various inflammatory conditions. However, despite extensive research in targeted drug development for NLRP3, including MCC950, clinical success remains elusive. Here, we discovered that the activated NLRP3 inflammasome complex (disc-NLRP3) and the activating mutation L351P exhibited resistance to MCC950. Through investigations using the small-molecule compound polydatin, HSP90α was found to stabilize both the resting (cage-NLRP3) and activated state (disc-NLRP3) of NLRP3 complexes, sustaining its activation. Our mechanistic studies revealed that polydatin specifically targets HSP90α, binding to it directly and subsequently interfering with the HSP90α-NLRP3 interaction. This disruption leads to the dissipation of cage-NLRP3, disc-NLRP3 complexes and NLRP3 L351P. Importantly, genetic and pharmacological inactivation of HSP90α effectively reduced NLRP3 inflammasome activation and alleviated cerulein-induced acute pancreatitis. These therapeutic effects highlight the clinical potential of HSP90α inhibition. Our findings demonstrate that HSP90α is crucial for the stability of both the resting and activated states of the NLRP3 inflammasome during its sustained activation, and targeting HSP90α represents a promising therapeutic strategy for diseases driven by the NLRP3 inflammasome.","PeriodicalId":21120,"journal":{"name":"Research","volume":"7 ","pages":"0551"},"PeriodicalIF":11.0,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11651664/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142847690","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Ononin Inhibits Tumor Bone Metastasis and Osteoclastogenesis By Targeting Mitogen-Activated Protein Kinase Pathway in Breast Cancer.

IF 11 1区综合性期刊

Research Pub Date : 2024-12-16 eCollection Date: 2024-01-01 DOI: 10.34133/research.0553

Kumar Ganesan, Cong Xu, Song Wu, Yue Sui, Bing Du, Jinhui Zhang, Fei Gao, Jianping Chen, Hailin Tang

{"title":"Ononin Inhibits Tumor Bone Metastasis and Osteoclastogenesis By Targeting Mitogen-Activated Protein Kinase Pathway in Breast Cancer.","authors":"Kumar Ganesan, Cong Xu, Song Wu, Yue Sui, Bing Du, Jinhui Zhang, Fei Gao, Jianping Chen, Hailin Tang","doi":"10.34133/research.0553","DOIUrl":"https://doi.org/10.34133/research.0553","url":null,"abstract":"Breast cancer (BC) often spreads to bones, leading to bone metastasis (BM). Current targeted therapies have limited effectiveness in the treatment of this condition. Osteoclasts, which contribute to bone destruction, are crucial in supporting tumor cell growth in the bones. Breast cancer bone metastasis (BCBM) treatments have limited efficacy and can cause adverse effects. Ononin exhibits anticancer properties against various cancers. The study examined the impact of ononin on the BCBM and the signaling pathways involved. Our study utilized a variety of experimental techniques, including cell viability assays, colony formation assays, wound-healing assays, Transwell migration assays, Western blot analysis, and tartrate-resistant acid phosphatase (TRAP) staining. We examined the effects of ononin on osteoclastogenesis induced in MDA-MB-231 conditioned medium- and RANKL-treated RAW 264.7 cells. In a mouse model of BCBM, ononin reduced tumor-induced bone destruction. Ononin treatment effectively inhibited proliferation and colony formation and reduced the metastatic capabilities of MDA-MB-231 cells by suppressing cell adhesion, invasiveness, and motility and reversing epithelial-mesenchymal transition (EMT) markers. Ononin markedly suppressed osteoclast formation and osteolysis-associated factors in MDA-MB-231 cells, as well as blocked the activation of the mitogen-activated protein kinase (MAPK) pathway in RAW 264.7 cells. Ononin treatment down-regulated the phosphorylation of MAPK signaling pathways, as confirmed using MAPK agonists or inhibitors. Ononin treatment had no adverse effects on the organ function. Our findings suggest that ononin has therapeutic potential as a BCBM treatment by targeting the MAPK pathway.","PeriodicalId":21120,"journal":{"name":"Research","volume":"7 ","pages":"0553"},"PeriodicalIF":11.0,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11648741/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142839140","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Tryptophan Ameliorates Metabolic Syndrome by Inhibiting Intestinal Farnesoid X Receptor Signaling: The Role of Gut Microbiota-Bile Acid Crosstalk.

IF 11 1区综合性期刊

Research Pub Date : 2024-12-13 eCollection Date: 2024-01-01 DOI: 10.34133/research.0515

Jiayi Chen, Hao Yang, Yingjie Qin, Xinbo Zhou, Qingquan Ma

{"title":"Tryptophan Ameliorates Metabolic Syndrome by Inhibiting Intestinal Farnesoid X Receptor Signaling: The Role of Gut Microbiota-Bile Acid Crosstalk.","authors":"Jiayi Chen, Hao Yang, Yingjie Qin, Xinbo Zhou, Qingquan Ma","doi":"10.34133/research.0515","DOIUrl":"10.34133/research.0515","url":null,"abstract":"Background and Aims: Metabolic syndrome (MS) is a progressive metabolic disease characterized by obesity and multiple metabolic disorders. Tryptophan (Trp) is an essential amino acid, and its metabolism is linked to numerous physiological functions and diseases. However, the mechanisms by which Trp affects MS are not fully understood. Methods and Results: In this study, experiments involving a high-fat diet (HFD) and fecal microbiota transplantation (FMT) were conducted to investigate the role of Trp in regulating metabolic disorders. In a mouse model, Trp supplementation inhibited intestinal farnesoid X receptor (FXR) signaling and promoted hepatic bile acid (BA) synthesis and excretion, accompanied by elevated levels of conjugated BAs and the ratio of non-12-OH to 12-OH BAs in hepatic and fecal BA profiles. As Trp alters the gut microbiota and the abundance of bile salt hydrolase (BSH)-enriched microbes, we collected fresh feces from Trp-supplemented mice and performed FMT and sterile fecal filtrate (SFF) inoculations in HFD-treated mice. FMT and SFF not only displayed lipid-lowering properties but also inhibited intestinal FXR signaling and increased hepatic BA synthesis. This suggests that the gut microbiota play a beneficial role in improving BA metabolism through Trp. Furthermore, fexaramine (a gut-specific FXR agonist) reversed the therapeutic effects of Trp, suggesting that Trp acts through the FXR signaling pathway. Finally, validation in a finishing pig model revealed that Trp improved lipid metabolism, enlarged the hepatic BA pool, and altered numerous glycerophospholipid molecules in the hepatic lipid profile. Conclusion: Our studies suggest that Trp inhibits intestinal FXR signaling mediated by the gut microbiota-BA crosstalk, which in turn promotes hepatic BA synthesis, thereby ameliorating MS.","PeriodicalId":21120,"journal":{"name":"Research","volume":"7 ","pages":"0515"},"PeriodicalIF":11.0,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11638488/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142829675","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A New Insight into the Mechanism of Atrazine-Induced Neurotoxicity: Triggering Neural Stem Cell Senescence by Activating the Integrated Stress Response Pathway. 阿特拉津诱导神经毒性机制的新见解：通过激活综合应激反应途径引发神经干细胞衰老。

IF 11 1区综合性期刊

Research Pub Date : 2024-12-13 eCollection Date: 2024-01-01 DOI: 10.34133/research.0547

Jian Chen, Xue-Yan Dai, Kanwar K Malhi, Xiang-Wen Xu, Yi-Xi Tang, Xiao-Wei Li, Jin-Long Li

{"title":"A New Insight into the Mechanism of Atrazine-Induced Neurotoxicity: Triggering Neural Stem Cell Senescence by Activating the Integrated Stress Response Pathway.","authors":"Jian Chen, Xue-Yan Dai, Kanwar K Malhi, Xiang-Wen Xu, Yi-Xi Tang, Xiao-Wei Li, Jin-Long Li","doi":"10.34133/research.0547","DOIUrl":"10.34133/research.0547","url":null,"abstract":"Atrazine (AT), a widely utilized chemical herbicide, causes widespread contamination of agricultural water bodies. Recently, exposure to AT has been linked to the development of age-related neurodegenerative diseases (NDs), suggesting its neurotoxicity potential. As an endocrine disruptor, AT targets the hypothalamus, a crucial part of the neuroendocrine system. However, the toxicological mechanism of AT exposure to the hypothalamus and its correlation with ND development remain unexplored. Our results indicated that AT exposure caused significant morphological and structural damage to the hypothalamus, leading to the loss of mature and intact neurons and microglial activation. Furthermore, hypothalamic neural stem cells (HtNSCs) were recruited to areas of neuronal damage caused by AT. Through in vivo and in vitro experiments, we clarified the outcomes of AT-induced HtNSC recruitment alongside the loss of mature/intact neurons. Mechanistically, AT induces senescence in these recruited HtNSCs by activating integrated stress response signaling. This consequently hinders the repair of damaged neurons by inhibiting HtNSC proliferation and differentiation. Overall, our findings underscore the pivotal role of the integrated stress response pathway in AT-induced HtNSC senescence and hypothalamic damage. Additionally, the present study offers novel perspectives to understand the mechanisms of AT-induced neurotoxicity and provides preliminary evidence linking AT contamination to the development of NDs.","PeriodicalId":21120,"journal":{"name":"Research","volume":"7 ","pages":"0547"},"PeriodicalIF":11.0,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11638487/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142829609","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0