MOLECULAR CELL
·
2024
·
IF 14.5
Zhenxi Zhang,Yanting Yang,Yang Chen,Jingyu Su,Wenjing Du
The functional integrity of CD8 + T cells is closely linked to metabolic reprogramming; therefore, understanding the metabolic basis of CD8 + T cell activation and antitumor immunity could provide insights into tumor immunotherapy. Here, we report that ME2 is critical for mouse CD8 + T cell activation and immune response against malignancy. ME2 deficiency suppresses CD8 + T cell activation and anti-tumor immune response in vitro and in vivo . Mechanistically, ME2 depletion blocks the TCA cycle flux, leading to the accumulation of fumarate. Fumarate directly binds to DAPK1 and inhibits its activity by competing with ATP for binding. Notably, pharmacological inhibition of DAPK1 abolishes the anti-tumor function conferred by ME2 to CD8 + T cells. Collectively, these findings demonstrate a role for ME2 in the regulation of CD8 + T cell metabolism and effector functions as well as an unexpected function for fumarate as a metabolic signal in the inhibition of DAPK1.
研究领域:
免疫学
·
肿瘤学
·
代谢生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHINESE JOURNAL OF POLYMER SCIENCE
·
2019
·Vol. 37
·期 6
·598-603
·
IF 2.804
Xia De-Yong,Jiang Qi-Min,Huang Wen-Yan,Yang Hong-Jun,Xue Xiao-Qiang,Jiang Li,Jiang Bi-Biao
The anionic polymerization of methyl methacrylate (MMA) was carried out using phosphazene base t -BuP 4 and ethyl acetate (EA) as the catalyst and the initiator, respectively. Gas chromatography (GC), size exclusion chromatography (SEC) measurements, and nuclear magnetic resonance (NMR) analyses were used to reveal the polymerization mechanism and to confirm the polymer structure. The results confirmed the proposed polymerization mechanism and the polymer structure, while the initiator efficiency was low. Meanwhile, the initiation by methoxy anion coming from hydrolysis of the ester bond in MMA was also observed. As a result, there is a marked deviation between the theoretical molecular weight and the measured molecular weight, and it is essential to carry out the polymerization at excessive dosage of t -BuP 4 for preparing polymers with narrow molecular weight distribution.
研究领域:
高分子化学
·
材料科学
✓ 已验证
产品关联
DOI
高影响因子
CELL
·
2024
·
IF 45.5
Shouyan Deng,Yibo Zhang,Huanbin Wang,Wenhua Liang,Lu Xie,Ning Li,Yuan Fang,Yiting Wang,Jiayang Liu,Hao Chi,Yufan Sun,Rui Ye,Lishen Shan,Jiawei Shi,Zan Shen,Yonggang Wang,Shuhang Wang,Jean-Philippe Brosseau,Feng Wang,Grace Liu,Yingfei Quan,Jie Xu
Cancer immunotherapy has transformed treatment possibilities, but its effectiveness differs significantly among patients, indicating the presence of alternative pathways for immune evasion. Here, we show that ITPRIPL1 functions as an inhibitory ligand of CD3ε, and its expression inhibits T cells in the tumor microenvironment. The binding of ITPRIPL1 extracellular domain to CD3ε on T cells significantly decreased calcium influx and ZAP70 phosphorylation, impeding initial T cell activation. Treatment with a neutralizing antibody against ITPRIPL1 restrained tumor growth and promoted T cell infiltration in mouse models across various solid tumor types. The antibody targeting canine ITPRIPL1 exhibited notable therapeutic efficacy against naturally occurring tumors in pet clinics. These findings highlight the role of ITPRIPL1 (or CD3L1, CD3ε ligand 1) in impeding T cell activation during the critical “signal one” phase. This discovery positions ITPRIPL1 as a promising therapeutic target against multiple tumor types.
研究领域:
免疫学
·
肿瘤学
·
医学
✓ 已验证
DOI
PubMed
高影响因子
ACTA PHYSIOLOGIAE PLANTARUM
·
2010
·Vol. 33
·期 4
·1271-1276
·
IF 1.232
Guan Yajing,Hu Jin,Li Yongping,Ma Wenguang,Zheng Yunye
Counterfeit seeds cause a large loss in seed industry and crop production. Present study was undertaken to find a new anti-counterfeiting technology by labeling seeds with a fluorescent compound, safranine T (ST). Response surface analysis (RSA) experiment with two factors (ST concentration and seed soaking time) of 14 combinations was performed to investigate the ST effects on seed vigor and fluorescence showing in seedlings of two tobacco varieties, MS Yunyan 85 and Honghua Dajinyuan. After soaking in ST solutions, tobacco seeds were germinated for 16 days, then the germination index (GI), vigor index (VI), length of roots and shoots were determined. The optimum combinations of ST concentration and soaking time on GI, VI and length of shoots and roots were 0.57–0.69 mg/ml and 6.77–9.34 h for MS Yunyan 85 and 0.51–0.80 mg/ml and 5.81–7.39 h for Honghua Dajinyuan, respectively. Meanwhile, tobacco seedlings, treated with ST solutions from 0.3 to 1.5 mg/ml showed obviously fluorescence under illumination of green light. It suggests that soaking tobacco seeds in safranine T solution of suitable concentration can be used as a labeling technique for anti-counterfeiting in tobacco seeds.
研究领域:
种子科学
·
农业生物技术
·
植物生理学
·
分析化学
·
作物生产
✓ 已验证
DOI
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
·
2020
·
IF 4.872
Ruifen Kang,Aneela Perveen,Chunmei Li
T-2 toxin is a kind of group A trichothecenes mycotoxins , frequently detected in various foods and feeds, having high toxic effects on both humans and animals. The present study aims to investigate the toxic effects of T-2 toxin exposure to ICR mice during pregnancy and lactation on liver glycolipid metabolism of young mice. The pregnant mice were given 0, 0.005 and 0.05 mg of T-2 toxin/kg bw daily through oral gavage from late gestation (GD 14) to the lactation (LD 21). Liver and serum samples of the young mice were collected on postnatal day 21 (PND 21), PND 28 and PND 56. The results showed that T-2 toxin increased the contents of triglycerides (TG), total cholesterol (T-CHO) and glucose in serum of young mice on PND 21 and PND 28. In addition, obvious lipid droplets of liver in T-2 toxin treatment groups were observed, especially in 0.05 mg group of PND 21and PND 28. Compared with the control group, T-2 treatment also increased the expressions of genes associated with liver glycolipid metabolism, such as PEPCK , Glut2 , Fas , Acox1 , Hmgcr , PPARα , Srebp1 and CD36 . These results demonstrated T-2 toxin exposure to pregnant mice could cause liver glycolipid metabolism disruption in the young mice and the toxic effects weakened on PND 56.
研究领域:
毒理学
·
营养学
✓ 已验证
DOI
PubMed
高影响因子
MICROCHIMICA ACTA
·
2016
·Vol. 184
·期 3
·687-691
·
IF 4.831
Hui Pan,Gao Wenyue,Nsabimana Jacques,Li Yunhui,Yang Xiuyun,Gao Ying,Shao Jing,Xu Guobao
The authors describe a method for amperometric determination of chloramine-T that is based on the indirect detection of chloramine-T by detecting p -quinone imine ( p -QI) that is generated by oxidation of p -aminophenylboronic acid by chloramine-T. p -QI can be detected with excellent selectivity and at low potential by using a glassy carbon electrode. Hence, the method displays attractive features such as high sensitivity, wide detection range and excellent selectivity. The electrode has two linear responses in the 50 nM to 100 μM concentration range and a 6 nM detection limit. Compared to other electrochemical methods, this assay has a detection limit that is better by three orders of magnitude. The relative standard deviation is 3.4% for the determination of 10 μM of the medical chloramine-T sample, and the recovery of a samples containing chloramine-T at a level of 10 μM is 115%.
Highly sensitive electrochemical detection of chloramine-T is achieved based on the reaction of chloramine-T with p -aminophenylboronic acid with a detection limit of 6 nM.
研究领域:
分析化学
·
医学检测
·
电化学
✓ 已验证
产品关联
DOI
高影响因子
Advanced Science
·
2024
·
IF 14.3
Jiaxiang Hu,Qingmiao Shi,Chen Xue,Qingqing Wang
Accumulating evidence suggests that berberine (BBR) exhibits anti-cancer effects in hepatocellular carcinoma (HCC). However, the mechanisms by which BBR regulates the immunological microenvironment in HCC has not been fully elucidated. In this study, a mouse model of orthotopic HCC is established and treated with varying doses of BBR. BBR showed effectiveness in reducing tumor burden in mice with HCC. Cytometry by time-of-flight depicted the alterations in the tumor immune landscape following BBR treatment, revealing the enhancement in the T lymphocytes effector function. In particular, BBR decreased the proportion of TCRb hi PD-1 hi CD69 + CD27 + effector CD8 + T lymphocytes and increased the proportion of Ly6C hi TCRb + CD69 + CD27 + CD62L + central memory CD8 + T lymphocytes. Single-cell RNA sequencing further elucidates the effects of BBR on transcriptional profiles of liver immune cells and confirms the phenotypical heterogeneity of T lymphocytes in HCC immune microenvironment. Additionally, it is found that BBR potentially regulated the antitumor immunity in HCC by modulating the receptor-ligand interaction among immune cells mediated by cytokines. In summary, the findings improve the understanding of BBR's impact on protecting against HCC, emphasizing BBR's role in regulating intrahepatic T cell heterogeneity. BBR has the potential to be a promising therapeutic strategy to hinder the advancement of HCC.
研究领域:
肿瘤学
·
免疫学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MEDIATORS OF INFLAMMATION
·
2025
·Vol. 2025
·期 1
·4955849
·
IF 4.2
Zhengrong Chen,Dingwei Yan,Suyu Guo,Yiyi Song,Xinxing Zhang,Wenjing Gu,Heting Dong,Li Huang
Background: This study aimed to explore the mechanisms underlying T-cell differentiation in asthma. Methods and Results: Flow cytometry was performed to detect Th cells. LC-MS/MS was performed to assess lipid metabolism. HE staining was performed to assess the pathological changes of the lung tissues. ELISA was performed to detect cytokine levels. The results of quantitative real-time polymerase chain reaction (qRT-PCR) and western blot showed that miR-192-5p expression was decreased, while SCD1 expression was increased in CD4 + T cells isolated from the peripheral blood of children with asthma. The dual luciferase reporter assay determined the direct interaction between miR-192-5p and SCD1. MiR-192-5p inhibitor reduced ASCL3 and PPARα, increased FASN and SREBP1c mRNA expression and protein levels in mouse spleen CD4 + T cells, and elevated Th2 and Th17 cells, but these effects were reversed by the SCD1 inhibitor. Oleic acid (OA) reduced Th1 cells and increased Th2 and Th17 cells in mouse spleen CD4 + T cells treated with an SCD1 inhibitor. Additionally, pri-miR-192-5p expression was increased in CD4 + T cells isolated from the peripheral blood of asthmatic children, and the deletion of METTL3 upregulated pri-miR-192-5p expression in an m6A-dependent manner. MiR-192-5p mimic and inhibitor both reversed miR-192-5p and SCD1 expression affected by overexpression or deletion of METTL3, both in vivo and in vitro . Furthermore, METTL3 overexpression attenuated lung inflammation, elevated Th1 cells, and reduced Th2 and Th17 cells in CD4 + T cells isolated from the peripheral blood of asthmatic mice. These effects were reversed by the miR-192-5p inhibitor. Conclusion: These results suggest that METTL3/miR-192-5p/SCD1 axis regulates lipid metabolism and affects T cell differentiation, thus affecting asthma progression. This study may provide novel insights into the pathogenesis of asthma and a new treatment strategy.
研究领域:
免疫学
·
分子生物学
·
呼吸病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Energy Storage
·
2019
·
IF 3.517
Yongyichuan Zhang,Xuelai Zhang,Xiaofeng Xu,Mengyao Lu
Phase change materials can store and release large amounts of heat over a small temperature range. Phase transition interval and phase change latent heat are important indicators for phase change materials, which determine phase change materials application in different temperature zones. Due to DSC has the quality error in sampling. Therefore, the T-history method is used here to derive the phase change interval, the phase change latent heat and the thermal conductivity of phase change materials. We chose CaCl 2 •6H 2 O composite SAT, DA-MA and OA phase change materials to improve the t-history method. The formula for phase transition interval, phase change latent heat and thermal conductivity is derived. The T-history method is more accurate and can compensate for the inaccuracy of DSC. The improved T-history method is not affected by mass, and the calculated thermophysical parameters are more representative, which is suitable for the parameter calculation of phase change materials with large mass.
研究领域:
材料科学
·
热物理学
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF INTERNATIONAL MEDICAL RESEARCH
·
2023
·
IF 1.6
Fang Wang,Xiu-Li Zhang,Jing-Ya Yang,Gang Zhou
ObjectiveOral lichen planus (OLP) is a T cell-mediated inflammatory condition in the oral cavity. Mucosal-associated invariant T (MAIT) cells are gaining more relevance in immune diseases because they can be activated by cytokines without T cell receptor stimulation. Herein, we tested the effect of interleukin-23 (IL-23) on the activation status of OLP MAIT cells.MethodsPeripheral blood mononuclear cells (PBMCs) isolated from OLP patients were stimulated by IL-23 in the absence or presence of phorbol myristate acetate (PMA) and ionomycin. The activation status of MAIT cells was analyzed by flow cytometry after staining for CD3, CD4, CD8, CD161, TCR Vα7.2, and CD69.ResultsThe fraction of MAIT cells in OLP peripheral blood was approximately 0.38% to 3.97%, and CD8+ subpopulations overwhelmed CD4+ cells. The mean percentages of OLP MAIT cells in PBMCs and CD8+MAIT cells in MAIT cells were approximately 40%. PMA and ionomycin significantly increased CD69 expression on OLP T cells, MAIT cells, and CD8+MAIT cells. Cells with enhanced activation had different responsiveness to exogenous IL-23, showing increased CD69 expression on OLP T cells, decreased CD69 on OLP CD8+MAIT cells, and no significant change on OLP MAIT cells.ConclusionsIL-23 showed different effects on the activation status of OLP MAIT cells and CD8+MAIT cells.
研究领域:
免疫学
·
皮肤科
·
口腔医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
IMMUNITY
·
2024
·
IF 25.5
Rui Ding,Xiaoyan Yu,Zhilin Hu,Yu Dong,Haiyan Huang,Yuerong Zhang,Qiaoqiao Han,Zhi-Yu Ni,Ren Zhao,Youqiong Ye,Qiang Zou
RNA splicing is involved in cancer initiation and progression, but how it influences host antitumor immunity in the metabolically abnormal tumor microenvironment (TME) remains unclear. Here, we demonstrate that lactate modulates Foxp3-dependent RNA splicing to maintain the phenotypic and functional status of tumor-infiltrating regulatory T (Treg) cells via CTLA-4. RNA splicing in Treg cells was correlated with the Treg cell signatures in the TME. Ubiquitin-specific peptidase 39 (USP39), a component of the RNA splicing machinery, maintained RNA-splicing-mediated CTLA-4 expression to control Treg cell function. Mechanistically, lactate promoted USP39-mediated RNA splicing to facilitate CTLA-4 expression in a Foxp3-dependent manner. Moreover, the efficiency of CTLA-4 RNA splicing was increased in tumor-infiltrating Treg cells from patients with colorectal cancer. These findings highlight the immunological relevance of RNA splicing in Treg cells and provide important insights into the environmental mechanism governing CTLA-4 expression in Treg cells.
研究领域:
免疫学
·
肿瘤学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Molecular Cell Biology
·
2022
·Vol. 14
·期 12
·
IF 8.185
Han Yuheng,Ouyang Xinxing,Chen Yao,Lai Shujing,Sun Hongxiang,Wu Ningbo,Ruan Chun,Lu Limin,Su Bing
It is well documented that the neonatal thymus-derived (neonatal-TD) regulatory T cells (Treg) are essential to prevent lethal autoimmune diseases and allergies, and neonatal and adult thymus possesses distinct output potentials for naïve T cells, including Treg. However, the molecular features and detailed functional differences between neonatal-TD and adult thymus-derived (adult-TD) T cells in terms of their ability to maintain immune homeostasis during long-term environmental influences are still largely unknown, partially due to the lack of appropriate animal models to precisely trace these cells at specific time points. In this study, neonatal-TD and adult-TD CD4+ T cells from the spleen and Peyer's patches were traced for 9 weeks by a T cell origin-time tracing mouse model and analysed by single-cell RNA sequencing. More Treg but fewer naïve T cells were found in neonatal-TD CD4+ T cells from both tissues than those from adult-TD counterparts. Interestingly, the neonatal-TD Treg in both the spleen and Peyer's patches exhibited augmented expression of Foxp3, Gata3, Ctla4, Icos, Il2ra, Tgfb1, and Nrp1, as well as enriched Gene Ontology terms like T cell activation and tolerance induction, indicating an enhanced immunosuppressive function. These results were further confirmed by flow cytometry analysis and in vitro immune suppression assays. Flow cytometry also revealed a significantly higher proportion of neonatal-TD Treg in total Treg than that of adult-TD counterparts, suggesting the longer lifespan of neonatal-TD Treg. To investigate the intrinsic features of neonatal-TD and adult-TD CD4+ T cells, a shortened tracing time was performed. Surprisingly, the neonatal-TD and adult-TD CD4+ T cells had similar proportions of Treg and did not exhibit significant differences in Foxp3, Gata3, Ctla4, Icos, Il2ra, and Tgfb1 expression levels after tracing for 12 days. On the other hand, neonatal-TD Treg present an increased Nrp1 expression level compared with adult-TD counterparts, indicating the enhanced stability. Together, our work reveals that the neonatal-TD Treg are more immunosuppressive, which is likely shaped primarily by environmental factors.
研究领域:
免疫学
·
分子生物学
·
基因组学
✓ 已验证
DOI
PubMed
高影响因子
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