EUROPEAN JOURNAL OF PHARMACOLOGY
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2025
·
IF 4.7
Fengjie Zhang,Shiyu Hu,Yuyuan Ying,Meiru Zhou,Xunuo Wen,Qingru Sun,Zhaohuan Lou,Jianli Gao
Thymus is the core organ that reflects the degree of aging, and the anti-aging effect of rapamycin(RAPA) has been confirmed by multiple studies, but the dynamic changes of the thymus after the administration of RAPA have been lacking systematic research. Here, we observed the involution of thymus induced by RAPA (1 mg/kg/day, i.p. for 3 days) and its regeneration kinetics after withdrawal of RAPA, to explore the possible mechanism of RAPA’s anti-aging effects based on changes in thymus function. The results show that the thymus weight decreased by 46.15% post-RAPA, then regenerated from 20.45 mg to 57.97 mg, reaching 1.3-fold baseline levels in age-matched controls. RAPA can cause acute involution in thymic structure and function, such as loss of medullary thymic epithelial cells (mTECs) and subcapsular thymic epithelial cells (sTECs), abnormal differentiation of thymocytes, reduction of peripheral T cell proportion, and up-regulation of Foxn1 and Klf6 mRNA levels. Regeneration featured expanded double positive (DP) T cells, CD3 + TCRβ + T cells, CD8 single-positive (SP) T cells, medullary dilatation, and thymocyte telomere elongation. IL-7 and MET have pro-regeneration effects, but neither of them could accelerate RAPA-mediated thymic regeneration. IL-7 can prolong telomere length of thymocytes and restore peripheral T cell homeostasis, while MET can promote T cell positive selection and increase Sirt3 and Gimap4 mRNA levels. These results demonstrate that RAPA triggers transient thymic suppression followed by thymus volume and functional recovery. It seems that RAPA-mediated immune reconstitution may be an important reason for the potential anti-aging effect of RAPA.
研究领域:
免疫学
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衰老研究
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药理学
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细胞生物学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Applied Sciences-Basel
·
2018
·Vol. 8
·期 12
·2530
·
IF 1.689
Nan Fang Nie,Xin Xing Zhang,Chu Shan Fang,Qiu Yan Zhu,Jiao Yang Lu,Fu Rui Zhang,Qing Feng Yao,Wei Tao Huang,Xue Zhi Ding,Li Qiu Xia
Game theory—the scientific study of interactive, rational decision making—describes the interaction of two or more players from macroscopic organisms to microscopic cellular and subcellular levels. Life based on molecules is the highest and most complex expression of molecular interactions. However, using simple molecules to expand game theory for molecular decision-making remains challenging. Herein, we demonstrate a proof-of-concept molecular game-theoretical system (molecular prisoner’s dilemma) that relies on formation of the thymine–Hg2+–thymine hairpin structure specifically induced by Hg2+and fluorescence quenching and molecular adsorption capacities of cobalt oxyhydroxide (CoOOH) nanosheets, resulting in fluorescence intensity and distribution change of polythymine oligonucleotide 33-repeat thymines (T33). The “bait” molecule, T33, interacted with two molecular players, CoOOH and Hg2+, in different states (absence = silence and presence = betrayal), regarded as strategies. We created conflicts (sharing or self-interest) of fluorescence distribution of T33, quantifiable in a 2 × 2 payoff matrix. In addition, the molecular game-theoretical-system based on T33 and CoOOH was used for sensing Hg2+over the range of 20 to 600 nM with the detection limit of 7.94 nM (3σ) and for determination of Hg2+in pond water. Inspired by the proof-of-concept for molecular game theory, various molecular decision-making systems could be developed, which would help promote molecular information processing and generating novel molecular intelligent decision systems for environmental monitoring and molecular diagnosis and therapy.Keywords:cobalt oxyhydroxide nanosheets;fluorescent sensing;game theory;Hg2+;thymine–Hg2+–thymine
研究领域:
分子生物学
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环境科学
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纳米技术
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产品关联
DOI
高影响因子
Analytical Methods
·
2014
·Vol. 6
·期 7
·2338-2342
·
IF 1.938
Ke Ma,Xing Li,Bin Xu,Wenjing Tian
A fluorescent turn-on approach for the sensitive and selective sensing of Hg2+ based on an aggregation-induced emission fluorescent molecule (DSA-T2) containing 9,10-distyrylanthracene as a fluorophore and thymine as a Hg2+ receptor, was developed. Under optimum conditions, a linear relationship (R2 = 0.9894) was obtained between the fluorescent intensity and the concentration of Hg2+ from 7 × 10−7 mol L−1 to 1 × 10−5 mol L−1. The theoretical detection limit of Hg2+ was evaluated to be 3.4 × 10−7 mol L−1. And the selectivity towards Hg2+ was good compared to other metal ions.
研究领域:
分析化学
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环境科学
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材料科学
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产品关联
DOI
高影响因子
Cell and Bioscience
·
2019
·Vol. 9
·期 1
·1-15
·
IF 3.355
Tan Jianxin,Wang Yajun,Wang Siliang,Wu Simeng,Yuan Zhe,Zhu Xike
Background Adipocyte accumulation is a predominant feature of age-related thymic involution, but the mechanisms responsible for thymic adipogenesis remain to be elucidated. The aim of this study was to identify key regulators in thymic adipogenesis. We used rosiglitazone, a potent peroxisome proliferator-activated receptor γ (PPARγ) agonist, to induce adipogenic differentiation of OP9-DL1 cells, and investigated the differentially expressed proteins during adipogenic differentiation by using label-free quantitative proteomics. Furthermore, the effects of transforming growth factor β1 (TGF-β1) on rosiglitazone-induced adipogenic differentiation of OP9-DL1 cells as well as the underlying mechanisms were also investigated. Results Proteomic analysis identified 139 proteins differed significantly in rosiglitazone-treated cells compared with dimethyl sulphoxide (DMSO)-treated cells. Rosiglitazone-induced adipogenic differentiation was inhibited by TGF-β1 treatment in OP9-DL1 cells and primary thymic stromal cells. Real-time PCR analysis showed significant increases in PPARγ and fatty acid binding protein 4 mRNA levels in rosiglitazone-treated cells, which were inhibited by TGF-β1 treatment. TGF-β1 down-regulated PPARγ expression at both mRNA and protein levels in OP9-DL1 cells. Chromatin immunoprecipitation analysis demonstrated that TGF-β1 enhanced the binding of Smad2/3 and histone deacetylase 1, but reduced the binding of H3K14ac to the promoter of PPARγ gene. TGF-β1 partially reversed the inhibitory effects of rosiglitazone on the expression of Axin2 and β-catenin protein levels. TGF-β1 inhibited rosiglitazone-induced adipogenic transformation in OP9-DL1 cells by down-regulation of PPARγ and activation of the canonical Wnt/β-catenin signaling pathway. Conclusion Taken together, activation of TGF-β pathway may serve as a useful strategy to prevent thymic adiposity in age-related thymic involution.
研究领域:
免疫学
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细胞生物学
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蛋白质组学
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分子生物学
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衰老研究
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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
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分子生物学
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基因组学
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DOI
PubMed
高影响因子
MICROCHIMICA ACTA
·
2019
·Vol. 186
·期 2
·1-7
·
IF 5.479
Song Xiaolei,Wang Yu,Liu Su,Zhang Xue,Wang Haiwang,Wang Jingfeng,Huang Jiadong
A colorimetric biosensor and visual test is described for the determination of mercury(II). It relies on the specific thymine-Hg(II)-thymine (T-Hg 2+ -T) interaction which induces a cyclic amplification process (caused by the enzyme exonuclease III) and the aggregation of gold nanoparticles. These results in a color change from red to violet. Under optimized conditions, this colorimetric assay (best performed at 524 nm) has a detection limit as low as 0.9 nM with a detection range over 4 orders of magnitude (from 1 nM to 10 μM).
Schematic of a colorimetric method for determination of mercury ions (Hg 2+ ) based on the thymine-Hg 2+ -thymine interaction-triggered cyclic enzymatic amplification and aggregation of gold nanoparticles with the aid of exonuclease III (Exo III).
研究领域:
分析化学
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环境科学
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纳米技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FOOD CONTROL
·
2018
·
IF 3.667
Xueqi Leng,Yuqin Tu,Yunping Wu,Yu Wang,Su Liu,Qianqian Pei,Xuejun Cui,Jiadong Huang
A fluorescence sensing strategy was described for the determination of melamine with ultrasensitivity and high specificity. This strategy relies on the combination of proximity ligation assay (PLA)-modulated thymine–melamine–thymine (T–melamine–T) triplex structure along with exonuclease III (Exo III)-aided recycling amplification. The reaction system involves three DNA probes (poly A, tDNA and molecular beacon (MB)). Probe ploy A is an adenine enriched sequence containing an apurinic/apyrimidinic site (AP site). It can provide a hydrophobic vacancy for specially recognizing melamine to bind the nucleobase through pseudo-base pairing and participate in PLA modulated T-melamine-T triplex structure. Probe tDNA can form T-melamine-T with probe poly A via PLA only in the presence of melamine. Probe MB is modified with a fluorophore at its 5′-terminus and a quencher at an internal position, which can self-hybridize to form a hairpin structure, positioning the fluorophore in close proximity to the quencher. Therefore, the binding of MB did not yield any fluorescence signal. However, in the presence of melamine, a T-melamine-T triplex structure is formed through PLA. Probe MB can hybridize with t T-melamine-T triplex structure to yield a substrate for interaction with Exo III. As a result, the T-melamine-T triplex structure is released. Next, the released T-melamine-T triplex structure will hybridize with another MB probe to achieve the Exo III-aided recycle amplification. This is the first example of PLA-modulated T-melamine-T triplex structure coupled with Exo III-aided recycling amplification. Under optimal conditions, the assay has a detection range over 4 orders of magnitude and a limit of detection of 4.4 nM. Moreover, the assay is rapid, simple and inexpensive. Hence, the strategy may open new avenues for ultrasensitive and highly specific detection of melamine encounted in food analysis .
研究领域:
分析化学
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食品科学
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分子生物学
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产品关联
DOI
高影响因子
MICROCHIMICA ACTA
·
2019
·Vol. 186
·期 4
·1-8
·
IF 5.479
Jin Huali,Zhang Mingli,Wei Min,Cheng Jun-Hu
The presented voltammetric mercury(II) sensor is based on the specific interaction between Hg(II) ion and thymine-thymine base pairs. Reduced graphene oxide is functionalized with gold nanorods and then loaded with thionine and streptavidin (RGO@AuNR-TH-SA). A T-rich thiolated DNA (S1) is firstly immobilized on a gold electrode. In the presence of Hg (II), the T-rich biotin-DNA (biotin-S2) binds to S1 via T-Hg(II)-T interaction. Then, the RGO@AuNR-TH-SA is linked to the gold electrode by specific binding between SA and biotin-S2. This produces an electrochemical signal (at −0.208 V vs. Ag/AgCl) of TH that depends on the concentration of Hg (II). The peak current increases linearly in the 1 to 200 nM Hg (II) concentration range, and the detection limit is 0.24 nM. The sensor is highly selective for Hg (II) over other environmentally relevant metal ions, even at concentration ratios of >1000.
Schematic representation of a voltammetric biosensor for mercury(II) using reduced graphene oxide@gold nanorods (RGO@AuNRs) and thymine-Hg(II)-thymine interaction. It is based on the fact that RGO@AuNR can strongly adsorb thionine (TH) and streptavidin to realize the signal amplification.
研究领域:
分析化学
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环境科学
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纳米技术
·
生物传感器
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产品关联
DOI
PubMed
高影响因子
Polymer Crystallization
·
2020
·Vol. 3
·期 5
·e10158
·
IF 0
Xiang Li,Xiaolei Dong,Jiale Zhou,Jianna Bao,Shichang Chen,Wangyang Lu,Xianming Zhang,Wenxing Chen
The end group modification of hydrogen bonding units has a significant effect on physical properties of covalent linked polymers. In this study, telechelic poly(ethylene glycol)s (PEG) with various molecular weights were functionalized by thymine (Thy), which was able to form self-complementary double hydrogen bonding. The physical properties of Thy-functionalized PEGs, including viscosity in solution or melt state, crystallization behavior, crystalline structure as well as lamellar structure were systemically investigated by comparison with hydroxyl-terminated PEGs. Crystallinity and melting temperature of linked PEG chains were decreased by the presence of Thy groups and the depression effects were strengthened by increase of Thy content. Crystallization rate and temperatures at which crystallization occurred were more complicated. Lower crystallization rate was obtained for Thy-functionalized PEGs with highest Thy content, a signature for confined crystallization by covalent links to Thy groups. However, in the case of moderate Thy content, the trend of crystallization rate was shifted to lower temperature regions, where the maximum and minimum of crystallization rates were comparable with free polymer chains. For Thy-functionalized PEGs with low Thy content, crystallization rates were similar with that of non-functionalized PEGs. The differences in supercoolings might give explanation on differences in crystallization behaviors among three conditions.
研究领域:
材料科学
·
高分子化学
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产品关联
DOI
ACS Applied Materials & Interfaces
·
2017
·
IF 7.504
Xin Liu,Qin Zhang,Zijian Gao,Ruibin Hou,Guanghui Gao
Bioinspired strategies have drawn much attention for designing intelligent hydrogels with promising performance. Herein, we present a bioinspired adhesive hydrogel driven by adenine and thymine, which are the basic units of DNA. The adhesive hydrogel exhibited promising adhesive property for the surface of various solid materials, including muscle tissues, plastics, rubbers, glasses, metals, ceramics, carnelians, and woods. The maximum peeling strength of hydrogels was 330 N m–1 on aluminum, superior to that of PAAm hydrogels with 70 N m–1. The strong adhesive behavior remained more than 30 times repeated peeling tests. Moreover, the swelling behavior, morphological structure, mechanical strength, and peeling adhesive strength were also investigated and confirmed the formation and various characteristics of adhesive hydrogels driven by adenine and thymine. Thus, the biomimetic strategy to design promising adhesive hydrogels can provide various opportunities in tissue engineering, such as wound dressing, bioglues, and tissue adhesives.
研究领域:
生物材料学
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组织工程学
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产品关联
DOI
PubMed
高影响因子
FOOD CHEMISTRY
·
2023
·
IF 8.8
Huanhuan Li,Qiyi Bei,Wenhao Zhang,Murugavelu Marimuthu,Md. Mehedi Hassan,Suleiman A. Haruna,Quansheng Chen
Mercury (Hg 2+ ) is a potentially toxic heavy metal ion found to be drastically deleterious to humans. Herein, an ultrasensitive fluorescence sensor was developed using three-dimensional upconversion nanoclusters (EBSUCNPs) and aptamer-modulated thymine-Hg 2+ -thymine strategy. The EBSUCNPs were used as the energy donors, the PDANPs served as the acceptors, and the aptamer was applied as an identification tag for Hg 2+ . Due to the energy transfer effect, the fluorescence of EBSUCNPs can be effectively quenched by Polydopamine nanoparticles (PDANPs). In the existence of Hg 2+ , T (thymine)-rich aptamers between EBSUCNPs and PDANPs were hybridized with Hg 2+ to yield thymine-Hg 2+ -thymine and folded back to hairpin structure, causing PDANPs to detach from the EBSUCNPS and the recovery of fluorescence. Under optimum conditions, the linear sensing range of Hg 2+ was 0.5–20 µg/L, and the detection limit was 0.28 µg/L. Furthermore, it exhibited excellent selectivity and anti-interference, which made it an ideal method for identifying Hg 2+ in spiked samples.
研究领域:
分析化学
·
环境科学
·
食品安全
·
纳米技术
·
生物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
POLYMER
·
2024
·
IF 4.1
Bin Pu,Gaolang Xiao,Juying Xiao,Hua-Bing Yin,Jin Wang
Self-healing materials based on photodimerization have advantages such as being fast, efficient, environmentally friendly and controllable. However, most of photoresponsive self-healing materials suffer from a problem that there is a compromise between the strength and the self-healing efficiency. Therefore, most of the research focuses on using flexible materials to reach high self-healing efficiency. The absorption wavelengths of some photosensitive groups are narrow, which limits the application fields of self-healing properties of self-repairing materials. Here, we use photodimerizable thymine as the photoresponsive group and exploit the sensitivity of a methoxyacetophenone photosensitizer to increase the self-healing efficiency of a rigid membrane material from beyond repairing to 85% recovery under the same conditions. The tensile strength of the self-healing material is 33.88 MPa, and the elastic modulus reaches 3 GPa after 80 min of photo-irradiation at 308 nm. The maximum thermogravimetric decomposition rate temperature exceeds 400 °C, exhibiting their excellent thermal stability. This strategy provides a novel and effective approach to endow rigid materials with high self-healing efficiency at benign conditions, and opens a new avenue to functionalise a wide range of rigid engineering materials.
研究领域:
材料科学
·
化学工程
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产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）