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FISH & SHELLFISH IMMUNOLOGY · 2018 · IF 3.185

Affinity maturation occurs in channel catfish (Ictalurus punctaus) following immunization with a T-cell dependent antigen

Liting Wu,Shengli Fu,Xiaoxue Yin,Wenna Leng,Zheng Guo,Anli Wang,Jianmin Ye

Affinity maturation of the antibody response , a process of antibody affinity increasing over response, is one of the key features of the mammalian immune system. However, the process is incompletely understood in teleost, including channel catfish ( Ictalurus punctaus ). In this study, IgM affinity maturation in channel catfish was investigated by estimating the kinetics of antibody affinity using ELISA and ELISPOT assays . Fish were immunized with a T-cell dependent antigen (TNP-KLH), and individual serum IgM antibody titers and affinities, and IgM + antibody-secreting cells (ASCs) in peripheral blood were analyzed over a period of 14 weeks. A detectable serum anti-TNP response developed by 2-weeks post-immunization, and the maximal antibody production was observed by 6-weeks post-immunization. The average affinity of anti-TNP serum antibody increased consistently and reached the maximum by 10-weeks post-immunization. The increase of antibody affinity beyond the point of optimal antibody titer revealed that the affinity maturation of IgM antibody response occurred in channel catfish. Dissection of dynamics of individual affinity subpopulations indicated that a significant proportion of low affinity subpopulations appeared at early response, and high affinity subpopulations appeared predominantly at later, resulting in a 100-fold increase in affinity over response. Additional, TNP + IgM + ASCs was detected by 2-weeks post-immunization and achieved the maximal number by 6-weeks post-immunization. Using an inhibition ELISPOT assay, the findings of a consistent increase in the average affinity of secreted IgM antibody by peripheral blood ASCs, as the immune response progressed, confirmed the occurrence of the affinity maturation. Taken together, the results of this study indicated that affinity maturation occurred in channel catfish following immunization with a TD antigen TNP-KLH.

研究领域: 免疫学 · 鱼类生物学
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INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES · 2025 ·Vol. 26 ·期 23 · IF 4.9

STING Restricts EV-A71 Infection by Regulating T Cell Development and Enhancing Immune Cell Effector Function

Huiqiang Wang,Ya Wang,Shuo Wu,Lijun Qiao,Wen Sheng,Haiyan Yan,Kun Wang,Ge Yang,Jiandong Jiang,Yuhuan Li

Previous studies have reported that Enterovirus A71 (EV-A71) infection could activate STING-related signaling pathways in vitro, but the role of STING in EV-A71 infection in vivo and the associated immune regulatory mechanisms remain unclear. Here, we used the STING-specific agonist diABZI to activate STING and STING-knockout mice to jointly study the role and mechanism of regulating STING on EV-A71 infection in vivo. The results showed that activating STING could inhibit the in vivo replication of EV-A71, alleviate clinical symptoms in infected mice, and increase the survival rate. Conversely, STING knockout significantly promoted viral replication in vivo and increased the lethality and severity of EV-A71 infection. Mechanistic studies further revealed that STING activation exerts its antiviral effects by stimulating interferon signaling pathways, upregulating the expression of interferon-stimulated genes (ISGs). Additionally, STING activation also modulated the serum cytokine response profile. Moreover, STING activation drove the expansion of diverse immune cell populations, including T cells, natural killer (NK) cells and myeloid cells. In contrast, STING knockout not only reduced the proportion of thymic T cells and impeded T cell developmental progression from double-positive (DP) to single-positive (SP) stages, but also impaired the effector functions of CD8+ T cells and NK cells during viral infection. In summary, this study demonstrates that STING activation effectively suppresses EV-A71 replication and mitigates infection symptoms by modulating immune and inflammatory responses. These findings provide a foundational framework for understanding how STING coordinates antiviral immunity and inform future investigations into STING-targeted therapies for viral infections.

CAS / MDL: 25322-68-3
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ANALYTICAL AND BIOANALYTICAL CHEMISTRY · 2022 ·Vol. 414 ·期 20 ·6149-6156 · IF 4.478

Telomere G-triplex lights up Thioflavin T for RNA detection: new wine in an old bottle

Qin Shanshan,Chen Xuliang,Xu Zhichen,Li Tao,Zhao Shuhong,Hu Rui,Zhu Jiang,Li Ying,Yang Yunhuang,Liu Maili

Few reports are found working on the features and functions of the human telomere G-triplex (ht-G3) though the telomere G-quadruplex has been intensely studied and widely implemented to develop various biosensors. We herein report that ht-G3 lights up Thioflavin T (ThT) and establish a sensitive biosensing platform for RNA detection by introducing a target recycling strategy. An optimal condition was selected out for ht-G3 to promote ThT to generate a strong fluorescence. Accordingly, an ht-G3-based molecular beacon was successfully designed against the corresponding RNA sequence of the SARS-CoV-2 N-gene. The sensitivity for the non-amplified RNA target achieves 0.01 nM, improved 100 times over the conventional ThT–based method. We believe this ht-G3/ThT–based label-free strategy could be widely applied for RNA detection.

CAS / MDL: 2390-54-7
研究领域: 生物化学 · 分子生物学 · 分析化学
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Biomaterials Science · 2021 ·Vol. 9 ·期 9 ·3453-3464 · IF 6.843

T cell membrane cloaking tumor microenvironment-responsive nanoparticles with a smart “membrane escape mechanism” for enhanced immune-chemotherapy of melanoma

Xiaofang Li,Wen Zhang,Jing Lin,Hao Wu,Yucen Yao,Jiayi Zhang,Chunrong Yang

The application of combination immune-chemotherapy makes up for the limitation of monotherapy and achieves superior antitumor activity against cancer. However, combinational therapy is always restricted by poor tumor targeted drug delivery efficacy. Herein, novel T cell membrane cloaking tumor microenvironment-responsive nanoparticles (PBA modified T cell membrane cloaking hyaluronic acid (HA)-disulfide bond-vitamin E succinate/curcumin, shortened as RCM@T) were developed. T cell membrane cloaking not only serves as a protection shell for sufficient drug delivery but also acts as a programmed cell death-1(PD-1) “antibody” to selectively bind the PD-L1 of tumor cells. When RCM@T is intravenously administrated into the blood stream, it accumulates at tumor sites and responds to an acidic pH to achieve a “membrane escape effect” and expose the HA residues of RCM for tumor targeted drug delivery. RCM accumulates in the cytoplasm via CD44 receptor mediated endocytosis and intracellularly releases antitumor drug in the intracellular redox microenvironment for tumor chemotherapy. T cell membrane debris targets the PD-L1of tumor cells for tumor immunotherapy, which not only directly kills tumor cells, but also improves the CD8+ T cell level and facilitates effector cytokine release. Taken together, the as-constructed RCM@T creates a new way for the rational design of a drug delivery system via the combination of stimuli-responsive drug release, chemotherapeutical agent delivery and cell membrane based immune checkpoint blockade immunotherapy.

研究领域: 肿瘤学 · 药理学 · 免疫疗法 · 纳米技术 · 药物递送系统
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SENSORS AND ACTUATORS B-CHEMICAL · 2020 · IF 7.1

Ultrasensitive and rapid detection of T-2 toxin using a target-responsive DNA hydrogel

Yunfeng Sun,Shuang Li,Ruipeng Chen,Pian Wu,Jun Liang

The T-2 toxin is generated as a secondary metabolite by various species of Fusarium that are found extensively in barley, wheat, maize, and oats; consequently, the development of methods that can rapidly and efficiently detect this toxin is vital. Herein, we report on a novel and highly sensitive method based on DNA hydrogels and etched gold nanorods (AuNRs) to detect the T-2 toxin. The T-2 toxin aptamer acts as a cross-linking agent for a hydrogel in which horseradish peroxidase (HRP) is uniformly embedded. The target T-2 toxin binds to the aptamer, causing the hydrogel to collapse and release the embedded HRP, which catalyzes the reaction of H 2 O 2 with KI to produce I 2 that etches the AuNRs. The UV spectrum of the AuNRs is blue-shifted following etching; this shift is proportional to the T-2-toxin content. This method offers a low limit of detection (0.87 pg mL −1 ), low limit of quantification (2.90 pg mL −1 ), and wide detection range (0.01–10000 ng mL −1 ). Moreover, coffee, corn, and soybean were assayed using the optimized method. The approach offers good recoveries and relative standard deviations of 93.72–103.07 % and 3.87–7.07 %, respectively. The total assay time was 1.5 h. Thus, the new method is promising as an ultrasensitive assay for detecting various small molecules in complex matrices.

研究领域: 分析化学 · 毒理学 · 食品科学 · 纳米技术
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ELECTROANALYSIS · 2014 ·Vol. 26 ·期 12 ·2739-2746 · IF 2.502

A High Sensitivity Electrochemical Sensor Based on Fe3+-Ion Molecularly Imprinted Film for the Detection of T-2 Toxin

Xing Gao,Wenying Cao,Miaomiao Chen,Huayu Xiong,Xiuhua Zhang,Shengfu Wang

The excellent detection sensitivity in various matrices of T-2 toxin (T-2), which has cytotoxic and immunosuppressive effects in DNA and RNA synthesis, is a highly desirable characteristic. A sensitive molecularly imprinted electrochemical sensor was constructed for the selective detection of T-2. In this study, iron ions (Fe 3+ ) were introduced to increase the chelation of the metal ions and templates for preparing molecularly imprinted polymers (MIPs). With the increased chelation of the metal ions and templates, the selectivity and sensitivity of the MIPs were effectively improved. The imprinted sensor was successfully employed to detect T-2 in cereals and human serum samples.

CAS / MDL: 2530-87-2
研究领域: 食品科学 · 生物医学工程 · 分析化学
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Advanced Science · 2023 · IF 15.1

Protein-Nanocaged Selenium Induces t(8;21) Leukemia Cell Differentiation via Epigenetic Regulation

Long Fang,Ruofei Zhang,Lin Shi,Jiaying Xie,Long Ma,Yili Yang,Xiyun Yan,Kelong Fan

The success of arsenic in degrading PML-RARα oncoprotein illustrates the great anti-leukemia value of inorganics. Inspired by this, the therapeutic effect of inorganic selenium on t(8; 21) leukemia is studied, which has shown promising anti-cancer effects on solid tumors. A leukemia-targeting selenium nanomedicine is rationally built with bioengineered protein nanocage and is demonstrated to be an effective epigenetic drug for inducing the differentiation of t(8;21) leukemia. The selenium drug significantly induces the differentiation of t(8;21) leukemia cells into more mature myeloid cells. Mechanistic analysis shows that the selenium is metabolized into bioactive forms in cells, which drives the degradation of the AML1-ETO oncoprotein by inhibiting histone deacetylases activity, resulting in the regulation of AML1-ETO target genes. The regulation results in a significant increase in the expression levels of myeloid differentiation transcription factors PU.1 and C/EBPα, and a significant decrease in the expression level of C-KIT protein, a member of the type III receptor tyrosine kinase family. This study demonstrates that this protein-nanocaged selenium is a potential therapeutic drug against t(8;21) leukemia through epigenetic regulation.

CAS / MDL: 616-91-1
研究领域: 肿瘤学 · 分子生物学 · 纳米技术 · 表观遗传学
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ACS Materials Letters · 2023 · IF 11.4

Chromium Nanoparticles Improve Macrophage and T Cell Infiltration for Cancer Immunotherapy

Quan Liu,Zhe Sun,Yanhong Duo,Lei Yin,Kongpeng Lv,Ludan Yue,Qian-Fang Meng,Dingmeng Nie,Jiaojuan Chen,Dixian Luo,Li-Ping Liu,Lang Rao

Immune checkpoint blockade has been regarded as a highly promising cancer immunotherapy approach. However, inefficient immune cell infiltration and the immunosuppressive tumor microenvironment (TME) remain significant causes of low clinical response rates. Here, we identified that trivalent chromium irons (Cr3+) could enhance tumor infiltration of immune cells including M1-type tumor-associated macrophages and CD8+ T cells. Mechanistically, this effect is dependent on the expression of macrophage inflammatory protein-1α (MIP-1α) and the PI3K/Akt/mTOR pathway. Moreover, the Cr-based nanoparticles (Cr NPs) exhibited superior photothermal properties under near-infrared laser irradiation, showing great potential in transforming “cold” tumors into “hot” ones. In combination with the PD-1/PD-L1 pathway inhibitor, we demonstrated that the Cr NPs significantly improved anticancer efficacy in mouse models of hepatoma and melanoma by increasing antitumor immune cell infiltration and relieving immunosuppressive TME. Overall, the Cr NPs offer a new dual-functional platform for local and systemic cancer treatments, paving the way toward cancer photometalloimmunotherapy.

CAS / MDL: 1308-38-9
研究领域: 肿瘤学 · 免疫学 · 纳米技术 · 生物医学工程
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TALANTA · 2016 · IF 4.035

“Molecular beacon”-hosted thioflavin T: Applications for label-free fluorescent detection of iodide and logic operations

Yan-Yun Li,Xiao-Qin Jiang,Ling-Fei Lu,Min Zhang,Guoyue Shi

In this work, we presented a simple, label-free and rapid-responsive fluorescence assay for iodide (I − ) detection based on “molecular beacon (MB)”-hosted thioflavin T (ThT), achieving a limit of detection as low as 158   nM. The proposed method exhibited very good selectivity to I − ions over other anions interference due to the strong binding force between I − ions with Hg 2+ . Upon the addition of I − ions, it would capture Hg 2+ from a T–Hg 2+ –T complex belonging to the MB-like DNA hairpin structure, which eventually quenched the initial fluorescence as output. In addition, it was successfully applied for operation of an integrated DNA logic gate system and to the determination of I − in real samples such as human urine.

CAS / MDL: 128-53-0
研究领域: 分析化学 · 生物化学 · 分子生物学 · 生物医学工程
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Science Advances · 2020 ·Vol. 6 ·期 47 · IF 13.117

Promoting the activation of T cells with glycopolymer-modified dendritic cells by enhancing cell interactions

Liyin Yu,Ruyan Feng,Lijuan Zhu,Qing Hao,Jiacheng Chu,Yan Gu,Yan Luo,Zexin Zhang,Gaojian Chen,Hong Chen

Dendritic cell (DC) modification to enhance antigen presentation is a valuable strategy in cancer immune therapy. Other than focusing on regulating interactions between DC and antigens, we intend to promote cell interactions between DC and T cell by cell surface engineering. T cell activation is greatly improved and generates higher tumor toxicity with the aid of the synthetic glycopolymer modified on the DC surface, although the glycopolymer alone shows no effect. The great promotion of DC–T cell attraction is revealed by cell image tracking in terms of both frequency and duration of contacts. Our findings provide a new method of T cell activation by these engineered “sweet DCs.” This strategy is beneficial for developing more efficient DC-based vaccines.

CAS / MDL: 68-12-2
研究领域: 免疫学 · 癌症研究 · 细胞生物学
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JOURNAL OF MASS SPECTROMETRY · 2017 ·Vol. 53 ·期 2 ·172-182 · IF 2.381

Accelerated, untargeted metabolomics analysis of cutaneous T-cell lymphoma reveals metabolic shifts in plasma and tumor adjacent skins of xenograft mice

Yunchen Le,Xiaoyan Shen,Hongyan Kang,Qizheng Wang,Kejia Li,Jie Zheng,Yunqiu Yu

Cutaneous T-cell lymphoma (CTCL) is a heterogeneous group of skin-homing T-cell neoplasms. Clinical management is stage based but diagnosis and prognosis could be extremely challenging. The presented study aims to explore the metabolic profiling of CTCL by an accelerated untargeted metabolomics data analysis tool “Mummichog” to facilitate the discoveries of potential biomarkers for clinical early stage diagnosis, prognosis, and treatments in CTCL. Ultra high-performance liquid chromatography–quadrupole time-of-flight–based untargeted metabolomics were conducted on the skin and plasma of CTCL mice. It showed that the metabolism of skin changed greatly versus control samples in the development of CTCL. Increased l -glutamate and decreased adenosine monophosphate were the most essential metabolic features of CTCL tumor and tumor adjacent skins. Unique metabolism changes in tumor adjacent non-involved skin tissues (ANIT) occurred in the progress of carcinogenesis, including upregulated cytidine-5′-triphosphate, aberrant biosynthesis of prostaglandins, pyrimidine, mevalonate pathway, and tryptophan degradation. Sharply elevated 5-phospho-α- d -ribose 1-diphosphate (PRPP) marked the final state of tumor in CTCL. In the plasma, systematic shifts in corticosterone, sphingolipid, and ceramide metabolism were found. These uncovered aberrant metabolites and metabolic pathways suggested that the metabolic reprogramming of PRPP in tumor tissues may cause the disturbance of cytidine and uridine metabolic homeostasis in ANIT. Accumulative cytidine-5′-triphosphate in ANIT may exert positive feedback on the PRPP level and leads to CTCL further development. In addition, the accelerated data analysis tool “Mummichog” showed good practicability and can be widely used in high-resolution liquid chromatography mass spectrometry–based untargeted metabolomics.

研究领域: 肿瘤学 · 代谢组学 · 分子生物学
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Water Conservation Science and Engineering · 2025 ·Vol. 10 ·期 3 ·1-16 · IF 1.9

Facile and Rapid Synthesis of Cerium-Modified UiO-66-NH2 for Efficient Removal of Safranine T from Aqueous Solutions

Li Zhengjie,Fang Chunxia,Ma Xilong,Liu Yixian,Xie Juan,Li Pengfei,Zhang Zhikun,Zhao Xudong,Sun Hua,Han Jilong

Herein, a facile and rapid preparation method was developed to synthesize Ce-doped UiO-66-NH 2 through a one-pot solvothermal method. This approach simultaneously introduces functional groups onto organic ligands and incorporating a novel metal into metal clusters. The incorporation of Ce ions effectively enlarged the pore size and increased the pore volume, thereby facilitating the diffusion of specific adsorbate molecules into the inner adsorption sites provided by the –NH 2 groups. Due to the favorable pore structures and more exposed adsorption sites, the safranine T (ST) adsorption capacity of Ce-doped UiO-66-NH 2 was ten times higher than the pristine UiO-66-NH 2 and reached 1340 mg/g at optimal adsorption conditions, surpassing most of the reported porous adsorbents. The kinetic and isotherm fitting results showed that the pseudo-second-order and Langmuir models described the adsorption behaviors of ST best, indicating a homogeneous, endothermic, and spontaneous monolayer adsorption process. The adsorption mechanism showed that the hydrogen bonding interaction and pore filling effect are identified as the main mechanism whilst electrostatic attraction interaction further enhances the adsorption capacity at optimal pH. Therefore, Ce-doped UiO-66-NH 2 can serve as a promising adsorbent for the removal of cationic dyes from textile wastewater, and the developed facile and rapid method offers a viable strategy to construct novel MOF-based adsorbents.

CAS / MDL: 16774-21-3
研究领域: 环境科学 · 材料科学 · 化学工程 · 纳米技术
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