ACS Nano
·
2023
·
IF 17.1
Jie Yan,Wenxi Li,Hao Tian,Bei Li,Xinying Yu,Guohao Wang,Wei Sang,Yunlu Dai
Cancer cells outcompete tumor-infiltrating T lymphocytes (TILs) for glucose uptake, manipulating a glucose-deprived tumor microenvironment (TME) with high accumulation of lactate, which impairs CD8+ TIL effector function, however supports the immune suppression of regulatory T (Treg) cells. Aerobic glycolysis inhibition coupled with mitochondrial dysfunction in cancer cells may reprogram TME to destabilize Treg cells and, more importantly, facilitate CD8+ T cell activation and cytotoxic killing. Here, a sono-metabolic cancer therapy via hyaluronic acid (HA)-modified metal-phenolic nanomedicine (HPP-Ca@GSK) is proposed to accomplish the aforementioned goals. Abrogating lactate dehydrogenase A (LDHA) by delivering GSK2837808A (GSK, LDHA inhibitor) successfully suppresses aerobic glycolysis in cancer cells and creates high-glucose, low-lactate conditions, satisfying the glucose nutrition required by CD8+ TILs but destabilizing Treg cells. Meanwhile, depending on ultrasound-mediated oxidative stress, more than 3-fold of calcium (from HPP-Ca@GSK) is mitochondrion-overloaded, amplifying mitochondrial dysfunction and promoting the cancer cellular release of damage-associated molecular patterns for more CD8+ T cell activation and tumor infiltration. In vitro and in vivo studies demonstrate that HPP-Ca@GSK-based sono-metabolic treatment exhibits impressive anticancer activity. Cooperating with anticytotoxic T lymphocyte-associated protein-4 antibodies for enhanced Treg cell destabilization further improves therapeutic efficacy. These findings provide a metabolic intervention strategy for cancer immunotherapy.
研究领域:
癌症免疫疗法
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纳米技术
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代谢工程
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生物医学工程
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肿瘤学
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免疫学
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DOI
PubMed
高影响因子
Cell Death & Disease
·
2025
·Vol. 16
·期 1
·1-14
·
IF 9.6
Liu Min,Li Yuanyuan,Deng Zhilin,Zhang Ke,Huang Shuying,Xia Jiamin,Feng Yi,Liang Yundan,Sun Chengfu,Liu Xindong,Li Shurong,Su Bingyin,dong Yong,Huang Sizhou
Mutation in genes involved in DNA replication continuously disrupt DNA replication and give rise to genomic instability, a critical driver of oncogenesis. To prevent leukemia, immature T lymphocytes with genomic instability often undergo rapid cell death during development. However, the mechanism by which immature T lymphocytes undergo rapid cell death upon genomic instability has been enigmatic. Here we show that zebrafish mcm5 mutation leads to DNA damage in immature T lymphocytes and the immature T cells sensitively undergo rapid cell death. Detailed analyses demonstrated that the immature T lymphocytes undergo rapid apoptosis via upregulation of tp53 and downregulation of bcl2 transcription in mcm5 mutants. Mechanistically, Mcm5 directly binds to Stat1a and facilitates its phosphorylation to enhance bcl2a expression under the conditions of DNA replication stress. However, in mcm5 mutants, the absence of the Mcm5-Stat1 complex decreases Stat1 phosphorylation and subsequent bcl2a transcription, accelerating apoptosis of immature T lymphocytes with genomic instability. Furthermore, our study shows that the role of Mcm5 in T-cell development is conserved in mice. In conclusion, our work identifies a role of Mcm5 in regulating T cell development via Stat1-Bcl2 cascade besides its role in DNA replication, providing a kind of mechanism by which immature T cells with gene mutation-induced DNA damage are rapidly cleared during T lymphocyte development.
研究领域:
免疫学
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遗传学
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肿瘤学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING SCIENCE
·
2018
·
IF 3.306
Xin Sun,Chunying Zhu,Taotao Fu,Youguang Ma,Huai Z. Li
Dynamics for droplet breakup with tunnels and formation of satellite droplets in a symmetric microfluidic T-junction are investigated using a high-speed digital camera. The breakup process of droplet could be divided into four sequential stages: squeezing, transition, pinch-off, and thread rupture stages. Effects of the viscosity ratio of both phases λ , the capillary number of the continuous phase Ca c , and the dimensionless droplet length l 0 / w c on the breakup process of droplet are analyzed. In the squeezing stage controlled by squeezing pressure, the variation of the minimum width of the droplet neck with time could be scaled as a power-law relationship with exponent related to λ and l 0 / w c . The transition stage is dominated by the velocity of the fluid, and the pinch-off stage is mainly driven by the capillary force. For these two stages, the evolution of the minimum width of the droplet neck with the remaining time could be described as other power-law relationship with exponent related to λ . In the thread rupture stage controlled by viscous stresses of both phases and the surface tension, the minimum width of droplet neck decreases linearly with time, and the coefficient of the linear function depends on λ . Additionally, for the formation of satellite droplets, the size of satellite droplet increases with the increase of superficial velocity of the fluid and droplet viscosity. Furthermore, a critical capillary number 0.03 is observed in low viscosity of the droplet, which divides the variation of the size of the main satellite droplet with the capillary number into constant area and growth zone.
研究领域:
流体力学
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生物工程
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产品关联
DOI
高影响因子
JOURNAL OF BIOMEDICAL SCIENCE
·
2023
·Vol. 30
·期 1
·1-19
·
IF 11
Li Peisi,Zhou Dawang,Chen Dongwen,Cheng Yikan,Chen Yuan,Lin Zhensen,Zhang Xi,Huang Zhihong,Cai Jiawei,Huang Wenfeng,Lin Yanyun,Ke Haoxian,Long Jiahui,Zou Yifeng,Ye Shubiao,Lan Ping
Background A large proportion of the patients with cancer do not respond to immunotherapies. Recent studies suggested an important role for tumor-infiltrating cytotoxic T lymphocytes (CTL) in enhancing response to immunotherapy. Here, we aim to identify gene that induce proliferative and cytotoxic states of CD8 + T cells, and to investigate its effect on CAR-T cells against colorectal cancer. Methods Correlation between the expression of IFI35 with the activation and cytotoxicity of CD8 + T cells was assessed with TCGA and proteomic databases. Then we constructed murine colon cancer cells over-expressing IFI35 and tested their effect on anti-tumor immunity in both immunodeficient and immunocompetent mouse models. Flow cytometry and immunohistochemistry were performed to assess the immune microenvironment. Western blot analysis was used to identify the potential down-stream signaling pathway regulated by IFI35. We further investigated the efficacy of the rhIFI35 protein in combination with immunotherapeutic treatment. Results The transcriptional and proteomic analysis of the activation and cytotoxicity of CD8 + T cells in human cancer samples demonstrated that IFI35 expression is correlated with increased CD8 + T cell infiltration and predicted a better outcome in colorectal cancer. The number and cytotoxicity of CD8 + T cells were significantly increased in IFI35-overexpressing tumors. Mechanistically, we identified that the IFNγ-STAT1-IRF7 axis stimulated IFI35 expression, and that IFI35-mediated regulation of CD8 + T cell proliferation and cytotoxicity was dependent on PI3K/AKT/mTOR signaling pathway in vitro. Furthermore, IFI35 protein enhanced the efficacy of CAR-T cells against colorectal cancer cells. Conclusion Our findings identify IFI35 as a new biomarker that can enhance the proliferation and function of CD8 + T cells, as well as increase the efficacy of CAR-T cells against colorectal cancer cells. Graphical Abstract
研究领域:
肿瘤学
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免疫学
·
分子生物学
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癌症免疫疗法
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF CLINICAL LABORATORY ANALYSIS
·
2017
·Vol. 32
·期 3
·e22311
·
IF 1.521
Jingkun Wang,Yizhen Fang,Peihua Li,Huayue Lin,Hongwei Jin,Lei Gao,Shengxiang Ge,Zhong-Ying Zhang
Background To evaluate the performance of a chemiluminescence detection kit for cardiac troponin T (cTnT). Methods According to the “Guiding principles on performance analysis of diagnostic reagents in vitro” and the Clinical and Laboratory Standards Institute (CLSI) Guidelines, we assessed the detection limit, linear range, reportable range, accuracy, precision, cross reactivity, interference factors, and matrix effect of the kit, and compared these parameters with that of the commercial electrochemiluminescence detection kit for cTnT (Roche). Results The minimum detection limit of the kit was 0.01 ng/mL. The linear range was 0.01 ng/mL-25 ng/mL. The reportable range was from 0.01 ng/mL to 100 ng/mL. Precision within the batch was 2.9%-6.4%, and precision between batches was 6.0%; the accuracy was good and the recovery rate reached 96.2%. The cross-reaction test demonstrated that there was no reactivity between cTnT and a variety of troponins. Test results deviated by less than ±10% in the presence of hemoglobin ≤1000 μg/mL, bilirubin ≤250 μg/mL, triglycerides ≤11.25 mg/mL, and rheumatoid factor ≤206 U/mL, suggesting that kit results were not significantly interfered with these factors. Results from the matrix-effect assessment revealed absence of a matrix effect in the tested serum samples. Correlation study revealed that the performance of the kit was very consistent with that of the Roche electrochemiluminescence detection kit (Kappa = 0.900, P < .001) with a high correlation ( r = .903, P < .001) and a total matching rate of 95.00%. Conclusion The performance of the evaluated chemiluminescence immunoquantitation kit for cTnT detection was acceptable in all tested parameters, fulfilling requirements for clinical applications.
研究领域:
医学检验
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生物化学
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产品关联
DOI
PubMed
高影响因子
MICROPOROUS AND MESOPOROUS MATERIALS
·
2021
·
IF 5.455
Gang Li,Shanhong Ma,Feng Ye,Yiwei Luo,Shuanshi Fan,Xuemei Lang,Yanhong Wang,Liang Zhou
The dehydration of bio-oil is of great importance for improving its heating value for application as a renewable transportation fuel, and a T-type zeolite membrane was proposed for bio-oil dehydration via pervaporation in the present study. The permeation results show that water could be highly selectively removed via pervaporation from bio-oil, but the membrane was easily fouled in bio-oil due to a complex composition, which led to a rapid decrease in the permeation flux. The flux of the fouled T-type zeolite membrane in bio-oil was effectively regenerated after calcination at 220 °C, and the T-type zeolite membrane showed excellent reusability and chemical stability in the bio-oil system. Insights into the transport behaviors demonstrate that water permeated through the membrane mainly via intercrystalline pores, while most intracrystalline pores were blocked during pervaporation due to the strong adsorption of organic components in the pores, which suggests that tailoring both the amount and size of intercrystalline pores in the membrane is of great significance to effectively enhance the bio-oil dehydration performance.
研究领域:
化学工程
·
可再生能源
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材料科学
✓ 已验证
产品关联
DOI
高影响因子
IMMUNITY
·
2024
·
IF 25.5
Jingjing Cong,Pianpian Liu,Zili Han,Wei Ying,Chaoliang Li,Yifei Yang,Shuling Wang,Jianbo Yang,Fei Cao,Juntao Shen,Yu Zeng,Yu Bai,Congzhao Zhou,Lilin Ye,Rongbin Zhou,Chunjun Guo,Chunlei Cang,Dennis L. Kasper,Xinyang Song,Lei Dai,Linfeng Sun,Wen Pan,Shu Zhu
Concentrations of the secondary bile acid, deoxycholic acid (DCA), are aberrantly elevated in colorectal cancer (CRC) patients, but the consequences remain poorly understood. Here, we screened a library of gut microbiota-derived metabolites and identified DCA as a negative regulator for CD8 + T cell effector function. Mechanistically, DCA suppressed CD8 + T cell responses by targeting plasma membrane Ca 2+ ATPase (PMCA) to inhibit Ca 2+ -nuclear factor of activated T cells (NFAT)2 signaling. In CRC patients, CD8 + T cell effector function negatively correlated with both DCA concentration and expression of a bacterial DCA biosynthetic gene. Bacteria harboring DCA biosynthetic genes suppressed CD8 + T cells effector function and promoted tumor growth in mice. This effect was abolished by disrupting bile acid metabolism via bile acid chelation, genetic ablation of bacterial DCA biosynthetic pathway, or specific bacteriophage. Our study demonstrated causation between microbial DCA metabolism and anti-tumor CD8 + T cell response in CRC, suggesting potential directions for anti-tumor therapy.
研究领域:
肿瘤学
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免疫学
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微生物学
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产品关联
DOI
PubMed
高影响因子
Nanoscale Research Letters
·
2020
·Vol. 15
·期 1
·1-10
·
IF 3.578
Tang Jianke,Meng Rongqian,Wang Qi,Zhang Shengjian,Li Qiaoling
The Ag 3 PO 4 /tetrapod-like ZnO whisker (T-ZnOw) heterostructures were prepared via a simple precipitation method. The obtained heterostructures were characterized by X-ray diffraction, scanning electron microscopy, transmission electron microscopy, high-resolution transmission electron microscopy, X-ray photoelectron spectroscopy, and UV-Vis diffuse reflectance spectroscopy. The photodegradation activity of Ag 3 PO 4 /T-ZnOw was evaluated by the degradation of Rhodamine B (RhB) under visible light irradiation. When the molar ratio of Ag 3 PO 4 to T-ZnOw was 10% (Ag 3 PO 4 /T-ZnOw-2), the highest degradation efficiency (92.9%) could be achieved among the heterostructures. The photodegradation rate constant of Ag 3 PO 4 /T-ZnOw-2 (0.05179 min −1 ) was 3.59 times that of T-ZnOw (0.01444 min −1 ). Besides, the Ag 3 PO 4 /T-ZnOw-2 photocatalyst still possessed a degradation efficiency of 77.8% after four successive cycles. The Ag 3 PO 4 /T-ZnOw-2 catalyst had much higher photocatalytic activity than pure T-ZnOw and better stability and reusability than pure Ag 3 PO 4 . The effect of different scavengers on degradation efficiency was investigated, and the possible photocatalytic mechanism of the Ag 3 PO 4 /T-ZnOw photocatalyst was also put forward.
研究领域:
材料科学
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环境科学
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化学工程
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2024
·Vol. 22
·期 1
·1-19
·
IF 10.6
Xie Shenxia,Shi Wei,Duan Siliang,Huang Xianing,Liu Aiqun,Hou Xiaoqiong,Lin Xuandong,Zhong Dani,Sun Shuyang,Ding Ziqiang,Yang Xiaomei,Chen Xiaoyuan,Lu Xiaoling
Background T cell-based immunotherapies are facing great challenges in the recruitment and activation of tumor-specific T cells against solid tumors. Among which, utilizing nanobody (Nb) or nanobodies (Nbs) to construct T cell engager has emerged as a more practical potential for enhancing the anti-tumor effectiveness of T cells. Here, we designed a new Nb-guided multifunctional T cell engager (Nb-MuTE) that not only recruited effector T cells into the tumor tissues, but also efficiently activated T cells anti-tumor immunity when synergies with photothermal effect. Results The Nb-MuTE, which was constructed based on an indocyanine green (ICG)-containing liposome with surface conjugation of CD105 and CD3 Nbs, and showed excellent targetability to both tumor and T cells, following enhancement of activation, proliferation and cytokine secretion of tumor-specific T cells. Notably, the immunological anti-tumor functions of Nb-MuTE-mediated T cells were further enhanced by the ICG-induced photothermal effect in vitro and in vivo. Conclusions Such a new platform Nb-MuTE provides a practical and “all-in-one” strategy to potentiate T cell responses for the treatment of solid tumor in clinic.
研究领域:
免疫治疗
·
癌症生物学
·
纳米技术
·
药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CATALYSIS TODAY
·
2021
·
IF 6.766
Lijie Pei,Jianxin Cao,Fei Liu,Anjie Yang,Mengqin Yao,Tianxiang Zhao,Xiaodan Wang,Sibudjing Kawi
The catalytic properties of bifunctional ZSM-5@t-ZrO 2 catalyst for methanol thiolation were revealed by using methanol and H 2 S as probe molecules. Taking the ZSM-5/t-ZrO 2 physically-blended catalyst, pure ZSM-5 and t-ZrO 2 as control catalysts, we investigated the characteristics of adsorption and transformation of different reaction molecules on or over different catalysts by combination of in-situ diffuse reflectance Fourier transform infrared spectroscopy (Drifts) and a variety of techniques including XRD, XPS, XRF, FT-IR, N 2 adsorption-desorption, CO 2 /NH 3 -TPD, and DSC. The results showed that the synergistic effect of acid sites between ZSM-5 phase and t-ZrO 2 phase in the bifunctional catalyst enhanced the adsorption and dissociation of methanol molecules, while the base sites in t-ZrO 2 phase were mainly responsible for the adsorption and dissociation of H 2 S molecules. Due to the small specific surface area of pure t-ZrO 2 catalyst, precursor species for sulfur deposition and carbon deposition were easily formed. Presulfurization could improve the initial activity of methanol thiolation and shorten the induction period. The dissociation of H 2 S at the base sites was the rate-determining step of the bimolecular reaction, and the appropriate increase of base sites in the bifunctional components could construct the matching formation rate of sulfhydryl and methoxy groups. At the same time, the special composite structure and meso-microporous system of ZSM-5@t-ZrO 2 could effectively reduce the formation rate of carbon and sulfur deposits.
研究领域:
催化化学
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材料科学
✓ 已验证
产品关联
DOI
高影响因子
ChemCatChem
·
2021
·Vol. 13
·期 13
·3184-3197
·
IF 5.686
Chao Huang,Can Zhu,Mingwei Zhang,Yongwu Lu,Qianhao Wang,Heming Qian,Jiangang Chen,Kegong Fang
Graphical Synergetic effect : The physically mixed CuCoAl|t-ZrO 2 multifunctional catalyst could achieve superior selectivity towards alcohols while simultaneously inhibiting the generation of hydrocarbons from CO hydrogenation. Selective synthesis of higher alcohols from syngas is promising but remains challenging owing to the low stability and selectivity towards higher alcohols. Here we introduce a CuCoAl|t-ZrO 2 (t denotes tetragonal crystal phase) multifunctional catalyst that can achieve an alcohol selectivity of 64.8 % with 79.6 % C 2+ OH, and a total selectivity of alcohols and olefins to 81.7 %. The proper proximity was tuned to increase selectivity towards alcohols and decrease the selectivity towards hydrocarbons. The lower surface [H*]/[C*] ratio due to the stronger basic sites of the CuCoAl|t-ZrO 2 limited alkyl (CH x ) species hydrogenation, and promoted CO insertion and carbon chain growth, resulting in improving the alcohols selectivity. Meanwhile, the weaker adsorption of bridge-type adsorbed CO and the lower decomposition rate of multi-bonded adsorbed CO over CuCoAl|t-ZrO 2 inhibited hydrocarbon generation. The selective promotion of the reaction route via the synergetic effect between CuCoAl and t-ZrO 2 was proposed to boost higher alcohols selectivity. This work may aid the rational design of effective multifunctional catalyst with synergistic effects for tuning selectivity.
研究领域:
催化化学
·
材料科学
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2025
·
IF 6.2
Si-Yi Han,Hong-Fu Zhao,Zi-Ying Zhao,Jing-Zhi Yu,Ying-Hua Zhang,Zhi-Shen Mu
Food-derived protein peptides with γ-aminobutyric acid transaminase (GABA-T) inhibitory activity possess the promising ability to alleviate anxiety and have become a market focus. This study prepared casein hydrolysate with valid GABA-T inhibitory activity using ultrasound-assisted enzymatic hydrolysis and obtained novel GABA-T inhibitory peptides through isolation and purification. The results demonstrated that ultrasonic pretreatment significantly improved the casein hydrolysis efficiency, enhanced GABA-T inhibitory activity by 19.32%, and allowed retention of 42.37% of the initial inhibitory activity after gastrointestinal digestion. Through peptidomics analysis, five novel GABA-T inhibitory peptides were identified from casein hydrolysate, including FFVAPFPE, VYPFPGPIPN, HLPLPL, FLPYPY, and WQVL (2.79 ± 0.14 to 8.49 ± 0.26 mM). Molecular docking results revealed that these five peptides bind to GABA-T through hydrogen bonds and hydrophobic interactions, with the Arg422 residue potentially serving as the key active site for GABA-T inhibition. This study demonstrates significant potential for both the high-value utilization of casein and the development of antianxiety functional foods targeting GABA-T.
研究领域:
食品科学
·
生物化学
·
神经药理学
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肽类研究
·
酶学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）