Advanced Science
·
2022
·Vol. 9
·期 32
·2203523
·
IF 17.521
Ming Shen,Chuanrong Chen,Qianqian Guo,Quan Wang,Jinghan Liao,Liting Wang,Jian Yu,Man Xue,Yourong Duan,Jiali Zhang
T-cell engagers (TCEs) represent a breakthrough in hematological malignancy treatment but are vulnerable to antigen escape and lack a vaccination effect. The “immunologically cold” solid tumor presents substantial challenges due to intratumor heterogeneity and an immunosuppressive tumor microenvironment (TME). Here, a methoxy poly(ethylene glycol) (mPEG)-masked CD44×PD-L1/CD3 trispecific T-cell nanoengager loaded with the STING agonist c-di-AMP (CDA) (PmTriTNE@CDA) for the treatment of triple-negative breast cancer (TNBC) is rationally designed. PmTriTNE@CDA shows tumor-specific accumulation and is preferentially unmasked in response to a weakly acidic TME to prevent on-target off-tumor toxicity. The unmasked CD44×PD-L1/CD3 trispecific T-cell nanoengager (TriTNE) targets dual tumor-associated antigens (TAAs) to redirect CD8+ T cells for heterogeneous TNBC lysis while achieving PD-L1 blockade. PmTriTNE synergized with CDA to transform the cold tumor into a hot tumor, eradicate the large established TNBC tumor, and induce protective immune memory in a 4T1 orthotopic tumor model without causing obvious toxicity. PmTriTNE@CDA shows potent efficacy in cell line-derived xenograft (CDX) and patient-derived xenograft (PDX) mouse models. This study serves as a proof-of-concept demonstration of a nanobased TCEs strategy to expand therapeutic combinations that previously could not be achieved due to systemic toxicity with the aim of overcoming TNBC heterogeneity and immunotherapy resistance.
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JOURNAL OF CHEMICAL AND ENGINEERING DATA
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2022
·
IF 3.119
Xinxin Cheng,Liang Yao,Ting Wang,Yanju Zhang,Rensong Wang,Peng Zhou,Wenge Yang,Bin Zhou,Li Mi,Yonghong Hu
Herein, the solubility and thermodynamic characterization solubility of 3,4,5-trimethoxycinnamic acid (TMCA) were studied by a static equilibrium method combined with high-performance liquid chromatography (HPLC), which provided a significant reference for crystallization and industrial separation of TMCA. First, the solubility data of TMCA was measured in 11 industrial common solvents and 4 binary mixed solvents at different temperatures (278.15–323.15 K) under atmospheric pressure. The results showed that the solubility of TMCA in the test solvents was positively correlated with temperature. In binary solvents, the increase in the mole fraction of the cosolvent also facilitated the dissolution of TMCA. Then, the monosolvent solubility data obtained in the experiment were fitted by the Buchowski–Ksiazaczak λh model and modified Apelblat model. The binary mixed solvent solubility data obtained in the experiment were fitted by the CNIBS/R–K model, Jouyban–Acree model, and SUN model. Meanwhile, the KAT-LSER model was also used to explore the effect of the solvation of TMCA. Furthermore, as can be seen from differential scanning calorimetry (DSC) and X-ray diffraction (XRD) analyses, the purity of the sample is without crystal transformation before and after dissolution, indicating that the physical and chemical properties of the TMCA sample are stable in the experimental process, and the experimental data have good accuracy and reliability.
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JOURNAL OF CHEMICAL AND ENGINEERING DATA
·
2022
·
IF 3.119
Tao Zhang,Liwei Zhuang,Dan Li,Lingzong Meng,Tianlong Deng,Yafei Guo,Yong Ma
The solubilities of salts, refractive indices, and pH values of the equilibrium liquid phases in the quaternary system LiCl–LiBO2–Li2B4O7–H2O at 323.15 K were investigated by the isothermal dissolution method for the first time. The dry-salt diagram of the quaternary system consisted of one invariant point, three univariant curves and three crystallization fields corresponding to LiCl·H2O, LiBO2·2H2O, and Li2B4O7·3H2O. The solution refractive indices and pH values change regularly with the changing of concentration. Combining the equilibrium constants for different boron species, the distributions of six boron species in the mixed solution in the systems LiCl–LiBO2–H2O, LiBO2–Li2B4O7–H2O, and LiCl–Li2B4O7–LiBO2–H2O were calculated with the total boron concentration and pH values. The main boron species in the mixed solution of the quaternary system are B3O3(OH)4–, B4O5(OH)42–, B(OH)3, and B5O6(OH)4–. The boron species distributions are mainly affected by the pH values and the concentration of total boron and LiCl in the solution. The results of phase diagram and boron species distribution in the quaternary system can supply foundation data for separating lithium borate from brines.
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CANCER LETTERS
·
2022
·
IF 9.756
Ying Zhou,Li Guan,Wei Li,Ruinan Jia,Lejiao Jia,Yuanyuan Zhang,Xin Wen,Sibo Meng,Daoxin Ma,Na Zhang,Min Ji,Yongjun Liu,Chunyan Ji
T-cell acute lymphoblastic leukemia (T-ALL) is a serious hematologic malignancy and glucocorticoid resistance is the main recurrent cause for a high relapsed and death rate. Here, we proposed an effective therapeutic regimen of combining gamma-secretase inhibitors (GSIs) with dexamethasone (DEX) to overcome glucocorticoid resistance. Moreover, the bone marrow targeting DT7 peptide-modified lecithin nanoparticles co-loaded with DEX and GSI (TLnp/D&G) were developed to enhance T-ALL cells recognition and endocytosis. In vitro cytotoxicity studies showed that TLnp/D&G significantly inhibited cell survival and promoted apoptosis of T-ALL cells. Mechanically, we found that GSIs promoted DEX-induced cell apoptosis by two main synergetic mechanisms: 1) GSIs significantly upregulated glucocorticoid receptor (GR) expression in T-ALL and restored the glucocorticoid-induced pro-apoptotic response. 2) Both DEX and GSI synergistically inhibited BCL2 and suppressed the survival of T-ALL cells. Furthermore, in vivo studies demonstrated that TLnp/D&G showed high bone marrow accumulation and better antileukemic efficacy both in leukemia bearing models and in systemic Notch1-induced T-ALL models, with excellent biosafety and reduced gastrointestinal toxicity. Overall, our study provides new strategies for the treatment of T-ALL and promising bone marrow targeting systems with high transformation potential.
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ENVIRONMENTAL POLLUTION
·
2019
·
IF 5.714
Lulu Lv,Junhao Qu,Zihua Yu,Daihuan Chen,Chunxia Zhou,Pengzhi Hong,Shengli Sun,Chengyong Li
Microplastics (particle size <5 mm) are an emerging contaminant for aquatic environmental, which have attracted increasing attention in worldwide range. In this study, an improved fluorescent staining method for detection and quantification of microplastics was developed based on thermal expansion and contraction. This method is effective in detection of polyethylene, polystyrene , polyvinyl chloride and polyethylene terephthalate plastic particles. In order to avoid error statistics caused by pretreatment , various characterizations of microplastics were measured after heated, such as microstructure, compositions and thermostability. The results showed that there was no significant damage to microplastics even under heating condition at 75 °C for 30 min, and the stained microplastics had strong stability for up to two months. Moreover, this method has been successfully applied to the quantification of microplastics in biological samples and result showed there were about 54 particles g −1 (dry weight) microplastics in the Sipunculus nudus. This new method provides a reliable method for quantitative analysis of microplastics in environment and biological tissue.
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JOURNAL OF CHEMICAL AND ENGINEERING DATA
·
2020
·
IF 2.369
Yajun Li,Xiaofang Li,Kui Wu
In this work, the solubility of N,N-dibenzylhydroxylamine (DBHA) in 17 pure solvents, including methanol, ethanol, n-propanol, n-butanol, acetone, ethyl acetate, dichloromethane, acetonitrile, isopropanol, n-octanol, cyclohexanone, 1,2-dichlorobenzene, toluene, isobutanol, n-pentanol, 1,2,4-trichlorobenzene, and tetrahydrofuran, was determined by a static gravimetric method with the temperature ranging from 273.15 to 323.35 K under atmospheric pressure. The solubility of DBHA was positively related to temperature in all selected solvents. Besides, the experimental solubility data were correlated with four thermodynamic models, i.e., the modified Apelblat equation, λh equation, nonrandom two-liquid (NRTL) equation, and the Wilson equation. The results indicated that all of the models could give satisfactory results and the NRTL equation provided the best fitting result. Furthermore, the dissolution thermodynamic parameters in the used solvents, including the Gibbs energy (ΔdisG), molar enthalpy (ΔdisH), and molar entropy (ΔdisS), were calculated according to the Wilson model, and it turned out that the dissolution process of DBHA was endothermic.
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Journal of Immunotoxicology
·
2019
·
IF 1.734
Penghuan Chang,Ling Huang,Mianqing Huang,Shuhong Tian,Zhaoxin Yang
Although T-cell-dependent antibody response (TDAR) assays with keyhole limpet hemocyanin (KLH) as specific antigen have many advantages, most experiments produce qualitative results based on antibody titers. It was hypothesized that if experimental conditions (like antigen coating concentration, serum dilution, and detecting [here, horseradish peroxidase-goat anti-mouse IgG] antibody dilution) could be optimized, the resulting measured value (here, optical density) could be used to directly analyze and evaluate the experimental results. This means specifically that the assay OD values could be used for approximate quantitative statistical analysis; it does not require a further conversion of the data into qualitative forms or require obtaining further titer data from additional experiments. As such, the use of this “improved” assay would: greatly reduce the complexity of experimental operations; improve overall sensitivity and practicality of traditional TDAR assays; and, allow for direct assessing of any immunosuppression caused by a test drug in a host. Here, KLH-immunized serum was obtained from BALB/c mice, and the means to detect serum anti-KLH antibodies by an indirect ELISA were optimized. The results indicated that in this system, the optimal KLH coating concentration was 80 μg/ml, the optimal dilution range of the serum (at immunization dose of 5 mg KLH/kg) was 1:200–1:800, and the optimal dilution of HRP-goat anti-mouse IgG antibody was 1:16,000. Methodology verification was performed and a regression model of y = 144.16x + 0.9815 (R2 = 0.9571, indicating very good linearity) was obtained. Intragroup precision was 7.51–9.40%; the intergroup coefficient of variation was 9.83–14.22%. The lower limit of detection was 0.1385. The present results showed this indirect ELISA exhibited very good linearity, accuracy, and precision.
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JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2018
·
IF 3.412
Fuqiang Liang,Yajing Fang,Weiwei Cao,Zhuo Zhang,Siyi Pan,Xiaoyun Xu
The current study evaluates the protective effects of tangeretin, a representative polymethoxyflavone (PMF) mainly isolated from the peels of citrus fruits, against tert-butyl hydroperoxide (t-BHP)-induced oxidative damage in HepG2 cells and the potential mechanisms of this protection. Tangeretin suppressed t-BHP-induced oxidative damage, as evaluated by cell viability, reactive-oxygen-species (ROS) levels, lactate dehydrogenase (LDH) leakage and glutathione (GSH) levels. Further mechanistic studies showed that tangeretin up-regulated the expression of heme oxygenase 1 (HO-1) and NAD(P)H quinone oxidoreductase 1 (NQO1). Moreover, tangeretin induced antioxidant-responsive-element (ARE)-dependent luciferase activation, nuclear factor (erythroid-derived 2)-like 2 (Nrf2) nuclear translocation, and mitogen-activated-protein-kinase (MAPK) phosphorylation. Results in the study indicate that the protective effects of tangeretin may be at least partly due to its capacity to up-regulate the antioxidant enzymes NQO1 and HO-1 via the MAPK–Nrf2–ARE signaling pathway. Tangeretin may play an effective protective role in liver injury.
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JOURNAL OF MOLECULAR LIQUIDS
·
2016
·
IF 2.74
Dongren Cai,Jinbei Yang,Hairong Da,Ling Li,Hongxing Wang,Ting Qiu
Densities, ρ and viscosities, η of N , N -dimethyl-N-(3-sulfopropyl)cyclohexylammo-nium tosylate ([CyN 1,1 PrSO 3 H][Tos]) with water and methanol were measured, at temperatures from 303.15 K to 328.15 K with 5 K interval and 0.1013 MPa, as a function of [CyN 1,1 PrSO 3 H][Tos] molality (or mass fraction). The isobaric thermal expansion coefficient , molecular volume, standard molar entropy, and lattice energy of the pure IL were obtained based on the density data of pure IL . The apparent molar volume , V φ , infinite dilution apparent molar expansibility, E φ ∞ and energy barrier, E were calculated from the experimental data. The Redlich-Mayer equation was used to evaluate infinite dilution apparent molar volume , V φ ∞ . In addition, viscosities can be described satisfactorily by Vogel-Fulcher-Tammann (VFT) equation. The V φ ∞ values of the IL in water are higher than those in methanol, which suggests that the ion-solvent interactions for [CyN 1,1 PrSO 3 H][Tos] + water binary system are stronger than those for [CyN 1,1 PrSO 3 H][Tos] + methanol. And the energy barrier values decrease with the drop of IL mass fraction in both systems, indicating that the viscosity changes of binary mixtures are more sensitive to the temperature at high composition of the IL.
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BIOCHEMICAL ENGINEERING JOURNAL
·
2017
·
IF 2.892
Ya-Jun Wang,Xiao-Peng Chen,Wei Shen,Zhi-Qiang Liu,Yu-Guo Zheng
In our previous work, we constructed a carbonyl reductase (CR) and glucose dehydrogenase (GDH) co-expression strain E. coli BL21(DE3)/pCDFDuet- gdh - cr , and a biocatalytic process of chiral diol t -butyl 6-cyano-(3 R ,5 R )-dihydroxyhexanoate ((3 R ,5 R )- 2 ) was established by using its free cells. Herein, a (3 R ,5 R )- 2 process with celite-polyethyleneimine (PEI)-glutaraldehyde (GA) immobilized E. coli BL21(DE3)/pCDFDuet- gdh - cr whole cells was developed for the first time. It was demonstrated that immobilization via cross-linking was preferred, and the optimized immobilization conditions were as follows: 0.6% (w/v) celite, 4% (w/v) PEI and 1% (w/v) GA, pH7. The immobilizate can be used at pH 7.0, 30 °C for intermittent 7 batch, yielding a total of 17.5 g (3 R ,5 R )- 2 per gram of celite-PEI-GAimmobilizates in de p (diastereomeric excess) >99.5%. Compared with the free cells, there was a dramatic improvement in celite- PEI-GA immobilizate stability and recyclability. In this way, a promising platform technology based on a combination of cells immobilization and multiple enzymes co-expression is constructed, enabling efficiently converting inexpensive prochiral ketones to high-valued chiral alcohols.
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FOOD CONTROL
·
2024
·
IF 5.6
Lidong Pang,Qunchao Su,Jingqi Cheng,Biqi Liu,Chaoxin Man,Ling Guo,Xinyan Yang,Qianyu Zhao,Yujun Jiang
The development of a simple, rapid, sensitive, and accurate method for detecting Escherichia coli O157:H7 in complex matrices is critical for ensuring food safety. In this study, a fluorescent biosensor employing aptamer (Apt) -functionalized magnetic beads and cascade strand displacement amplification (SDA) was devised for the detection of E. coli O157:H7 in milk samples. E. coli O157:H7 is captured by the aptamer, causing the complementary DNA (cDNA) to not bind to the aptamer and to be released into the supernatant. Following magnetic separation, the cDNA present in the supernatant initiates the opening of the hairpin (HP) structures. This enables primers to attach to the opened HP, triggering the initial SDA process, which generates a substantial quantity of double-stranded DNA (dsDNA) and recycles cDNA to open more HP structures. The dsDNA activates a second SDA, producing single-stranded DNA (ssDNA) for template binding and instigating a third SDA process. Triple SDA leads to the production of numerous G-quadruplex sequences and the formation of a G-quadruplex structure in the presence of K + . The inclusion of ThT into the G-quadruplex significantly enhances fluorescence. Under optimal conditions, this approach can detect E. coli O157:H7 at levels as low as 10 1 CFU/mL in pure cultures within 2.5 h, with a broad linear detection range of 10 1 –10 6 CFU/mL. This method exhibits remarkable specificity towards the target bacteria over non-target bacteria. Furthermore, the technique has been effectively utilized for the detection of E. coli O157:H7 in milk samples. Notably, the method involves only two main steps, identification and amplification, significantly reducing contamination risks and minimizing operational steps.
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ADVANCED MATERIALS
·
2025
·
IF 26.8
Yinghao Ding,Xueying Zhu,Jian Wen,Junchao Xiong,Shengyi Zhang,Zhimou Yang,Zhi-Wen Hu
Antigen presentation deficiency restricted by class I major histocompatibility complex (MHC-I) causes low antigenicity and antigen escape in tumors, thereby limiting T-cell immunotherapy outcomes. Here, a combined tumor immunotherapy is developed, in which tumors can present exogenous non-tumor antigens, and adoptively transferred CD8 + T cells specific for these antigens are re-targeted to attack tumors. The approach leverages a cascade-responsive peptide self-assembly to co-deliver suitable antigens and the chemotherapeutic drug camptothecin (CPT) to tumors. As a proof-of-concept, to re-target ovalbumin (OVA)-specific OT-I CD8 + T cells against tumors, PSA (Nap-GFFpYE-ss-Ag) and CPSA (CPT-GFFpYE-ss-Ag) are constructed, containing an OVA-derived epitope OVA 257-264 and/or CPT. The design enables the release of a unique N-terminal extended OVA 257-264 and CPT into the cytosol. As a result, the extended antigen is efficiently presented on the tumor surface by MHC-I, and CPT further enhances this presentation. When combined with adoptively transferred OT-I CD8 + T cells, the approach effectively facilitates CD8 + T cell infiltration and tumor inhibition. Additionally, CPSA treatment sensitizes immune responses to programmed cell death-ligand 1 (PD-L1) blockade, allowing the approach to synergize with an anti-PD-L1 antibody for improved tumor eradication.
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