EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
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2025
·
IF 5.9
Kan Li,Shengbin Gui,Ningning Wang,Xiao Li,Chunqin Zhao,Mingyu Liu,Zhen Zhang
Intravenously administered nanoparticles (NPs) often bind with plasma proteins, forming protein corona that prompt rapid systemic clearance, a primary challenge in nanomedicine. In this study, we developed a pH- and GSH-sensitive “stealth” nanodelivery system, PTX@NPs-aPD1-IL, for sequential drug release. By using a biocompatible choline-based ionic liquid (IL) as the coating for NPs, the interaction and adsorption of NPs with serum proteins were reduced, achieving targeted delivery to the lung organ and increasing drug accumulation. In the weakly acidic extracellular tumor microenvironment (pH 6.5), the anti-PD-1 antibody (aPD-1) was first released to block the PD-1/PD-L1 pathway and restore the immunocidal function of T cells. In the highly reductive intracellular environment of tumor cells, the disulfide bonds were cleaved, causing NPs to rupture and release paclitaxel (PTX). It induced tumor cell apoptosis and triggered immunogenic cell death (ICD), promoted dendritic cells (DCs) maturation and activated T cells for chemo-immunotherapy. In the mouse orthotopic lung cancer model, PTX@NPs-aPD1-IL exhibited superior efficacy to other treatment groups at the same dose. This was due to the significantly increase in the release of immune factors, including TNF-α and IFN-γ, and the promotion of CD8 + T cells recruitment, which induced a stronger immune response, and thus enhanced the anti-lung cancer effect. In summary, PTX@NPs-aPD1-IL provided a promising strategy for effective chemo-immunotherapy for lung cancer through sequential release profile.
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JOURNAL OF CHEMICAL AND ENGINEERING DATA
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2025
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IF 2.1
Shengchao Xu,Wanting Ma,Qifeng Wei,Xiulian Ren
Long-chain 1-alkanols and N-dodecyl-2-pyrrolidone (NDP) exhibit significant potential in the field of solvent extraction. Investigating their physicochemical properties is valuable for understanding mass transfer, heat transfer, and the fluid transport process. In this study, we investigated the effect of the alkyl chain length of 1-alkanols (C4/C6/C8/C10) on NDP organic liquid mixtures. The densities and viscosities were measured at temperatures ranging from 303.15 to 323.15 K and atmospheric pressure. Excess properties, including excess molar volume (VmE), viscosity deviation (Δη), and the excess Gibbs free energy of activation of viscous flow (ΔG*E), were calculated and correlated by Redlich–Kister equation to identify the differences between real and ideal solutions. It was found that the steric hindrance increased with the alkyl chain length increasing from C4 to C10 for 1-alkanols, leading to weaker molecular interactions in the mixtures. Furthermore, the Fourier transform infrared spectroscopy (FT-IR) and UV–vis spectra confirmed the presence of intermolecular hydrogen bond interactions between the −OH group of 1-alkanols and the –C═O group of NDP. Finally, the conductor-like screening model for realistic solvation (COSMO-RS) and Gaussian spectra further proved the hydrogen bond interactions. Overall, this study reported a range of physicochemical properties from both experimental and theoretical perspectives, which can be used to guide industrial production.
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Food and Bioprocess Technology
·
2024
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IF 5.3
Cao Zhaoxin,Su Jingyi,Luo Yali,Wang Xinyu,Liu Zhiming,Chen Yanqi,Zou Yijing,Shen Wen,Ge Xuemei
Carvacrol essential oil has broad-spectrum antibacterial properties, but the essential oil is volatile and unstable for long-term storage and use. In order to improve the relevant properties of carvacrol, in the present study, carvacrol was encapsulated with β-cyclodextrin (β-CD) using the saturated aqueous solution method, and response surface analysis was carried out, which gave a high encapsulation rate (63.58 ± 3.74%). The success encapsulation of carvacrol was confirmed by scanning electron microscopy (SEM), Fourier infrared spectroscopy (FTIR), X-ray diffraction (XRD), and thermogravimetric analysis (TGA). The release performance of the encapsulants was also tested at different temperature and humidity levels. In addition, polyethylene glycol (PEG) composite carvacrol-inclusive preservation paper prepared by these anhydrous conditions showed high antibacterial activity against Streptomyces fructus Monilinia fructicola , the main pathogen of peaches. Also, PEG was used to form the film in the anhydrous condition with the inclusion compound and ethylene inhibitor 1-methylcyclopropene (1-MCP) to obtain the film coated paper, and its effect on postharvest preservation quality of peach was studied. The results showed that PEG + Carvacrol-β-CD + 1-MCP-α-CD inclusion complexes (ICs) effectively prolonged the storage time and improved the fruit quality and enzyme activity of peach. This study provides a solution for the preparation of controlled-release coated paper with essential oils and 1-MCP bioactives to extend the shelf life of fruits and vegetables. Graphical Abstract
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JOURNAL OF THE EUROPEAN CERAMIC SOCIETY
·
2024
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IF 5.8
Bei Ren,Ziqian Meng,Bixian Zhang,Sihao Jian,Chufei Cheng,Jiadong Hou,Ruixin Hao,Bo Li,Yang Miao,Chao Ma,Weihua Ji
High-entropy fluorite oxide ceramics are promising candidates for spacecraft applications due to their excellent high-temperature thermal-mechanical properties. In this work, four kinds of high-entropy fluorite oxide ceramics ((ZrHfCeYEr) (1-x)/5 Ti x )O 2-δ (HEFOs, x = 0, 0.025, 0.05, 0.075) with different Ti 4+ contents were successfully synthesized through solid-state reaction method with conventional sintering. They all exhibited phase stability when annealed at 1500 ℃ for 20 h. When the content of Ti 4+ was increased to x = 0.075, the thermal conductivity reduced to1.34 W·m −1 ·K −1 at 1100 ℃, and the hardness and elastic modulus increased to 14.01 GPa and 205.70 GPa, respectively. Furthermore, the cyclic thermal shock resistance of HEFOs at different temperatures was investigated. The initial flexural strength reached 219.03 MPa when the content of Ti 4+ was increased to x = 0.075. After 60 thermal shock cycles at 1200 ℃ and 1500 ℃, the residual strength ratios were 97.56 % and 83.36 %, respectively. The results of this study establish the foundation for future applications of high-entropy fluorite oxide ceramics in spacecraft hot-end components.
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World Journal of Stem Cells
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2025
·Vol. 17
·期 7
·104607
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IF 3.6
Kun Wang,Wei Lin,Jun-Yong Han,Jin-Yan Chen,Rong-Hua Liu,Zhen Yu,Jing-Jun Jin
BACKGROUND Type 1 diabetes (T1D) results from the autoimmune-mediated loss of pancreatic β-cells. Current insulin therapies offer symptomatic relief but fall short of providing a definitive cure. Islet cell transplantation, while promising, faces limitations related to donor scarcity, procedural complexities, and the necessity for long-term immunosuppression. Consequently, there is an urgent need for innovative strategies aimed at β-cell regeneration. Patient-derived induced pluripotent stem cells (iPSCs), obtained from peripheral blood mononuclear cells (PBMCs) of T1D patients, hold great potential as a source of cells for therapeutic purposes. Therefore, the differentiation of T1D-iPSCs into functional pancreatic β-cells is a critical step toward effective β-cell replacement therapy. AIM To assess the potential of patient-derived T1D-β-like cells (differentiated from T1D-iPSCs reprogrammed from T1D-PBMCs) for restoring β-cell function in T1D. METHODS T1D-iPSCs were reprogrammed from T1D-PBMCs using an episomal vector-based approach. Pluripotency was confirmed by flow cytometry (FCM), quantitative real-time polymerase chain reaction, genomic stability analysis, and teratoma formation assays. Differentiation into pancreatic β-cells was optimized using triiodothyronine (T3), vitamin C (Vc), and an adenovirus (M3C) encoding pancreatic duodenal homeobox-1, neurogenin 3 ( Ngn3 ), and MAF bZIP transcription factor A ( MafA ). Following characterization of β-cell features by immunofluorescence, quantitative real-time polymerase chain reaction, and flow cytometry, therapeutic efficacy was assessed through blood glucose monitoring after transplantation under the renal capsule of streptozotocin-induced diabetic mice. RESULTS T1D-iPSCs were successfully generated from T1D-PBMCs. These cells exhibited the hallmark characteristics of pluripotent stem cells, including appropriate morphology, differentiation potential, genomic integrity, and expression of pluripotency-associated genes. Differentiation yielded insulin-positive (insulin + ) pancreatic β-like cells that, at the mRNA level, expressed key β-cell markers such as pancreatic duodenal homeobox-1, Ngn3 , MafA , NeuroD , glucagon-like peptide-1 receptor, Nkx6.1 , glucose transporter 2, and Kir6.2 . Notably, the T3 + Vc group displayed the lowest Ngn3 expression (1.31 ± 0.38 vs 1.96 ± 0.25 vs 2.51 ± 0.24, P < 0.01), while the M3C + T3 + Vc group exhibited the highest MafA expression (0.49 ± 0.11 vs 0.32 ± 0.06 vs 0.29 ± 0.08, P < 0.05). Both in vitro and in vivo assessments confirmed the insulin secretion ability of the generated β-like cells; however, they did not demonstrate appropriate modulation of insulin release in response to variations in extracellular glucose concentrations. CONCLUSION T1D-iPSCs derived from T1D-PBMCs can be differentiated into insulin + β-like cells, albeit with functional immaturity. These cells represent a potential source of seed cells for β-cell replacement therapy in T1D.
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Experimental Hematology & Oncology
·
2025
·Vol. 14
·期 1
·1-17
·
IF 13.5
Ren Xueting,Wu Jinpeng,Li Jing,Zhai Zhen,Li Xiang,Guan Feng,Wang Meng,Ma Xiaobin,Tan Zengqi,Kang Huafeng,Lin Shuai
Background The abundance of PD-L1 on the surface of tumor cells is a critical factor in sensitizing these cells to T cell-mediated immune killing. While abnormal glycosylation of PD-L1 is known to influence its expression and function, the precise regulatory mechanisms remain unclear.Methods This study utilized bioinformatics analysis to explore the role of MGAT3, a key gene involved in the formation of the bisecting GlcNAc structure, in breast cancer (BC). Experimental approaches were employed to increase bisecting GlcNAc levels in BC cells, followed by assessments of PD-L1 expression, CD8+ T cell-mediated cytotoxicity, extracellular vesicle (EV)-associated PD-L1, and PD-L1/PD-1 interaction. Additionally, forskolin, a bisecting GlcNAc agonist, was combined with anti-PD-L1 antibody to evaluate its antitumor effects in vivo.Results MGAT3 was found to be expressed at low levels in BC tissues but positively correlated with CD8+ T cell infiltration. Elevating bisecting GlcNAc levels in BC cells significantly enhanced the cytotoxic efficacy of CD8+ T cells. High bisecting GlcNAc modification promoted PD-L1 degradation via the lysosomal pathway, reducing PD-L1 expression and its binding to PD-1. Furthermore, increased bisecting GlcNAc levels reduced PD-L1 in tumor cell-derived EVs, impairing the EVs’ ability to block CD8+ T cells and indirectly enhancing T cell cytotoxicity. The combined use of forskolin and anti-PD-L1 antibody significantly increased CD8+ T cell abundance and activity, achieving a more effective antitumor response in vivo.Conclusion sThese findings demonstrate that enhancing bisecting GlcNAc modification in BC cells promotes PD-L1 degradation and inhibits its binding to PD-1, thereby boosting CD8+ T cell-mediated cytotoxicity, providing a promising strategy for immune modulation in BC therapy.
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CHEMICO-BIOLOGICAL INTERACTIONS
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2025
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IF 5.4
Xiangyun Tan,Yuan Yang,Junjie Hu,Yan Meng,Liang Chen,Guohua Zheng,Han Xiao,Zhenpeng Qiu
Intrahepatic cholangiocarcinoma (iCCA) is a malignant liver tumor with insidious onset, limited treatments, and poor prognosis. Recent studies show celecoxib exerts marked cytotoxic effects on cholangiocarcinoma cell lines, suggesting its potential as an iCCA therapy. However, the potential molecular and cellular mechanisms that link celecoxib treatment to its toxicological outcomes remain unclear. In this study, we induced iCCA in mice by overexpressing AKT and YapS127A (hereafter referred to as AKT/YapS127A) and administered celecoxib continuously to evaluate its antitumor effects in vivo . The results demonstrate that celecoxib effectively inhibited tumor growth in AKT/YapS127A-driven iCCA mice. Mechanistically, celecoxib boosted levels of cell cycle inhibitors p21 Waf1/Cip1 and p27 Kip1 , leading to cell cycle arrest. It also promoted apoptosis by downregulating the expression of anti-apoptotic proteins Mcl-1 and Bcl-2. These effects were associated with the modulation of the AKT/mTORC1 signaling pathway. Consistently, celecoxib recapitulated AKT/mTORC1 inhibition and subsequent cell cycle/apoptotic regulator alterations in iCCA cell lines. Collectively, our study elucidates the molecular mechanisms through which celecoxib exerts its anti-tumor effects in iCCA, demonstrating its capacity to induce cytotoxic outcomes via the precise regulation of the AKT/mTORC1 pathway. These findings deepen understanding of the toxicological actions of celecoxib and provide critical insights for developing targeted iCCA therapies.
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FOOD CHEMISTRY
·
2025
·
IF 9.8
Mengting Yu,Chengdeng Chi,Shuangxia Huang,Xiaoxi Li
This study presented a novel strategy to regulate postprandial glucose levels by engineering colon-targeted nanoparticles with tailored lecithin distribution for enhancing Glucagon-like peptide-1 (GLP-1) secretion. GLP-1 plays a pivotal role in regulating postprandial glucose homeostasis. Firstly, type I starch-lecithin complex (OSL) was fabricated with excellent digestion resistance (47.89 % resistant starch) and self-assembly performance (0.58 mg/mL CMC). Lecithin solutions were then incorporated into OSL to form OSL/lecithin nanoparticles (180–200 nm, negatively charged surface) with different distribution ratios of lecithin inside and outside starch helical cavity. With distribution ratio of lecithin increased from 1:1.25 to 1:10, β-lactoglobulin colon release improved by 21.67 %. Microbial fermentation led OSL/Lecithin based nanoparticles to release β-lactoglobulin, lecithin, reducing sugars, and SCFAs, which collectively boosted GLP-1 secretion by 169.48 % and 36.07 % compared with β-lactoglobulin and mixed OSL/Lecithin, respectively. This research offered a new strategy for targeted delivery of bioactive molecules to modulate GLP-1 secretion.
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ACS Applied Polymer Materials
·
2024
·
IF 4.4
Shuai Han,Junjian Yu,Fei Wang,Xiangwei Li,Hongzhe Ni,Yuchao Wang,Zhe Wang
Zeolite is a commonly utilized filler in mixed matrix membranes (MMMs) to enhance the effectiveness of gas separation due to its molecular sieving properties with high separation coefficients. However, the compatibility and suitability between the zeolite and the polymer membrane are prerequisites for preparing homogeneous membranes and an essential factor affecting gas separation performance. Herein, we synthesized nucleus-crown-crown structures by surface modification of SOD zeolite and prepared MMMs by doping them into Polymers of Intrinsic Microporosity (PIM-1) for efficient gas separation. FTIR, XRD, SEM, and TGA characterized the fillers and the MMMs. The average particle size of the filler was estimated to be approximately 552.43 nm by SEM images. The surface-modified SOD zeolite facilitates the rapid permeation of specific gas molecules and enhances the dispersion of SOD zeolite in the PIM-1 membrane, thereby improving gas separation performance. Compared with pure PIM-1 membrane, the MMMs with a loading of 7 wt % exhibited CO2 and H2 permeabilities reaching up to 7000.0 and 3600.0 Barrer; their selectivities for CO2/N2 and H2/N2 were measured at 17.7 and 9.29, respectively. MMMs with the best fill ratios exceeded the 2008 Robeson upper limits. The methods for surface modification of SOD zeolites provide a new way for the application of SOD zeolite in the area of gas separation.
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CHINESE JOURNAL OF CHEMICAL ENGINEERING
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2024
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IF 3.7
Bharat Prasad Sharma,Tianzhang Wang,Yufeng Liang,Jinping Xiong,Liangrong Yang,Zheng Li
Simultaneous recovery of Ni and Co from Fe(III) and Al is a critical challenge in hydrometallurgical processes. Recognized solvent extraction systems often struggle with selectivity and effective performance in mixed metal ion environments. Herein, a new synergistic solvent extraction (SSX) system comprised of a novel pyridine analog, N,N -bis(pyridin-2-ylmethyl) dodecan-1-amine (BPMDA), and dinonylnaphthalene sulfonic acid (DNNSA) with tributyl phosphate as phase modifier is introduced. The SSX system demonstrates high extraction performance achieving >90% for Ni and >97% for Co in a single-stage extraction process, with high selectivity. Under optimal conditions, the selectivity sequence is observed as Co 2+ (>97%) > Ni 2+ (>90%) > Mn 2+ (<20%) > Fe 3+ (<10%) > Mg 2+ (<5%) > Al 3+ (<2%) > Ca 2+ (<1%). Spectroscopic analysis evidences the preferential binding of BPMDA with Ni and Co in the presence of DNNSA, concurrently achieving a significant reduction in the co-extraction of Fe(III) and Al. The selective complexation of Ni and Co using the SSX system offers a highly efficient and selective approach for their extraction, with promising potential for applications in recovery-based processes.
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CELL RESEARCH
·
2023
·Vol. 33
·期 12
·923-939
·
IF 44.1
Liu Rui,Zeng Lin-Wen,Li Hui-Fang,Shi Jun-Ge,Zhong Bo,Shu Hong-Bing,Li Shu
Combination therapy with PD-1 blockade and IL-2 substantially improves anti-tumor efficacy comparing to monotherapy. The underlying mechanisms responsible for the synergistic effects of the combination therapy remain enigmatic. Here we show that PD-1 ligation results in BATF-dependent transcriptional induction of the membrane-associated E3 ubiquitin ligase MARCH5, which mediates K27-linked polyubiquitination and lysosomal degradation of the common cytokine receptor γ chain (γ c ). PD-1 ligation also activates SHP2, which dephosphorylates γ c Y357 , leading to impairment of γ c family cytokine-triggered signaling. Conversely, PD-1 blockade restores γ c level and activity, thereby sensitizing CD8 + T cells to IL-2. We also identified Pitavastatin Calcium as an inhibitor of MARCH5, which combined with PD-1 blockade and IL-2 significantly improves the efficacy of anti-tumor immunotherapy in mice. Our findings uncover the mechanisms by which PD-1 signaling antagonizes γ c family cytokine-triggered immune activation and demonstrate that the underlying mechanisms can be exploited for increased efficacy of combination immunotherapy of cancer.
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APPLIED CATALYSIS B-ENVIRONMENTAL
·
2025
·
IF 21.1
Baozhen Li,Jun Zuo,Tiantian Liu,Mengjia Zhu,Kun Jiang,Zhuangzhuang Ren,Hua Yang,Yu Tang,Li Tan,Lizhi Wu
The mildly selective oxidation of methane to oxygenates in the aqueous phase is of great significance for methane upgrade, while it suffers low conversion and multiple oxidation products. Fe-based zeolite, especially Fe/ZSM-5 with heteroatom Al is the most widely investigated catalyst for this reaction, while the Fe supported pure Si-based zeolite without Al is rarely reported. Herein, a series of Fe-S-1 catalysts without introducing heteroatom Al is synthesized via facial dissolution-crystallization method and applied for methane selective oxidation to formic acid. The optimized 0.5Fe-S-1 shows a superior performance with the formic acid space time yield of 49751 µmol·g cat −1 ·h −1 and a liquid-phase formic acid selectivity of 93 % at 70 °C with H 2 O 2 as the oxidant, and present an excellent stability without obvious deactivation after five cycles, which outperforms all previously reported Al-free Fe/Silicalite-1 catalysts, and is comparable with conventional Fe/ZSM-5. Combined with multifarious characterizations including TEM, UV-Vis, Raman, NH 3 -TPD, Py-IR and XAS etc., two kinds of Fe species including the mononuclear tetrahedrally coordinated framework Fe 3+ species and mononuclear octahedral coordinated extra-framework Fe 3+ species are highly dispersed over Fe-S-1 even with a high Fe loading of 1.5 wt%, in which the framework Fe 3+ species content is positively correlated with the catalyst acidity and could provide acid sites to adsorb reactants and then extra-framework Fe 3+ species could activate methane/H 2 O 2 effectively. And the further EPR, in-situ FT-IR characterizations and control experiments demonstrates that the methane selective oxidation to formic acid follows a radical mechanism, in which ·CH 3 combines with ·OH or ·OOH to form CH 3 OH, and then further oxidized to HCOOH and finally over-oxidized to CO 2 .
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危险品化学品经营许可证（带存储）