Materials Today Bio
·
2025
·
IF 10.2
Yeyang Sun,Xietao Ye,Lin Yang,Shuo Dong,Chen Chen,Yani Wang,Jianan Qiao,Congyan Liu,Yuping Liu,Yan Chen
Programmed cell death protein 1 (PD-1) inhibitors are integral to contemporary cancer immunotherapy. However, their objective response rate in microsatellite-stable colorectal cancer (MSS CRC) remains below 5 %. This limited efficacy is primarily due to insufficient tumor-infiltrating lymphocytes (TILs), a consequence of the combined effects of low tumor immunogenicity and impaired dendritic cell (DC)-mediated antigen presentation. The combination of ursolic acid (Ua) and ginsenoside Rg3 (Rg3) enhances TIL infiltration by inducing immunogenic cell death (ICD) in tumor cells and promoting DC maturation. Due to their poor oral bioavailability, an oral ZIF nanoplatform was engineered with a chitosan oligosaccharide (Cos) and inulin (In) bilayer coating [(In/Cos)@Ua-Rg3-ZIF] for targeted delivery of Ua and Rg3 to the CRC microenvironment. Efficient dual-drug co-loading was achieved with a loading efficiency of 24.07 wt%. After oral administration, the (In/Cos) coating protects the formulation from degradation in the upper gastrointestinal tract, while specific enzymatic cleavage by colonic microbiota releases Ua-Rg3-ZIF into tumor tissues. The ZIF platform responds to elevated adenosine triphosphate (ATP) in the tumor microenvironment, enabling controlled release of Ua and Rg3 to enhance cytotoxic T lymphocyte (CTL) levels. In vivo studies demonstrate that combining (In/Cos)@Ua-Rg3-ZIF with α-PD-1 results in an 80.86 % tumor inhibition rate, significantly outperforming monotherapies. This strategy presents an innovative oral delivery system capable of resisting gastrointestinal degradation and facilitating microbiota-responsive drug release, effectively enhancing antitumor immunity and improving the therapeutic outcome of immunotherapy in MSS CRC.
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JOURNAL OF COLLOID AND INTERFACE SCIENCE
·
2023
·
IF 9.9
Xiushuai Guan,Xiaochao Zhang,Changming Zhang,Rui Li,Jianxin Liu,Yunfang Wang,Yawen Wang,Caimei Fan,Zhong Li
Photocatalysis CO 2 reduction into high-value-added chemical feedstocks is desirable for simultaneously addressing the solar energy storage, CO 2 excess and energy shortage issues. In this work, a kind of original S-scheme BiOBr-(0 0 1)/Bi 2 SiO 5 /Bi (OSB) heterostructure photocatalyst with rich oxygen vacancies is in-situ synthesized, which significantly promotes the photocatalytic CO 2 reduction performance. Interestingly, the lower formation energy of oxygen vacancy exhibits the easy feasibility on the BiOBr-(0 0 1) surface via the assistant of ultrasound. There exists the highest photocatalytic CO 2 reduction activity to CO of 234.05 μmol g -1 h −1 for OSB-20 sample (ultrasound time: 20 min), higher 3.3 times than OSB-0 sample (without ultrasound). Combined with experimental and calculated results, the significative formation mechanism, widened light-response range, highly-efficient separation/transfer paths and improved redox-reduction abilities of photogenerated electron-hole pairs for S-scheme OSB-20 heterostructure are investigated and proposed. Our findings provide new insights for the construction and synthesis of the S-scheme Bi-based heterojunction photocatalyst system.
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EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
·
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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BIOMEDICAL CHROMATOGRAPHY
·
2024
·Vol. 38
·期 8
·e5931
·
IF 1.8
Xu Ji,Liangxi Li,Kaiyue Zhang,Xinyi Yuan,Qian Li,Ge Bai
As a result of the lack of modern techniques, the study of Tibetan medicine has been hindered in identifying bioactive compounds. Herein, we established a chromatographic approach using an immobilized angiotensin II type 1 receptor (AT 1 R) via a one-step method triggered by haloalkane dehalogenase. The bioactive compounds from Choerospondias axillaris (Guangzao) were screened and identified using the immobilized AT 1 R followed by MS. Frontal analysis (FA) and adsorption energy distribution (AED) were used to evaluate the association constants. Molecular docking was used to investigate the binding configurations, and the surface efficiency index, binding efficiency index, and ligand-lipophilicity efficiency (LLE) were calculated to assess the drug-like properties. The results identified naringenin, pinocembrin, and chrysin as the compounds that specifically bind to AT 1 R in Guangzao. FA and AED confirmed that there is only one type of binding site between these compounds and AT 1 R. The association constants were (2.40 ± 0.02) × 10 4 M −1 for naringenin (5.22 ± 0.26) × 10 4 M −1 for pinocembrin, and (4.27 ± 0.14) × 10 4 M −1 for chrysin, respectively. These compounds can bind with AT 1 R through the orthosteric binding pocket. Naringenin exhibited better LLE than pinocembrin and chrysin. These results confirmed the feasibility of using the immobilized AT 1 R column for screening and analyzing bioactive compounds in Tibetan medicines.
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Food Science & Nutrition
·
2025
·Vol. 13
·期 3
·e70105
·
IF 3.8
Heting Zhou,Xinyue Zheng,Shaolin Huang,Xiaomeng Wang,Ting Zhou,Shuwen Zhang,Yihan Ling,Wenxi Wang,Xingjie Li,Shouqian Li,Yongmei Xie,Wenya Yin
Pulmonary fibrosis (PF) is a chronic and progressive lung disease, and oxidative stress plays a critical role in its pathogenesis. Rosa roxburghii Tratt, known for its anti-inflammatory and antioxidant properties, has been shown to alleviate fibrosis. This study aimed to explore whether two Rosa roxburghii fermentation broths (RRFBs) (with different proportions) could attenuate bleomycin (BLM)-induced PF in mice and to elucidate the molecular mechanisms. The results revealed that RRFBs reduced structural lung damage, collagen deposition, and lung inflammation. RRFBs also suppressed fibrotic markers (Collagen I, Vimentin, and α-SMA) while enhancing epithelial marker E-cadherin expression. Additionally, RRFBs alleviated BLM-induced oxidative stress and apoptosis by activating the Nrf2/HO-1/NQO1 signaling pathway and facilitating Nrf2 nuclear translocation. Furthermore, RRFBs attenuated the BLM-induced changes in the gut microbiota; in particular, they decreased the abundance of the pathogenic bacterium Proteus and increased the abundance of the probiotics Ileibacterium and Dubosiella . Spearman correlation analysis revealed a strong association between oxidative stress inhibition and gut microbiota composition. These results indicated that RRFBs could exert lung-protective effects by inhibiting oxidative stress and alleviating intestinal disturbances.
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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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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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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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CHEMICO-BIOLOGICAL INTERACTIONS
·
2025
·
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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Nano Research
·
2024
·Vol. 17
·期 7
·5786-5794
·
IF 9.5
Yang Chaoxin,Cai Zhengwei,Liang Jie,Dong Kai,Li Zixiao,Sun Hang,Sun Shengjun,Zheng Dongdong,Zhang Hui,Luo Yongsong,Yao Yongchao,Wang Yan,Ren Yuchun,Liu Qian,Li Luming,Chu Wei,Sun Xuping,Tang Bo
Seawater electrolysis, especially in coastlines, is widely considered as a sustainable way of making clean and high-purity H 2 from renewable energy; however, the practical viability is challenged severely by the limited anode durability resulting from side reactions of chlorine species. Herein, we report an effective Cl − blocking barrier of NiFe-layer double hydroxide (NiFe-LDH) to harmful chlorine chemistry during alkaline seawater oxidation (ASO), a pre-formed surface-derived NiFe-phosphate (Pi) outer-layer. Specifically, the PO 4 3− -enriched outer-layer is capable of physically and electrostatically inhibiting Cl − adsorption, which protects active Ni 3+ sites during ASO. The NiFe-LDH with the NiFe-Pi outer-layer (NiFe-LDH@NiFe-Pi) exhibits higher current densities ( j ) and lower overpotentials to afford 1 A·cm −2 ( η 1000 of 370 mV versus η 1000 of 420 mV) than the NiFe-LDH in 1 M KOH + seawater. Notably, the NiFe-LDH@NiFe-Pi also demonstrates longer-term electrochemical durability than NiFe-LDH, attaining 100-h duration at the j of 1 A·cm −2 . Additionally, the importance of surface-derived PO 4 3− -enriched outer-layer in protecting the active centers, γ-NiOOH, is explained by ex situ characterizations and in situ electrochemical spectroscopic studies.
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EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
·
2022
·Vol. 26
·期 2
·e202201275
·
IF 3.261
Cai-Yan Zhang,Ke Cao,Han-Bo Yang,Linhai Jiang,Bo Li,Junxiao Yang
The Cu(OTf) 2 /NBS promoted cyclization of 1-cinnamyl alcohol- o -carboranes for synthesis of o -carborane substituted oxetanes has been developed. A series of substituted oxetanes has been synthesized with moderate to good yields, which would be an important synthon for design novel reactions in oxetane chemistry as well as carborane chemistry. Graphical Cu(OTf) 2 /NBS promoted cyclization of 1-cinnamyl alcohol- o -carboranes offers a novel synthon of o -carborane substituted oxetane.
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APPLIED ORGANOMETALLIC CHEMISTRY
·
2013
·Vol. 27
·期 3
·148-154
·
IF 2.011
Li Qiang Wu
Nano n -propylsulfonated γ-Al 2 O 3 is easily prepared by the reaction of nano γ-Al 2 O 3 with 1,3-propanesultone. This reagent can be used as an efficient catalyst for the synthesis of spiro [indoline-3,4-pyrazolo[3,4- e ][1,4]thiazepine]diones in aqueous media. This new method consistently has the advantages of excellent yields and short reaction times. Further, the catalyst can be reused and recovered several times. Copyright © 2013 John Wiley & Sons, Ltd.
研究领域:
催化化学
·
有机合成
·
绿色化学
·
纳米材料
·
药物化学
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