AMERICAN JOURNAL OF PATHOLOGY
·
2025
·Vol. 195
·期 12
·2320-2335
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IF 3.6
Jing Li,Meixue Chen,Lingling Lu,Yinmiao Wang,Wei Wu,Yanhong Feng
Pediatric asthma is a respiratory disease in which M2 macrophages play a critical role. Here, the role and molecular mechanism of lysophosphatidic acid receptor 5 ( LPAR5 ) were investigated in pediatric asthma through in vivo and in vitro experiments. LPAR5 expression was increased in peripheral blood mononuclear cells from children with asthma. In an ovalbumin-induced neonatal asthmatic mouse model, LPAR5 antagonist alleviated airway inflammation by suppressing the release of inflammatory cytokines and inflammatory cell infiltration. Ovalbumin-induced M2 macrophage activation in neonatal mouse lung tissue was suppressed by LPAR5 antagonist, accompanied by decreased YM1 protein (encoded by chitinase 3 like 1) secretion. Differentiated THP-1 cells were stimulated with IL-4 to mimic M2 macrophages in vitro . M2 macrophage activation was reduced by both LPAR5 antagonist or LPAR5 knockdown. Furthermore, KLF transcription factor 5 ( KLF5 ) was significantly up-regulated and positively correlated with LPAR5 expression in peripheral blood mononuclear cells from children with asthma. KLF5 bound to the promoter of LPAR5 and transcriptionally promoted LPAR5 expression. LPAR5 overexpression increased M2 macrophage activation in KLF5-depleted THP-1 cells. The underlying mechanism of LPAR5 was investigated by phosphorylomics analysis, which identified mitogen-activated protein kinase kinase kinase 7 as a possible downstream effector. The results showed that LPAR5 antagonist attenuated airway inflammation in neonatal mice by decreasing M2 macrophage activation. KLF5 positively regulates the expression of LPAR5, which further increased the phosphorylation of mitogen-activated protein kinase kinase kinase 7 protein in macrophages. This article highlights that LPAR5 might serve as a potential target in pediatric asthma.
研究领域:
呼吸病学
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免疫学
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分子生物学
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儿科医学
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信号转导
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炎症性疾病
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转化医学
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MICROCHEMICAL JOURNAL
·
2025
·
IF 5.1
Ruimin Li,Yilin Gong,Shuibin Cen,Xueguo Song,Hua Xiang,Runkun Zhang
A novel dual-color method for glucose detection has been devised, leveraging the combination of 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium (ABTS 2− ) and acid violet 7, based on the catalytic properties of G-quadruplex DNAzymes. In the presence of K + , the oligonucleotide 5′-GTGGGTAGGGCGGGTTGG-3′ (PS2.M) forms a G-quadruplex structure. When bound to hemin, this structure mimics horseradish peroxidase (HRP) and catalyzes the oxidation of colorless ABTS 2− to green ABTS •− by H 2 O 2 . The H 2 O 2 is produced through the reaction between glucose and oxygen, catalyzed by glucose oxidase. By linking these two reactions, the oxidation of glucose can be translated into a color change in ABTS 2− . Under optimal conditions, the absorbance at 420 nm (A 420 nm ) is directly proportional to the glucose concentration within a range of 1.0 μM to 40.0 μM. The linear regression equation is A = 0.175 + 0.0334C (C: μM, R = 0.998), with a detection limit of 0.1 μM (3σ/slope). Furthermore, the introduction of acid violet 7 as a reference molecule enables the green color intensity change to be transduced into a color transition from red to gray and then to green, facilitating high-resolution semi-quantitative analysis of glucose by visual inspection. Importantly, our proposed method has been validated through its application to the detection of glucose concentrations in human serum, yielding promising results that underscore its potential for clinical diagnostics and research applications. Our findings represent a substantial advancement in the field of glucose detection and offer a promising alternative to existing methods.
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DALTON TRANSACTIONS
·
2020
·Vol. 49
·期 24
·8122-8135
·
IF 4.174
Jialin Yu,Qi Gao,Lijuan Zhang,Yunshan Zhou,Yuxu Zhong,Jianbo Yin,Yuanyuan Zhou,Fangsheng Tao,Yong'an Wang
ε-[Al13O4(OH)24(H2O)12]7+, which shares similarity with the phosphotriesterase active site ZnII–OH–ZnII, was specially chosen to interact with the cluster α-PMo10V2O405− to form a new three-dimensional intercluster, which crystallized in the monoclinic space group P21/m with Z = 2, for the decontamination of chemical warfare agents. The experimental results showed that 50 mg of the compound decontaminated 96.4% (within 120 min) and 99.5% (within 40 min) of sulfur mustard (HD) (4 μL) and soman (GD) (4 μL), respectively, in ambient conditions. The decontamination processes followed first-order reaction kinetics with a rate constant and half-life of 0.01234 min−1 and 56.15 min for HD and 0.1198 min−1 and 5.78 min for GD, respectively. It was concluded that the α-PMo10V2O405− moiety was responsible for the catalytic oxidation of HD into non-toxic sulfoxide, while the ε-[Al13O4(OH)24(H2O)12]7+ moiety was responsible for the catalytic hydrolysis of HD and GD into nontoxic hydrolysates. Besides, the compound showed notable efficacy for the decontamination of HD on guinea pig skin and of GD on Kunming mouse skin, indicating high potential for use in human skin protection and treatment.
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POSTHARVEST BIOLOGY AND TECHNOLOGY
·
2023
·
IF 7
Jialin Duan,Zhiyan Xu,Yunmin Shi,Lanxiang Jiang,Yali Fan,Yulin Li,Ming Ni,Jianjun Hou
The yellowing and quality deterioration are important factors to shorten the storage period of peeled water chestnuts (PWCs). Integration of 4-OH-7-C 3 HO-coumarin and controlled atmosphere (CA) storage (Ne, O 2 ) to extend the storage period of PWCs has not been studied. The objective of the investigation was to reveal the mechanics with that integration of 4-OH-7-C 3 HO-coumarin (1.2 %) and CA storage (81.2 % Ne, 18.8 % O 2 ) extended the storage period of PWCs. PWCs were treated with 4-OH-7-C 3 HO-coumarin (1.2 %), CA storage (81.2 % Ne, 18.8% O 2 ), and integration of 4-OH-7-C 3 HO-coumarin (1.2 %) and CA storage (81.2 % Ne, 18.8 % O 2 ). The yellowing degree, weight loss, yellowing substance contents, enzymatic activities, total soluble solids content, titratable acidity content, ascorbic acid content, and microbe of PWCs were detected. 4-OH-7-C 3 HO-coumarin (1.2 %), CA storage (81.2 % Ne, 18.8 % O 2 ), and integration of 4-OH-7-C 3 HO-coumarin (1.2 %) and CA storage (81.2 % Ne, 18.8 % O 2 ) extended the storage period by 3, 9 and 12 d. Integration of 4-OH-7-C 3 HO-coumarin (1.2 %) and CA storage (81.2 % Ne, 18.8% O 2 ) was the best. On day 12, integration of 4-OH-7-C 3 HO-coumarin (1.2 %) and CA storage (81.2 % Ne, 18.8 % O 2 ) reduced the yellowing degree from 99.5% to 0, the peroxidase activity from 35,603.37 to 28,504.61 U s −1 kg, the eriodictyol content from 3.09 × 10 −4 % to 0, the weight loss from 5.24 % to 0. Integration of 4-OH-7-C 3 HO-coumarin (1.2 %) and CA storage (81.2 % Ne, 18.8 % O 2 ) increased the total soluble solids content from 9.37 % to 13.49%, the titratable acidity content from 5.67 × 10 −3 % to 8.62 × 10 −3 % , and the titratable acidity content from 8 × 10 −5 % to 8.55 × 10 −5 %. Integration of 4-OH-7-C 3 HO-coumarin (1.2 %) and CA storage (81.2 % Ne, 18.8 % O 2 ) can be employed to extend the storage period of PWCs. This study provided a theoretical basis for the practical application of integration of 4-OH-7-C 3 HO-coumarin and CA storage (Ne, O 2 ) to extend the storage period of PWCs.
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NEW JOURNAL OF CHEMISTRY
·
2014
·Vol. 38
·期 10
·4938-4945
·
IF 3.159
Wei Shi,Qiang Cheng,Lian Duan,Yang Ding,Zhongduo Xiong,Xiaoxia Li,Aihua Xu
Dioxygen from air is the cleanest and the most abundant oxidative agent; it is of great significance to activate dioxygen to reactive oxygen species for environmental pollutant transformation and degradation. In this work, the simple cobalt(II) ion was found to exhibit high efficiency for p-aminophenol oxidation in bicarbonate aqueous solution with dioxygen as the oxidant at room temperature; simultaneously, the azo dye, Acid Orange 7, can be decolorized by the system. The formed reactive species was carefully studied by electron spin resonance and spin-trapping technologies and radical scavenging measurements. The metal-bound hydroxyl radical, which originated from a Fenton-like reaction between the Co2+–HCO3− complex and the intermediate of H2O2, was suggested as the main reactive species. This study can provide new insight into the mechanism of the molecular oxygen activation by simple metal complexes and their application to the removal or transformation of pollutants under mild reaction conditions.
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ANALYTICAL CHEMISTRY
·
2019
·
IF 6.35
Nianzu Liu,Jingyao Song,Yanwei Lu,Jason J. Davis,Fengxian Gao,Xiliang Luo
The rapid, convenient, and selective assaying of clinical targets directly in complex biological media brings with it the potential to revolutionize diagnostics. One major hurdle to impact is retention of selectivity and a tight control of nonspecific surface interactions or biofouling. We report herein, the construction of an antifouling interface through the covalent attachment of designed branched zwitterionic peptides onto electrodeposited polyaniline film. The antifouling capability of the designed branched peptide significantly outperforms that of the commonly used PEG and linear peptides. The interfaces modified with branched peptides are exceptionally effective in reducing a nonspecific protein and cell adsorption, as verified by electrochemical and fluorescent characterization. The derived sensors with mucin1 protein (MUC1) aptamer as the recognition element detect MUC1-positive MCF-7 breast cancer cells in human serum with high sensitivity and selectivity. The linear response range of the cytosensor for the MCF-7 cell is from 50 to 106 cells/mL, with a limit of detection as low as 20 cells/mL. More importantly, the assaying performances remain unchanged in human serum owing to the presence of branched antifouling peptide, indicating feasibility of the cytosensor for practical cancer cell quantification in complex samples.
研究领域:
生物传感器
·
癌症诊断
·
材料科学
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分析化学
·
生物医学工程
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ChemMedChem
·
2016
·Vol. 12
·期 3
·235-249
·
IF 2.98
Silong Zhang,Zhiyong Wang,Zhiye Hu,Changhao Li,Chu Tang,Kathryn E. Carlson,Junjie Luo,Chune Dong,John A. Katzenellenbogen,Jian Huang,Hai-Bing Zhou
Graphical Add a new element ! This is the first report of selenophene-core compounds as estrogen receptor (ER) ligands. In transcription assays, several selenophenes were profiled as superagonists for ERα; moreover, a few selenophenes exhibited antiproliferative activity similar to that of 4-hydroxytamoxifen in MCF-7 breast cancer cells while being nontoxic toward normal VERO cells. These new ligands could act as models for the development of novel agents leading to improved therapeutics that target the ER. The importance of the heterocyclic core elements with peripheral phenolic and alkyl substituents as a dominant structural motif of ligands for the estrogen receptor (ER) has been well recognized. In this study we expanded the structural diversity of core elements by preparing selenium-containing heterocycles and exploring the activities of these selenophenes on the two ERs, ERα and ERβ. Careful structure–activity relationship (SAR) analysis of their ER binding affinities showed that most selenophenes are ERβ-selective, with the position of the phenol substituents on the selenophene core and the nature of these substituents having a marked effect on their binding affinities. The compound bis(2-fluoro-4-hydroxyphenyl)selenophene ( 2 f ) has the highest relative binding affinity (RBA) of 24.3 for ERβ. In transcription assays, most selenophenes were found to exhibit partial to full agonist activity for both ER subtypes, with compounds bis(2-methyl-4-hydroxyphenyl)selenophene ( 2 b ), bis(4-fluoro-3-hydroxyphenyl)3-bromoselenophene ( 6 f ), and 2,3,5-tris(hydroxyphenyl)thiophenes ( 8 b and 8 d ) profiling as superagonists for ERα; however, several compounds display a range of ERα or ERβ antagonistic activities. A few selenophenes exhibited antiproliferative activity, with compound 8 c showing antiproliferative effects similar to that of 4-hydroxytamoxifen in breast cancer MCF-7 cells while being nontoxic to normal VERO cells. These new ligands could act as models for the development of novel agents leading to improved therapeutics that target the estrogen receptor.
研究领域:
药理学
·
化学
·
癌症研究
·
分子生物学
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Petroleum Exploration and Development
·
2026
·Vol. 53
·期 1
·191-204
·
IF 10.7
Jianming FAN,Rui CHANG,Youan HE,Zhouhua WANG,Xintong ZHANG,Bo WANG,Liangbing CHENG,Kai XU,Ameng WU,Huang LIU,Hanmin TU,Ping GUO,Shuoshi WANG,Yisheng HU
This paper proposes an approach to determing the optimal cluster spacing for volume fracturing in shale oil reservoirs based on three scales, i.e. microscopic capillary displacement, large-scale core imbibition, and macroscopic reservoir nuclear magnetic resonance (NMR) logging. Through flow experiments using capillary with different diameters and lengths, and large-scale core counter-current and dynamic imbibition tests, and combing with the NMR logging data of single wells, a graded optimization criterion for cluster spacing is established. The proposed approach was tested in the shale oil reservoir in the seventh member of the Triassic Yanchang Formation (Change 7 Member), the Ordos Basin. The following findings are obtained. First, in the Chang 7 reservoir, oil in pores smaller than 8 μm requires a threshold pressure, and for 2–8 μm pores, the movable drainage distance ranges from 0.7 m to 4.6 m under a pressure difference of 27 mPa. Second, the large-scale core imbibition tests show a counter-current imbibition distance of only 10 cm, but a dynamic imbibition distance up to 30 cm. Third, in-situ NMR logging results verified that the post-fracturing matrix drainage radius around fractures is 0–4 m, which is consistent with those of capillary flow experiments and large-scale core imbibition tests. The main pore-size range (2–8 μm) of the Chang 7 reservoir corresponds to a permeability interval of (0.1–0.4)×10 −3 μm 2 . Accordingly, a graded optimization criterion for cluster spacing is proposed as follows: for reservoirs with permeability less than 0.20×10 −3 μm 2 , the cluster spacing should be reduced to smaller than 4.2 m; for reservoirs with permeability of (0.2–0.4)×10 −3 μm 2 , the cluster spacing should be designed as 4.2–9.2 m. Field application on a pilot platform, where the cluster spacing was reduced to 4.0–6.0 m, yielded an increased initial oil production by approximately 36.6% over a 100-m horizontal reservoir section as compared with untested similar platforms.
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Food Bioscience
·
2026
·
IF 6.2
Zixian Xia,Xiaoyan Guan,Rui Liu,Yeting Wu,Yingying Li,Mengmeng Liu,Yifeng Ding,Xiaohong Wang,Youyou Lu
Bifidobacterium faces major challenges in the gastrointestinal tract, including inactivation under acidic conditions and insufficient targeted release. In this study, three novel heterologous dual-protein complex systems were constructed by lactoferrin (LF) with α-lactalbumin (ALA), β-lactoglobulin (BLG), casein (CN). Subsequently, sodium alginate (SA) -cross-linked gel microcapsules loaded with these dual-protein complexes and B. animalis F1-7. The optimal preparation conditions for the dual-protein were as follows: ALA/LF = 1.5, 50 °C; BLG/LF = 2, 50 °C; CN/LF = 0.5, 25 °C. Incorporation of SA and endogenous emulsification method enabled efficient encapsulation of B . animalis F1-7, achieving encapsulation efficiency exceeding 90%. B. animalis F1-7@SA-(LF-ALA/BLG/CN) exhibited strong acid resistance, favorable intestinal responsiveness, and significantly improved microbial viability. The microcapsules enhanced gastric acid tolerance primarily through a spatial barrier effect, while the incorporation of dual-protein components contributed to matrix structural reinforcement and digestion-responsive release behavior. This integrated “physical protection-structural modulation” strategy also conferred excellent 28-day storage stability. In vitro experiments by mice/human feces, combined with 16S rRNA and metabolomics analysis, revealed that the composite microcapsules effectively regulated the structure of the microbial community and altered metabolite profiles (e.g. , pathways involved in nitrogen metabolism). Overall, this study provided reproducible preparation parameters and a theoretical basis for SA-based dual-protein composite encapsulation delivery systems, and offered a promising strategy to address the coordinated challenges of activity, controlled release, and storage stability of sensitive food bioactive microorganisms or nutrients.
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INORGANIC CHEMISTRY
·
2023
·
IF 4.6
Xu Xu,Xiang Li,Guibin Liu,Xixi Wei,Daming Feng,Lei Zhang
In recent years, efficient oil–water separation has gradually become an indispensable part of environmental treatment. Superhydrophobic/superoleophilic materials with excellent self-cleaning performance are urgently required and remain challenging in the investigation of practical, rapid, and efficient separation of oil–water mixture and emulsion, especially those with robust surfaces that can be used in harsh conditions. In this work, a novel superhydrophobic/superoleophilic material was first fabricated by in situ constructing PDMS@ZIF-7/Cu3(PO4)2 hierarchical architectures on a copper mesh, which was adopted as a high flux and efficient separation material for gravity-driven separation of oil–water mixture as well as emulsion. The introduction of crucial Cu3(PO4)2 nanosheet interlayers created the ideal hierarchical structures and serve as partial templates for the subsequent in situ growth of hydrophobic ZIF-7 nanosheets. An improved superhydrophobicity (CA = 155°), permeation flux (102,000 L m–2 h–1), and preferred self-cleaning property were thus achieved by such manipulation of the copper mesh. The PDMS@ZIF-7/Cu3(PO4)2 mesh exhibited exceptional separation efficiency for diverse oil–water mixtures and emulsions attributed to the superhydrophobicity and the demulsification ability and considerable stability to cope with extreme environments including sunlight resistance, low temperature, and corrosion resistance, which prompted its promising applicability in cleaning emulsified wastewater.
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BIOCHEMICAL PHARMACOLOGY
·
2022
·
IF 6.1
Yin-Peng Bai,Cheng-Jie Yang,Nan Deng,Mi Zhang,Zhi-Jun Zhang,Lei Li,Yong Zhou,Xiong-Fei Luo,Chuan-Rui Xu,Bao-Qi Zhang,Yue Ma,Ying-Qian Liu
A series of new 7-ethyl-10-fluoro-20-O-(cinnamic acid ester)-camptothecin derivatives were synthesized and evaluated for cytotoxicity against four human tumor cell lines including HepG2 (hepatocellular carcinoma), SW480 (colorectal cancer), A2780 (ovarian cancer), and Hucct1 (intrahepatic cholangiocarcinoma). The results of cytotoxic activities in vitro showed that most of the camptothecin derivatives harbor promising cytotoxic activity against tested tumor cell lines. Among them, compound XJS-11 exhibited broad-spectrum inhibitory activities against HepG2, SW480, A2780, and Hucct1 cell lines with IC 50 values of 0.03, 0.09, 0.22, and 0.32 μM, respectively. Further investigation demonstrated that compound XJS-11 exhibited more effective growth inhibition against a variety of human hepatoma cells (Sk-hep-1, Hep3B and Huh7) and lower cytotoxicity against immortalized normal human liver cell line L02 than the positive control topotecan . Especially, XJS-11 showed higher selective toxicity in two kinds of human hepatoma cells and immortalized normal human liver cell line (IC 50(L-02) /IC 50(HepG2) = 113.20; IC 50(L-02) /IC 50(Hep3B) = 85.60) than topotecan (IC 50(L-02) /IC 50(HepG2) = 9.45; IC 50(L-02) /IC 50(Hep3B) = 8.52). Mechanistically, XJS-11 induced cell cycle arrest and cell apoptosis in HepG2 and Hep3B cells by inhibiting Top I activity in a manner similar to that of topotecan. Meanwhile, XJS-11 could attenuate the tumor growth in both xenograft and primary HCC mouse models. In addition, the acute toxicity assay showed that XJS-11 did not cause lethality or significant body weight loss with a single intraperitoneal dose at 100 mg/kg or with an intraperitoneal dose at 25 mg/kg for 7 days. Moreover, unlike topotecan, XJS-11 had no apparent toxicity to the mouse liver, kidney, and hemopoietic system of the C57BL/6 mice. Taken together, XJS-11 merits further development as a new generation of the camptothecin-derived drug candidate.
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PHYTOMEDICINE
·
2025
·
IF 8.3
Haoyun Bai,Tong Wu,Yanni Lv,Wenhao Chen,Yuhan Jiang,Fayuan Chen,Ping Su,Heshui Yu,Langchong He,Zheng Li,Shengli Han
Background Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKI) are widely regarded as the most promising strategy to treat non-small cell lung cancer (NSCLC). While the existing development model cannot meet the requirements. Methods Here, we developed a drug prediction and screening platform based on state-of-the-art deep learning (DL) algorithms and cell membrane chromatography (CMC). Using this platform, we discovered several novel EGFR antagonists from massive molecules. The interactions between target compounds and EGFR were investigated using frontal analysis, Surface plasmon resonance analysis, cellular thermal shift assay, and molecule docking. Xenografts models were established to study the anti-tumor activity of most promising compound. Proteomics, immunofluorescence, and Western blots were conducted to explore its mechanism. Results The deep neural network had good performance, with an area under the curve of 0.950 ± 0.012. Among the top 100 molecules predicted by the model, 25 compounds had retention on SNAP-tagged (ST)-EGFR/CMC, of which 12 molecules exhibited significant anti-tumor activity. Interaction analysis revealed that Geraniin, Brazilin, and 7-Epitaxol would directly bind to EGFR and inhibit its activation. 7-Epitaxol exhibited significant anti-tumor activity in vivo and in vitro . 7-Epitaxol combined with EGFR and inhibited its phosphorylation, blocked PI3K/AKT pathways, thereby exerting its anti-tumor activity by promoting autophagy in A549 cells. Conclusion The results provide a novel and powerful platform for drug discovery and development in NSCLC research. By using this platform, Geraniin, Brazilin, and 7-epitaxol were identified as novel EGFR antagonists. We also innovatively demonstrated that 7-epitaxol promotes autophagy in NSCLC.
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