Frontiers in Nutrition
·
2025
·
IF 5.1
Siyu Dai,Cunjie Li,Dagang Li,Hong Wang
Introduction: This study investigates the effects of α-GML on intestinal epithelial tight junction (TJ) protein expression and its molecular mechanisms. Recognizing the critical role of TJ proteins in intestinal barrier function and the potential of α-GML to enhance this barrier, we employ the IPEC-J2 cell model. Our aim is to validate the regulatory impact ofα-GML on TJ protein expression and elucidate the underlying signaling pathways, thereby offering new strategies for intestinal health maintenance.Methods: Utilized Data-Independent Acquisition (DIA) analysis to identify optimal targets of α-GML in modulating Tight Junction (TJ) protein expression. Treated cells with specific inhibitors of PKC and MAPK to assess their role in TJ regulation by α-GML. Co-treated cells with the MAPK inhibitor SCH772984 and α-GML to study the effects on p-ATF-2 expression. Evaluated the effects of SCH772984 and ATF-2 overexpression on the protein expression levels of phosphorylated ATF-2, ZO-1, and OCLN.Results: Revealed that α-GML’s modulation of TJ proteins might involve the PKC/MAPK signaling pathway, leading to ATF-2 phosphorylation. Both PKC and MAPK inhibitors reduced TJ protein expression (p < 0.05, p < 0.01 or p < 0.001), indicating their involvement in α-GML’s regulation. SCH772984 counteracted α-GML-induced upregulation of p-ATF-2 (p < 0.05), suggesting MAPK’s role in this process. Identified potential ATF-2 binding sites on ZO-1 and OCLN promoters. ATF-2 significantly enhanced ZO-1 promoter activity (p < 0.001). SCH772984 reduced phosphorylated ATF-2, ZO-1, and OCLN levels (p < 0.05 or p < 0.01), while ATF-2 overexpression rescued this decrease (p < 0.05 or p < 0.01), confirming ATF-2’s role in TJ protein upregulation via the MAPK pathway.Discussion: Our study indicated that α-GML enhanced the expression of TJ proteins through the PKC/MAPK/ATF-2 pathway, thereby enhancing the barrier function of intestinal epithelial cells.
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ADVANCED FUNCTIONAL MATERIALS
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2025
·
IF 19
Jian Zhang,Jia-Fang Xie,Jie-Jie Chen,Wen-Wei Li,Jia-Cheng E. Yang,Yu-Ming Zheng,Han-Qing Yu
Heterogeneous peroxymonosulfate (PMS) activation is of great potential for sustainably degrading antibiotics included emerging contaminants from water. However, developing synthetic metal catalysts with incompatible mass transfer and optimized metal sites to effectively enable low-levels PMS activation and antibiotics removal is challenging. Herein, a protein-like Co catalyst of spatially hierarchical hydrophilicity is synthesized by constructing flower-like Mg/Al layered double hydroxide (LDH) on super-active carbon (AC) to disperse thin-layer Co(OH) 2 along the edge of LDH. The resulting AC-LDH@Co(OH) 2 catalyst demonstrates an impressive antibiotic removal of ≈80% within 15 s and turnover frequency of 45.72 min −1 based on catalyst mass by activating 0.075 mM PMS, surpassing single-atom catalysts included reports. In a fixed-bed reactor with secondary wastewater effluent, AC-LDH@Co(OH) 2 realizes complete removal of norfloxacin for 66 h with neutral effluent pH and negligible metal leaching. Experiments combined with theoretical computations reveal that the protein-like complex not only accelerates transfer of low-levels hydrophilic PMS and hydrophobic antibiotics, but also stably confines Co sites with regulated electronic structure for multiply reactive oxygen species generation.
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ACS Nano
·
2022
·
IF 18.027
Yuyue Mo,Feng Zhang,Hefeng Dong,Xingzhen Zhang,Shoujian Gao,Shenxiang Zhang,Jian Jin
Membrane fouling is a persistent and crippling challenge for oily wastewater treatment due to the high susceptibility of membranes to contamination. A feasible strategy is to design a robust and stable hydration layer on the membrane surface to prevent contaminates. A hydrogel illustrates a distinct category of materials with outstanding antifouling performance but is limited by its weak mechanical property. In this research, we report a reinforced hydrogel on a membrane by in situ growing ultrasmall hydrophilic Cu3(PO4)2 nanoparticles in a copper alginate (CuAlg) layer via metal-ion-coordination-mediated mineralization. The embeddedness of hydrophilic Cu3(PO4)2 nanoparticle with a size of 3–5 nm endows the CuAlg/Cu3(PO4)2 composite hydrogel with enhanced mechanical property as well as reinforced hydrate ability. The as-prepared CuAlg/Cu3(PO4)2 modified membrane exhibits a superior oil-repulsive property and achieves a nearly zero flux decline for separating surfactant stabilized oil-in-water emulsions with a high permeate flux up to ∼1330 L m–2 h–1 bar–1. Notably, it is capable of keeping similar permeate flux for both pure water and oil-in-water emulsions during filtration, which is superior to the currently reported membranes, indicating its super-antifouling properties.
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MOLECULAR HUMAN REPRODUCTION
·
2025
·Vol. 31
·期 4
·
IF 3.5
He Dongjie,Ren Xingxing,Mao Jing,Shi Shaoqi,Song Yanli,Xiao Huidongzi,Wei Aiwu
We have previously shown that ligustilide (LIG) treatment can restore endometrial receptivity and promote implantation in pregnant rats with low endometrial receptivity (LER). Using mRNA sequencing technology, we found that desmoglein-2 (Dsg2) is one of the differentially expressed genes, which is downregulated in rats with LER but elevated after LIG treatment. DSG2 is an adhesion protein that exists in epithelial tissues and serves as a crucial component of the junction complex for intercellular adhesion. The ability to adhere between cells is considered essential for successful embryo implantation. Hence, we speculated that DSG2 might be involved in the mechanism by which LIG treats LER. Immunofluorescence staining, western blots, and immunohistochemical staining were performed to confirm the restored expression of DSG2 by LIG treatment in the endometrial tissues of LER rats. Then, we investigated the effect of DSG2 on endometrial receptivity by injecting small interfering (si)Dsg2 (for silencing Dsg2 expression) into one uterine horn of a pregnant rat and siNC (for a normal control) into the other. It was found that the side of the endometrium injected with siDsg2 showed significant changes in the expression of multiple receptivity-related molecules and obvious embryo loss. In addition, we found that these receptivity-related molecules were affected by siDsg2 in Ishikawa (an endometrial cell line) cells. Dsg2 knockdown reduced the ability of Ishikawa cells to adhere to trophoblastic spheroids. Furthermore, the effect of LIG on endometrial cell–trophoblast adhesion was partially abolished by Dsg2 silencing. In conclusion, our findings suggest that the protective effect of LIG against LER might be achieved by increasing DSG2 expression. DSG2 enhancement might become a novel strategy for the development of LIG-inspired treatments to improve endometrial receptivity.
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FOOD RESEARCH INTERNATIONAL
·
2025
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IF 8
Xiangxin Wang,Qingxue Chen,Shubo Luo,Dongying Cui,Sinan Mu,Jufang Li,Qinggang Xie,Bailiang Li,Hong You
The Maillard reaction enhances flavor in thermally processed infant formula (IF) yet generates furfural derivatives such as 2-furfural and 5-hydroxymethylfurfural (5-HMF), raising safety concerns. This study assessed the toxicity of these compounds using both wild-type and transgenic zebrafish models, while establishing quantitative concentration-specific toxicity relationships. Stored IF produced elevated levels of 2-furfural and 5-HMF compared to normal IF, leading to immune, nervous, and liver toxicity in exposed zebrafish. Both compounds induced immunotoxicity at maximum non-lethal concentrations and hepatotoxicity across tested doses. Notably, 5-HMF showed minimal neurotoxicity and gastrointestinal (GI) effects, while 2-furfural induced neurotoxicity at its lowest concentration and GI toxicity at 10 % lethal concentration (LC 10 ). Moreover, high levels of these compounds in powdered IF can elicit immune, hepatic, and neurotoxicity, but not GI toxicity, with differences from pure compounds likely attributable to the influence of the complex dairy matrix. To our knowledge, this is the first study using the zebrafish model to systematically evaluate the immunotoxicity, neurotoxicity, hepatotoxicity and GI effects of 2-furfural and 5-HMF, and to establish quantitative, concentration-dependent, organ-specific toxicity relationships. These findings reveal the safety risks of these Maillard-derived compounds and highlight the need to optimize thermal processing to reduce their formation and improve infant-formula safety.
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International Journal of Nanomedicine
·
2025
·
IF 6.5
Yabing Xing,Wentao Hu,Yuxin Li,Yuru Zhang,Yulu Zhang,Binghua Wang,Xinhong Guo
Purpose 2-Methoxyestradiol (2-ME) has been demonstrated to possess extensive antitumor effects; however, various challenges have impeded its clinical utilization. In this study, we aimed to design a novel oral delivery system for 2-ME using a dual-target modification strategy to address the inherent drawbacks associated with poor absorption and rapid elimination, as well as to enhance oral bioavailability and antitumor effects.Methods Mannose(M)-modified zein (MZ) and cysteine(C)-modified zein (CZ) were synthesized. Glucose transporter (GLUT)-targeted adhesive nanoparticles (NPs), designated as 2-ME-CMZ (1:1:9)-NPs, were prepared via a solvent evaporation method using MZ, CZ, and Zein at a mass ratio of 1:1:9. Their in vitro and in vivo properties, including in vitro release, adhesion, antitumor effects etc. were evaluated.Results Compared with 2-ME-NPs, 2-ME-CMZ (1:1:9)-NPs showed a 3.89-fold increase in mucin adsorption in simulated intestinal fluid (SIF), a 0.61-fold extension of mean residence time (MRT), and a 1.2-fold increase in Caco-2 cell uptake, thereby prolonging the maintenance time of effective concentration (MTEC) after single-dose administration by 2.53-fold and enhancing oral bioavailability by 3.7-fold and tumor growth inhibition rate by 1.06-fold. Interestingly, for 2-ME-CMZ (1:1:9)-NPs, their cellular uptake was related to the mediation of multiple subtypes of GLUT with relative specificity, and they significantly enhanced the original cellular uptake pathway of 2-ME-NPs and showed higher tumor distribution than 2-ME-NPs. However, merely modifying 2-ME-NPs with mannose only increased the oral bioavailability of 2-ME-NPs by 0.44-fold.Conclusion Compared with 2-ME-NPs, 2-ME-CMZ (1:1:9)-NPs significantly enhanced absorption through the mediation of multiple subtypes of GLUT, enhancing their original cellular uptake pathway and prolonging absorption time. These findings demonstrated that 2-ME-CMZ (1:1:9)-NPs are an extremely promising oral drug delivery system for 2-ME, and endowing GLUT-targeted drug-loaded nanoparticles with adhesion is an effective strategy for fully leveraging the role of GLUT in mediating oral absorption.
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JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
·
2025
·Vol. 29
·期 6
·e70470
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IF 4.2
Chuchu Xu,Renjun Zhu,Qingfeng Dai,Yaoqing Li,Gengyuan Hu,Kelong Tao,Yuhong Xu,Guangen Xu,Guolin Zhang
The main reason for the failure of chemotherapy therapies based on 5-Fluorouracil (5-Fu) is the development of resistance to 5-Fu in cancer patients, particularly those with colorectal cancer. Tissue inhibitor of metalloproteinases 2 (TIMP-2) has been shown to be associated with colorectal cancer (CRC), but its correlation with 5-Fu resistance in colorectal cancer has not been thoroughly studied. We screen the expression of different cytokines through Cytokine array. CCK-8 assay was conducted to evaluate the IC 50 of 5-Fu and cell proliferation. ELISA and RT-qPCR were performed to detect TIMP-2 expression levels in cells and patient serum. Western blotting was utilised to analyse the differences in the expression of proteins related to signalling pathways in cells. Through cytokine array screening, we found that the expression of TIMP-2 was significantly increased in CRC drug-resistant cell lines. In addition, the expression of TIMP-2 in the serum of patients with CRC resistance to 5-Fu was significantly increased. Subsequent mechanistic experiments showed that TIMP-2 regulated the resistance of CRC cells to 5-Futhrough the JAK–STAT signalling pathway. Moreover, anti-TIMP-2 antibody or small molecule drug LY2784544 targeting the JAK–STAT signalling pathway can effectively reverse the resistance of CRC cells to 5-Fu. It is exactly TIMP-2 that mediates the resistance of CRC to 5-Fu through the JAK–STAT signalling pathway. Targeting drugs for TIMP-2 or the JAK–STAT signalling pathway are expected to be opportunities to reverse 5-Fu resistance in CRC.
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ACS Synthetic Biology
·
2025
·
IF 3.9
Bicheng Yu,Wei Song,Shenjie Wang,Wanqing Wei,Guipeng Hu,Xiaomin Li,Cong Gao,Jia Liu,Jian Wen,Jing Wu
2-Pyrrolidone is an important chemical intermediate with broad applications in the materials and pharmaceutical industries. Traditional petrochemical synthesis methods pose significant environmental challenges. In the case of biosynthesis, the limited thermostability of coenzyme A ligase (CaiC) represents a major barrier to industrial-scale production. This study focused on enhancing the thermostability and catalytic efficiency of EcCaiC through protein engineering. Conserved sequences were identified, and flexible regions were targeted for virtual mutagenesis using FoldX and Rosetta. The resulting mutant, M3, exhibited a 7.86-fold increase in half-life(t1/2) at 55 °C and a Tm of 59.3 °C. Additionally, the catalytic efficiency (kcat/Km) of M3 improved by 52.8%, reaching 5.73 mM–1 s–1 compared to the wild type. Subsequently, EcCaiCM3 was introduced into Corynebacterium glutamicum S9114, with targeted knockout of byproduct synthesis genes. Finally, fed-batch fermentation in a 5 L bioreactor achieved a 2-pyrrolidone yield of 58.28 g/L, a glucose conversion rate of 0.32 g/g, and a productivity of 0.97 g/L/h. This work establishes an efficient biosynthetic platform for 2-pyrrolidone, providing a robust foundation for its industrial production.
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PLASMA SCIENCE & TECHNOLOGY
·
2025
·
IF 1.8
Ruiting Jian,Qirui Zou,Jianjun Yan,Bowen Liu,Lijun Sang,Zhongwei Liu
Cr(VI), a hazardous heavy metal pollutant found in wastewater, exerts detrimental effects on biological system and the human body. Efficient photocatalytic reduction of Cr(VI) to Cr(III) using high-performance materials offers a viable approach for chromium decontamination. In the current work, the defective UiO-66-(OH)2 with enhanced photocatalytic activity was developed by the plasma treatment. These defects not only triggered an expansion in mesoporous domains and increased the BET surface area of the UiO-66-(OH)2 system, thereby exposing more adsorption and photocatalytically active sites, but also created additional electron migration pathways, enhancing the separation of photogenerated e-/h+ pairs. When subjected to an operating power of 15 W, chamber pressure at 20 Pa, and a 300-second treatment period, UiO-66-(OH)2 exhibited a removal efficiency of 83 %. This work explored a novel way for the construction of the defective MOFs and broadened the utilizationation of MOFs in the fields of photoreduction of heavy metal ions in water.
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JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2018
·
IF 3.412
Fei Zhou,Weisu Huang,Maiquan Li,Yongheng Zhong,Mengmeng Wang,Baiyi Lu
Acteoside and salidroside are major phenylethanoid glycosides (PhGs) in Osmanthus fragrans Lour. flowers with extensive pharmacological activities and poor oral bioavailability. The absorption mechanisms of these two compounds remain unclear. This study aimed to investigate the bioaccessibility of these compounds using an in vitro gastrointestinal digestion model and to examine the absorption and transport mechanisms of PhGs using the Caco-2 cell model. The in vitro digestion model revealed that the bioaccessibility of salidroside (98.7 ± 1.35%) was higher than that of acteoside (50.1 ± 3.04%), and the superior bioaccessibility of salidroside can be attributed to its stability. The absorption percentages of total phenylethanoid glycoside, salidroside, and acteoside were 1.42–1.54%, 2.10–2.68%, and 0.461–0.698% in the Caco-2 model, respectively. Salidroside permeated Caco-2 cell monolayers through passive diffusion. At the concentration of 200 μg/mL, the apparent permeability (Papp) of salidroside in the basolateral (BL)-to-apical (AP) direction was 23.7 ± 1.33 × 10–7 cm/s, which was 1.09-fold of that in the AP-to-BL direction (21.7 ± 1.38 × 10–7 cm/s). Acteoside was poorly absorbed with low Papp (AP to BL) (4.75 ± 0.251 × 10–7 cm/s), and its permeation mechanism was passive diffusion with active efflux mediated by P-glycoprotein (P-gp). This study clarified the bioaccessibility, absorption, and transport mechanisms of PhGs. It also demonstrated that the low bioavailability of acteoside might be attributed to its poor bioaccessibility, low absorption, and P-gp efflux transporter.
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MICROCHIMICA ACTA
·
2022
·Vol. 189
·期 8
·1-10
·
IF 6.408
Zhao Tingting,Yan Weizhen,Dong Fengqi,Hu Xinlong,Xu Yanli,Wang Zhenyu,Shen Yating,Wang Wanrong,Zhao Ye,Wei Wenmei
COVID-19 necessitates the development of reliable and convenient diagnostic tools. In this work, a facile 3D-printed smartphone platform was constructed that achieved reliable visual detection of SARS-CoV-2 by eliminating the effect of ambient light and fixing the camera position relative to the sample. The oligonucleotide probe is modified with orange-red-emitting TAMRA working as an internal standard and green-emitting FAM serving as a sensitive sensing agent. Under 365-nm UV excitation, the emission wavelengths of TAMRA and FAM are 580 nm and 518 nm, respectively. When the probes interact with the targets, the green fluorescence gradually restores while the orange-red fluorescence remains stable. Thus, a striking color transition from orange-red to green could be observed by the naked eye. The detection limit of SARS-CoV-2 nucleic acid is 0.23 nM, and the entire process of color change could be completed in 25 min. Furthermore, the RGB value analysis of the sample solution was conducted using a smartphone for reliable and reproducible discrimination of SARS-CoV-2. The proposed smartphone platform might establish a general method for visual detection of SARS-CoV-2 nucleic acid as well as other virus-related diseases. Graphical abstract
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BIOSENSORS & BIOELECTRONICS
·
2019
·
IF 9.518
Xiaoxi Guo,Shuping Liu,Minghui Yang,Huitong Du,Fengli Qu
Photoelectrochemical (PEC) biosensor for highly sensitive detection of breast cancer biomarker human epidermal growth factor receptor-2 (HER2) is reported utilizing a dual signal amplification strategy. The biosensor was prepared based on tungsten sulfide nanowire array on Ti mesh (WS 2 NW/TM). Such WS 2 NW/TM electrode can generate photoelectric signal under visible light excitation . The HER2 aptamer was wrapped onto the nanowire array surface for specific binding with HER2 molecules, and gold nanoparticles (Au NPs) that modified with glucose oxidase (GOx) and HER2 binding peptide was utilized for signal amplification. The H 2 O 2 that generated by GOx catalyzed glucose reaction and localized surface plasmon resonance of Au NPs can both enhance the PEC current intensity of the biosensor, leading to dual signal amplification. The PEC current intensity is enhanced linearly with HER2 concentration in the 0.5–10 ng/mL range with limit of detection of 0.36 ng/mL. Such biosensor was applied for the detection of HER2 in breast cancer serum samples with detection results in good agreement with commercial ELISA results.
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