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ANALYTICAL CHEMISTRY · 2018 · IF 6.042

Electrochemical Impedance Spectroscopy for Real-Time Detection of Lipid Membrane Damage Based on a Porous Self-Assembly Monolayer Support

Meng Zhang,Qingyu Zhai,Liping Wan,Li Chen,Yu Peng,Chunyan Deng,Juan Xiang,Jiawei Yan

Layer-by-layer dissolution and permeable pore formation are two typical membrane damage pathways, which induce membrane function disorder and result in serious disease, such as Alzheimer’s disease, Keshan disease, Sickle-cell disease, and so on. To effectively distinguish and sensitively monitor these two typical membrane damage pathways, a facile electrochemical impedance strategy was developed on a porous self-assembly monolayer (pSAM) supported bilayer lipid membrane (BLM). The pSAM was prepared by selectively electrochemical reductive desorption of the mercaptopropionic acid in a mixed mercaptopropionic acid/11-mercaptoundecanoic acid self-assembled monolayer, which created plenty of nanopores with tens of nanometers in diameter and several nanometers in height (defined as inner-pores). The ultralow aspect ratio of the inner-pores was advantageous to the mass transfer of electrochemical probe [Fe(CN)6]3–/4–, simplifying the equivalent electric circuit for electrochemical impedance spectroscopy analysis at the electrode/membrane interface. [Fe(CN)6]3–/4– transferring from the bulk solution into the inner-pore induce significant changes of the interfacial impedance properties, improving the detection sensitivity. Based on these, the different membrane damage pathways were effectively distinguished and sensitively monitored with the normalized resistance-capacitance changes of inner-pore-related parameters including the electrolyte resistance within the pore length (Rpore) and the metal/inner-pore interfacial capacitance (Cpore) and the charge-transfer resistance (Rct-in) at the metal/inner-pore interface.

研究领域: 生物物理学 · 分析化学 · 医学
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Environmental Science-Nano · 2025 · IF 5.1

Violet Phosphorus Nanosheets Exhibit Higher Toxicity in the Freshwater Microalgae Tetradesmus obliquus than Black Phosphorus Nanosheets

Haoxiang Zhang,Fan Zhang,Zhuang Wang,Willie Peijnenburg

The potential environmental risks of two-dimensional (2D) phosphorene nanomaterials are gaining attention as their promising applications continue to expand. Violet phosphorus (VP) has been demonstrated to be a more stable phosphorene nanomaterial compared to black phosphorus (BP). However, current research has primarily focused on the toxic effects of BP, with limited information available regarding the toxicity of VP. This study comparatively analyzed the ecotoxicity and mechanisms of action of environmentally relevant concentration exposures of the common green algae Tetradesmus obliquus to BP and VP nanosheets. The results revealed that VP exhibited a greater growth inhibitory effect on the algae compared to BP, which was linked to disruptions in cell membrane function. Both BP and VP induced intracellular oxidative stress responses, yet they did not cause oxidative damage to algal cells. Transcriptional responses suggested that the number of differentially expressed genes in the algae exposed to VP was 29 times higher than that in the algae exposed to BP. Metabolomic analysis indicated that the number of differentially expressed metabolites induced by VP exposure in the algae was twice as high as the changes induced by BP. Furthermore, integrated transcriptome and metabolome analyses highlighted significant differences between BP and VP in core pathways, key metabolites, and driving genes. The findings of this study underscore the importance of considering the impact of different types of phosphorene materials when assessing their environmental risks.

CAS / MDL: 596-09-8 62669-70-9
研究领域: 环境毒理学 · 纳米生物学 · 水生生态学 · 分子生态毒理学 · 环境科学 · 藻类生理学 · 组学分析
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BMC Ophthalmology · 2020 ·Vol. 20 ·期 1 ·1-10 · IF 1.413

Protection of retinal function and morphology in MNU-induced retinitis pigmentosa rats by ALDH2: an in-vivo study

Yan Weiming,Long Pan,Wei Dongyu,Yan Weihua,Zheng Xiangrong,Chen Guocang,Wang Jiancong,Zhang Zuoming,Chen Tao,Chen Meizhu

Background Retinitis pigmentosa (RP) is a kind of inherited retinal degenerative diseases characterized by the progressive loss of photoreceptors. RP has been a conundrum without satisfactory countermeasures in clinic until now. Acetaldehyde dehydrogenase 2 (ALDH2), a major enzyme involved in aldehyde detoxification, has been demonstrated to be beneficial for a growing number of human diseases, such as cardiovascular dysfunction, diabetes mellitus and neurodegeneration. However, its protective effect against RP remains unknown. Our study explored the impact of ALDH2 on retinal function and structure in N-methyl-N-nitrosourea (MNU)-induced RP rats.Methods Rats were gavaged with 5 mg/kg Alda-1, an ALDH2 agonist, 5 days before and 3 days after MNU administration. Assessments of retinal function and morphology as well as measurement of specific proteins expression level were conducted.Results Electroretinogram recordings showed that Alda-1 administration alleviated the decrease in amplitude caused by MNU, rendering protection of retinal function. Mitigation of photoreceptor degeneration in MNU-treated retinas was observed by optical coherence tomography and retinal histological examination. In addition, Western blotting results revealed that ALDH2 protein expression level was upregulatedwith increased expression of SIRT1 protein after the Alda-1 intervention. Besides, endoplasmic reticulum stress (ERS) was reduced according to the significant downregulation of GRP78 protein, while apoptosis was ameliorated as shown by the decreased expression of PARP1 protein.Conclusion sTogether, our data demonstrated that ALDH2 could provide preservation of retinal function and morphology against MNU-induced RP, with the underlying mechanism at least partly related to the modulation of SIRT1, ERS and apoptosis.

CAS / MDL: 684-93-5
研究领域: 眼科学 · 药理学 · 神经科学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY · 2019 · IF 3.061

Ecotoxicological effects on Scenedesmus obliquus and Danio rerio Co-exposed to polystyrene nano-plastic particles and natural acidic organic polymer

Yinghan Liu,Zhuang Wang,Se Wang,Hao Fang,Nan Ye,Degao Wang

The importance of attention to unravel the interaction of nano-plastic particles (NPs) with natural acidic organic polymer (NAOP) in freshwater environment should not be neglected. However, toxicological data available for the interaction between NPs and NAOP remain limited. Here, we investigate the toxicological effects of three model polystyrene (PS) NPs with different functional groups (unmodified, amino- and carboxyl-modified PS NPs) on two freshwater organisms of different trophic levels ( Scenedesmus obliquus and Danio rerio ) in the absence and presence of two classes of NAOP, namely fulvic acid and humic acid. The NAOP interaction with the NPs is shown to alter oxidative stress and disturb membrane function in S. obliquus cells to a certain extent. Combined oxidative stress responses to the NPs and NAOP in D. rerio as a function of their mixture levels showed inhibition, alleviation, and reinforce. Changes in cellular oxidative stress and membrane function depended on the concentration and types of both NPs and NAOP. Furthermore, the characterization parameters of the NPs were important for the explanation of the ecotoxicological mechanism of the NPs in the presence of NAOP. Our findings emphasized the critical role of NAOP in the fate and toxicity of plastic particles in freshwater environment.

CAS / MDL: 9003-53-6
研究领域: 环境科学 · 生态学 · 毒理学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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EXPERIMENTAL EYE RESEARCH · 2015 · IF 2.709

A novel imidazopyridine derivative, X22, prevents the retinal ischemia-reperfusion injury via inhibition of MAPKs

Yang Bian,Luqing Ren,Lei Wang,Shanmei Xu,Jianjian Tao,Xiuhua Zhang,Yi Huang,Yuanyuan Qian,Xin Zhang,Zongming Song,Wencan Wu,Yi Wang,Guang Liang

Inflammation is a pathological hallmark of ischemia reperfusion (I/R) injury. The present study was conducted to explore the ability of a new anti-inflammatory compound, X22, to attenuate retinal I/R injury via cytokine-inhibitory mechanism. For the in vitro experiment, ARPE-19 cells were pretreated with X22 (5 or 10 μM) or saline for 2 h, followed by stimulation with tert-butyl hydroperoxide (TBHP, 1000 μM) for an indicated amount of time. The expression of inflammatory mediators , cell viability , and cell apoptosis were evaluated. For the in vivo experiment, the rats were randomized to receive treatment with saline or X22 (0.1 μM/kg, 3 μL) before the induction of I/R injury. Histological evaluation, apoptosis of retinal cells, macrophage infiltration, and retina functional changes were further determined. Our data showed that pretreatment with X22 significantly inhibited TBHP-induced inflammatory cytokine expression in ARPE-19 cells. The anti-inflammatory activity of X22 may be associated with its inhibition on MAPKs, rather than NF-κB. Subsequently, our data proved that TBHP induced apoptosis in ARPE-19 cells, while pretreatment of X22 significantly suppressed TBHP-caused ARPE-19 apoptosis. Finally, the in vivo data revealed that X22 administration maintained better inner retinal layer structures, reduced apoptosis of retinal ganglion cell, and improved retinal function in retinal I/R rat models, which were accompanied with a remarkable decrease in retinal macrophage infiltration. These results suggest that the novel compound X22 is a potential agent for the treatment of retinal I/R-related diseases via the MAPKs-targeting anti-inflammatory mechanism and deserves the further development.

研究领域: 眼科学 · 药理学 · 炎症研究 · 神经保护
✓ 已验证 DOI PubMed 高影响因子
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Antibiotics-Basel · 2025 ·Vol. 15 ·期 1 · IF 4.6

β,β-Dimethylacrylalkannin Restores Colistin Efficacy Against mcr- and TCS-Mediated Resistant Gram-Negative Bacteria via Membrane Disturbance

Yongqing Liu,Huangwei Song,Muchen Zhang,Junyao Jiang,Yan Zhang,Jian Xu,Xi Xia,Shangshang Qin,Jianzhong Shen,Yang Wang

Background:The reintroduction of colistin has led to the rapid emergence of colistin-resistant strains, significantly diminishing its therapeutic efficacy. This presents a need for effective adjuvants to restore colistin efficacy.Approach: We screened the colistin adjuvants through a high-throughput method and then evaluated their synergistic effects and underlying mechanisms.Results: We identified β,β-dimethylacrylalkannin (β,β-Dim), a naphthoquinone compound derived from Lithospermum erythrorhizon, as a potent colistin adjuvant (fractional inhibitory concentration index (FICI) < 0.5). β,β-Dim enhanced colistin activity against 4 of 6 susceptible strains and all 18 colistin-resistant strains carrying either plasmid-bornemcrgenes (mcr-1,mcr-3,mcr-8, andmcr-9) or chromosomal two-component system (TCS) mutations (pmrA/B,phoP, andmgrB). These strains includedKlebsiella pneumoniae,Escherichia coli,SalmonellaTyphimurium,Pseudomonas aeruginosa, andAcinetobacter baumannii. The combination reduced the minimum inhibitory concentrations (MICs) of colistin by 4–1024-fold (from 512 to ≤2 µg/mL). Mechanistically, colistin-mediated outer membrane permeabilization facilitates β,β-Dim entry. Once internalized, β,β-Dim interacts with cytoplasmic membrane phospholipids and disrupts membrane biofunction. Further analysis showed that LPS transport and efflux pump activity were impaired, leading to LPS accumulation in the cytoplasmic membrane and increased intracellular colistin content. These processes elevated reactive oxygen species (ROS) production and markedly reduced ATP levels. In a murine infection model, β,β-Dim (2 mg/kg) combined with colistin (0.2 mg/kg) markedly increased survival from 20% (colistin alone) to 80%.Conclusions:These findings highlight that β,β-Dim combined with colistin is a promising therapeutic strategy for infections caused by colistin-resistant pathogens.

✓ 已验证 产品关联 DOI PubMed 高影响因子
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SCIENCE OF THE TOTAL ENVIRONMENT · 2023 · IF 9.8

Phosphorus conditions change the cellular responses of Microcystis aeruginosa to perfluorooctanoic acid

Hanqi Wu,Weizheng Zhang,Xuhui Huang,Peng Gu,Qi Li,Xingzhang Luo,Zheng Zheng

Perfluorooctanoic acid (PFOA), a widespread and emerging organic contaminant of aquatic environments, has high bioaccumulation potential and high toxicity. Consequently, major concerns have been raised worldwide regarding the management of this pollutant in aquatic ecosystems. To thoroughly understand PFOA's toxic effects on aquatic organisms, systematic investigations were conducted on the cellular responses of Microcystis aeruginosa to the environmental concentrations of PFOA under various concentrations as well as phosphorus (P) conditions (concentrations and forms). The results showed that P conditions remarkably affected cyanobacterial growth as well as photosynthetic pigment content, triggered oxidative stress to disrupt the function and structure of the cell membrane, and caused changes in the extracellular and intracellular contents of microcystin-LR (MC-LR). Furthermore, PFOA (100 μg/L) was absorbed by cyanobacterial cells through the stimulation of the secretion of extracellular polymeric substances (EPS) by M. aeruginosa . After entering the cyanobacterial cells, PFOA inhibited photosynthesis, reduced P absorption, induced oxidative damage, lead to a loss of cell integrity evident in scanning electron microscope images, and increased mcy A gene expression to promote MC-LR production. Moreover, the limited P concentration and forms conditions led to increased PFOA absorption by cyanobacterial cells, which further upregulated mcy A gene expression and increased the risk of MC-LR diffusion into the aquatic environment. Our present study provided a theoretical basis and new ideas for understanding and addressing safety issues related to the presence of PFOA in aquatic environments with varying nutritional statuses.

研究领域: 环境科学 · 水生毒理学 · 生态毒理学 · 微生物学 · 分子生物学
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Journal of Ovarian Research · 2024 ·Vol. 17 ·期 1 ·1-13 · IF 3.8

Hyperinsulinemia impairs decidualization via AKT-NR4A1 signaling: new insight into polycystic ovary syndrome (PCOS)-related infertility

Jiang Nan-Xing,Zhao Wei-Jie,Shen Hao-Ran,Du Dan-feng,Li Xue-Lian

Background Investigating the underlying molecular mechanisms responsible for endometrial dysfunction in women with PCOS is essential, particularly focusing on the role of hyperinsulinemia.Methods We explored the role of insulin in the decidualization process using a synthetic decidualization assay. To dissect the effects of PI3K/AKT-NR4A signaling, we employed small interfering RNAs (siRNAs) targeting the NR4A genes and inhibitors of the PI3K/AKT pathway. We also investigated the disruption of AKT-NR4A1 signaling in the endometrium of PCOS female rats induced with dehydroepiandrosterone (DHEA). Quantitative real-time PCR (qRT-PCR) and Western blot (WB) analyses were utilized to evaluate gene expression regulation.Results Insulin was found to suppress the expression of decidualization markers in human endometrial stromal cells (hESC) in a dose-dependent manner, concurrently triggering an inappropriate activation of the PI3K/AKT pathway. Members of the NR4A family, as downstream effectors in the PI3K/AKT pathway, were implicated in the insulin-induced disruptions during the decidualization process. Moreover, the endometrium of PCOS models showed significantly elevated levels of phosphorylated (Ser473) AKT, with a corresponding reduction in Nr4a1 protein.Conclusion sOur research demonstrates that insulin negatively regulates decidualization in hESC via the PI3K/AKT-NR4A pathway. In vivo analysis revealed a significant dysregulation of the AKT-NR4A1 pathway in the endometrium of PCOS rats. These findings offer novel insights into the pathogenesis of infertility and endometrial disorders associated with hyperinsulinemia in PCOS.

研究领域: 内分泌学 · 生殖生物学 · 分子生物学 · 妇科学
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DESALINATION · 2024 · IF 8.3

Nanofiltration membrane functionalization with enhanced hardness cation removal using a mono-component interlayer

Rukang Tian,Hao Zhang,Jingjun Wang,Dilnur Dilxat,Tao Xie,Qi Qi,Yunkun Wang

Current drinking water treatment demands new nanofiltration (NF) membranes to achieve efficient separation performance of both divalent hardness cations and new contaminants (ECs). In this work, we utilized sodium alginate as an interlayer to fabricate modified NF membrane with enhanced separation capacity. The interlayer was formed on substrate before interfacial polymerization reaction, controlling the irregular mass transfer of piperazine monomers and forming a crosslinked network at the bottom of the active layer to enhance the separation performance. Alginate modification method was proved achieving excellent separation of hardness cations by the surface potential shift and sharpened pore size distribution , while exhibiting high rejection for SO 4 2− (≥99.00 %) by maintaining a negative membrane surface charge. The modified membrane provided efficient hardness removal (90.79 % for Ca 2+ , 95.94 % for Mg 2+ ) and enhanced anionic ECs rejection (95.24 % for PFOA, 98.44 % for PFOS), while maintaining operational stability, thus providing drinking water treatment potential for groundwater with high total dissolved solids.

研究领域: 环境工程 · 水处理 · 膜科学 · 材料科学
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Frontiers in Pharmacology · 2022 · IF 5.988

Natural Antibacterial and Antivirulence Alkaloids From Macleaya cordata Against Methicillin-Resistant Staphylococcus aureus

Liu Zhi-Hai,Wang Wei-Mei,Zhang Zhen,Sun Liang,Wu Shuai-Cheng

The emergence and spread of antibiotic-resistant bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA), underly the urgent need to develop novel antibacterial drugs. Macleaya cordata, a traditional medicinal plant, has been widely used in livestock animals, plants, and humans. Alkaloids are the primary bioactive compounds of Macleaya cordata and exhibit antibacterial, antiinflammatory, and antioxidant activities. Nevertheless, the antibacterial compounds and mode of action of Macleaya cordata remain unclear. In the present study, we investigated the antibacterial activity and mode of action of alkaloids from Macleaya cordata. Sanguinarine, 6-ethoxysanguinarine (6-ES), 6-methoxydihydrosanguinarine (6-MS), chelerythrine (CH), and dihydrochelerythrine (DICH) exhibited good antibacterial activity against Gram-positive bacteria, including MRSA. 6-ES rapidly killed MRSA, possibly by interfering with membrane and metabolic functions including ROS production by targeting the membrane and FtsZ in S. aureus. Additionally, 6-ES directly suppressed the hemolytic activity of α-hemolysin, alleviated inflammatory responses, and eliminated intracellular MRSA, as well as displayed low development of drug resistance, in vitro. Finally, a 6-ES-loaded thermosensitive hydrogel promoted wound healing in mice infected with MRSA. These results supported 6-ES as a novel potential candidate or leading compound with antibacterial, antivirulence, and host immunomodulatory activities in fighting against bacterial infections.

CAS / MDL: 53213-94-8
研究领域: 药理学 · 微生物学 · 传染病学 · 植物科学
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JOURNAL OF ETHNOPHARMACOLOGY · 2024 · IF 4.8

Diterpenoids of Caryopteris trichosphaera W. W. Sm. inhibiting MRSA and VRE in vitro and in vivo

Qing-Yu Lu,Zhao-Jie Wang,Li-Yu Bai,Wen-Biao Zu,Zhong-Shun Zhou,Yan-Yan Zhu,Yun-Li Zhao,Xiao-Dong Luo

Ethnopharmacological relevance Caryopteris trichosphaera W. W. Sm., a traditional ethnic medicine, was recorded in the Compendium of Materia Medica for treating wound infection by pathogenic infection. However, its antibacterial potential and bioactive compositions against drug-resistant bacteria need to be validated. Aim of the study To investigate the chemical constituents of C. trichosphaera and explore its anti-MRSA component in vitro and in vivo , together with the antibacterial mechanism. Materials and methods Bioactive constituents investigation was carried out by phytochemical method and antibacterial screening. The antibacterial mechanism was predicted by network pharmacology, which was further validated by time-kill analysis, membrane function tests, multigenerational resistance induction assay and biofilm test, and metabolomics analysis in vitro. In addition, MRSA-induced epidermal infection in mice was selected to evaluate its pharmacological effect in vivo . Results Six antibacterial diterpenoids against MRSA and VRE with MIC values 4–32 μg/mL from C. trichosphaera were reported for the first time, in which the major compound cativic acid ( 1 ) disrupted MRSA cell membranes by modulating permeability, depolarization, and fluidity while increasing reactive oxygen species (ROS) and malondialdehyde (MDA) levels. It also displayed remarkable anti-biofilm activity without inducing bacterial resistance or cytotoxicity. Moreover, cativic acid affected MRSA biosynthesis of cofactors, amino acid biosynthesis, nucleotide metabolism by metabolomics analysis. Furthermore, cativic acid accelerated wound healing in MRSA-infected mouse skin wounds, even better than vancomycin. Conclusions The results supported the traditional use of C. trichosphaera , and presented unreported anti-MRSA agent, cativic acid, as a plant-derived bactericide in vitro and in vivo for the first time.

CAS / MDL: 298-93-1
研究领域: 药理学 · 微生物学 · 民族药理学 · 植物化学 · 传染病学
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Small Structures · 2024 · IF 13.9

Chitosan-Stabilized PtAu Nanoparticles with Multienzyme-Like Activity for Mixed Bacteria Infection Wound Healing and Insights into Its Antibacterial Mechanism

Yujuan Wen,Wenxin Chen,Ruimei Wu,Jianpeng Guo,Xin Liu,Boling Shi,Cunshan Zhang,Lina Wu,Yanjie Zheng,Ailin Liu,Liqing Lin

Traditional antibacterial agents are often observed to be ineffective because bacteria evolved to strains with greater antibiotic resistance. Here, vigorous chitosan-stabilized PtAu nanoparticles (CSPA) with multienzyme-like activity are successfully fabricated, which serve an effective artificial nanozyme to enhance antibacterial activity for mixed bacterial infection wound treatment. Ultrasmall size CSPA exhibits excellent hydrophilicity and biocompatibility, possesses strong oxidase- and peroxidase-like activity generating a substantial amount of ROS ( O 2 − $$ {\mathrm{O}}_{2}^{-}$$ , 1 O 2 , ·OH) to cause oxidative damage to bacteria, also demonstrates nicotinamide adenine dinucleotide dehydrogenase-like activity disrupting the bacterial respiratory chains, and subsequently impedes adenosine triphosphate production. CSPA exhibits favorable broad-spectrum antibacterial activity at very low concentrations, prevents bacterial resistance, and completely inhibits bacterial biofilm formation. Antibacterial Mechanism of CSPA by the transcriptomics is further revealed that CSPA can induce bacterial oxidative stress, hinder bacterial energy metabolism, and disrupt the synthesis and function of bacterial cell walls and cell membranes. In vivo, CSPA inhibits the mixed bacterial population at the wound site and promotes wound healing in rats. This study introduces a novel antibacterial approach, providing important insight into the antibacterial mechanism of CSPA nanozymes and promoting the advancement of nanocatalytic materials in biomedical applications.

研究领域: 纳米技术 · 生物医学工程 · 材料科学 · 微生物学 · 药学
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