SCIENCE OF THE TOTAL ENVIRONMENT
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2022
·
IF 10.753
Xu Shi,Tong Xu,Wei Cui,Xue Qi,Shiwen Xu
Environmental harmful pollutants microplastics (MPs) and di (2-ethyl) hexyl phthalate (DEHP) are widely residual in the environment, which may cause lesion to multiple apparatus by inducing oxidative stress, threatening the health of human and animals. Neutrophil extracellular traps (Nets) are involved in skin wound healing. Most studies focused on the individual effects of different poisons on animals and ecosystems, but there are few studies on the accumulation and interaction of multiple poisons. The purpose of this study is to explore the effect of DEHP and MPs co-exposure on skin wound healing and the formation of Nets. For this purpose, we detected this hypothesis by replicating the DEHP and MPs-exposed skin wound model in mice, as well as the co-culture system of neutrophil and fibroblast. The results displayed that MPs and DEHP exposure delayed skin healing, which was more pronounced in the combined exposure group. In vitro and in vivo experiments confirmed that compared with the DEHP or MPs group, the DEHP+MPs group had more significant oxidative stress, increased Nets release and inflammatory factors, and inhibited the Wnt/β-catenin pathway and fibrosis-related factors. N -acetylcysteine (NAC) attenuated these phenomena. Through the co-culture system, we confirmed that the overproduction of Nets induced fibroblasts to exacerbate inflammatory responses and inhibit Wnt pathway and fibrosis. Overall, DEHP and MPs can produce synergistic toxic injury in mice skin wounds, and the excessive activation of ROS/Nets can aggravate inflammatory and inhibit fibrosis, resulting in delayed wound healing.
研究领域:
环境科学
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毒理学
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细胞生物学
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免疫学
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DOI
PubMed
高影响因子
CANCER LETTERS
·
2024
·
IF 9.1
Ying Ning,Yu Chen,Tian Tian,Xinyan Gao,Xiaolan Liu,Jia Wang,Huijun Chu,Chenyang Zhao,Yufei Yang,Ke Lei,He Ren,Zhumei Cui
Neutrophil extracellular traps (NETs) have been shown to promote the metastatic potential of many kinds of tumors. Our study aimed to investigate the role and mechanisms of NETs in lymph node metastasis (LNM) of cervical cancer (CCa), and evaluated the therapeutic value of targeting NETs in CCa. Immunohistochemistry demonstrated that neutrophil infiltration and NETs formation were increased in CCa patients with LNM, as well as confirming a positive correlation between S100A7 expression and neutrophil infiltration in CCa. NETs enhanced the migratory capability of CCa by activating the P38-MAPK/ERK/NFκB pathway through interaction with TLR2. Digesting NETs with deoxyribonuclease 1 (DNase 1) or inhibiting TLR2 with chloroquine eliminated the NETs-induced metastatic potential of CCa. Additionally, NETs promoted lymphangiogenesis and increased the permeability of lymphatic vessels, thus facilitating translymphatic movement of CCa. CCa-derived S100A7 exhibited a chemotactic effect on neutrophils and promoted NETs generation by elevating ROS levels rather than activating autophagy in neutrophils. The mouse model with footpad implantation illustrated that DNase 1 effectively reduced LNM in LPS-induced mice and in mice seeded with S100A7-overexpressing CCa cells. In conclusion, our study reveals a new tumor-promoting mechanism of S100A7, clarifies the crucial role and mechanism of NETs in LNM of CCa, and indicates that the NETs-targeted therapy emerges as a promising anti-metastasis therapy in CCa.
研究领域:
肿瘤学
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免疫学
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分子生物学
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癌症治疗
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DOI
PubMed
高影响因子
ACS Nano
·
2026
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IF 17.3
Yang Chen,Ranjie Lei,Qi Guo,Kehao Liu,Huaiyi Cheng,Sanyang Yu,Yuzhou Li,Ping He,Sheng Yang
Cationic materials serve as a critical strategy for capturing neutrophil extracellular traps (NETs), which are structured around negatively charged DNA and represent a key pro-inflammatory pathogenic factor. However, their application is constrained by the inherent cytotoxicity of positive charges. Here, we develop a charge-adaptive neutrophil-targeted nanoparticle system (CPS@BA) through conjugating sialic acid (SA) to carboxymethyl chitosan (CMCS)–polyethylenimine (PEI) copolymer and physically encapsulating the calcium chelator BAPTA-AM (BA). This smart nanoparticle exhibits charge adaptability, dynamically and reversibly responding to acidic transitions in the pathological milieu. When sensing the acidic milieu on activated neutrophil surfaces, CPS@BA reverses its charge from negative to positive, thereby facilitating rapid NETs capture. Once inflammation is resolved and the pH returns to neutral, the residual CPS@BA reversibly switches back to biocompatible negative charges, effectively minimizing cationic biotoxicity. Meanwhile, charge adaptation triggers a cascade of size adaptation, enabling CPS@BA to ingeniously regulate the release of BA, which could suppress further NETs formation by chelating intracellular Ca2+ and inhibiting PAD4 enzymatic activation. As a result, the simultaneous clearance and inhibition of NETs effectively block the detrimental crosstalk between NETs and macrophages by interrupting the CXCL3–CXCR2 axis. This intervention rescues mitochondrial dysfunction and promotes metabolic reprogramming in pro-inflammatory macrophages, ultimately alleviating inflammatory bone resorption in experimental periodontitis. Overall, this study presents a secure and reversible charge-adaptive strategy capable of simultaneously clearing and inhibiting NETs, holding broad potential for the treatment of all free DNA-driven inflammatory diseases.
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DOI
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
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2025
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IF 4.7
Mei Bai,Ning An,Meng Cheng,Jia Qin,Jie Wang,Rumeng Jia,Wentao Liu,Jingcai Cheng,Qiang Xu,Xuefeng Wu
Neutrophil extracellular traps (NETs) play a key role in the development of psoriasis, a chronic inflammatory skin condition. We demonstrate the effects and possible mechanisms of phenethyl isothiocyanate (PEITC) in inhibiting NETs and alleviating psoriasis. In response to imiquimod (IMQ), multiple symptoms including scaly plaques and associated skin inflammations were induced in mice. IMQ additionally promotes the formation of NETs and the levels of inflammatory factors. Interestingly, a natural compound PEITC exerted an intensive activity in the treatment of psoriasis. It improved lesions and ameliorated ischemic coagulation symptoms in the dorsal skin of mice. PEITC also significantly reduced the expression of inflammatory factors in mice skin with an inhibition on NETs-related molecules, such as myeloperoxidase, neutrophil elastase and citrullinated histone H3. 16S rRNA sequencing analysis demonstrated that IMQ treatment induced significant gut microbiota dysbiosis in mice, suggesting potential detrimental effects on intestinal microbial homeostasis. However, PEITC administration did not show a statistically significant ameliorative effect on this IMQ-induced microbial imbalance. In vitro experiments demonstrated that PEITC significantly suppressed lipopolysaccharide (LPS)-induced NET formation, suggesting that its therapeutic effects in psoriasis may be due to the inhibition of bacterially driven neutrophil activation. Therefore, we identified PAD4, an important enzyme for post-translational modification of proteins in the production of NETs, as a new potential target of PEITC. Taken together, our findings suggest that PEITC could be a novel potential therapeutic drug to relieve psoriasis via the inhibition of NETs both in vitro and in vivo .
研究领域:
免疫学
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皮肤病学
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微生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
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2025
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IF 11.5
Ying Zhang,Shiqi Lin,Xiao Xu,Yufan Yao,Shufan Feng,Sida Jiang,Yuqian Wang,Wei He,Ran Mo
Dysregulation of growth factor expression causes impaired healing of diabetic foot ulcer (DFU). Platelet-derived growth factor (PDGF)-containing gel has been clinically applied for topical treatment of DFU. Recruitment of neutrophils stimulated by PDGF favors the wound healing of DFU. However, overactivation of neutrophils induced by hyperglycemia causes massive generation and long-term persistence of neutrophil extracellular traps (NETs), ultimately leading to unexpected skin damage and delayed wound repair. Here, we engineer a hierarchically-assembled hydrogel to achieve local release of the growth factor, PDGF-BB and the NET scavenger, deoxyribonuclease (DNase) I with distinct kinetics for enhanced healing of DFU. The hydrogel is constructed by crosslinking of anti-bacterial quaternized chitosan and hypochlorite-degradable nanogel via a copper-free click reaction, in which PDGF-BB is loaded in the hydrogel matrix while DNase I is encapsulated in the inner nanogel. Programmable release of combinatorial therapeutics is implemented by the hydrogel in response to the wound microenvironment. We show that the hierarchical hydrogel co-loaded with PDGF-BB and DNase I promotes neutrophil recruitment, increases endothelial cell migration, degrades excess NETs, and prevents wound infection for accelerating the wound closure in the diabetic mouse wound models.
研究领域:
生物材料学
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医学工程
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再生医学
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DOI
PubMed
高影响因子
ACS Nano
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2025
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IF 16
Lizhi OuYang,Ze Lin,Xi He,Jiaqi Sun,Jiewen Liao,Yuheng Liao,Xudong Xie,Weixian Hu,Ruiyin Zeng,Ranyang Tao,Mengfei Liu,Yun Sun,Bobin Mi,Guohui Liu
Thetreatment of infected wounds is currently a major challenge in clinical medicine, and enhancing antimicrobial and angiogenic capacity is one of the most common strategies. However, the current treatment makes it difficult to balance the antimicrobial effect in the early stage and the angiogenic effect in the later stages of wound healing, leading to an increased rate of poor prognosis. Here, we present a nanoconductive hydrogel EF@S-HGM, consisting of HGM with ECGS, FMLP, and SWCNT. The host–guest supramolecular macromolecule (HGM) hydrogel is biocompatible and can be injected in situ in the wound. The endothelial cell growth factor (ECGS) accelerates vascular remodeling and repairs wounds by promoting the proliferation of endothelial cells. N-Formyl-Met-Leu-Phe (FMLP) recruits neutrophils and increases the antimicrobial capacity. Single-walled carbon nanotubes (SWCNT) make the hydrogel conductive, enabling the hydrogel to utilize the endogenous electric field in the wound to recruit multiple kinds of cells. In addition, we found that the EF@S-HGM hydrogel activates the glucocorticoid receptor senescence pathway and promotes the formation of NET, which enhances the antimicrobial effect. As tissue-engineered skin, the conductive hydrogel EF@S-HGM is a promising material for regenerative medicine that may provide a potential option for the treatment and care of infected wounds and significantly improve patient outcomes and prognosis.
研究领域:
生物医学工程
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再生医学
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免疫学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Immunology
·
2025
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IF 5.9
Rongrong Huang,Ranran Chen,Lijuan Xing,Lianhao Wu,Wenwen Zhu,Junsong Jing,Ting Zhou,Yueguo Wu,Sheng Zhang,Zhenqiang You
Background Viral pneumonia is the most common and lethal pandemic disease, but there are no broad-spectrum antiviral drugs with high genetic barriers to resistance. To elucidate the mechanisms of viral pneumonia progression and potential targets for its treatment. Methods Viral pneumonia models were induced by the PR8 virus strain in wild-type (WT) and STING knockout (STING-KO) mice. Series of molecular biology techniques were used to evaluate the severity of pneumonia and cytokine levels. Results In this study, STING (stimulator of interferon genes) was activated in the lungs of virus-infected mice, leading to cytokine production and amplification of the immune response, thereby causing rapid deterioration of symptoms. Furthermore, excessive activation of innate immune response via STING was prevented by a STING inhibitor (C-176), which significantly reduced viral lung inflammation. The formation of neutrophil extracellular traps (NETs) was similarly suppressed during viral pneumonia treatment with STING inhibitors (C-176), and NETs formation and STING expression were positively correlated, indicating that STING plays an important role in NETs formation. Symptoms of pneumonia in STING-KO mice infected with PR8 were significantly milder than those in WT mice, and NETs were less likely to form in the lung tissue of STING-KO mice. Additionally, transcriptomic analysis revealed that STING-mediated regulation of NETs may be associated with gasdermin D (GSDMD), and immunoprecipitation experiments revealed that STING, GSDMD, and NETs-related proteins interact with each other. Immunofluorescence assays revealed that in neutrophils from WT mice, STING and GSDMD were colocalized on the membrane after viral infection, whereas in neutrophils from STING-KO mice, GSDMD expression was decreased after exposure to the virus. Conclusions Our study demonstrated that targeted intervention with STING alleviated pneumonia by inhibiting inflammation and NETs formation. The study also revealed that blocking STING could inhibit the activation of GSDMD to inhibit NETs formation, slowing the progression of viral pneumonia.
研究领域:
免疫学
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病毒学
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分子生物学
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呼吸病学
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药理学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2020
·Vol. 30
·期 13
·1909554
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IF 16.836
Hui Liu,Shichao Zhang,Lifang Liu,Jianyong Yu,Bin Ding
Particulate matter (PM) pollution in air is thought to be an important mortality risk factor globally. Most existing air filters face the extreme challenge of effectively removing PM 0.3 , which has the most penetration particle size (MPPS) of ≈0.3 µm yet is particularly harmful. Here, an innovative in situ electret electrospinning/netting technique that can manipulate both solution phase separation and crystal phase transition is reported to develop self-polarized polyvinylidene fluoride nanofiber/net membranes with 2D networks and superior surface adhesion. By combining the true nanoscale diameter (≈21 nm), small pore size (≈0.26 µm), and highly electret surface (6.8 kV potential) of the 2D nanonets, the synergistic effect of sieving and adhesion for MPPS PM 0.3 is achieved. Such double capture characteristic enables the high-efficiency (≈99.998%) capture of PM 0.3 while maintaining low air resistance (≈0.1% atmosphere pressure). Moreover, the nanofiber/net filters show integrated properties of superhydrophobicity, desirable transparency (91%), and long-term stability. The synthesis of such attractive nanomaterials presents a promising attempt toward the development of high-performance filtration/separation materials for numerous applications.
研究领域:
材料科学
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环境科学
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纳米技术
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DOI
高影响因子
Small
·
2017
·Vol. 13
·期 46
·1702139
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IF 8.643
Fenglei Zuo,Shichao Zhang,Hui Liu,Hao Fong,Xia Yin,Jianyong Yu,Bin Ding
The filtration performance and light transmittance of nanofiber air filters are restricted by their thick fiber diameter, large pore size, and substrate dependence, which can be solved by constructing substrate-free fibrous membranes with true nanoscale diameters and ultrathin thicknesses, however, it has proven to be extremely challenging. Herein, a roust approach is presented to create free-standing polyurethane (PU) nanofiber/nets air filters composed of bonded nanofibers and 2D nanonets for particular matter (PM) capture via combining electrospinning/netting technique and facile peel off process from designed substrates. This strategy causes widely distributed Steiner-tree structured nanonets with diameters of ≈20 nm and bonded scaffold nanofibers to assemble into ultrathin membranes with small pore size, high porosity, and robust mechanical strength on a large scale based on ionic liquid inspiration and surface structure optimization of receiver substrates. As a consequence, the resulting free-standing PU nanofiber/nets filters exhibit high PM 1–0.5 removal efficiency of >99.00% and PM 2.5–1 removal efficiency of >99.73%, maintaining high light transmittance of ≈70% and low pressure drop of 28 Pa; even achieve >99.97% removal efficiency with ≈40% transmittance for PM 0.3 filtration, and robust purification capacity for real smoke PM 2.5 , making them promising high-efficiency and transparent filtration materials for various filtration and separation applications.
研究领域:
材料科学
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环境科学
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DOI
PubMed
高影响因子
RSC Advances
·
2025
·Vol. 15
·期 19
·14821
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IF 4.6
Huan Xu,Dengwei He,Huimin Tao
Methicillin-resistant Staphylococcus aureus (MRSA) has spread across diverse global environments, and MRSA-related infection is a major threat to public health. Implant-associated infection (IAI) caused by MRSA remains a tough global clinical problem. Conventional antibiotic therapy has limited efficacy in treating MRSA-related IAI, and antibiotic abuse has resulted in the emergence of multidrug-resistant bacteria. Hence, there is a necessity to explore more effective approaches to deal with MRSA-related IAI. Herein, inspired by neutrophil extracellular traps (NETs) released by neutrophils to kill microorganisms, this study proposes a novel biomimetic nano-NET strategy using an epsilon-poly- l -lysine-coated CuO 2 nanoplatform, denoted as PCPNAs. The function-adaptive nanoplatform exhibited excellent Fenton-like performance, including robust ROS generation and GSH scavenging ability. PCPNAs showed >90% cell viability in mammalian cells and reduced bacterial burden by 7.65 log 10 CFU in vitro . Moreover, the positively charged PCPNAs could easily bind to negatively charged MRSA cells through charge-coupling and simultaneously exerted a trapping effect on MRSA cells. Notably, PCPNAs self-assembled into web-like structures to physically trap and kill biofilm bacteria, achieving 99.58% biofilm eradication. Furthermore, PCPNAs showed satisfactory biocompatibility in vivo and displayed ideal anti-bacterial and anti-inflammatory effects in a mouse model with implant-associated infection. With further development and optimization, the biomimetic nano-NET strategy based on PCPNAs provides a new therapeutic option for the treatment of MRSA-related implant-associated infection. Schematic of a biomimetic nano-NET strategy based on PCPNAs for the treatment of MRSA-related implant-associated infections.
研究领域:
医学
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微生物学
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纳米医学
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感染病学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF MATERIALS SCIENCE
·
2026
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IF 4.4
Li Zhu,Sun Ningxin,Li Shiwei,Yang Jiaao,Guo Yi,Dong Lijie
Biofouling on marine aquaculture nets poses significant challenges to the economic viability and environmental sustainability of mariculture. This study developed a novel composite coating PS- b -PDMS/CaO 2 on the net surface by incorporating oxygen-releasing calcium peroxide nanoparticles (CaO 2 NPs) into a polystyrene-polydimethylsiloxane block copolymer (PS- b -PDMS). This coating synergistically combines low surface energy with a sustained oxygen-enriched microenvironment and enhanced reactive oxygen species (ROS) generation, resulting in significantly enhanced antifouling performance. Experiments demonstrated that the coating achieved outstanding antifouling efficacy, with antibacterial rates exceeding 99% against Escherichia coli, Staphylococcus aureus, and the marine bacterium Pseudomonas aeruginosa, anti-diatom adhesion rates of 92.18%, and anti-protein adhesion rates of 96.82%, with an optimal loading of 0.6 wt%. Moreover, the coating improved the mechanical properties (~ 35.53 MPa) while preserving the low-surface-energy characteristics and sustained oxygen release for over 60 h. A 90-day marine field test verified minimal biological fouling on the PS- b -PDMS/CaO 2 -0.6 coating surface, showing excellent real-sea antifouling performance and structural stability, indicating the long-term serviceability of aquaculture nets in marine environments. This study proposes a novel technical pathway for the development of environmentally friendly, long-term stable, and high-performance antifouling and antibacterial coatings that can effectively adapt to complex marine environments. Graphical abstract
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高影响因子
Journal of Materials Chemistry A
·
2014
·Vol. 2
·期 22
·8246-8251
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IF 0
Aisheng Huang,Qian Liu,Nanyi Wang,Jürgen Caro
Inspired by the bio-adhesive ability of the marine mussel, highly hydrogen permselective ZIF-8 membranes were prepared on polydopamine functionalized stainless-steel-nets (SSNs). With polydopamine functionalization of SSNs under mild conditions, the nucleation and growth of well-intergrown ZIF-8 membranes were promoted through the formation of strong non-covalent and covalent bonds, which was helpful to enhance the membrane’s separation selectivity while maintaining high permeance. For binary mixtures at 100 °C and 1 bar, the mixture separation factors of H2–CO2, H2–N2, H2–CH4 and H2–C3H8, were found to be 8.1, 15.0, 23.2 and 329.7, which by far exceed the corresponding Knudsen coefficients and those of the as-reported ZIF-8 membranes. The ZIF-8 membranes also displayed high permeances, with the H2 permeance higher than 2.1 × 10−5 mol m−2 s−1 Pa−1 due to the high void volume of the SSNs.
研究领域:
材料科学
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膜技术
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气体分离
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金属有机框架材料（MOFs）
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DOI
危险品化学品经营许可证（带存储）