Cell Death & Disease
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2020
·Vol. 11
·期 5
·1-12
·
IF 6.304
Ye Shuangyan,Xu Pengfei,Huang Mengqiu,Chen Xi,Zeng Sisi,Wang Qianli,Chen Jianping,Li Keyi,Gao Wenwen,Liu Ruiyuan,Liu Jingxian,Shao Yihao,Zhang Hui,Xu Yang,Zhang Qianbing,Zhong Zhuo,Wei Zibo,Wang Jiale,Hao Bingtao,Huang Wenhua,Liu Qiuzhen
Tempol (4-hydroxy-2,2,6,6-Tetramethylpiperidine-1-oxyl, TPL), a nitroxide compound, inhibits proliferation and increases the vulnerability of cancer cells to apoptosis induced by cytotoxic agents. However, the molecular mechanism of TPL inhibiting cancer cell proliferation has not been fully understood. In this study, we evaluated the metabolic effect of TPL on cancer cells and explored its cancer therapeutic potential. Extracellular flow assays showed that TPL inhibited cellular basal and maximal oxygen consumption rates of mitochondrial. 13 C metabolic flux analysis showed that TPL treatment had minimal effect on glycolysis. However, we found that TPL inhibits glutamine metabolism by interfering with the oxidative tricarboxylic acid cycle (TCA) process and reductive glutamine process. We found that the inhibitory effect of TPL on metabolism occurs mainly on the step from citrate to α-ketoglutarate or vice versa. We also found that activity of isocitrate dehydrogenase IDH1 and IDH2, the key enzymes in TCA, were inhibited by TPL treatment. In xenograft mouse model, TPL treatment reduced tumor growth by inhibiting cellular proliferation of xenograft tumors. Thus, we provided a mechanism of TPL inhibiting cancer cell proliferation by interfering with glutamine utilization that is important for survival and proliferation of cancer cells. The study may help the development of a therapeutic strategy of TPL combined with other anticancer medicines.
研究领域:
癌症生物学
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代谢生物学
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药理学
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PubMed
高影响因子
Bioactive Materials
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2022
·
IF 16.874
Rui Wang,Jian Lu,Jiasheng Yin,Han Chen,Hongmei Liu,Fei Xu,Tongtong Zang,Rende Xu,Chenguang Li,Yizhe Wu,Qilin Wu,Xiang Fei,Meifang Zhu,Li Shen,Junbo Ge
An increased level of reactive oxygen species (ROS) plays a major role in endothelial dysfunction and vascular smooth muscle cell (VSMC) proliferation during in-stent thrombosis and restenosis after coronary artery stenting. Herein, we report an electrospun core-shell nanofiber coloaded with 4-hydroxy-2,2,6,6-tetramethylpiperidine 1-oxyl (TEMPOL) and rapamycin (RAPA) that correspondingly serves as an ROS scavenger and VSMC inhibitor. This system has the potential to improve the biocompatibility of current drug-eluting stent (DES) coatings with the long-term and continuous release of TEMPOL and rapamycin. Moreover, the RAPA/TEMPOL-loaded membrane selectively inhibited the proliferation of VSMCs while sparing endothelial cells (ECs). This membrane demonstrated superior ROS-scavenging, anti-inflammatory and antithrombogenic effects in ECs. In addition, the membrane could maintain the contractile phenotype and mitigate platelet-derived growth factor BB (PDGF-BB)-induced proliferation of VSMCs. In vivo results further revealed that the RAPA/TEMPOL-loaded covered stents promoted rapid restoration of vascular endothelium compared with DES and persistently impeded inflammation and neointimal hyperplasia in porcine models.
研究领域:
生物医学工程
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药学
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心脏病学
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材料科学
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DOI
PubMed
高影响因子
Journal of Energy Storage
·
2023
·
IF 9.4
Qinzheng Hu,Shuzhen Cui,Kanjun Sun,Xiuting Shi,Wenxing Miao,Xiangbing Wang,Hui Peng,Guofu Ma
In recent years, the research focus of flexible supercapacitor is to improve its energy density . The recently reported improved energy storage method is to introducing suitable redox-additive in gel electrolytes to enhance their redox-activity. Herein, a novel stretchable, redox-active and double-network 4-hydroxy-2,2,6,6-tetramethylpiperidine 1-oxy-containing polyacrylamide/alginate/H 2 SO 4 (PAM/SA/H 2 SO 4 /TEMPOL) hydrogel electrolyte is prepared by radical cross-linking polymerization and solvent displacement process. The PAM/SA/H 2 SO 4 /TEMPOL hydrogel possesses superior stretchability (750 %) because of the electrostatic interactions between the -NH 3+ groups of the PAM and the -COO − groups of SA . In addition, the introduction of the TEMPOL additive into PAM/SA/H 2 SO 4 /TEMPOL hydrogel electrolyte of flexible EDLC can gain a high specific capacitance (386 F g −1 ) and high energy density of 24.5 Wh kg −1 , which is due to dual redox reactions both positive/negative electrode. This study provides a new strategy for designing a multifunctional redox hydrogel electrolyte.
研究领域:
材料科学
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电化学
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能源存储
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DOI
高影响因子
VETERINARY MICROBIOLOGY
·
2026
·
IF 2.8
Leyu Hu,Lexi Gao,Xingwei Fu,Zesheng Rong,Yue Cheng,Yuhan Hou,Lu Han,Xin Ran,Guiwen Guan,Ting Zhou,Lingling Chang,Xiaomin Zhao,Qian Du,Yong Huang,Dewen Tong,Mingjun Zhu
PEDV infection induces intracellular iron accumulation in host cells. • Iron promotes CoV replication by enhancing Fe-S cluster-dependent RdRp activity. • TEMPOL suppresses CoV replication by disrupting viral Fe-S cluster integrity. • TEMPOL exhibits broad-spectrum anti-CoV activity in vitro and in vivo. • TEMPOL effectively counteracts iron-exacerbated viral pathogenesis in vivo. Coronaviruses (CoVs) can cause severe respiratory and enteric diseases, posing major threats to human health and the livestock industry. However, the host metabolic mechanisms underlying viral replication remain unclear. Using porcine epidemic diarrhea virus (PEDV) as the primary model, this study investigated the role of iron metabolism in CoV replication and its mechanisms. Our results showed that PEDV infection markedly induced intracellular iron accumulation, while exogenous iron supplementation enhanced viral replication and iron chelation suppressed it. Mechanistically, iron enhances viral replication by promoting the formation of iron-sulfur (Fe-S) clusters, essential cofactors for the viral RNA-dependent RNA polymerase (RdRp). Based on these findings, we further evaluated the antiviral activity of TEMPOL, a small molecule targeting viral Fe-S clusters. TEMPOL reduced RdRp activity and effectively inhibited PEDV replication. Moreover, TEMPOL exhibited broad-spectrum antiviral activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), infectious bronchitis virus (IBV), and porcine deltacoronavirus (PDCoV). Importantly, TEMPOL effectively reversed FAC-promoted viral pathogenesis, alleviating tissue lesions and clinical symptoms across multiple CoV animal models. Collectively, this study reveals a key role of iron metabolism in CoV replication and suggests that targeting viral Fe-S clusters may provide a novel strategy for anti-CoV therapy against diverse CoVs.
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PubMed
高影响因子
RSC Advances
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2023
·Vol. 13
·期 24
·16211-16221
·
IF 3.9
Chunxiao Wang,Ruifu Zhao,Zhen Wang,Tingting Xu,Peng Huang
Atherosclerosis (AS), a chronic inflammatory disease, is the leading cause of death worldwide. Anti-oxidative therapy has been developed for AS therapy in light of the critical role of ROS in pathogenesis of AS, but current anti-oxidants have exhibited limited outcomes in the clinic. Herein, new ROS-eliminating liposome-like NPs (Tempol-Lips) were assembled from synthetic lipids that covalently conjugated two Tempol molecules with phosphatidylcholine by esterification reaction. The obtained Tempol-Lips can be efficiently internalized into inflammatory macrophages and attenuated inflammation via scavenging overproduced intracellular ROS. After i.v. administration, Tempol-Lips with nanoscale character accumulated in the plaques of ApoE−/− mice through passive targeting and significantly inhibited the pathogenesis of AS, compared with those treated with control drugs. The therapeutic benefits of Tempol-Lips primarily are ascribed to the reduced local and systematic oxidative stress and inflammation. Preliminary studies in vivo further demonstrated Tempol-Lips were safe and biocompatible after long-term i.v. injection. Conclusively, Tempol-Lips can be developed as a novel anti-AS nanotherapy with potential translation in the clinic.
研究领域:
心血管疾病
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纳米医学
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药学
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分子生物学
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DOI
PubMed
高影响因子
TOXICOLOGY LETTERS
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2019
·
IF 3.499
Lingmin Zhang,Qingqing Xia,Yingying Zhou,Jie Li
Excessive accumulation of cadmium (Cd) in retina plays an important role in tobacco smoking-associated age-related macular degeneration (AMD). Plenty of evidence has revealed that the retinal pigment epithelium (RPE) is the primary site of pathology in AMD. Our current study demonstrated that Cd induced apoptosis in a human RPE cell line ARPE-19 cells, as it dose-dependently caused cell viability loss and activated caspase-3. The reactive oxygen species (ROS) were confirmed to be important mediators for Cd-triggered cell death in ARPE-19 cells. We found that endoplasmic reticulum (ER) stress was activated as its marker BiP was remarkably upregulated by Cd-exposure. Whereas the antioxidants N-acetylcysteine (NAC) and Tempol significantly suppressed the expression of BiP and CHOP, suggesting that ROS generation is an early trigger of Cd-activated ER stress. Furthermore, we found that Cd-induced oxidative stress significantly increased autophagic flux and p62 expression. A temporal impact of Cd exposure is possibly existed in p62 expression in ARPE-19 cells. Moreover, an ER stress inhibitor salubrinal diminished Cd-induced LC3BII expression and attenuated cytotoxicity, indicating that ER stress mediates autophagy and was implicated in apoptosis of Cd-exposed ARPE-19 cells. However, CHOP expression may not exert impact on the regulation of Cd-caused autophagy. Additionally, inhibition of autophagy with si-Beclin 1 and 3-Methyladenine significantly ameliorated Cd-induced CHOP expression and cytotoxicity, indicating that autophagy was detrimental in Cd-accumulated ARPE-19 cells, and a positive feedback regulation mechanism may exist between Cd-triggered ER stress and autophagy. Taken together, these results suggest that Cd-caused ER stress and autophagy are implicated in RPE cell death associated retinopathies especially related to smoking.
研究领域:
毒理学
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眼科学
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细胞生物学
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分子生物学
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DOI
PubMed
高影响因子
ACS Applied Polymer Materials
·
2025
·
IF 4.7
Md Alim Uddin,Yihua Shen,Li Wang,Haojie Yu,Huanan Wang,Xunchun Yuan,Abdul Basit,Muhammad Owais Malik,Khan Manqoosh Awan,Lichang Xu,Xiwang Yuan,Qiang Li
Because it is noninvasive and radiation-free, magnetic resonance imaging (MRI) is a commonly used imaging method that is very helpful for the early detection and monitoring of malignant growths. The development of alternative imaging probes is essential to reducing the toxicity of contrast agents (CAs) based on metals, such as gadolinium (Gd), which are used in clinical settings. Our goal is to create innovative MRI contrast agents that do not require metallic components and have great stability and relaxivity while still exhibiting excellent efficacy. In this work, the esterification reaction and ring-opening polymerization methods used to successfully synthesize pectin-nitroxide nanoconjugates are demonstrated, and their effective use as a CA for MRI is established. For each radical, the nanoconjugates have a favorable longitudinal water 1H relaxivity of 0.23 and 0.41 mM–1 s–1 for the pectin-TEMPO (PT) and pectin-PGTEMPO (PPGT). The PPGT exhibits notable characteristics like nontoxicity in vivo and resistance to quenching. For longer than 3 h, the PPGT in Wistar female rats shows increased MRI contrast. Comparable contrast enhancement is achieved with PPGT at 3.85 times lower (0.026 mmol/kg) than the standard dose (0.1 mmol/kg). Consequently, the PPGT shows promise as a workable metal-free MRI CA.
研究领域:
医学影像学
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生物材料学
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DOI
高影响因子
Journal of Environmental Chemical Engineering
·
2025
·
IF 7.2
Ya-Nan Wang,Yaxin Guo,Jinsong Peng,Jianwei Zhao,Lei Yang,Haiyan Song,Chunxia Chen
s Photocatalytic H 2 O 2 production represents a sustainable and promising avenue for energy and environment. Photoproduction of H 2 O 2 in seawater is potentially an alternative to meet the needs of H 2 O 2 utilization in ocean, while with challenges of competitive ions influence and unsolved photocatalytic mechanism. Herein, we constructed a S-scheme heterojunction with the lamellated WO 3 coated CdS semiconductors for photoproduction of H 2 O 2 in actual seawater. Fragmented WO 3 uniformly spread on surface of dispersed CdS spheres by two steps including calcination and ultrasound. Photocatalyst achieved considerable 1.00 mmol·g cat −1 ·h −1 of H 2 O 2 productivity in seawater without electron-proton donors and pure O 2 , 9.3 % of apparent quantum yield (AQY), as well as good reusability. A co-catalysis concept was proposed to explore specific role of ions in seawater on H 2 O 2 photoproduction. S-scheme heterojunction contributed to migration of electrons and holes on interface between WO 3 and CdS, and further promoted separation of photocarriers, and further opened another channel for H 2 O 2 generation. Accumulated electrons in conduction band (CB) of CdS involved in the main route of two-electron reduction of O 2 for H 2 O 2 production, also promoted generation of •O 2 - for opening the auxiliary route. WO 3 /CdS heterojunction provided fundamentals and opportunities for H 2 O 2 production and applications in abundant seawater as a sustainable way.
研究领域:
环境科学
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材料科学
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DOI
高影响因子
Nature Communications
·
2025
·Vol. 16
·期 1
·1-14
·
IF 15.7
Li Suiqin,Wang Shibin,Wang Yuhang,He Jiahui,Li Kai,Gerken James B.,Stahl Shannon S.,Zhong Xing,Wang Jianguo
Electrochemical alcohol oxidation (EAO) represents an effective method for the production of high-value carbonyl products. However, its industrial viability is hindered by suboptimal efficiency stemming from low reaction rates. Here, we present a synergistic electrocatalysis approach that integrates an active electrode and aminoxyl radical to enhance the performance of EAO. The optimal aminoxyl radical (4-acetamido-2,2,6,6-tetramethylpiperidine 1-oxyl) and Ni 0.67 V 0.33 -layered double hydroxide (LDH) are screen as cooperative electrocatalysts by integrating theoretical predictions and experiments. The Ni 0.67 V 0.33 -LDH facilitates the adsorption and activation of N -(1-hydroxy-2,2,6,6-tetramethylpiperidin-4-yl)acetamide (ACTH) via interactions with ketonic oxygen, thereby improving selectivity and yield at high current densities. The electrolysis process is scaled up to produce 200 g of the steroid carbonyl product 8b (19-Aldoandrostenedione), achieving a yield of 91% and a productivity of 243 g h -1 . These results represent a promising method for accelerating electron transfer to enhance alcohol oxidation, highlighting its potential for practical electrosynthesis applications.
研究领域:
电化学
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催化化学
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材料科学
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产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
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2024
·
IF 13.3
Danyang Wang,Shiwen Zhao,Jianke Li,Lin Shi,Yuhuan Zhang
The increasing bacterial resistance caused by the abuse of antibiotics has become an urgent global healthcare challenge. Recent advances in nanozymes represent one feasible solution. However, efforts have mainly focused on mimicking natural enzymes for comparable biocatalytic activities, as preparing nanozymes with superior antibacterial properties remains challenging. In this study, inspired by the Fe catalytic site in horseradish peroxidase (HRP), we synthesized defect-rich ruthenium oxide/iridium oxide heterojunction nanosheets (RuO 2 /IrO 2 ), using Ru, which possesses a similar electronic structure to Fe, as the catalytic site to enhance antibacterial properties. Benefiting from the typically high catalytic activity of Ru in various reactions and the unique Ir-mediated defect-rich heterostructure, RuO 2 /IrO 2 exhibits dramatically enhanced biocatalytic activities in generating reactive oxygen species crucial for eradicating bacteria. In particular, RuO 2 /IrO 2 exhibited both oxidase and peroxidase-mimicking activities with catalytic efficiency 10 3 to 10 4 times higher than that of HRP. It exhibited superior antibacterial properties as well as high biosafety , effectively eliminating H 2 O 2 toxicity during in vivo anti-infection measures. Minimum inhibitory concentration (MIC) values of RuO 2 /IrO 2 against Staphylococcus aureus and Escherichia coli were 31.25 and 15.62 μg mL −1 , respectively. This study offers a promising potential design for antibacterial nanozymes.
研究领域:
生物化学
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纳米医学
·
微生物学
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DOI
高影响因子
APPLIED SURFACE SCIENCE
·
2025
·
IF 6.9
Xin Liang,Laishi Li,Yusheng Wu,Feng Liu,Yuzheng Wang
The efficiency of Fenton-like catalysts was critically affected by the rapid transfer of Fe 2+ /Fe 3+ , a process that was essential for the formation of active free radicals by H 2 O 2 . Herein, we synthesized CuS/Fe 3 O 4 @MIL-100(Fe) (CFM) ternary composites using hydrothermal and in-situ growth methods to enhance the degradation of oxytetracycline hydrochloride (OTC-HCl) in a Fenton-like photocatalytic system. The incorporation of CuS as a co-catalyst into the double iron-based system significantly enhanced photocatalytic activity, achieving a 95.31 % degradation efficiency for OTC-HCl within 50 min under optimized conditions. The catalyst had good reusability, has 86.64 % degradation efficiency after five magnetic recovery cycles, and still showed good catalytic performance in the presence of five different concentrations of common anions. Further analysis using active species quenching and electron paramagnetic resonance (EPR) experiments revealed the role of oxygen-containing radicals in the process. Liquid chromatography-mass spectrometry (LC-MS) and density functional theory (DFT) calculations provided OTC-HCl degradation pathways and intermediates. X-ray Photoelectron Spectroscopy (XPS) analysis indicated that CuS enhanced the performance of the bis-iron-based materials by improving the transfer efficiency of Fe 2+ /Fe 3+ and Cu + /Cu 2+ ions, which in turn accelerated the generation of reactive radicals from H 2 O 2 .
研究领域:
环境科学
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材料科学
·
催化化学
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DOI
高影响因子
Nanomaterials
·
2024
·Vol. 14
·期 24
·2048
·
IF 4.4
Shuo Yang,Wenhui Li,Kaiyue Li,Ping Huang,Yuquan Zhuo,Keyan Liu,Ziwen Yang,Donglai Han
Photocatalytic technology holds significant promise for sustainable development and environmental protection due to its ability to utilize renewable energy sources and degrade pollutants efficiently. In this study, BiOI nanosheets (NSs) were synthesized using a simple water bath method with varying amounts of mannitol and reaction temperatures to investigate their structural, morphological, photoelectronic, and photocatalytic properties. Notably, the introduction of mannitol played a critical role in inducing a transition in BiOI from an n-type to a p-type semiconductor, as evidenced by Mott–Schottky (M-S) and band structure analyses. This transformation enhanced the density of holes (h + ) as primary charge carriers and resulted in the most negative conduction band (CB) position (−0.822 V vs. NHE), which facilitated the generation of superoxide radicals (·O 2− ) and enhanced photocatalytic activity. Among the samples, the BiOI-0.25-60 NSs (synthesized with 0.25 g of mannitol at 60 °C) exhibited the highest performance, characterized by the largest specific surface area (24.46 m 2 /g), optimal band gap energy (2.28 eV), and efficient photogenerated charge separation. Photocatalytic experiments demonstrated that BiOI-0.25-60 NSs achieved superior methylene blue (MB) degradation efficiency of 96.5% under simulated sunlight, 1.14 times higher than BiOI-0-70 NSs. Additionally, BiOI-0.25-60 NSs effectively degraded tetracycline (TC), 2,4-dichlorophenol (2,4-D), and rhodamine B (Rh B). Key factors such as photocatalyst concentration, MB concentration, and solution pH were analyzed, and the BiOI-0.25-60 NSs demonstrated excellent recyclability, retaining over 94.3% of their activity after three cycles. Scavenger tests further identified ·O 2− and h + as the dominant active species driving the photocatalytic process. In this study, the pivotal role of mannitol in modulating the semiconductor characteristics of BiOI nanomaterials is underscored, particularly in promoting the n-type to p-type transition and enhancing photocatalytic efficiency. These findings provide a valuable strategy for designing high-performance p-type photocatalysts for environmental remediation applications.
研究领域:
材料科学
·
环境科学
·
半导体物理
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PubMed
高影响因子
危险品化学品经营许可证（带存储）