Oxidative Medicine and Cellular Longevity
·
2018
·
IF 4.936
Xinnong Liu,Qingtian Zhu,Min Zhang,Tao Yin,Rong Xu,Weiming Xiao,Jian Wu,Bin Deng,Xuefeng Gao,Weijuan Gong,Guotao Lu,Yanbing Ding
Oxidative stress plays a crucial role in the pathogenesis of acute pancreatitis (AP). Isoliquiritigenin (ISL) is a flavonoid monomer with confirmed antioxidant activity. However, the specific effects of ISL on AP have not been determined. In this study, we aimed to investigate the protective effect of ISL on AP using two mouse models. In the caerulein-induced mild acute pancreatitis (MAP) model, dynamic changes in oxidative stress injury of the pancreatic tissue were observed after AP onset. We found that ISL administration reduced serum amylase and lipase levels and alleviated the histopathological manifestations of pancreatic tissue in a dose-dependent manner. Meanwhile, ISL decreased the oxidative stress injury and increased the protein expression of the Nrf2/HO-1 pathway. In addition, after administering a Nrf2 inhibitor (ML385) or HO-1 inhibitor (zinc protoporphyrin) to block the Nrf2/HO-1 pathway, we failed to observe the protective effects of ISL on AP in mice. Furthermore, we found that ISL mitigated the severity of pancreatic tissue injury and pancreatitis-associated lung injury in a severe acute pancreatitis model induced by L-arginine. Taken together, our data for the first time confirmed the protective effects of ISL on AP in mice via inhibition of oxidative stress and modulation of the Nrf2/HO-1 pathway.
研究领域:
药理学
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胃肠病学
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病理学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Food & Function
·
2020
·Vol. 11
·期 12
·10852-10863
·
IF 4.171
Mingbao Gu,Jie Jin,Chenghao Ren,Ximiao Chen,Weiyang Gao,Xiangyang Wang,Yaosen Wu,Naifeng Tian,Zongyou Pan,Aimin Wu,Yifei Zhou,Xiaolei Zhang
As an ordinary joint vestigial disease, osteoarthritis (OA) contributes to a considerable proportion of disability cases worldwide. Inflammation, as the main pathological factor, mediates the occurrence and development of OA. Akebia Saponin D (ASD), also known as Asperosaponin VI, is one of the active components extracted from Dipsaci Radix and is rich in Dipsacus loose tea. It has shown sound therapeutic effects on various diseases; nevertheless, its role in OA therapy is not completely understood. This study demonstrated the anti-inflammatory activity of ASD in OA through a series of in vivo and in vitro experiments. In vitro experiments revealed that ASD might prohibit the production of inflammatory mediators in IL-1β treated chondrocytes such as COX-2, iNOS, NO, PGE2, IL-6, and TNF-α. Meanwhile, it may also inhibit the production of ADAMTS-5 and MMP13 and promote the production of Aggrecan and Collagen II. The mechanism study demonstrated that ASD exerted an anti-inflammatory effect by activating the NRF2 target, upregulating the expression of HO-1, and preventing P65 from binding to DNA. In vivo experiments demonstrated that ASD might improve the progression of OA in a DMM mouse model. These research results provide evidence for the potential application of ASD in OA therapy.
研究领域:
药理学
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风湿病学
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炎症研究
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骨科
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DOI
PubMed
高影响因子
ENVIRONMENTAL TOXICOLOGY
·
2024
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IF 4.4
Lei Huang,Jiayi Wang,Jieqin Yu,Mengxuan Bian,Xingdong Xiang,Guanjie Han,Weisin Chen,Ning Wang,Jun Ge,Shunyi Lu,Jian Zhang
Osteoporosis (OP) can result in slower bone regeneration than the normal condition due to abnormal oxidative stress and high levels of reactive oxygen species (ROS), a condition detrimental for bone formation, making the OP-related bone healing a significant clinical challenge. As the osteogenic differentiation ability of bone marrow mesenchymal stem cells (BMSCs) is closely related to bone regeneration; currently, this study assessed the effects of Picein on BMSCs in vitro and bone regeneration in osteoporotic bone defect in vivo. Cell viability was determined by CCK-8 assay. The production of (ROS), malonaldehyde, superoxide dismutase activities, and glutathione was evaluated by using commercially available kits, and a flow cytometry analysis was adopted to detect macrophage polarization. Osteogenic capacity of BMSCs was evaluated by alkaline phosphatase (ALP) activity, ALP staining, and Alizarin red S staining. The expression of osteogenic-related proteins (OPN, Runx-2, OCN) and osteogenic-related genes (ALP, BMP-4, COL-1, and Osterix) were evaluated by Western blotting and real-time PCR (RT-PCR). In addition, proliferation, migration ability, and angiogenic capacity of human umbilical vein endothelial cells (HUVECs) were evaluated by EdU staining, scratch test, transwell assay, and tube formation assay, respectively. Angiogenic-related genes (VEGF, vWF, CD31) were also evaluated by RT-PCR. Results showed that Picein alleviated erastin-induced oxidative stress, enhanced osteogenic differentiation capacity of BMSCs, angiogenesis of HUVECs, and protects cells against ferroptosis through Nrf2/HO-1/GPX4 axis. Moreover, Picein regulate immune microenvironment by promoting the polarization of M2 macrophages in vitro. In addition, Picein also reduce the inflammation levels and promotes bone regeneration in osteoporotic bone defect in OP rat models in vivo. Altogether, these results suggested that Picein can promote bone regeneration and alleviate oxidative stress via Nrf2/HO-1/GPX4 pathway, offering Picein as a novel antioxidant agent for treating osteoporotic bone defect.
研究领域:
药理学
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骨生物学
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氧化应激
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干细胞研究
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炎症
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再生医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF HAZARDOUS MATERIALS
·
2021
·
IF 10.588
Kailian Zhang,Man Zhou,Kai Yang,Changlin Yu,Ping Mu,Zhenzhen Yu,Kangqiang Lu,Weiya Huang,Wenxin Dai
The low-usage of solar energy and the sluggish separation efficiency of the photogenerated electrons/holes pairs are the obstacles in the practical application of photocatalysts. The integration of upconversion and Z-scheme heterojunction is expected to break the barriers to achieve the efficient charge separation and broaden near-infrared light absorption . Herein, an effective indirect Z scheme AgInS 2 /In 2 S 3 heterostructure with carbon quantum dots (CQDs, as the electron conduction medium) and Lu 3 NbO 7 :Yb, Ho (as upconversion function) has been successfully synthesized. Consequently, the Lu 3 NbO 7 : Yb, Ho/CQDs/AgInS 2 /In 2 S 3 heterostructure exhibited superior photocatalytic activities for Cr(VI) reduction and H 2 O 2 production, reducing 99.9% of Cr(VI)(20 ppm, 15 min) and 78.5% of Cr(VI) (40 ppm, 30 min) with visible light irradiation as well as 94.0% of Cr(VI) (20 ppm, 39 min) under NIR light irradiation. Simultaneously, the heterostructure could generate 902.9 μM H 2 O 2 for 5 h under visible light irradiation. The intensive photocatalytic properties could primarily be attributed to the boosted light absorption capacity, the improved solar-to-energy conversion by the remarkable upconversion capacity of Lu 3 NbO 7 : Yb, Ho/CQDs and the faster charge transfer through a Z-schematic pathway. This work is anticipated to open a novel “window” for designing the efficient photocatalysts by coupling of Lu 3 NbO 7 : Yb, Ho and CQDs.
研究领域:
材料科学
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环境科学
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光化学
·
纳米技术
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产品关联
DOI
PubMed
高影响因子
SENSORS AND ACTUATORS B-CHEMICAL
·
2025
·
IF 7.7
Lei Shen,Ze Zhang,Xinying Guo,Zelin Zhong,Jia Zhang,Chengcheng Zhang,Hongmei Liu,Shuxiang Wang,Jinchao Zhang,Caixia Yin,Yutao Yang
Epilepsy is a chronic brain disease with various causes, among which oxidative stress-induced neuronal damage is a significant pathological factor and has been widely studied as one of the key pathogenic mechanisms. Hydrogen peroxide (H₂O₂), a representative reactive oxygen species (ROS), plays an important role in epilepsy. However, real-time imaging capable of revealing the distribution of H₂O₂ in the living brain remains limited. To address this, we developed a feasible fluorescent probe library based on the unique reaction between the α-ketoester moiety and H₂O₂, combined with dicyanoisophorone derivatives possessing excellent optical performance. In consequence, DCI-BT-PY was optimized as a novel fluorescent probe for H₂O₂ through parallel testing of its physicochemical and optical properties. Notably, due to its good blood-brain barrier (BBB) penetration, DCI-BT-PY was used to monitor H₂O₂ upregulation in the brains of epileptic mice, revealing a close relationship between H₂O₂ and epilepsy. Furthermore, using the Sombati epilepsy model of hippocampal neuronal cells and the mouse model of epilepsy, the neuroprotective effect of curcumin on oxidative stress injury of nerve cells was explored, showing that it may alleviate epilepsy by activation of the Nrf2/HO-1 signaling pathway for suppressing the neurotoxic damage. This finding offers new insights into the pathogenesis and treatment of epilepsy. Additionally, this work provides a reliable tool for evaluating H 2 O 2 fluctuations in the brains of epilepsy-induced mice, thereby establishing a solid foundation for antioxidant therapies targeting epilepsy.
研究领域:
神经科学
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药理学
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生物化学
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分子生物学
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医学影像学
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神经病学
✓ 已验证
DOI
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2023
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IF 5.6
WenBin Liu,ZhengWei Tan,YueChao Zhao,YanNa Zhao,XiaoLing Yu,BoLin Wang,FengLin Shen,Ai Mi,JinJian Lan,RuiLan Gao
Panaxadiol saponin (PND) is a latent targeted drug for the treatment of aplastic anemia (AA). In this study, we examined the effects of PND on ferroptosis in iron-overload AA and Meg-01 cells. We utilized RNA-seq to analyze differentially expressed genes in iron-induced Meg-01 cells treated with PND. The effects of PND or combined with deferasirox (DFS) on iron deposition, labile iron pool (LIP), several ferroptosis events, apoptosis, mitochondrial structure, as well as ferroptosis-, Nrf2/HO-1-, and PI3K/AKT/mTOR pathway-related markers in iron-induced Meg-01 cells were examined by Prussian-blue staining, flow cytometer, ELISA, Hoechst 33342 staining, transmission electron microscope, and Western blot assays, respectively. Additionally, an AA mice model with iron overload was established. Then, the blood routine was assessed, and the number of bone marrow-derived mononuclear cells (BMMNCs) in mice was counted. Also, serum iron, ferroptosis events, apoptosis, histology, T lymphocyte percentage, ferroptosis-, Nrf2/HO-1-, and PI3K/AKT/mTOR signaling-related targets in primary megakaryocytes of AA mice with iron overload were assessed by commercial kits, TUNEL staining, hematoxylin and eosin (H&E) staining, Prussian blue staining, flow cytometer, and qRT-PCR analysis, respectively. PND suppressed iron-triggered iron overload, and apoptosis, and ameliorated mitochondrial morphology in Meg-01 cells. Importantly, PND ameliorated ferroptosis-, Nrf2/HO-1-, and PI3K/AKT/mTOR signaling-related marker expressions in iron-induced Meg-01 cells or primary megakaryocytes of AA mice with iron overload. Moreover, PND ameliorated body weight, peripheral blood cell counts, the number of BMMNCs, and histological injury in the iron-overload AA mice. Also, PND improved the percentage of T lymphocytes in the iron-overload AA mice. PND attenuates ferroptosis against iron-overload AA mice and Meg-01 cells via activating Nrf2/HO-1 and PI3K/AKT/mTOR pathway and is a promising novel therapeutic candidate for AA.
研究领域:
药理学
·
血液学
·
细胞生物学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
CELL STRESS & CHAPERONES
·
2023
·
IF 3.8
He Xin,Wang Juan,Sun Lei,Ma Wenqi,Li Miao,Yu Shanshan,Zhou Qi,Jiang Jue
Mastitis is a disease involved in inflammation of breast which affects human and animals. Wogonin is one bioactive compound from many Chinese herbal medicines, which have multiple properties, including anti-inflammatory activity. However, the roles of wogonin in mastitis progression are largely undefined. Mastitis models were established using LPS-treated mice and mammary epithelial cells (MECs). Infiltration of inflammatory cells was analyzed by hematoxylin-eosin staining and myeloperoxidase (MPO) activity. Inflammatory cytokine (TNF-α and IL-1β) levels were detected via ELISA. The phosphorylation and total of Akt and NF-κB levels and content of Nrf2 and HO-1 were measured via western blot. Cell viability was examined by CCK-8 assay. Oxidative stress was assessed by ROS generation and levels of MDA, GSH, and SOD. Wogonin attenuated LPS-induced infiltration of inflammatory cells, increase of MPO activity and levels of TNF-α and IL-1β, and activation of the Akt/NF-κB pathway in murine mammary gland tissues, and promoted activation of Nrf2/HO-1 signaling. Wogonin did not affect MEC viability, but mitigated LPS-induced inflammation in MECs by reducing TNF-α and IL-1β levels. Wogonin relieved LPS-induced oxidative stress in MECs through decreasing ROS generation and MDA level and increasing GSH and SOD levels. Wogonin repressed LPS-induced activation of the Akt/NF-κB pathway in MECs and increased Nrf2/HO-1 signaling activation. Activated Akt/NF-κB signaling or Nrf2/HO-1 signaling inactivation reversed the suppressive effects of wogonin on LPS-induced inflammation and oxidative stress in MECs. Wogonin mitigates LPS-induced inflammation and oxidative stress of MECs via suppressing activation of the Akt/NF-κB signaling and activating Nrf2/HO-1 pathway, indicating the therapeutic potential of wogonin in mastitis.
研究领域:
药理学
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免疫学
·
细胞生物学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF NEUROTRAUMA
·
2023
·
IF 4.2
Hongxing Tang,Kejun He,Kun Zhao,Chen Zheng,Weichi Wu,Weilin Jin,Lixuan Yang,Baoshu Xie
Hinokitiol (β-thujaplicin, HIK) is a natural monoterpene small molecule compound showing various biological effects including antibacterial, anti- inflammatory and anti-tumor. Ferroptosis, a new form of iron-dependent cell death, has been demonstrated as one of the pathophysiological mechanisms of traumatic brain injury (TBI). However, the effect of hinokitiol on neuronal ferroptosis after traumatic brain injury has not been reported. Here, we show that hinokitiol alleviated excessive glutamate-induced intracellular reactive oxygen species (ROS), lipid peroxidation, and Fe2+ accumulation in HT-22. Moreover, hinokitiol upregulated heme oxygenase-1 (HO-1) expression, promoted nuclear factor-erythroid factor 2-related factor 2 (Nrf2) nuclear translocation, and inhibited the activation of microglia and astrocyte after TBI. Furthermore, hinokitiol remarkably reduced brain tissue lesions, mitigated neuron loss, iron deposition and attenuated neurologic impairment in the CCI-constructed TBI model in vivo. These results suggest that hinokitiol has neuroprotective effects on rescuing cells from TBI-induced neuronal ferroptosis. In summary, we reveal a novel role of hinokitiol in TBI, which has neuroprotective effects on rescuing cells from TBI-induced neuronal ferroptosis. Moreover, hinokitiol through activating the Nrf2/Keap1/HO-1 signaling pathway significantly reduces the neuronal damage, suggesting that it is a potential therapeutic candidate for TBI.
研究领域:
神经科学
·
药理学
·
细胞生物学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2024
·
IF 4.4
Chencen Lai,Shuo Zhang,Zhiyu Chen,Xiaoyu Fu,Min Zhang,Pengjiao Wang,Xiuli Gao
Pyroptosis induced by oxidative stress is a significant contributor to mental health disorders, including depression (+)-Catechin (CA), a polyphenolic compound prevalent in various food sources, has been substantiated by prior research to exhibit potent antioxidant properties and potential antidepressant effects. Nonetheless, the precise antidepressive mechanisms and effects of CA remain incompletely elucidated. In this study, we employed corticosterone (CORT) and PC12 cells to develop a cellular model of depression, aiming to investigate the protective effects of CA against CORT-induced cellular damage. Our objective was to elucidate the underlying mechanisms of protective action. We utilized transcriptomic analysis to identify differentially expressed genes and employed bioinformatics approaches to predict the potential mechanisms of CA’s protective effects in PC12 cells. These transcriptomic predictions were subsequently validated through western blot analysis. The findings indicated that CA possesses the capacity to mitigate oxidative stress and suppress pyroptosis in PC12 cells via the activation of the PI3K/AKT signaling pathway. This activation subsequently modulates the Nrf2/HO1/NF-κB pathways, thereby providing protection to PC12 cells against damage induced by CORT. Furthermore, we investigated the interaction between CA and the Keap1 protein employing molecular docking and protein thermal shift assays. We propose that CA can activate Nrf2 through two mechanisms to decrease reactive oxygen species (ROS) levels and inhibit pyroptosis: one mechanism involves the activation of the PI3K/AKT signaling pathway, and the other involves direct binding to Keap1, leading to an increase in p-Nrf2.
研究领域:
神经科学
·
药理学
·
细胞生物学
·
分子生物学
·
生物信息学
✓ 已验证
DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2021
·
IF 5.34
Shusheng Fan,Xiaoyun Liu,Yu Wang,Xueyang Ren,Yue Liu,Ying Dong,Qiqi Fan,Jing Wei,Jiamu Ma,Axiang Yu,Ruolan Song,Hong Sui,Meng Shen,Fang Fang,Qing Xia,Gaimei She
Background Thymus quinquecostatus Celak. has been widely used as a spice and a folk medicine for relieving exterior syndrome and alleviating pain in China. Purpose To explore the protective effects and the underlying mechanism against cerebral ischemia-reperfusion injury (CIRI) of the T. quinquecostatus combining with its chemical composition. Study design and methods High-polar extract (HPE) was extracted from T. quinquecostatus and polyphenols in HPE were enriched to obtain polyphenol-rich fraction (PRF) using Macroporous resin. The free radicals and zebrafish embryos were used to compare the antioxidant activities of HPE and PRF in vitro and in vivo . Then, the transient middle cerebral artery occlusion (tMCAO) model was established in rats. Neurological deficit score, infarction rate, morphology and apoptosis of neurons were examined to investigate the protective effects of PRF on CIRI. The mRNA and protein levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and hemeoxygenase-1 (HO-1) and the activities of downstream antioxidant enzymes in ischemia tissues were determined to clarify the underlying mechanisms. Also, reactive oxygen species (ROS) level in zebrafish embryos were detected after incubation with PRF for a short time (2 h) to investigate whether PRF could directly eliminate free radicals. Finally, chemical composition of PRF were analyzed to investigate the material basis for antioxidant activity and anti-CIRI effect. Results Compared with HPE, PRF showed stronger antioxidant activities. PRF exhibited obvious protective effects including ameliorating neurological deficit, lowering infarction rate, and improving the cellular morphology in hippocampus CA1 and cortex after tMCAO. TUNEL staining suggested PRF dose-dependently improved the apoptosis of the neurons in ischemic cortex. RT-qPCR and Western Blot results suggested that PRF regulated oxidative stress (OS) via activating the Keap1/Nrf2/HO-1 signaling pathway . Also, PRF could directly scavenge excessive ROS in zebrafish embryos after a short-time PRF incubation. The anti-CIRI effect might be primarily attributed to the abundant polyphenols in PRF, including flavonoids , polymethoxylated flavonoids, flavonoid glycosides , and phenolic acids. Conclusion T. quinquecostatus contains abundant polyphenols and exhibited a good protective effect against CIRI via dual antioxidant mechanisms, providing a reference for further research and application for this plant.
研究领域:
药理学
·
神经科学
·
分子生物学
·
植物科学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF MOLECULAR LIQUIDS
·
2017
·
IF 3.648
Yong Zhou,Yinyan Gong,Yongli Huang,Zengsheng Ma,Xi Zhang,Chang Q. Sun
Solvation of acid, base, and salt is ubiquitously important to all subject areas in chemistry , health care and life science. However, fine resolution of the solvation dynamics, solute-solvent molecular interactions , and solute capability of transforming the hydrogen bond (O:H O, or HB) and surface stress remain great challenge. Incorporating the notion of O:H O bond cooperativity with a strategy of differential phonon spectroscopy (DPS) has enabled resolution on the fraction and stiffness of the solvent HB from the mode of water to the hydration shells upon NaOH, NaI and HI solvation. Results show that Na + and I + ionic polarization shortens the H O bond and stiffens its phonon from 3200 to 3500 cm − 1 in the hydration shells. The H + in the HI solution forms a H ↔ H anti-HB that disrupts the solution network and surface stress. The excessive electron lone pairs of OH – form the O : ⇔ : O super-HB that compresses the network, sharing the same effect of mechanical compression shifting the H O phonon from above 3100 cm − 1 to its below; the solute H O bond performs the same to the H O dangling bond at surface featured at 3610 cm − 1 . The fraction coefficients or phonon abundance transition, f H = 0, f HO ∝ C, and f x ∝ 1-exp(− C/C 0 ) (x = Na + and I − and C the solute concentration) towards saturation, feature the solute capability of HB transformation. Practice not only confirms the essentiality of the H ↔ H anti-HB point fragilization, the O : ⇔ : O super-HB point compression, and the ionic polarization to the performance of the respective HI, NaOH, and NaI solutions, but also demonstrate the power of the DPS that enables fine-resolution of solvation dynamics and solute capabilities.
研究领域:
化学
·
医疗保健
·
生命科学
·
物理化学
·
光谱学
✓ 已验证
DOI
高影响因子
INORGANIC CHEMISTRY
·
2022
·
IF 5.436
Min Chen,Zhengli Liang,Xiaoxiao Wang,Jiehua Li,Xingguo Chen,Xingxing Jiang,Zheshuai Lin,Zhen Ma,Hongming Liu
A series of lanthanide-containing water-resistant nitrates, namely RE(OH)2NO3 (RE = Tb(1), Dy(2), Ho(3), and Er(4)), was obtained through the hydrothermal process. As possible nonlinear optical materials, they feature a layered isomorph composed of an [REO3(OH)6] polyhedron and an [NO3] triangle, and the synergistic arrangement of the [REO3(OH)6] and [NO3] groups in their structures leads to their obvious second-order nonlinear optical effect. Nevertheless, the unique optical absorption caused by the electronic transitions on 4f–4f orbitals of lanthanides results in their second harmonic generation responses of different strengths, with 1 exhibiting 5.07 times that of KDP, but 2–4 showing less than half of KDP. In addition, 1 possesses an outstanding water-resistant capacity and a transparent cut-off edge around 300 nm, foreshadowing its potential value as a nonlinear optical crystal. Moreover, 1 is found to emit characteristic green fluorescence due to the typical 5D4 → 7F5 transitions of the excited Tb3+ ions
研究领域:
材料科学
·
光学
·
化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）