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NEUROTOXICITY RESEARCH · 2016 ·Vol. 31 ·期 2 ·259-268 · IF 3.14

Kukoamine A Prevents Radiation-Induced Neuroinflammation and Preserves Hippocampal Neurogenesis in Rats by Inhibiting Activation of NF-κB and AP-1

Zhang Yaqiong,Gao Lingyue,Cheng Zhihua,Cai Jiayi,Niu Yixuan,Meng Weihong,Zhao Qingchun

Impaired hippocampal neurogenesis and neuroinflammation are involved in the pathogenesis of radiation-induced brain injury. Kukoamine A (KuA) was demonstrated to have neuroprotective effects through inhibiting oxidative stress and apoptosis after whole-brain irradiation (WBI) in rats. The aim of this study was to investigate whether administration of KuA would prevent radiation-induced neuroinflammation and the detrimental effect on hippocampal neurogenesis. For this study, male Wistar rats received either sham irradiation or WBI (30 Gy single dose of X-rays) followed by the immediate injection of either KuA or vehicle intravenously. The dose of KuA was 5, 10, and 20 mg/kg, respectively. The levels of pro-inflammatory cytokines were assayed by ELISA kits. The newborn neurons were detected by 5-bromo-2-deoxyuridine (BrdU)/neuronal nuclei (NeuN) double immunofluorescence. Microglial activation was measured by Iba-1 immunofluorescence. The expression of Cox-2 and the activation of nuclear factor κB (NF-κB), activating protein 1(AP-1), and PPARδ were evaluated by western blot. WBI led to a significant increase in the level of TNF-α, IL-1β, and Cox-2, and it was alleviated by KuA administration. KuA attenuated microglial activation in rat hippocampus after WBI. Neurogenesis impairment induced by WBI was ameliorated by KuA. Additionally, KuA alleviated the increased translocation of NF-κB p65 subunit and phosphorylation of c-jun induced by WBI and elevated the expression of PPARδ. These data indicate that KuA could ameliorate the neuroinflammatory response and protect neurogenesis after WBI, partially through regulating the activation of NF-κB, AP-1, and PPARδ.

CAS / MDL: 59-14-3
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JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY · 2024 · IF 2.7

Effects of organochlorine pesticides on human and rat 17β-hydroxysteroid dehydrogenase 1 activity: Structure-activity relationship and in silico docking analysis

Chaochao Gong,Sailing Chen,Yunbing Tang,Huiqian Chen,Jianghuan Xie,Yanning Lv,Zhefan Shen,Yang Zhu,Shaowei Wang,Ren-shan Ge,Junzhao Zhao

The objective of this study was to examine the effect of 11 organochlorine pesticides on human and rat 17β-Hydroxysteroid dehydrogenase 1 (17β-HSD1) in human placental and rat ovarian microsome and on estradiol production in BeWo cells. The results showed that the IC 50 values for endosulfan, fenhexamid, chlordecone, and rhothane on human 17β-HSD1 were 21.37, 73.25, 92.80, and 117.69 μM. Kinetic analysis revealed that endosulfan acts as a competitive inhibitor, fenhexamid as a mixed/competitive inhibitor, chlordecone and rhothane as a mixed/uncompetitive inhibitor. In BeWo cells, all insecticides except endosulfan significantly decreased estradiol production at 100 μM. For rats, the IC 50 values for dimethomorph, fenhexamid, and chlordecone were 11.98, 36.92, and 109.14 μM. Dimethomorph acts as a mixed inhibitor, while fenhexamid acts as a mixed/competitive inhibitor. Docking analysis revealed that endosulfan and fenhexamid bind to the steroid-binding site of human 17β-HSD1. On the other hand, chlordecone and rhothane binds to a different site other than the steroid and NADPH-binding site. Dimethomorph binds to the steroid/NADPH binding site, and fenhexamid binds to the steroid binding site of rat 17β-HSD1. Bivariate correlation analysis showed a positive correlation between IC 50 values and LogP for human 17β-HSD1, while a slight negative correlation was observed between IC 50 values and the number of HBA. ADMET analysis provided insights into the toxicokinetics and toxicity of organochlorine pesticides. In conclusion, this study identified the inhibitory effects of 3–4 organochlorine pesticides and binding mechanisms on human and rat 17β-HSD1, as well as their impact on hormone production.

CAS / MDL: 110488-70-5
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ACS Applied Materials & Interfaces · 2024 · IF 8.3

Capillary Force-Assisted CsPbBr3–xIx (x = 0, 1) Columnar Crystal Film for X-ray Detectors with Ultrahigh Electric Field and Sensitivity

Sixin Chen,Meng Xu,Zhaolin Song,Yiran Shi,Ruichen Bai,Wanqi Jie,Menghua Zhu

Inorganic halide perovskite thin-film X-ray detectors have attracted great research interest in recent years due to their high sensitivity, low detection limit, and facile fabrication process. The poor crystal quality of the thin film with uncontrollable thickness and low background voltage during detection limits its practical application. Here, a high-quality CsPbBr3–xIx (x = 0, 1) columnar crystal film is prepared by an improved melt-confined method with a porous anodic aluminum oxide (AAO) template, which stabilizes the disorder perovskite systems of CsPbBr2I by stress. The AAO-CsPbBr3–xIx (x = 0) detectors exhibit high detection accuracy and photoelectric conversion capability with an ultrahigh sensitivity of 32,399.5 μC·Gyair–1·cm–2 at 2142.9 V mm–1 under 20 kVp X-rays and 19,217.4 μC·Gyair–1·cm–2 with a higher background electric field of 6666.7 V mm–1 for AAO-CsPbBr3–xIx (x = 1). Moreover, the AAO-CsPbBr3–xIx (x = 1) film detector acquires a lower detection limit of 7.65 nGy·s–1 and a higher X-ray imaging spatial resolution of 1.6 LP/mm and 8.6 nGy·s–1 and 1.4 LP/mm for AAO-CsPbBr3–xIx (x = 0). The facile, high-quality columnar crystal film devices display great potential for low-energy and low-dose X-ray imaging in flat panel detection applications.

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BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS · 2025 · IF 2.2

Deficiency of Calpain-1 attenuates atherosclerotic plaque and calcification and improves vasomotor dysfunction in Apolipoprotein E knockout mice through inhibiting inflammation

Youming Shi,Wenjiao Gu,Yujie Wei,Shuangyi Li,Shining Zhang,Ying jiang,Chuanjian Chen,Ting Liu,Limei Shuai,Xiaochun Zhou,Futian Tang

Purpose Atherosclerosis (AS) and atherosclerotic calcification (AC) are closely related to the cardiovascular diseases, largely due to its induction of vasomotor dysfunction. We previously reported that Calpain-1 inhibitor attenuated AS and AC. The present study was designed to investigate the effects and potential mechanisms of Calpain-1 knockout (Calpain-1 KO) in Apolipoprotein E KO (ApoE KO) mice on AS, AC, aortic vasomotor function as well as the liver dysfunction. Methods We hybridized ApoE KO mice with Calpain-1 KO mice to obtain ApoE /Calpain-1 double KO (A×C DKO) mice. The formation of AS and AC was evaluated and liver function was determined. Aortic vasomotor function was assessed. Contents of TNF-α, IL-6, IL-18, IL-1β and NO and the activity of AST, ALT, ALP and eNOS in serum were quantified. The mRNA expression of CD68, SR-A, CD36, PPAR-γ, LXR-α, ABCA1, BMP-2, OPN, ALP and Runx2 in aorta and/or liver were measured. Results The results showed that in comparison to C57 mice, ApoE KO mice demonstrated the significant increases in the areas of AS and AC, the increases in the mRNA expression of CD68 in the aorta, the increases in the AST, ALT and ALP activity in serum. ApoE KO mice also showed the dysfunction of the aortic contraction induced by phenylephrine and of the relaxation induced by acetylcholine. However, compared with ApoE KO mice, A×C DKO mice exhibited the significant attenuation of AS and AC and the downregulation of mRNA expression of CD68 in aorta. A×C DKO mice revealed the reduction of AST, ALT and ALP activity in serum, the improvements in aortic contraction and relaxation as well as the increases in eNOS activity and NO content in serum. A×C DKO mice also showed the decreases in the contents of TNF-α, IL-6, IL-18 and IL-1β in serum. The mRNA expression of CD68 in aorta, SR-A and CD36 in both aorta and liver of A×C DKO mice was downregulated, while that of PPAR-γ, LXR-α, and ABCA1 was upregulated in comparison of ApoE KO mice. In addition, the mRNA expression of BMP-2, OPN, ALP and Runx2 in aorta of A×C DKO mice was downregulated in comparison of ApoE KO mice. Conclusion The results suggested that deficiency of Calpain-1 attenuated the formation of AS and AC and improved vasomotor and liver dysfunction in ApoE KO mice through anti-inflammation, and modulation of the mRNA expression of genes related to AS and AC.

CAS / MDL: 59-42-7
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PeerJ · 2017 · IF 2.177

Interactions of 172 plant extracts with human organic anion transporter 1 (SLC22A6) and 3 (SLC22A8): a study on herb-drug interactions

Hang Lu,Zhiqiang Lu,Xue Li,Gentao Li,Yilin Qiao,Robert P. Borris,Youcai Zhang

Background Herb-drug interactions (HDIs) resulting from concomitant use of herbal products with clinical drugs may cause adverse reactions. Organic anion transporter 1 (OAT1) and 3 (OAT3) are highly expressed in the kidney and play a key role in the renal elimination of substrate drugs. So far, little is known about the herbal extracts that could modulate OAT1 and OAT3 activities. Methods HEK293 cells stably expressing human OAT1 (HEK-OAT1) and OAT3 (HEK-OAT3) were established and characterized. One hundred seventy-two extracts from 37 medicinal and economic plants were prepared. An initial concentration of 5 µg/ml for each extract was used to evaluate their effects on 6-carboxylfluorescein (6-CF) uptake in HEK-OAT1 and HEK-OAT3 cells. Concentration-dependent inhibition studies were conducted for those extracts with more than 50% inhibition to OAT1 and OAT3. The extract of Juncus effusus , a well-known traditional Chinese medicine, was assessed for its effect on the in vivo pharmacokinetic parameters of furosemide, a diuretic drug which is a known substrate of both OAT1 and OAT3. Results More than 30% of the plant extracts at the concentration of 5 µg/ml showed strong inhibitory effect on the 6-CF uptake mediated by OAT1 (61 extracts) and OAT3 (55 extracts). Among them, three extracts for OAT1 and fourteen extracts for OAT3 were identified as strong inhibitors with IC 50 values being <5 µg/ml. Juncus effusus showed a strong inhibition to OAT3 in vitro , and markedly altered the in vivo pharmacokinetic parameters of furosemide in rats. Conclusion The present study identified the potential interactions of medicinal and economic plants with human OAT1 and OAT3, which is helpful to predict and to avoid potential OAT1- and OAT3-mediated HDIs.

CAS / MDL: 3301-79-9
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MOLECULAR PHARMACEUTICS · 2024 · IF 4.5

G45 and V386 in Transmembrane Domains 1 and 8 Are Critical for the Activation of OATP1B3-Mediated E17βG Uptake by Clotrimazole

Wanjun Han,Zheyue Bo,Ting Liang,Han Liu,Lanjing Li,Zhening Guo,Ru Huan,Bruno Hagenbuch,Chunshan Gui

Organic anion-transporting polypeptides (OATPs) 1B1 and 1B3 are two highly homologous transport proteins. However, OATP1B1- and 1B3-mediated estradiol-17β-glucuronide (E17βG) uptake can be differentially affected by clotrimazole. In this study, by functional characterization on chimeric transporters and single mutants, we find that G45 in transmembrane domain 1 (TM1) and V386 in TM8 are critical for the activation of OATP1B3-mediated E17βG uptake by clotrimazole. However, the effect of clotrimazole on the function of OATP1B3 is substrate-dependent as clotrimazole does not stimulate OATP1B3-mediated uptake of 4′,5′-dibromofluorescein (DBF) and rosuvastatin. In addition, clotrimazole is not transported by OATP1B3, but it can efficiently permeate the plasma membrane due to its lipophilic properties. Homology modeling and molecular docking indicate that E17βG binds in a substrate binding pocket of OATP1B3 through hydrogen bonding and hydrophobic interactions, among which its sterol scaffold forms hydrophobic contacts with V386. In addition, a flexible glycine residue at position 45 is essential for the activation of OATP1B3. Finally, clotrimazole is predicted to bind at an allosteric site, which mainly consists of hydrophobic residues located at the cytoplasmic halves of TMs 4, 5, 10, and 11.

CAS / MDL: 64-18-6 15087-02-2
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CHEMICAL ENGINEERING JOURNAL · 2024 · IF 13.3

Fabrication of gold nanoparticles supported on hollow microsphere of nanosized TS-1 for the epoxidation of propylene with H2 and O2

Leilei Hou,Siyang Yan,Liping Liu,Jiaxu Liu,Guang Xiong

The TS-1 microsphere was facilely prepared via a direct spray drying of the mixture containing the nanocrystal TS-1 and mother liquor. The calcined TS-1 zeolites possess a hollow structure and numerous intercrystalline mesopores, which may facilitate the diffusion properties. Au nanoparticles were loaded on TS-1 support by utilizing a deposition–precipitation process to prepare the Au/TS-1-M catalysts for propylene epoxidation in the presence of H 2 and O 2 conditions. The effects of the Ti and Au loadings on the structure, porosity, morphology, and catalytic performances of the Au/TS-1 catalysts have been investigated by various techniques. Under the optimized synthesis conditions (Si/Ti molar ratio = 57, 0.49 wt% Au), a propylene conversion of 6.1 % and a PO selectivity of 91.7 % were obtained on the Au/TS-1 catalyst. A PO formation rate of 186.8 g PO ·kg cat. −1 ·h −1 was achieved at the 20th hour.

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Journal of Water Process Engineering · 2024 · IF 6.3

Flocculation behavior and interaction mechanism of carboxymethyl chitosan/chitosan-based graft flocculants on kaolinite (00−1) surface: Experiment and DFT calculation

Fengyang Liu,Wenjie Zou,Wei Zhao

Chitosan-based flocculants represent a highly promising alternative to industrial synthetic organic flocculants, offering exceptional environmental friendliness and efficiency. The carboxymethyl chitosan- graft -poly (acrylamide-dimethyl diallyl ammonium chloride) (CMCPD) and chitosan- graft -poly (acrylamide-dimethyl diallyl ammonium chloride) (CPD) were successful synthesized using UV-induced graft polymerization. The flocculation behavior and mechanism of these two chitosan-graft-copolymers on kaolinite suspension were investigated employing settling test and density functional theory calculation of the structural units of CMCPD and CPD on the kaolinite (00–1) surface. Experimental results indicated that the CMCPD had a greater settling rate of 19.47 m/h at the dosage of 80 g/t than CPD (12.96 m/h). The simulation results revealed distinct adsorption conformations of CMCPD and CPD units on the kaolinite (00–1) surface, characterized by an inclined posture and a horizontal posture, respectively. The stable adsorption of CPD can be attributed to the electrostatic attraction, which is evidenced by its higher adsorption energy (−4.74 eV) on the kaolinite (00–1) surface compared to CMCPD (−3.63 eV). It should be noted that both the adsorption energy and conformation play crucial roles in determining the flocculation efficiency of a flocculant. The inclined adsorption of CMCPD not only displayed electrostatic attraction but also enhanced its bridging ability, leading to a rapid increase in floc size and settling rate. The settling performance was significantly influenced by the bridging effect exerted by flocculants. This study holds great significance for the advancement of novel and efficient flocculant development.

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APPLIED SURFACE SCIENCE · 2024 · IF 6.3

Fabrication of mixed matrix membranes based on PVDF matrix and ZrT-1-NH2 filler for efficient adsorptive removal of Orange G

Bao-Xu Jiang,Shuang-Bao Li,Ting-Ting Xu,Jian Li,Yu-Teng Zhang

Adsorption membranes have become a hot spot for wastewater treatment in recent years. Due to the lack of active sites in traditional inert materials such as polyvinylidene fluoride (PVDF) membranes, it is difficult to bind pollutants in water with high affinity. Therefore, in this study, ZrT-1-NH 2 /PVDF mixed matrix membranes (MMMs) were prepared by combining an amino-functionalized Zr-based metal–organic cage (ZrT-1-NH 2 ) with a polymer substrate via non-solvent-induced phase separation method for the efficient removal of Orange G (OG) from water. This method has many advantages such as simplicity in operation, high applicability, controllable MOFs loading. The structural characteristics and adsorption properties and of MMMs were also investigated through a series of characterizations and experiments. The result shows that in a 100 mL OG solution with an initial concentration of 50 mg/L and pH=3, M60 exhibited significant adsorption capacity, the removal efficiency reached 97.23 %, with an adsorption capacity of 64.18 mg/g, which is much higher than the pristine PVDF membrane. It is mainly attributed to electrostatic interactions and hydrogen bonding interactions between ZrT-1-NH 2 and OG molecules. This is consistent with the DFT calculations. The introduction of ZrT-1-NH 2 filler improves the performance of PVDF membranes and expands their potential applications.

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FOOD CHEMISTRY · 2024 · IF 8.5

Kelp nanocellulose combined with fucoxanthin achieves lipid-lowering function by reducing oxidative stress with activation of Nrf2/HO-1/NQO1 pathway

Kuiyou Wang,Kexin Huang,Xueqian Li,Hao Wu,Li Wang,Fengyu Bai,Mingqian Tan,Wentao Su

This study innovatively utilized kelp-derived nanocellulose and sodium caseinate (SC) to prepare fucoxanthin (Fx)-loaded nanoparticles, exploring their efficacy in reducing oxidative stress and inhibiting lipid accumulation. 2, 2, 6, 6-Tetramethylpiperidine-1-oxyl (TEMPO)-mediated oxidation produced well-dispersed, kelp-derived nanocellulose. When these celluloses were mixed with SC at varying mass ratios, the composite nanoparticles showed excellent stability. Specifically, at a TEMPO-oxidized kelp nanocellulose (TKNC) to SC mass ratio of 1:3, the encapsulation efficiency for Fx reached 82.2 %, with a retention of 56.12 % after 14 days of storage. In vitro , the nanoparticles demonstrated good biocompatibility and were efficiently absorbed by cells, significantly enhancing Fx bioavailability . This enhanced delivery efficiency alleviates oxidative stress by activating the Nrf2/HO-1/NQO1 signaling pathways and effectively inhibits lipid droplet formation induced by excessive free fatty acids (FFAs). Moreover, distribution studies in mice revealed effective accumulation of nanoparticles in the intestines and liver, indicating their potential for targeted drug delivery. These findings provide strong experimental support for the use of TKNC and SC as biocompatible materials in nanoparticles for drug delivery and treatment applications.

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JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY · 2024 · IF 5.7

Key Contributions of the Overexpressed Plutella xylostella Sigma Glutathione S-Transferase 1 Gene (PxGSTs1) in the Resistance Evolution to Multiple Insecticides

Jiyuan Liu,Zhen Tian,Ruichi Li,Shujun Ni,Hong Sun,Fei Yin,Zhenyu Li,Yalin Zhang,Yifan Li

The overexpression of insect detoxification enzymes is a typical adaptive evolutionary strategy for insects to cope with insecticide pressure. In this study, we identified a glutathione S-transferase (GST) gene, PxGSTs1, that exhibited pronounced expression in the field-resistant population of Plutella xylostella. By using RNAi (RNA interference), the transgenic fly models, and quantitative real-time polymerase chain reaction (RT-qPCR) methods, we confirmed that the augmented expression of PxGSTs1 mediates the resistance of P. xylostella to various types of insecticides, including chlorantraniliprole, novaluron, λ-cyhalothrin, and abamectin. PxGSTs1 was found to bolster insecticide resistance in two ways: direct detoxification and enhancing antioxidative defenses. In addition, our findings demonstrated that pxy-miR-8528a exerts a pivotal influence on forming insecticide resistance in P. xylostella by downregulating PxGSTs1 expression. In summary, we elucidated the multifaceted molecular and biochemical underpinnings of PxGSTs1-driven insecticide resistance in P. xylostella. Our results provide a new perspective for understanding the insecticide resistance mechanism of P. xylostella.

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COLLOIDS AND SURFACES B-BIOINTERFACES · 2024 · IF 5.4

Lipase in-situ immobilized in covalent organic framework: Enzymatic properties and application in the preparation of 1, 3-dioleoyl-2-palmitoylglycerol

Ting Feng,Jiani Shi,Jiaojiao Xia,Xuemei Ren,Onyinye Idowu Adesanya,Hongbo Suo,Bin Zou

In this study, the critical importance of designing an appropriate immobilized carrier and method for free lipase to ensure exceptional biological catalytic activity and stability was emphasized. Covalent organic frameworks (COF-1) were synthesized as a novel porous carrier with an azine structure (-C N-N C-) through the condensation of hydrazine hydrate and benzene-1,3,5-tricarbaldehyde at room temperature. Simultaneously, Rhizomucor miehei lipase (RML) was immobilized within the COF-1 carrier using an in-situ aqueous phase method. Characterization of the carrier and RML@COF-1 and evaluation of the lipase properties of RML and RML@COF-1 through p -Nitrophenyl palmitate hydrolysis were conducted. Additionally, application in the synthesis of 1, 3-dioleoyl-2-palmitoylglycerol (OPO) was explored. The results showed that RML@COF-1 exhibited a high enzymatic loading of 285.4 mg/g. Under 60℃ conditions, the activity of RML@COF-1 was 2.31 times higher than that of free RML, and RML@COF-1 retained 77.25% of its original activity after 10 cycles of repeated use, indicating its excellent thermal stability and repeatability. Under the optimal conditions (10%, 1:8 PPP/OA, 45℃, 5 h), the yield of OPO reached 47.35%, showcasing the promising application prospects of the novel immobilized enzyme synthesized via in-situ aqueous phase synthesis for OPO preparation.

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