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BIOSCIENCE REPORTS · 2020 ·Vol. 40 ·期 7 · IF 2.942

Artesunate inhibits osteoclastogenesis through the miR-503/RANK axis

Huang Ming-Zhi,Zhuang Yong,Ning Xu,Zhang Hao,Shen Zhi-Min,Shang Xian-Wen

Osteoporosis is a metabolic bone disease that is characterized by decreased bone density and strength due to excessive loss of bone protein and mineral content, which can be induced by increased osteoclast activity. Developing agents targeting osteoclast activation is considered to be the most effective method to reverse bone destruction and alleviate the pain caused by osteoporosis. MTT assay was conducted to detect the cell viability after artesunate treatment of RAW264.7 cells. TRACP staining and pit formation assays were performed to examine the TRACP-positive cells and pit-forming activity of osteoclasts. qRT-PCR and Western blot analysis were performed to assess the mRNA and protein expression levels of the osteoclastogenesis-related genes NFATc1, TRAP, and cathepsin k. The protein levels of RANK, p-Akt, p-p38, and p-ERK were examined by Western blotting. Luciferase reporter assay was conducted to determine whether miR-503 targeted RANK directly. Artesunate inhibited TRACP-positive cells and the pit-forming activity of osteoclasts. However, artesunate increased the expression of miR-503. Artesunate suppressed osteoclastogenesis-related gene expression and RANKL-induced activation of MAPKs and the AKT pathway. In addition, miR-503 inhibited RANK expression by directly targeting RANK during osteoclast differentiation. Artesunate inhibited osteoclastogenesis and osteoclast functions in vitro by regulating the miR-503/RANK axis and suppressing the MAPK and AKT pathways, which resulted in decreased expression of osteoclastogenesis-related markers.

CAS / MDL: 88495-63-0
研究领域: 药理学 · 骨骼生物学 · 分子生物学
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BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS · 2025 · IF 2.2

Apelin-13 treats postmenopausal osteoporosis by reducing mitochondrial oxidative phosphorylation and modulating the OPG/RANK/RANKL/IGF-1 pathway

XiaoRong Meng,Dandan Meng,Chenhui Xiang,Lingling Pu,Xiaofei Yin,Jing Yang

Objective Postmenopausal osteoporosis (PMOP) is a prevalent metabolic bone disorder characterized by decreased bone mineral density and an increased risk of fractures. This study aims to investigate the molecular mechanisms underlying the therapeutic effects of Apelin-13 in PMOP. Methods A PMOP model was established using mouse embryonic pre-osteoblast MC3T3-E1 cells treated with dexamethasone (DEX). A variety of experimental techniques—including MTT assays, Western blotting, flow cytometry, immunofluorescence staining, mitochondrial membrane potential assays, and ELISA—were employed to elucidate the potential mechanisms through which Apelin-13 exerts its therapeutic effects. Results Apelin-13 significantly enhanced osteoblast activity and effectively reversed the inhibitory effects of DEX on cell proliferation. It suppressed apoptosis by modulating the expression of apoptosis-related proteins. Furthermore, Apelin-13 promoted osteogenic differentiation, upregulated osteogenic protein expression, increased alkaline phosphatase (ALP) activity, and facilitated calcium nodule formation. It also improved mitochondrial function by reducing levels of reactive oxygen species (ROS) and malondialdehyde (MDA), boosting antioxidant enzyme activity, and activating the Nuclear factor erythroid 2-related factor 2 (NRF2) signaling pathway. Critically, Apelin-13 was found to regulate the OPG/RANK/RANKL/IGF-1 signaling axis, and its pro-osteogenic effects were significantly enhanced when used in combination with SPA0355. Conclusion Apelin-13 exhibits promising therapeutic potential for PMOP in in vitro models by modulating key processes related to bone metabolism. It achieves this by attenuating mitochondrial oxidative phosphorylation and regulating the OPG/RANK/RANKL/IGF-1 pathway, thereby laying a foundation for future in vivo studies and clinical applications.

研究领域: 骨生物学 · 内分泌代谢病学 · 分子药理学 · 细胞信号转导 · 氧化应激与抗氧化 · 骨骼系统疾病 · 转化医学
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FASEB JOURNAL · 2020 ·Vol. 34 ·期 3 ·3583-3593 · IF 4.966

Amyloid β peptide promotes bone formation by regulating Wnt/β-catenin signaling and the OPG/RANKL/RANK system

Bu Yang,Shangfu Li,Zheng Chen,Feng Feng,Lei He,Bin Liu,Tianwei He,Xuan Wang,Ruiqiang Chen,Zihao Chen,Peigen Xie,Limin Rong

Background Amyloid β peptide (Aβ) is involved in osteoporosis, but the effects of Aβ on osteoblast and bone formation remain unclear. In this study, we investigated the effect of Aβ on bone formation. Methods An animal model of osteoporosis was established by ovariectomy in C57BL/6 mice. The mice received intraperitoneal injection of Aβ. The effect of Aβ on the osteogenic differentiation of human bone marrow stromal stem cells (hBMSCs) and differentiation of both pre-osteoblasts and pre-osteoclasts in a co-culture system were investigated. Results In the animal study, intraperitoneal injection of Aβ for 8 weeks promoted early and late osteogenic differentiation of hBMSCs. Aβ treatment significantly elevated osterix + (osteoblastic) cells but decreased TRAP + cells (osteoclasts) in the distal femur bone. In vitro study showed that Aβ treatment significantly enhanced matrix mineralization and osteogenic markers (Runx2 and osteocalcin). Aβ treatment activated Wnt/β-catenin signaling in hBMSCs. The effect of Aβ was blocked by DKK1 (a Wnt/β-catenin inhibitor) treatment. In the co-culture system, Aβ treatment significantly increased the ALP activities of MC3T3-E1 cells (pre-osteoblasts) but reduced the TRAP + RAW264.7 cells (pre-osteoclasts). Aβ treatment upregulated TCF1 and OPG proteins in MC3T3-E1 cells. Aβ treatment upregulated IκB-α but downregulated NFATc1protein in RAW264.7 cells. These effects were blocked by XAV-939 (a Wnt signaling antagonist), and then rescued by additional Wnt3a (a Wnt agonist). Conclusion Aβ treatment simultaneously promoted osteogenic differentiation via Wnt/β-catenin signaling, and inhibited osteoclasts differentiation via the OPG/RANKL/RANK system, suggesting Aβ is a positive regulator of osteoblast differentiation and bone formation.

CAS / MDL: 130-22-3
研究领域: 生物学 · 医学 · 细胞生物学 · 分子生物学
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Food & Function · 2022 ·Vol. 13 ·期 11 ·6419-6432 · IF 6.317

Anti-osteoporosis effects and regulatory mechanism of Lindera aggregata based on network pharmacology and experimental validation

Furong Wang,Pengze Rong,Juan Wang,Xiao Yu,Na Wang,Shengyu Wang,Zikai Xue,Junnan Chen,Wenlong Meng,Xin Peng

Osteoporosis (OP) is characterized by the flaccidity of bones or bone bi-disease caused by kidney deficiency. Lindera aggregate has been used to strengthen kidney function in China for thousands of years. It has been approved by Chinese Pharmacopoeia that the root of Lindera aggregata (RLA) can replenish and tonify the kidney, which is thought to be an effective way to alleviate OP. In this study, a network pharmacology approach was applied to explore the active components and potential mechanisms of RLA in osteoporosis treatment. Then, the ethanolic extract of the root of L. aggregata (EERL) was prepared and these predicted results were validated by prednisone-induced zebrafish embryos model. Moreover, the candidate compounds were identified by UPLC-ESI-MS/MS. The anti-OP results showed that EERL could significantly reverse the bone loss of zebrafish induced by prednisone. The mRNA expressions results showed that EERL decreased osteoclast bone resorption by regulating the RANK/RANKL/OPG system. Also, it increased bone formation by regulating the gene expressions of spp1, mmp2, mmp9, runx2b, alp, and entpd5a. Our results demonstrated the reliability of the network pharmacology method, and also revealed the anti-OP effect and potential mechanism of RLA.

研究领域: 药理学 · 分子生物学 · 中医药学 · 斑马鱼研究
✓ 已验证 DOI PubMed 高影响因子
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FUEL PROCESSING TECHNOLOGY · 2020 · IF 4.982

Hydrogen peroxide oxidation degradation of a low-rank Naomaohu coal

Yankun Xiong,Lijun Jin,Yang Li,Jialong Zhu,Haoquan Hu

A mild controllable oxidation method was developed to depolymerize the macromolecular aromatic clusters of NMH coal into water-soluble products (WSPs) without ring-open reaction. Hydrogen peroxide (H 2 O 2 ) was employed to oxidize coal sample at 60 °C, and the effect of reaction time on coal conversion and oxidation products was studied. The results showed that H 2 O 2 is able to break bridge bonds and side chains connected to aromatic clusters, while C ar -C ar bonds of arene keep unchanged at same conditions. After 10 h oxidation, the coal conversion is 83.4 wt% and the aromaticity of oxidation residue is 7.43%, indicating most of aromatics have transferred to WSPs. The aromatic ring distribution in WSP can reflect that of NMH coal to some extent, where 1-ring, 2-ring and 3-ring compounds account for 58.4 mol%, 19.9 mol% and 21.7 mol%, respectively. Moreover, the pyrolysis of NMH coal and oxidation residue was conducted on an online pyrolysis-vacuum ultraviolet photoionization mass spectrometry , and the oxidation of several typical model compounds was also carried out to understand the oxidation mechanism. The results showed that the PhO-RPh bonds between aromatic clusters are most easily destroyed by H 2 O 2 . H 2 O 2 oxidation degradation of coal are accompanied by generation of alkenes and decarboxylic reaction.

研究领域: 化学工程 · 煤炭科学
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iScience · 2023 · IF 5.8

Social rank-dependent effects of testosterone on huddling strategies in mice

Ye Zhao,Xueyong Yin,Yang Yu,Shihao Huang,Hao Feng,Shuang Wang,Yiming Cai,Ruofan Zhao,Shuai Gao,Ye Liu,Zhengxin Zhang,Xinyu Zhao,Ruonan Qiao,Jialin Yuan,Weichen Guan,Huiping Yang,Yun Shi,Haishui Shi

Huddling behavior, a typical social interaction among animals, has the benefits of obtaining social support and adapting environment. Huddling behavior is determined by social (social hierarchy), environmental factors (stress events), and the neuroendocrine system. Nevertheless, the huddling behavior of different social hierarchies and the underlying mechanisms have not been fully elucidated. In the present study, acute 2-methyl-2-thiazoline (2 MT) can induce huddling behavior and significantly increase serum levels of testosterone (T) in mice; and the increased T level was positively correlated with huddling behavior. Further, the T treatment significantly increased the huddling behavior in mice under 2 MT exposure condition. More interestingly, T can quickly promote dominant individuals to occupy safe positions when huddling together under predator odor. Collectively, T can rapidly regulate the individual's adaptive response to threats in a social rank-dependent manner, which provides a new perspective for the in-depth study of the influencing factors and underlying mechanisms of huddling behavior.

研究领域: 神经生物学 · 内分泌学 · 行为学
✓ 已验证 DOI PubMed 高影响因子
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POWDER TECHNOLOGY · 2020 · IF 4.142

Flotation intensification of low-rank coal using a new compound collector

Chunyun Zhu,Yaowen Xing,Yangchao Xia,Yongtian Wang,Guosheng Li,Xiahui Gui

Traditional non-polar oil collectors cannot achieve high recovery of low-rank coal because of the presence of oxygen-containing groups at coal surface. In this study, a new mixture of fossil oil and oxygen containing compound (FO) was used to enhance low-rank coal flotation compared with that using traditional collector, diesel oil. The oil droplet-particle detachment, induction-time, stability of the bubble-particle aggregate, attachment angle test and chemical force microscopy (CFM) were selected to further analyze the strengthening mechanism of collectors. The results show that higher yield was obtained using FO than that using diesel. Compared with diesel, FO was easier to adhere and spread on coal surface. The shorter induction time, higher amplitude and bigger attachment angle in presence of FO indicated that the FO treatment enabled the particles to much easily adhere to bubble. CFM provided a new insight into intensification mechanism of collector by the direct measurement of interaction force.

CAS / MDL: 71310-21-9
研究领域: 化学工程 · 矿物加工 · 煤炭科学
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MOLECULES · 2022 ·Vol. 27 ·期 19 ·6460 · IF 4.927

Effect of Ultrasonic Pretreatment on Flocculation Filtration of Low-Rank Coal Slurry

Aosheng Yang,Yinfei Liao,Maoyan An,Yijun Cao,Zhe Yang,Hourui Ren,Hailong Su,Qiqi Zou,Luojian Chen

The efficient filtration of low-rank coal (LRC) slurry was significantly beneficial to the production process of wet coal beneficiation. However, relatively few studies have been reported on novel pretreatment methods for the efficient filtration of LRC slurry. In this paper, the mechanism of ultrasonic pretreatment to promote flocculation and filtration of slurry was studied. The hydrophobic variation of the slurry surface was measured by contact angle and XPS. The flocculation properties of slurry were characterized using zeta potential and FBRM. The effects of filter cake porosity and ultrasonic pretreatment on slurry filtration resistance were calculated by L-F NMR and Darcy’s theory. The results showed that the ultrasonic pretreatment promoted the flocculation and filtration performance of LRC slurry, increased the filtration rate, and decreased the cake moisture content. Meanwhile, the contact angle of LRC increased significantly from 50.1° to 67.8° after ultrasonic pretreatment, and the surface tension of the filtrate decreased from 69.5 to 53.31 mN/m. Ultrasonic pretreatment reduced the absolute value of the zeta potential of coal slurry from 24.8 to 21.0 mV, and the average chord length of flocs increased from 5–10 μm to 25–30 μm, thus weakening the electrostatic repulsion between coals to promote floc formation. In addition, the pore tests and filtration theory calculations showed that the ultrasonic pretreatment significantly improved the permeability of the filter cake to water and reduced the resistance to slurry during filtration. In particular, the mesopore porosity increased by 9.18%, and the permeability increased by 2.937 × 108m2. Therefore, this contributed to the reduction of slurry filtration resistance. This research provides an efficient method for promoting the efficient filtration of slurry.

研究领域: 矿物加工工程 · 化学工程 · 环境工程
✓ 已验证 DOI 高影响因子
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INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES · 2025 ·Vol. 26 ·期 24 ·12151 · IF 4.9

A Novel RANKL/RANK Inhibitor IMB-R38 Inhibits Osteoporosis Through Regulating Bone Metabolism

Yuyan Zhang,Xinwei Wei,Ren Sheng,Guijun Yang,Xiaowan Han,Jingrui Wang,Chao Liu,Shunwang Li,Lijuan Lei,Weilian Jiang,Yang Lun,Shuyi Si,Jing Zhang,Yanni Xu

Osteoporosis is a systemic skeletal disease that severely impairs the health of the elderly population. The interaction between the receptor activator of the NF-κB ligand (RANKL) and its receptor RANK is critical for osteoclast differentiation and function. Therefore, targeting the RANKL/RANK interaction represents a promising strategy for osteoporosis. In this study, we employed a newly established yeast two-hybrid system based on RANKL/RANK interaction and identified IMB-R38, a novel benzamide compound that dose-dependently blocked RANKL/RANK interaction by inhibiting the growth of AH109 cells harboring pAD-RANKL/pBD-RANK plasmids in quadruple-dropout medium. IMB-R38 significantly suppressed osteoclast differentiation, disrupted F-actin ring formation, and downregulated the expression of osteoclast-specific genes, including NFATc1 and MMP9 in RANKL-induced RAW264.7 macrophages. IMB-R38 also promoted osteoblast differentiation by upregulating the expression of osteogenic genes. Importantly, in a dexamethasone (DXM)-induced osteoporotic zebrafish model, IMB-R38 significantly increased bone mineralization, with anti-osteoporosis efficacy superior to that of alendronate sodium (Alen). RT-qPCR assays showed that IMB-R38 significantly upregulated the mRNA expression of osteogenesis genes (Bmp2,Runx2a,Runx2b,Sp7,Alp, andOc) while markedly downregulating that of the osteoclastogenesis genes (Mmp9,Mmp13,andMmp2) compared with the DXM group. Mechanistically, an SPR assay confirmed that IMB-R38 directly binds with RANK but not RANKL to disrupt RANKL/RANK interaction. Furthermore, Asp168 of RANK was identified as a key amino acid that mediates both RANKL interaction and IMB-R38 binding. The inhibition of RANKL/RANK by IMB-R38 suppressed JNK phosphorylation and, consequently, osteoclast differentiation and function. Collectively, our findings identify IMB-R38 as a novel RANKL/RANK inhibitor with therapeutic potential for osteoporosis through its regulation of bone metabolism.

研究领域: 药理学 · 骨骼生物学 · 分子医学 · 药物发现
✓ 已验证 DOI PubMed 高影响因子
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SEPARATION SCIENCE AND TECHNOLOGY · 2017 · IF 1.106

Combination of viscosity regulator and frother to enhance low-rank coal flotation performance

Shiwei Wang,Xiuxiang Tao

This study investigated the synergistic effect of viscosity regulators (polyethylene glycol, sodium carboxymethyl cellulose, and polyacrylamide) and frother (2-octanol) on upgrading the flotation performance of low-rank coal. The results of flotation tests were consistent with the analysis of induction time and supported by the results of SEM, viscosity, foaming ability, and foam layer stability. In the present work, it was observed that the highest combustible matter recovery was obtained by mixing the polyethylene glycol (PEG300) with 2-octanol, which increased from 32.9% to about 64.4% accompanied by a little increase of ash content (0.54%). Therefore, it demonstrated that the combination of PEG300 and 2-octanol provided the highest combustible matter recovery and better flotation selectivity.

研究领域: 矿物加工工程 · 化学工程
✓ 已验证 DOI 高影响因子
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COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS · 2026 · IF 5.4

Interfacial mechanisms of benzene ring substituent position effects in low-rank coal flotation

Deke Zhang,Xicheng Bao,Yulong Cheng,Hongji Chen,Yaowen Xing,Xiahui Gui

Aromatic collectors have demonstrated excellent performance in enhancing the flotation of low-rank coal (LRC). However, the effect of the substituent position on their flotation efficiency is still not clear, stemming from a poor understanding of their molecular behavior at the LRC interface. Flotation tests, density functional theory (DFT) calculations, and molecular dynamics (MD) simulations were conducted to systematically compare the ortho-, meta-, and para-substituted isomers: diethyl phthalate (DEP), diethyl isophthalate (DIP), and diethyl terephthalate (DTP). At 4000 g/t collector dosage, DIP delivers the highest combustible recovery (51.40 %) and the largest first-order rate constant ( k  = 0.90), compared with DEP (40.64 %, k  = 0.48) and DTP (45.64 %, k  = 0.56). DFT-derived molecular electrostatic potential calculations indicate that DIP has the lowest molecular polarity index (MPI) of the three collectors (DEP > DTP > DIP). This lower polarity, combined with a smaller exposed polar surface, promotes its durable adsorption on oxygen-rich LRC. Interaction Region Indicator ( IRI ) and Hirshfeld surface analyses show that interfacial contact strength correlates with the extent of hydrogen-bonding patches at the collector-coal interface. MD simulations further indicate that DIP has more stable adsorption configurations, with more favorable adsorption energies, larger collector-coal solvent-accessible surface areas ( SASA ), and lower mean-squared displacements ( MSD ). Collectively, these results establish a clear structure-performance relationship: the balanced polarity and low steric hindrance of the meta isomer yield the most robust adsorption on LRC, while the para isomer is intermediate and the ortho isomer is weakest. These insights provide a quantitative basis for rapid screening and rational design of high-efficiency collectors for enhanced coal recovery.

CAS / MDL: 123-96-6
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Journal of Cleaner Production · 2020 · IF 7.246

Enhanced floatability of low rank coal using surface functionalized polystyrene nanoparticles as collectors

Yinfei Liao,Maoyan An,Xiaodong Hao,Xingwei Song,Zhe Yang,Hourui Ren,Zechen Liu

Low rank coal (LRC) is difficult to be upgraded by flotation due to the rich oxygen-containing functional groups on its surface. The main objective of this study was to identify the feasibility of surface functionalized polystyrene nanoparticles as LRC flotation collectors. Tetrahydrofurfuryl-functionalized polystyrene nanoparticles (TFPNs) and hydroxyl-functionalized polystyrene nanoparticles (HFPNs) were prepared by emulsion polymerization , and their properties were characterized by X-ray photoelectron spectroscopy (XPS), Transmission electron microscopy (TEM), Zeta potential and particle size measurement. The effect of nanoparticles properties on the LRC flotation was investigated and the performance between TFPNs, HFPNs, polystyrene nanoparticles (PNs) and diesel oil (DO), was compared. The results show that the LRC flotation recovery of PNs was 2.82%–16.86% higher than that of DO, while that of TFPNs and HFPNs exceeded 28.30%–34.33% and 3.58%–18.92%, respectively, which indicated that the performance of PNs was improved by immobilizing tetrahydrofurfuryl or hydroxyl onto the surface. But surface functionalization degree (SFD) should be kept in an appropriate range, i.e. 5.78%–6.56% for TFPNs, 3.94%–5.62% for HFPNs. TFPNs and HFPNs can specifically deposit onto the LRC with the hydrogen bonding function. By improving the hydrophobicity and roughness with deposited nanoparticles, the flotation performance of LRC was significantly enhanced. The performance of TFPNs was superior to that of HFPNs, which resulted from the strong ability to form hydrogen bond for hydroxyl that reduced nanoparticle hydrophobicity. Effective nanoparticle collectors for LRC flotation were likely to be TFPNs with ∼50 nm diameter, positive Zeta potential and SFD around 6.56%. The balance among colloidal stability, hydrophobicity and selectivity of nanoparticles was an effective way to reduce the dosage of nanoparticle collector and promote its industrial application. The results of this study introduce a new class of special collectors for enhancing LRC flotation and put forward its path to commercial utilization.

研究领域: 矿物加工工程 · 材料科学与工程
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