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INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES · 2025 ·Vol. 26 ·期 5 ·2027 · IF 4.9

The GPR30-Mediated BMP-6/HEP/FPN Signaling Pathway Inhibits Ferroptosis in Bone Marrow Mesenchymal Stem Cells to Alleviate Osteoporosis

Shuangliu Chen,Jiřimutu Xiao,Shijie Zhou,Taxi Wumiti,Zitong Zhao,Ruihua Zhao,Yalan Pan,Qing Wang,Yong Ma,Lan Wu,Yang Guo

Dysregulated iron metabolism-induced ferroptosis is considered a key pathological mechanism in the development of osteoporosis (OP). G protein-coupled receptor 30 (GPR30, also known as Gper1) is an estrogen-binding receptor that has shown therapeutic benefits in patients with certain degenerative diseases. Moreover, several studies have demonstrated the anti-ferroptotic effects of estrogen receptor activation. However, its role in the prevention and treatment of OP remains unclear, and there are currently no reports on the anti-ferroptotic function of GPR30 in OP. Therefore, this study aimed to investigate the ferroptosis-related effects and mechanisms of GPR30 in the context of OP. In vivo and in vitro experiments were conducted using wild-type (WT)C57BL/6female mice and GPR30-knockout (GPR30-KO)C57BL/6Jfemale mice. The microarchitecture of the distal femur was assessed using micro-computed tomography (micro-CT), and histomorphological changes were analyzed via hematoxylin and eosin (H&E) staining. Bone marrow mesenchymal stem cells (BMSCs) were isolated and cultured to establish an iron overload model using ferric ammonium citrate (FAC). Interventions included GPR30 overexpression via transfection and BMP-6 inhibition using LDN-214117. Cell viability was evaluated with the CCK-8 assay, while osteogenic differentiation and mineralization levels were assessed using ALP and Alizarin Red S (ARS) staining. Iron accumulation was detected via Prussian blue staining, oxidative stress levels were evaluated using ROS staining, and mitochondrial membrane potential changes were analyzed using JC-1 staining. Transmission electron microscopy (TEM) was employed to observe mitochondrial ultrastructural changes. Additionally, key gene and protein expression levels were measured using immunofluorescence and Western blotting. The micro-CT analysis revealed significant bone microarchitecture deterioration and bone loss in the GPR30-KO mouse model. At the cellular level, GPR30 overexpression markedly reduced iron accumulation and oxidative stress in BMSCs, restored the mitochondrial membrane potential, and improved the mitochondrial ultrastructure. Furthermore, GPR30 enhanced osteogenic differentiation in BMSCs by promoting the activation of the BMP-6/HEP/FPN signaling pathway, leading to increased expression of osteogenic markers. The protective effects of GPR30 were reversed by the BMP-6 inhibitor LDN-214117, indicating that BMP-6 is a critical mediator in GPR30-regulated iron metabolism and ferroptosis inhibition. GPR30 inhibits ferroptosis in BMSCs and enhances osteogenic differentiation by activating the BMP-6/HEP/FPN signaling pathway. This provides new insights and potential therapeutic targets for the treatment of osteoporosis OP.

CAS / MDL: 50-02-2
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CHINESE JOURNAL OF POLYMER SCIENCE · 2026 · IF 4

Synthesis of a Biomass Tyramine-derived Hydroxyl-amide Nucleating Agent and Its Effect on Crystallization and Properties of Polyamide 6

Wu Jia-Le,Xiao Wen-Hao,Wu Jing-Bo,Lin Jiang-Hua,Xu Rui-Jie,Lei Cai-Hong

The chemical structure of polyamide 6 (PA6) dictates that only 50% of hydrogen bonds participate in crystallization during the crystallization process, resulting in the properties of its products being significantly dependent on the molding process. Therefore, the design and development of nucleating agents suitable for PA6 holds great practical significance for high-performance PA6 materials. Amide-based nucleating agents can effectively improve the crystallization rate by increasing intermolecular hydrogen bond density. Further introduction of hydroxyl groups can enhance the hydrogen bonding interactions between the nucleating agent and PA6. In this study, a hydroxyl-containing amide-based nucleating agent, BHT, was designed and synthesized using a tyramine-based biomass as the raw material. These results demonstrated that BHT exhibited good structural compatibility with PA6. After adding 1 wt% BHT, the crystallization temperature of PA6 increased from 170.9 °C to 193.3 °C, the crystallinity increased 16.6%, the heat distortion temperature and Vicat softening temperature rose to 89.5 and 187.8 °C, respectively, the haze decreased to 46%, achieving the synergistic optimization of mechanical, thermal, and optical properties. The in situ time-resolved FTIR results indicated that the addition of BHT increased the enthalpy of hydrogen bond formation during the nucleation stage, facilitated the segmental conformation adjustment of PA6, and enhanced the molar concentration of trans-conformations, ultimately leading to an improvement in the crystallization rate.

CAS / MDL: 872-50-4 68-12-2
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Journal of Physical Chemistry C · 2017 · IF 4.536

Electrochemical Properties and Redox Mechanism of Na2Ni0.4Co0.6[Fe(CN)6] Nanocrystallites as High-Capacity Cathode for Aqueous Sodium-Ion Batteries

Wanfeng Li,Fang Zhang,Xingde Xiang,Xiucheng Zhang

Nickel-based ferrocyanides have attracted wide interest as cathode for aqueous sodium-ion batteries in fields of sustainable energies such as wind and solar, owing to excellent cycling stability and high-rate capability. However, they suffer from low specific capacities (∼60 mAh g–1). Herein, Na2Ni0.4Co0.6[Fe(CN)6] nanocrystallites are reported for the first time as high-capacity cathode for aqueous sodium-ion batteries. Its electrochemical properties and redox mechanism have been understood by combining the X-ray diffraction technique, Fourier-transform infrared spectroscopy, cyclic voltammetry, electrochemical impedance microscopy, and charge/discharge measurements. It is revealed that the material undergoes a reversible three-step single-phase reaction mechanism during Na extraction through sequential electrochemical oxidation of nitrogen-coordinated Co2+ ions and carbon-coordinated Fe2+ ions and achieves superior electrochemical performance with a high reversible capacity of 85 mAh g–1 at 0.5 C, an average operating potential of 0.62 V (vs Ag/AgCl), and a high capacity retention of 90% after 100 cycles. The combination of high specific energy and good cycling performance enables the Na2Ni0.4Co0.6[Fe(CN)6] material exhibiting promising application for high-performance aqueous sodium-ion batteries.

研究领域: 电化学 · 储能 · 材料科学 · 电池技术
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EUROPEAN JOURNAL OF PHARMACOLOGY · 2026 · IF 4.7

6-Methoxydihydrosanguinarine synergizes with cisplatin to enhance lung cancer cell death via ROS-mediated autophagy, ER stress, and JNK activation

Wenying Fu,Ying Yan,Chongchong Shu,Chenxin Xu,Yinghua Chen,Yiqun Xia,Jundixia Chen,Yunzhi Chen,Ri Cui,Peng Zou,Daoyong Ni

6-Methoxydihydrosanguinarine is a natural alkaloid derived from medicinal plants that exhibits significant antitumor activity, making it a promising candidate for cancer therapy. However, the exact molecular mechanisms underlying its effects require further investigation. In this study, we investigated the cytotoxicity and underlying mechanisms of 6-Methoxydihydrosanguinarine in human non-small cell lung cancer (NSCLC) cells. Our findings reveal that reactive oxygen species (ROS) accumulation is the key driver of its antitumor activity. Mechanistically, 6-Methoxydihydrosanguinarine activates the JNK signaling pathway and induces endoplasmic reticulum (ER) stress, both of which can be reversed by the ROS scavenger N-acetylcysteine (NAC). Interestingly, 6-Methoxydihydrosanguinarine also activates autophagy, and inhibition of autophagy reverses the JNK and ER stress pathway activation induced by 6-Methoxydihydrosanguinarine. Notably, 6-Methoxydihydrosanguinarine synergistically enhances cisplatin-induced NSCLC cell death, and this synergistic effect is abolished by NAC, highlighting the critical role of ROS accumulation in their combined efficacy. This study systematically elucidates the molecular mechanisms of 6-Methoxydihydrosanguinarine against NSCLC, revealing that, in addition to the JNK and autophagy pathways, ER stress also mediates its antitumor effects. Moreover, our data establish a rationale for exploring 6-Methoxydihydrosanguinarine in NSCLC therapy and highlight its combination with cisplatin as a potentially effective strategy.

CAS / MDL: 5142-23-4
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SEPARATION AND PURIFICATION TECHNOLOGY · 2023 · IF 8.6

Enhanced 2, 6-dimethylpyrazine removal by catalytic ozonation with legumes biochar: The roles of oxygen- and nitrogen-containing functional groups

Shiwen Dong,Wen Xu,Qingqing Guo,Kai Luo,Haijun Cheng,Juntao Tang,Da Wang,Zhiqiao He,Lizhang Wang,Shuang Song,Jun Ma

Designing efficient and environmentally friendly catalysts is essential to activating ozonation for wastewater remediation. This study prepared soybean biochar (SB), adzuki beans biochar (AB), and mung beans biochar (MB) catalysts using moldy legumes as precursors. The biochars were characterized to investigate the surface characters’ effect on ozone activation toward 2, 6-dimethylpyrazine (2,6-DMP) degradation. All prepared samples drastically facilitated the degradation more than with sole ozonation. It was found that at pH 7 with 10 mg L −1 catalysts, the removal rates of 5 μM 2,6-DMP were 88.3 %, 90.7 %, and 87.3 % by SB, MB, and AB at 30 min, respectively. The surface-area-normalized reaction rate constants (k obs /S BET ) showed that AB exhibited the best catalytic activity with the rate of 1.5 × 10 −2 mg·m 2 ·min −1 , which is 2.3- and 23.1-fold higher than that of SB and MB, respectively. Further characterization confirmed that oxygen- (C–O/C = O and –OH) and nitrogen-containing groups (pyridine N and pyrrole N) were crucial to the catalytic degradation, as electron transfer was promoted to form more ROS. In addition, the quenching test and electron paramagnetic resonance (EPR) revealed OH, O 2 − , and 1 O 2 as the main reactive oxygen species (ROS) during the heterogeneous catalytic ozonation (HCO), indicating that 2,6-DMP degradation followed the radical and non-radical oxidation pathways. Overall, this study helped to understand the relationship between surface functional groups and intrinsic activity. It also provided a new direction for utilizing agricultural waste.

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International Journal of Electrochemical Science · 2023 · IF 1.5

Voltammetric Determination of 6-mercaptopurine at Co(III) Trisphenanthroline Complex and DNA Decorated with Grpahene Oxide Modified Glassy Carbon Electrode

Zhihong Yan,Hong Li

A Cobalt (III) trisphenanthroline complex ([Co(phen)3] 3+ ) has been adsorption assembled on a glassy carbon electrode (GCE) modified with DNA decorated with graphene oxide (GO) by multiple sweep voltammetry. In the present protocol, GO is served as a functional unit of DNA to greatly improve the efficient immobilization of DNA on the GC electrode and also offer a favorable microenvironment to keep the DNA structure of double-stranded (dsDNA), which facilitates the intercalation of redoxactive [Co(phen)3] 3+ . The evidences from scanning electron microscope, X-ray diffraction, cyclic voltammetry, electrochemical impedance spectroscopy, emission spectroscopy and differential pulse voltammetry reveal that [Co(phen)3] 3+ can be assembled on the surfaces of GO-decorated dsDNA driven by electrostatic attraction, intercalation and π-stacking interaction. Furthermore, the highly stable [Co(phen)3] 3+ /GO-dsDNA/GCE is used to the highly selective determination of 6- mercaptopurine (6-MP) in the human blood with satisfactory. The reduction peak current was linear to 6-MP concentration in the range from 5×10 -8 to 2×10 -6 M 6-MP, and the detection limit is 1.5×10 -8 M ( S / N = 3)

CAS / MDL: 50-44-2
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CNS Neuroscience & Therapeutics · 2023 · IF 5.5

Piperine improves levodopa availability in the 6-OHDA-lesioned rat model of Parkinson's disease by suppressing gut bacterial tyrosine decarboxylase

Xiaolu Hu,Lan Yu,Yatong Li,Xiaoxi Li,Yimeng Zhao,Lijuan Xiong,Jiaxuan Ai,Qijun Chen,Xing Wang,Xiaoqing Chen,Yinying Ba,Yaonan Wang,Xia Wu

Aim Tyrosine decarboxylase (TDC) presented in the gut-associated strain Enterococcus faecalis can convert levodopa (L-dopa) into dopamine (DA), and its increased abundance would potentially minimize the availability and efficacy of L-dopa. However, the known human decarboxylase inhibitors are ineffective in this bacteria-mediated conversion. This study aims to investigate the inhibition of piperine (PIP) on L-dopa bacterial metabolism and evaluates the synergistic effect of PIP combined with L-dopa on Parkinson's disease (PD). Methods Metagenomics sequencing was adopted to determine the regulation of PIP on rat intestinal microbiota structure, especially on the relative abundance of E. faecalis . Then, the inhibitory effects of PIP on L-dopa conversion and TDC expression of E. faecalis were tested in vitro. We examined the synergetic effect of the combination of L-dopa and PIP on 6-hydroxydopamine (6-OHDA)-lesioned rats and tested the regulations of L-dopa bioavailability and brain DA level by pharmacokinetics study and MALDI-MS imaging. Finally, we evaluated the microbiota-dependent improvement effect of PIP on L-dopa availability using pseudo-germ-free and E. faecalis -transplanted rats. Results We found that PIP combined with L-dopa could better ameliorate the move disorders of 6-OHDA-lesioned rats by remarkably improving L-dopa availability and brain DA level than L-dopa alone, which was associated with the effect of PIP on suppressing the bacterial decarboxylation of L-dopa via effectively downregulating the abnormal high abundances of E. faecalis and TDC in 6-OHDA-lesioned rats. Conclusion Oral administration of L-dopa combined with PIP can improve L-dopa availability and brain DA level in 6-OHDA-lesioned rats by suppressing intestinal bacterial TDC.

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Particuology · 2022 · IF 3.251

Poly(N-isopropylmethacrylamide-co-4-acrylamidobenzo-18-crown-6) microgels with expanded networks for excellent adsorption of lead(II) ions

Fang Wang,Zhuang Liu,Rui Xie,Xiao-Jie Ju,Wei Wang,Da-Wei Pan,Liang-Yin Chu

Lead(II) (Pb 2+ ) ions are toxic heavy metal ions that can accumulate in the human body through water and cause severe health problems, including neurotoxicity, nephrotoxicity, hematological toxicity and even genotoxicity effects. To remove Pb 2+ selectively and effectively from aqueous solutions, we develop a novel type of Pb 2+ -recognizable microgels with excellent adsorption capacity to Pb 2+ , which are fabricated from 4-acrylamidobenzo-18-crown-6 (B18C6Am) and N -isopropylmethacrylamide (NIPMAM) monomers by precipitation copolymerization method. The prepared poly( N -isopropylmethacrylamide- co -4-acrylamidobenzo-18-crown-6) (PNMB) microgels exhibit expanded structures, because the electron-donating methyl groups at α-carbon could descend the polarity of C O in the NIPMAM monomers and thus weaken the polymer segment···segment interactions. The expanded structures of PNMB microgels are beneficial for adsorption of Pb 2+ due to the low steric hindrance in the polymeric networks. The Pb 2+ adsorption isotherms of PNMB microgels are consistent with the Langmuir model for monolayer adsorption. The results indicate that the prepared Pb 2+ -recognizable PNMB microgels are highly promising for the selective removal of lead(II) ions from aqueous solutions.

CAS / MDL: 2997-92-4
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European Journal of Inflammation · 2022 · IF 0.424

Appropriate supplementation of testosterone alleviates post-stroke damage via decreasing inflammation and oxidative stress in aged male C57BL/6 mice

Jianguo Wang,Yuefei Zhou,Lijun He

Stroke injury is closely related to testosterone levels. Testosterone supplementation in elderly men is seen to protect the cardiovascular system and reduce the risk of stroke. But this medication method is controversial. This study aims to investigate the effect of long-term testosterone supplementation on brain injury after stroke in aged mice. 60 male C57BL/6 mice,12-months of age were divided into 3 groups: low-dose group, high-dose group, and control group, each group was injected subcutaneously with 100 μL of sesame oil or 5 mg/kg or 50 mg/kg of testosterone (in 100 μL of sesame oil) twice per week, respectively. One week after the injection, stroke was induced by light. After the stroke, the injection continued for 6 weeks. The motion ability was measured by rotating rod and tail suspension. The brain injury was observed by naked eyes and TTC staining. In addition, we measured the inflammation (Tnf-α, Il-6, and Mcp-1) and oxidative stress (Malondialdehyde (MDA) and T-AOC) in the injured tissue 72 h post-stroke. Low-dose testosterone supplementation improved the motion ability and decreased brain injury. It also decreased the inflammatory factors (Tnf-α, Il-6, and Mcp-1), decreased MDA product, and increased T-AOC. High-dose testosterone supplementation not only reduced the motion ability and aggravated stroke injury, but also increased the inflammation, MDA level and decreased T-AOC level. In summary, supplementation of testosterone at normal levels in elderly mice can alleviate post-stroke injury by reducing inflammation and oxidative stress; however, excessive supplementation may cause unexpected injuries. This study has important implications for the application of testosterone replacement therapy.

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JOURNAL OF MOLECULAR LIQUIDS · 2022 · IF 6.633

Structures of 18-crown-6/Cs+ complexes in aqueous solutions by wide angle X-ray scattering and density functional theory

Zhuanfang Jing,Yongquan Zhou,Wenqian Zhang,Toshio Yamaguchi,Koji Yoshida,Guangguo Wang,Li Han

Wide angle X-ray scattering (WAXS) and density functional theory (DFT) were employed to study the structures of aqueous 18-crown-6/CsCl solutions with CsCl concentrations of 0.25, 0.50 and 1.00 mol·L -1 . The empirical potential structure refinement (EPSR) modelling was adopted to get the pair distribution functions (PDFs), coordination numbers ( CN ), coordination number distributions (CND), angle distribution functions (ADFs), independent gradient model (IGM) and spatial density functions (SDFs) for the 18-crown-6 hydration, the complexation of 18-crown-6 and Cs + , the hydration of 18-crown-6/Cs + complex, and the association of Cl - and 18-crown-6/Cs + complex. Judging from the distance and orientation of water molecules, and the IGM between 18-crown-6 and water molecules, the oxygen atoms of 18-crown-6 (Oc) and the hydrogen atoms of water molecules (Hw) form strong hydrogen bonds, and these water molecules were distributed on both sides of the 18-crown-6 ring plane. However, the hydrogen atoms of 18-crown-6 (Hc) hardly form hydrogen bonds with the oxygen atoms of water molecules (Ow). Cs + is located directly above the 18-crown-6 ring plane of 0.35 to 2.05 Å away from the centroid of 18-crown-6, and forms 18-crown-6/Cs + complex with six Oc at r Cs + - O c  = 3.06 Å. When the concentrations of CsCl are 0.25, 0.50 and 1.00 mol·L -1 , the complexation percentage of 18-crown-6 to Cs + are about 100%, 58% and 54%, respectively. No classic 2:1 “sandwich” 18-crown-6/Cs + complex structure was found in the solutions we surveyed. Both interaction energies and solvation stability energies reveal that the hydrates of 18-crown-6/Cs + complexes were formed in aqueous solutions. Cs + uncomplexed with 18-crown-6 hydrates with eight water molecules in aqueous solution, while Cs + can also hydrate with about four water molecules when it complexes with 18-crown-6. The results of atomic pair distances, the dipole distance of water molecules, the SDF and the IGM indicate that although water molecules can be located on both sides of the 18-crown-6 ring plane when the hydrates are formed, they hydrate with Cs + on the side where Cs + only existed. Cs + of 18-crown-6/Cs + complex associates with Cl - with the r Cs + - Cl - = 3.79 Å by electrostatic attraction.

CAS / MDL: 7647-17-8
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Cell Death Discovery · 2022 ·Vol. 8 ·期 1 ·1-10 · IF 7.109

Ferroptosis, a new target for treatment of renal injury and fibrosis in a 5/6 nephrectomy-induced CKD rat model

Wang Jingyu,Wang Yaqing,Liu Yi,Cai Xintian,Huang Xin,Fu Wenjing,Wang Lei,Qiu Lihua,Li Junying,Sun Li

Ferroptosis is a non-traditional form of regulated cell death, characterized by iron overload and lipid peroxidation. Exploration of ferroptosis in chronic kidney disease (CKD) has been extremely limited to date. In this study, we established a rat model of CKD by 5/6 nephrectomy, treated CKD rats with the ferroptosis inducer, cisplatin (CDDP), and the ferroptosis inhibitor, deferoxamine mesylate (DFO), and observed the resulting pathologic changes (injury markers and fibrosis) and ferroptotic biochemical indices. Kidney iron deposition, lipid peroxidation, mitochondrial defects, ferroptosis marker induction, and TUNEL staining positivity were detected in CKD group rats. Further, treatment with CDDP or DFO influenced renal injury and fibrosis by affecting ferroptosis, rather than apoptosis, and ferroptosis occurs in the remnant kidney due to disordered iron metabolism. In conclusion, our study shows for the first time that 5/6 nephrectomy induces ferroptosis in the remnant kidney and clarifies the underlying pathogenesis. Moreover, we demonstrate that ferroptosis is involved in CKD progression and represents a therapeutic target in chronic kidney injury and renal fibrosis.

CAS / MDL: 28718-90-3
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POLYMER DEGRADATION AND STABILITY · 2022 · IF 5.204

A phosphorus-containing flame retardant with thermal feature suitable for polyamide 6 and its filaments with enhanced anti-dripping performance

Yanlu Sun,Zhengqi Wang,Dequn Wu,Xueli Wang,Jianyong Yu,Ruchao Yuan,Faxue Li

The absence of flame retardant with suitable thermal feature and high flame retardancy has greatly limited the development of flame-retardant polyamide 6 (PA6). In this work, a phosphorus-containing flame retardant (CBPB) with appropriate flame responsive nitrile groups was synthesized, and its melting temperature, cross-linking temperature and initial degradation temperature exactly matched the thermal feature of flame retardant suitable for PA6. PA6/CBPB composites (FR-PA6s) were prepared by melt-blending various contents of CBPB into PA6 matrix. The UL-94 and limiting oxygen index (LOI) of FR-PA6s reached V-0 and 32.0% respectively once 8 wt% of CBPB was added to PA6 matrix. As a representative, FR-PA6-6 (6 wt% of CBPB in PA6 matrix) was successfully melt-spun into filaments with good mechanical properties. The filament strand was self-extincted within 4 s and only one droplet was generated after ignited in the vertical burning tests. The corresponding anti-dripping and flame-retardant mechanism were also explored. Suppression of melt-dripping of FR-PA6s was formed due to the chemical cross-linking of nitrile groups of CBPB at ∼290 °C, which significantly exceeded the general processing temperature of PA6 (∼260 °C) and so the processability of FR-PA6s was slightly affected. The enhanced flame resistance of FR-PA6s was contributed to the quenching effect of PO· and PO 2 · radicals as well as the diluting effect of NH 3 in the gas phase.

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