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Science Advances · 2022 ·Vol. 8 ·期 40 · IF 14.957

NIR-photocatalytic regulation of arthritic synovial microenvironment

Bin Zhao,Lingting Zeng,Danyang Chen,Songqing Xie,Zhaokui Jin,Guanglin Li,Wei Tang,Qianjun He

Synovial microenvironment (SME) plays a vital role in the formation of synovial pannus and the induction of cartilage destruction in arthritis. In this work, a concept of the photocatalytic regulation of SME is proposed for arthritis treatment, and monodispersive hydrogen–doped titanium dioxide nanorods with a rutile single-crystal structure are developed by a full-solution method to achieve near infrared–photocatalytic generation of hydrogen molecules and simultaneous depletion of overexpressed lactic acid (LA) for realizing SME regulation in a collagen-induced mouse model of rheumatoid arthritis. Mechanistically, locally generated hydrogen molecules scavenge overexpressed reactive oxygen species to mediate the anti-inflammatory polarization of macrophages, while the simultaneous photocatalytic depletion of overexpressed LA inhibits the inflammatory/invasive phenotypes of synoviocytes and macrophages and ameliorates the abnormal proliferation of synoviocytes, thereby remarkably preventing the synovial pannus formation and cartilage destruction. The proposed catalysis-mediated SME regulation strategy will open a window to realize facile and efficient arthritis treatment.

CAS / MDL: 7439-93-2
研究领域: 生物医学工程 · 材料科学 · 风湿病学
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PHYSICAL CHEMISTRY CHEMICAL PHYSICS · 2022 ·Vol. 24 ·期 44 ·27406-27412 · IF 3.945

Effects of polyacrylic acid molecular weights on V2C-MXene nanocoatings for obtaining ultralow friction and ultralow wear in an ambient working environment

Xuan Yin,Haohao Chen,Lai Jiang,Chang Liang,Haosheng Pang,Dameng Liu,Bing Zhang

Two modified V2C-MXene nanocoatings are prepared through different molecular weights of polyacrylic acid (polyacrylic acid with ∼4 50 000 is marked as LPAA, and polyacrylic acid with ∼4 000 000 is marked as HPAA) and two-dimensional V2C-MXene. Their properties are characterized using a ball-on-disc tribometer, three-dimensional white-light interferometry topography images, optical microscope, Raman spectrometer, focused ion beam/scanning electron microscope and high-resolution transmission electron microscope/energy dispersive X-ray spectrometer (HRTEM/EDS). As a result, an ultralow friction (μ ≈ 0.073 ± 0.024) and an ultralow wear (3.41 × 10−7 mm3 N−1 m−1 for ball scar, and 7.49 × 10−8 mm3 N−1 m−1 for disc track) are achieved for the LPAA@V2C vs. steel ball system tested under 4 N in the air through tribo-physicochemical interactions. During the rubbing process, the LPAA@V2C nanocoating is transferred onto counter-bodies to form mixed-phase lubricative tribofilms. Monitoring via a HRTEM/EDS, the mixed-phase lubricative tribofilms are found to be mainly composed of amorphous carbon phases containing O and V and layered nano-debris along the sliding surface. The tribofilm's stable structure is the key to realizing ultralow friction and ultralow wear through the LPAA modification. These findings disclose that MXene-based nanomaterials can be applied for material engineering and mechanical engineering under common working conditions.

研究领域: 材料科学 · 机械工程
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Frontiers in Pharmacology · 2022 · IF 5.988

Myricitrin inhibits fibroblast-like synoviocyte-mediated rheumatoid synovial inflammation and joint destruction by targeting AIM2.

Chuyu Shen,Meilin Xu,Siqi Xu,Shuoyang Zhang,Wei Lin,Hao Li,Shan Zeng,Qian Qiu,Liuqin Liang,Youjun Xiao,Hanshi Xu

Objective: To explore the effect and underlying mechanism of Myricitrin (Myr) in regulating fibroblast-like synoviocyte (FLS)-mediated synovitis and joint destruction in RA. Methods: FLSs were isolated from synovial tissues from patients with RA. Gene expression was measured using quantitative RT-qPCR. Protein expression was detected by immunohistochemistry or Western blot. Cell apoptosis was performed by an Annexin-PI staining assay. EdU incorporation was used to assess the proliferation of RA FLS. Transwell assay was used to characterize the cell migration and invasion ability of RA FLS. The potential target of Myr was identified by RNA sequencing analysis. The in vivo effect of Myr was assessed in a collagen-induced arthritis (CIA) model. Results: Myr treatment inhibited the lamellipodia formation, migration, and invasion, but not the apoptosis and proliferation, of RA FLSs. Myr also reduced the expression of CCL2, IL-6, IL-8, MMP-1, MMP-3, and MMP-13 induced by TNF-α. The RNA-seq results indicated that AIM2 may be a target gene of Myr in RA FLSs. Furthermore, compared to healthy controls, AIM2 expression showed higher levels in synovial tissues and FLSs from RA patients. AIM2 knockdown also inhibited RA FLS migration, invasion, cytokine, and MMP expression. In addition, either Myr treatment or AIM2 knockdown reduced the phosphorylation of AKT induced by TNF-α stimulation. Importantly, Myr administration relieved arthritis symptoms and inhibited AIM2 expression in the synovium of CIA mice. Conclusion: Our results indicate that Myr exerts an anti-inflammatory and anti-invasion effect in RA FLSs and provide evidence of the therapeutic potential of Myr for RA.

研究领域: 风湿病学 · 免疫学 · 药理学 · 分子生物学
✓ 已验证 DOI PubMed 高影响因子
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Machines · 2024 ·Vol. 12 ·期 11 ·817 · IF 2.1

PDA Nanoparticle-Induced Lubricating Film Formation in Marine Environments: An Active Approach

Xinqi Zou,Zhenghao Ge,Chaobao Wang,Yuyang Xi

The low viscosity of water-lubricated films compromises their load-bearing capacity, posing challenges for practical application. Enhancing the lubrication stability of these films under load is critical for the successful use of seawater-lubricated bearings in engineering. Polydopamine (PDA) shows great potential to address this issue due to its strong bio-inspired adhesion and hydration lubrication properties. Thus, PDA nanoparticles and seawater suspensions were synthesized to promote adhesive lubricating film formation under dynamic friction. The lubrication properties of PDA suspensions were evaluated on Cu ball and ultra-high molecular weight polyethylene (UHMWPE) tribo-pairs, with a detailed comparison to seawater. The results show PDA nanoparticles provide excellent adhesion and lubrication, enhancing the formation of lubricating films during friction with seawater. Under identical conditions, PDA suspensions demonstrated the lowest friction coefficient and minimal wear. At 3 N, friction decreased by 56% and wear by 47% compared to distilled water. These findings suggest a novel strategy for using PDA as a lubricant in seawater for engineering applications.

CAS / MDL: 64-17-5 7732-18-5
研究领域: 材料科学 · 海洋工程
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Regenerative Therapy · 2025 · IF 3.5

DDIT4 participates in high glucose-induced fibroblast-like synoviocytes overactivation and cartilage injury by regulating glycolysis

Shuo Qiang,Cheng Cheng,Yonghui Dong,Chao Tang,Jia Zheng,Yunke Liu

Objective More and more evidence show that diabetes is closely related to osteoarthritis (OA). However, the role and mechanism of DNA damage-inducible transcript 4 protein (DDIT4) in diabetic OA (DOA) have not been clarified. Methods We collected OA patients and non-OA subjects who underwent total knee replacement surgery, and analyzed the DDIT4 expression in synovial samples using RT-qPCR. The cell viability of fibroblast-like synoviocytes (FLSs) was measured by CCK-8 assay. Annexin V-FITC/PI double staining was used to detect the cell apoptosis. Scratch and Transwell assays were used to determine cell migration and invasion, respectively. Results The levels of cellular inflammatory factors (IL-1β, IL-6 and TNF-α), oxidative stress and glycolysis related indicators were detected by using kits. Western blot was used to determine the expression of DDIT4, Aggrecan, COL3A1, MMP3, MMP13, HK2, PFKP and PKM2 in FLSs or ATDC5 cells. The results showed that the expression level of DDIT4 was significantly reduced in the synovial samples of OA patients and primary FLSs. Functional studies showed that DDIT4 overexpression inhibited the overactivation, migration, and invasion of FLSs, as well as alleviated chondrocyte injury co-cultured with FLSs. Importantly, the expression of DDIT4 was down-regulated in patients with DOA and closely related to DOA. Further research found that high glucose (HG) promoted excessive activation, migration, and invasion of FLSs, and exacerbated the followed chondrocyte injury. Overexpression of DDIT4 alleviated HG-induced abnormal function of FLSs and injury to chondrocytes. Importantly, DDIT4 inhibited lactate synthesis, glucose uptake, LDH activity, extracellular acidification rate, oxygen consumption rate, and expression levels of glycolysis related protein (HK2, PFKP, PKM2) in HG-induced FLSs. And the glycolysis inhibitors (Cyto-B and 3BrPA) alleviated the injury of ATDC5 chondrocytes co-cultured with FLSs. Conclusions DDIT4 participates in HG-induced FLSs overactivation and inflammation response, as well as chondrocyte injury and OA progression by regulating glycolysis processes.

CAS / MDL: 50-00-0
研究领域: 医学 · 分子生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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TRIBOLOGY INTERNATIONAL · 2024 · IF 6.1

Effects of sodium ions on the tribological and antioxidation properties of borates

Yinglei Wu,Emile van der Heide,Sirui Wang

A borate ester (BMBS) and its sodium salts (BMBSNa) were synthesized and used as multifunctional lubricant additives in oleic acid. Results showed that BMBSNa possessed better anti-oxidation and tribological properties than BMBS. Worn surfaces analysis revealed that BMBSNa was more favorable to forming boundary film containing h-BN and FeS. Theoretical calculation suggested that BMBSNa had a higher chemical reactivity and better metal adsorption ability than BMBS. Fukui indices showed that sodium ions favor free radical reaction. Radial distribution functions (RDF) indicated that sodium ions help the adsorption of BMBSNa on the iron surface. It can be concluded that sodium ions benefit the oxidation resistance of base oil, and contribute to forming good boundary lubrication film to achieve good tribological properties.

CAS / MDL: 112-80-1
研究领域: 材料科学 · 化学工程
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TRIBOLOGY LETTERS · 2016 ·Vol. 64 ·期 1 ·1-9 · IF 1.758

Tribological Investigation of Two Different Layered Zirconium Phosphates as Grease Additives Under Reciprocating Sliding Test

Chen Li,Zhang Xiaosheng,Xu Hong,Dong Jinxiang

The tribological properties of α-Zr(HPO 4 )·H 2 O and Cu(OH) 2 Zr(HPO 4 ) 2 ·2H 2 O (α-ZrP and Cu-α-ZrP, respectively) were investigated in lithium grease by using an optimol SRV-V oscillating reciprocating friction and wear tester (SRV). α-ZrP had excellent anti-wear and friction-reducing properties regardless of the applied load, frequency, and test duration. The applied load for α-ZrP reached 600 N, and the corresponding friction coefficient was 0.082. At 60 Hz, the wear volume rate was 11.16 × 10 −9  mm 3 /Nm. The tribological properties of Cu-α-ZrP were dependent on the test conditions, especially at higher frequency. The α-ZrP worn steel surfaces were smooth and shallow as indicated from scanning electron microscopy and a three-dimensional non-contact surface mapping profiler. Related elements were detected by energy-dispersive X-ray spectroscopy on the rubbed surfaces. A boundary solid film may form on the worn surfaces after friction tests. In reciprocating mode, α-ZrP stuck on the contacting surfaces, which enabled it to form a stable solid lubricant film more effectively than Cu-α-ZrP. The crystal structure may be important for film strength under high loads, especially at high speed.

CAS / MDL: 1317-33-5
研究领域: 材料科学 · 摩擦学
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PHYTOMEDICINE · 2023 · IF 7.9

Sesamol serves as a p53 stabilizer to relieve rheumatoid arthritis progression and inhibits the growth of synovial organoids

Xian Lin,Tengyu Lin,Xiaocheng Wang,Jiaxin He,Xu Gao,Shuyan Lyu,Qingwen Wang,Jian Chen

Background Rheumatoid arthritis (RA) is an autoimmune disease known as a leading cause of disability with considerable mortality. Developing alternative drugs and targets for RA treatment is an urgent issue. Sesamol is a phenolic compound isolated from natural food sesame ( Sesamum indicum L.) with various biological activities. Purpose The current research intended to illuminate the bioactivity and mechanisms of sesamol in RA fibroblast-like synoviocytes (FLS), and aimed to estimate the potential clinical application value of sesamol in RA treatment. Methods CCK-8, EdU, and flow cytometry assays, as well as transwell tests were applied to observe the effects of sesamol on the abnormal functions of RA-FLS. Moreover, synovial organoids and a collagen-induced arthritis (CIA) mouse model were constructed to further explore the therapeutic capacity of sesamol on RA. Furthermore, RNA sequencing combined with quantitative real-time PCR assay, Western blot as well as co-immunoprecipitation were employed to clarify the mechanism of sesamol in regulating RA progression. Results Sesamol suppressed the proliferation through inhibiting DNA replication, triggering cell cycle arrest and apoptosis of RA-FLS. Besides, sesamol impaired RA-FLS migration and invasion. Interestingly, sesamol inhibited the growth of constructed synovial organoids and alleviated RA symptoms in CIA mice. Moreover, RNA sequencing further implicated p53 signaling as a downstream pathway of sesamol. Furthermore, sesamol was shown to decrease p53 ubiquitination and degradation, thereby activating p53 signaling. Finally, bioinformatics analyses also highlighted the importance of sesamol-regulated networks in the progression of RA. Conclusions Our investigation demonstrated that sesamol served as a novel p53 stabilizer to attenuate the abnormal functions of RA-FLS via facilitating the activation of p53 signaling. Moreover, our study highlighted that sesamol might be an effective lead compound or candidate drug and p53 could be a promising target for the therapy of RA.

CAS / MDL: 66-81-9
研究领域: 药理学 · 免疫学 · 分子生物学 · 风湿病学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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ACS Nano · 2025 · IF 16

Dual-Pronged Attack: Biomimetic Multi-Functional MOFs for Rheumatoid Arthritis Therapy via Inhibiting Synovial Hyperplasia and Improving Immune Microenvironment

Meng-Wen Ma,Kai-Lin He,Sui Zhou,Yong-Guo Hu,Kai Cheng,Jin-Xuan Fan,Bo Liu,Ling-Li Dong,Yuan-Di Zhao

Fibroblast-like synoviocytes (FLSs) and synovial macrophages (SMs) contribute significantly to the occurrence and development of rheumatoid arthritis (RA). Although therapeutic strategies targeting FLSs or SMs have achieved certain results, monotherapy often fails to effectively alleviate synovitis. By loading methotrexate (MTX) and glucose oxidase (GOx) in the zinc imidazole framework-8 (ZIF-8) and incorporating with the platinum nanoparticles (Pt NPs) and macrophage membranes, multifunctional probe mZPMG NPs were prepared. The mZPMG NPs can synergistically inhibit the abnormal proliferation of FLSs through drug therapy and starvation therapy, while eliminating excessive reactive oxygen species (ROS) and promoting the polarization of SMs toward M2-type macrophages. Oxygen generated through the ROS scavenging process can enhance the efficiency of the GOx starvation treatment. The in vivo experiments demonstrated that the clinical score of collagen-induced arthritis mice treated with the mZPMG NPs was 72.92% lower than those treated with PBS. Meanwhile, the mice in the mZPMG group exhibited obvious suppression of synovial hyperplasia, inflammatory infiltration, and cartilage erosion. Therefore, this study proposed to adopt a “dual pronged attack” strategy in inhibiting the abnormal proliferation of FLSs and reducing the abundance of SMs to achieve macrophage repolarization, which provides a promising platform for the comprehensive treatment of RA.

研究领域: 纳米医学 · 免疫治疗 · 风湿病学 · 药物递送 · 生物材料 · 炎症性疾病
✓ 已验证 产品关联 DOI PubMed 高影响因子
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TRIBOLOGY LETTERS · 2022 ·Vol. 70 ·期 4 ·1-11 · IF 3.327

Composite Lubricating Films with Silane Coupling Agent-Modified Carbon Nanotubes on a Silicon Substrate with Enhanced Wear-Resistant Properties

Liu Sisi,Deng Yuxing,Sun He,Jiang Shengqiang,Liu Jingang

A modified carbon nanotube composite film was designed and prepared by self-assembled molecular film technology. The carbon nanotubes modified by 3-glycidoxypropyltrimethoxy-silane (KH560) were grafted onto a silicon substrate by using N-3-(trimethoxysilyl)propylethyl-enediamine (DA) molecules as an intermediate connecting layer. Compared with the silicon surface, the surface wettability of the modified carbon nanotube composite thin film changes from super-hydrophilic to hydrophobic. At the nanoscale, the surface adhesion and friction forces decreased by nearly 91% and 87%, respectively, and at the microscale, the friction coefficient was reduced by 84%. The anti-wear lifetime is prolonged to 72 min under an applied load of 1 N, which is over 35 times longer than that of silicon. Due to the great wear-resistant properties of modified carbon nanotubes, they are expected to be widely used in micro/nanoelectromechanical systems.

研究领域: 材料科学 · 纳米技术 · 表面工程
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Frontiers in Immunology · 2023 · IF 7.3

A comprehensive analysis of biomarkers associated with synovitis and chondrocyte apoptosis in osteoarthritis

Ling Yang,Xueyuan Yu,Meng Liu,Yang Cao

Introduction Osteoarthritis (OA) is a chronic disease with high morbidity and disability rates whose molecular mechanism remains unclear. This study sought to identify OA markers associated with synovitis and cartilage apoptosis by bioinformatics analysis. Methods A total of five gene-expression profiles were selected from the Gene Expression Omnibus database. We combined the GEO with the GeneCards database and performed Gene Ontology and Kyoto Encyclopedia of Genes and Genome analyses; then, the least absolute shrinkage and selection operator (LASSO) algorithm was used to identify the characteristic genes, and a predictive risk score was established. We used the uniform manifold approximation and projection (UMAP) method to identify subtypes of OA patients, while the CytoHubba algorithm and GOSemSim R package were used to screen out hub genes. Next, an immunological assessment was performed using single-sample gene set enrichment analysis and CIBERSORTx. Results A total of 56OA-related differential genes were selected, and 10 characteristic genes were identified by the LASSO algorithm. OA samples were classified into cluster 1 and cluster 2 subtypes byUMAP, and the clustering results showed that the characteristic genes were significantly different between these groups. MYOC, CYP4B1, P2RY14, ADIPOQ, PLIN1, MFAP5, and LYVE1 were highly expressed in cluster 2, and ANKHLRC15, CEMIP, GPR88, CSN1S1, TAC1, and SPP1 were highly expressed in cluster 1. Protein–protein interaction network analysis showed that MMP9, COL1A, and IGF1 were high nodes, and the differential genes affected the IL-17 pathway and tumor necrosis factor pathway. The GOSemSim R package showed that ADIPOQ, COL1A, and SPP1 are closely related to the function of 31 hub genes. In addition, it was determined that mmp9 and Fos interact with multiple transcription factors, and the ssGSEA and CIBERSORTx algorithms revealed significant differences in immune infiltration between the two OA subtypes. Finally, a qPCR experiment was performed to explore the important genes in rat cartilage and synovium tissues; the qPCR results showed that COL1A and IL-17A were both highly expressed in synovitis tissues and cartilage tissues of OA rats, which is consistent with the predicted results. Discussion In the future, common therapeutic targets might be found forsimultaneous remissions of both phenotypes of OA.

研究领域: 医学 · 生物信息学
✓ 已验证 DOI PubMed 高影响因子
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INTERNATIONAL IMMUNOPHARMACOLOGY · 2025 · IF 4.7

The protective role of TRIM16 in rheumatoid arthritis: mechanisms of modulating ferroptosis

Nannan Xu,Wenyi Fu,Jiake Wu,Shuai Zhao,Chunyang Tian

Rheumatoid arthritis (RA) is one of the most common chronic inflammatory autoimmune diseases, and ferroptosis has been associated with its pathogenesis. TRIM16 belongs to the TRIM protein family and possesses various biological function. However, the role of TRIM16 in RA has not been reported. Our results showed that TRIM16 was upregulated in collagen-induced arthritis (CIA) mice, and TRIM16 overexpression alleviated joint inflammation. Notably, the level of 4-HNE was decreased in CIA mice, whereas TRIM16 overexpression restored it. The expression of GPX4 and SLC7A11 was upregulated in CIA mice, whereas TRIM16 overexpression significantly suppressed their levels, suggesting that TRIM16 promotes ferroptosis. We then detected TRIM16 expression in TNF-α-induced fibroblast-like synoviocytes (FLS), and found that TNF-α stimulation reduced TRIM16 expression. Overexpression of TRIM16 increased the lipid ROS, Fe 2+ levels, and LDH activity, while reducing GSH-PX and GSH activities. Moreover, TNF-α treatment increased GPX4 and SLC7A11 expression but decreased ACSL4 levels, and TRIM16 overexpression reversed these effects. TRIM16 knockdown reduced lipid ROS levels and increased GPX4 and SLC7A11 expression. Furthermore, Fer-1 treatment reduced lipid ROS levels and increased GPX4 and SLC7A11 expression. Mechanistically, TRIM16 directly binds to Snai1, promoted its K48-linked ubiquitination, and specifically ubiquitinates Snai1 at the K146 site. Overexpression of Snai1 decreased the lipid ROS levels and increased the GSH content. Our study identifies TRIM16 as a promoter of ferroptosis in TNF-α-induced FLS by enhancing Snai1 ubiquitination and degradation. In summary, our study presented that TRIM16 plays a protective role in RA.

CAS / MDL: 66-81-9
研究领域: 免疫学 · 分子生物学 · 风湿病学 · 细胞死亡机制 · 信号转导
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