| 1. |
- Liu, Huan, et al.
(author)
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The first human induced pluripotent stem cell line of Kashin–Beck disease reveals involvement of heparan sulfate proteoglycan biosynthesis and PPAR pathway
- 2022
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In: The FEBS Journal. - : John Wiley & Sons. - 1742-464X .- 1742-4658. ; 289:1, s. 279-293
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Journal article (peer-reviewed)abstract
- OBJECTIVE: Kashin-Beck disease (KBD) is an endemic osteochondropathy. Due to a lack of suitable animal or cellular disease models, the research progress on KBD has been limited. Our goal was to establish the first disease-specific human induced pluripotent stem cells (hiPSCs) cellular disease model of KBD, and to explore its etiology and pathogenesis exploiting transcriptome sequencing.METHODS: HiPSCs were reprogrammed from dermal fibroblasts of two KBD and one healthy control donors via integration-free vectors. Subsequently, hiPSCs were differentiated into chondrocytes through three-week culture. Gene expression profiles in KBD, normal primary chondrocytes and hiPSC-derived chondrocytes were defined by RNA sequencing. A Venn diagram was constructed to show the number of shared differentially expressed genes (DEGs) between KBD and normal. Gene oncology and Kyoto Encyclopedia of Genes and Genomes annotations were performed, and six DEGs were further validated in other individuals by real-time quantitative reverse transcription PCR (RT-qPCR).RESULTS: KBD cellular disease models were successfully established by generation of hiPSC lines. Seventeen consistent and significant DEGs present in all compared groups (KBD and normal) were identified. RT-qPCR validation gave consistent results with the sequencing data. Glycosaminoglycan biosynthesis-heparan sulfate/heparin, PPAR signaling pathway and cell adhesion molecules (CAMs) pathways were identified to be significantly altered in KBD.CONCLUSION: Differentiated chondrocytes deriving from KBD-origin hiPSCs provide the first cellular disease model for etiological studies of KBD. This study also provides new sights into the pathogenesis and etiology of KBD and is likely to inform the development of targeted therapeutics for its treatment.
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| 2. |
- Ning, Yujie, et al.
(author)
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Comparative analysis of the gut microbiota composition between knee osteoarthritis and Kashin-Beck disease in Northwest China
- 2022
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In: Arthritis Research & Therapy. - : BioMed Central. - 1478-6354 .- 1478-6362. ; 24:1
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Journal article (peer-reviewed)abstract
- Background: Osteoarthritis (OA) and Kashin-Beck disease (KBD) both are two severe osteochondral disorders. In this study, we aimed to compare the gut microbiota structure between OA and KBD patients.Methods: Fecal samples collected from OA and KBD patients were used to characterize the gut microbiota using 16S rDNA gene sequencing. To identify whether gut microbial changes at the species level are associated with the genes or functions of the gut bacteria between OA and KBD groups, metagenomic sequencing of fecal samples from OA and KBD subjects was performed.Results: The OA group was characterized by elevated Epsilonbacteraeota and Firmicutes levels. A total of 52 genera were identified to be significantly differentially abundant between the two groups. The genera Raoultella, Citrobacter, Flavonifractor, g__Lachnospiraceae_UCG-004, and Burkholderia-Caballeronia-Paraburkholderia were more abundant in the OA group. The KBD group was characterized by higher Prevotella_9, Lactobacillus, Coprococcus_2, Senegalimassilia, and Holdemanella. The metagenomic sequencing showed that the Subdoligranulum_sp._APC924/74, Streptococcus_parasanguinis, and Streptococcus_salivarius were significantly increased in abundance in the OA group compared to those in the KBD group, and the species Prevotella_copri, Prevotella_sp._CAG:386, and Prevotella_stercorea were significantly decreased in abundance in the OA group compared to those in the KBD group by using metagenomic sequencing.Conclusion: Our study provides a comprehensive landscape of the gut microbiota between OA and KBD patients and provides clues for better understanding the mechanisms underlying the pathogenesis of OA and KBD.
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| 3. |
- Ning, Yujie, et al.
(author)
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Genetic Variants and Protein Alterations of Selenium- and T-2 Toxin-Responsive Genes Are Associated With Chondrocytic Damage in Endemic Osteoarthropathy
- 2022
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In: Frontiers in Genetics. - : Frontiers Media S.A.. - 1664-8021. ; 12
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Journal article (peer-reviewed)abstract
- The mechanism of environmental factors in Kashin-Beck disease (KBD) remains unknown. We aimed to identify single nucleotide polymorphisms (SNPs) and protein alterations of selenium- and T-2 toxin-responsive genes to provide new evidence of chondrocytic damage in KBD. This study sampled the cubital venous blood of 258 subjects including 129 sex-matched KBD patients and 129 healthy controls for SNP detection. We applied an additive model, a dominant model, and a recessive model to identify significant SNPs. We then used the Comparative Toxicogenomics Database (CTD) to select selenium- and T-2 toxin-responsive genes with the candidate SNP loci. Finally, immunohistochemistry was applied to verify the protein expression of candidate genes in knee cartilage obtained from 15 subjects including 5 KBD, 5 osteoarthritis (OA), and 5 healthy controls. Forty-nine SNPs were genotyped in the current study. The C allele of rs6494629 was less frequent in KBD than in the controls (OR = 0.63, p = 0.011). Based on the CTD database, PPARG, ADAM12, IL6, SMAD3, and TIMP2 were identified to interact with selenium, sodium selenite, and T-2 toxin. KBD was found to be significantly associated with rs12629751 of PPARG (additive model: OR = 0.46, p = 0.012; dominant model: OR = 0.45, p = 0.049; recessive model: OR = 0.18, p = 0.018), rs1871054 of ADAM12 (dominant model: OR = 2.19, p = 0.022), rs1800796 of IL6 (dominant model: OR = 0.30, p = 0.003), rs6494629 of SMAD3 (additive model: OR = 0.65, p = 0.019; dominant model: OR = 0.52, p = 0.012), and rs4789936 of TIMP2 (recessive model: OR = 5.90, p = 0.024). Immunohistochemistry verified significantly upregulated PPARG, ADAM12, SMAD3, and TIMP2 in KBD compared with OA and normal controls (p < 0.05). Genetic polymorphisms of PPARG, ADAM12, SMAD3, and TIMP2 may contribute to the risk of KBD. These genes could promote the pathogenesis of KBD by disturbing ECM homeostasis.
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| 4. |
- Sun, Weiwei, et al.
(author)
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Monodispersed FeS 2 Electrocatalyst Anchored to Nitrogen-Doped Carbon Host for Lithium–Sulfur Batteries
- 2022
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In: Advanced Functional Materials. - : Wiley. - 1616-3028 .- 1616-301X. ; 32:43
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Journal article (peer-reviewed)abstract
- Despite their high theoretical energy density, lithium–sulfur (Li–S) batteries are hindered by practical challenges including sluggish conversion kinetics and shuttle effect of polysulfides. Here, a nitrogen-doped continuous porous carbon (CPC) host anchoring monodispersed sub-10 nm FeS2 nanoclusters (CPC@FeS2) is reported as an efficient catalytic matrix for sulfur cathode. This host shows strong adsorption of polysulfides, promising the inhibition of polysulfide shuttle and the promoted initial stage of catalytic conversion process. Moreover, fast lithium ion (Li-ion) diffusion and accelerated solid–solid conversion kinetics of Li2S2 to Li2S on CPC@FeS2 host guarantee boosted electrochemical kinetics for conversion process of sulfur species in Li–S cell, which gives a high utilization of sulfur under practical conditions of high loading and low electrolyte/sulfur (E/S) ratio. Therefore, the surfur cathode (S/CPC@FeS2) delivers a high specific capacity of 1459 mAh g−1 at 0.1 C, a stable cycling over 900 cycles with ultralow fading rate of 0.043% per cycle, and an enhanced rate capability compared with cathode only using carbon host. Further demonstration of this cathode in Li–S pouch cell shows a practical energy density of 372 Wh kg−1 with a sulfur loading of 7.1 mg cm−2 and an E/S ratio of 4 µL mg−1.
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| 5. |
- Zhou, Yao, et al.
(author)
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Insight Into Space Charge Suppression by Interfacial Deep Traps in Polymer Nanocomposites
- 2022
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In: IEEE Transactions on Dielectrics and Electrical Insulation. - 1558-4135 .- 1070-9878. ; 29:6, s. 2402-2404
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Journal article (peer-reviewed)abstract
- Polymer nanocomposites are attractive for HVDC insulation applications, especially for HVDC cables, due to their ability to suppress space charge accumulation through interfacial effects. However, direct evidence to support the existence of interfacial effects at the nanoscale is still lacking. Therefore, rational design and molecular engineering of the interfaces to improve the insulation properties of polymer nanocomposites remain unavailable. Here, we show that efficient space charge suppression can be achieved in polymer nanocomposites at temperatures up to 100 °C by introducing local deep traps through carefully designed nanoparticle/polymer interfaces. The local interfacial deep traps are directly detected at the nanoscale using intermodulation electrostatic force microscopy (ImEFM). This work provides a deep understanding of the interfacial effects in polymer nanocomposites and will enable the rational design of interfaces for high-performance insulation materials.
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