Post-trauma osteoarthritis (PTOA) is the most common articular disease characterized by degeneration and destruction of articular cartilage (Bultink and Lems, Curr. Rheumatol Rep., 2013, 15, 328). ...Inflammatory response of local joint tissue induced by trauma is the most critical factor accelerating osteoarthritis (OA) progression (
Sharma et al., 2019
; Osteoarthritis. Cartilage, 28, 658–668). M1/M2 macrophages polarization and repolarization participates in local inflammation, which plays a major role in the progression of OA (
Zhang et al., 2018
; Ann. Rheum. Dis., 77, 1524–1534). The regulating effect of macrophage polarization has been reported as a potential therapy to alleviate OA progression. Synovitis induced by polarized macrophages could profoundly affect the chondrocyte and cartilage matrix (
Zhang et al., 2018
; Ann. Rheum. Dis., 77, 1524–1534). Generally, anti-inflammatory medications widely used in clinical practice have serious side effects. Therefore, we focus on exploring a new therapeutic strategy with fewer side effects to alleviate the synovitis. Angelicin (ANG) is traditional medicine used in various folk medicine. Previous studies have revealed that angelicin has an inhibitory effect on inflammation (
Wei et al., 2016
; Inflammation, 39, 1876–1882), tumor growth (
Li et al., 2016
; Oncology reports, 36, 3,504–3,512;
Wang et al., 2017
; Molecular Medicine Reports, 16, 5441–5449), DNA damage (
Li et al., 2019
; Exp. Ther. Med., 18, 1899–1906), and virus proliferation (
Li et al., 2018
; Front. Cell. Infect. Microbiol., 8, 178). But its specific effects on influencing the process of OA were rarely reported. In this study, the molecular mechanism of angelicin
in vivo
and
in vitro
was clearly investigated. Results showed that angelicin could regulate the M1/M2 ratio and function and alleviate the development of PTOA in the meanwhile. Bone marrow monocytes were isolated and induced by macrophage colony-stimulating factor (M-CSF), lipopolysaccharide (LPS) and interferon (IFN)-γ for M1 polarization and interleukin (IL)-4/IL-13 for M2 polarization. Subsequently, repolarization intervention was performed. The results indicate that angelicin can repolarize M1 toward M2 macrophages by upregulating the expression of CD9. Besides, angelicin can also protect and maintain M2 polarization in the presence of LPS/IFN-γ, and subsequently downregulate the expression of inflammatory mediators such as IL-1β and TNF-α. Mechanistically, angelicin can activate the p-STAT3/STAT3 pathway by conducting CD9/gp130 to repolarize toward M2 macrophages. These results suggest angelicin can alleviate the progression of OA by regulating M1/M2 polarization via the STAT3/p-STAT3 pathway. Therefore, angelicin may have a promising application and potential therapeutic value in OA clinical treatment.
In-field earthworm density can be increased by planting oilseed rape during the non-rice growing season as compared to maintaining the rice-growing fields in fallow. This study was conducted to ...determine the effect on rice yield of earthworm castings produced during the oilseed rape-growing season in rice-oilseed rape cropping fields and to identify the critical factors that contribute to the yield effect. Field microplot experiments were conducted in 2016 and 2017. In 2016, a rice cultivar was grown under a factorial combination of absence (EC
: 0 kg m
) and presence of earthworm castings (EC
: 17 kg m
) with three N application rates (9, 12 and 15 g m
). In 2017, nine rice cultivars were grown under EC
and EC
with the moderate N rate as was used in 2016. Results showed that application of earthworm castings produced during the oilseed rape-growing season in rice-oilseed rape cropping fields had a significant positive yield effect on rice. This was attributed to increased panicle m
and total aboveground biomass while spikelets panicle
, spikelet filling percentage, grain weight, and harvest index were not affected. Our study indirectly provides a new evidence that oilseed rape is an excellent previous crop for cereals.
•Existing CO2 HPWHs in industrial and residential sectors are reviewed.•Performance restricted by the pinch point effect is analyzed.•Limitations in CO2 compressors and lubrication are revealed for ...the first time.•Current enhancements to overcome the limitations are summarized.
In the context of the Montreal Protocol, CO2 is considered as an appropriate natural refrigerant with an Ozone Depletion Potential (ODP) of zero and a Global Warming Potential (GWP) of one. A CO2 heat pump water heater (HPWH) can provide hot water with a relatively high COP and consume significantly less energy than all electric or gas water heaters. This study reviews and analyses the existing CO2 HPWHs both in industrial and residential sectors, where the low-temperature and high-temperature systems are classified by the heat delivery temperature of below and above 80 °C, respectively. The significance and features of existing CO2 HPWHs are also summarised in this study. Moreover, the performance limitations of current CO2 HPWHs are discussed considering the temperature gliding matching, and the technical constraints in both CO2 compressors and heat exchangers. Due to the drastic variation of CO2 heat capacity with temperature and pressure, the heat exchange process between sCO2 and water is affected by the pinch point. The temperature gliding matching can be enhanced by optimising the parameters in both the CO2 and water sides, using zeotropic refrigerant mixtures, or adding new devices or cycles to the existing CO2 system. Another way to improve the system performance is increasing the discharge pressure or discharge temperature, while current CO2 reciprocating compressors have an upper-temperature limit of 140 °C and upper-pressure limit of 140 bar, as well as some constraints in the heat exchangers. Due to the decomposition risk of lubricant in the compressor, two types of oil-free compressors (turbo and scroll) have been described. But it is found that the turbo-compressor is hard to provide a competitive efficiency when the pressure is high, and there is a significant leakage flow in a scroll compressor.
This paper rigorously validates the RANS models against the DNS on predicting turbulent flow and heat transfer of highly buoyant horizontal supercritical fluids. The low-Reynolds number turbulence ...models of RNG, AKN, V2F and (k−ω) SST that are recommended in literature are selected. Also, the LS model demonstrating good performance in some in-house CFD codes has been reimplemented via User-Defined Functions (UDFs) and examined for supercritical simulations, in particular with strong buoyancy effects. The results indicated that the AKN model works best among the tested models on the reproductions of some bulk parameters that are of interest (such as wall temperature, Nusselt number and skin friction coefficient) and the distortions of the turbulent velocity profile caused by the strong buoyancy, closely followed by the V2F model. The UDFs implemented LS model exhibits much better performances than the originally incorporated version in FLUENT, which is attributed to the more proper model implementation that leads to better treatments on the fluid flow and heat transfer, especially in the near-wall regions. Regarding the reproductions on the turbulence kinetic energy generations under the studied conditions, the RANS models are unable to give satisfactory results, the simulated suppression in the top half is more drastic. Similar to the vertical supercritical fluids, with quite high-strength buoyancy, the heat transfer recovers around the horizontal pipe top wall but the RANS models' response to the “recovery” is poor. The model performance on reproducing the turbulent statistics is closely related to the implementation of the vital structural parameters.
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Period1 (PER1) is an important core clock gene, which regulates normal cell proliferations and physiological rhythms of human beings. Recent studies have showed aberrant expressions and altered ...rhythms of PER1 were highly correlated to the carcinogenesis and development of malignant tumors. However, there is no study on the correlation of aberrant expressions and altered rhythms of PER1 with the growth, proliferation and metastasis of buccal squamous cell carcinoma (BSCC). In this study, PER1 and MMP-2 expression in the cancerous and adjacent noncancerous tissues of 38 patients with BSCC and its correlations with patients' clinical pathologic characteristics were investigated. A mouse model of BSCC was also established and mice were sacrificed at 4 different time points in a period of 24 hours. Xenografted tumor weight, proliferation index (PI), and mitotic index (MI) of tumors in the 4 time groups were detected. Results showed that PER1 expression was significantly down-regulated in cancerous tissues of patients with BSCC (P<0.05). PER1 expression was significantly down-regulated in patients of T3∼T4 staging and those with lymph node metastasis compared to that of T1∼T2 staging and those without lymph node metastasis (P<0.05), respectively. PER1 mRNA expression, MI and tumor weight had significant differences among the 4 time groups, which PI all confirmed to circadian rhythms. MI, PI, MMP-2 mRNA and tumor weight had negative correlation with PER1 mRNA expression. Peak value of PER1 mRNA expression and trough values of MI, PI and tumor weight all appeared in middle activity phase, whereas trough value of PER1 mRNA expression and peak values of MI, PI and tumor weight all occurred in middle rest phase. Our study suggested that aberrant expression of PER1 had significant correlation with the growth, proliferation and metastasis of BSCC and it might act as an anti-oncogene.
The mechanism associated with improvement of soil nutritional status by oilseed rape crop, leading to better performance of rice crop, in rice-oilseed rape cropping systems is little known. The ...present study was aimed to test the hypothesis that earthworm casts produced during oilseed rape-growing season have positive effects on grain yield and fertilizer nitrogen (N) utilization in the subsequent flooded rice crop. A 15N-tracing pot experiment was conducted to determine the effects of earthworm casts collected from oilseed rape fields on yield attributes in rice and the fate of fertilizer N. Soil treated with earthworm casts (soil: earthworm casts = 4: 1, w/w) (EC1) produced 39% higher grain yield than soil only (EC0). EC1 had 18% more panicle number and 10% higher spikelet filling percentage than EC0. Aboveground biomass and harvest index were higher in EC1 than in EC0 by 20% and 15%, respectively. SPAD values in flag leaves were 10% and 22% higher under EC1 than EC0 at 15 and 20 days after heading, respectively. EC1 had 19% higher total N uptake and 18% higher physiological N-use efficiency than EC0. These positive effects of earthworm casts on yield attributes offset negative effects of decreasing N rate from 0.74 g pot-1 (equivalent to the recommended field rate of 150 kg ha-1) to 0.44 g pot-1 (equivalent to 60% of the recommended rate). Fertilizer N retention rate was 7% higher while fertilizer N loss rate was 6% lower in EC1 than in EC0. Our study suggests that earthworm casts produced during oilseed rape-growing season are expected to have the following benefits on the subsequent flooded rice system: (1) improving growth and physiological processes in rice plants and consequently increasing rice grain yield, and (2) increasing fertilizer N retention rate and hence decreasing fertilizer N loss rate and reducing environmental risk.
More than 50% of prostate cancer (PCa) patients have bone metastasis with osteoblastic lesions. MiR-18a-5p is associated with the development and metastasis of PCa, but it remains unclear whether it ...is involved in osteoblastic lesions. We first found that miR-18a-5p was highly expressed in the bone microenvironment of patients with PCa bone metastases. To address how miR-18a-5p affects PCa osteoblastic lesions, antagonizing miR-18a-5p in PCa cells or pre-osteoblasts inhibited osteoblast differentiation in vitro. Moreover, injection of PCa cells with miR-18a-5p inhibition improved bone biomechanical properties and bone mineral mass in vivo. Furthermore, miR-18a-5p was transferred to osteoblasts by exosomes derived from PCa cells and targeted the Hist1h2bc gene, resulting in Ctnnb1 up-regulation in the Wnt/β-catenin signaling pathway. Translationally, antagomir-18a-5p significantly improved bone biomechanical properties and alleviated sclerotic lesions from osteoblastic metastases in BALB/c nude mice. These data suggest that inhibition of exosome-delivered miR-18a-5p ameliorates PCa-induced osteoblastic lesions.
Osteoarthritis (OA) is a chronic degenerative joint disease that primarily affects middle-aged and elderly individuals. The decline in chondrocyte function plays a crucial role in the development of ...OA. Inflammasome-mediated chondrocyte pyroptosis is implicated in matrix degradation and cartilage degeneration in OA patients. Guanylate binding protein 5 (GBP5), a member of the GTPase family induced by Interferon-γ (IFN-γ), significantly influences cellular inflammatory responses, including intracellular inflammasome activation and cytokine release. However, the role of GBP5 in chondrocyte pyroptosis and OA progression remains unclear.
In this study, we used tumor necrosis factor-α (TNF-α) to induce inflammation and created an OA mouse model with surgically-induced destabilization of the medial meniscus (DMM). We isolated and cultured primary chondrocytes from the knee joints of suckling C57 mice. TNF-α-stimulated primary chondrocytes served as an in vitro model for OA and underwent RNA sequencing. Chondrocytes were transfected with GBP5-overexpression plasmids and small interfering RNA and were subsequently treated with TNF-α. We assessed the expression of cartilage matrix components (COL2A1 and aggrecan), catabolic factors (MMP9 and MMP13), and NLRP3 inflammasome pathway genes (NLRP3, Caspase1, GSDMD, Pro-IL-1β, and Pro-Caspase1) using RT-qPCR and Western blotting. We analyzed the expression of GBP5, NLRP3, and Caspase1 in the cartilage of DMM-induced post-traumatic OA mice and human OA patients. Immunohistochemistry (IHC) was used to detect the expression of GBP5, NLRP3 and GSDMD in cartilage specimens from OA patients and mouse DMM models. Chondrocyte pyroptosis was assessed using flow cytometry, and the levels of interleukin-1β (IL-1β) and interleukin-18 (IL-18) were measured with ELISA. We conducted double luciferase reporter gene and chromatin immunoprecipitation (ChIP) assays to confirm the relationship between IRF1 and GBP5.
GBP5 expression increased in TNF-α-induced chondrocytes, as revealed by RNA sequencing. GBP5 inhibited COL2A1 and aggrecan expression while promoting the expression of MMP9, MMP13, NLRP3, Caspase1, GSDMD, Pro-IL-1β, and Pro-Caspase1. GBP5 expression also increased in the cartilage of DMM-induced post-traumatic OA mice and human OA patients. Knockout of GBP5 reduced chondrocyte injury in OA mice. GBP5 promoted chondrocyte pyroptosis and the production of IL-1β and IL-18. Additionally, we found that IRF1 bound to the promoter region of GBP5, enhancing its expression. After co-transfected with ad-IRF1 and siGBP5, the expression of pyroptosis-related genes was significantly decreased compared with ad-IRF1 group.
The IRF1/GBP5 axis enhances extracellular matrix (ECM) degradation and promotes pyroptosis during OA development, through the NLRP3 inflammasome signaling pathway.
This study underscores the significance of the IRF1/GBP5 axis in NLRP3 inflammasome-mediated chondrocyte pyroptosis and osteoarthritic chondrocyte injury. Modulating IRF1 and GBP5 expression could serve as a novel therapeutic target for OA.
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Recently, extracellular matrix-based tissue-engineered bone is a promising approach to repairing bone defects, and the seed cells are mostly mesenchymal stem cells. However, bone remodelling is a ...complex biological process, in which osteoclasts perform bone resorption and osteoblasts dominate bone formation. The interaction and coupling of these two kinds of cells is the key to bone repair. Therefore, the extracellular matrix secreted by the mesenchymal stem cells alone cannot mimic a complex bone regeneration microenvironment, and the addition of extracellular matrix by preosteoclasts may contribute as an effective strategy for bone regeneration. Here, we established the mesenchymal stem cell/preosteoclast extracellular matrix -based tissue-engineered bones and demonstrated that engineered-scaffolds based on mesenchymal stem cell/ preosteoclast extracellular matrix significantly enhanced osteogenesis in a 3 mm rat femur defect model compared with mesenchymal stem cell alone. The bioactive proteins released from the mesenchymal stem cell/ preosteoclast extracellular matrix based tissue-engineered bones also promoted the migration, adhesion, and osteogenic differentiation of mesenchymal stem cells in vitro. As for the mechanisms, the iTRAQ-labeled mass spectrometry was performed, and 608 differentially expressed proteins were found, including the IGFBP5 and CXCL12. Through in vitro studies, we proved that CXCL12 and IGFBP5 proteins, mainly released from the preosteoclasts, contributed to mesenchymal stem cells migration and osteogenic differentiation, respectively. Overall, our research, for the first time, introduce pre-osteoclast into the tissue engineering of bone and optimize the strategy of constructing extracellular matrix–based tissue-engineered bone using different cells to simulate the natural bone regeneration environment, which provides new sight for bone tissue engineering.
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