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Abstract Background Human adipose-derived stem cells (ADSCs) exert a strong anti-inflammatory effect, and synovium-derived stem cells (SDSCs) have high chondrogenic potential. Thus, this study aims to investigate whether a combination of human ADSCs and SDSCs will have a synergistic effect that will increase the chondrogenic potential of osteoarthritis (OA) chondrocytes in vitro and attenuate the cartilage degeneration of early and advanced OA in vitro. Methods ADSCs, SDSCs, and chondrocytes were isolated from OA patients who underwent total knee arthroplasty. The ADSCs–SDSCs mixed cell ratios were 1:0 (ADSCs only), 8:2, 5:5 (5A5S), 2:8, and 0:1 (SDSCs only). The chondrogenic potential of the OA chondrocytes was evaluated in vitro with a transwell assay or pellet culture with various mixed cell groups. The mixed cell group with the highest chondrogenic potential was then selected and injected into the knee joints of nude rats of early and advanced OA stages in vivo. The animals were then evaluated 12 and 20 weeks after surgery through gait analysis, von frey test, microcomputed tomography, MRI, and immunohistochemical and histological analyses. Finally, the mechanisms underlying these findings were investigated through the RNA sequencing of tissue samples in vivo and Western blot of the OA chondrocyte autophagy pathway. Results Among the MSCs treatment groups, 5A5S had the greatest synergistic effect that increased the chondrogenic potential of OA chondrocytes in vitro and inhibited early and advanced OA in vivo. The 5A5S group significantly reduced cartilage degeneration, synovial inflammation, pain sensation, and nerve invasion in subchondral nude rat OA, outperforming both single-cell treatments. The underlying mechanism was the activation of chondrocyte autophagy via the FoxO1 signaling pathway. Conclusion A combination of human ADSCs and SDSCs demonstrated higher potential than a single type of stem cell, demonstrating potential as a novel treatment for OA.

A deep understanding of the effects of the inorganic characteristics of Xinjiang coals on combustion particulate generation is of great significance for their clean and efficient utilization. This work investigated the inorganic characteristics of Wucaiwan coal (WCW), Wanxiang coal (WX), Tianchi coal (TC), and Xiheishan coal (XHS) and the their relationship with the production of ultrafine particulates during combustion. The results show that the four Xinjiang coals are mainly lignites with low ash and sulfur contents. Coal ashes are enriched in basic elements. Among them, the content of Na2O (3.58%−7.13%) is commonly higher than that of conventional utility coals. The ashes of WCW and WX coals have higher contents of CaO (> 33%), but low contents of SiO2 and Al2O3. WX coal is particularly characterized by high Na and Cl. The Na in coal is primarily water soluble(62.3%−90.6%). The K is mainly HCl insoluble. The Fe occurs primarily as HCl soluble and insoluble forms. And the distribution of Ca and Mg in different forms varies according to coal types. The composition of ultrafine particulate matter from Xinjiang coal combustion is dominated by Na, K, Cl, and S. The particle size range of the ultrafine particulate matter is accurately defined by using the condition that the mass fraction of Na2O+K2O+Cl+SO3 is higher than 50%. The ultrafine particulate matter of WCW, TC and XHS coals has similar particle size ranges (≤0.07 μm); while the ultrafine particulate matter of WX coal, which has the highest content of Na in the water-soluble form, has a wider particle size range (≤0.76 μm). The generation of ultrafine particulate matter (y) is found to be highly linearly and positively correlated with the total amount of water-soluble (Na+K) (x) in the coal, with the relationship equation y = 0.528x−0.239 and the correlation coefficient of 0.948.

Abstract Skeletal disorders are commonly diagnosed by X-ray imaging, but the radiation limits its use. Optical imaging through the near-infrared-II window (NIR-II, 1000–1700 nm) can penetrate deep tissues without radiation risk, but the targeting of contrast agent is non-specific. Here, we report that lanthanide-doped nanocrystals can passively target the bone marrow, which can be effective for over two months. We therefore develop the high-resolution NIR-II imaging method for bone disease diagnosis, including the 3D bone imaging instrumentation to show the intravital bone morphology. We demonstrate the monitoring of 1 mm bone defects with spatial resolution comparable to the X-ray imaging result. Moreover, NIR-II imaging can reveal the early onset inflammation as the synovitis in the early stage of rheumatoid arthritis, comparable to micro computed tomography (μCT) in diagnosis of osteoarthritis, including the symptoms of osteophyte and hyperostosis in the knee joint.

Background Extracellular vesicles derived from mesenchymal stem cells (MSCs) show great promise in treating osteoarthritis (OA). However, studies from the perspective of clinical feasibility that consider an accessible cell source and a scalable preparationmethod forMSC-extracellular vesicles are lacking. Questions/purposes (1) Does an infrapatellar fat pad obtained from patients undergoing TKA provide a suitable source to provide MSC-extracellular vesicles purified by anion exchange chromatography? Using an in vivo mouse model for OA in the knee, (2) how does injection of the infrapatellar fat pad-derived MSC-extracellular vesicles alter gait, cartilage structure and composition, protein expression (Type II collagen, MMP13, and ADAMTS5), subchondral bone remodeling and osteophytes, and synovial inflammation? Methods The infrapatellar fat pad was collected from three patients (all female; 62, 74, 77 years) during TKA for infrapatellar fat pad-derived MSC culturing. Patients with infection, rheumatic arthritis, and age > 80 years were excluded. MSC-extracellular vesicles were purified by anion exchange chromatography. For the animal study, we used 30 male C57BL/6 mice aged 10 weeks, divided into six groups. MSC-extracellular vesicles were injected weekly into the joint of an OA mouse model during ACL transection (ACLT). To answer our first research question, we characterized MSCs based on their proliferative potential, differentiation capacity, and surface antigen expression, and we characterized MSC-extracellular vesicles by size, morphology, protein marker expression, and miRNA profile. To answer our second research question, we evaluated the effects of MSC-extracellular vesicles in the OA mouse model with quantitative gait analysis (mean pressure, footprint area, stride length, and propulsion time), histology (Osteoarthritis Research Society International Score based on histologic analysis [0 = normal to 24 = very severe degeneration]), immunohistochemistry staining of joint sections (protein expression of Type II collagen, MMP13, and ADAMTS5), and micro-CT of subchondral bone (BV/TV and Tb.Pf) and osteophyte formation. We also examined the mechanism of action of MSCextracellular vesicles by immunofluorescent staining of the synovium membrane (number of M1 and M2 macrophage cells) and by analyzing their influence on the expression of inflammatory factors (relative mRNA level and protein expression of IL-1β, IL-6, and TNF-α) in lipopolysaccharide-induced macrophages. Results Infrapatellar fat pads obtained from patients undergoing TKA provide a suitable cell source for producing MSC-extracellular vesicles, and anion exchange chromatography is applicable for isolating MSC-extracellular vesicles. Cultured MSCs were spindle-shaped, proliferative at Passage 4 (doubling time of 42.75 ± 1.35 hours), had trilineage differentiation capacity, positively expressed stem cell surface markers (CD44, CD73, CD90, and CD105), and negatively expressed hematopoietic markers (CD34 and CD45). MSC-extracellular vesicles purified by anion exchange chromatography had diameters between 30 and 200 nm and a typical cup shape, positively expressed exosomal marker proteins (CD63, CD81, CD9, Alix, and TSG101), and carried plentiful miRNA. Compared with the ACLT group, the ACLT + extracellular vesicle group showed alleviation of pain 8 weeks after the injection, indicated by increased area (0.67 ± 0.15 cm² versus 0.20 ± 0.03 cm², -0.05 [95% confidence interval -0.09 to -0.01]; p = 0.01) and stride length (5.08 60.53 cm versus 6.20 ± 0.33 cm, -1.12 [95% CI -1.86 to -0.37]; p = 0.005) and decreased propulsion time (0.2260.06 s versus 0.1160.04 s, 0.11 [95% CI 0.03 to 0.19]; p = 0.007) in the affected hindlimb. Compared with the ACLT group, the ACLT + extracellular vesicles group had lower Osteoarthritis Research Society International scores after 4 weeks (8.80 ± 2.28 versus 4.80 ± 2.28, 4.00 [95% CI 0.68 to 7.32]; p = 0.02) and 8 weeks (16.00 ± 3.16 versus 9.6062.51, 6.40 [95% CI 2.14 to 10.66]; p = 0.005). In the ACLT + extracellular vesicles group, there was moresevere OA at 8 weeks than at 4 weeks (9.60 ± 2.51 versus 4.80 ± 2.28, 4.80 [95% CI 0.82 to 8.78]; p = 0.02), indicating MSC-extracellular vesicles could only delay but not fully suppress OA progression. Compared with the ACLT group, the injection of MSC-extracellular vesicles increased Type II collagen expression, decreased MMP13 expression, and decreased ADAMTS5 expression at 4 and 8 weeks. Compared with the ACLT group, MSCextracellular vesicle injection alleviated osteophyte formation at 8 weeks and inhibited bone loss at 4 weeks. MSC-extracellular vesicle injection suppressed inflammation; the ACLT + extracellular vesicles group had fewer M1 type macrophages than the ACLT group. Compared with lipopolysaccharide-treated cells, MSCextracellular vesicles reduced mRNA expression and inhibited IL-1β, IL-6, and TNF-α in cells. Conclusion Using an OA mouse model, we found that infrapatellar fat pad-derived MSC-extracellular vesicles could delay OA progression via alleviating pain and suppressing cartilage degeneration, osteophyte formation, and synovial inflammation. The autologous origin of extracellular vesicles and scalable purification method make our strategy potentially viable for clinical translation. Clinical Relevance Infrapatellar fat pad-derived MSCextracellular vesicles isolated by anion exchange chromatography can suppress OA progression in a mouse model. Further studies with large-animal models, larger animal groups, and subsequent clinical trials are necessary to confirm the feasibility of this technique for clinical OA treatment. [ABSTRACT FROM AUTHOR]

The high proportion of renewable energy and power electronic equipment is emerging as a significant trend and key characteristic of the power system development driven by the dual promotion of the energy transformation and scientific technological advancement. Major modifications have been made to the dynamic behavior of the new power system. The traditional small signal stability analysis approach is difficult to apply, and there are still urgent issues to be resolved for the quick change of operating conditions. In this paper, a Lyapunov direct analysis method of gradient dynamic deviation based on phasor measurement unit (PMU) data is proposed to analyze the small signal stability of the new power system. First, the PMU data matrix is used to reduce the dimension to obtain the low dimension matrix, which is substituted into the power system matrix model with a doubly-fed induction generator (DFIG). The diagonal matrix is obtained by solving the Lyapunov equation, and the positive definiteness of the matrix is determined to judge the system stability. Then, the dynamic deviation of corresponding state variable is calculated by solving the obtained diagonal matrix. The gradient descent method is applied to the corresponding state variable curve to iterate the extreme point value of curve. The time-weighted dynamic deviation of the whole oscillation process is calculated by time weighting, which provides guidance for the subsequent configuration position of damping stability controller, i.e., power system stabilizer (PSS). The method can improve the small interference stability of the system. The effectiveness of the fast stability analysis of the new power system is verified by simulations of the new England 10-machine 39-bus system with DFIG.