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Systemic application of glucocorticoids is an essential anti-inflammatory and immune-modulating therapy for severe inflammatory or autoimmunity conditions. However, its long-term effects on articular cartilage of patients' health need to be further investigated. In this study, we studied the effects of dexamethasone (Dex) on the homeostasis of articular cartilage and the progress of destabilization of medial meniscus (DMM)-induced osteoarthritis (OA) in adult mice. Long-term administration of Dex aggravates the proteoglycan loss of articular cartilage and drastically accelerates cartilage degeneration under surgically induced OA conditions. In addition, Dex increases calcium content in calcified cartilage layer of mice and the samples from OA patients with a history of long-term Dex treatment. Moreover, long term usage of Dex results in decrease subchondral bone mass and bone density. Further studies showed that Dex leads to calcification of extracellular matrix of chondrocytes partially through activation of AKT, as well as promotes apoptosis of chondrocytes in calcified cartilage layer. Besides, Dex weakens the stress-response autophagy with the passage of time. Taken together, our data indicate that long-term application of Dex may predispose patients to OA and or even accelerate the OA disease progression development of OA patients.

This work reports our discoveries from the first exploration in microwave pyrolysis of a metal–organic framework. A time- and energy-efficient approach was developed for direct fabrication of electrochemical single-atom catalysts (E-SACs) without the requirement of post-treatment. The most unique structure of the fabricated E-SAC is that the Cu catalytic sites were not in the amorphous carbon matrix as those achieved via traditional pyrolysis but in the basal planes of pristine holey graphene nanoplatelets. The as-prepared Cu-E-SAC exhibits excellent catalytic activity and selectivity in reducing oxygen to water in both acidic and alkaline media. The desired direct 4e– pathway is more favorable in acidic versus alkaline media, which is different from all the Cu-E-SACs reported so far and most transition-metal-based E-SACs. The superior performance is attributed to the unique structure of the catalytic sites. The large graphene domains in the holey graphene materials provide higher delocalized electron-rich π band and increase the d-orbital energy level of the Cu centers. Consequently, their binding strength for molecular oxygen is largely enhanced, improving the oxygen reduction reaction and likely promoting a direct 4e– pathway with minimized generation of a peroxide byproduct. Considering the high conductivity and excellent stability against oxidation of the holey graphene material, this work, for the first time, suggests that the contradictory structural requirement of a carbon matrix for high catalytic activity and long-term durability can be unified and simultaneously satisfied. Combined with the merits of simplicity and rapidness for fabricating both holey graphene and E-SACs, this work provides a possible strategy to address the critical challenges of precious metal-free single-atom catalysts.

Exosomes participate in many physiological and pathological processes by regulating cell–cell communication, which are involved in numerous diseases, including osteoarthritis (OA). Exosomes are detectable in the human articular cavity and were observed to change with OA progression. Several joint cells, including chondrocytes, synovial fibroblasts, osteoblasts, and tenocytes, can produce and secrete exosomes that influence the biological effects of targeted cells. In addition, exosomes from stem cells can protect the OA joint from damage by promoting cartilage repair, inhibiting synovitis, and mediating subchondral bone remodeling. This review summarizes the roles and therapeutic potential of exosomes in OA and discusses the perspectives and challenges related to exosome-based treatment for OA patients in the future.

Systemic application of glucocorticoids is an essential anti-inflammatory and immune-modulating therapy for severe inflammatory or autoimmunity conditions. However, its long-term effects on articular cartilage of patients' health need to be further investigated. In this study, we studied the effects of dexamethasone (Dex) on the homeostasis of articular cartilage and the progress of destabilization of medial meniscus (DMM)-induced osteoarthritis (OA) in adult mice. Long-term administration of Dex aggravates the proteoglycan loss of articular cartilage and drastically accelerates cartilage degeneration under surgically induced OA conditions. In addition, Dex increases calcium content in calcified cartilage layer of mice and the samples from OA patients with a history of long-term Dex treatment. Moreover, long term usage of Dex results in decrease subchondral bone mass and bone density. Further studies showed that Dex leads to calcification of extracellular matrix of chondrocytes partially through activation of AKT, as well as promotes apoptosis of chondrocytes in calcified cartilage layer. Besides, Dex weakens the stress-response autophagy with the passage of time. Taken together, our data indicate that long-term application of Dex may predispose patients to OA and or even accelerate the OA disease progression development of OA patients.

ObjectivesThis study aims to investigate the role and mechanism of FGFR3 in macrophages and their biological effects on the pathology of arthritis.MethodsMice with conditional knockout of FGFR3 in myeloid cells (R3cKO) were generated. Gait behaviours of the mice were monitored at different ages. Spontaneous synovial joint destruction was evaluated by digital radiographic imaging and μCT analysis; changes of articular cartilage and synovitis were determined by histological analysis. The recruitment of macrophages in the synovium was examined by immunostaining and monocyte trafficking assay. RNA-seq analysis, Western blotting and chemotaxis experiment were performed on control and FGFR3-deficient macrophages. The peripheral blood from non-osteoarthritis (OA) donors and patients with OA were analysed. Mice were treated with neutralising antibody against CXCR7 to investigate the role of CXCR7 in arthritis.ResultsR3cKO mice but not control mice developed spontaneous cartilage destruction in multiple synovial joints at the age of 13 months. Moreover, the synovitis and macrophage accumulation were observed in the joints of 9-month-old R3cKO mice when the articular cartilage was not grossly destructed. FGFR3 deficiency in myeloid cells also aggravated joint destruction in DMM mouse model. Mechanically, FGFR3 deficiency promoted macrophage chemotaxis partly through activation of NF-κB/CXCR7 pathway. Inhibition of CXCR7 could significantly reverse FGFR3-deficiency-enhanced macrophage chemotaxis and the arthritic phenotype in R3cKO mice.ConclusionsOur study identifies the role of FGFR3 in synovial macrophage recruitment and synovitis, which provides a new insight into the pathological mechanisms of inflammation-related arthritis.

Objective To explore the effect of dexamethasone (Dex) infusion on articular cartilage and the underlying mechanisms in vitro and in vivo. Methods Destabilization of medial meniscus (DMM)-induced OA mouse model was used in this study. The mice with Dex treatment were sacrificed and then the knee joint samples were obtained for pathological analysis. Mouse primary chondrocytes were isolated and cultured in the presence or absence of Dex, which were used for calcification analysis and western blot assay. Results Dex accelerated the loss of articular cartilage matrix in mice, while it aggravated the damage of cartilage in DMM-induced OA model at the late stage. The calcium content in calcified cartilage layer in the joints from Dex treated OA mice was significantly higher than that from control mice. Dex treatment enhanced mineralization of articular cartilage matrix and leaded to massive apoptosis of chondrocytes in OA model. In addition, Dex caused autophagy of chondrocytes in the early stage, which was decreased at the late stage of Dex treatment. Moreover, we found that the effect of Dex on the mineralization of articular cartilage matrix in mice was related to AKT activation. Conclusions Continuous infusion of Dex can enhance the calcification of cartilage via AKT activation and increase chondrocyte apoptosis through inhibiting autophagy, which aggravates the damage of articular cartilage and accelerates the progression of OA in vivo.

Background: Recruit training injuries have caused serious problems for troop training and medical support. The lower limbs is the site where recruit injuries occur the most. Bio-impedance (BIA) measures body composition quickly and accurately. Our aim was to identify the risk factors for lower limbs training injuries to recruits due to body composition.Methods: A total of 282 recruits were included. Before training, use BodyStat QuadScan 4000 multifrequency BIA system to measure the body composition of recruits. After training, they were divided into two groups according to the occurrence of lower limb training injuries. The basic characteristics of the two recruits were compared by Wilcoxon rank sum test. Receiver operator characteristic (ROC) curves was performed on the indicators with statistical difference between the two groups to find the cutoff point. Finally, multivariate logistic regression analysis was used to find the risk factors of lower limb training injuries.Results: Compared with the lower limb uninjured group, the lean mass percentage (P = 0.003), TBW percentage (P = 0.010), extracellular water (ECW) percentage (P = 0.023), intracellular water(ICW) percentage (P = 0.027), 3rd space water (P = 0.021) and basal metabolic rate(BMR)/total weight (P = 0.014) of the lower limb injury group was higher. On the contrary, the body fat percentage (P = 0.003) and body fat mass index (BFMI) (P = 0.005) of the lower limb injury group was lower. The results of multivariate logistic regression analysis showed that TBW percentage > 65.350% (P = 0.050, OR=2.085) and 3rd space water >0.950 (P = 0.045, OR=2.342) were independent risk factors for lower limb injuries.Conclusions: TBW percentage> 65.35% and 3rd space water >0.950 were independent risk of lower limb training injuries. These recruits need to be paid more attention during training.

Synovitis plays an important role in the pathogenesis of arthritis, which is closely related to the joint swell and pain of patients. The purpose of this study was to investigate the anti-inflammatory effects of pulsed electromagnetic fields (PEMF) on synovitis and its underlying mechanisms. Destabilization of the medial meniscus (DMM) model and air pouch inflammation model were established to induce synovitis in C57BL/6 mice. The mice were then treated by PEMF (pulse waveform, 1.5 mT, 75 Hz, 10% duty cycle). The synovitis scores as well as the levels of IL-1β and TNF-α suggested that PEMF reduced the severity of synovitis in vivo. Moreover, the proportion of neutrophils in the synovial-like layer was decreased, while the proportion of macrophages increased after PEMF treatment. In addition, the phagocytosis of apoptotic neutrophils by macrophages (efferocytosis) was enhanced by PEMF. Furthermore, the data from western blot assay showed that the phosphorylation of P38 was inhibited by PEMF. In conclusion, our current data show that PEMF noninvasively exhibits the anti-inflammatory effect on synovitis via upregulation of the efferocytosis in macrophages, which may be involved in the phosphorylation of P38.

This study aims to evaluate the applicability of the degraded stiffness matrix and the redefined characteristic length models in the finite element analysis of composite laminates under low-velocity impact. Implemented by the user-defined VUMAT subroutine in ABAQUS, various damage models are used to predict the damage behavior in the composite laminates, meanwhile, the user-defined VUCHARLENGTH subroutine is applied to define the characteristic length to match the damage mode. Cohesive elements are inserted between the adjacent piles to model the delamination. The applicability of different damage models is investigated by comparing the global mechanical response and local damage behavior. A new characteristic length calculation method is proposed to apply in the low-velocity impact simulation for laminates. The numerical results show that the degraded stiffness matrix proposed by both Maimi and Matzenmiller can accurately predict the global mechanical responses in the complicated damage accumulation case, while the model of PEE (the principle of energy equivalence) and Linde aren’t suitable for the low-velocity impact simulation. As for the characteristic length model, the redefined characteristic length model can obtain more accurate global mechanical responses with the impact energy increasing compared with the predictions of default characteristic length model.

Synovitis is implicated in the pathology of osteoarthritis (OA) and significantly contributes to the development of OA. As a noninvasive physical therapy, low-intensity pulsed ultrasound (LIPUS) has been reported to possess anti-inflammatory effect in recent years. However, the role of LIPUS on synovitis of OA and the underlying mechanisms are little known. The present study showed that LIPUS ameliorated synovial inflammation in destabilization of the medial meniscus (DMM) mouse model and air pouch model, and alleviated pain gait patterns of DMM mouse. LIPUS dramatically inhibited the production of mature IL1B/IL-1β (interleukin 1 beta) in vitro and in vivo. In addition, LIPUS upregulated the macroautophagy/autophagy level as well as accelerated the formation of an SQSTM1 (sequestosome1)-PKM (pyruvate kinase, muscle) complex in the lipopolysaccharide (LPS)-adenosine triphosphate (ATP)-treated macrophages. Besides, LIPUS downregulated the level of PKM2 in LPS-ATP-treated macrophages, which could be reversed by SQSTM1 knockdown. In brief, the present study for the first time demonstrates that LIPUS inhibits the production of mature IL1B partially via SQSTM1-dependent autophagic degradation of PKM2 in LPS-ATP-treated macrophages, which may further ameliorate the synovial inflammation and gait patterns in animal models. Our data provide new clues for the treatments of synovitis and other inflammatory diseases using LIPUS. ABBREVIATIONS: 3-MA: 3-methyladenene; ATG7: autophagy-related 7; ATP: adenosine triphosphate; BafA1: bafilomycin A(1); BMDMs: bone marrow derived macrophages; CHX: cycloheximide; DMM: destabilization of the medial meniscus; ELISA: enzyme-linked immunosorbent assay; GFP: green fluorescent protein; IL1B/IL-1β: interleukin 1 beta; LIPUS: low-intensity pulsed ultrasound; LIR: LC3-interacting region; LPS: lipopolysaccharide; MAP1LC3B/LC3B: microtubule associated protein 1 light chain 3 beta; MDP: muramyl dipeptide; NFKB/NF-κB: nuclear factor kappa B; NLRP3: NLR family, pyrin domain containing 3; OA: osteoarthritis; PKM/PKM2: pyruvate kinase M1/2; PMA: phorbol-12-myristate-13-acetate; PYCARD/ASC; PYD and CARD domain containing; RFP: red fluorescent protein; siRNAs: small interfering RNAs; SQSTM1: sequestosome 1; TEM: transmission electron microscopy

Surface functionalization of inorganic nanomaterials through chemical binding of organic ligands on the surface unsaturated atoms, forming unique organic-inorganic interfaces, is a powerful approach for creating special functions for inorganic nanomaterials. Herein, we report the synthesis of hierarchical MgO nanocrystal clusters (NCs) with an organic-inorganic interface induced multi-fluorescence and their application as new alternative labels for cellular imaging. The synthetic method was established by a dissolution and regrowth process with the assistance of carboxylic acid, in which the as-prepared MgO NCs were modified with carboxylic groups at the coordinatively unsaturated atoms of the surface. By introducing acetic acid to partially replace oleic acid in the reaction, the optical absorption of the produced MgO NCs was progressively engineered from the UV to the visible region. Importantly, with wider and continuous absorption profile, those MgO NCs presented bright and tunable multicolor emissions from blue-violet to green and yellow, with the highest absolute quantum yield up to (33±1) %. The overlap for the energy levels of the inorganic-organic interface and low-coordinated states stimulated a unique fluorescence resonance energy transfer phenomenon. Considering the potential application in cellular imaging, such multi-fluorescent MgO NCs were further encapsulated with a silica shell to improve the water solubility and stability. As expected, the as-formed MgO@SiO2 NCs possessed great biocompatibility and high performance in cellular imaging.

Surface engineering of crystals at nanoscale level by precisely and rationally exposing specific facets proved to be highly effective in enhancing the performance of inorganic functional nanocrystals. To do so, a comprehensive understanding of the growth mechanism was of great importance. By using hematite (α-Fe2O3) as an example, in this paper we demonstrated high effectiveness of controlling supersaturation of growth monomers in engineering the exposed facets of nanocrystals. Under surfactant-free hydrothermal conditions, a series of morphology evolution of α-Fe2O3 nanocrystals from {012} faceted pseudocubes to {113} faceted hexagonal bipyramids and {001} faceted nanoplates were successfully activated through concentration-, reaction time-, and solvent-dependent hydrolysis of ferric acetylacetonate. High supersaturation was eventually proven to be conducive to the formation of facets with high surface energy. Furthermore, the α-Fe2O3 nanocrystals enclosed with facets of high surface energy exhibited excellent catalytic activity and gas-sensing ability. The present work will deepen our understanding of thermodynamics and kinetic control over the morphology of nanocrystals as well as our understanding of surface-related performance of inorganic functional nanocrystals.

The shape of it: A series of anatase TiO(2) nanocrystals with exposed high-energy {001} facets or high-index {103}, {102} facets and/or low-energy {101} facets were successfully synthesized via a fluorine-free route, and crystal-facet-dependent photodegradation activities were found to follow the sequence of {001}{102}≈{103}{101} (see picture; the scale bars are 200 nm).

Fe incorporated TiO(2) nanotube arrays (Fe-TiO(2)NTs) were prepared by an ultrasound-assisted impregnating-calcination method. Scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), and UV-vis diffuse reflectance spectroscopy (DRS) indicated that α-Fe(2)O(3) nanoparticles were deposited into the TiO(2) nanotubes, and in the mean time, some Fe(3+) ions were doped into TiO(2) lattice. The absorption of Fe-TiO(2)NTs in the visible light region increased with the increase of Fe content. The photocatalytic activity of Fe-TiO(2)NTs was evaluated by the degradation of methylene blue aqueous solution under visible light irradiation. The results demonstrated that the Fe-TiO(2)NTs exhibited significantly enhanced photocatalytic activity compared with pure TiO(2)NTs. Photoluminescence (PL) and electrochemical impedance spectroscopy (EIS) analyses further confirmed that the increased photocatalytic activity of the Fe-TiO(2)NTs was attributed to an enhanced separation and transfer of photogenerated charge carriers.

Anatase TiO2 nanoparticles exposed with a remarkable amount (60%) of high-energy (001) facets were synthesized via a fluorine-free hydrothermal route, using K-titanate nanowires as a precursor and urea as a surface regulator. The carbonate ions were found to play a key role in the formation of the exposed (001) facets.