Nanofat lysate ameliorates pain and cartilage degradation of osteoarthritis through activation of TGF-β–Smad2/3 signaling of chondrocytes

Introduction: Nanofat is an effective cell therapy for osteoarthritis (OA). However, it has clinical limitations due to its short half-life. We developed Nanofat lysate (NFL) to overcome the defect of Nanofat and explore its anti-OA efficacy and mechanism.Methods: Monoiodoacetate (MIA) was employed to establish rat OA model. For pain assessment, paw withdrawal latency (PWL) and thermal withdrawal latency (TWL) were evaluated. Degeneration of cartilage was observed by histopathological and immunohistochemical examination. Primary chondrocytes were treated with TNF-α to establish the cellular model of OA. MTT, wound healing, and transwell assays were performed to assess effects of NFL on chondrocytes. RNA-seq, qPCR and Western blot assays were conducted to clarify the mechanism of NFL.Results and Discussion: The animal data showed that PWL and TWL values, Mankin’s and OARSI scorings, and the Col2 expression in cartilage were significantly improved in the NFL-treated OA rats. The cellular data showed that NFL significantly improved the proliferation, wound healing, and migration of chondrocytes. The molecular data showed that NFL significantly restored the TNF-α-altered anabolic markers (Sox9, Col2 and ACAN) and catabolic markers (IL6 and Mmp13). The RNA-seq identified that TGF-β-Smad2/3 signaling pathway mediated the efficacy of NFL, which was verified by qPCR and Western blot that NFL significantly restored the abnormal expressions of TGFβR2, phosphorylated-Smad2, phosphorylated-Smad2/3, Col2, Mmp13 and Mmp3. After long-term storage, NFL exerted similar effects as its fresh type, indicating its advantage of storability. In sum, NFL was developed as a new therapeutic approach and its anti-OA efficacy and mechanism that mediated by TGF-β-Smad2/3 signaling was determined for the first time. Besides, the storability of NFL provided a substantial advantage than other living cell-based therapies

A transfer learning-based YOLO network for sewer defect detection in comparison to classic object detection methods

Deep learning has shown promising performance in automated sewer defect detection, however, is generally data-driven and computationally intensive. Transfer learning (TL) solves the problem of data limitations and avoids the need to build models from scratch. This study compared the performance of a TL-based YOLO network (with 11 pretrained backbone CNNs) with four mainstream object detection methods (ODMs) for detecting five types of sewer defects. Results showed that the transferred YOLO methods generally outperformed the other ODMs, with improved detection precision, computation speed and intersection over union (IoU). Among the CNNs, Resnet18 achieved the best performance, while Inceptionresnetv2 was the least effective. The ODMs worked best in detecting disjoint, whereas tree root and crack were most challenging to predict. The work not only illustrated the benefits of TL, but also provided technical guidance to practitioners who lack expertise in ODMs and rely on TL for better sewer defect detection

Crack Initiation Characteristics of Gas-Containing Coal under Gas Pressures

In deep coal mines, coal before the working face is subjected to coupled high mining-induced stress and gas pressure. Such condition may facilitate crack formation and propagation in the coal seam, leading to serious coal and gas disasters. In this study, the mechanical properties (i.e., uniaxial compressive strength, tensile strength, and fracture toughness) of gas-containing coal with four levels of initial gas pressure (i.e., 0.0, 0.5, 1.0, and 1.5 MPa) were investigated by uniaxial compression, Brazilian disc, and notched semicircular bending loading test. A newly developed gas-sealing device and an RMT-150 rock mechanics testing machine were used. Fracture modes under different initial gas pressures were also determined. A theoretical method of fracture mechanics was used to analyze crack initiation characteristics under gas adsorption state. Results show that the uniaxial compressive strength, tensile strength, and fracture toughness of gas-containing coal decreased with increasing initial gas pressure. The tensional fracture occurred in gas-containing coal under uniaxial compressive loading with high gas pressure. Cracks in gas-containing coal propagated under small external loads due to the increase in effective stress of crack tip and decrease in cracking strength. This study provided evidence for modifications of the support design of working face in deep coal mines. Furthermore, the correlations between fracture toughness, compressive strength, and tensile strength of gas-containing coal were investigated

Macroscopic assembly of oppositely charged polyelectrolyte hydrogels

Stimulus-responsive hydrogels are assembled into soft devices that transform their shape upon external stimuli. It is very important to understand the macroscopic assembly mechanisms and to modulate the interface stability of assemblies. In this study, polyelectrolyte hydrogels with outstanding mechanical performances and opposite charges were assembled into soft devices via electrostatic association. The interface strength could be tuned by varying the net charge density, which depends on the concentration of charged/chargeable monomers, the pH of the buffer solution, and the ionic strength of the solution. We propose that charge screening at the interface by free counterions causes a reduction of interface strength, whereas charge redistribution is helpful to strengthen the interface of the assemblies. The understanding of macroscopic assembly mechanisms provides significant guidelines for designing novel soft transducers and drivers and engineering their interface strength

Tough and Self-Recoverable Hydrogels Crosslinked by Triblock Copolymer Micelles and Fe3+ Coordination

Tough hydrogels have great potentials in soft robotics, artificial muscles, tissue replacement, and so on. Here we introduce novel tough hydrogels crosslinked by triblock copolymer (F127DA) micelles and metal coordination. The gels showed outstanding tensile strength (similar to 1-11 MPa), toughness (similar to 4-32 MJ m(-3)), and excellent self-recovery properties (similar to 56.8-87.2% toughness recovery in 9 min at room temperature). The mechanical and self-recovery properties could be manipulated by varying contents of micelles and/or COO- groups. Dynamic mechanical analysis of the hydrogels revealed apparent activation energy and relaxations for both physical interactions. In situ small-angle X-ray scattering measurements on hydrogels upon stretching revealed micelle deformations. XPS measurements on hydrogels before and after stretching revealed significant changes in the binding energy of Fe3+ ions in the gels, suggesting the rupture of coordination bonds. The experimental results strongly suggest a synergistic effect from the micelle-crosslinking and Fe3+-COO- coordination on the strength, toughness, and self-recovery of the hydrogels. (C) 2018 Wiley Periodicals, Inc

Tough and Self-Recoverable Hydrogels Crosslinked by Triblock Copolymer Micelles and Fe3+ Coordination

Tough hydrogels have great potentials in soft robotics, artificial muscles, tissue replacement, and so on. Here we introduce novel tough hydrogels crosslinked by triblock copolymer (F127DA) micelles and metal coordination. The gels showed outstanding tensile strength (similar to 1-11 MPa), toughness (similar to 4-32 MJ m(-3)), and excellent self-recovery properties (similar to 56.8-87.2% toughness recovery in 9 min at room temperature). The mechanical and self-recovery properties could be manipulated by varying contents of micelles and/or COO- groups. Dynamic mechanical analysis of the hydrogels revealed apparent activation energy and relaxations for both physical interactions. In situ small-angle X-ray scattering measurements on hydrogels upon stretching revealed micelle deformations. XPS measurements on hydrogels before and after stretching revealed significant changes in the binding energy of Fe3+ ions in the gels, suggesting the rupture of coordination bonds. The experimental results strongly suggest a synergistic effect from the micelle-crosslinking and Fe3+-COO- coordination on the strength, toughness, and self-recovery of the hydrogels. (C) 2018 Wiley Periodicals, Inc

Altered Functional Connectivity within and between Brain Modules in Absence Epilepsy: A Resting-State Functional Magnetic Resonance Imaging Study

Functional connectivity has been correlated with a patient’s level of consciousness and has been found to be altered in several neuropsychiatric disorders. Absence epilepsy patients, who experience a loss of consciousness, are assumed to suffer from alterations in thalamocortical networks; however, previous studies have not explored the changes at a functional module level. We used resting-state functional magnetic resonance imaging to examine the alteration in functional connectivity that occurs in absence epilepsy patients. By parcellating the brain into 90 brain regions/nodes, we uncovered an altered functional connectivity within and between functional modules. Some brain regions had a greater number of altered connections and therefore behaved as key nodes in the changed network pattern; these regions included the superior frontal gyrus, the amygdala, and the putamen. In particular, the superior frontal gyrus demonstrated both an increased value of connections with other nodes of the frontal default mode network and a decreased value of connections with the limbic system. This divergence is positively correlated with epilepsy duration. These findings provide a new perspective and shed light on how functional connectivity and the balance of within/between module connections may contribute to both the state of consciousness and the development of absence epilepsy

DataSheet3_Intra-articular injection of placental mesenchymal stromal cells ameliorates pain and cartilage anabolism/catabolism in knee osteoarthritis.PDF

Background: Knee Osteoarthritis (kOA), the most common joint degenerative disorder, lacks effective therapeutics. Placenta-derived mesenchymal stromal cells (PMSCs) are effective in tissue repairing and generation, which have potential in treating kOA. This study aimed to determine the anti-kOA efficacy of PMSCs and to explore its action mode.Methods: Flow cytometry and three-line differentiation were performed for identification of PMSCs. In vivo, a rat kOA model established by anterior cruciate ligament transection (ACLT) surgery was used to evaluate the efficacy of PMSCs. Histopathological HE and SO staining with Osteoarthritis Research Society International scoring were conducted, and cartilage expressions of MMP13 and Col2 were measured by immunohistochemistry. Pain behavior parameters by mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL), were measured. In vitro, wound healing and cell immunofluorescence assays were conducted to detect the proliferation and migration ability of chondrocytes treated with PMSCs conditioned medium (PMSCs-CM). Quantitative real-time PCR (qRT-PCR) and Western blot (WB) assays were applied to explore the molecular action of PMSCs on chondrocytes.Results: The results of flow cytometry indicated that the surface markers of PMSCs (CD73 > 95%, CD90 > 95%, and CD34 Conclusion: This study demonstrated PMSCs’ anti-kOA efficacy and its paracrine-based action mode, providing novel knowledge of PMSCs and suggesting it as a promising cell therapy for treatment of kOA.</p