Stepwise dual-release microparticles of BMP-4 and SCF in induced pluripotent stem cell spheroids enhance differentiation into hematopoietic stem cells.

Recently, the formation of three-dimensional (3D) cell aggregates known as embryoid bodies (EBs) grown in media supplemented with HSC-specific morphogens has been utilized for the directed differentiation of embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), into clinically relevant hematopoietic stem cells (HSCs). However, delivering growth factors and nutrients have become ineffective in inducing synchronous differentiation of cells due to their 3D conformation. Moreover, irregularly sized EBs often lead to the formation of necrotic cores in larger EBs, impairing differentiation. Here, we developed two gelatin microparticles (GelMPs) with different release patterns and two HSC-related growth factors conjugated to them. Slow and fast releasing GelMPs were conjugated with bone morphogenic factor-4 (BMP-4) and stem cell factor (SCF), respectively. The sequential presentation of BMP-4 and SCF in GelMPs resulted in efficient and effective hematopoietic differentiation, shown by the enhanced gene and protein expression of several mesoderm and HSC-related markers, and the increased concentration of released HSC-related cytokines. In the present study, we were able to generate CD34+, CD133+, and FLT3+ cells with similar cellular and molecular morphology as the naïve HSCs that can produce colony units of different blood cells, in vitro.

Ultrasound-triggered three dimensional hyaluronic acid hydrogel promotes in vitro and in vivo reprogramming into induced pluripotent stem cells.

Cellular reprogramming technologies have been developed with different physicochemical factors to improve the reprogramming efficiencies of induced pluripotent stem cells (iPSCs). Ultrasound is a clinically applied noncontact biophysical factor known for regulating various cellular behaviors but remains uninvestigated for cellular reprogramming. Here, we present a new reprogramming strategy using low-intensity ultrasound (LIUS) to improve cellular reprogramming of iPSCs in vitro and in vivo. Under 3D microenvironment conditions, increased LIUS stimulation shows enhanced cellular reprogramming of the iPSCs. The cellular reprogramming process facilitated by LIUS is accompanied by increased mesenchymal to epithelial transition and histone modification. LIUS stimulation transiently modulates the cytoskeletal rearrangement, along with increased membrane fluidity and mobility to increase HA/CD44 interactions. Furthermore, LIUS stimulation with HA hydrogel can be utilized in application of both human cells and in vivo environment, for enhanced reprogrammed cells into iPSCs. Thus, LIUS stimulation with a combinatorial 3D microenvironment system can improve cellular reprogramming in vitro and in vivo environments, which can be applied in various biomedical fields.

In situ fabricated ZnO nanostructures within carboxymethyl cellulose-based ternary hydrogels for wound healing applications.

Zinc oxide nanostructures (ZnO NS) were fabricated in situ within a ternary hydrogel system composed of carboxymethyl cellulose-agarose-polyvinylpyrrolidone (CAP@ZnO TNCHs) by a one-pot method employing moist-heat solution casting. The percentages of CMC and ZnO NS were varied in the CAP hydrogel films and then they were investigated by different techniques, such as ATR/FTIR, TGA, XRD, XPS, and FE-SEM analysis. Furthermore, the mechanical properties, hydrophilicity, swelling, porosity, and antibacterial activity of the CAP@ZnO TNCHs were studied. In-vitro biocompatibility assays were performed with skin fibroblast (CCD-986sk) cells. In-vitro culture of CCD-986sk fibroblasts showed that the ZnO NS facilitated cell adhesion and proliferation. Furthermore, the application of CAP@ZnO TNCHs enhanced cellular interactions and physico-chemical, antibacterial bacterial, and biological performance relative to unmodified CAP hydrogels. Also, an in vivo wound healing study verified that the CAP@ZnO TNCHs promoted wound healing significantly within 18 days, an effect superior to that of unmodified CAP hydrogels. Hence, these newly developed cellulose-based ZnO TNCHs are promising materials for wound healing applications.

Therapeutic potential of mesenchymal stem cells from human iPSC-derived teratomas for osteochondral defect regeneration.

Human induced pluripotent stem cells (iPSCs) hold great promise for personalized medicine, as they can be differentiated into specific cell types, especially mesenchymal stem cells (MSCs). Therefore, our study sought to assess the feasibility of deriving MSCs from teratomas generated from human iPSCs. Teratomas serve as a model to mimic multilineage human development, thus enriching specific somatic progenitors and stem cells. Here, we discovered a small, condensed mass of MSCs within iPSC-generated teratomas. Afterward, we successfully isolated MSCs from this condensed mass, which was a byproduct of teratoma development. To evaluate the characteristics and cell behaviors of iPSC-derived MSCs (iPSC-MSCs), we conducted comprehensive assessments using qPCR, immunophenotype analysis, and cell proliferation-related assays. Remarkably, iPSC-MSCs exhibited an immunophenotype resembling that of conventional MSCs, and they displayed robust proliferative capabilities, similar to those of higher pluripotent stem cell-derived MSCs. Furthermore, iPSC-MSCs demonstrated the ability to differentiate into multiple lineages in vitro. Finally, we evaluated the therapeutic potential of iPSC-MSCs using an osteochondral defect model. Our findings demonstrated that teratomas are a promising source for the isolation of condensed MSCs. More importantly, our results suggest that iPSC-MSCs derived from teratomas possess the capacity for tissue regeneration, highlighting their promise for future therapeutic applications.

Cellulose graphitic carbon directed iron oxide interfaced polypyrrole electrode materials for high performance supercapacitors.

The rising demand for green and clean energy urges the enlargement of economical and proficient electrode materials for supercapacitors. Herein, we designed a novel electrode material by porous cellulose graphitic carbon (CC) derived from bio-waste cornhusk via the pyrolysis route, and α-Fe2O3 decorated nanostructure with CC (CCIO) was achieved in situ pyrolysis of corn-husk and Fe(NO3)3·9H2O metal salt followed by a coating of polypyrrole (CCIOP). The CC, CCIO, and CCIOP nanocomposite electrodes were characterized by XRD, Raman, FTIR, FE-SEM/EDX, FE-TEM, XPS, and BET analysis. The CCIOP nanocomposite electrode exhibits an enhanced specific capacitance (Csp) of 290.9 F/g, which is substantial to its pristine CC (128.3 F/g), PPy (140.3 F/g), and CCIO (190.7 F/g). The Csp of CCIOP in a three-electrode system, using 1 M Na2SO4 electrolyte exhibits excellent capacity retention of 79.1 % even at a high current density of 10 A/g. The as-fabricated asymmetric supercapacitor (ASC) delivered a remarkable capacity retention of 88.7 % with a coulombic efficiency of 98.8 % even after 3000 cycles. The study shows successful utilization of cellulose from bio-waste cornhusk into a substantial template applicable in future alternative energy storage devices.

Fabrication of Ru loaded MgB2 with guar gum hybrid for photocatalytic degradation of crystal violet.

Today, dyes/pigment-based materials are confronting a serious issue in harming marine ecology. Annihilate these serious water pollutants using photoactive 2D nanohybrid catalysts showed promising comparativeness over available photocatalysts. In the present work, a facile route to decorate Ruthenium (Ru) on 2D MgB2 flower-like nanostructures was developed via ecofriendly guar gum biopolymer substantial template (MgB2/GG@Ru NFS) and its photocatalytic performance was reported. Synthesis of MgB2@Ru, MgB2/GG@Ru NFS and commercial MgB2, was studied by FTIR, XRD, FE-SEM, EDX, AFM, TEM, UV-vis spectra, and XPS analysis. From the results, the MgB2/GG@Ru NFS exhibited a superior photocatalytic performance (99.7 %) than its precursors MgB2@Ru (79.7 %), and MgB2 (53.7 %), with the degradation efficiency of the crystal violet (CV) within 100 min under visible light irradiation. The proposed photo-catalyst MgB2/GG@Ru NFS showed negligible loss of photocatalytic activity even after five successive cycles, revealing its reusability and enhanced stability due to the network structure. The photocatalytic mechanism for MgB2/GG@Ru NFS was evaluated by trapping experiment of active species, verifying that superoxide (O2-) and electron (e-) contributed significant role in the dye degradation.

Emerging nano-scale delivery systems for the treatment of osteoporosis.

Osteoporosis is a pathological condition characterized by an accelerated bone resorption rate, resulting in decreased bone density and increased susceptibility to fractures, particularly among the elderly population. While conventional treatments for osteoporosis have shown efficacy, they are associated with certain limitations, including limited drug bioavailability, non-specific administration, and the occurrence of adverse effects. In recent years, nanoparticle-based drug delivery systems have emerged as a promising approach for managing osteoporosis. Nanoparticles possess unique physicochemical properties, such as a small size, large surface area-to-volume ratio, and tunable surface characteristics, which enable them to overcome the limitations of conventional therapies. These nanoparticles offer several advantages, including enhanced drug stability, controlled release kinetics, targeted bone tissue delivery, and improved drug bioavailability. This comprehensive review aims to provide insights into the recent advancements in nanoparticle-based therapy for osteoporosis. It elucidates the various types of nanoparticles employed in this context, including silica, polymeric, solid lipid, and metallic nanoparticles, along with their specific processing techniques and inherent properties that render them suitable as potential drug carriers for osteoporosis treatment. Furthermore, this review discusses the challenges and future suggestions associated with the development and translation of nanoparticle drug delivery systems for clinical use. These challenges encompass issues such as scalability, safety assessment, and regulatory considerations. However, despite these challenges, the utilization of nanoparticle-based drug delivery systems holds immense promise in revolutionizing the field of osteoporosis management by enabling more effective and targeted therapies, ultimately leading to improved patient outcomes.

Progress and emerging techniques for biomaterial-based derivation of mesenchymal stem cells (MSCs) from pluripotent stem cells (PSCs).

The use of mesenchymal stem cells (MSCs) for clinical purposes has skyrocketed in the past decade. Their multilineage differentiation potentials and immunomodulatory properties have facilitated the discovery of therapies for various illnesses. MSCs can be isolated from infant and adult tissue sources, which means they are easily available. However, this raises concerns because of the heterogeneity among the various MSC sources, which limits their effective use. Variabilities arise from donor- and tissue-specific differences, such as age, sex, and tissue source. Moreover, adult-sourced MSCs have limited proliferation potentials, which hinders their long-term therapeutic efficacy. These limitations of adult MSCs have prompted researchers to develop a new method for generating MSCs. Pluripotent stem cells (PSCs), such as embryonic stem cells and induced PSCs (iPSCs), can differentiate into various types of cells. Herein, a thorough review of the characteristics, functions, and clinical importance of MSCs is presented. The existing sources of MSCs, including adult- and infant-based sources, are compared. The most recent techniques for deriving MSCs from iPSCs, with a focus on biomaterial-assisted methods in both two- and three-dimensional culture systems, are listed and elaborated. Finally, several opportunities to develop improved methods for efficiently producing MSCs with the aim of advancing their various clinical applications are described.

MMP13-Overexpressing Mesenchymal Stem Cells Enhance Bone Tissue Formation in the Presence of Collagen Hydrogel.

BACKGROUND: Matrix metalloproteinases (MMPs) are proteins involved in the repair and remodeling the extracellular matrix (ECM). MMP13 is essential for bone development and healing through the remodeling of type I collagen (COL1), the main component of the ECM in bone tissue. Mesenchymal stem cells (MSCs)-based cell therapy has been considered a promising approach for bone regeneration because of their osteogenic properties. However, the approaches using MSC to completely regenerate bone tissue have been limited. To overcome the limitation, genetic engineering of MSC could be a strategy for promoting regeneration efficacy. METHODS: We performed in vitro and in vivo experiments using MMP13-overexpressing MSCs in the presence of COL1. To examine MMP13-overexpressing MSCs in vivo, we prepared a fibrin/COL1-based hydrogel to encapsulate MSCs and subcutaneously implanted gel-encapsulated MSCs in nude mice. We found that the osteogenic marker genes, ALP and RUNX2, were upregulated in MMP13-overexpressing MSCs through p38 phosphorylation. In addition, MMP13 overexpression in MSCs stimulated the expression of integrin α3, which is up-stream receptor of p38, and substantially increased osteogenic differentiation potential of MSCs. Bone tissue formation in MMP13-overexpressing MSCs was significantly higher than that in control MSCs. Taken together, our findings demonstrate that MMP13 is not only an essential factor for bone development and bone healing but also has a pivotal role in promoting osteogenic differentiation of MSCs to induce bone formation. CONCLUSION: MSCs Genetically engineered to overexpress MMP13, which have a powerful potential to differentiate into the osteogenic cells, might be beneficial in bone disease therapy.

Generation of bioactive MSC-EVs for bone tissue regeneration by tauroursodeoxycholic acid treatment.

Extracellular vesicles (EVs) are nano-sized carriers that reflect the parent cell's information and are known to mediate cell-cell communication. In order to overcome the disadvantages of mesenchymal stem cells (MSCs) in cell therapy, such as unexpected differentiation leading to tumorization, immune rejection, and other side effects, EVs derived from MSCs (MSC-EVs) with the tissue regenerative function have been studied as new cell-free therapeutics. However, therapeutic applications of EVs require overcoming several challenges. First, the production efficiency of MSC-EVs should be increased at least as much as the quantity of them are required to their clinical application; second, MSC-EVs needs to show various functionality further, thereby increasing tissue regeneration efficiency. In this study, we treated tauroursodeoxycholic acid (TUDCA), a biological derivative known to regulate cholesterol, to MSCs and investigated whether TUDCA treatment would be able to increase EV production efficiency and tissue regenerative capacity of EVs. Indeed, it appears that TUDCA priming to MSC increases the yield of MSC-EVs >2 times by reducing the cellular cholesterol level in MSCs and increasing the exocytosis-related CAV1 expression. Interestingly, it was found that the EVs derived from TUDCA-primed MSCs (T-EV) contained higher amounts of anti-inflammatory cytokines (IL1RN, IL6, IL10, and IL11) and osteogenic proteins (ALP, RUNX2, BMP2, BMPR1, and BMPR2) than those in control MSC-EVs (C-EV). Besides, it was shown that T-EV not only regulated M1/M2 macrophages differentiation of monocytes, also effectively increased the osteogenic differentiation of MSCs as well as bone tissue regeneration in a bone defect rat model. Based on these results, it is concluded that TUDCA treatment to MSC as a new approach endows EV with high-yield production and functionality. Thus, we strongly believe T-EV would be a powerful therapeutic material for bone tissue regeneration and potentially could be expanded to other types of tissue regeneration for clinical applications.

Combinatorial Effect of Mesenchymal Stem Cells and Extracellular Vesicles in a Hydrogel on Cartilage Regeneration.

BACKGROUND: Mesenchymal stem cells (MSCs) are used for tissue regeneration due to their wide differentiation capacity and anti-inflammatory effects. Extracellular vesicles (EVs) derived from MSCs are also known for their regenerative effects as they contain nucleic acids, proteins, lipids, and cytokines similar to those of parental cells. There are several studies on the use of MSCs or EVs for tissue regeneration. However, the combinatorial effect of human MSCs (hMSCs) and EVs is not clear. In this study, we investigated the combinatorial effect of hMSCs and EVs on cartilage regeneration via co-encapsulation in a hyaluronic-acid (HA)-based hydrogel. METHODS: A methacrylic-acid-based HA hydrogel was prepared to encapsulate hMSCs and EVs in hydrogels. Through in vitro and in vivo analyses, we investigated the chondrogenic potential of the HA hydrogel-encapsulated with hMSCs and EVs. RESULTS: Co-encapsulation of hMSCs with EVs in the HA hydrogel increased the chondrogenic differentiation of hMSCs and regeneration of damaged cartilage tissue compared with that of the HA hydrogel loaded with hMSCs only. CONCLUSION: Co-encapsulation of hMSCs and EVs in the HA hydrogel effectively enhances cartilage tissue regeneration due to the combinatorial therapeutic effect of hMSCs and EVs. Thus, in addition to cartilage tissue regeneration for the treatment of osteoarthritis, this approach would be a useful strategy to improve other types of tissue regeneration.

Induction of T-helper-17-cell-mediated anti-tumour immunity by pathogen-mimicking polymer nanoparticles.

The effectivity of cancer immunotherapies is hindered by immunosuppressive tumour microenvironments that are poorly infiltrated by effector T cells and natural killer cells. In infection and autoimmune disease, the recruitment and activation of effector immune cells is coordinated by pro-inflammatory T helper 17 (TH17) cells. Here we show that pathogen-mimicking hollow nanoparticles displaying mannan (a polysaccharide that activates TH17 cells in microbial cell walls) limit the fraction of regulatory T cells and induce TH17-cell-mediated anti-tumour responses. The nanoparticles activate the pattern-recognition receptor Dectin-2 and Toll-like receptor 4 in dendritic cells, and promote the differentiation of CD4+ T cells into the TH17 phenotype. In mice, intra-tumoural administration of the nanoparticles decreased the fraction of regulatory T cells in the tumour while markedly increasing the fractions of TH17 cells (and the levels of TH17-cell-associated cytokines), CD8+ T cells, natural killer cells and M1-like macrophages. The anti-tumoural activity of the effector cells was amplified by an agonistic antibody against the co-stimulatory receptor OX40 in multiple mouse models. Nanomaterials that induce TH17-cell-mediated immune responses may have therapeutic potential.

Preclinical Study of Human Bone Marrow-Derived Mesenchymal Stem Cells Using a 3-Dimensional Manufacturing Setting for Enhancing Spinal Fusion.

Spinal fusion surgery is a surgical technique that connects one or more vertebrae at the same time to prevent movement between the vertebrae. Although synthetic bone substitutes or osteogenesis-inducing recombinant proteins were introduced to promote bone union, the rate of revision surgery is still high due to pseudarthrosis. To promote successful fusion after surgery, stem cells with or without biomaterials were introduced; however, conventional 2D-culture environments have resulted in a considerable loss of the innate therapeutic properties of stem cells. Therefore, we conducted a preclinical study applying 3D-spheroids of human bone marrow-dewrived mesenchymal stem cells (MSCs) to a mouse spinal fusion model. First, we built a large-scale manufacturing platform for MSC spheroids, which is applicable to good manufacturing practice (GMP). Comprehensive biomolecular examinations, which include liquid chromatography-mass spectrometry and bioinformatics could suggest a framework of quality control (QC) standards for the MSC spheroid product regarding the identity, purity, viability, and potency. In our animal study, the mass-produced and quality-controlled MSC spheroids, either undifferentiated or osteogenically differentiated were well-integrated into decorticated bone of the lumbar spine, and efficiently improved angiogenesis, bone regeneration, and mechanical stability with statistical significance compared to 2D-cultured MSCs. This study proposes a GMP-applicable bioprocessing platform and QC directions of MSC spheroids aiming for their clinical application in spinal fusion surgery as a new bone graft substitute.

Therapeutic potential of epiphyseal growth plate cells for bone regeneration in an osteoporosis model.

Bone growth occurs in the epiphyseal growth plate (EGP) and epiphyseal growth plate cells (EGPCs) exist in EGP. EGPCs, including skeletal stem cells (SSCs), are cells that induce bone growth and development through endochondral ossification. Recently, the superiority of bone regeneration through endochondral ossification has been reported. Our study compared EGPCs with bone marrow-derived mesenchymal stem cells (BM-MSCs) and suggested the therapeutic potential of new bone regeneration. In this study, we analyzed the characteristics between EGPCs and BM-MSCs based on morphological characteristics and molecular profiles. EGPCs expressed chondrogenic and osteogenic markers higher than BM-MSCs. Additionally, in co-culture with BM-MSCs, EGPCs induced an increase in chondrogenic, osteogenic, and hypertrophic markers of BM-MSCs. Finally, EGPCs induced higher bone regeneration than BM-MSCs in the osteoporosis model. Overall, we suggest the possibility of EGPCs as cell therapy for effective bone regeneration.

CRISPR/Cas9 and Nanotechnology Pertinence in Agricultural Crop Refinement.

The CRISPR/Cas9 (Clustered Regularly Interspaced Short Palindromic Repeats/CRISPR-associated protein 9) method is a versatile technique that can be applied in crop refinement. Currently, the main reasons for declining agricultural yield are global warming, low rainfall, biotic and abiotic stresses, in addition to soil fertility issues caused by the use of harmful chemicals as fertilizers/additives. The declining yields can lead to inadequate supply of nutritional food as per global demand. Grains and horticultural crops including fruits, vegetables, and ornamental plants are crucial in sustaining human life. Genomic editing using CRISPR/Cas9 and nanotechnology has numerous advantages in crop development. Improving crop production using transgenic-free CRISPR/Cas9 technology and produced fertilizers, pesticides, and boosters for plants by adopting nanotechnology-based protocols can essentially overcome the universal food scarcity. This review briefly gives an overview on the potential applications of CRISPR/Cas9 and nanotechnology-based methods in developing the cultivation of major agricultural crops. In addition, the limitations and major challenges of genome editing in grains, vegetables, and fruits have been discussed in detail by emphasizing its applications in crop refinement strategy.

Early Prediction of Sepsis Onset Using Neural Architecture Search Based on Genetic Algorithms.

Sepsis is a life-threatening condition with a high mortality rate. Early prediction and treatment are the most effective strategies for increasing survival rates. This paper proposes a neural architecture search (NAS) model to predict the onset of sepsis with a low computational cost and high search performance by applying a genetic algorithm (GA). The proposed model shares the weights of all possible connection nodes internally within the neural network. Externally, the search cost is reduced through the weight-sharing effect between the genotypes of the GA. A predictive analysis was performed using the Medical Information Mart for Intensive Care III (MIMIC-III), a medical time-series dataset, with the primary objective of predicting sepsis onset 3 h before occurrence. In addition, experiments were conducted under various prediction times (0-12 h) for comparison. The proposed model exhibited an area under the receiver operating characteristic curve (AUROC) score of 0.94 (95% CI: 0.92-0.96) for 3 h, which is 0.31-0.26 higher than the scores obtained using the Sequential Organ Failure Assessment (SOFA), quick SOFA (qSOFA), and Simplified Acute Physiology Score (SAPS) II scoring systems. Furthermore, the proposed model exhibited a 12% improvement in the AUROC value over a simple model based on the long short-term memory neural network. Additionally, it is not only optimally searchable for sepsis onset prediction, but also outperforms conventional models that use similar predictive purposes and datasets. Notably, it is sufficiently robust to shape changes in the input data and has less structural dependence.

SPRY4 acts as an indicator of osteoarthritis severity and regulates chondrocyte hypertrophy and ECM protease expression.

Osteoarthritis (OA) causes serious changes in the metabolic and signaling pathways of chondrocytes, including the mitogen-activated protein kinase (MAPK) pathway. However, the role of sprouty RTK signaling antagonist 4 (SPRY4), an inhibitor of MAPK, in the human cartilage tissues and chondrocytes remains to be understood. Here, using SPRY4 gene delivery into healthy and degenerated chondrocytes, we elucidated the role of SPRY4 in preventing chondrocyte hypertrophy. In addition to using the human cartilage tissues with the destabilization of the medial meniscus (DMM) model in Sprague-Dawley (SD) rats, the role of SPRY4 in cartilage tissues and chondrocytes was explored through their molecular and histological analyses. In order to determine the effects of SPRY4 on healthy human chondrocyte hypertrophy, small interfering RNA (siRNA) was used to knock down SPRY4. Lentiviral transduction of SPRY4 into degenerated human chondrocytes allowed us to investigate its ability to prevent hypertrophy. SPRY4 expression levels were higher in healthy human cartilage tissue and chondrocytes than in degenerated human cartilage tissues and hypertrophy-induced chondrocytes. The knockdown of SPRY4 in healthy chondrocytes caused an increase in hypertrophy, senescence, reactive oxygen species (ROS) production, and extracellular matrix (ECM) protease expression. However, all these factors decreased upon overexpression of SPRY4 in degenerated chondrocytes via regulation of the MAPK signaling pathway. We conclude that SPRY4 is a crucial indicator of osteoarthritis (OA) severity and could play an important role in preventing OA in the cartilage by inhibiting chondrocyte hypertrophy.

Functional Duality of Chondrocyte Hypertrophy and Biomedical Application Trends in Osteoarthritis.

Chondrocyte hypertrophy is one of the key indicators in the progression of osteoarthritis (OA). However, compared with other OA indications, such as cartilage collapse, sclerosis, inflammation, and protease activation, the mechanisms by which chondrocyte hypertrophy contributes to OA remain elusive. As the pathological processes in the OA cartilage microenvironment, such as the alterations in the extracellular matrix, are initiated and dictated by the physiological state of the chondrocytes, in-depth knowledge of chondrocyte hypertrophy is necessary to enhance our understanding of the disease pathology and develop therapeutic agents. Chondrocyte hypertrophy is a factor that induces OA progression; it is also a crucial factor in the endochondral ossification. This review elaborates on this dual functionality of chondrocyte hypertrophy in OA progression and endochondral ossification through a description of the characteristics of various genes and signaling, their mechanism, and their distinguishable physiological effects. Chondrocyte hypertrophy in OA progression leads to a decrease in chondrogenic genes and destruction of cartilage tissue. However, in endochondral ossification, it represents an intermediate stage at the process of differentiation of chondrocytes into osteogenic cells. In addition, this review describes the current therapeutic strategies and their mechanisms, involving genes, proteins, cytokines, small molecules, three-dimensional environments, or exosomes, against the OA induced by chondrocyte hypertrophy. Finally, this review proposes that the contrasting roles of chondrocyte hypertrophy are essential for both OA progression and endochondral ossification, and that this cellular process may be targeted to develop OA therapeutics.

A refraction correction for buried interfaces applied to in situ grazing-incidence X-ray diffraction studies on Pd electrodes.

In situ characterization of electrochemical systems can provide deep insights into the structure of electrodes under applied potential. Grazing-incidence X-ray diffraction (GIXRD) is a particularly valuable tool owing to its ability to characterize the near-surface structure of electrodes through a layer of electrolyte, which is of paramount importance in surface-mediated processes such as catalysis and adsorption. Corrections for the refraction that occurs as an X-ray passes through an interface have been derived for a vacuum-material interface. In this work, a more general form of the refraction correction was developed which can be applied to buried interfaces, including liquid-solid interfaces. The correction is largest at incidence angles near the critical angle for the interface and decreases at angles larger and smaller than the critical angle. Effective optical constants are also introduced which can be used to calculate the critical angle for total external reflection at the interface. This correction is applied to GIXRD measurements of an aqueous electrolyte-Pd interface, demonstrating that the correction allows for the comparison of GIXRD measurements at multiple incidence angles. This work improves quantitative analysis of d-spacing values from GIXRD measurements of liquid-solid systems, facilitating the connection between electrochemical behavior and structure under in situ conditions.

Estimation of the Continuous Walking Angle of Knee and Ankle (Talocrural Joint, Subtalar Joint) of a Lower-Limb Exoskeleton Robot Using a Neural Network.

A lower-limb exoskeleton robot identifies the wearer's walking intention and assists the walking movement through mechanical force; thus, it is important to be able to identify the wearer's movement in real-time. Measurement of the angle of the knee and ankle can be difficult in the case of patients who cannot move the lower-limb joint properly. Therefore, in this study, the knee angle as well as the angles of the talocrural and subtalar joints of the ankle were estimated during walking by applying the neural network to two inertial measurement unit (IMU) sensors attached to the thigh and shank. First, for angle estimation, the gyroscope and accelerometer data of the IMU sensor were obtained while walking at a treadmill speed of 1 to 2.5 km/h while wearing an exoskeleton robot. The weights according to each walking speed were calculated using a neural network algorithm programmed in MATLAB software. Second, an appropriate weight was selected according to the walking speed through the IMU data, and the knee angle and the angles of the talocrural and subtalar joints of the ankle were estimated in real-time during walking through a feedforward neural network using the IMU data received in real-time. We confirmed that the angle estimation error was accurately estimated as 1.69° ± 1.43 (mean absolute error (MAE) ± standard deviation (SD)) for the knee joint, 1.29° ± 1.01 for the talocrural joint, and 0.82° ± 0.69 for the subtalar joint. Therefore, the proposed algorithm has potential for gait rehabilitation as it addresses the difficulty of estimating angles of lower extremity patients using torque and EMG sensors.